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Repository: INK-USC/TriggerNER
Branch: master
Commit: c01d9500ad2c
Files: 38
Total size: 7.8 MB
Directory structure:
gitextract_tt3m6fwi/
├── .gitignore
├── README.md
├── common/
│ ├── __init__.py
│ ├── instance.py
│ └── sentence.py
├── config/
│ ├── __init__.py
│ ├── config.py
│ ├── eval.py
│ ├── reader.py
│ └── utils.py
├── dataset/
│ ├── BC5CDR/
│ │ ├── dev.txt
│ │ ├── test.txt
│ │ ├── train.txt
│ │ ├── train_20.txt
│ │ └── trigger_20.txt
│ ├── CONLL/
│ │ ├── dev.txt
│ │ ├── test.txt
│ │ ├── train.txt
│ │ ├── train_20.txt
│ │ └── trigger_20.txt
│ └── Laptop-reviews/
│ ├── test.txt
│ ├── train.txt
│ ├── train_20.txt
│ ├── trigger_20.txt
│ └── trigger_turk.txt
├── model/
│ ├── __init__.py
│ ├── charbilstm.py
│ ├── linear_crf_inferencer.py
│ ├── soft_attention.py
│ ├── soft_encoder.py
│ ├── soft_inferencer.py
│ ├── soft_inferencer_naive.py
│ └── soft_matcher.py
├── naive.py
├── requirments.txt
├── semi_supervised.py
├── supervised.py
└── util.py
================================================
FILE CONTENTS
================================================
================================================
FILE: .gitignore
================================================
dataset/glove*
.DS_Store
.idea/*
__pycache__/*
config/__pycache__/*
model/__pycache__/*
common/__pycache__/*
dataset/CONLL/train_manual.txt
dataset/BC5CDR/train_manual.txt
dataset/Laptop-reviews/train_manual.txt
================================================
FILE: README.md
================================================
# TriggerNER
Code & Data for ACL 2020 paper:
[TriggerNER: Learning with Entity Triggers as Explanations for Named Entity Recognition](https://arxiv.org/abs/2004.07493)
Authors: [Bill Yuchen Lin*](https://yuchenlin.xyz), [Dong-Ho Lee*](https://danny-lee.info/), Ming Shen, [Ryan Moreno](https://ryan-moreno.github.io/), Xiao Huang, [Prashant Shiralkar](https://sites.google.com/site/shiralkarprashant/), [Xiang Ren](http://ink-ron.usc.edu/xiangren/)
We introduce **entity triggers**, an effective proxy of human explanations for facilitating label-efficient learning of NER models.
We crowd-sourced 14k entity triggers for two well-studied NER datasets.
Our proposed model, name Trigger Matching Network, jointly learns trigger representations and soft matching module with self-attention such that can generalize to unseen sentences easily for tagging.
Expriments show that the framework is significantly more cost-effective such that usinng 20% of the trigger-annotated sentences can result in a comparable performance of conventional supervised approaches using 70% training data.
<p align="center"><img src="figure/trig.png" width="800"/></p>
If you make use of this code or the entity triggers in your work, please kindly cite the following paper:
```bibtex
@inproceedings{TriggerNER2020,
title={TriggerNER: Learning with Entity Triggers as Explanations for Named Entity Recognition},
author={Bill Yuchen Lin and Dong-Ho Lee and Ming Shen and Ryan Moreno and Xiao Huang and Prashant Shiralkar and Xiang Ren},
booktitle={Proceedings of ACL},
year={2020}
}
```
## Quick Links
* [Requirements](#Requirements)
* [Trigger Dataset](#Trigger-Dataset)
* [Train and Test](#train-and-test)
## Trigger Dataset
The concept of **entity triggers**, a novel form of explanatory annotation for named entity recognition problems.
We crowd-source and publicly release 14k annotated entity triggers on two popular datasets:
CoNLL03 (generic domain), BC5CDR (biomedical domain).
`dataset/` saves CONLL, BC5CDR, and Laptop-Reviews dataset. For each directory,
* `train.txt, test.txt, dev.txt` are original dataset
* `train_20.txt` is for cutting out the original train dataset into 20% for baseline setting. The dataset is used in `naive.py`
* `trigger_20.txt` is trigger dataset. The dataset is used in `supervised.py` and `semi_supervised.py`.
To enable 3% of original training dataset, you should use `--percentage 15` since the dataset we used for supervised.py and semi_supervised.py is 20% of original training data with triggers.
## Requirements
Python >= 3.6 and PyTorch >= 0.4.1
```bash
python -m pip install -r requirements.txt
```
## Train and Test
* Train/Test Baseline (Bi-LSTM / CRF with 20 % of training dataset) :
```
python naive.py --dataset CONLL
python naive.py --dataset BC5CDR
```
* Train/Test Trigger Matching Network in supervised setting :
```
python supervised.py --dataset CONLL
python supervised.py --dataset BC5CDR
```
* Train/Test Trigger Matching Network in semi-supervised setting (self-training) :
```
python semi_supervised.py --dataset CONLL
python semi_supervised.py --dataset BC5CDR
```
Our code is based on https://github.com/allanj/pytorch_lstmcrf.
[INK Lab](http://inklab.usc.edu/) at USC
================================================
FILE: common/__init__.py
================================================
from common.instance import Instance
from common.sentence import Sentence
================================================
FILE: common/instance.py
================================================
#
# @author: Allan
# edited by Dong-Ho Lee
#
from common.sentence import Sentence
from typing import List
class Instance:
"""
This class is the basic Instance for a datasample
"""
def __init__(self, input: Sentence, output: List[str] = None, embedding = None, trigger_label = None, trigger_positions = None, trigger_key = None) -> None:
"""
Constructor for the instance.
:param input: sentence containing the words
:param output: a list of labels
"""
self.input = input
self.output = output
self.elmo_vec = embedding #used for loading the ELMo vector.
self.word_ids = None
self.char_ids = None
self.output_ids = None
self.is_prediction = None
self.trigger_label = trigger_label
self.trigger_positions = trigger_positions
self.trigger_key = trigger_key
self.trigger_vec = None
self.trigger_matching_label = None
def __len__(self):
return len(self.input)
================================================
FILE: common/sentence.py
================================================
#
# @author: Allan
# edited by Dong-Ho Lee
#
from typing import List
class Sentence:
"""
The class for the input sentence
"""
def __init__(self, words: List[str], pos_tags:List[str] = None):
"""
:param words:
:param pos_tags: By default, it is not required to have the pos tags, in case you need it/
"""
self.words = words
self.pos_tags = pos_tags
def __len__(self):
return len(self.words)
================================================
FILE: config/__init__.py
================================================
from config.config import Config, ContextEmb, PAD, START, STOP
from config.eval import Span, evaluate_batch_insts
from config.reader import Reader
from config.utils import log_sum_exp_pytorch, simple_batching, lr_decay, get_optimizer, write_results, batching_list_instances
================================================
FILE: config/config.py
================================================
#
# @author: Allan
# edited by Dong-Ho Lee
#
import numpy as np
from tqdm import tqdm
from typing import List, Tuple, Dict, Union
from common import Instance
import torch
from enum import Enum
import os
from termcolor import colored
START = "<START>"
STOP = "<STOP>"
PAD = "<PAD>"
UNK = "<UNK>"
class ContextEmb(Enum):
none = 0
elmo = 1
bert = 2 # not support yet
flair = 3 # not support yet
class Config:
def __init__(self, args) -> None:
"""
Construct the arguments and some hyperparameters
:param args:
"""
# Predefined label string.
self.PAD = PAD
self.B = "B-"
self.I = "I-"
self.S = "S-"
self.E = "E-"
self.O = "O"
self.START_TAG = START
self.STOP_TAG = STOP
self.UNK = "<UNK>"
self.unk_id = -1
# Model hyper parameters
self.embedding_file = args.embedding_file
self.embedding_dim = args.embedding_dim
self.context_emb = ContextEmb[args.context_emb]
self.context_emb_size = 0
self.embedding, self.embedding_dim = self.read_pretrain_embedding()
self.word_embedding = None
self.seed = args.seed
self.digit2zero = args.digit2zero
self.hidden_dim = args.hidden_dim
self.rep_hidden_dim = args.hidden_dim
self.use_brnn = True
self.num_layers = 1
self.dropout = args.dropout
self.char_emb_size = 25
self.charlstm_hidden_dim = 50
self.use_char_rnn = args.use_char_rnn
self.use_crf_layer = args.use_crf_layer
# Data specification
self.percentage = args.percentage
self.dataset = args.dataset
self.train_file = "dataset/" + self.dataset + "/train_20.txt"
self.train_all_file = "dataset/" + self.dataset + "/train.txt"
if self.dataset == "Laptop-reviews":
self.dev_file = "dataset/" + self.dataset + "/test.txt"
else:
self.dev_file = "dataset/" + self.dataset + "/dev.txt"
self.test_file = "dataset/" + self.dataset + "/test.txt"
self.trigger_file = "dataset/" + self.dataset + "/trigger_20.txt"
self.label2idx = {}
self.idx2labels = []
self.char2idx = {}
self.idx2char = []
self.num_char = 0
self.train_num = args.train_num
self.dev_num = args.dev_num
self.test_num = args.test_num
# Training hyperparameter
self.model_folder = args.model_folder
self.optimizer = args.optimizer.lower()
self.trig_optimizer = args.trig_optimizer.lower()
self.learning_rate = args.learning_rate
self.momentum = args.momentum
self.l2 = args.l2
self.num_epochs = args.num_epochs
self.num_epochs_soft = args.num_epochs_soft
self.use_dev = True
self.batch_size = args.batch_size
self.clip = 5
self.lr_decay = args.lr_decay
self.device = torch.device(args.device)
self.ds_setting = args.ds_setting
print(self.ds_setting)
def read_pretrain_embedding(self) -> Tuple[Union[Dict[str, np.array], None], int]:
"""
Read the pretrained word embeddings, return the complete embeddings and the embedding dimension
:return:
"""
print("reading the pretraing embedding: %s" % (self.embedding_file))
if self.embedding_file is None:
print("pretrain embedding in None, using random embedding")
return None, self.embedding_dim
else:
exists = os.path.isfile(self.embedding_file)
if not exists:
print(colored("[Warning] pretrain embedding file not exists, using random embedding", 'red'))
return None, self.embedding_dim
# raise FileNotFoundError("The embedding file does not exists")
embedding_dim = -1
embedding = dict()
with open(self.embedding_file, 'r', encoding='utf-8') as file:
for line in tqdm(file.readlines()):
line = line.strip()
if len(line) == 0:
continue
tokens = line.split()
if embedding_dim < 0:
embedding_dim = len(tokens) - 1
else:
# print(tokens)
# print(embedding_dim)
assert (embedding_dim + 1 == len(tokens))
embedd = np.empty([1, embedding_dim])
embedd[:] = tokens[1:]
first_col = tokens[0]
embedding[first_col] = embedd
return embedding, embedding_dim
def build_word_idx(self, train_insts: List[Instance], dev_insts: List[Instance] = None, test_insts: List[Instance] = None) -> None:
"""
Build the vocab 2 idx for all instances
:param train_insts:
:param dev_insts:
:param test_insts:
:return:
"""
self.word2idx = dict()
self.idx2word = []
self.word2idx[self.PAD] = 0
self.idx2word.append(self.PAD)
self.word2idx[self.UNK] = 1
self.unk_id = 1
self.idx2word.append(self.UNK)
self.char2idx[self.PAD] = 0
self.idx2char.append(self.PAD)
self.char2idx[self.UNK] = 1
self.idx2char.append(self.UNK)
# extract char on train, dev, test
if dev_insts is not None and test_insts is not None:
whole_sets = train_insts + dev_insts + test_insts
else:
whole_sets = train_insts
for inst in whole_sets:
for word in inst.input.words:
if word not in self.word2idx:
self.word2idx[word] = len(self.word2idx)
self.idx2word.append(word)
# extract char only on train (doesn't matter for dev and test)
for inst in train_insts:
for word in inst.input.words:
for c in word:
if c not in self.char2idx:
self.char2idx[c] = len(self.idx2char)
self.idx2char.append(c)
self.num_char = len(self.idx2char)
def add_word_idx(self, match_insts):
for inst in match_insts:
for word in inst.input.words:
if word not in self.word2idx:
self.word2idx[word] = len(self.word2idx)
self.idx2word.append(word)
def build_emb_table(self) -> None:
"""
build the embedding table with pretrained word embeddings (if given otherwise, use random embeddings)
:return:
"""
print("Building the embedding table for vocabulary...")
scale = np.sqrt(3.0 / self.embedding_dim)
if self.embedding is not None:
print("[Info] Use the pretrained word embedding to initialize: %d x %d" % (len(self.word2idx), self.embedding_dim))
self.word_embedding = np.empty([len(self.word2idx), self.embedding_dim])
for word in self.word2idx:
if word in self.embedding:
self.word_embedding[self.word2idx[word], :] = self.embedding[word]
elif word.lower() in self.embedding:
self.word_embedding[self.word2idx[word], :] = self.embedding[word.lower()]
else:
# self.word_embedding[self.word2idx[word], :] = self.embedding[self.UNK]
self.word_embedding[self.word2idx[word], :] = np.random.uniform(-scale, scale, [1, self.embedding_dim])
else:
self.word_embedding = np.empty([len(self.word2idx), self.embedding_dim])
for word in self.word2idx:
self.word_embedding[self.word2idx[word], :] = np.random.uniform(-scale, scale, [1, self.embedding_dim])
def build_label_idx(self, insts: List[Instance]) -> None:
"""
Build the mapping from label to index and index to labels.
:param insts: list of instances.
:return:
"""
#self.triggerlabel = {}
self.label2idx[self.PAD] = len(self.label2idx)
self.idx2labels.append(self.PAD)
for inst in insts:
for label in inst.output:
if label not in self.label2idx:
self.idx2labels.append(label)
self.label2idx[label] = len(self.label2idx)
#if label not in [START,STOP,PAD,UNK,'O','T'] and label.split('-')[1] not in self.triggerlabel:
# self.triggerlabel[label.split('-')[1]] = len(self.triggerlabel)
self.label2idx[self.START_TAG] = len(self.label2idx)
self.idx2labels.append(self.START_TAG)
self.label2idx[self.STOP_TAG] = len(self.label2idx)
self.idx2labels.append(self.STOP_TAG)
self.label_size = len(self.label2idx)
#self.trig_label_size = len(self.triggerlabel)
self.start_label_id = self.label2idx[self.START_TAG]
self.stop_label_id = self.label2idx[self.STOP_TAG]
print("#labels: {}".format(self.label_size))
print("label 2idx: {}".format(self.label2idx))
def use_iobes(self, insts: List[Instance]) -> None:
"""
Use IOBES tagging schema to replace the IOB tagging schema in the instance
:param insts:
:return:
"""
for inst in insts:
output = inst.output
for pos in range(len(inst)):
curr_entity = output[pos]
if pos == len(inst) - 1:
if curr_entity.startswith(self.B):
output[pos] = curr_entity.replace(self.B, self.S)
elif curr_entity.startswith(self.I):
output[pos] = curr_entity.replace(self.I, self.E)
else:
next_entity = output[pos + 1]
if curr_entity.startswith(self.B):
if next_entity.startswith(self.O) or next_entity.startswith(self.B):
output[pos] = curr_entity.replace(self.B, self.S)
elif curr_entity.startswith(self.I):
if next_entity.startswith(self.O) or next_entity.startswith(self.B):
output[pos] = curr_entity.replace(self.I, self.E)
def map_insts_ids(self, insts: List[Instance]):
"""
Create id for word, char and label in each instance.
:param insts:
:return:
"""
for inst in insts:
words = inst.input.words
inst.word_ids = []
inst.char_ids = []
inst.output_ids = [] if inst.output else None
for word in words:
if word in self.word2idx:
inst.word_ids.append(self.word2idx[word])
else:
inst.word_ids.append(self.word2idx[self.UNK])
char_id = []
for c in word:
if c in self.char2idx:
char_id.append(self.char2idx[c])
else:
char_id.append(self.char2idx[self.UNK])
inst.char_ids.append(char_id)
if inst.output:
for label in inst.output:
if label in self.label2idx:
inst.output_ids.append(self.label2idx[label])
else:
inst.output_ids.append(self.label2idx['O'])
================================================
FILE: config/eval.py
================================================
#
# @author: Allan
# edited by Dong-Ho Lee
#
import numpy as np
from overrides import overrides
from typing import List
from common import Instance
import torch
class Span:
"""
A class of `Span` where we use it during evaluation.
We construct spans for the convenience of evaluation.
"""
def __init__(self, left: int, right: int, type: str):
"""
A span compose of left, right (inclusive) and its entity label.
:param left:
:param right: inclusive.
:param type:
"""
self.left = left
self.right = right
self.type = type
def __eq__(self, other):
return self.left == other.left and self.right == other.right and self.type == other.type
def __hash__(self):
return hash((self.left, self.right, self.type))
def evaluate_batch_insts(batch_insts: List[Instance],
batch_pred_ids: torch.LongTensor,
batch_gold_ids: torch.LongTensor,
word_seq_lens: torch.LongTensor,
idx2label: List[str],
use_crf_layer: bool = True) -> np.ndarray:
"""
Evaluate a batch of instances and handling the padding positions.
:param batch_insts: a batched of instances.
:param batch_pred_ids: Shape: (batch_size, max_length) prediction ids from the viterbi algorithm.
:param batch_gold_ids: Shape: (batch_size, max_length) gold ids.
:param word_seq_lens: Shape: (batch_size) the length for each instance.
:param idx2label: The idx to label mapping.
:return: numpy array containing (number of true positive, number of all positive, number of true positive + number of false negative)
You can also refer as (number of correctly predicted entities, number of entities predicted, number of entities in the dataset)
"""
p = 0
total_entity = 0
total_predict = 0
word_seq_lens = word_seq_lens.tolist()
for idx in range(len(batch_pred_ids)):
length = word_seq_lens[idx]
output = batch_gold_ids[idx][:length].tolist()
prediction = batch_pred_ids[idx][:length].tolist()
prediction = prediction[::-1] if use_crf_layer else prediction
output = [idx2label[l] for l in output]
prediction =[idx2label[l] for l in prediction]
batch_insts[idx].prediction = prediction
#convert to span
output_spans = set()
start = -1
for i in range(len(output)):
if output[i].startswith("B-"):
start = i
if output[i].startswith("E-"):
end = i
output_spans.add(Span(start, end, output[i][2:]))
if output[i].startswith("S-"):
output_spans.add(Span(i, i, output[i][2:]))
predict_spans = set()
for i in range(len(prediction)):
if prediction[i].startswith("B-"):
start = i
if prediction[i].startswith("E-"):
end = i
predict_spans.add(Span(start, end, prediction[i][2:]))
if prediction[i].startswith("S-"):
predict_spans.add(Span(i, i, prediction[i][2:]))
total_entity += len(output_spans)
total_predict += len(predict_spans)
p += len(predict_spans.intersection(output_spans))
# In case you need the following code for calculating the p/r/f in a batch.
# (When your batch is the complete dataset)
# precision = p * 1.0 / total_predict * 100 if total_predict != 0 else 0
# recall = p * 1.0 / total_entity * 100 if total_entity != 0 else 0
# fscore = 2.0 * precision * recall / (precision + recall) if precision != 0 or recall != 0 else 0
return np.asarray([p, total_predict, total_entity], dtype=int)
================================================
FILE: config/reader.py
================================================
#
# @author: Allan
# edited by Dong-Ho Lee
#
from tqdm import tqdm
from common import Sentence, Instance
from typing import List
import re
from copy import deepcopy
import random
random.seed(1337)
class Reader:
def __init__(self, digit2zero:bool=True):
"""
Read the dataset into Instance
:param digit2zero: convert the digits into 0, which is a common practice for LSTM-CRF.
"""
self.digit2zero = digit2zero
self.vocab = set()
def read_txt(self, file: str, number: int = -1) -> List[Instance]:
print("Reading file: " + file)
insts = []
with open(file, 'r', encoding='utf-8') as f:
words = []
labels = []
for line in tqdm(f.readlines()):
line = line.rstrip()
if line == "":
insts.append(Instance(Sentence(words), labels))
words = []
labels = []
if len(insts) == number:
break
continue
word, label = line.split()
if self.digit2zero:
word = re.sub('\d', '0', word) # replace digit with 0.
words.append(word)
self.vocab.add(word)
labels.append(label)
print("number of sentences: {}".format(len(insts)))
return insts
def read_trigger_txt(self, file: str, percentage, number: int = -1) -> List[Instance]:
label_vocab = dict()
print("Reading file: " + file)
insts = []
max_length = 0
with open(file, 'r', encoding='utf-8') as f:
words = []
labels = []
word_index = 0
for line in tqdm(f.readlines()):
line = line.rstrip()
if line == "":
# check the sequence of index to find entity which consists of multiple words
entity_dict = dict()
for ent in labels:
if ent[0].startswith("B-") or ent[0].startswith("I-") or ent[0].startswith("T-"):
if ent[0].split("-")[1] not in entity_dict:
entity_dict[ent[0].split("-")[1]] = [[words[ent[1]], ent[1]]]
else:
entity_dict[ent[0].split("-")[1]].append([words[ent[1]], ent[1]])
# entity word, index, type
trigger_positions = []
trigger_keys = []
for key in entity_dict:
if key in ['0','1','2','3','4','5','6','7','8','9']:
trigger_positions.append([i[1] for i in entity_dict[key]])
trigger_keys.append(" ".join(i[0] for i in entity_dict[key]))
else:
if key not in label_vocab:
label_vocab[key] = len(label_vocab)
trigger_label = label_vocab[key]
final_labels = []
for label in labels:
if label[0].startswith("T"):
final_labels.append("O")
else:
final_labels.append(label[0])
for trigger_position, trigger_key in zip(trigger_positions, trigger_keys):
insts.append(Instance(Sentence(words), final_labels, None, trigger_label, trigger_position, trigger_key))
#insts.append(Instance(Sentence(words), labels, None, trigger_label, trigger_positions))
if len(words) > max_length:
max_length = len(words)
words = []
labels = []
word_index = 0
if len(insts) == number:
break
continue
word, label = line.split()
if self.digit2zero:
word = re.sub('\d', '0', word) # replace digit with 0.
words.append(word)
self.vocab.add(word)
labels.append([label, word_index])
word_index += 1
print("number of sentences: {}".format(len(insts)))
return insts, max_length, len(label_vocab)
def merge_labels(self, dataset):
inst_dictionary = dict()
for inst in dataset:
key = " ".join(word for word in inst.input.words)
if key not in inst_dictionary:
inst_dictionary[key] = [inst]
else:
inst_dictionary[key].append(inst)
for key in inst_dictionary:
candidate_labels = []
for inst in inst_dictionary[key]:
candidate_labels.append(inst.output)
final_labels = []
for j in range(len(candidate_labels[0])):
is_entity = False
for i in range(len(candidate_labels)):
if candidate_labels[i][j] != 'O':
final_labels.append(candidate_labels[i][j])
is_entity = True
break
if is_entity == False:
final_labels.append('O')
for inst in inst_dictionary[key]:
inst.output = final_labels
def trigger_percentage(self, dataset, percentage):
inst_dictionary = dict()
for inst in dataset:
key = " ".join(word for word in inst.input.words)
if key not in inst_dictionary:
inst_dictionary[key] = [inst]
else:
inst_dictionary[key].append(inst)
numbers = int(len(inst_dictionary) * percentage / 100)
new_inst_keys = list(inst_dictionary.keys())
random.shuffle(new_inst_keys)
new_inst_keys = new_inst_keys[:numbers]
new_inst = []
for key in new_inst_keys:
new_inst.extend(inst_dictionary[key])
return new_inst
================================================
FILE: config/utils.py
================================================
#
# @author: Allan
# edited by Dong-Ho Lee
#
from typing import List
from common import Instance
import torch.optim as optim
import pickle
import os.path
from config import PAD, ContextEmb, Config
from termcolor import colored
import torch
import torch.nn as nn
def log_sum_exp_pytorch(vec: torch.Tensor) -> torch.Tensor:
"""
Calculate the log_sum_exp trick for the tensor.
:param vec: [batchSize * from_label * to_label].
:return: [batchSize * to_label]
"""
maxScores, idx = torch.max(vec, 1)
maxScores[maxScores == -float("Inf")] = 0
maxScoresExpanded = maxScores.view(vec.shape[0] ,1 , vec.shape[2]).expand(vec.shape[0], vec.shape[1], vec.shape[2])
return maxScores + torch.log(torch.sum(torch.exp(vec - maxScoresExpanded), 1))
def batching_list_instances(config: Config, insts: List[Instance], is_soft=False, is_naive=False):
train_num = len(insts)
batch_size = config.batch_size
total_batch = train_num // batch_size + 1 if train_num % batch_size != 0 else train_num // batch_size
batched_data = []
for batch_id in range(total_batch):
one_batch_insts = insts[batch_id * batch_size:(batch_id + 1) * batch_size]
batched_data.append(simple_batching(config, one_batch_insts, is_soft, is_naive))
return batched_data
def simple_batching(config, insts: List[Instance], is_soft=False, is_naive=False):
batch_size = len(insts)
batch_data = insts
label_size = config.label_size
word_seq_len = torch.LongTensor(list(map(lambda inst: len(inst.input.words), batch_data)))
max_seq_len = word_seq_len.max()
char_seq_len = torch.LongTensor([list(map(len, inst.input.words)) + [1] * (int(max_seq_len) - len(inst.input.words)) for inst in batch_data])
max_char_seq_len = char_seq_len.max()
context_emb_tensor = None
if config.context_emb != ContextEmb.none:
emb_size = insts[0].elmo_vec.shape[1]
context_emb_tensor = torch.zeros((batch_size, max_seq_len, emb_size))
word_seq_tensor = torch.zeros((batch_size, max_seq_len), dtype=torch.long)
label_seq_tensor = torch.zeros((batch_size, max_seq_len), dtype=torch.long)
char_seq_tensor = torch.zeros((batch_size, max_seq_len, max_char_seq_len), dtype=torch.long)
annotation_mask = None
if batch_data[0].is_prediction is not None:
annotation_mask = torch.zeros((batch_size, max_seq_len, label_size), dtype=torch.long)
trigger_label_seq_tensor = None
if batch_data[0].trigger_label is not None and is_naive == False:
trigger_label_seq_tensor = torch.LongTensor(list(map(lambda inst: inst.trigger_label, batch_data)))
trigger_vec_tensor = None
if batch_data[0].trigger_vec is not None and is_naive == False:
trigger_vec_tensor = []
for idx in range(batch_size):
word_seq_tensor[idx, :word_seq_len[idx]] = torch.LongTensor(batch_data[idx].word_ids)
if batch_data[idx].output_ids:
label_seq_tensor[idx, :word_seq_len[idx]] = torch.LongTensor(batch_data[idx].output_ids)
if config.context_emb != ContextEmb.none:
context_emb_tensor[idx, :word_seq_len[idx], :] = batch_data[idx].elmo_vec[1:batch_data[idx].elmo_vec.shape[0] - 1, :]
if batch_data[idx].is_prediction is not None:
for pos in range(len(batch_data[idx].input)):
if batch_data[idx].is_prediction[pos]:
annotation_mask[idx, pos, :] = 1
annotation_mask[idx, pos, config.start_label_id] = 0
annotation_mask[idx, pos, config.stop_label_id] = 0
else:
annotation_mask[idx, pos, batch_data[idx].output_ids[pos]] = 1
annotation_mask[idx, word_seq_len[idx]:, :] = 1
for word_idx in range(word_seq_len[idx]):
char_seq_tensor[idx, word_idx, :char_seq_len[idx, word_idx]] = torch.LongTensor(batch_data[idx].char_ids[word_idx])
for wordIdx in range(word_seq_len[idx], max_seq_len):
char_seq_tensor[idx, wordIdx, 0: 1] = torch.LongTensor([config.char2idx[PAD]])
if batch_data[idx].trigger_vec is not None and is_naive == False:
trigger_vec_tensor.append(batch_data[idx].trigger_vec)
word_seq_tensor = word_seq_tensor.to(config.device)
label_seq_tensor = label_seq_tensor.to(config.device)
char_seq_tensor = char_seq_tensor.to(config.device)
word_seq_len = word_seq_len.to(config.device)
char_seq_len = char_seq_len.to(config.device)
annotation_mask = annotation_mask.to(config.device) if annotation_mask is not None else None
trigger_label_seq_tensor = trigger_label_seq_tensor.to(config.device) if trigger_label_seq_tensor is not None else None
trigger_position_seq_tensor = [batch_data[idx].trigger_positions for idx in range(batch_size)] if batch_data[0].trigger_positions is not None else None
if is_soft:
return word_seq_tensor, word_seq_len, context_emb_tensor, char_seq_tensor, char_seq_len, annotation_mask, label_seq_tensor, torch.stack(trigger_vec_tensor)
else:
return word_seq_tensor, word_seq_len, context_emb_tensor, char_seq_tensor, char_seq_len, annotation_mask, label_seq_tensor, trigger_position_seq_tensor, trigger_label_seq_tensor
def lr_decay(config, optimizer: optim.Optimizer, epoch: int) -> optim.Optimizer:
"""
Method to decay the learning rate
:param config: configuration
:param optimizer: optimizer
:param epoch: epoch number
:return:
"""
lr = config.learning_rate / (1 + config.lr_decay * (epoch - 1))
for param_group in optimizer.param_groups:
param_group['lr'] = lr
print('learning rate is set to: ', lr)
return optimizer
def load_bert_vec(file: str, insts: List[Instance]):
if os.path.exists(file.split('.')[0]+'.vec'):
f = open(file.split('.')[0]+'.vec', 'rb')
bert_embedding = pickle.load(f)
f.close()
size = 0
for vec, inst in zip(bert_embedding, insts):
inst.elmo_vec = vec
size = vec.shape[1]
assert (vec.shape[0] == len(inst.input.words)+2)
return size
else:
f = open(file.split('.')[0]+'.vec', 'wb')
sentence_list = []
for sent in insts:
sentence = " ".join(str(w) for w in sent.input.words)
sentence_list.append(sentence)
sentence_list = tuple(sentence_list)
bert_embedding = get_bert_embedding(sentence_list)
pickle.dump(bert_embedding, f)
f.close()
size = 0
for vec, inst in zip(bert_embedding, insts):
inst.elmo_vec = vec
size = vec.shape[1]
assert (vec.shape[0] == len(inst.input.words)+2)
return size
def get_bert_embedding(batch):
tokenizer = BertTokenizer.from_pretrained('bert-base-uncased', do_lower_case=True)
bert = BertModel.from_pretrained('bert-base-uncased')
final_dataset = []
for sentence in tqdm(batch):
tokenized_sentence = ["[CLS]"] + tokenizer.tokenize(sentence) + ["[SEP]"]
# pooling operation (BERT - first)
isSubword = False
firstSubwordList = []
for t_id, token in enumerate(tokenized_sentence):
if token.startswith("#") == False:
isSubword = False
firstSubwordList.append(t_id)
if isSubword:
continue
if token.startswith("#"):
isSubword = True
input_ids = torch.tensor(tokenizer.convert_tokens_to_ids(tokenized_sentence)).unsqueeze(0)
outputs = bert(input_ids)
embeddings = outputs[0][0]
sentence_embedding = tuple()
for ind in firstSubwordList:
sentence_embedding = sentence_embedding + (embeddings[:, ind, :],)
sentence_embedding = torch.cat(sentence_embedding, dim=0)
final_dataset.append(sentence_embedding)
return final_dataset
def get_optimizer(config: Config, model: nn.Module, name=None):
params = model.parameters()
if name is not None and name == "adam":
print(colored("Using Adam", 'yellow'))
return optim.Adam(params)
elif name is not None and name == "sgd":
print(
colored("Using SGD: lr is: {}, L2 regularization is: {}".format(config.learning_rate, config.l2), 'yellow'))
return optim.SGD(params, lr=config.learning_rate, weight_decay=float(config.l2))
elif config.optimizer.lower() == "sgd":
print(
colored("Using SGD: lr is: {}, L2 regularization is: {}".format(config.learning_rate, config.l2), 'yellow'))
return optim.SGD(params, lr=config.learning_rate, weight_decay=float(config.l2))
elif config.optimizer.lower() == "adam":
print(colored("Using Adam", 'yellow'))
return optim.Adam(params)
else:
print("Illegal optimizer: {}".format(config.optimizer))
exit(1)
def write_results(filename: str, insts):
f = open(filename, 'w', encoding='utf-8')
for inst in insts:
for i in range(len(inst.input)):
words = inst.input.words
output = inst.output
prediction = inst.prediction
assert len(output) == len(prediction)
f.write("{}\t{}\t{}\t{}\n".format(i, words[i], output[i], prediction[i]))
f.write("\n")
f.close()
================================================
FILE: dataset/BC5CDR/dev.txt
================================================
22 B-Chemical
- I-Chemical
oxacalcitriol I-Chemical
suppresses O
secondary B-Disease
hyperparathyroidism I-Disease
without O
inducing O
low B-Disease
bone I-Disease
turnover I-Disease
in O
dogs O
with O
renal B-Disease
failure I-Disease
. O
BACKGROUND O
: O
Calcitriol B-Chemical
therapy O
suppresses O
serum O
levels O
of O
parathyroid O
hormone O
( O
PTH O
) O
in O
patients O
with O
renal B-Disease
failure I-Disease
but O
has O
several O
drawbacks O
, O
including O
hypercalcemia B-Disease
and O
/ O
or O
marked O
suppression B-Disease
of I-Disease
bone I-Disease
turnover I-Disease
, O
which O
may O
lead O
to O
adynamic B-Disease
bone I-Disease
disease I-Disease
. O
A O
new O
vitamin B-Chemical
D I-Chemical
analogue O
, O
22 B-Chemical
- I-Chemical
oxacalcitriol I-Chemical
( O
OCT B-Chemical
) O
, O
has O
been O
shown O
to O
have O
promising O
characteristics O
. O
This O
study O
was O
undertaken O
to O
determine O
the O
effects O
of O
OCT B-Chemical
on O
serum O
PTH O
levels O
and O
bone O
turnover O
in O
states O
of O
normal O
or O
impaired B-Disease
renal I-Disease
function I-Disease
. O
METHODS O
: O
Sixty O
dogs O
were O
either O
nephrectomized O
( O
Nx O
, O
N O
= O
38 O
) O
or O
sham O
- O
operated O
( O
Sham O
, O
N O
= O
22 O
) O
. O
The O
animals O
received O
supplemental O
phosphate B-Chemical
to O
enhance O
PTH O
secretion O
. O
Fourteen O
weeks O
after O
the O
start O
of O
phosphate B-Chemical
supplementation O
, O
half O
of O
the O
Nx O
and O
Sham O
dogs O
received O
doses O
of O
OCT B-Chemical
( O
three O
times O
per O
week O
) O
; O
the O
other O
half O
were O
given O
vehicle O
for O
60 O
weeks O
. O
Thereafter O
, O
the O
treatment O
modalities O
for O
a O
subset O
of O
animals O
were O
crossed O
over O
for O
an O
additional O
eight O
months O
. O
Biochemical O
and O
hormonal O
indices O
of O
calcium B-Chemical
and O
bone O
metabolism O
were O
measured O
throughout O
the O
study O
, O
and O
bone O
biopsies O
were O
done O
at O
baseline O
, O
60 O
weeks O
after O
OCT B-Chemical
or O
vehicle O
treatment O
, O
and O
at O
the O
end O
of O
the O
crossover O
period O
. O
RESULTS O
: O
In O
Nx O
dogs O
, O
OCT B-Chemical
significantly O
decreased O
serum O
PTH O
levels O
soon O
after O
the O
induction O
of O
renal B-Disease
insufficiency I-Disease
. O
In O
long O
- O
standing O
secondary B-Disease
hyperparathyroidism I-Disease
, O
OCT B-Chemical
( O
0 O
. O
03 O
microg O
/ O
kg O
) O
stabilized O
serum O
PTH O
levels O
during O
the O
first O
months O
. O
Serum O
PTH O
levels O
rose O
thereafter O
, O
but O
the O
rise O
was O
less O
pronounced O
compared O
with O
baseline O
than O
the O
rise O
seen O
in O
Nx O
control O
. O
These O
effects O
were O
accompanied O
by O
episodes O
of O
hypercalcemia B-Disease
and O
hyperphosphatemia B-Disease
. O
In O
animals O
with O
normal O
renal O
function O
, O
OCT B-Chemical
induced O
a O
transient O
decrease O
in O
serum O
PTH O
levels O
at O
a O
dose O
of O
0 O
. O
1 O
microg O
/ O
kg O
, O
which O
was O
not O
sustained O
with O
lowering O
of O
the O
doses O
. O
In O
Nx O
dogs O
, O
OCT B-Chemical
reversed O
abnormal O
bone O
formation O
, O
such O
as O
woven B-Disease
osteoid I-Disease
and O
fibrosis B-Disease
, O
but O
did O
not O
significantly O
alter O
the O
level O
of O
bone O
turnover O
. O
In O
addition O
, O
OCT B-Chemical
improved O
mineralization O
lag O
time O
, O
( O
that O
is O
, O
the O
rate O
at O
which O
osteoid O
mineralizes O
) O
in O
both O
Nx O
and O
Sham O
dogs O
. O
CONCLUSIONS O
: O
These O
results O
indicate O
that O
even O
though O
OCT B-Chemical
does O
not O
completely O
prevent O
the O
occurrence O
of O
hypercalcemia B-Disease
in O
experimental O
dogs O
with O
renal B-Disease
insufficiency I-Disease
, O
it O
may O
be O
of O
use O
in O
the O
management O
of O
secondary B-Disease
hyperparathyroidism I-Disease
because O
it O
does O
not O
induce O
low B-Disease
bone I-Disease
turnover I-Disease
and O
, O
therefore O
, O
does O
not O
increase O
the O
risk O
of O
adynamic B-Disease
bone I-Disease
disease I-Disease
. O
Hypotension B-Disease
, O
bradycardia B-Disease
, O
and O
asystole B-Disease
after O
high O
- O
dose O
intravenous O
methylprednisolone B-Chemical
in O
a O
monitored O
patient O
. O
We O
report O
a O
case O
of O
hypotension B-Disease
, O
bradycardia B-Disease
, O
and O
asystole B-Disease
after O
intravenous O
administration O
of O
high O
- O
dose O
methylprednisolone B-Chemical
in O
a O
73 O
- O
year O
- O
old O
patient O
who O
underwent O
electrocardiographic O
( O
ECG O
) O
monitoring O
throughout O
the O
episode O
. O
There O
was O
a O
history O
of O
ischemic B-Disease
cardiac B-Disease
disease I-Disease
9 O
years O
earlier O
. O
The O
patient O
was O
admitted O
with O
a O
pulmonary B-Disease
- I-Disease
renal I-Disease
syndrome I-Disease
with O
hemoptysis B-Disease
, O
rapidly O
progressive O
renal B-Disease
failure I-Disease
, O
and O
hypoxemia B-Disease
that O
required O
mechanical O
ventilation O
in O
the O
intensive O
care O
unit O
. O
After O
receiving O
advanced O
cardiopulmonary O
resuscitation O
, O
the O
patient O
recovered O
cardiac O
rhythm O
. O
The O
ECG O
showed O
a O
junctional O
rhythm O
without O
ventricular B-Disease
arrhythmia I-Disease
. O
This O
study O
reviews O
the O
current O
proposed O
mechanisms O
of O
sudden B-Disease
death I-Disease
after O
a O
high O
dose O
of O
intravenous O
methylprednisolone B-Chemical
( O
IVMP B-Chemical
) O
. O
These O
mechanisms O
are O
not O
well O
understood O
because O
, O
in O
most O
cases O
, O
the O
patients O
were O
not O
monitored O
at O
the O
moment O
of O
the O
event O
. O
Rapid O
infusion O
and O
underlying O
cardiac B-Disease
disease I-Disease
were O
important O
risk O
factors O
in O
the O
case O
reported O
here O
, O
and O
the O
authors O
discount O
ventricular B-Disease
arrhythmia I-Disease
as O
the O
main O
mechanism O
. O
Worsening O
of O
levodopa B-Chemical
- O
induced O
dyskinesias B-Disease
by O
motor O
and O
mental O
tasks O
. O
Ten O
patients O
who O
had O
Parkinson B-Disease
' I-Disease
s I-Disease
disease I-Disease
with O
disabling O
dyskinesia B-Disease
were O
included O
in O
this O
study O
to O
evaluate O
the O
role O
of O
mental O
( O
mental O
calculation O
) O
and O
motor O
( O
flexion O
/ O
extension O
of O
right O
fingers O
, O
flexion O
/ O
extension O
of O
left O
fingers O
, O
flexion O
/ O
extension O
of O
the O
neck O
, O
speaking O
aloud O
) O
tasks O
on O
the O
worsening O
of O
peak O
- O
dose O
dyskinesia B-Disease
following O
administration O
of O
an O
effective O
single O
dose O
of O
apomorphine B-Chemical
. O
Compared O
with O
the O
score O
at O
rest O
( O
1 O
. O
3 O
+ O
/ O
- O
0 O
. O
3 O
) O
, O
a O
significant O
aggravation O
of O
the O
dyskinesia B-Disease
score O
was O
observed O
during O
speaking O
aloud O
( O
5 O
. O
2 O
+ O
/ O
- O
1 O
. O
1 O
, O
p O
< O
0 O
. O
05 O
) O
, O
movements O
of O
right O
( O
4 O
. O
5 O
+ O
/ O
- O
1 O
. O
0 O
, O
p O
< O
0 O
. O
05 O
) O
and O
left O
( O
3 O
. O
7 O
+ O
/ O
- O
0 O
. O
8 O
, O
p O
< O
0 O
. O
05 O
) O
fingers O
, O
movements O
of O
the O
neck O
( O
5 O
. O
1 O
+ O
/ O
- O
1 O
. O
0 O
, O
p O
< O
0 O
. O
05 O
) O
, O
and O
mental O
calculation O
( O
3 O
. O
1 O
+ O
/ O
- O
1 O
. O
0 O
, O
p O
< O
0 O
. O
05 O
) O
. O
These O
results O
suggest O
that O
activation O
tasks O
such O
as O
" O
speaking O
aloud O
" O
could O
be O
used O
for O
objective O
assessment O
of O
dyskinesia B-Disease
severity O
. O
Urine O
N O
- O
acetyl O
- O
beta O
- O
D O
- O
glucosaminidase O
- O
- O
a O
marker O
of O
tubular O
damage O
? O
BACKGROUND O
: O
Although O
an O
indicator O
of O
renal B-Disease
tubular I-Disease
dysfunction I-Disease
, O
an O
increased O
urinary O
N O
- O
acetyl O
- O
beta O
- O
D O
- O
glucosaminidase O
( O
NAG O
) O
activity O
might O
reflect O
increased O
lysosomal O
activity O
in O
renal O
tubular O
cells O
. O
METHODS O
: O
Puromycin B-Chemical
aminonucleoside I-Chemical
( O
PAN B-Chemical
) O
was O
administered O
to O
Sprague O
Dawley O
rats O
to O
induce O
proteinuria B-Disease
. O
Total O
protein O
, O
albumin O
, O
NAG O
activity O
and O
protein O
electrophoretic O
pattern O
were O
assessed O
in O
daily O
urine O
samples O
for O
33 O
days O
. O
The O
morphological O
appearance O
of O
the O
kidneys O
was O
examined O
on O
days O
three O
, O
four O
, O
six O
, O
eight O
and O
thirty O
three O
and O
the O
NAG O
isoenzyme O
patterns O
on O
days O
zero O
, O
four O
, O
eight O
and O
thirty O
three O
. O
RESULTS O
: O
Following O
intravenous O
PAN B-Chemical
urine O
volume O
and O
urine O
NAG O
activity O
increased O
significantly O
by O
day O
two O
, O
but O
returned O
to O
normal O
by O
day O
four O
. O
After O
day O
four O
all O
treated O
animals O
exhibited O
a O
marked O
rise O
in O
urine O
albumin O
, O
total O
protein O
excretion O
and O
NAG O
activity O
. O
Electrophoresis O
showed O
a O
generalised O
increase O
in O
middle O
and O
high O
molecular O
weight O
urine O
proteins O
from O
day O
four O
onwards O
. O
Protein O
droplets O
first O
appeared O
prominent O
in O
tubular O
cells O
on O
day O
four O
. O
Peak O
urine O
NAG O
activity O
and O
a O
change O
in O
NAG O
isoenzyme O
pattern O
coincided O
with O
both O
the O
peak O
proteinuria B-Disease
and O
the O
reduction O
in O
intracellular O
protein O
and O
NAG O
droplets O
( O
day O
six O
onwards O
) O
. O
CONCLUSIONS O
: O
This O
animal O
model O
demonstrates O
that O
an O
increase O
in O
lysosomal O
turnover O
and O
hence O
urine O
NAG O
activity O
, O
occurs O
when O
increased O
protein O
is O
presented O
to O
the O
tubular O
cells O
. O
Urine O
NAG O
activity O
is O
thus O
a O
measure O
of O
altered O
function O
in O
the O
renal O
tubules O
and O
not O
simply O
an O
indicator O
of O
damage O
. O
Cauda B-Disease
equina I-Disease
syndrome I-Disease
after O
spinal O
anaesthesia O
with O
hyperbaric O
5 O
% O
lignocaine B-Chemical
: O
a O
review O
of O
six O
cases O
of O
cauda B-Disease
equina I-Disease
syndrome I-Disease
reported O
to O
the O
Swedish O
Pharmaceutical O
Insurance O
1993 O
- O
1997 O
. O
Six O
cases O
of O
cauda B-Disease
equina I-Disease
syndrome I-Disease
with O
varying O
severity O
were O
reported O
to O
the O
Swedish O
Pharmaceutical O
Insurance O
during O
the O
period O
1993 O
- O
1997 O
. O
All O
were O
associated O
with O
spinal O
anaesthesia O
using O
hyperbaric O
5 O
% O
lignocaine B-Chemical
. O
Five O
cases O
had O
single O
- O
shot O
spinal O
anaesthesia O
and O
one O
had O
a O
repeat O
spinal O
anaesthetic O
due O
to O
inadequate O
block O
. O
The O
dose O
of O
hyperbaric O
5 O
% O
lignocaine B-Chemical
administered O
ranged O
from O
60 O
to O
120 O
mg O
. O
Three O
of O
the O
cases O
were O
most O
likely O
caused O
by O
direct O
neurotoxicity B-Disease
of O
hyperbaric O
5 O
% O
lignocaine B-Chemical
. O
In O
the O
other O
3 O
cases O
, O
direct O
neurotoxicity B-Disease
was O
also O
probable O
, O
but O
unfortunately O
radiological O
investigations O
were O
not O
done O
to O
definitely O
exclude O
a O
compressive O
aetiology O
. O
All O
cases O
sustained O
permanent O
neurological B-Disease
deficits I-Disease
. O
We O
recommend O
that O
hyperbaric O
lignocaine B-Chemical
should O
be O
administered O
in O
concentrations O
not O
greater O
than O
2 O
% O
and O
at O
a O
total O
dose O
preferably O
not O
exceeding O
60 O
mg O
. O
Systemic O
toxicity B-Disease
following O
administration O
of O
sirolimus B-Chemical
( O
formerly O
rapamycin B-Chemical
) O
for O
psoriasis B-Disease
: O
association O
of O
capillary B-Disease
leak I-Disease
syndrome I-Disease
with O
apoptosis O
of O
lesional O
lymphocytes O
. O
BACKGROUND O
: O
Sirolimus B-Chemical
( O
formerly O
rapamycin B-Chemical
) O
is O
an O
immunosuppressive O
agent O
that O
interferes O
with O
T O
- O
cell O
activation O
. O
After O
2 O
individuals O
with O
psoriasis B-Disease
developed O
a O
capillary B-Disease
leak I-Disease
syndrome I-Disease
following O
treatment O
with O
oral O
sirolimus B-Chemical
lesional O
skin O
cells O
and O
activated O
peripheral O
blood O
cells O
were O
analyzed O
for O
induction O
of O
apoptosis O
. O
OBSERVATIONS O
: O
A O
keratome O
skin O
specimen O
from O
1 O
patient O
with O
sirolimus B-Chemical
- O
induced O
capillary B-Disease
leak I-Disease
syndrome I-Disease
had O
a O
2 O
. O
3 O
- O
fold O
increase O
in O
percentage O
of O
apoptotic O
cells O
( O
to O
48 O
% O
) O
compared O
with O
an O
unaffected O
sirolimus B-Chemical
- O
treated O
patient O
with O
psoriasis B-Disease
( O
21 O
% O
) O
. O
Activated O
peripheral O
blood O
T O
cells O
from O
patients O
with O
psoriasis B-Disease
tended O
to O
exhibit O
greater O
spontaneous O
or O
dexamethasone B-Chemical
- O
induced O
apoptosis O
than O
did O
normal O
T O
cells O
, O
particularly O
in O
the O
presence O
of O
sirolimus B-Chemical
. O
CONCLUSIONS O
: O
Severe O
adverse O
effects O
of O
sirolimus B-Chemical
include O
fever B-Disease
, O
anemia B-Disease
, O
and O
capillary B-Disease
leak I-Disease
syndrome I-Disease
. O
These O
symptoms O
may O
be O
the O
result O
of O
drug O
- O
induced O
apoptosis O
of O
lesional O
leukocytes O
, O
especially O
activated O
T O
lymphocytes O
, O
and O
possibly O
release O
of O
inflammatory O
mediators O
. O
Because O
patients O
with O
severe O
psoriasis B-Disease
may O
develop O
capillary B-Disease
leak I-Disease
from O
various O
systemic O
therapies O
, O
clinical O
monitoring O
is O
advisable O
for O
patients O
with O
inflammatory B-Disease
diseases I-Disease
who O
are O
treated O
with O
immune O
modulators O
. O
Effect O
of O
lithium B-Chemical
maintenance O
therapy O
on O
thyroid O
and O
parathyroid O
function O
. O
OBJECTIVES O
: O
To O
assess O
changes O
induced O
by O
lithium B-Chemical
maintenance O
therapy O
on O
the O
incidence O
of O
thyroid O
, O
parathyroid O
and O
ion O
alterations O
. O
These O
were O
evaluated O
with O
respect O
to O
the O
duration O
of O
lithium B-Chemical
therapy O
, O
age O
, O
sex O
, O
and O
family O
history O
( O
whether O
or O
not O
the O
patient O
had O
a O
first O
- O
degree O
relative O
with O
thyroid B-Disease
disease I-Disease
) O
. O
DESIGN O
: O
Prospective O
study O
. O
SETTING O
: O
Affective O
Disorders O
Clinic O
at O
St O
. O
Mary O
' O
s O
Hospital O
, O
Montreal O
. O
PATIENTS O
: O
One O
hundred O
and O
one O
patients O
( O
28 O
men O
and O
73 O
women O
) O
with O
bipolar B-Disease
disorder I-Disease
receiving O
lithium B-Chemical
maintenance O
therapy O
ranging O
from O
1 O
year O
' O
s O
to O
32 O
years O
' O
duration O
. O
The O
control O
group O
consisted O
of O
82 O
patients O
with O
no O
psychiatric B-Disease
or O
endocrinological O
diagnoses O
from O
the O
hospital O
' O
s O
out O
- O
patient O
clinics O
. O
OUTCOME O
MEASURES O
: O
Laboratory O
analyses O
of O
calcium B-Chemical
, O
magnesium B-Chemical
and O
thyroid O
- O
stimulating O
hormone O
levels O
performed O
before O
beginning O
lithium B-Chemical
therapy O
and O
at O
biannual O
follow O
- O
up O
. O
RESULTS O
: O
Hypothyroidism B-Disease
developed O
in O
40 O
patients O
, O
excluding O
8 O
patients O
who O
were O
hypothyroid B-Disease
at O
baseline O
. O
All O
patients O
having O
first O
- O
degree O
relatives O
affected O
by O
thyroid B-Disease
illness I-Disease
had O
accelerated O
onset O
of O
hypothyroidism B-Disease
( O
3 O
. O
7 O
years O
after O
onset O
of O
lithium B-Chemical
therapy O
) O
compared O
with O
patients O
without O
a O
family O
history O
( O
8 O
. O
6 O
years O
after O
onset O
of O
lithium B-Chemical
therapy O
) O
. O
Women O
over O
60 O
years O
of O
age O
were O
more O
often O
affected O
by O
hypothyroidism B-Disease
than O
women O
under O
60 O
years O
of O
age O
( O
34 O
. O
6 O
% O
versus O
31 O
. O
9 O
% O
) O
. O
Magnesium B-Chemical
levels O
in O
patients O
on O
lithium B-Chemical
treatment O
were O
unchanged O
from O
baseline O
levels O
. O
After O
lithium B-Chemical
treatment O
, O
calcium B-Chemical
levels O
were O
higher O
than O
either O
baseline O
levels O
or O
control O
levels O
. O
Thus O
, O
lithium B-Chemical
treatment O
counteracted O
the O
decrease O
in O
plasma O
calcium B-Chemical
levels O
associated O
with O
aging O
. O
CONCLUSIONS O
: O
Familial O
thyroid B-Disease
illness I-Disease
is O
a O
risk O
factor O
for O
hypothyroidism B-Disease
and O
hypercalcemia B-Disease
during O
lithium B-Chemical
therapy O
. O
Severe O
immune O
hemolytic B-Disease
anemia I-Disease
associated O
with O
prophylactic O
use O
of O
cefotetan B-Chemical
in O
obstetric O
and O
gynecologic O
procedures O
. O
Second O
- O
and O
third O
- O
generation O
cephalosporins B-Chemical
, O
especially O
cefotetan B-Chemical
, O
are O
increasingly O
associated O
with O
severe O
, O
sometimes O
fatal O
immune O
hemolytic B-Disease
anemia I-Disease
. O
We O
noticed O
that O
10 O
of O
our O
35 O
cases O
of O
cefotetan B-Chemical
- O
induced O
hemolytic B-Disease
anemias I-Disease
were O
in O
patients O
who O
had O
received O
cefotetan B-Chemical
prophylactically O
for O
obstetric O
and O
gynecologic O
procedures O
. O
Eight O
of O
these O
cases O
of O
severe O
immune O
hemolytic B-Disease
anemia I-Disease
are O
described O
. O
Effects O
of O
nonsteroidal O
anti O
- O
inflammatory O
drugs O
on O
hemostasis O
in O
patients O
with O
aneurysmal B-Disease
subarachnoid I-Disease
hemorrhage I-Disease
. O
Platelet O
function O
is O
impaired O
by O
nonsteroidal O
anti O
- O
inflammatory O
drugs O
( O
NSAIDs O
) O
with O
prominent O
anti O
- O
inflammatory O
properties O
. O
Their O
safety O
in O
patients O
undergoing O
intracranial O
surgery O
is O
under O
debate O
. O
Patients O
with O
aneurysmal B-Disease
subarachnoid I-Disease
hemorrhage I-Disease
( O
SAH B-Disease
) O
were O
randomized O
to O
receive O
either O
ketoprofen B-Chemical
, O
100 O
mg O
, O
three O
times O
a O
day O
( O
ketoprofen B-Chemical
group O
, O
n O
= O
9 O
) O
or O
a O
weak O
NSAID O
, O
acetaminophen B-Chemical
, O
1 O
g O
, O
three O
times O
a O
day O
( O
acetaminophen B-Chemical
group O
, O
n O
= O
9 O
) O
starting O
immediately O
after O
the O
diagnosis O
of O
aneurysmal B-Disease
SAH B-Disease
. O
Treatment O
was O
continued O
for O
3 O
days O
postoperatively O
. O
Test O
blood O
samples O
were O
taken O
before O
treatment O
and O
surgery O
as O
well O
as O
on O
the O
first O
, O
third O
, O
and O
fifth O
postoperative O
mornings O
. O
Maximal O
platelet B-Disease
aggregation I-Disease
induced O
by O
6 O
microM O
of O
adenosine B-Chemical
diphosphate I-Chemical
decreased O
after O
administration O
of O
ketoprofen B-Chemical
. O
Aggregation O
was O
lower O
( O
P O
< O
. O
05 O
) O
in O
the O
ketoprofen B-Chemical
group O
than O
in O
the O
acetaminophen B-Chemical
group O
just O
before O
surgery O
and O
on O
the O
third O
postoperative O
day O
. O
In O
contrast O
, O
maximal O
platelet B-Disease
aggregation I-Disease
increased O
in O
the O
acetaminophen B-Chemical
group O
on O
the O
third O
postoperative O
day O
as O
compared O
with O
the O
pretreatment O
platelet B-Disease
aggregation I-Disease
results O
( O
P O
< O
. O
05 O
) O
. O
One O
patient O
in O
the O
ketoprofen B-Chemical
group O
developed O
a O
postoperative O
intracranial O
hematoma B-Disease
. O
Coagulation O
( O
prothrombin O
time O
[ O
PT O
] O
, O
activated O
partial O
thromboplastin O
time O
[ O
APPT O
] O
, O
fibrinogen O
concentration O
, O
and O
antithrombin O
III O
[ O
AT O
III O
] O
) O
was O
comparable O
between O
the O
two O
groups O
. O
Ketoprofen B-Chemical
but O
not O
acetaminophen B-Chemical
impaired O
platelet O
function O
in O
patients O
with O
SAH B-Disease
. O
If O
ketoprofen B-Chemical
is O
used O
before O
surgery O
on O
cerebral O
artery B-Disease
aneurysms I-Disease
, O
it O
may O
pose O
an O
additional O
risk O
factor O
for O
hemorrhage B-Disease
. O
Nitric B-Chemical
oxide I-Chemical
synthase O
expression O
in O
the O
course O
of O
lead B-Chemical
- O
induced O
hypertension B-Disease
. O
We O
recently O
showed O
elevated O
reactive O
oxygen B-Chemical
species O
( O
ROS O
) O
, O
reduced O
urinary O
excretion O
of O
NO B-Chemical
metabolites O
( O
NOx O
) O
, O
and O
increased O
NO B-Chemical
sequestration O
as O
nitrotyrosine B-Chemical
in O
various O
tissues O
in O
rats O
with O
lead B-Chemical
- O
induced O
hypertension B-Disease
. O
This O
study O
was O
designed O
to O
discern O
whether O
the O
reduction O
in O
urinary O
NOx O
in O
lead B-Chemical
- O
induced O
hypertension B-Disease
is O
, O
in O
part O
, O
due O
to O
depressed O
NO B-Chemical
synthase O
( O
NOS O
) O
expression O
. O
Male O
Sprague O
- O
Dawley O
rats O
were O
randomly O
assigned O
to O
a O
lead B-Chemical
- O
treated O
group O
( O
given O
lead B-Chemical
acetate I-Chemical
, O
100 O
ppm O
, O
in O
drinking O
water O
and O
regular O
rat O
chow O
) O
, O
a O
group O
given O
lead B-Chemical
and O
vitamin B-Chemical
E I-Chemical
- O
fortified O
chow O
, O
or O
a O
normal O
control O
group O
given O
either O
regular O
food O
and O
water O
or O
vitamin B-Chemical
E I-Chemical
- O
fortified O
food O
for O
12 O
weeks O
. O
Tail O
blood O
pressure O
, O
urinary O
NOx O
excretion O
, O
plasma O
malondialdehyde B-Chemical
( O
MDA B-Chemical
) O
, O
and O
endothelial O
and O
inducible O
NOS O
( O
eNOS O
and O
iNOS O
) O
isotypes O
in O
the O
aorta O
and O
kidney O
were O
measured O
. O
The O
lead B-Chemical
- O
treated O
group O
exhibited O
a O
rise O
in O
blood O
pressure O
and O
plasma O
MDA B-Chemical
concentration O
, O
a O
fall O
in O
urinary O
NOx O
excretion O
, O
and O
a O
paradoxical O
rise O
in O
vascular O
and O
renal O
tissue O
eNOS O
and O
iNOS O
expression O
. O
Vitamin B-Chemical
E I-Chemical
supplementation O
ameliorated O
hypertension B-Disease
, O
lowered O
plasma O
MDA B-Chemical
concentration O
, O
and O
raised O
urinary O
NOx O
excretion O
while O
significantly O
lowering O
vascular O
, O
but O
not O
renal O
, O
tissue O
eNOS O
and O
iNOS O
expression O
. O
Vitamin B-Chemical
E I-Chemical
supplementation O
had O
no O
effect O
on O
either O
blood O
pressure O
, O
plasma O
MDA B-Chemical
, O
or O
NOS O
expression O
in O
the O
control O
group O
. O
The O
study O
also O
revealed O
significant O
inhibition O
of O
NOS O
enzymatic O
activity O
by O
lead B-Chemical
in O
cell O
- O
free O
preparations O
. O
In O
conclusion O
, O
lead B-Chemical
- O
induced O
hypertension B-Disease
in O
this O
model O
was O
associated O
with O
a O
compensatory O
upregulation O
of O
renal O
and O
vascular O
eNOS O
and O
iNOS O
expression O
. O
This O
is O
, O
in O
part O
, O
due O
to O
ROS O
- O
mediated O
NO B-Chemical
inactivation O
, O
lead B-Chemical
- O
associated O
inhibition O
of O
NOS O
activity O
, O
and O
perhaps O
stimulatory O
actions O
of O
increased O
shear O
stress O
associated O
with O
hypertension B-Disease
. O
Glyceryl B-Chemical
trinitrate I-Chemical
induces O
attacks O
of O
migraine B-Disease
without I-Disease
aura I-Disease
in O
sufferers O
of O
migraine B-Disease
with I-Disease
aura I-Disease
. O
Migraine B-Disease
with I-Disease
aura I-Disease
and O
migraine B-Disease
without I-Disease
aura I-Disease
have O
the O
same O
pain B-Disease
phase O
, O
thus O
indicating O
that O
migraine B-Disease
with I-Disease
aura I-Disease
and O
migraine B-Disease
without I-Disease
aura I-Disease
share O
a O
common O
pathway O
of O
nociception O
. O
In O
recent O
years O
, O
increasing O
evidence O
has O
suggested O
that O
the O
messenger O
molecule O
nitric B-Chemical
oxide I-Chemical
( O
NO B-Chemical
) O
is O
involved O
in O
pain B-Disease
mechanisms O
of O
migraine B-Disease
without I-Disease
aura I-Disease
. O
In O
order O
to O
clarify O
whether O
the O
same O
is O
true O
for O
migraine B-Disease
with I-Disease
aura I-Disease
, O
in O
the O
present O
study O
we O
examined O
the O
headache B-Disease
response O
to O
intravenous O
infusion O
of O
glyceryl B-Chemical
trinitrate I-Chemical
( O
GTN B-Chemical
) O
( O
0 O
. O
5 O
microg O
/ O
kg O
/ O
min O
for O
20 O
min O
) O
in O
12 O
sufferers O
of O
migraine B-Disease
with I-Disease
aura I-Disease
. O
The O
specific O
aim O
was O
to O
elucidate O
whether O
an O
aura O
and O
/ O
or O
an O
attack O
of O
migraine B-Disease
without I-Disease
aura I-Disease
could O
be O
induced O
. O
Fourteen O
healthy O
subjects O
served O
as O
controls O
. O
Aura O
symptoms O
were O
not O
elicited O
in O
any O
subject O
. O
Headache B-Disease
was O
more O
severe O
in O
migraineurs B-Disease
than O
in O
the O
controls O
during O
and O
immediately O
after O
GTN B-Chemical
infusion O
( O
p O
= O
0 O
. O
037 O
) O
as O
well O
as O
during O
the O
following O
11 O
h O
( O
p O
= O
0 O
. O
008 O
) O
. O
In O
the O
controls O
, O
the O
GTN B-Chemical
- O
induced O
headache B-Disease
gradually O
disappeared O
, O
whereas O
in O
migraineurs B-Disease
peak O
headache B-Disease
intensity O
occurred O
at O
a O
mean O
time O
of O
240 O
min O
post O
- O
infusion O
. O
At O
this O
time O
the O
induced O
headache B-Disease
in O
6 O
of O
12 O
migraineurs B-Disease
fulfilled O
the O
diagnostic O
criteria O
for O
migraine B-Disease
without I-Disease
aura I-Disease
of O
the O
International O
Headache B-Disease
Society O
. O
The O
results O
therefore O
suggest O
that O
NO B-Chemical
is O
involved O
in O
the O
pain B-Disease
mechanisms O
of O
migraine B-Disease
with I-Disease
aura I-Disease
. O
Since O
cortical O
spreading O
depression B-Disease
has O
been O
shown O
to O
liberate O
NO B-Chemical
in O
animals O
, O
this O
finding O
may O
help O
our O
understanding O
of O
the O
coupling O
between O
cortical O
spreading O
depression B-Disease
and O
headache B-Disease
in O
migraine B-Disease
with I-Disease
aura I-Disease
. O
Rapid O
reversal O
of O
life O
- O
threatening O
diltiazem B-Chemical
- O
induced O
tetany B-Disease
with O
calcium B-Chemical
chloride I-Chemical
. O
We O
describe O
a O
patient O
who O
developed O
tetany B-Disease
with O
sudden O
respiratory B-Disease
arrest I-Disease
after O
the O
infusion O
of O
intravenous O
diltiazem B-Chemical
. O
The O
administration O
of O
calcium B-Chemical
chloride I-Chemical
rapidly O
resolved O
the O
patient O
' O
s O
tetany B-Disease
with O
prompt O
recovery O
of O
respiratory O
function O
, O
averting O
the O
need O
for O
more O
aggressive O
airway O
management O
and O
ventilatory O
support O
. O
The O
emergency O
physician O
should O
be O
aware O
that O
life O
- O
threatening O
tetany B-Disease
may O
accompany O
the O
administration O
of O
intravenous O
diltiazem B-Chemical
and O
that O
calcium B-Chemical
chloride I-Chemical
may O
be O
a O
rapid O
and O
effective O
remedy O
. O
Predictors O
of O
decreased B-Disease
renal I-Disease
function I-Disease
in O
patients O
with O
heart B-Disease
failure I-Disease
during O
angiotensin B-Chemical
- O
converting O
enzyme O
inhibitor O
therapy O
: O
results O
from O
the O
studies O
of O
left B-Disease
ventricular I-Disease
dysfunction I-Disease
( O
SOLVD O
) O
BACKGROUND O
: O
Although O
angiotensin B-Chemical
- O
converting O
enzyme O
inhibitor O
therapy O
reduces O
mortality O
rates O
in O
patients O
with O
congestive B-Disease
heart I-Disease
failure I-Disease
( O
CHF B-Disease
) O
, O
it O
may O
also O
cause O
decreased B-Disease
renal I-Disease
function I-Disease
. O
Little O
information O
is O
available O
to O
predict O
which O
patients O
are O
at O
highest O
risk O
for O
this O
complication O
. O
OBJECTIVE O
: O
To O
quantify O
specific O
clinical O
predictors O
of O
reduction B-Disease
in I-Disease
renal I-Disease
function I-Disease
in O
patients O
with O
CHF B-Disease
who O
are O
prescribed O
angiotensin B-Chemical
- O
converting O
enzyme O
inhibitor O
therapy O
. O
METHOD O
: O
We O
analyzed O
data O
from O
the O
Studies O
of O
Left B-Disease
Ventricular I-Disease
Dysfunction I-Disease
( O
SOLVD O
) O
, O
a O
randomized O
, O
double O
- O
blind O
, O
placebo O
- O
controlled O
trial O
of O
enalapril B-Chemical
for O
the O
treatment O
of O
CHF B-Disease
. O
There O
were O
3379 O
patients O
randomly O
assigned O
to O
enalapril B-Chemical
with O
a O
median O
follow O
- O
up O
of O
974 O
days O
and O
3379 O
patients O
randomly O
assigned O
to O
placebo O
with O
a O
mean O
follow O
- O
up O
of O
967 O
days O
. O
Decreased B-Disease
renal I-Disease
function I-Disease
was O
defined O
as O
a O
rise O
in O
serum O
creatinine B-Chemical
> O
/ O
= O
0 O
. O
5 O
mg O
/ O
dL O
( O
44 O
micromol O
/ O
L O
) O
from O
baseline O
. O
We O
used O
time O
- O
to O
- O
event O
analysis O
to O
identify O
potential O
predictors O
of O
decrease O
in O
renal O
function O
including O
age O
, O
baseline O
ejection O
fraction O
, O
baseline O
creatinine B-Chemical
, O
low O
systolic O
blood O
pressure O
( O
< O
100 O
mm O
Hg O
) O
, O
history O
of O
hypertension B-Disease
, O
diabetes B-Disease
, O
and O
use O
of O
antiplatelet O
, O
diuretic B-Chemical
, O
and O
beta O
- O
blocker O
therapy O
. O
RESULTS O
: O
Patients O
randomly O
assigned O
to O
enalapril B-Chemical
had O
a O
33 O
% O
greater O
likelihood O
of O
decreased B-Disease
renal I-Disease
function I-Disease
than O
controls O
( O
P O
= O
. O
003 O
) O
. O
By O
multivariate O
analysis O
, O
in O
both O
the O
placebo O
and O
enalapril B-Chemical
groups O
older O
age O
, O
diuretic B-Chemical
therapy O
, O
and O
diabetes B-Disease
were O
associated O
with O
decreased B-Disease
renal I-Disease
function I-Disease
, O
whereas O
beta O
- O
blocker O
therapy O
and O
higher O
ejection O
fraction O
were O
renoprotective O
. O
Older O
age O
was O
associated O
with O
a O
greater O
risk O
of O
developing O
decreased B-Disease
renal I-Disease
function I-Disease
in O
both O
groups O
, O
but O
significantly O
more O
so O
in O
the O
enalapril B-Chemical
group O
( O
enalapril B-Chemical
: O
risk O
ratio O
[ O
RR O
] O
1 O
. O
42 O
per O
10 O
years O
, O
95 O
% O
confidence O
interval O
[ O
CI O
] O
1 O
. O
32 O
- O
1 O
. O
52 O
with O
enalapril B-Chemical
; O
placebo O
: O
RR O
1 O
. O
18 O
, O
95 O
% O
CI O
1 O
. O
12 O
- O
1 O
. O
25 O
) O
. O
Diuretic B-Chemical
therapy O
was O
likewise O
associated O
with O
a O
greater O
risk O
of O
decreased B-Disease
renal I-Disease
function I-Disease
in O
the O
enalapril B-Chemical
group O
( O
RR O
1 O
. O
89 O
, O
95 O
% O
CI O
1 O
. O
70 O
- O
2 O
. O
08 O
) O
than O
in O
the O
placebo O
group O
( O
RR O
1 O
. O
35 O
, O
95 O
% O
CI O
1 O
. O
09 O
- O
1 O
. O
66 O
) O
. O
Conversely O
, O
enalapril B-Chemical
had O
a O
relative O
renoprotective O
effect O
( O
RR O
1 O
. O
33 O
, O
95 O
% O
CI O
1 O
. O
13 O
- O
1 O
. O
53 O
) O
compared O
with O
placebo O
( O
RR O
1 O
. O
96 O
, O
95 O
% O
CI O
1 O
. O
57 O
- O
2 O
. O
44 O
) O
in O
patients O
with O
diabetes B-Disease
. O
A O
lower O
risk O
of O
renal B-Disease
impairment I-Disease
was O
seen O
in O
both O
groups O
with O
beta O
- O
blocker O
therapy O
( O
RR O
0 O
. O
70 O
, O
95 O
% O
CI O
0 O
. O
57 O
- O
0 O
. O
85 O
) O
and O
higher O
baseline O
ejection O
fraction O
( O
RR O
0 O
. O
93 O
per O
5 O
% O
increment O
, O
95 O
% O
CI O
0 O
. O
91 O
- O
0 O
. O
96 O
) O
. O
CONCLUSIONS O
: O
Enalapril B-Chemical
use O
caused O
a O
33 O
% O
increase O
in O
the O
risk O
of O
decreased B-Disease
renal I-Disease
function I-Disease
in O
patients O
with O
CHF B-Disease
. O
Diuretic B-Chemical
use O
and O
advanced O
age O
increased O
this O
risk O
. O
Diabetes B-Disease
was O
associated O
with O
an O
increased O
risk O
of O
renal B-Disease
impairment I-Disease
in O
all O
patients O
with O
CHF B-Disease
, O
but O
this O
risk O
was O
reduced O
in O
the O
enalapril B-Chemical
group O
compared O
with O
the O
placebo O
group O
. O
beta O
- O
Blocker O
therapy O
and O
higher O
ejection O
fraction O
were O
renoprotective O
in O
all O
patients O
regardless O
of O
therapy O
. O
Hypomania B-Disease
- O
like O
syndrome O
induced O
by O
olanzapine B-Chemical
. O
We O
report O
a O
female O
patient O
with O
a O
diagnosis O
of O
a O
not O
otherwise O
specified O
psychotic B-Disease
disorder I-Disease
( O
DSM O
- O
IV O
) O
who O
developed O
hypomania B-Disease
shortly O
after O
the O
introduction O
of O
olanzapine B-Chemical
treatment O
. O
Acetazolamide B-Chemical
- O
induced O
Gerstmann B-Disease
syndrome I-Disease
. O
Acute O
confusion B-Disease
induced O
by O
acetazolamide B-Chemical
is O
a O
well O
known O
adverse O
drug O
reaction O
in O
patients O
with O
renal B-Disease
impairment I-Disease
. O
We O
report O
a O
case O
of O
acetazolamide B-Chemical
- O
induced O
Gerstmann B-Disease
syndrome I-Disease
in O
a O
patient O
with O
normal O
renal O
function O
, O
to O
highlight O
predisposing O
factors O
that O
are O
frequently O
overlooked O
. O
Vasopressin B-Chemical
in O
the O
treatment O
of O
milrinone B-Chemical
- O
induced O
hypotension B-Disease
in O
severe O
heart B-Disease
failure I-Disease
. O
The O
use O
of O
phosphodiesterase O
inhibitors O
such O
as O
milrinone B-Chemical
in O
the O
treatment O
of O
severe O
heart B-Disease
failure I-Disease
is O
frequently O
restricted O
because O
they O
cause O
vasodilation O
and O
hypotension B-Disease
. O
In O
patients O
with O
decompensated O
heart B-Disease
failure I-Disease
with O
hypotension B-Disease
after O
treatment O
with O
milrinone B-Chemical
, O
low O
doses O
of O
vasopressin B-Chemical
restored O
blood O
pressure O
without O
inhibiting O
the O
inotropic O
effect O
of O
milrinone B-Chemical
. O
Treatment O
of O
tacrolimus B-Chemical
- O
related O
adverse O
effects O
by O
conversion O
to O
cyclosporine B-Chemical
in O
liver O
transplant O
recipients O
. O
When O
tacrolimus B-Chemical
side O
effects O
persist O
despite O
dose O
reduction O
, O
conversion O
to O
cyclosporine B-Chemical
- O
based O
immunosuppression O
( O
CyA O
) O
is O
necessary O
. O
We O
characterized O
tacrolimus B-Chemical
side O
effects O
that O
warranted O
discontinuation O
of O
the O
drug O
, O
and O
outcomes O
after O
conversion O
. O
Of O
388 O
liver O
recipients O
who O
received O
tacrolimus B-Chemical
as O
primary O
immunosuppression O
, O
70 O
required O
conversion O
to O
CyA O
. O
We O
recorded O
indication O
for O
conversion O
, O
whether O
conversion O
was O
early O
or O
late O
after O
transplantation O
, O
tacrolimus B-Chemical
dose O
and O
trough O
blood O
level O
at O
conversion O
, O
and O
incidence O
of O
rejection O
after O
conversion O
. O
Conversion O
was O
early O
in O
29 O
patients O
( O
41 O
. O
4 O
% O
) O
and O
late O
in O
41 O
( O
58 O
. O
6 O
% O
) O
. O
Indications O
for O
early O
conversion O
were O
neurotoxicity B-Disease
( O
20 O
) O
, O
( B-Disease
insulin I-Disease
- I-Disease
dependent I-Disease
) I-Disease
diabetes I-Disease
mellitus I-Disease
( O
IDDM B-Disease
) O
( O
5 O
) O
, O
nephrotoxicity B-Disease
( O
3 O
) O
, O
gastrointestinal B-Disease
( I-Disease
GI I-Disease
) I-Disease
toxicity I-Disease
( O
6 O
) O
, O
and O
cardiomyopathy B-Disease
( O
1 O
) O
, O
and O
for O
late O
conversion O
were O
neurotoxicity B-Disease
( O
15 O
) O
, O
IDDM B-Disease
( O
12 O
) O
, O
nephrotoxicity B-Disease
( O
3 O
) O
, O
GI B-Disease
toxicity I-Disease
( O
5 O
) O
, O
hepatotoxicity B-Disease
( O
6 O
) O
, O
post B-Disease
- I-Disease
transplant I-Disease
lmphoproliferate I-Disease
disease I-Disease
( O
PTLD B-Disease
) O
( O
2 O
) O
, O
cardiomyopathy B-Disease
( O
1 O
) O
, O
hemolytic B-Disease
anemia I-Disease
( O
1 O
) O
, O
and O
pruritus B-Disease
( O
1 O
) O
. O
All O
early O
- O
conversion O
patients O
showed O
improvement O
/ O
resolution O
of O
symptoms O
. O
Among O
late O
- O
conversion O
patients O
, O
37 O
( O
90 O
. O
2 O
% O
) O
had O
improvement O
/ O
resolution O
; O
in O
4 O
( O
9 O
. O
8 O
% O
) O
, O
adverse O
effects O
persisted O
. O
The O
overall O
rejection O
rate O
was O
30 O
% O
. O
Sixty O
- O
two O
patients O
( O
88 O
. O
6 O
% O
) O
are O
alive O
with O
functioning O
grafts O
686 O
+ O
/ O
- O
362 O
days O
( O
range O
, O
154 O
- O
1433 O
days O
) O
after O
conversion O
. O
When O
tacrolimus B-Chemical
side O
effects O
are O
unresponsive O
to O
dose O
reduction O
, O
conversion O
to O
CyA O
can O
be O
accomplished O
safely O
, O
with O
no O
increased O
risk O
of O
rejection O
and O
excellent O
long O
- O
term O
outcome O
. O
Ocular O
manifestations O
of O
juvenile B-Disease
rheumatoid I-Disease
arthritis I-Disease
. O
We O
followed O
210 O
cases O
of O
juvenile B-Disease
rheumatoid I-Disease
arthritis I-Disease
closely O
for O
eleven O
years O
. O
Thirty O
- O
six O
of O
the O
210 O
patients O
( O
17 O
. O
2 O
% O
) O
developed O
iridocyclitis B-Disease
. O
Iridocyclitis B-Disease
was O
seen O
most O
frequently O
in O
young O
female O
patients O
( O
0 O
to O
4 O
years O
) O
with O
the O
monoarticular O
or O
pauciatricular O
form O
of O
the O
arthritis B-Disease
. O
However O
, O
30 O
% O
of O
the O
patients O
developed O
uveitis B-Disease
after O
16 O
years O
of O
age O
. O
Although O
61 O
% O
of O
patients O
had O
a O
noncontributory O
ocular O
history O
on O
entry O
, O
42 O
% O
had O
active O
uveitis B-Disease
on O
entry O
. O
Our O
approach O
was O
effective O
in O
detecting O
uveitis B-Disease
in O
new O
cases O
and O
exacerbations O
of O
uveitis B-Disease
in O
established O
cases O
. O
Forty O
- O
four O
percent O
of O
patients O
with O
uveitis B-Disease
had O
one O
or O
more O
identifiable O
signs O
or O
symptoms O
, O
such O
as O
red O
eye O
, O
ocular B-Disease
pain I-Disease
, O
decreased B-Disease
visual I-Disease
acuity I-Disease
, O
or O
photophobia B-Disease
, O
in O
order O
of O
decreasing O
frequency O
. O
Even O
after O
early O
detection O
and O
prompt O
treatment O
, O
41 O
% O
of O
cases O
of O
uveitis B-Disease
did O
not O
respond O
to O
more O
than O
six O
months O
of O
intensive O
topical O
treatment O
with O
corticosteroids B-Chemical
and O
mydriatics O
. O
Despite O
this O
, O
there O
was O
a O
dramatic O
decrease O
in O
the O
50 O
% O
incidence O
of O
blinding O
complications O
of O
uveitis B-Disease
cited O
in O
earlier O
studies O
. O
Cataract B-Disease
and O
band B-Disease
keratopathy I-Disease
occurred O
in O
only O
22 O
and O
13 O
% O
of O
our O
group O
, O
respectively O
. O
We O
used O
chloroquine B-Chemical
or O
hydroxychloroquine B-Chemical
in O
173 O
of O
210 O
cases O
and O
found O
only O
one O
case O
of O
chorioretinopathy B-Disease
attributable O
to O
these O
drugs O
. O
Systemically O
administered O
corticosteroids B-Chemical
were O
used O
in O
75 O
of O
210 O
cases O
; O
a O
significant O
number O
of O
posterior O
subcapsular O
cataracts B-Disease
was O
found O
. O
Typical O
keratoconjunctivitis B-Disease
sicca O
developed O
in O
three O
of O
the O
uveitis B-Disease
cases O
. O
This O
association O
with O
uveitis B-Disease
and O
JRA O
was O
not O
noted O
previously O
. O
Surgical O
treatment O
of O
cataracts B-Disease
, O
band B-Disease
keratopathy I-Disease
, O
and O
glaucoma B-Disease
achieved O
uniformly O
discouraging O
results O
. O
Cyclophosphamide B-Chemical
- O
induced O
cystitis B-Disease
in O
freely O
- O
moving O
conscious O
rats O
: O
behavioral O
approach O
to O
a O
new O
model O
of O
visceral B-Disease
pain I-Disease
. O
PURPOSE O
: O
To O
develop O
a O
model O
of O
visceral B-Disease
pain I-Disease
in O
rats O
using O
a O
behavioral O
approach O
. O
Cyclophosphamide B-Chemical
( O
CP B-Chemical
) O
, O
an O
antitumoral O
agent O
known O
to O
produce O
toxic O
effects O
on O
the O
bladder O
wall O
through O
its O
main O
toxic O
metabolite O
acrolein B-Chemical
, O
was O
used O
to O
induce O
cystitis B-Disease
. O
MATERIALS O
AND O
METHODS O
: O
CP B-Chemical
was O
administered O
at O
doses O
of O
50 O
, O
100 O
and O
200 O
mg O
. O
/ O
kg O
. O
i O
. O
p O
. O
to O
male O
rats O
, O
and O
their O
behavior O
observed O
and O
scored O
. O
The O
effects O
of O
morphine B-Chemical
( O
0 O
. O
5 O
to O
4 O
mg O
. O
/ O
kg O
. O
i O
. O
v O
. O
) O
on O
CP B-Chemical
- O
induced O
behavioral O
modifications O
were O
tested O
administered O
alone O
and O
after O
naloxone B-Chemical
( O
1 O
mg O
. O
/ O
kg O
. O
s O
. O
c O
. O
) O
. O
In O
addition O
, O
90 O
minutes O
after O
CP B-Chemical
injection O
, O
that O
is O
, O
at O
the O
time O
of O
administration O
of O
morphine B-Chemical
, O
the O
bladder O
was O
removed O
in O
some O
rats O
for O
histological O
examination O
. O
Finally O
, O
to O
show O
that O
the O
bladder O
is O
essential O
for O
the O
CP B-Chemical
- O
induced O
behavioral O
modifications O
, O
female O
rats O
also O
received O
CP B-Chemical
at O
doses O
of O
200 O
mg O
. O
/ O
kg O
. O
i O
. O
p O
. O
and O
of O
20 O
mg O
. O
by O
the O
intravesical O
route O
, O
and O
acrolein B-Chemical
at O
doses O
of O
0 O
. O
5 O
mg O
. O
by O
the O
intravesical O
route O
and O
of O
5 O
mg O
. O
/ O
kg O
. O
i O
. O
v O
. O
RESULTS O
: O
CP B-Chemical
dose O
- O
relatedly O
induced O
marked O
behavioral O
modifications O
in O
male O
rats O
: O
breathing O
rate O
decrease O
, O
closing O
of O
the O
eyes O
and O
occurrence O
of O
specific O
postures O
. O
Morphine B-Chemical
dose O
- O
dependently O
reversed O
these O
behavioral B-Disease
disorders I-Disease
. O
A O
dose O
of O
0 O
. O
5 O
mg O
. O
/ O
kg O
. O
produced O
a O
reduction O
of O
almost O
50 O
% O
of O
the O
behavioral O
score O
induced O
by O
CP B-Chemical
200 O
mg O
. O
/ O
kg O
. O
This O
effect O
was O
completely O
prevented O
by O
pretreatment O
with O
naloxone B-Chemical
. O
At O
the O
time O
of O
administration O
of O
morphine B-Chemical
, O
histological O
modifications O
of O
the O
bladder O
wall O
, O
such O
as O
chorionic O
and O
muscle O
layer O
edema B-Disease
, O
were O
observed O
. O
In O
female O
rats O
, O
CP B-Chemical
200 O
mg O
. O
/ O
kg O
. O
i O
. O
p O
. O
produced O
the O
same O
marked O
behavioral O
modifications O
as O
those O
observed O
in O
male O
rats O
. O
Administered O
at O
the O
dose O
of O
20 O
mg O
. O
intravesically O
, O
CP B-Chemical
did O
not O
produce O
any O
behavioral O
effects O
, O
whereas O
acrolein B-Chemical
at O
0 O
. O
5 O
mg O
. O
intravesically O
induced O
behavioral O
modifications O
identical O
to O
those O
under O
CP B-Chemical
200 O
mg O
. O
/ O
kg O
. O
i O
. O
p O
. O
, O
with O
the O
same O
maximal O
levels O
. O
Conversely O
, O
acrolein B-Chemical
5 O
mg O
. O
/ O
kg O
. O
i O
. O
v O
. O
did O
not O
produce O
any O
behavioral O
effects O
at O
all O
. O
CONCLUSIONS O
: O
Overall O
, O
these O
results O
indicate O
that O
this O
experimental O
model O
of O
CP B-Chemical
- O
induced O
cystitis B-Disease
may O
be O
an O
interesting O
new O
behavioral O
model O
of O
inflammatory O
visceral B-Disease
pain I-Disease
, O
allowing O
a O
better O
understanding O
of O
these O
painful B-Disease
syndromes I-Disease
and O
thus O
a O
better O
therapeutic O
approach O
to O
them O
. O
Prednisolone B-Chemical
- O
induced O
muscle B-Disease
dysfunction I-Disease
is O
caused O
more O
by O
atrophy B-Disease
than O
by O
altered O
acetylcholine B-Chemical
receptor O
expression O
. O
Large O
doses O
of O
glucocorticoids O
can O
alter O
muscle O
physiology O
and O
susceptibility O
to O
neuromuscular O
blocking O
drugs O
by O
mechanisms O
not O
clearly O
understood O
. O
We O
investigated O
the O
effects O
of O
moderate O
and O
large O
doses O
of O
prednisolone B-Chemical
on O
muscle O
function O
and O
pharmacology O
, O
and O
their O
relationship O
to O
changes O
in O
muscle O
size O
and O
acetylcholine B-Chemical
receptor O
( O
AChR O
) O
expression O
. O
With O
institutional O
approval O
, O
35 O
Sprague O
- O
Dawley O
rats O
were O
randomly O
allocated O
to O
receive O
daily O
subcutaneous O
doses O
of O
10 O
mg O
/ O
kg O
prednisolone B-Chemical
( O
P10 O
group O
) O
, O
100 O
mg O
/ O
kg O
prednisolone B-Chemical
( O
P100 O
group O
) O
, O
or O
an O
equal O
volume O
of O
saline O
( O
S O
group O
) O
for O
7 O
days O
. O
A O
fourth O
group O
of O
rats O
was O
pair O
fed O
( O
food O
restricted O
) O
with O
the O
P100 O
rats O
for O
7 O
days O
( O
FR O
group O
) O
. O
On O
Day O
8 O
, O
the O
nerve O
- O
evoked O
peak O
twitch O
tensions O
, O
tetanic B-Disease
tensions O
, O
and O
fatigability O
, O
and O
the O
dose O
- O
response O
curves O
of O
d B-Chemical
- I-Chemical
tubocurarine I-Chemical
in O
the O
tibialis O
cranialis O
muscle O
were O
measured O
in O
vivo O
and O
related O
to O
muscle O
mass O
or O
expression O
of O
AChRs O
. O
Rate O
of O
body O
weight O
gain O
was O
depressed O
in O
the O
P100 O
, O
FR O
, O
and O
P10 O
groups O
compared O
with O
the O
S O
group O
. O
Tibialis O
muscle O
mass O
was O
smaller O
in O
the O
P100 O
group O
than O
in O
the O
P10 O
or O
S O
groups O
. O
The O
evoked O
peak O
twitch O
and O
tetanic B-Disease
tensions O
were O
less O
in O
the O
P100 O
group O
than O
in O
the O
P10 O
or O
S O
groups O
, O
however O
, O
tension O
per O
milligram O
of O
muscle O
mass O
was O
greater O
in O
the O
P100 O
group O
than O
in O
the O
S O
group O
. O
The O
50 O
% O
effective O
dose O
of O
d B-Chemical
- I-Chemical
tubocurarine I-Chemical
( O
microg O
/ O
kg O
) O
in O
the O
tibialis O
muscle O
was O
smaller O
in O
the O
P10 O
( O
33 O
. O
6 O
+ O
/ O
- O
5 O
. O
4 O
) O
than O
in O
the O
S O
( O
61 O
. O
9 O
+ O
/ O
- O
5 O
. O
0 O
) O
or O
the O
P100 O
( O
71 O
. O
3 O
+ O
/ O
- O
9 O
. O
6 O
) O
groups O
. O
AChR O
expression O
was O
less O
in O
the O
P10 O
group O
than O
in O
the O
S O
group O
. O
The O
evoked O
tensions O
correlated O
with O
muscle O
mass O
( O
r O
( O
2 O
) O
= O
0 O
. O
32 O
, O
P O
< O
0 O
. O
001 O
) O
, O
however O
, O
not O
with O
expression O
of O
AChR O
. O
The O
50 O
% O
effective O
dose O
of O
d B-Chemical
- I-Chemical
tubocurarine I-Chemical
did O
not O
correlate O
with O
muscle O
mass O
or O
AChR O
expression O
. O
Our O
results O
suggest O
that O
the O
neuromuscular B-Disease
dysfunction I-Disease
after O
prednisolone B-Chemical
is O
dose O
- O
dependent O
, O
and O
derives O
primarily O
from O
muscle B-Disease
atrophy I-Disease
and O
derives O
less O
so O
from O
changes O
in O
AChR O
expression O
. O
IMPLICATIONS O
: O
The O
mechanisms O
by O
which O
chronic O
glucocorticoid O
therapy O
alters O
neuromuscular O
physiology O
and O
pharmacology O
are O
unclear O
. O
We O
suggest O
that O
the O
observed O
effects O
are O
dose O
- O
dependent O
and O
derive O
primarily O
from O
muscle B-Disease
atrophy I-Disease
and O
derive O
less O
from O
changes O
in O
acetylcholine B-Chemical
receptor O
expression O
. O
Apomorphine B-Chemical
: O
an O
underutilized O
therapy O
for O
Parkinson B-Disease
' I-Disease
s I-Disease
disease I-Disease
. O
Apomorphine B-Chemical
was O
the O
first O
dopaminergic O
drug O
ever O
used O
to O
treat O
symptoms O
of O
Parkinson B-Disease
' I-Disease
s I-Disease
disease I-Disease
. O
While O
powerful O
antiparkinsonian O
effects O
had O
been O
observed O
as O
early O
as O
1951 O
, O
the O
potential O
of O
treating O
fluctuating O
Parkinson B-Disease
' I-Disease
s I-Disease
disease I-Disease
by O
subcutaneous O
administration O
of O
apomorphine B-Chemical
has O
only O
recently O
become O
the O
subject O
of O
systematic O
study O
. O
A O
number O
of O
small O
scale O
clinical O
trials O
have O
unequivocally O
shown O
that O
intermittent O
subcutaneous O
apomorphine B-Chemical
injections O
produce O
antiparkinsonian O
benefit O
close O
if O
not O
identical O
to O
that O
seen O
with O
levodopa B-Chemical
and O
that O
apomorphine B-Chemical
rescue O
injections O
can O
reliably O
revert O
off O
- O
periods O
even O
in O
patients O
with O
complex O
on O
- O
off O
motor O
swings O
. O
Continuous O
subcutaneous O
apomorphine B-Chemical
infusions O
can O
reduce O
daily O
off O
- O
time O
by O
more O
than O
50 O
% O
in O
this O
group O
of O
patients O
, O
which O
appears O
to O
be O
a O
stronger O
effect O
than O
that O
generally O
seen O
with O
add O
- O
on O
therapy O
with O
oral O
dopamine B-Chemical
agonists O
or O
COMT O
inhibitors O
. O
Extended O
follow O
- O
up O
studies O
of O
up O
to O
8 O
years O
have O
demonstrated O
long O
- O
term O
persistence O
of O
apomorphine B-Chemical
efficacy O
. O
In O
addition O
, O
there O
is O
convincing O
clinical O
evidence O
that O
monotherapy O
with O
continuous O
subcutaneous O
apomorphine B-Chemical
infusions O
is O
associated O
with O
marked O
reductions O
of O
preexisting O
levodopa B-Chemical
- O
induced O
dyskinesias B-Disease
. O
The O
main O
side O
effects O
of O
subcutaneous O
apomorphine B-Chemical
treatment O
are O
related O
to O
cutaneous O
tolerability O
problems O
, O
whereas O
sedation O
and O
psychiatric B-Disease
complications O
play O
a O
lesser O
role O
. O
Given O
the O
marked O
degree O
of O
efficacy O
of O
subcutaneous O
apomorphine B-Chemical
treatment O
in O
fluctuating O
Parkinson B-Disease
' I-Disease
s I-Disease
disease I-Disease
, O
this O
approach O
seems O
to O
deserve O
more O
widespread O
clinical O
use O
. O
Probing O
peripheral O
and O
central O
cholinergic O
system O
responses O
. O
OBJECTIVE O
: O
The O
pharmacological O
response O
to O
drugs O
that O
act O
on O
the O
cholinergic O
system O
of O
the O
iris O
has O
been O
used O
to O
predict O
deficits O
in O
central O
cholinergic O
functioning O
due O
to O
diseases O
such O
as O
Alzheimer B-Disease
' I-Disease
s I-Disease
disease I-Disease
, O
yet O
correlations O
between O
central O
and O
peripheral O
responses O
have O
not O
been O
properly O
studied O
. O
This O
study O
assessed O
the O
effect O
of O
normal O
aging O
on O
( O
1 O
) O
the O
tropicamide B-Chemical
- O
induced O
increase O
in O
pupil O
diameter O
, O
and O
( O
2 O
) O
the O
reversal O
of O
this O
effect O
with O
pilocarpine B-Chemical
. O
Scopolamine B-Chemical
was O
used O
as O
a O
positive O
control O
to O
detect O
age O
- O
dependent O
changes O
in O
central O
cholinergic O
functioning O
in O
the O
elderly O
. O
DESIGN O
: O
Randomized O
double O
- O
blind O
controlled O
trial O
. O
PARTICIPANTS O
: O
Ten O
healthy O
elderly O
( O
mean O
age O
70 O
) O
and O
9 O
young O
( O
mean O
age O
33 O
) O
volunteers O
. O
INTERVENTIONS O
: O
Pupil O
diameter O
was O
monitored O
using O
a O
computerized O
infrared O
pupillometer O
over O
4 O
hours O
. O
The O
study O
involved O
4 O
sessions O
. O
In O
1 O
session O
, O
tropicamide B-Chemical
( O
20 O
microL O
, O
0 O
. O
01 O
% O
) O
was O
administered O
to O
one O
eye O
and O
placebo O
to O
the O
other O
. O
In O
another O
session O
, O
tropicamide B-Chemical
( O
20 O
microL O
, O
0 O
. O
01 O
% O
) O
was O
administered O
to O
both O
eyes O
, O
followed O
23 O
minutes O
later O
by O
the O
application O
of O
pilocarpine B-Chemical
( O
20 O
microL O
, O
0 O
. O
1 O
% O
) O
to O
one O
eye O
and O
placebo O
to O
the O
other O
. O
All O
eye O
drops O
were O
given O
in O
a O
randomized O
order O
. O
In O
2 O
separate O
sessions O
, O
a O
single O
dose O
of O
scopolamine B-Chemical
( O
0 O
. O
5 O
mg O
, O
intravenously O
) O
or O
placebo O
was O
administered O
, O
and O
the O
effects O
on O
word O
recall O
were O
measured O
using O
the O
Buschke O
Selective O
Reminding O
Test O
over O
2 O
hours O
. O
OUTCOME O
MEASURES O
: O
Pupil O
size O
at O
time O
points O
after O
administration O
of O
tropicamide B-Chemical
and O
pilocarpine B-Chemical
; O
scopolamine B-Chemical
- O
induced O
impairment B-Disease
in I-Disease
word I-Disease
recall I-Disease
. O
RESULTS O
: O
There O
was O
no O
significant O
difference O
between O
elderly O
and O
young O
volunteers O
in O
pupillary O
response O
to O
tropicamide B-Chemical
at O
any O
time O
point O
( O
p O
> O
0 O
. O
05 O
) O
. O
The O
elderly O
group O
had O
a O
significantly O
greater O
pilocarpine B-Chemical
- O
induced O
net O
decrease O
in O
pupil O
size O
85 O
, O
125 O
, O
165 O
and O
215 O
minutes O
after O
administration O
, O
compared O
with O
the O
young O
group O
( O
p O
< O
0 O
. O
05 O
) O
. O
Compared O
with O
the O
young O
group O
, O
the O
elderly O
group O
had O
greater O
scopolamine B-Chemical
- O
induced O
impairment B-Disease
in I-Disease
word I-Disease
recall I-Disease
60 O
, O
90 O
and O
120 O
minutes O
after O
administration O
( O
p O
< O
0 O
. O
05 O
) O
. O
CONCLUSION O
: O
There O
is O
an O
age O
- O
related O
pupillary O
response O
to O
pilocarpine B-Chemical
that O
is O
not O
found O
with O
tropicamide B-Chemical
. O
Thus O
, O
pilocarpine B-Chemical
may O
be O
useful O
to O
assess O
variations O
in O
central O
cholinergic O
function O
in O
elderly O
patients O
. O
Pain B-Disease
responses O
in O
methadone B-Chemical
- O
maintained O
opioid O
abusers O
. O
Providing O
pain B-Disease
management O
for O
known O
opioid O
abusers O
is O
a O
challenging O
clinical O
task O
, O
in O
part O
because O
little O
is O
known O
about O
their O
pain B-Disease
experience O
and O
analgesic O
requirements O
. O
This O
study O
was O
designed O
to O
describe O
pain B-Disease
tolerance O
and O
analgesic O
response O
in O
a O
sample O
of O
opioid B-Disease
addicts I-Disease
stabilized O
in O
methadone B-Chemical
- O
maintenance O
( O
MM O
) O
treatment O
( O
n O
= O
60 O
) O
in O
comparison O
to O
matched O
nondependent O
control O
subjects O
( O
n O
= O
60 O
) O
. O
By O
using O
a O
placebo O
- O
controlled O
, O
two O
- O
way O
factorial O
design O
, O
tolerance O
to O
cold O
- O
pressor O
( O
CP O
) O
pain B-Disease
was O
examined O
, O
both O
before O
and O
after O
oral O
administration O
of O
therapeutic O
doses O
of O
common O
opioid O
( O
hydromorphone B-Chemical
2 O
mg O
) O
and O
nonsteroidal O
anti O
- O
inflammatory O
( O
ketorolac B-Chemical
10 O
mg O
) O
analgesic O
agents O
. O
Results O
showed O
that O
MM O
individuals O
were O
significantly O
less O
tolerant O
of O
CP O
pain B-Disease
than O
control O
subjects O
, O
replicating O
previous O
work O
. O
Analgesic O
effects O
were O
significant O
neither O
for O
medication O
nor O
group O
. O
These O
data O
indicate O
that O
MM O
opioid O
abusers O
represent O
a O
pain B-Disease
- I-Disease
intolerant I-Disease
subset O
of O
clinical O
patients O
. O
Their O
complaints O
of O
pain B-Disease
should O
be O
evaluated O
seriously O
and O
managed O
aggressively O
. O
High O
- O
dose O
methylprednisolone B-Chemical
may O
do O
more O
harm O
for O
spinal B-Disease
cord I-Disease
injury I-Disease
. O
Because O
of O
the O
National O
Acute O
Spinal B-Disease
Cord I-Disease
Injury I-Disease
Studies O
( O
NASCIS O
) O
, O
high O
- O
dose O
methylprednisolone B-Chemical
became O
the O
standard O
of O
care O
for O
the O
acute O
spinal B-Disease
cord I-Disease
injury I-Disease
. O
In O
the O
NASCIS O
, O
there O
was O
no O
mention O
regarding O
the O
possibility O
of O
acute O
corticosteroid B-Chemical
myopathy B-Disease
that O
high O
- O
dose O
methylprednisolone B-Chemical
may O
cause O
. O
The O
dosage O
of O
methylprednisolone B-Chemical
recommended O
by O
the O
NASCIS O
3 O
is O
the O
highest O
dose O
of O
steroids B-Chemical
ever O
being O
used O
during O
a O
2 O
- O
day O
period O
for O
any O
clinical O
condition O
. O
We O
hypothesize O
that O
it O
may O
cause O
some O
damage B-Disease
to I-Disease
the I-Disease
muscle I-Disease
of O
spinal B-Disease
cord I-Disease
injury I-Disease
patients O
. O
Further O
, O
steroid B-Chemical
myopathy B-Disease
recovers O
naturally O
and O
the O
neurological O
improvement O
shown O
in O
the O
NASCIS O
may O
be O
just O
a O
recording O
of O
this O
natural O
motor O
recovery O
from O
the O
steroid B-Chemical
myopathy B-Disease
, O
instead O
of O
any O
protection O
that O
methylprednisolone B-Chemical
offers O
to O
the O
spinal B-Disease
cord I-Disease
injury I-Disease
. O
To O
our O
knowledge O
, O
this O
is O
the O
first O
discussion O
considering O
the O
possibility O
that O
the O
methylprednisolone B-Chemical
recommended O
by O
NASCIS O
may O
cause O
acute O
corticosteroid B-Chemical
myopathy B-Disease
. O
Conversion O
to O
rapamycin B-Chemical
immunosuppression O
in O
renal O
transplant O
recipients O
: O
report O
of O
an O
initial O
experience O
. O
BACKGROUND O
: O
The O
aim O
of O
this O
study O
is O
to O
evaluate O
the O
effects O
of O
RAPA B-Chemical
conversion O
in O
patients O
undergoing O
cyclosporine B-Chemical
( O
CsA B-Chemical
) O
or O
tacrolimus B-Chemical
( O
Tac B-Chemical
) O
toxicity B-Disease
. O
METHODS O
: O
Twenty O
renal O
transplant O
recipients O
were O
switched O
to O
fixed O
dose O
rapamycin B-Chemical
( O
RAPA B-Chemical
) O
( O
5 O
mg O
/ O
day O
) O
0 O
to O
204 O
months O
posttransplant O
. O
Drug O
monitoring O
was O
not O
initially O
used O
to O
adjust O
doses O
. O
The O
indications O
for O
switch O
were O
chronic O
CsA B-Chemical
or O
Tac B-Chemical
nephrotoxicity B-Disease
( O
12 O
) O
, O
acute O
CsA B-Chemical
or O
Tac B-Chemical
toxicity B-Disease
( O
3 O
) O
, O
severe O
facial B-Disease
dysmorphism I-Disease
( O
2 O
) O
, O
posttransplant B-Disease
lymphoproliferative I-Disease
disorder I-Disease
( O
PTLD B-Disease
) O
in O
remission O
( O
2 O
) O
, O
and O
hepatotoxicity B-Disease
in O
1 O
. O
Follow O
- O
up O
is O
7 O
to O
24 O
months O
. O
RESULTS O
: O
In O
the O
12 O
patients O
switched O
because O
of O
chronic O
nephrotoxicity B-Disease
there O
was O
a O
significant O
decrease O
in O
serum O
creatinine B-Chemical
[ O
233 O
+ O
/ O
- O
34 O
to O
210 O
+ O
/ O
- O
56 O
micromol O
/ O
liter O
( O
P O
< O
0 O
. O
05 O
) O
at O
6 O
months O
] O
. O
Facial B-Disease
dysmorphism I-Disease
improved O
in O
two O
patients O
. O
No O
relapse O
of O
PTLD B-Disease
was O
observed O
. O
Five O
patients O
developed O
pneumonia B-Disease
( O
two O
Pneumocystis B-Disease
carinii I-Disease
pneumonia I-Disease
, O
one O
infectious B-Disease
mononucleosis I-Disease
with O
polyclonal O
PTLD B-Disease
lung O
infiltrate O
) O
and O
two O
had O
bronchiolitis B-Disease
obliterans I-Disease
. O
There O
were O
no O
deaths O
. O
RAPA B-Chemical
was O
discontinued O
in O
four O
patients O
, O
because O
of O
pneumonia B-Disease
in O
two O
, O
PTLD B-Disease
in O
one O
, O
and O
oral O
aphtous B-Disease
ulcers I-Disease
in O
one O
. O
RAPA B-Chemical
levels O
were O
high O
( O
> O
15 O
ng O
/ O
ml O
) O
in O
7 O
of O
13 O
( O
54 O
% O
) O
patients O
. O
CONCLUSIONS O
: O
RAPA B-Chemical
conversion O
provides O
adequate O
immunosuppression O
to O
enable O
CsA B-Chemical
withdrawal O
. O
However O
, O
when O
converting O
patients O
to O
RAPA B-Chemical
drug O
levels O
should O
be O
monitored O
to O
avoid O
over O
- O
immunosuppression O
and O
adequate O
antiviral O
and O
Pneumocystis B-Disease
carinii I-Disease
pneumonia I-Disease
prophylaxis O
should O
be O
given O
. O
Electro O
- O
oculography O
, O
electroretinography O
, O
visual O
evoked O
potentials O
, O
and O
multifocal O
electroretinography O
in O
patients O
with O
vigabatrin B-Chemical
- O
attributed O
visual B-Disease
field I-Disease
constriction I-Disease
. O
PURPOSE O
: O
Symptomatic O
visual B-Disease
field I-Disease
constriction I-Disease
thought O
to O
be O
associated O
with O
vigabatrin B-Chemical
has O
been O
reported O
. O
The O
current O
study O
investigated O
the O
visual O
fields O
and O
visual O
electrophysiology O
of O
eight O
patients O
with O
known O
vigabatrin B-Chemical
- O
attributed O
visual B-Disease
field I-Disease
loss I-Disease
, O
three O
of O
whom O
were O
reported O
previously O
. O
Six O
of O
the O
patients O
were O
no O
longer O
receiving O
vigabatrin B-Chemical
. O
METHODS O
: O
The O
central O
and O
peripheral O
fields O
were O
examined O
with O
the O
Humphrey O
Visual O
Field O
Analyzer O
. O
Full O
visual O
electrophysiology O
, O
including O
flash O
electroretinography O
( O
ERG O
) O
, O
pattern O
electroretinography O
, O
multifocal O
ERG O
using O
the O
VERIS O
system O
, O
electro O
- O
oculography O
, O
and O
flash O
and O
pattern O
visual O
evoked O
potentials O
, O
was O
undertaken O
. O
RESULTS O
: O
Seven O
patients O
showed O
marked O
visual B-Disease
field I-Disease
constriction I-Disease
with O
some O
sparing O
of O
the O
temporal O
visual O
field O
. O
The O
eighth O
exhibited O
concentric O
constriction O
. O
Most O
electrophysiological O
responses O
were O
usually O
just O
within O
normal O
limits O
; O
two O
patients O
had O
subnormal O
Arden O
electro O
- O
oculography O
indices O
; O
and O
one O
patient O
showed O
an O
abnormally O
delayed O
photopic O
b O
wave O
. O
However O
, O
five O
patients O
showed O
delayed O
30 O
- O
Hz O
flicker O
b O
waves O
, O
and O
seven O
patients O
showed O
delayed O
oscillatory O
potentials O
. O
Multifocal O
ERG O
showed O
abnormalities O
that O
sometimes O
correlated O
with O
the O
visual O
field O
appearance O
and O
confirmed O
that O
the O
deficit O
occurs O
at O
the O
retinal O
level O
. O
CONCLUSION O
: O
Marked O
visual B-Disease
field I-Disease
constriction I-Disease
appears O
to O
be O
associated O
with O
vigabatrin B-Chemical
therapy O
. O
The O
field O
defects O
and O
some O
electrophysiological O
abnormalities O
persist O
when O
vigabatrin B-Chemical
therapy O
is O
withdrawn O
. O
Myocardial B-Disease
ischemia I-Disease
due O
to O
coronary B-Disease
artery I-Disease
spasm I-Disease
during O
dobutamine B-Chemical
stress O
echocardiography O
. O
Dobutamine B-Chemical
stress O
echocardiography O
( O
DSE O
) O
is O
a O
useful O
and O
safe O
provocation O
test O
for O
myocardial B-Disease
ischemia I-Disease
. O
Until O
now O
, O
the O
test O
has O
been O
focused O
only O
on O
the O
organic O
lesion O
in O
the O
coronary O
artery O
, O
and O
positive O
DSE O
has O
indicated O
the O
presence O
of O
significant O
fixed O
coronary B-Disease
artery I-Disease
stenosis I-Disease
. O
The O
aim O
of O
the O
present O
study O
is O
to O
examine O
whether O
myocardial B-Disease
ischemia I-Disease
due O
to O
coronary B-Disease
spasm I-Disease
is O
induced O
by O
dobutamine B-Chemical
. O
We O
performed O
DSE O
on O
51 O
patients O
with O
coronary B-Disease
spastic I-Disease
angina I-Disease
but O
without O
significant O
fixed O
coronary B-Disease
artery I-Disease
stenosis I-Disease
. O
All O
patients O
had O
anginal B-Disease
attacks O
at O
rest O
with O
ST O
elevation O
on O
the O
electrocardiogram O
( O
variant B-Disease
angina I-Disease
) O
. O
Coronary O
spasm O
was O
induced O
by O
intracoronary O
injection O
of O
acetylcholine B-Chemical
, O
and O
no O
fixed O
coronary B-Disease
artery I-Disease
stenosis I-Disease
was O
documented O
on O
angiograms O
in O
all O
patients O
. O
DSE O
was O
performed O
with O
intravenous O
dobutamine B-Chemical
infusion O
with O
an O
incremental O
doses O
of O
5 O
, O
10 O
, O
20 O
, O
30 O
, O
and O
40 O
microg O
/ O
kg O
/ O
min O
every O
5 O
minutes O
. O
Of O
the O
51 O
patients O
, O
7 O
patients O
showed O
asynergy O
with O
ST O
elevation O
. O
All O
7 O
patients O
( O
13 O
. O
7 O
% O
) O
had O
chest B-Disease
pain I-Disease
during O
asynergy O
, O
and O
both O
chest B-Disease
pain I-Disease
and O
electrocardiographic O
changes O
were O
preceded O
by O
asynergy O
. O
These O
findings O
indicate O
that O
dobutamine B-Chemical
can O
provoke O
coronary B-Disease
spasm I-Disease
in O
some O
patients O
with O
coronary B-Disease
spastic I-Disease
angina I-Disease
. O
When O
DSE O
is O
performed O
to O
evaluate O
coronary B-Disease
artery I-Disease
disease I-Disease
, O
not O
only O
fixed O
coronary B-Disease
stenosis I-Disease
, O
but O
also O
coronary B-Disease
spasm I-Disease
should O
be O
considered O
as O
a O
genesis O
of O
asynergy O
. O
Effect O
of O
intravenous O
metoprolol B-Chemical
or O
intravenous O
metoprolol B-Chemical
plus O
glucagon O
on O
dobutamine B-Chemical
- O
induced O
myocardial B-Disease
ischemia I-Disease
. O
STUDY O
OBJECTIVE O
: O
To O
determine O
the O
effect O
of O
metoprolol B-Chemical
on O
dobutamine B-Chemical
stress O
testing O
with O
technetium B-Chemical
- I-Chemical
99m I-Chemical
sestamibi I-Chemical
single O
- O
photon O
emission O
computed O
tomography O
imaging O
and O
ST O
- O
segment O
monitoring O
, O
and O
to O
assess O
the O
impact O
of O
intravenous O
glucagon O
on O
metoprolol B-Chemical
' O
s O
effects O
. O
DESIGN O
: O
Randomized O
, O
double O
- O
blind O
, O
placebo O
- O
controlled O
trial O
. O
SETTING O
: O
Community O
hospital O
. O
PATIENTS O
: O
Twenty O
- O
two O
patients O
with O
known O
reversible O
perfusion O
defects O
. O
INTERVENTION O
: O
Patients O
underwent O
dobutamine B-Chemical
stress O
tests O
per O
standard O
protocol O
. O
Before O
dobutamine B-Chemical
was O
begun O
, O
no O
therapy O
was O
given O
during O
the O
first O
visit O
, O
and O
patients O
were O
randomized O
on O
subsequent O
visits O
to O
receive O
metoprolol B-Chemical
or O
metoprolol B-Chemical
plus O
glucagon O
1 O
mg O
. O
Metoprolol B-Chemical
was O
dosed O
to O
achieve O
a O
resting O
predobutamine B-Chemical
heart O
rate O
below O
65 O
beats O
/ O
minute O
or O
a O
total O
intravenous O
dose O
of O
20 O
mg O
. O
MEASUREMENTS O
AND O
MAIN O
RESULTS O
: O
Metoprolol B-Chemical
reduced O
maximum O
heart O
rate O
31 O
% O
, O
summed O
stress O
scores O
29 O
% O
, O
and O
summed O
difference O
scores O
43 O
% O
versus O
control O
. O
Metoprolol B-Chemical
plus O
glucagon O
also O
reduced O
the O
maximum O
heart O
rate O
29 O
% O
versus O
control O
. O
Summed O
stress O
and O
summed O
difference O
scores O
were O
not O
significantly O
reduced O
, O
although O
they O
were O
18 O
% O
and O
30 O
% O
lower O
, O
respectively O
, O
than O
control O
. O
No O
significant O
differences O
were O
found O
in O
any O
parameter O
between O
metoprolol B-Chemical
and O
metoprolol B-Chemical
- O
glucagon O
. O
CONCLUSION O
: O
During O
dobutamine B-Chemical
stress O
testing O
, O
metoprolol B-Chemical
attenuates O
or O
eliminates O
evidence O
of O
myocardial B-Disease
ischemia I-Disease
. O
Glucagon O
1 O
mg O
, O
although O
somewhat O
effective O
, O
does O
not O
correct O
this O
effect O
to O
the O
extent O
that O
it O
can O
be O
administered O
clinically O
. O
Evidence O
of O
functional O
somatotopy O
in O
GPi O
from O
results O
of O
pallidotomy O
. O
The O
objective O
of O
this O
study O
was O
to O
explore O
the O
functional O
anatomy O
of O
the O
globus O
pallidus O
internus O
( O
GPi O
) O
by O
studying O
the O
effects O
of O
unilateral O
pallidotomy O
on O
parkinsonian B-Disease
' O
off O
' O
signs O
and O
levodopa B-Chemical
- O
induced O
dyskinesias B-Disease
( O
LID B-Disease
) O
. O
We O
found O
significant O
positive O
correlations O
between O
the O
preoperative O
levodopa B-Chemical
responsiveness O
of O
motor O
signs O
and O
the O
levodopa B-Chemical
responsiveness O
of O
scores O
in O
timed O
tests O
( O
Core O
Assessment O
Program O
for O
Intracerebral O
Transplantations O
) O
in O
the O
contralateral O
limbs O
and O
the O
improvement O
in O
these O
scores O
after O
surgery O
, O
whereas O
there O
was O
no O
correlation O
with O
the O
improvement O
in O
LID B-Disease
. O
We O
also O
found O
a O
highly O
significant O
correlation O
( O
P O
: O
< O
0 O
. O
0001 O
, O
r O
= O
0 O
. O
8 O
) O
between O
the O
volume O
of O
the O
ventral O
lesion O
in O
the O
GPi O
and O
the O
improvement O
in O
LID B-Disease
in O
the O
contralateral O
limbs O
, O
whereas O
there O
was O
no O
correlation O
between O
the O
ventral O
volume O
and O
the O
improvement O
in O
parkinsonian B-Disease
' O
off O
' O
signs O
. O
The O
volumes O
of O
the O
total O
lesion O
cylinder O
and O
the O
dorsal O
lesion O
did O
not O
correlate O
with O
the O
outcome O
of O
either O
dyskinesias B-Disease
or O
parkinsonian B-Disease
' O
off O
' O
signs O
. O
The O
differential O
predictive O
value O
of O
levodopa B-Chemical
responsiveness O
for O
the O
outcome O
of O
parkinsonian B-Disease
' O
off O
' O
signs O
and O
LID B-Disease
and O
the O
different O
correlations O
of O
ventral O
lesion O
volume O
with O
dyskinesias B-Disease
and O
parkinsonian B-Disease
' O
off O
' O
signs O
indicate O
that O
different O
anatomical O
or O
pathophysiological O
substrates O
may O
be O
responsible O
for O
the O
generation O
of O
parkinsonian B-Disease
' O
off O
' O
signs O
and O
dyskinesias B-Disease
. O
Whereas O
cells O
in O
a O
wider O
area O
of O
the O
GPi O
may O
be O
implicated O
in O
parkinsonism B-Disease
, O
the O
ventral O
GPi O
seems O
to O
be O
crucial O
for O
the O
manifestation O
of O
LID B-Disease
. O
We O
suggest O
that O
our O
observations O
are O
additional O
proof O
of O
the O
functional O
somatotopy O
of O
the O
systems O
within O
the O
GPi O
that O
mediate O
parkinsonism B-Disease
and O
dyskinesias B-Disease
, O
especially O
along O
the O
dorsoventral O
trajectory O
used O
in O
pallidotomy O
. O
The O
outcome O
of O
pallidotomy O
in O
which O
the O
lesion O
involves O
the O
ventral O
and O
dorsal O
GPi O
could O
be O
the O
net O
effect O
of O
alteration O
in O
the O
activity O
of O
pathways O
which O
mediate O
different O
symptoms O
, O
and O
hence O
could O
be O
variable O
. O
Screening O
for O
stimulant O
use O
in O
adult O
emergency O
department O
seizure B-Disease
patients O
. O
OBJECTIVE O
: O
The O
objective O
of O
this O
study O
was O
to O
determine O
the O
prevalence O
of O
positive O
plasma O
drug O
screening O
for O
cocaine B-Chemical
or O
amphetamine B-Chemical
in O
adult O
emergency O
department O
seizure B-Disease
patients O
. O
METHODS O
: O
This O
prospective O
study O
evaluated O
consecutive O
eligible O
seizure B-Disease
patients O
who O
had O
a O
plasma O
sample O
collected O
as O
part O
of O
their O
clinical O
evaluation O
. O
Plasma O
was O
tested O
for O
amphetamine B-Chemical
and O
the O
cocaine B-Chemical
metabolite O
benzoylecgonine B-Chemical
using O
enzyme O
- O
mediated O
immunoassay O
methodology O
. O
Plasma O
samples O
with O
benzoylecgonine B-Chemical
greater O
than O
150 O
ng O
/ O
mL O
or O
an O
amphetamine B-Chemical
greater O
than O
500 O
ng O
/ O
mL O
were O
defined O
as O
positive O
. O
Patient O
demographics O
, O
history O
of O
underlying O
drug O
or O
alcohol B-Chemical
- O
related O
seizure B-Disease
disorder O
, O
estimated O
time O
from O
seizure B-Disease
to O
sample O
collection O
, O
history O
or O
suspicion O
of O
cocaine B-Disease
or I-Disease
amphetamine I-Disease
abuse I-Disease
, O
results O
of O
clinical O
urine O
testing O
for O
drugs O
of O
abuse O
, O
and O
assay O
results O
were O
recorded O
without O
patient O
identifiers O
. O
RESULTS O
: O
Fourteen O
of O
248 O
( O
5 O
. O
6 O
% O
, O
95 O
% O
CI O
2 O
. O
7 O
% O
- O
8 O
. O
5 O
% O
) O
plasma O
samples O
were O
positive O
by O
immunoassay O
testing O
for O
benzoylecgonine B-Chemical
and O
no O
samples O
( O
0 O
% O
, O
95 O
% O
CI O
0 O
- O
1 O
. O
2 O
% O
) O
were O
positive O
for O
amphetamine B-Chemical
. O
Positive O
test O
results O
were O
more O
common O
in O
patient O
visits O
where O
there O
was O
a O
history O
or O
suspicion O
of O
cocaine B-Disease
or I-Disease
amphetamine I-Disease
abuse I-Disease
( O
p O
< O
0 O
. O
0005 O
) O
. O
CONCLUSIONS O
: O
During O
this O
study O
period O
, O
routine O
plasma O
screening O
for O
cocaine B-Chemical
and O
amphetamines B-Chemical
in O
adult O
seizure B-Disease
patients O
had O
a O
low O
yield O
. O
As O
a O
result O
, O
routine O
plasma O
screening O
would O
yield O
few O
cases O
of O
stimulant O
drug O
in O
which O
there O
was O
neither O
a O
history O
nor O
suspicion O
of O
drug B-Disease
abuse I-Disease
in O
this O
population O
. O
Contribution O
of O
sodium B-Chemical
valproate I-Chemical
to O
the O
syndrome B-Disease
of I-Disease
inappropriate I-Disease
secretion I-Disease
of I-Disease
antidiuretic I-Disease
hormone I-Disease
. O
We O
report O
the O
case O
of O
a O
62 O
- O
year O
- O
old O
man O
who O
was O
administered O
sodium B-Chemical
valproate I-Chemical
( O
VPA B-Chemical
) O
and O
who O
subsequently O
developed O
the O
syndrome B-Disease
of I-Disease
inappropriate I-Disease
secretion I-Disease
of I-Disease
antidiuretic I-Disease
hormone I-Disease
( O
SIADH B-Disease
) O
. O
He O
had O
been O
taking O
VPA B-Chemical
for O
treatment O
of O
idiopathic O
generalized O
tonic B-Disease
- I-Disease
clonic I-Disease
convulsions I-Disease
since O
he O
was O
56 O
years O
old O
. O
After O
substituting O
VPA B-Chemical
with O
zonisamide B-Chemical
, O
the O
serum O
sodium B-Chemical
level O
returned O
to O
normal O
. O
We O
consider O
this O
episode O
of O
SIADH B-Disease
to O
be O
the O
result O
of O
a O
combination O
of O
factors O
including O
a O
weakness B-Disease
of I-Disease
the I-Disease
central I-Disease
nervous I-Disease
system I-Disease
and O
the O
long O
- O
term O
administration O
of O
VPA B-Chemical
. O
Association O
of O
nitric B-Chemical
oxide I-Chemical
production O
and O
apoptosis O
in O
a O
model O
of O
experimental O
nephropathy B-Disease
. O
BACKGROUND O
: O
In O
recent O
studies O
increased O
amounts O
of O
nitric B-Chemical
oxide I-Chemical
( O
NO B-Chemical
) O
and O
apoptosis O
have O
been O
implicated O
in O
various O
pathological O
conditions O
in O
the O
kidney O
. O
We O
have O
studied O
the O
role O
of O
NO B-Chemical
and O
its O
association O
with O
apoptosis O
in O
an O
experimental O
model O
of O
nephrotic B-Disease
syndrome I-Disease
induced O
by O
a O
single O
injection O
of O
adriamycin B-Chemical
( O
ADR B-Chemical
) O
. O
METHODS O
: O
The O
alteration O
in O
the O
NO B-Chemical
pathway O
was O
assessed O
by O
measuring O
nitrite B-Chemical
levels O
in O
serum O
/ O
urine O
and O
by O
evaluating O
the O
changes O
in O
vascular O
reactivity O
of O
the O
isolated O
perfused O
rat O
kidney O
( O
IPRK O
) O
system O
. O
Rats O
were O
stratified O
into O
control O
groups O
and O
ADR B-Chemical
- O
induced O
nephropathy B-Disease
groups O
. O
These O
two O
groups O
were O
then O
divided O
into O
: O
group O
1 O
, O
animals O
receiving O
saline O
; O
and O
group O
2 O
, O
animals O
receiving O
aminoguanidine B-Chemical
( O
AG B-Chemical
) O
which O
is O
a O
specific O
inhibitor O
of O
inducible O
- O
NO B-Chemical
synthase O
. O
On O
day O
21 O
, O
rats O
were O
sacrificed O
after O
obtaining O
material O
for O
biochemical O
analysis O
. O
RESULTS O
: O
Histopathological O
examination O
of O
the O
kidneys O
of O
rats O
treated O
with O
ADR B-Chemical
revealed O
focal O
areas O
of O
mesangial B-Disease
proliferation I-Disease
and O
mild O
tubulointerstitial B-Disease
inflammation I-Disease
. O
They O
also O
had O
significantly O
higher O
levels O
of O
proteinuria B-Disease
compared O
with O
control O
and O
treatment O
groups O
( O
P O
< O
0 O
. O
05 O
) O
. O
Urine O
nitrite B-Chemical
levels O
were O
significantly O
increased O
in O
the O
ADR B-Chemical
- O
nephropathy B-Disease
group O
( O
P O
< O
0 O
. O
05 O
) O
. O
In O
the O
IPRK O
phenylephrine B-Chemical
and O
acetylcholine B-Chemical
related O
responses O
were O
significantly O
impaired O
in O
the O
ADR B-Chemical
- O
nephropathy B-Disease
group O
. O
Apoptosis O
was O
not O
detected O
in O
controls O
. O
However O
, O
in O
the O
ADR B-Chemical
- O
nephropathy B-Disease
group O
, O
numerous O
apoptotic O
cells O
were O
identified O
in O
the O
tubulointerstitial O
areas O
. O
Double O
staining O
revealed O
numerous O
interstitial O
apoptotic O
cells O
to O
stain O
for O
ED1 O
, O
a O
marker O
for O
monocytes O
/ O
macrophages O
. O
Treatment O
with O
AG B-Chemical
prevented O
the O
impairment O
of O
renal O
vascular O
bed O
responses O
and O
reduced O
both O
urine O
nitrite B-Chemical
levels O
and O
apoptosis O
to O
control O
levels O
. O
CONCLUSION O
: O
We O
suggest O
that O
interactions O
between O
NO B-Chemical
and O
apoptosis O
are O
important O
in O
the O
pathogenesis O
of O
the O
ADR B-Chemical
- O
induced O
nephrosis B-Disease
. O
Dual O
effects O
of O
melatonin B-Chemical
on O
barbiturate B-Chemical
- O
induced O
narcosis B-Disease
in O
rats O
. O
Melatonin B-Chemical
affects O
the O
circadian O
sleep O
/ O
wake O
cycle O
, O
but O
it O
is O
not O
clear O
whether O
it O
may O
influence O
drug O
- O
induced O
narcosis B-Disease
. O
Sodium B-Chemical
thiopenthal I-Chemical
was O
administered O
intraperitoneally O
into O
male O
rats O
pre O
- O
treated O
with O
melatonin B-Chemical
( O
0 O
. O
05 O
, O
0 O
. O
5 O
, O
5 O
and O
50 O
mg O
/ O
kg O
) O
. O
Melatonin B-Chemical
pre O
- O
treatment O
affected O
in O
a O
dual O
manner O
barbiturate B-Chemical
narcosis B-Disease
, O
however O
, O
no O
dose O
- O
effect O
correlation O
was O
found O
. O
In O
particular O
, O
low O
doses O
reduced O
the O
latency O
to O
and O
prolonged O
the O
duration O
of O
barbiturate B-Chemical
narcosis B-Disease
. O
In O
contrast O
, O
the O
highest O
dose O
of O
melatonin B-Chemical
( O
50 O
mg O
/ O
kg O
) O
caused O
a O
paradoxical O
increase O
in O
the O
latency O
and O
produced O
a O
sustained O
reduction O
of O
the O
duration O
of O
narcosis B-Disease
, O
and O
a O
reduction O
in O
mortality O
rate O
. O
Melatonin B-Chemical
0 O
. O
5 O
and O
5 O
mg O
/ O
kg O
influenced O
the O
duration O
but O
not O
the O
latency O
of O
ketamine B-Chemical
- O
or O
diazepam B-Chemical
- O
induced O
narcosis B-Disease
. O
Thus O
, O
the O
dual O
action O
of O
melatonin B-Chemical
on O
pharmacological O
narcosis B-Disease
seems O
to O
be O
specific O
for O
the O
barbiturate B-Chemical
mechanism O
of O
action O
. O
Reduced O
cardiotoxicity B-Disease
and O
preserved O
antitumor O
efficacy O
of O
liposome O
- O
encapsulated O
doxorubicin B-Chemical
and O
cyclophosphamide B-Chemical
compared O
with O
conventional O
doxorubicin B-Chemical
and O
cyclophosphamide B-Chemical
in O
a O
randomized O
, O
multicenter O
trial O
of O
metastatic O
breast B-Disease
cancer I-Disease
. O
PURPOSE O
: O
To O
determine O
whether O
Myocet B-Chemical
( O
liposome O
- O
encapsulated O
doxorubicin B-Chemical
; O
The O
Liposome O
Company O
, O
Elan O
Corporation O
, O
Princeton O
, O
NJ O
) O
in O
combination O
with O
cyclophosphamide B-Chemical
significantly O
reduces O
doxorubicin B-Chemical
cardiotoxicity B-Disease
while O
providing O
comparable O
antitumor O
efficacy O
in O
first O
- O
line O
treatment O
of O
metastatic O
breast B-Disease
cancer I-Disease
( O
MBC B-Disease
) O
. O
PATIENTS O
AND O
METHODS O
: O
Two O
hundred O
ninety O
- O
seven O
patients O
with O
MBC B-Disease
and O
no O
prior O
chemotherapy O
for O
metastatic O
disease O
were O
randomized O
to O
receive O
either O
60 O
mg O
/ O
m O
( O
2 O
) O
of O
Myocet B-Chemical
( O
M O
) O
or O
conventional O
doxorubicin B-Chemical
( O
A O
) O
, O
in O
combination O
with O
600 O
mg O
/ O
m O
( O
2 O
) O
of O
cyclophosphamide B-Chemical
( O
C O
) O
, O
every O
3 O
weeks O
until O
disease O
progression O
or O
unacceptable O
toxicity B-Disease
. O
Cardiotoxicity B-Disease
was O
defined O
by O
reductions O
in O
left O
- O
ventricular O
ejection O
fraction O
, O
assessed O
by O
serial O
multigated O
radionuclide O
angiography O
scans O
, O
or O
congestive B-Disease
heart I-Disease
failure I-Disease
( O
CHF B-Disease
) O
. O
Antitumor O
efficacy O
was O
assessed O
by O
objective O
tumor B-Disease
response O
rates O
( O
World O
Health O
Organization O
criteria O
) O
, O
time O
to O
progression O
, O
and O
survival O
. O
RESULTS O
: O
Six O
percent O
of O
MC O
patients O
versus O
21 O
% O
( O
including O
five O
cases O
of O
CHF B-Disease
) O
of O
AC O
patients O
developed O
cardiotoxicity B-Disease
( O
P O
= O
. O
0002 O
) O
. O
Median O
cumulative O
doxorubicin B-Chemical
dose O
at O
onset O
was O
more O
than O
2 O
, O
220 O
mg O
/ O
m O
( O
2 O
) O
for O
MC O
versus O
480 O
mg O
/ O
m O
( O
2 O
) O
for O
AC O
( O
P O
= O
. O
0001 O
, O
hazard O
ratio O
, O
5 O
. O
04 O
) O
. O
MC O
patients O
also O
experienced O
less O
grade O
4 O
neutropenia B-Disease
. O
Antitumor O
efficacy O
of O
MC O
versus O
AC O
was O
comparable O
: O
objective O
response O
rates O
, O
43 O
% O
versus O
43 O
% O
; O
median O
time O
to O
progression O
, O
5 O
. O
1 O
% O
versus O
5 O
. O
5 O
months O
; O
median O
time O
to O
treatment O
failure O
, O
4 O
. O
6 O
versus O
4 O
. O
4 O
months O
; O
and O
median O
survival O
, O
19 O
versus O
16 O
months O
. O
CONCLUSION O
: O
Myocet B-Chemical
improves O
the O
therapeutic O
index O
of O
doxorubicin B-Chemical
by O
significantly O
reducing O
cardiotoxicity B-Disease
and O
grade O
4 O
neutropenia B-Disease
and O
provides O
comparable O
antitumor O
efficacy O
, O
when O
used O
in O
combination O
with O
cyclophosphamide B-Chemical
as O
first O
- O
line O
therapy O
for O
MBC B-Disease
. O
The O
role O
of O
nitrergic O
system O
in O
lidocaine B-Chemical
- O
induced O
convulsion B-Disease
in O
the O
mouse O
. O
The O
effects O
of O
N B-Chemical
- I-Chemical
nitro I-Chemical
- I-Chemical
L I-Chemical
- I-Chemical
arginine I-Chemical
- I-Chemical
methyl I-Chemical
ester I-Chemical
( O
L B-Chemical
- I-Chemical
NAME I-Chemical
) O
a O
nitric B-Chemical
oxide I-Chemical
( O
NO B-Chemical
) O
synthase O
inhibitor O
and O
L B-Chemical
- I-Chemical
arginine I-Chemical
, O
a O
NO B-Chemical
precursor O
, O
were O
investigated O
on O
lidocaine B-Chemical
- O
induced O
convulsions B-Disease
. O
In O
the O
first O
experiment O
, O
four O
groups O
of O
mice O
received O
physiological O
saline O
( O
0 O
. O
9 O
% O
) O
, O
L B-Chemical
- I-Chemical
arginine I-Chemical
( O
300 O
mg O
/ O
kg O
, O
i O
. O
p O
. O
) O
, O
L B-Chemical
- I-Chemical
NAME I-Chemical
( O
100 O
mg O
/ O
kg O
, O
i O
. O
p O
. O
) O
and O
diazepam B-Chemical
( O
2 O
mg O
/ O
kg O
) O
, O
respectively O
. O
Thirty O
minutes O
after O
these O
injections O
, O
all O
mice O
received O
lidocaine B-Chemical
( O
50 O
mg O
/ O
kg O
, O
i O
. O
p O
. O
) O
. O
In O
the O
second O
experiment O
, O
four O
groups O
of O
mice O
received O
similar O
treatment O
in O
the O
first O
experiment O
, O
and O
30 O
min O
after O
these O
injections O
, O
all O
mice O
received O
a O
higher O
dose O
of O
lidocaine B-Chemical
( O
80 O
mg O
/ O
kg O
) O
. O
L B-Chemical
- I-Chemical
NAME I-Chemical
( O
100 O
mg O
/ O
kg O
, O
i O
. O
p O
. O
) O
and O
diazepam B-Chemical
( O
2 O
mg O
/ O
kg O
) O
significantly O
decreased O
the O
incidence O
of O
lidocaine B-Chemical
( O
50 O
mg O
/ O
kg O
) O
- O
induced O
convulsions B-Disease
. O
In O
contrast O
, O
the O
L B-Chemical
- I-Chemical
arginine I-Chemical
treatment O
increased O
the O
incidence O
of O
lidocaine B-Chemical
( O
80 O
mg O
/ O
kg O
, O
i O
. O
p O
. O
) O
- O
induced O
convulsions B-Disease
significantly O
. O
These O
results O
may O
suggest O
that O
NO B-Chemical
is O
a O
proconvulsant O
mediator O
in O
lidocaine B-Chemical
- O
induced O
convulsions B-Disease
. O
Erythropoietin O
restores O
the O
anemia B-Disease
- O
induced O
reduction O
in O
cyclophosphamide B-Chemical
cytotoxicity B-Disease
in O
rat O
tumors B-Disease
. O
The O
aim O
of O
this O
study O
was O
to O
examine O
the O
impact O
of O
anemia B-Disease
prevention O
by O
recombinant O
human O
erythropoietin O
( O
rHuEPO O
) O
treatment O
on O
the O
cytotoxicity B-Disease
of O
cyclophosphamide B-Chemical
in O
solid O
experimental O
tumors B-Disease
. O
Anemia B-Disease
was O
induced O
using O
a O
single O
dose O
of O
carboplatin B-Chemical
( O
50 O
mg O
/ O
kg O
i O
. O
v O
. O
) O
resulting O
in O
a O
long O
- O
lasting O
reduction O
( O
30 O
% O
) O
of O
the O
hemoglobin O
concentration O
. O
In O
a O
second O
group O
, O
the O
development O
of O
anemia B-Disease
was O
prevented O
by O
rHuEPO O
( O
1000 O
IU O
/ O
kg O
) O
administered O
s O
. O
c O
. O
three O
times O
/ O
week O
starting O
7 O
days O
before O
carboplatin B-Chemical
application O
. O
Four O
days O
after O
carboplatin B-Chemical
treatment O
, O
tumors B-Disease
( O
DS O
- O
sarcoma B-Disease
of O
the O
rat O
) O
were O
implanted O
s O
. O
c O
. O
onto O
the O
hind O
food O
dorsum O
. O
Neither O
carboplatin B-Chemical
nor O
rHuEPO O
treatment O
influenced O
tumor B-Disease
growth O
rate O
per O
se O
. O
When O
tumors B-Disease
were O
treated O
with O
a O
single O
dose O
of O
cyclophosphamide B-Chemical
( O
60 O
mg O
/ O
kg O
i O
. O
p O
. O
) O
5 O
days O
after O
implantation O
, O
a O
growth O
delay O
with O
a O
subsequent O
regrowth O
of O
the O
tumors B-Disease
was O
observed O
. O
In O
the O
anemia B-Disease
group O
, O
the O
growth O
delay O
was O
significantly O
shorter O
compared O
with O
nonanemic O
controls O
( O
13 O
. O
3 O
days O
versus O
8 O
. O
6 O
days O
) O
. O
In O
the O
group O
where O
anemia B-Disease
was O
prevented O
by O
rHuEPO O
treatment O
, O
growth O
delay O
was O
comparable O
with O
that O
of O
nonanemic O
controls O
( O
13 O
. O
3 O
days O
) O
. O
These O
results O
suggest O
that O
chemotherapy O
- O
induced O
anemia B-Disease
reduces O
cytotoxicity B-Disease
of O
cyclophosphamide B-Chemical
in O
tumors B-Disease
, O
whereas O
correction O
of O
anemia B-Disease
by O
rHuEPO O
treatment O
( O
epoetin O
alpha O
) O
increases O
the O
sensitivity O
, O
probably O
as O
a O
result O
of O
an O
improved O
oxygen B-Chemical
supply O
to O
tumor B-Disease
tissue O
. O
Fatal O
haemorrhagic B-Disease
myocarditis I-Disease
secondary O
to O
cyclophosphamide B-Chemical
therapy O
. O
Haemorrhagic B-Disease
myocarditis I-Disease
is O
a O
rare O
but O
important O
complication O
of O
cyclophosphamide B-Chemical
therapy O
. O
Echocardiographic O
identification O
of O
the O
disorder O
can O
be O
made O
. O
We O
believe O
that O
the O
ultrasound O
features O
of O
this O
disorder O
have O
not O
been O
previously O
reported O
. O
Effects O
of O
verapamil B-Chemical
on O
atrial B-Disease
fibrillation I-Disease
and O
its O
electrophysiological O
determinants O
in O
dogs O
. O
BACKGROUND O
: O
Atrial B-Disease
tachycardia I-Disease
- O
induced O
remodeling O
promotes O
the O
occurrence O
and O
maintenance O
of O
atrial B-Disease
fibrillation I-Disease
( O
AF B-Disease
) O
and O
decreases O
L O
- O
type O
Ca B-Chemical
( O
2 O
+ O
) O
current O
. O
There O
is O
also O
a O
clinical O
suggestion O
that O
acute O
L O
- O
type O
Ca B-Chemical
( O
2 O
) O
channel O
blockade O
can O
promote O
AF B-Disease
, O
consistent O
with O
an O
AF B-Disease
promoting O
effect O
of O
Ca B-Chemical
( O
2 O
+ O
) O
channel O
inhibition O
. O
METHODS O
: O
To O
evaluate O
the O
potential O
mechanisms O
of O
AF B-Disease
promotion O
by O
Ca B-Chemical
( O
2 O
+ O
) O
channel O
blockers O
, O
we O
administered O
verapamil B-Chemical
to O
morphine B-Chemical
- O
chloralose B-Chemical
anesthetized O
dogs O
. O
Diltiazem B-Chemical
was O
used O
as O
a O
comparison O
drug O
and O
autonomic O
blockade O
with O
atropine B-Chemical
and O
nadolol B-Chemical
was O
applied O
in O
some O
experiments O
. O
Epicardial O
mapping O
with O
240 O
epicardial O
electrodes O
was O
used O
to O
evaluate O
activation O
during O
AF B-Disease
. O
RESULTS O
: O
Verapamil B-Chemical
caused O
AF B-Disease
promotion O
in O
six O
dogs O
, O
increasing O
mean O
duration O
of O
AF B-Disease
induced O
by O
burst O
pacing O
, O
from O
8 O
+ O
/ O
- O
4 O
s O
( O
mean O
+ O
/ O
- O
S O
. O
E O
. O
) O
to O
95 O
+ O
/ O
- O
39 O
s O
( O
P O
< O
0 O
. O
01 O
vs O
. O
control O
) O
at O
a O
loading O
dose O
of O
0 O
. O
1 O
mg O
/ O
kg O
and O
228 O
+ O
/ O
- O
101 O
s O
( O
P O
< O
0 O
. O
0005 O
vs O
. O
control O
) O
at O
a O
dose O
of O
0 O
. O
2 O
mg O
/ O
kg O
. O
Underlying O
electrophysiological O
mechanisms O
were O
studied O
in O
detail O
in O
five O
additional O
dogs O
under O
control O
conditions O
and O
in O
the O
presence O
of O
the O
higher O
dose O
of O
verapamil B-Chemical
. O
In O
these O
experiments O
, O
verapamil B-Chemical
shortened O
mean O
effective O
refractory O
period O
( O
ERP O
) O
from O
122 O
+ O
/ O
- O
5 O
to O
114 O
+ O
/ O
- O
4 O
ms O
( O
P O
< O
0 O
. O
02 O
) O
at O
a O
cycle O
length O
of O
300 O
ms O
, O
decreased O
ERP O
heterogeneity O
( O
from O
15 O
+ O
/ O
- O
1 O
to O
10 O
+ O
/ O
- O
1 O
% O
, O
P O
< O
0 O
. O
05 O
) O
, O
heterogeneously O
accelerated O
atrial O
conduction O
and O
decreased O
the O
cycle O
length O
of O
AF B-Disease
( O
94 O
+ O
/ O
- O
4 O
to O
84 O
+ O
/ O
- O
3 O
ms O
, O
P O
< O
0 O
. O
005 O
) O
. O
Diltiazem B-Chemical
did O
not O
affect O
ERP O
, O
AF B-Disease
cycle O
length O
or O
AF B-Disease
duration O
, O
but O
produced O
conduction O
acceleration O
similar O
to O
that O
caused O
by O
verapamil B-Chemical
( O
n O
= O
5 O
) O
. O
In O
the O
presence O
of O
autonomic O
blockade O
, O
verapamil B-Chemical
failed O
to O
promote O
AF B-Disease
and O
increased O
, O
rather O
than O
decreasing O
, O
refractoriness O
. O
Neither O
verapamil B-Chemical
nor O
diltiazem B-Chemical
affected O
atrial O
conduction O
in O
the O
presence O
of O
autonomic O
blockade O
. O
Epicardial O
mapping O
suggested O
that O
verapamil B-Chemical
promoted O
AF B-Disease
by O
increasing O
the O
number O
of O
simultaneous O
wavefronts O
reflected O
by O
separate O
zones O
of O
reactivation O
in O
each O
cycle O
. O
CONCLUSIONS O
: O
Verapamil B-Chemical
promotes O
AF B-Disease
in O
normal O
dogs O
by O
promoting O
multiple O
circuit O
reentry O
, O
an O
effect O
dependent O
on O
intact O
autonomic O
tone O
and O
not O
shared O
by O
diltiazem B-Chemical
. O
Calcitonin O
gene O
- O
related O
peptide O
levels O
during O
nitric B-Chemical
oxide I-Chemical
- O
induced O
headache B-Disease
in O
patients O
with O
chronic O
tension B-Disease
- I-Disease
type I-Disease
headache I-Disease
. O
It O
has O
been O
proposed O
that O
nitric B-Chemical
oxide I-Chemical
( O
NO B-Chemical
) O
induced O
headache B-Disease
in O
primary B-Disease
headaches I-Disease
may O
be O
associated O
with O
release O
of O
calcitonin O
gene O
- O
related O
peptide O
( O
CGRP O
) O
. O
In O
the O
present O
study O
we O
aimed O
to O
investigate O
plasma O
levels O
of O
CGRP O
during O
headache B-Disease
induced O
by O
the O
NO B-Chemical
donor O
glyceryl B-Chemical
trinitrate I-Chemical
( O
GTN B-Chemical
) O
in O
16 O
patients O
with O
chronic O
tension B-Disease
- I-Disease
type I-Disease
headache I-Disease
and O
16 O
healthy O
controls O
. O
The O
subjects O
were O
randomly O
allocated O
to O
receive O
0 O
. O
5 O
microg O
/ O
kg O
/ O
min O
GTN B-Chemical
or O
placebo O
over O
20 O
min O
on O
two O
headache B-Disease
- O
free O
days O
. O
Blood O
samples O
were O
collected O
at O
baseline O
, O
10 O
, O
20 O
and O
60 O
min O
after O
start O
of O
infusion O
. O
Both O
patients O
and O
controls O
developed O
significantly O
stronger O
immediate O
headache B-Disease
on O
the O
GTN B-Chemical
day O
than O
on O
the O
placebo O
day O
and O
the O
headache B-Disease
was O
significantly O
more O
pronounced O
in O
patients O
than O
in O
controls O
. O
There O
was O
no O
difference O
between O
the O
area O
under O
the O
CGRP O
curve O
( O
AUCCGRP O
) O
on O
GTN B-Chemical
vs O
. O
placebo O
day O
in O
either O
patients O
( O
P O
= O
0 O
. O
65 O
) O
or O
controls O
( O
P O
= O
0 O
. O
48 O
) O
. O
The O
AUCCGRP O
recorded O
on O
the O
GTN B-Chemical
day O
did O
not O
differ O
between O
patients O
and O
controls O
( O
P O
= O
0 O
. O
36 O
) O
. O
Both O
in O
patients O
and O
controls O
, O
CGRP O
levels O
changed O
significantly O
over O
time O
, O
on O
both O
the O
GTN B-Chemical
and O
placebo O
days O
( O
P O
< O
0 O
. O
05 O
) O
. O
The O
present O
study O
indicates O
that O
NO B-Chemical
- O
induced O
immediate O
headache B-Disease
is O
not O
associated O
with O
release O
of O
CGRP O
. O
Fluconazole B-Chemical
- O
induced O
torsade B-Disease
de I-Disease
pointes I-Disease
. O
OBJECTIVE O
: O
To O
present O
a O
case O
of O
fluconazole B-Chemical
- O
associated O
torsade B-Disease
de I-Disease
pointes I-Disease
( O
TDP B-Disease
) O
and O
discuss O
fluconazole B-Chemical
' O
s O
role O
in O
causing O
TDP B-Disease
. O
CASE O
SUMMARY O
: O
A O
68 O
- O
year O
- O
old O
white O
woman O
with O
Candida O
glabrata O
isolated O
from O
a O
presacral O
abscess O
developed O
TDP B-Disease
eight O
days O
after O
commencing O
oral O
fluconazole B-Chemical
The O
patient O
had O
no O
other O
risk O
factors O
for O
TDP B-Disease
, O
including O
coronary B-Disease
artery I-Disease
disease I-Disease
, O
cardiomyopathy B-Disease
, O
congestive B-Disease
heart I-Disease
failure I-Disease
, O
and O
electrolyte O
abnormalities O
There O
was O
a O
temporal O
association O
between O
the O
initiation O
of O
fluconazole B-Chemical
and O
TDP B-Disease
. O
The O
TDP B-Disease
resolved O
when O
fluconazole B-Chemical
was O
discontinued O
; O
however O
, O
the O
patient O
continued O
to O
have O
premature B-Disease
ventricular I-Disease
contractions I-Disease
and O
nonsustained O
ventricular B-Disease
tachycardia I-Disease
( O
NSVT B-Disease
) O
until O
six O
days O
after O
drug O
cessation O
DISCUSSION O
: O
Use O
of O
the O
Naranjo O
probability O
scale O
indicates O
a O
probable O
relationship O
between O
the O
use O
of O
fluconazole B-Chemical
and O
the O
development O
of O
TDP B-Disease
. O
The O
possible O
mechanism O
is O
depression B-Disease
of O
rapidly O
activating O
delayed O
rectifier O
potassium B-Chemical
currents O
. O
In O
our O
patient O
, O
there O
was O
no O
other O
etiology O
identified O
that O
could O
explain O
QT B-Disease
prolongation I-Disease
or O
TDP B-Disease
The O
complete O
disappearance O
of O
NSVT B-Disease
and O
premature B-Disease
ventricular I-Disease
contractions I-Disease
followed O
by O
normalization O
of O
QT O
interval O
after O
the O
drug O
was O
stopped O
strongly O
suggests O
fluconazole B-Chemical
as O
the O
etiology O
. O
CONCLUSIONS O
: O
Clinicians O
should O
be O
aware O
that O
fluconazole B-Chemical
, O
even O
at O
low O
doses O
, O
may O
cause O
prolongation B-Disease
of I-Disease
the I-Disease
QT I-Disease
interval I-Disease
, O
leading O
to O
TDP B-Disease
. O
Serial O
electrocardiographic O
monitoring O
may O
be O
considered O
when O
fluconazole B-Chemical
is O
administered O
in O
patients O
who O
are O
at O
risk O
for O
ventricular B-Disease
arrhythmias I-Disease
. O
Cutaneous B-Disease
leucocytoclastic I-Disease
vasculitis I-Disease
associated O
with O
oxacillin B-Chemical
. O
A O
67 O
- O
year O
- O
old O
man O
who O
was O
treated O
with O
oxacillin B-Chemical
for O
one O
week O
because O
of O
Staphylococcus B-Disease
aureus I-Disease
bacteremia I-Disease
, O
developed O
renal B-Disease
failure I-Disease
and O
diffuse O
, O
symmetric O
, O
palpable O
purpuric B-Disease
lesions I-Disease
on O
his O
feet O
. O
Necrotic B-Disease
blisters I-Disease
were O
noted O
on O
his O
fingers O
. O
Skin O
biopsies O
showed O
findings O
diagnostic O
of O
leucocytoclastic B-Disease
vasculitis I-Disease
. O
Oxacillin B-Chemical
was O
discontinued O
and O
patient O
was O
treated O
with O
corticosteroids B-Chemical
. O
The O
rash B-Disease
disappeared O
after O
three O
weeks O
and O
renal O
function O
returned O
to O
normal O
. O
Leucocytoclastic B-Disease
vasculitis I-Disease
presents O
as O
palpable O
purpura B-Disease
of O
the O
lower O
extremities O
often O
accompanied O
by O
abdominal B-Disease
pain I-Disease
, O
arthralgia B-Disease
, O
and O
renal B-Disease
involvement I-Disease
. O
Etiologic O
factors O
or O
associated O
disorders O
include O
infections B-Disease
, O
medications O
, O
collagen B-Disease
vascular I-Disease
disease I-Disease
and O
neoplasia B-Disease
. O
However O
, O
in O
half O
of O
the O
cases O
no O
etiologic O
factor O
is O
identified O
. O
Usually O
it O
is O
a O
self O
- O
limited O
disorder O
, O
but O
corticosteroid B-Chemical
therapy O
may O
be O
needed O
in O
life O
- O
threatening O
cases O
since O
early O
treatment O
with O
corticosteroids B-Chemical
in O
severe O
cases O
can O
prevent O
complications O
. O
Oxacillin B-Chemical
should O
be O
included O
among O
the O
drugs O
that O
can O
cause O
leucocytoclastic B-Disease
vasculitis I-Disease
. O
The O
renal O
pathology O
in O
a O
case O
of O
lithium B-Chemical
- O
induced O
diabetes B-Disease
insipidus I-Disease
. O
A O
case O
of O
lithium B-Chemical
- O
induced O
diabetes B-Disease
insipidus I-Disease
is O
reported O
. O
At O
necropsy O
microscopy O
shoed O
unique O
and O
extensive O
damage O
to O
cells O
lining O
the O
distal O
nephron O
. O
It O
is O
suggested O
that O
these O
changes O
represent O
a O
specific O
toxic O
effect O
of O
lithium B-Chemical
, O
reported O
here O
for O
the O
first O
time O
in O
man O
. O
Cholestatic B-Disease
jaundice I-Disease
associated O
with O
the O
use O
of O
metformin B-Chemical
. O
We O
report O
a O
patient O
who O
developed O
cholestatic B-Disease
jaundice I-Disease
shortly O
after O
initiation O
of O
treatment O
with O
metformin B-Chemical
hydrochloride I-Chemical
. O
Ultrasound O
of O
the O
liver O
and O
abdominal O
CT O
were O
normal O
. O
An O
ERCP O
showed O
normal O
biliary O
anatomy O
. O
A O
percutaneous O
liver O
biopsy O
was O
obtained O
showing O
marked O
cholestasis B-Disease
, O
with O
portal O
edema B-Disease
, O
ductular O
proliferation O
, O
and O
acute O
inflammation B-Disease
. O
Metformin B-Chemical
hydrochloride I-Chemical
was O
discontinued O
, O
and O
the O
patient O
' O
s O
jaundice B-Disease
resolved O
slowly O
over O
a O
period O
of O
several O
months O
. O
Given O
the O
onset O
of O
his O
jaundice B-Disease
2 O
wk O
after O
the O
initiation O
of O
metformin B-Chemical
, O
we O
believe O
that O
this O
case O
represents O
an O
example O
of O
metformin B-Chemical
- O
associated O
hepatotoxicity B-Disease
, O
the O
first O
such O
case O
reported O
. O
Systemic O
toxicity B-Disease
and O
resuscitation O
in O
bupivacaine B-Chemical
- O
, O
levobupivacaine B-Chemical
- O
, O
or O
ropivacaine B-Chemical
- O
infused O
rats O
. O
We O
compared O
the O
systemic O
toxicity B-Disease
of O
bupivacaine B-Chemical
, O
levobupivacaine B-Chemical
, O
and O
ropivacaine B-Chemical
in O
anesthetized O
rats O
. O
We O
also O
compared O
the O
ability O
to O
resuscitate O
rats O
after O
lethal O
doses O
of O
these O
local O
anesthetics O
. O
Bupivacaine B-Chemical
, O
levobupivacaine B-Chemical
, O
or O
ropivacaine B-Chemical
was O
infused O
at O
a O
rate O
of O
2 O
mg O
. O
kg O
( O
- O
1 O
) O
. O
min O
( O
- O
1 O
) O
while O
electrocardiogram O
, O
electroencephalogram O
, O
and O
arterial O
pressure O
were O
continuously O
monitored O
. O
When O
asystole B-Disease
was O
recorded O
, O
drug O
infusion O
was O
stopped O
and O
a O
resuscitation O
sequence O
was O
begun O
. O
Epinephrine B-Chemical
0 O
. O
01 O
mg O
/ O
kg O
was O
administered O
at O
1 O
- O
min O
intervals O
while O
external O
cardiac O
compressions O
were O
applied O
. O
Resuscitation O
was O
considered O
successful O
when O
a O
systolic O
arterial O
pressure O
> O
or O
= O
100 O
mm O
Hg O
was O
achieved O
within O
5 O
min O
. O
The O
cumulative O
doses O
of O
levobupivacaine B-Chemical
and O
ropivacaine B-Chemical
that O
produced O
seizures B-Disease
were O
similar O
and O
were O
larger O
than O
those O
of O
bupivacaine B-Chemical
. O
The O
cumulative O
doses O
of O
levobupivacaine B-Chemical
that O
produced O
dysrhythmias B-Disease
and O
asystole B-Disease
were O
smaller O
than O
the O
corresponding O
doses O
of O
ropivacaine B-Chemical
, O
but O
they O
were O
larger O
than O
those O
of O
bupivacaine B-Chemical
. O
The O
number O
of O
successful O
resuscitations O
did O
not O
differ O
among O
groups O
. O
However O
, O
a O
smaller O
dose O
of O
epinephrine B-Chemical
was O
required O
in O
the O
Ropivacaine B-Chemical
group O
than O
in O
the O
other O
groups O
. O
We O
conclude O
that O
the O
systemic O
toxicity B-Disease
of O
levobupivacaine B-Chemical
is O
intermediate O
between O
that O
of O
ropivacaine B-Chemical
and O
bupivacaine B-Chemical
when O
administered O
at O
the O
same O
rate O
and O
that O
ropivacaine B-Chemical
- O
induced O
cardiac B-Disease
arrest I-Disease
appears O
to O
be O
more O
susceptible O
to O
treatment O
than O
that O
induced O
by O
bupivacaine B-Chemical
or O
levobupivacaine B-Chemical
. O
Amphotericin B-Chemical
B I-Chemical
- O
induced O
seizures B-Disease
in O
a O
patient O
with O
AIDS B-Disease
. O
OBJECTIVE O
: O
To O
report O
a O
case O
of O
multiple O
episodes O
of O
seizure B-Disease
activity O
in O
an O
AIDS B-Disease
patent O
following O
amphotericin B-Chemical
B I-Chemical
infusion O
. O
CASE O
SUMMARY O
: O
A O
46 O
- O
year O
- O
old O
African O
- O
American O
man O
experienced O
recurrent O
grand B-Disease
mal I-Disease
seizures I-Disease
during O
intravenous O
infusion O
of O
amphotericin B-Chemical
B I-Chemical
, O
then O
petit O
mal O
seizures B-Disease
as O
the O
infusion O
was O
stopped O
and O
the O
drug O
concentrations O
decreased O
with O
time O
. O
The O
patients O
concurrent O
medications O
included O
didanosine B-Chemical
, O
hydroxyzine B-Chemical
, O
promethazine B-Chemical
, O
hydrocortisone B-Chemical
, O
and O
prochlorperazine B-Chemical
. O
Despite O
administration O
of O
phenytoin B-Chemical
and O
lorazepam B-Chemical
, O
the O
seizures B-Disease
persisted O
and O
occurred O
only O
during O
amphotercin B-Chemical
B I-Chemical
administration O
. O
DISCUSSION O
: O
AIDS B-Disease
and O
cryptococcal B-Disease
meningitis I-Disease
, O
both O
of O
which O
the O
patient O
had O
, O
can O
potentially O
cause O
seizures B-Disease
. O
The O
patient O
had O
a O
history O
of O
alcohol B-Disease
abuse I-Disease
; O
alcohol B-Chemical
intake O
as O
well O
as O
withdrawal O
can O
also O
cause O
seizures B-Disease
. O
Didanosine B-Chemical
also O
has O
a O
potential O
for O
inducing O
seizures B-Disease
. O
However O
, O
these O
other O
potential O
causes O
of O
seizure B-Disease
were O
ruled O
out O
. O
The O
time O
course O
of O
events O
suggested O
that O
amphotericin B-Chemical
B I-Chemical
was O
the O
cause O
of O
the O
seizures B-Disease
in O
this O
AIDS B-Disease
patient O
. O
CONCLUSIONS O
: O
Amphotericin B-Chemical
B I-Chemical
seems O
to O
be O
the O
probable O
cause O
of O
the O
seizures B-Disease
. O
To O
date O
, O
only O
three O
cases O
of O
seizures B-Disease
associated O
with O
amphotericin B-Chemical
B I-Chemical
have O
been O
reported O
in O
the O
literature O
, O
but O
healthcare O
providers O
should O
be O
aware O
of O
the O
potential O
for O
this O
rare O
adverse O
effect O
. O
Sirolimus B-Chemical
and O
mycophenolate B-Chemical
mofetil I-Chemical
for O
calcineurin O
- O
free O
immunosuppression O
in O
renal O
transplant O
recipients O
. O
Calcineurin O
inhibitors O
, O
such O
as O
cyclosporine B-Chemical
and O
tacrolimus B-Chemical
, O
have O
been O
available O
for O
almost O
20 O
years O
. O
Although O
these O
drugs O
are O
highly O
effective O
and O
represent O
the O
mainstay O
of O
transplant O
immunosuppression O
, O
they O
are O
associated O
with O
acute O
and O
chronic O
nephrotoxicity B-Disease
. O
Acute O
nephrotoxicity B-Disease
, O
which O
occurs O
in O
the O
early O
period O
after O
transplantation O
, O
leads O
to O
a O
higher O
rate O
of O
dialysis O
, O
and O
chronic O
nephrotoxicity B-Disease
may O
eventually O
result O
in O
graft O
loss O
. O
Acute O
and O
chronic O
nephrotoxicity B-Disease
is O
becoming O
more O
common O
as O
the O
use O
of O
marginal O
kidneys O
for O
transplantation O
increases O
. O
Two O
recently O
available O
immunosuppressive O
agents O
, O
mycophenolate B-Chemical
mofetil I-Chemical
and O
sirolimus B-Chemical
( O
rapamycin B-Chemical
) O
, O
have O
no O
nephrotoxicity B-Disease
. O
The O
use O
of O
these O
drugs O
in O
combination O
with O
other O
agents O
has O
led O
to O
the O
development O
of O
new O
paradigms O
of O
immunosuppressive O
therapy O
. O
This O
paper O
reviews O
the O
results O
of O
clinical O
trials O
that O
have O
investigated O
these O
new O
approaches O
to O
immunosuppression O
in O
renal O
transplant O
recipients O
. O
Tolerability O
of O
nimesulide B-Chemical
and O
paracetamol B-Chemical
in O
patients O
with O
NSAID B-Chemical
- O
induced O
urticaria B-Disease
/ O
angioedema B-Disease
. O
Previous O
studies O
evaluated O
the O
tolerance O
of O
nimesulide B-Chemical
and O
paracetamol B-Chemical
in O
subjects O
with O
cutaneous O
, O
respiratory O
and O
anaphylactoid O
reactions O
induced O
by O
nonsteroidal B-Chemical
anti I-Chemical
- I-Chemical
inflammatory I-Chemical
drugs I-Chemical
( O
NSAIDs B-Chemical
) O
. O
In O
this O
study O
we O
investigated O
tolerability O
and O
reliability O
of O
nimesulide B-Chemical
and O
paracetamol B-Chemical
in O
a O
very O
large O
number O
of O
patients O
with O
an O
exclusive O
well O
- O
documented O
history O
of O
NSAID B-Chemical
- O
induced O
urticaria B-Disease
/ O
angioedema B-Disease
. O
Furthermore O
, O
we O
evaluated O
whether O
some O
factors O
have O
the O
potential O
to O
increase O
the O
risk O
of O
reaction O
to O
paracetamol B-Chemical
and O
nimesulide B-Chemical
. O
A O
single O
- O
placebo O
- O
controlled O
oral O
challenge O
procedure O
with O
nimesulide B-Chemical
or O
paracetamol B-Chemical
was O
applied O
to O
829 O
patients O
with O
a O
history O
of O
NSAID B-Chemical
- O
induced O
urticaria B-Disease
/ O
angioedema B-Disease
. O
A O
total O
of O
75 O
/ O
829 O
( O
9 O
. O
4 O
% O
) O
patients O
experienced O
reactions O
to O
nimesulide B-Chemical
or O
paracetamol B-Chemical
. O
Of O
the O
715 O
patients O
tested O
with O
nimesulide B-Chemical
62 O
( O
8 O
. O
6 O
% O
) O
showed O
a O
positive O
test O
, O
while O
of O
114 O
subjects O
submitted O
to O
the O
challenge O
with O
paracetamol B-Chemical
, O
13 O
( O
9 O
. O
6 O
% O
) O
did O
not O
tolerate O
this O
drug O
. O
Furthermore O
, O
18 O
. O
28 O
% O
of O
patients O
with O
a O
history O
of O
chronic O
urticaria B-Disease
and O
11 O
. O
8 O
% O
of O
subjects O
with O
an O
history O
of O
NSAID B-Chemical
- O
induced O
urticaria B-Disease
/ O
angioedema B-Disease
or O
angioedema B-Disease
alone O
( O
with O
or O
without O
chronic O
urticaria B-Disease
) O
resulted O
to O
be O
intolerant O
to O
alternative O
drugs O
. O
Taken O
together O
, O
our O
results O
confirm O
the O
good O
tolerability O
of O
nimesulide B-Chemical
and O
paracetamol B-Chemical
in O
patients O
who O
experienced O
urticaria B-Disease
/ O
angioedema B-Disease
caused O
by O
NSAIDs B-Chemical
. O
However O
, O
the O
risk O
of O
reaction O
to O
these O
alternative O
study O
drugs O
is O
statistically O
increased O
by O
a O
history O
of O
chronic O
urticaria B-Disease
and O
, O
above O
all O
, O
by O
a O
history O
of O
NSAID B-Chemical
- O
induced O
angioedema B-Disease
. O
Comparison O
of O
aqueous O
and O
gellan O
ophthalmic O
timolol B-Chemical
with O
placebo O
on O
the O
24 O
- O
hour O
heart O
rate O
response O
in O
patients O
on O
treatment O
for O
glaucoma B-Disease
. O
PURPOSE O
: O
Topical O
beta O
- O
blocker O
treatment O
is O
routine O
therapy O
in O
the O
management O
of O
patients O
with O
glaucoma B-Disease
. O
Therapy O
results O
in O
systemic O
absorption O
, O
however O
, O
the O
degree O
of O
reduction O
of O
resting O
and O
peak O
heart O
rate O
has O
not O
been O
quantified O
. O
DESIGN O
: O
This O
trial O
evaluated O
the O
effect O
of O
placebo O
, O
0 O
. O
5 O
% O
aqueous O
timolol B-Chemical
( O
timolol B-Chemical
solution O
) O
and O
a O
0 O
. O
5 O
% O
timolol B-Chemical
suspension O
that O
forms O
a O
gel O
on O
application O
to O
the O
conjunctiva O
( O
timolol B-Chemical
gellan O
) O
on O
the O
24 O
- O
hour O
heart O
rate O
in O
patients O
currently O
being O
treated O
for O
glaucoma B-Disease
to O
quantify O
the O
reduction O
in O
mean O
heart O
rate O
. O
METHODS O
: O
Forty O
- O
three O
Caucasian O
patients O
with O
primary O
open B-Disease
- I-Disease
angle I-Disease
glaucoma I-Disease
or O
ocular B-Disease
hypertension I-Disease
with O
a O
mean O
( O
+ O
/ O
- O
SD O
) O
age O
of O
63 O
( O
+ O
/ O
- O
8 O
) O
years O
were O
randomized O
and O
crossed O
over O
in O
a O
double O
- O
masked O
manner O
to O
14 O
days O
of O
treatment O
with O
placebo O
( O
morning O
and O
evening O
in O
both O
eyes O
) O
, O
timolol B-Chemical
solution O
( O
morning O
and O
evening O
in O
both O
eyes O
) O
, O
or O
timolol B-Chemical
gellan O
( O
morning O
in O
both O
eyes O
with O
placebo O
in O
the O
evening O
) O
. O
On O
the O
13th O
day O
of O
each O
period O
, O
heart O
rate O
was O
recorded O
continuously O
during O
a O
typical O
, O
ambulant O
24 O
- O
hour O
period O
. O
RESULTS O
: O
Both O
timolol B-Chemical
solution O
and O
timolol B-Chemical
gellan O
reduced O
the O
mean O
24 O
- O
hour O
heart O
rate O
compared O
with O
placebo O
( O
P O
< O
or O
= O
. O
001 O
) O
, O
and O
this O
reduction O
was O
most O
pronounced O
during O
the O
daytime O
( O
- O
7 O
. O
5 O
% O
change O
in O
mean O
heart O
rate O
, O
- O
5 O
. O
7 O
beats O
/ O
min O
) O
. O
Timolol B-Chemical
gellan O
showed O
a O
numerically O
but O
not O
significantly O
smaller O
reduction O
in O
24 O
- O
hour O
heart O
rate O
, O
compared O
with O
timolol B-Chemical
solution O
. O
During O
the O
night O
, O
the O
mean O
12 O
- O
hour O
heart O
rate O
on O
placebo O
and O
timolol B-Chemical
gellan O
were O
both O
significantly O
less O
than O
on O
timolol B-Chemical
solution O
; O
the O
difference O
between O
solution O
and O
gellan O
treatments O
was O
statistically O
significant O
( O
P O
= O
. O
01 O
) O
. O
CONCLUSIONS O
: O
Both O
timolol B-Chemical
solution O
and O
timolol B-Chemical
gellan O
decrease O
the O
mean O
24 O
- O
hour O
heart O
rate O
compared O
with O
placebo O
. O
This O
response O
was O
most O
pronounced O
during O
the O
active O
daytime O
period O
. O
These O
data O
quantify O
the O
modest O
bradycardia B-Disease
associated O
with O
ophthalmic O
beta O
- O
blocker O
therapy O
in O
a O
typical O
patient O
population O
on O
therapy O
for O
glaucoma B-Disease
. O
Although O
exercise O
performance O
was O
not O
assessed O
in O
this O
trial O
, O
reductions O
of O
this O
magnitude O
should O
not O
have O
substantial O
clinical O
consequences O
. O
Management O
strategies O
for O
ribavirin B-Chemical
- O
induced O
hemolytic B-Disease
anemia I-Disease
in O
the O
treatment O
of O
hepatitis B-Disease
C I-Disease
: O
clinical O
and O
economic O
implications O
. O
OBJECTIVES O
: O
Recently O
published O
studies O
have O
demonstrated O
increased O
efficacy O
and O
cost O
- O
effectiveness O
of O
combination O
therapy O
with O
interferon O
and O
alpha O
- O
2b O
/ O
ribavirin B-Chemical
compared O
with O
interferon B-Chemical
- I-Chemical
alpha I-Chemical
monotherapy O
in O
the O
treatment O
of O
chronic B-Disease
hepatitis I-Disease
C I-Disease
( O
CHC B-Disease
) O
. O
Combination O
therapy O
is O
associated O
with O
a O
clinically O
important O
adverse O
effect O
: O
ribavirin B-Chemical
- O
induced O
hemolytic B-Disease
anemia I-Disease
( O
RIHA B-Disease
) O
. O
The O
objective O
of O
this O
study O
was O
to O
evaluate O
the O
direct O
health O
- O
care O
costs O
and O
management O
of O
RIHA B-Disease
during O
treatment O
of O
CHC B-Disease
in O
a O
clinical O
trial O
setting O
. O
METHODS O
: O
A O
systematic O
literature O
review O
was O
conducted O
to O
synthesize O
information O
on O
the O
incidence O
and O
management O
of O
RIHA B-Disease
. O
Decision O
- O
analytic O
techniques O
were O
used O
to O
estimate O
the O
cost O
of O
treating O
RIHA B-Disease
. O
Uncertainty O
was O
evaluated O
using O
sensitivity O
analyses O
. O
RESULTS O
: O
RIHA B-Disease
, O
defined O
as O
a O
reduction O
in O
hemoglobin O
to O
less O
than O
100 O
g O
/ O
L O
, O
occurs O
in O
approximately O
7 O
% O
to O
9 O
% O
of O
patients O
treated O
with O
combination O
therapy O
. O
The O
standard O
of O
care O
for O
management O
of O
RIHA B-Disease
is O
reduction O
or O
discontinuation O
of O
the O
ribavirin B-Chemical
dosage O
. O
We O
estimated O
the O
direct O
cost O
of O
treating O
clinically O
significant O
RIHA B-Disease
to O
be O
170 O
per O
patient O
receiving O
combination O
therapy O
per O
48 O
- O
week O
treatment O
course O
( O
range O
68 O
- O
692 O
) O
. O
The O
results O
of O
the O
one O
- O
way O
sensitivity O
analyses O
ranged O
from O
57 O
to O
317 O
. O
In O
comparison O
, O
the O
cost O
of O
48 O
weeks O
of O
combination O
therapy O
is O
16 O
, O
459 O
. O
CONCLUSIONS O
: O
The O
direct O
cost O
of O
treating O
clinically O
significant O
RIHA B-Disease
is O
1 O
% O
( O
170 O
/ O
16 O
, O
459 O
) O
of O
drug O
treatment O
costs O
. O
Questions O
remain O
about O
the O
optimal O
dose O
of O
ribavirin B-Chemical
and O
the O
incidence O
of O
RIHA B-Disease
in O
a O
real O
- O
world O
population O
. O
Despite O
these O
uncertainties O
, O
this O
initial O
evaluation O
of O
the O
direct O
cost O
of O
treating O
RIHA B-Disease
provides O
an O
estimate O
of O
the O
cost O
and O
management O
implications O
of O
this O
clinically O
important O
adverse O
effect O
. O
Preliminary O
efficacy O
assessment O
of O
intrathecal O
injection O
of O
an O
American O
formulation O
of O
adenosine B-Chemical
in O
humans O
. O
BACKGROUND O
: O
Preclinical O
studies O
of O
intrathecal O
adenosine B-Chemical
suggest O
it O
may O
be O
effective O
in O
the O
treatment O
of O
acute B-Disease
and I-Disease
chronic I-Disease
pain I-Disease
in O
humans O
, O
and O
preliminary O
studies O
in O
volunteers O
and O
patients O
with O
a O
Swedish O
formulation O
of O
adenosine B-Chemical
suggests O
it O
may O
be O
effective O
in O
hypersensitivity B-Disease
states O
but O
not O
with O
acute O
noxious O
stimulation O
. O
The O
purpose O
of O
this O
study O
was O
to O
screen O
for O
efficacy O
of O
a O
different O
formulation O
of O
adenosine B-Chemical
marketed O
in O
the O
US O
, O
using O
both O
acute O
noxious O
stimulation O
and O
capsaicin B-Chemical
- O
evoked O
mechanical O
hypersensitivity B-Disease
. O
METHODS O
: O
Following O
Food O
and O
Drug O
Administration O
and O
institutional O
review O
board O
approval O
and O
written O
informed O
consent O
, O
65 O
volunteers O
were O
studied O
in O
two O
trials O
: O
an O
open O
- O
label O
, O
dose O
- O
escalating O
trial O
with O
intrathecal O
adenosine B-Chemical
doses O
of O
0 O
. O
25 O
- O
2 O
. O
0 O
mg O
and O
a O
double O
- O
blind O
, O
placebo O
- O
controlled O
trial O
of O
adenosine B-Chemical
, O
2 O
mg O
. O
Cerebrospinal O
fluid O
was O
obtained O
for O
pharmacokinetic O
analysis O
, O
and O
pain B-Disease
ratings O
in O
response O
to O
acute O
heat O
stimuli O
and O
areas O
of O
mechanical B-Disease
hyperalgesia I-Disease
and O
allodynia B-Disease
after O
intradermal O
capsaicin B-Chemical
injection O
were O
determined O
. O
RESULTS O
: O
Adenosine B-Chemical
produced O
no O
effect O
on O
pain B-Disease
report O
to O
acute O
noxious O
thermal O
or O
chemical O
stimulation O
but O
reduced O
mechanical B-Disease
hyperalgesia I-Disease
and O
allodynia B-Disease
from O
intradermal O
capsaicin B-Chemical
injection O
for O
at O
least O
24 O
h O
. O
In O
contrast O
, O
residence O
time O
of O
adenosine B-Chemical
in O
cerebrospinal O
fluid O
was O
short O
( O
< O
4 O
h O
) O
. O
CONCLUSIONS O
: O
These O
results O
show O
selective O
inhibition O
by O
intrathecal O
adenosine B-Chemical
of O
hypersensitivity B-Disease
, O
presumed O
to O
reflect O
central O
sensitization O
in O
humans O
after O
peripheral O
capsaicin B-Chemical
injection O
. O
The O
long O
- O
lasting O
effect O
is O
consistent O
with O
that O
observed O
in O
preliminary O
reports O
of O
patients O
with O
chronic O
neuropathic B-Disease
pain I-Disease
and O
is O
not O
due O
to O
prolonged O
residence O
of O
adenosine B-Chemical
in O
cerebrospinal O
fluid O
. O
Delayed O
- O
onset O
heparin B-Chemical
- O
induced O
thrombocytopenia B-Disease
. O
BACKGROUND O
: O
Heparin B-Chemical
- O
induced O
thrombocytopenia B-Disease
presents O
5 O
to O
12 O
days O
after O
heparin B-Chemical
exposure O
, O
with O
or O
without O
arterial B-Disease
or I-Disease
venous I-Disease
thromboemboli I-Disease
. O
Delayed O
recognition O
and O
treatment O
of O
heparin B-Chemical
- O
induced O
thrombocytopenia B-Disease
contribute O
to O
poor O
patient O
outcomes O
. O
OBJECTIVE O
: O
To O
describe O
and O
increase O
awareness O
of O
a O
clinical O
scenario O
in O
which O
the O
onset O
or O
manifestations O
of O
heparin B-Chemical
- O
induced O
thrombocytopenia B-Disease
are O
delayed O
. O
DESIGN O
: O
Retrospective O
case O
series O
. O
SETTING O
: O
Three O
large O
urban O
hospitals O
( O
with O
active O
cardiovascular O
surgery O
programs O
) O
. O
PATIENTS O
: O
14 O
patients O
seen O
over O
a O
3 O
- O
year O
period O
in O
whom O
heparin B-Chemical
- O
induced O
thrombocytopenia B-Disease
became O
apparent O
on O
delayed O
presentation O
with O
thromboembolic B-Disease
complications O
. O
MEASUREMENTS O
: O
Platelet O
counts O
, O
onset O
of O
objectively O
determined O
thromboembolism B-Disease
, O
results O
of O
heparin B-Chemical
- O
induced O
platelet O
factor O
4 O
antibody O
tests O
, O
and O
outcomes O
. O
RESULTS O
: O
Patients O
went O
home O
after O
hospitalizations O
that O
had O
included O
heparin B-Chemical
exposure O
- O
- O
in O
most O
cases O
, O
with O
no O
thrombocytopenia B-Disease
recognized O
- O
- O
only O
to O
return O
to O
the O
hospital O
( O
median O
, O
day O
14 O
) O
with O
thromboembolic B-Disease
complications O
. O
Thromboemboli B-Disease
were O
venous O
( O
12 O
patients O
, O
7 O
with O
pulmonary B-Disease
emboli I-Disease
) O
or O
arterial O
( O
4 O
patients O
) O
or O
both O
. O
Platelet O
counts O
were O
mildly O
decreased O
in O
all O
but O
2 O
patients O
on O
second O
presentation O
. O
On O
readmission O
, O
11 O
patients O
received O
therapeutic O
heparin B-Chemical
, O
which O
worsened O
the O
patients O
' O
clinical O
condition O
and O
, O
in O
all O
11 O
cases O
, O
decreased O
the O
platelet O
count O
( O
mean O
at O
readmission O
, O
143 O
x O
10 O
( O
9 O
) O
cells O
/ O
L O
; O
mean O
nadir O
after O
heparin B-Chemical
re O
- O
exposure O
, O
39 O
x O
10 O
( O
9 O
) O
cells O
/ O
L O
) O
. O
Results O
of O
serologic O
tests O
for O
heparin B-Chemical
- O
induced O
antibodies O
were O
positive O
in O
all O
patients O
. O
Subsequent O
treatments O
included O
alternative O
anticoagulants O
( O
11 O
patients O
) O
, O
thrombolytic O
drugs O
( O
3 O
patients O
) O
, O
inferior O
vena O
cava O
filters O
( O
3 O
patients O
) O
and O
, O
eventually O
, O
warfarin B-Chemical
( O
11 O
patients O
) O
. O
Three O
patients O
died O
. O
CONCLUSIONS O
: O
Delayed O
- O
onset O
heparin B-Chemical
- O
induced O
thrombocytopenia B-Disease
is O
increasingly O
being O
recognized O
. O
To O
avoid O
disastrous O
outcomes O
, O
physicians O
must O
consider O
heparin B-Chemical
- O
induced O
thrombocytopenia B-Disease
whenever O
a O
recently O
hospitalized O
patient O
returns O
with O
thromboembolism B-Disease
; O
therapy O
with O
alternative O
anticoagulants O
, O
not O
heparin B-Chemical
, O
should O
be O
initiated O
. O
Treatment O
of O
risperidone B-Chemical
- O
induced O
hyperprolactinemia B-Disease
with O
a O
dopamine B-Chemical
agonist O
in O
children O
. O
BACKGROUND O
: O
Risperidone B-Chemical
, O
a O
potent O
antagonist O
of O
both O
serotonergic O
( O
5HT2A O
) O
and O
dopaminergic O
D2 O
receptors O
is O
associated O
with O
hyperprolactinemia B-Disease
in O
adults O
and O
children O
. O
Chronically O
elevated O
prolactin O
levels O
in O
children O
with O
prolactinomas B-Disease
may O
be O
associated O
with O
arrested O
growth O
and O
development O
resulting O
in O
either O
delayed B-Disease
puberty I-Disease
or O
short O
stature O
. O
These O
possibilities O
stress O
the O
importance O
of O
developing O
a O
safe O
and O
effective O
approach O
to O
drug O
- O
induced O
hyperprolactinemia B-Disease
in O
youth O
. O
We O
report O
the O
successful O
treatment O
of O
risperidone B-Chemical
- O
induced O
hyperprolactinemia B-Disease
with O
cabergoline B-Chemical
in O
youth O
. O
METHODS O
: O
We O
undertook O
a O
retrospective O
case O
review O
of O
four O
children O
with O
risperidone B-Chemical
- O
induced O
hyperprolactinemia B-Disease
treated O
with O
cabergoline B-Chemical
. O
RESULTS O
: O
Four O
males O
( O
age O
6 O
- O
11 O
years O
) O
with O
Diagnostic O
and O
Statistical O
Manual O
of O
Mental B-Disease
Disorders I-Disease
( O
fourth O
edition O
) O
bipolar B-Disease
disorder I-Disease
or O
psychoses B-Disease
, O
with O
risperidone B-Chemical
- O
induced O
elevations O
in O
serum O
prolactin O
levels O
( O
57 O
. O
5 O
- O
129 O
ng O
/ O
mL O
, O
normal O
5 O
- O
15 O
ng O
/ O
mL O
) O
, O
were O
treated O
with O
cabergoline B-Chemical
( O
mean O
dose O
2 O
. O
13 O
+ O
/ O
- O
0 O
. O
09 O
mg O
/ O
week O
) O
. O
When O
serum O
prolactin O
levels O
normalized O
in O
all O
four O
subjects O
( O
mean O
11 O
. O
2 O
+ O
/ O
- O
10 O
. O
9 O
ng O
/ O
mL O
) O
, O
the O
cabergoline B-Chemical
dose O
was O
reduced O
to O
1 O
mg O
/ O
week O
in O
three O
of O
four O
subjects O
. O
The O
mean O
duration O
of O
therapy O
with O
cabergoline B-Chemical
was O
523 O
. O
5 O
+ O
/ O
- O
129 O
. O
7 O
days O
, O
and O
the O
mean O
duration O
of O
therapy O
with O
risperidone B-Chemical
was O
788 O
. O
5 O
+ O
/ O
- O
162 O
. O
5 O
days O
. O
Cabergoline B-Chemical
was O
well O
tolerated O
without O
adverse O
effects O
. O
CONCLUSIONS O
: O
Cabergoline B-Chemical
may O
be O
useful O
for O
the O
treatment O
of O
risperidone B-Chemical
- O
induced O
hyperprolactinemia B-Disease
in O
youth O
; O
however O
, O
further O
research O
is O
needed O
. O
Acute O
cholestatic B-Disease
hepatitis I-Disease
after O
exposure O
to O
isoflurane B-Chemical
. O
OBJECTIVE O
: O
To O
report O
a O
case O
of O
acute O
cholestatic B-Disease
hepatitis I-Disease
following O
exposure O
to O
the O
inhalational O
anesthetic O
isoflurane B-Chemical
. O
CASE O
SUMMARY O
: O
A O
70 O
- O
year O
- O
old O
healthy O
woman O
from O
Iraq O
developed O
acute O
cholestatic B-Disease
hepatitis I-Disease
3 O
weeks O
following O
repair O
of O
the O
right O
rotator O
cuff O
under O
general O
anesthesia O
. O
There O
was O
no O
evidence O
for O
viral O
, O
autoimmune O
, O
or O
metabolic O
causes O
of O
hepatitis B-Disease
. O
No O
other O
medications O
were O
involved O
except O
for O
dipyrone B-Chemical
for O
analgesia B-Disease
. O
The O
alanine B-Chemical
aminotransferase O
was O
elevated O
to O
a O
peak O
concentration O
of O
1533 O
U O
/ O
L O
and O
the O
serum O
bilirubin B-Chemical
reached O
a O
peak O
of O
17 O
. O
0 O
mg O
/ O
dL O
. O
There O
was O
slow O
improvement O
over O
4 O
months O
. O
Accidental O
reexposure O
by O
the O
patient O
to O
dipyrone B-Chemical
was O
uneventful O
. O
DISCUSSION O
: O
The O
clinical O
and O
histologic O
picture O
of O
this O
case O
resembles O
halothane B-Disease
hepatitis I-Disease
, O
which O
has O
a O
significant O
mortality O
rate O
. O
CONCLUSIONS O
: O
Isoflurane B-Chemical
, O
a O
common O
anesthetic O
agent O
, O
can O
cause O
severe O
cholestatic B-Disease
hepatitis I-Disease
. O
Torsade B-Disease
de I-Disease
pointes I-Disease
induced O
by O
metoclopramide B-Chemical
in O
an O
elderly O
woman O
with O
preexisting O
complete O
left B-Disease
bundle I-Disease
branch I-Disease
block I-Disease
. O
There O
is O
a O
growing O
list O
of O
drugs O
implicated O
in O
acquired O
long B-Disease
QT I-Disease
syndrome I-Disease
and O
torsade B-Disease
de I-Disease
pointes I-Disease
. O
However O
, O
the O
torsadogenic O
potential O
of O
metoclopramide B-Chemical
, O
a O
commonly O
used O
antiemetic O
and O
prokinetic O
drug O
, O
has O
not O
been O
reported O
in O
the O
literature O
, O
despite O
its O
chemical O
similarity O
to O
procainamide B-Chemical
. O
We O
report O
on O
a O
92 O
- O
year O
- O
old O
woman O
with O
preexisting O
complete O
left B-Disease
bundle I-Disease
branch I-Disease
block I-Disease
who O
developed O
torsade B-Disease
de I-Disease
pointes I-Disease
after O
intravenous O
and O
oral O
administration O
of O
metoclopramide B-Chemical
. O
This O
patient O
also O
developed O
torsade B-Disease
de I-Disease
pointes I-Disease
when O
cisapride B-Chemical
and O
erythromycin B-Chemical
were O
given O
simultaneously O
. O
These O
two O
episodes O
were O
suppressed O
successfully O
after O
discontinuing O
the O
offending O
drugs O
and O
administering O
class O
IB O
drugs O
. O
This O
is O
the O
first O
documentation O
that O
metoclopramide B-Chemical
provokes O
torsade B-Disease
de I-Disease
pointes I-Disease
clinically O
. O
Metoclopramide B-Chemical
should O
be O
used O
cautiously O
in O
patients O
with O
a O
risk O
of O
torsade B-Disease
de I-Disease
pointes I-Disease
. O
Dopamine B-Chemical
D2 O
receptor O
signaling O
controls O
neuronal O
cell O
death O
induced O
by O
muscarinic O
and O
glutamatergic O
drugs O
. O
Dopamine B-Chemical
( O
DA B-Chemical
) O
, O
through O
D1 O
/ O
D2 O
receptor O
- O
mediated O
signaling O
, O
plays O
a O
major O
role O
in O
the O
control O
of O
epileptic B-Disease
seizures I-Disease
arising O
in O
the O
limbic O
system O
. O
Excitotoxicity B-Disease
leading O
to O
neuronal O
cell O
death O
in O
the O
affected O
areas O
is O
a O
major O
consequence O
of O
seizures B-Disease
at O
the O
cellular O
level O
. O
In O
this O
respect O
, O
little O
is O
known O
about O
the O
role O
of O
DA B-Chemical
receptors O
in O
the O
occurrence O
of O
epilepsy B-Disease
- O
induced O
neuronal O
cell O
death O
. O
Here O
we O
analyze O
the O
occurrence O
of O
seizures B-Disease
and O
neurotoxicity B-Disease
in O
D2R O
- O
/ O
- O
mice O
treated O
with O
the O
cholinergic O
agonist O
pilocarpine B-Chemical
. O
We O
compared O
these O
results O
with O
those O
previously O
obtained O
with O
kainic B-Chemical
acid I-Chemical
( O
KA B-Chemical
) O
, O
a O
potent O
glutamate B-Chemical
agonist O
. O
Importantly O
, O
D2R O
- O
/ O
- O
mice O
develop O
seizures B-Disease
at O
doses O
of O
both O
drugs O
that O
are O
not O
epileptogenic O
for O
WT O
littermates O
and O
show O
greater O
neurotoxicity B-Disease
. O
However O
, O
pilocarpine B-Chemical
- O
induced O
seizures B-Disease
result O
in O
a O
more O
widespread O
neuronal O
death O
in O
both O
WT O
and O
D2R O
- O
/ O
- O
brains O
in O
comparison O
to O
KA B-Chemical
. O
Thus O
, O
the O
absence O
of O
D2R O
lowers O
the O
threshold O
for O
seizures B-Disease
induced O
by O
both O
glutamate B-Chemical
and O
acetylcholine B-Chemical
. O
Moreover O
, O
the O
dopaminergic O
control O
of O
epilepsy B-Disease
- O
induced O
neurodegeneration B-Disease
seems O
to O
be O
mediated O
by O
distinct O
interactions O
of O
D2R O
signaling O
with O
these O
two O
neurotransmitters O
. O
Steroid B-Chemical
structure O
and O
pharmacological O
properties O
determine O
the O
anti O
- O
amnesic B-Disease
effects O
of O
pregnenolone B-Chemical
sulphate I-Chemical
in O
the O
passive O
avoidance O
task O
in O
rats O
. O
Pregnenolone B-Chemical
sulphate I-Chemical
( O
PREGS B-Chemical
) O
has O
generated O
interest O
as O
one O
of O
the O
most O
potent O
memory O
- O
enhancing O
neurosteroids O
to O
be O
examined O
in O
rodent O
learning O
studies O
, O
with O
particular O
importance O
in O
the O
ageing O
process O
. O
The O
mechanism O
by O
which O
this O
endogenous O
steroid B-Chemical
enhances O
memory O
formation O
is O
hypothesized O
to O
involve O
actions O
on O
glutamatergic O
and O
GABAergic O
systems O
. O
This O
hypothesis O
stems O
from O
findings O
that O
PREGS B-Chemical
is O
a O
potent O
positive O
modulator O
of O
N B-Chemical
- I-Chemical
methyl I-Chemical
- I-Chemical
d I-Chemical
- I-Chemical
aspartate I-Chemical
receptors O
( O
NMDARs O
) O
and O
a O
negative O
modulator O
of O
gamma B-Chemical
- I-Chemical
aminobutyric I-Chemical
acid I-Chemical
( O
A O
) O
receptors O
( O
GABA B-Chemical
( O
A O
) O
Rs O
) O
. O
Moreover O
, O
PREGS B-Chemical
is O
able O
to O
reverse O
the O
amnesic B-Disease
- O
like O
effects O
of O
NMDAR O
and O
GABA B-Chemical
( O
A O
) O
R O
ligands O
. O
To O
investigate O
this O
hypothesis O
, O
the O
present O
study O
in O
rats O
examined O
the O
memory O
- O
altering O
abilities O
of O
structural O
analogs O
of O
PREGS B-Chemical
, O
which O
differ O
in O
their O
modulation O
of O
NMDAR O
and O
/ O
or O
GABA B-Chemical
( O
A O
) O
R O
function O
. O
The O
analogs O
tested O
were O
: O
11 B-Chemical
- I-Chemical
ketopregnenolone I-Chemical
sulphate I-Chemical
( O
an O
agent O
that O
is O
inactive O
at O
GABA B-Chemical
( O
A O
) O
Rs O
and O
NMDARs O
) O
, O
epipregnanolone B-Chemical
( I-Chemical
[ I-Chemical
3beta I-Chemical
- I-Chemical
hydroxy I-Chemical
- I-Chemical
5beta I-Chemical
- I-Chemical
pregnan I-Chemical
- I-Chemical
20 I-Chemical
- I-Chemical
one I-Chemical
] I-Chemical
sulphate I-Chemical
, O
an O
inhibitor O
of O
both O
GABA B-Chemical
( O
A O
) O
Rs O
and O
NMDARs O
) O
, O
and O
a O
newly O
synthesized O
( O
- O
) O
PREGS B-Chemical
enantiomer O
( O
which O
is O
identical O
to O
PREGS B-Chemical
in O
effects O
on O
GABA B-Chemical
( O
A O
) O
Rs O
and O
NMDARs O
) O
. O
The O
memory O
- O
enhancing O
effects O
of O
PREGS B-Chemical
and O
its O
analogs O
were O
tested O
in O
the O
passive O
avoidance O
task O
using O
the O
model O
of O
scopolamine B-Chemical
- O
induced O
amnesia B-Disease
. O
Both O
PREGS B-Chemical
and O
its O
( O
- O
) O
enantiomer O
blocked O
the O
effects O
of O
scopolamine B-Chemical
. O
The O
results O
show O
that O
, O
unlike O
PREGS B-Chemical
, O
11 B-Chemical
- I-Chemical
ketopregnenolone I-Chemical
sulphate I-Chemical
and O
epipregnanolone B-Chemical
sulphate I-Chemical
failed O
to O
block O
the O
effect O
of O
scopolamine B-Chemical
, O
suggesting O
that O
altering O
the O
modulation O
of O
NMDA B-Chemical
receptors O
diminishes O
the O
memory O
- O
enhancing O
effects O
of O
PREGS B-Chemical
. O
Moreover O
, O
enantioselectivity O
was O
demonstrated O
by O
the O
ability O
of O
natural O
PREGS B-Chemical
to O
be O
an O
order O
of O
magnitude O
more O
effective O
than O
its O
synthetic O
enantiomer O
in O
reversing O
scopolamine B-Chemical
- O
induced O
amnesia B-Disease
. O
These O
results O
identify O
a O
novel O
neuropharmacological O
site O
for O
the O
modulation O
of O
memory O
processes O
by O
neuroactive O
steroids B-Chemical
. O
Activation O
of O
poly B-Chemical
( I-Chemical
ADP I-Chemical
- I-Chemical
ribose I-Chemical
) I-Chemical
polymerase O
contributes O
to O
development O
of O
doxorubicin B-Chemical
- O
induced O
heart B-Disease
failure I-Disease
. O
Activation O
of O
the O
nuclear O
enzyme O
poly B-Chemical
( I-Chemical
ADP I-Chemical
- I-Chemical
ribose I-Chemical
) I-Chemical
polymerase O
( O
PARP O
) O
by O
oxidant O
- O
mediated O
DNA O
damage O
is O
an O
important O
pathway O
of O
cell O
dysfunction O
and O
tissue O
injury O
in O
conditions O
associated O
with O
oxidative O
stress O
. O
Increased O
oxidative O
stress O
is O
a O
major O
factor O
implicated O
in O
the O
cardiotoxicity B-Disease
of O
doxorubicin B-Chemical
( O
DOX B-Chemical
) O
, O
a O
widely O
used O
antitumor O
anthracycline B-Chemical
antibiotic O
. O
Thus O
, O
we O
hypothesized O
that O
the O
activation O
of O
PARP O
may O
contribute O
to O
the O
DOX B-Chemical
- O
induced O
cardiotoxicity B-Disease
. O
Using O
a O
dual O
approach O
of O
PARP O
- O
1 O
suppression O
, O
by O
genetic O
deletion O
or O
pharmacological O
inhibition O
with O
the O
phenanthridinone O
PARP O
inhibitor O
PJ34 B-Chemical
, O
we O
now O
demonstrate O
the O
role O
of O
PARP O
in O
the O
development O
of O
cardiac B-Disease
dysfunction I-Disease
induced O
by O
DOX B-Chemical
. O
PARP O
- O
1 O
+ O
/ O
+ O
and O
PARP O
- O
1 O
- O
/ O
- O
mice O
received O
a O
single O
injection O
of O
DOX B-Chemical
( O
25 O
mg O
/ O
kg O
i O
. O
p O
) O
. O
Five O
days O
after O
DOX B-Chemical
administration O
, O
left O
ventricular O
performance O
was O
significantly O
depressed O
in O
PARP O
- O
1 O
+ O
/ O
+ O
mice O
, O
but O
only O
to O
a O
smaller O
extent O
in O
PARP O
- O
1 O
- O
/ O
- O
ones O
. O
Similar O
experiments O
were O
conducted O
in O
BALB O
/ O
c O
mice O
treated O
with O
PJ34 B-Chemical
or O
vehicle O
. O
Treatment O
with O
a O
PJ34 B-Chemical
significantly O
improved O
cardiac B-Disease
dysfunction I-Disease
and O
increased O
the O
survival O
of O
the O
animals O
. O
In O
addition O
PJ34 B-Chemical
significantly O
reduced O
the O
DOX B-Chemical
- O
induced O
increase O
in O
the O
serum O
lactate B-Chemical
dehydrogenase O
and O
creatine B-Chemical
kinase O
activities O
but O
not O
metalloproteinase O
activation O
in O
the O
heart O
. O
Thus O
, O
PARP O
activation O
contributes O
to O
the O
cardiotoxicity B-Disease
of O
DOX B-Chemical
. O
PARP O
inhibitors O
may O
exert O
protective O
effects O
against O
the O
development O
of O
severe O
cardiac B-Disease
complications I-Disease
associated O
with O
the O
DOX B-Chemical
treatment O
. O
Spironolactone B-Chemical
: O
is O
it O
a O
novel O
drug O
for O
the O
prevention O
of O
amphotericin B-Chemical
B I-Chemical
- O
related O
hypokalemia B-Disease
in O
cancer B-Disease
patients O
? O
OBJECTIVE O
: O
Nephrotoxicity B-Disease
is O
the O
major O
adverse O
effect O
of O
amphotericin B-Chemical
B I-Chemical
( O
AmB B-Chemical
) O
, O
often O
limiting O
administration O
of O
full O
dosage O
. O
Selective O
distal O
tubular O
epithelial O
toxicity B-Disease
seems O
to O
be O
responsible O
for O
the O
profound O
potassium B-Chemical
wasting O
that O
is O
a O
major O
clinical O
side O
effect O
of O
treatment O
with O
AmB B-Chemical
. O
Potassium B-Chemical
depletion O
also O
potentiates O
the O
tubular O
toxicity B-Disease
of O
AmB B-Chemical
. O
This O
study O
was O
designed O
to O
assess O
the O
ability O
of O
spironolactone B-Chemical
to O
reduce O
potassium B-Chemical
requirements O
and O
to O
prevent O
hypokalemia B-Disease
in O
neutropenic B-Disease
patients O
on O
AmB B-Chemical
treatment O
. O
METHODS O
: O
In O
this O
study O
26 O
patients O
with O
various O
hematological B-Disease
disorders I-Disease
were O
randomized O
to O
receive O
either O
intravenous O
AmB B-Chemical
alone O
or O
AmB B-Chemical
and O
oral O
spironolactone B-Chemical
100 O
mg O
twice O
daily O
when O
developing O
a O
proven O
or O
suspected O
fungal B-Disease
infection I-Disease
. O
RESULTS O
: O
Patients O
receiving O
concomitant O
AmB B-Chemical
and O
spironolactone B-Chemical
had O
significantly O
higher O
plasma O
potassium B-Chemical
levels O
than O
those O
receiving O
AmB B-Chemical
alone O
( O
P O
= O
0 O
. O
0027 O
) O
. O
Those O
patients O
receiving O
AmB B-Chemical
and O
spironolactone B-Chemical
required O
significantly O
less O
potassium B-Chemical
supplementation O
to O
maintain O
their O
plasma O
potassium B-Chemical
within O
the O
normal O
range O
( O
P O
= O
0 O
. O
022 O
) O
. O
Moreover O
, O
urinary O
potassium B-Chemical
losses O
were O
significantly O
less O
in O
patients O
receiving O
AmB B-Chemical
and O
spironolactone B-Chemical
than O
those O
receiving O
AmB B-Chemical
alone O
( O
P O
= O
0 O
. O
040 O
) O
. O
CONCLUSION O
: O
This O
study O
showed O
that O
spironolactone B-Chemical
can O
reduce O
potassium B-Chemical
requirements O
and O
prevent O
hypokalemia B-Disease
by O
reducing O
urinary O
potassium B-Chemical
loss O
in O
neutropenic B-Disease
patients O
on O
AmB B-Chemical
treatment O
. O
Erectile B-Disease
dysfunction I-Disease
occurs O
following O
substantia O
nigra O
lesions O
in O
the O
rat O
. O
Erectile O
function O
was O
assessed O
6 O
weeks O
following O
uni O
- O
and O
bilateral O
injections O
of O
6 B-Chemical
- I-Chemical
hydroxydopamine I-Chemical
in O
the O
substantia O
nigra O
nucleus O
of O
the O
brain O
. O
Behavioral O
apomorphine B-Chemical
- O
induced O
penile O
erections O
were O
reduced O
( O
5 O
/ O
8 O
) O
and O
increased O
( O
3 O
/ O
8 O
) O
in O
uni O
- O
and O
bilateral O
lesioned O
animals O
. O
Intracavernous O
pressures O
, O
following O
electrical O
stimulation O
of O
the O
cavernous O
nerve O
, O
decreased O
in O
lesioned O
animals O
. O
Lesions O
of O
the O
substantia O
nigra O
were O
confirmed O
by O
histology O
. O
Concentration O
of O
dopamine B-Chemical
and O
its O
metabolites O
were O
decreased O
in O
the O
striatum O
of O
substantia O
nigra O
lesioned O
rats O
. O
Lesions O
of O
the O
substantia O
nigra O
are O
therefore O
associated O
with O
erectile B-Disease
dysfunction I-Disease
in O
rats O
and O
may O
serve O
as O
a O
model O
to O
study O
erectile B-Disease
dysfunction I-Disease
in O
Parkinson B-Disease
' I-Disease
s I-Disease
disease I-Disease
. O
Nicotine B-Chemical
potentiation O
of O
morphine B-Chemical
- O
induced O
catalepsy B-Disease
in O
mice O
. O
In O
the O
present O
study O
, O
effects O
of O
nicotine B-Chemical
on O
catalepsy B-Disease
induced O
by O
morphine B-Chemical
in O
mice O
have O
been O
investigated O
. O
Morphine B-Chemical
but O
not O
nicotine B-Chemical
induced O
a O
dose O
- O
dependent O
catalepsy B-Disease
. O
The O
response O
of O
morphine B-Chemical
was O
potentiated O
by O
nicotine B-Chemical
. O
Intraperitoneal O
administration O
of O
atropine B-Chemical
, O
naloxone B-Chemical
, O
mecamylamine B-Chemical
, O
and O
hexamethonium B-Chemical
to O
mice O
reduced O
catalepsy B-Disease
induced O
by O
a O
combination O
of O
morphine B-Chemical
with O
nicotine B-Chemical
. O
Intracerebroventricular O
injection O
of O
atropine B-Chemical
, O
hexamethonium B-Chemical
, O
and O
naloxone B-Chemical
also O
decreased O
catalepsy B-Disease
induced O
by O
morphine B-Chemical
plus O
nicotine B-Chemical
. O
Intraperitoneal O
administration O
of O
atropine B-Chemical
, O
but O
not O
intraperitoneal O
or O
intracerebroventricular O
injection O
of O
hexamethonium B-Chemical
, O
decreased O
the O
effect O
of O
a O
single O
dose O
of O
morphine B-Chemical
. O
It O
was O
concluded O
that O
morphine B-Chemical
catalepsy B-Disease
can O
be O
elicited O
by O
opioid O
and O
cholinergic O
receptors O
, O
and O
the O
potentiation O
of O
morphine B-Chemical
induced O
by O
nicotine B-Chemical
may O
also O
be O
mediated O
through O
cholinergic O
receptor O
mechanisms O
. O
Force O
overflow O
and O
levodopa B-Chemical
- O
induced O
dyskinesias B-Disease
in O
Parkinson B-Disease
' I-Disease
s I-Disease
disease I-Disease
. O
We O
assessed O
force O
coordination O
of O
the O
hand O
in O
Parkinson B-Disease
' I-Disease
s I-Disease
disease I-Disease
and O
its O
relationship O
to O
motor O
complications O
of O
levodopa B-Chemical
therapy O
, O
particularly O
to O
levodopa B-Chemical
- O
induced O
dyskinesias B-Disease
( O
LID B-Disease
) O
. O
We O
studied O
two O
groups O
of O
Parkinson B-Disease
' I-Disease
s I-Disease
disease I-Disease
patients O
with O
( O
Parkinson B-Disease
' I-Disease
s I-Disease
disease I-Disease
+ O
LID B-Disease
, O
n O
= O
23 O
) O
and O
without O
levodopa B-Chemical
- O
induced O
dyskinesias B-Disease
( O
Parkinson B-Disease
' I-Disease
s I-Disease
disease I-Disease
- O
LID B-Disease
, O
n O
= O
10 O
) O
, O
and O
age O
- O
matched O
healthy O
controls O
. O
The O
motor O
score O
of O
the O
Unified O
Parkinson B-Disease
' I-Disease
s I-Disease
Disease I-Disease
Rating O
Scale O
, O
a O
dyskinesia B-Disease
score O
and O
force O
in O
a O
grip O
- O
lift O
paradigm O
were O
assessed O
ON O
and O
OFF O
levodopa B-Chemical
. O
A O
pathological O
increase O
of O
forces O
was O
seen O
in O
ON O
- O
state O
in O
Parkinson B-Disease
' I-Disease
s I-Disease
disease I-Disease
+ O
LID B-Disease
only O
. O
In O
Parkinson B-Disease
' I-Disease
s I-Disease
disease I-Disease
+ O
LID B-Disease
, O
the O
force O
involved O
in O
pressing O
down O
the O
object O
before O
lifting O
was O
significantly O
increased O
by O
levodopa B-Chemical
( O
by O
61 O
% O
, O
P O
< O
0 O
. O
05 O
) O
. O
An O
overshooting O
of O
peak O
grip O
force O
by O
51 O
% O
( O
P O
< O
0 O
. O
05 O
) O
and O
of O
static O
grip O
force O
by O
45 O
% O
( O
P O
< O
0 O
. O
01 O
) O
was O
observed O
in O
the O
ON O
- O
compared O
with O
the O
OFF O
- O
drug O
condition O
. O
In O
contrast O
, O
no O
excessive O
force O
was O
found O
in O
Parkinson B-Disease
' I-Disease
s I-Disease
disease I-Disease
- O
LID B-Disease
. O
Peak O
grip O
force O
in O
ON O
- O
state O
was O
140 O
% O
( O
P O
< O
0 O
. O
05 O
) O
higher O
in O
Parkinson B-Disease
' I-Disease
s I-Disease
disease I-Disease
+ O
LID B-Disease
than O
in O
Parkinson B-Disease
' I-Disease
s I-Disease
disease I-Disease
- O
LID B-Disease
, O
while O
static O
grip O
force O
was O
increased O
by O
138 O
% O
( O
P O
< O
0 O
. O
01 O
) O
between O
groups O
. O
Severity O
of O
peak O
- O
dose O
dyskinesias B-Disease
was O
strongly O
correlated O
with O
grip O
force O
in O
ON O
- O
state O
( O
r O
= O
0 O
. O
79 O
with O
peak O
force O
, O
P O
< O
0 O
. O
01 O
) O
. O
No O
correlation O
was O
observed O
between O
forces O
and O
the O
motor O
score O
as O
well O
as O
with O
the O
daily O
dose O
of O
dopaminergic O
medication O
. O
Force O
excess O
was O
only O
observed O
in O
patients O
with O
LID B-Disease
and O
motor O
fluctuations O
. O
A O
close O
relationship O
was O
seen O
between O
the O
overshooting O
of O
forces O
and O
dyskinesias B-Disease
in O
the O
ON O
- O
drug O
condition O
. O
We O
postulate O
that O
both O
LID B-Disease
and O
grip O
force O
excess O
share O
common O
pathophysiological O
mechanisms O
related O
to O
motor O
fluctuations O
. O
Behavioral O
effects O
of O
MK B-Chemical
- I-Chemical
801 I-Chemical
on O
reserpine B-Chemical
- O
treated O
mice O
. O
The O
effects O
of O
dizocilpine B-Chemical
( O
MK B-Chemical
- I-Chemical
801 I-Chemical
) O
, O
a O
noncompetitive O
N B-Chemical
- I-Chemical
methyl I-Chemical
- I-Chemical
D I-Chemical
- I-Chemical
aspartate I-Chemical
( O
NMDA B-Chemical
) O
receptor O
antagonist O
, O
were O
studied O
on O
dopamine B-Chemical
- O
related O
behaviors O
induced O
by O
reserpine B-Chemical
treatments O
. O
This O
study O
focuses O
on O
behavioral O
syndromes O
that O
may O
used O
as O
models O
for O
Parkinson B-Disease
' I-Disease
s I-Disease
disease I-Disease
, O
or O
tardive B-Disease
dyskinesia I-Disease
, O
and O
its O
response O
after O
glutamatergic O
blockage O
. O
Reserpine B-Chemical
( O
1 O
mg O
/ O
kg O
) O
, O
administered O
once O
every O
other O
day O
for O
4 O
days O
, O
produced O
increases O
in O
orofacial B-Disease
dyskinesia I-Disease
, O
tongue O
protrusion O
and O
vacuous O
chewing O
in O
mice O
, O
which O
are O
signs O
indicative O
of O
tardive B-Disease
dyskinesia I-Disease
. O
Reserpine B-Chemical
also O
produced O
tremor B-Disease
and O
catalepsy B-Disease
, O
which O
are O
signs O
suggestive O
of O
Parkinson B-Disease
' I-Disease
s I-Disease
disease I-Disease
. O
MK B-Chemical
- I-Chemical
801 I-Chemical
( O
0 O
. O
1 O
mg O
/ O
kg O
) O
, O
administered O
30 O
min O
before O
the O
observation O
test O
, O
prevented O
the O
vacuous O
chewing O
movements O
, O
tongue O
protrusions O
and O
catalepsy B-Disease
induced O
by O
reserpine B-Chemical
. O
However O
, O
MK B-Chemical
- I-Chemical
801 I-Chemical
injection O
produced O
a O
significant O
increase O
of O
tremor B-Disease
in O
reserpine B-Chemical
- O
treated O
mice O
. O
Reserpine B-Chemical
( O
1 O
mg O
/ O
kg O
) O
, O
administered O
90 O
min O
before O
the O
test O
and O
followed O
by O
apomophine B-Chemical
injection O
( O
0 O
. O
1 O
mg O
/ O
kg O
) O
5 O
min O
before O
the O
test O
, O
did O
not O
produce O
oral B-Disease
dyskinesia I-Disease
in O
mice O
. O
On O
the O
other O
hand O
, O
reserpine B-Chemical
induced O
increases O
in O
tremor B-Disease
and O
catalepsy B-Disease
compared O
to O
control O
mice O
. O
MK B-Chemical
- I-Chemical
801 I-Chemical
( O
0 O
. O
1 O
mg O
/ O
kg O
) O
administration O
attenuated O
the O
catalepsy B-Disease
and O
tremor B-Disease
induced O
by O
reserpine B-Chemical
. O
Pretreatment O
with O
reserpine B-Chemical
( O
1 O
mg O
/ O
kg O
) O
24 O
h O
before O
the O
observation O
test O
produced O
increases O
in O
vacuous O
chewing O
movements O
and O
tongue O
protrusion O
, O
as O
well O
as O
increases O
in O
tremor B-Disease
and O
catalepsy B-Disease
, O
whereas O
MK B-Chemical
- I-Chemical
801 I-Chemical
( O
0 O
. O
1 O
mg O
/ O
kg O
) O
injection O
90 O
min O
before O
the O
test O
reversed O
the O
effects O
of O
reserpine B-Chemical
. O
These O
results O
show O
that O
reserpine B-Chemical
produces O
different O
and O
abnormal B-Disease
movements I-Disease
, O
which O
are O
related O
to O
dose O
and O
schedule O
employed O
and O
can O
be O
considered O
as O
parkinsonian B-Disease
- O
like O
and O
tardive B-Disease
dsykinesia I-Disease
signs O
. O
The O
glutamatergic O
blockage O
produced O
by O
NMDA B-Chemical
can O
restore O
these O
signs O
, O
such O
as O
vacuous O
chewing O
movements O
, O
tongue O
protrusions O
, O
catalepsy B-Disease
and O
tremor B-Disease
according O
to O
the O
employed O
model O
. O
Risperidone B-Chemical
- O
associated O
, O
benign O
transient O
visual B-Disease
disturbances I-Disease
in O
schizophrenic B-Disease
patients O
with O
a O
past O
history O
of O
LSD B-Chemical
abuse O
. O
Two O
schizophrenic B-Disease
patients O
, O
who O
had O
a O
prior O
history O
of O
LSD B-Chemical
abuse O
and O
who O
had O
previously O
developed O
EPS B-Disease
with O
classic O
antipsychotics O
, O
were O
successfully O
treated O
with O
risperidone B-Chemical
. O
They O
both O
reported O
short O
episodes O
of O
transient O
visual B-Disease
disturbances I-Disease
, O
which O
appeared O
immediately O
after O
starting O
treatment O
with O
risperidone B-Chemical
. O
This O
imagery O
resembled O
visual B-Disease
disturbances I-Disease
previously O
experienced O
as O
" O
flashbacks O
" O
related O
to O
prior O
LSD B-Chemical
consumption O
. O
Risperidone B-Chemical
administration O
was O
continued O
and O
the O
visual B-Disease
disturbances I-Disease
gradually O
wore O
off O
. O
During O
a O
six O
- O
month O
follow O
- O
up O
period O
, O
there O
was O
no O
recurrence O
of O
visual B-Disease
disturbances I-Disease
. O
This O
phenomenon O
may O
be O
interpreted O
as O
a O
benign O
, O
short O
- O
term O
and O
self O
- O
limiting O
side O
effect O
which O
does O
not O
contraindicate O
the O
use O
of O
risperidone B-Chemical
or O
interfere O
with O
treatment O
. O
Conclusions O
based O
on O
two O
case O
reports O
should O
be O
taken O
with O
appropriate O
caution O
. O
Topiramate B-Chemical
- O
induced O
nephrolithiasis B-Disease
. O
Topiramate B-Chemical
is O
a O
recently O
developed O
antiepileptic O
medication O
that O
is O
becoming O
more O
widely O
prescribed O
because O
of O
its O
efficacy O
in O
treating O
refractory B-Disease
seizures I-Disease
. O
Urologists O
should O
be O
aware O
that O
this O
medication O
can O
cause O
metabolic B-Disease
acidosis I-Disease
in O
patients O
secondary O
to O
inhibition O
of O
carbonic O
anhydrase O
. O
In O
addition O
, O
a O
distal O
tubular O
acidification O
defect O
may O
result O
, O
thus O
impairing O
the O
normal O
compensatory O
drop O
in O
urine O
pH O
. O
These O
factors O
can O
lead O
to O
the O
development O
of O
calcium B-Chemical
phosphate I-Chemical
nephrolithiasis B-Disease
. O
We O
report O
the O
first O
two O
cases O
of O
topiramate B-Chemical
- O
induced O
nephrolithiasis B-Disease
in O
the O
urologic O
literature O
. O
Ketamine B-Chemical
in O
war O
/ O
tropical O
surgery O
( O
a O
final O
tribute O
to O
the O
racemic O
mixture O
) O
. O
A O
technique O
of O
continuous O
intravenous O
anaesthesia O
with O
ketamine B-Chemical
was O
used O
successfully O
during O
the O
Somalia O
civil O
war O
in O
1994 O
and O
in O
north O
Uganda O
in O
1999 O
for O
64 O
operations O
in O
62 O
patients O
, O
aged O
from O
6 O
weeks O
to O
70 O
years O
, O
undergoing O
limb O
and O
abdominal O
surgery O
including O
caesarian O
sections O
and O
interventions O
in O
neonates O
. O
Operations O
lasting O
up O
to O
2h O
could O
be O
performed O
in O
the O
absence O
of O
sophisticated O
equipment O
such O
as O
pulse O
oximeters O
or O
ventilators O
in O
patients O
on O
spontaneous O
ventilation O
breathing O
air O
/ O
oxygen B-Chemical
only O
. O
After O
premedication O
with O
diazepam B-Chemical
, O
glycopyrrolate B-Chemical
and O
local O
anaesthesia O
, O
and O
induction O
with O
standard O
doses O
of O
ketamine B-Chemical
, O
a O
maintenance O
dose O
of O
10 O
- O
20 O
microg O
/ O
kg O
/ O
min O
of O
ketamine B-Chemical
proved O
safe O
and O
effective O
. O
Emphasis O
was O
placed O
on O
bedside O
clinical O
monitoring O
, O
relying O
heavily O
on O
the O
heart O
rate O
. O
Diazepam B-Chemical
, O
unless O
contraindicated O
or O
risky O
, O
remains O
the O
only O
necessary O
complementary O
drug O
to O
ketamine B-Chemical
as O
it O
buffers O
its O
cardiovascular O
response O
and O
decreases O
the O
duration O
and O
intensity O
of O
operative O
and O
postoperative O
hallucinations B-Disease
. O
Local O
anaesthetic O
blocks O
were O
useful O
in O
decreasing O
the O
requirement O
for O
postoperative O
analgesia B-Disease
. O
An O
antisialogue O
was O
usually O
unnecessary O
in O
operations O
lasting O
up O
to O
2 O
h O
, O
glycopyrrolate B-Chemical
being O
the O
best O
choice O
for O
its O
lowest O
psychotropic O
and O
chronotropic O
effects O
, O
especially O
in O
a O
hot O
climate O
. O
Experience O
in O
war O
/ O
tropical O
settings O
suggests O
this O
technique O
could O
be O
useful O
in O
civilian O
contexts O
such O
as O
outdoor O
life O
- O
saving O
emergency O
surgery O
or O
in O
mass O
casualties O
where O
, O
e O
. O
g O
. O
amputation O
and O
rapid O
extrication O
were O
required O
. O
Intravenous O
ribavirin B-Chemical
treatment O
for O
severe O
adenovirus B-Disease
disease I-Disease
in O
immunocompromised O
children O
. O
BACKGROUND O
: O
Adenovirus O
is O
an O
important O
cause O
of O
morbidity O
and O
mortality O
in O
the O
immunocompromised O
host O
. O
The O
incidence O
of O
severe O
adenovirus B-Disease
disease I-Disease
in O
pediatrics O
is O
increasing O
in O
association O
with O
growing O
numbers O
of O
immunocompromised O
children O
, O
where O
case O
fatality O
rates O
as O
high O
as O
50 O
% O
to O
80 O
% O
have O
been O
reported O
. O
There O
are O
no O
approved O
antiviral O
agents O
with O
proven O
efficacy O
for O
the O
treatment O
of O
severe O
adenovirus B-Disease
disease I-Disease
, O
nor O
are O
there O
any O
prospective O
randomized O
, O
controlled O
trials O
of O
potentially O
useful O
anti O
- O
adenovirus O
therapies O
. O
Apparent O
clinical O
success O
in O
the O
treatment O
of O
severe O
adenovirus B-Disease
disease I-Disease
is O
limited O
to O
a O
few O
case O
reports O
and O
small O
series O
. O
Experience O
is O
greatest O
with O
intravenous O
ribavirin B-Chemical
and O
cidofovir B-Chemical
. O
Ribavirin B-Chemical
, O
a O
guanosine B-Chemical
analogue O
, O
has O
broad O
antiviral O
activity O
against O
both O
RNA O
and O
DNA O
viruses O
, O
including O
documented O
activity O
against O
adenovirus O
in O
vitro O
. O
Ribavirin B-Chemical
is O
licensed O
in O
aerosol O
form O
for O
the O
treatment O
of O
respiratory B-Disease
syncytial I-Disease
virus I-Disease
infection I-Disease
, O
and O
orally O
in O
combination O
with O
interferon O
to O
treat O
hepatitis B-Disease
C I-Disease
. O
Intravenous O
ribavirin B-Chemical
is O
the O
treatment O
of O
choice O
for O
infection B-Disease
with I-Disease
hemorrhagic I-Disease
fever I-Disease
viruses I-Disease
. O
The O
most O
common O
adverse O
effect O
of O
intravenous O
ribavirin B-Chemical
is O
reversible O
mild O
anemia B-Disease
. O
The O
use O
of O
cidofovir B-Chemical
in O
severe O
adenovirus B-Disease
infection I-Disease
has O
been O
limited O
by O
adverse O
effects O
, O
the O
most O
significant O
of O
which O
is O
nephrotoxicity B-Disease
. O
OBJECTIVE O
: O
We O
report O
our O
experience O
with O
intravenous O
ribavirin B-Chemical
therapy O
for O
severe O
adenovirus B-Disease
disease I-Disease
in O
a O
series O
of O
immunocompromised O
children O
and O
review O
the O
literature O
. O
DESIGN O
/ O
METHODS O
: O
We O
retrospectively O
reviewed O
the O
medical O
records O
of O
5 O
children O
treated O
with O
intravenous O
ribavirin B-Chemical
for O
documented O
severe O
adenovirus B-Disease
disease I-Disease
. O
Two O
patients O
developed O
adenovirus O
hemorrhagic B-Disease
cystitis I-Disease
after O
cardiac O
and O
bone O
marrow O
transplants O
, O
respectively O
. O
The O
bone O
marrow O
transplant O
patient O
also O
received O
intravenous O
cidofovir B-Chemical
for O
progressive O
disseminated O
disease O
. O
An O
additional O
3 O
children O
developed O
adenovirus B-Disease
pneumonia I-Disease
; O
2 O
were O
neonates O
, O
1 O
of O
whom O
had O
partial O
DiGeorge B-Disease
syndrome I-Disease
. O
The O
remaining O
infant O
had O
recently O
undergone O
a O
cardiac O
transplant O
. O
Intravenous O
ribavirin B-Chemical
was O
administered O
on O
a O
compassionate O
- O
use O
protocol O
. O
RESULTS O
: O
Complete O
clinical O
recovery O
followed O
later O
by O
viral O
clearance O
was O
observed O
in O
2 O
children O
: O
the O
cardiac O
transplant O
recipient O
with O
adenovirus O
hemorrhagic B-Disease
cystitis I-Disease
and O
the O
immunocompetent O
neonate O
with O
adenovirus B-Disease
pneumonia I-Disease
. O
The O
remaining O
3 O
children O
died O
of O
adenovirus B-Disease
disease I-Disease
. O
Intravenous O
ribavirin B-Chemical
therapy O
was O
well O
tolerated O
. O
Use O
of O
cidofovir B-Chemical
in O
1 O
child O
was O
associated O
with O
progressive B-Disease
renal I-Disease
failure I-Disease
and O
neutropenia B-Disease
. O
DISCUSSION O
: O
Our O
series O
of O
patients O
is O
representative O
of O
the O
spectrum O
of O
immunocompromised O
children O
at O
greatest O
risk O
for O
severe O
adenovirus B-Disease
disease I-Disease
, O
namely O
solid O
- O
organ O
and O
bone O
marrow O
transplant O
recipients O
, O
neonates O
, O
and O
children O
with O
immunodeficiency B-Disease
. O
Although O
intravenous O
ribavirin B-Chemical
was O
not O
effective O
for O
all O
children O
with O
severe O
adenovirus B-Disease
disease I-Disease
in O
this O
series O
or O
in O
the O
literature O
, O
therapy O
is O
unlikely O
to O
be O
of O
benefit O
if O
begun O
late O
in O
the O
course O
of O
the O
infection B-Disease
. O
Early O
identification O
, O
eg O
by O
polymerase O
chain O
reaction O
of O
those O
patients O
at O
risk O
of O
disseminated O
adenovirus B-Disease
disease I-Disease
may O
permit O
earlier O
antiviral O
treatment O
and O
better O
evaluation O
of O
therapeutic O
response O
. O
CONCLUSIONS O
: O
Two O
of O
5 O
children O
with O
severe O
adenovirus B-Disease
disease I-Disease
treated O
with O
intravenous O
ribavirin B-Chemical
recovered O
. O
The O
availability O
of O
newer O
rapid O
diagnostic O
techniques O
, O
such O
as O
polymerase O
chain O
reaction O
, O
may O
make O
earlier O
, O
more O
effective O
treatment O
of O
adenovirus B-Disease
infection I-Disease
possible O
. O
Given O
the O
seriousness O
and O
increasing O
prevalence O
of O
adenovirus B-Disease
disease I-Disease
in O
certain O
hosts O
, O
especially O
children O
, O
a O
large O
, O
multicenter O
clinical O
trial O
of O
potentially O
useful O
anti O
- O
adenoviral O
therapies O
, O
such O
as O
intravenous O
ribavirin B-Chemical
, O
is O
clearly O
required O
to O
demonstrate O
the O
most O
effective O
and O
least O
toxic O
therapy O
. O
Delayed O
asystolic B-Disease
cardiac B-Disease
arrest I-Disease
after O
diltiazem B-Chemical
overdose B-Disease
; O
resuscitation O
with O
high O
dose O
intravenous O
calcium B-Chemical
. O
A O
51 O
year O
old O
man O
took O
a O
mixed O
overdose B-Disease
including O
1 O
. O
8 O
- O
3 O
. O
6 O
g O
of O
diltiazem B-Chemical
, O
paracetamol B-Chemical
, O
aspirin B-Chemical
, O
isosorbide B-Chemical
nitrate B-Chemical
, O
and O
alcohol B-Chemical
. O
He O
initially O
presented O
to O
hospital O
after O
six O
hours O
with O
mild O
hypotension B-Disease
and O
was O
treated O
with O
activated O
charcoal O
and O
intravenous O
fluids O
. O
Eighteen O
hours O
after O
the O
overdose B-Disease
he O
had O
two O
generalised O
tonic B-Disease
- I-Disease
clonic I-Disease
seizures I-Disease
. O
The O
patient O
remained O
unresponsive O
with O
junctional O
bradycardia B-Disease
, O
unrecordable O
blood O
pressure O
, O
and O
then O
became O
asystolic B-Disease
. O
He O
was O
resuscitated O
with O
high O
dose O
( O
13 O
. O
5 O
g O
) O
intravenous O
calcium B-Chemical
and O
adrenaline B-Chemical
( O
epinephrine B-Chemical
) O
. O
He O
required O
inotropic O
support O
and O
temporary O
pacing O
over O
the O
next O
48 O
hours O
. O
This O
case O
suggests O
there O
is O
a O
role O
for O
aggressive O
high O
dose O
intravenous O
calcium B-Chemical
therapy O
in O
severe O
diltiazem B-Chemical
overdose B-Disease
, O
particularly O
with O
the O
onset O
of O
asystole B-Disease
. O
It O
should O
be O
considered O
early O
in O
cases O
of O
cardiac B-Disease
arrest I-Disease
after O
diltiazem B-Chemical
overdose B-Disease
. O
The O
case O
also O
highlights O
the O
problems O
with O
delayed O
toxicity B-Disease
when O
whole O
bowel O
irrigation O
is O
not O
administered O
. O
Low B-Chemical
- I-Chemical
molecular I-Chemical
- I-Chemical
weight I-Chemical
heparin I-Chemical
for O
the O
treatment O
of O
patients O
with O
mechanical O
heart O
valves O
. O
BACKGROUND O
: O
The O
interruption O
of O
oral O
anticoagulant O
( O
OAC O
) O
administration O
is O
sometimes O
indicated O
in O
patients O
with O
mechanical O
heart O
valves O
, O
mainly O
before O
noncardiac O
surgery O
, O
non O
- O
surgical O
interventions O
, O
and O
pregnancy O
. O
Unfractionated B-Chemical
heparin I-Chemical
( O
UH B-Chemical
) O
is O
currently O
the O
substitute O
for O
selected O
patients O
. O
Low B-Chemical
- I-Chemical
molecular I-Chemical
- I-Chemical
weight I-Chemical
heparin I-Chemical
( O
LMWH B-Chemical
) O
offers O
theoretical O
advantages O
over O
UH B-Chemical
, O
but O
is O
not O
currently O
considered O
in O
clinical O
guidelines O
as O
an O
alternative O
to O
UH B-Chemical
in O
patients O
with O
prosthetic O
valves O
. O
HYPOTHESIS O
: O
The O
aim O
of O
the O
present O
study O
was O
to O
review O
the O
data O
accumulated O
so O
far O
on O
the O
use O
of O
LMWH B-Chemical
in O
this O
patient O
population O
and O
to O
discuss O
its O
applicability O
in O
common O
practice O
. O
METHODS O
: O
For O
this O
paper O
, O
the O
current O
medical O
literature O
on O
LMWH B-Chemical
in O
patients O
with O
mechanical O
heart O
valves O
was O
extensively O
reviewed O
. O
RESULTS O
: O
There O
were O
eight O
series O
and O
six O
case O
reports O
. O
None O
of O
the O
studies O
was O
randomized O
, O
and O
only O
one O
was O
prospective O
. O
Data O
to O
establish O
the O
thromboembolic B-Disease
risk O
were O
incomplete O
. O
After O
excluding O
case O
reports O
, O
the O
following O
groups O
were O
constructed O
: O
( O
a O
) O
short O
- O
term O
administration O
, O
after O
valve O
insertion O
( O
n O
= O
212 O
) O
; O
( O
b O
) O
short O
- O
term O
, O
perioperative O
( O
noncardiac O
) O
/ O
periprocedural O
( O
n O
= O
114 O
) O
; O
( O
c O
) O
long O
- O
term O
, O
due O
to O
intolerance O
to O
OAC O
( O
n O
= O
16 O
) O
; O
( O
d O
) O
long O
- O
term O
, O
in O
pregnancy O
( O
n O
= O
10 O
) O
. O
The O
incidence O
rate O
of O
thromboembolism B-Disease
was O
0 O
. O
9 O
% O
for O
all O
the O
studies O
and O
0 O
. O
5 O
, O
0 O
, O
20 O
, O
and O
0 O
% O
in O
groups O
a O
, O
b O
, O
c O
, O
and O
d O
, O
respectively O
; O
for O
hemorrhage B-Disease
, O
the O
overall O
rate O
was O
3 O
. O
4 O
% O
( O
3 O
. O
8 O
, O
2 O
. O
6 O
, O
10 O
, O
and O
0 O
% O
for O
the O
respective O
groups O
) O
. O
CONCLUSIONS O
: O
In O
patients O
with O
mechanical O
heart O
valves O
, O
short O
- O
term O
LMWH B-Chemical
therapy O
compares O
favorably O
with O
UH B-Chemical
. O
Data O
on O
mid O
- O
and O
long O
- O
term O
LMWH B-Chemical
administration O
in O
these O
patients O
are O
sparse O
. O
Further O
randomized O
studies O
are O
needed O
to O
confirm O
the O
safety O
and O
precise O
indications O
for O
the O
use O
of O
LMWH B-Chemical
in O
patients O
with O
mechanical O
heart O
valves O
. O
Cardiac B-Disease
arrest I-Disease
after O
intravenous O
metoclopramide B-Chemical
- O
a O
case O
of O
five O
repeated O
injections O
of O
metoclopramide B-Chemical
causing O
five O
episodes O
of O
cardiac B-Disease
arrest I-Disease
. O
We O
describe O
a O
patient O
where O
intravenous O
injection O
of O
metoclopramide B-Chemical
was O
immediately O
followed O
by O
asystole B-Disease
repeatedly O
. O
The O
patient O
received O
metoclopramide B-Chemical
10 O
mg O
i O
. O
v O
. O
five O
times O
during O
48 O
h O
. O
After O
interviewing O
the O
attending O
nurses O
and O
reviewing O
the O
written O
documentation O
, O
it O
is O
clear O
that O
every O
administration O
of O
metoclopramide B-Chemical
was O
immediately O
( O
within O
s O
) O
followed O
by O
asystole B-Disease
. O
The O
asystole B-Disease
lasted O
15 O
- O
30 O
s O
on O
four O
occasions O
, O
on O
one O
occasion O
it O
lasted O
2 O
min O
. O
The O
patient O
received O
atropine B-Chemical
0 O
. O
5 O
- O
1 O
mg O
and O
chest O
compressions O
, O
before O
sinus O
rhythm O
again O
took O
over O
. O
We O
interpret O
this O
as O
episodes O
of O
cardiac B-Disease
arrest I-Disease
caused O
by O
metoclopramide B-Chemical
. O
The O
rapid O
injection O
via O
the O
central O
venous O
route O
and O
the O
concomitant O
tapering O
of O
dopamine B-Chemical
infusion O
might O
have O
contributed O
in O
precipitating O
the O
adverse O
drug O
reaction O
. O
Immunohistochemical O
study O
on O
inducible O
type O
of O
nitric B-Chemical
oxide I-Chemical
( O
iNOS O
) O
, O
basic O
fibroblast O
growth O
factor O
( O
bFGF O
) O
and O
tumor B-Disease
growth O
factor O
- O
beta1 O
( O
TGF O
- O
beta1 O
) O
in O
arteritis B-Disease
induced O
in O
rats O
by O
fenoldopam B-Chemical
and O
theophylline B-Chemical
, O
vasodilators O
. O
Arteritis B-Disease
induced O
in O
rats O
by O
vasodilators O
, O
fenoldopam B-Chemical
and O
theophylline B-Chemical
, O
was O
examined O
immunohistochemically O
for O
expressions O
of O
inducible O
type O
of O
nitric B-Chemical
oxide I-Chemical
synthase O
( O
iNOS O
) O
, O
basic O
fibroblast O
growth O
factor O
( O
bFGF O
) O
and O
tumor B-Disease
growth O
factor O
- O
beta1 O
( O
TGF O
- O
b
gitextract_tt3m6fwi/ ├── .gitignore ├── README.md ├── common/ │ ├── __init__.py │ ├── instance.py │ └── sentence.py ├── config/ │ ├── __init__.py │ ├── config.py │ ├── eval.py │ ├── reader.py │ └── utils.py ├── dataset/ │ ├── BC5CDR/ │ │ ├── dev.txt │ │ ├── test.txt │ │ ├── train.txt │ │ ├── train_20.txt │ │ └── trigger_20.txt │ ├── CONLL/ │ │ ├── dev.txt │ │ ├── test.txt │ │ ├── train.txt │ │ ├── train_20.txt │ │ └── trigger_20.txt │ └── Laptop-reviews/ │ ├── test.txt │ ├── train.txt │ ├── train_20.txt │ ├── trigger_20.txt │ └── trigger_turk.txt ├── model/ │ ├── __init__.py │ ├── charbilstm.py │ ├── linear_crf_inferencer.py │ ├── soft_attention.py │ ├── soft_encoder.py │ ├── soft_inferencer.py │ ├── soft_inferencer_naive.py │ └── soft_matcher.py ├── naive.py ├── requirments.txt ├── semi_supervised.py ├── supervised.py └── util.py
SYMBOL INDEX (88 symbols across 17 files)
FILE: common/instance.py
class Instance (line 8) | class Instance:
method __init__ (line 13) | def __init__(self, input: Sentence, output: List[str] = None, embeddin...
method __len__ (line 32) | def __len__(self):
FILE: common/sentence.py
class Sentence (line 8) | class Sentence:
method __init__ (line 13) | def __init__(self, words: List[str], pos_tags:List[str] = None):
method __len__ (line 22) | def __len__(self):
FILE: config/config.py
class ContextEmb (line 21) | class ContextEmb(Enum):
class Config (line 28) | class Config:
method __init__ (line 29) | def __init__(self, args) -> None:
method read_pretrain_embedding (line 104) | def read_pretrain_embedding(self) -> Tuple[Union[Dict[str, np.array], ...
method build_word_idx (line 139) | def build_word_idx(self, train_insts: List[Instance], dev_insts: List[...
method add_word_idx (line 180) | def add_word_idx(self, match_insts):
method build_emb_table (line 187) | def build_emb_table(self) -> None:
method build_label_idx (line 210) | def build_label_idx(self, insts: List[Instance]) -> None:
method use_iobes (line 238) | def use_iobes(self, insts: List[Instance]) -> None:
method map_insts_ids (line 262) | def map_insts_ids(self, insts: List[Instance]):
FILE: config/eval.py
class Span (line 12) | class Span:
method __init__ (line 17) | def __init__(self, left: int, right: int, type: str):
method __eq__ (line 28) | def __eq__(self, other):
method __hash__ (line 31) | def __hash__(self):
function evaluate_batch_insts (line 35) | def evaluate_batch_insts(batch_insts: List[Instance],
FILE: config/reader.py
class Reader (line 14) | class Reader:
method __init__ (line 16) | def __init__(self, digit2zero:bool=True):
method read_txt (line 24) | def read_txt(self, file: str, number: int = -1) -> List[Instance]:
method read_trigger_txt (line 48) | def read_trigger_txt(self, file: str, percentage, number: int = -1) ->...
method merge_labels (line 113) | def merge_labels(self, dataset):
method trigger_percentage (line 142) | def trigger_percentage(self, dataset, percentage):
FILE: config/utils.py
function log_sum_exp_pytorch (line 16) | def log_sum_exp_pytorch(vec: torch.Tensor) -> torch.Tensor:
function batching_list_instances (line 28) | def batching_list_instances(config: Config, insts: List[Instance], is_so...
function simple_batching (line 39) | def simple_batching(config, insts: List[Instance], is_soft=False, is_nai...
function lr_decay (line 110) | def lr_decay(config, optimizer: optim.Optimizer, epoch: int) -> optim.Op...
function load_bert_vec (line 125) | def load_bert_vec(file: str, insts: List[Instance]):
function get_bert_embedding (line 158) | def get_bert_embedding(batch):
function get_optimizer (line 189) | def get_optimizer(config: Config, model: nn.Module, name=None):
function write_results (line 210) | def write_results(filename: str, insts):
FILE: model/charbilstm.py
class CharBiLSTM (line 10) | class CharBiLSTM(nn.Module):
method __init__ (line 12) | def __init__(self, config, print_info: bool = True):
method forward (line 27) | def forward(self, char_seq_tensor: torch.Tensor, char_seq_len: torch.T...
FILE: model/linear_crf_inferencer.py
class LinearCRF (line 11) | class LinearCRF(nn.Module):
method __init__ (line 13) | def __init__(self, config, print_info: bool = True):
method forward (line 37) | def forward(self, lstm_scores, word_seq_lens, tags, mask):
method forward_unlabeled (line 51) | def forward_unlabeled(self, all_scores: torch.Tensor, word_seq_lens: t...
method forward_labeled (line 76) | def forward_labeled(self, all_scores: torch.Tensor, word_seq_lens: tor...
method calculate_all_scores (line 99) | def calculate_all_scores(self, lstm_scores: torch.Tensor) -> torch.Ten...
method decode (line 113) | def decode(self, features, wordSeqLengths, annotation_mask = None) -> ...
method constrainted_viterbi_decode (line 123) | def constrainted_viterbi_decode(self, all_scores: torch.Tensor, word_s...
FILE: model/soft_attention.py
class SoftAttention (line 12) | class SoftAttention(nn.Module):
method __init__ (line 13) | def __init__(self, config):
method attention (line 24) | def attention(self, lstm_output, mask):
method forward (line 49) | def forward(self, sentence_vec, sentence_mask, trigger_vec, trigger_ma...
FILE: model/soft_encoder.py
class SoftEncoder (line 14) | class SoftEncoder(nn.Module):
method __init__ (line 15) | def __init__(self, config, encoder = None):
method forward (line 41) | def forward(self, word_seq_tensor: torch.Tensor,
FILE: model/soft_inferencer.py
class SoftSequence (line 19) | class SoftSequence(nn.Module):
method __init__ (line 20) | def __init__(self, config, softmatcher, encoder=None, print_info=True):
method forward (line 45) | def forward(self, word_seq_tensor: torch.Tensor,
method decode (line 100) | def decode(self, word_seq_tensor: torch.Tensor,
class SoftSequenceTrainer (line 152) | class SoftSequenceTrainer(object):
method __init__ (line 153) | def __init__(self, model, config, dev, test, triggers):
method train_model (line 169) | def train_model(self, num_epochs, train_data, eval):
method self_training (line 194) | def self_training(self, num_epochs, train_data, unlabeled_data):
method evaluate_model (line 226) | def evaluate_model(self, batch_insts_ids, name: str, insts, triggers):
method weakly_labeling (line 245) | def weakly_labeling(self, batch_insts_ids, insts, triggers):
method weak_label_selftrain (line 281) | def weak_label_selftrain(self, unlabeled_data, triggers):
FILE: model/soft_inferencer_naive.py
class SoftSequenceNaive (line 16) | class SoftSequenceNaive(nn.Module):
method __init__ (line 17) | def __init__(self, config, encoder=None, print_info=True):
method forward (line 30) | def forward(self, word_seq_tensor: torch.Tensor,
method decode (line 54) | def decode(self, word_seq_tensor: torch.Tensor,
class SoftSequenceNaiveTrainer (line 68) | class SoftSequenceNaiveTrainer(object):
method __init__ (line 69) | def __init__(self, model, config, dev, test):
method train_model (line 83) | def train_model(self, num_epochs, train_data):
method evaluate_model (line 108) | def evaluate_model(self, batch_insts_ids, name: str, insts):
FILE: model/soft_matcher.py
class ContrastiveLoss (line 21) | class ContrastiveLoss(nn.Module):
method __init__ (line 22) | def __init__(self, margin, device):
method forward (line 28) | def forward(self, output1, output2, target, size_average=True):
class SoftMatcher (line 36) | class SoftMatcher(nn.Module):
method __init__ (line 37) | def __init__(self, config, num_classes):
method forward (line 48) | def forward(self, word_seq_tensor: torch.Tensor,
class SoftMatcherTrainer (line 62) | class SoftMatcherTrainer(object):
method __init__ (line 63) | def __init__(self, model, config, dev, test):
method train_model (line 78) | def train_model(self, num_epochs, train_data):
method test_model (line 102) | def test_model(self, test_data):
method get_triggervec (line 125) | def get_triggervec(self, data):
FILE: naive.py
function parse_arguments (line 13) | def parse_arguments(parser):
FILE: semi_supervised.py
function parse_arguments (line 21) | def parse_arguments(parser):
function main (line 61) | def main():
FILE: supervised.py
function parse_arguments (line 15) | def parse_arguments(parser):
FILE: util.py
function remove_duplicates (line 20) | def remove_duplicates(features, labels, triggers, dataset):
Condensed preview — 38 files, each showing path, character count, and a content snippet. Download the .json file or copy for the full structured content (9,857K chars).
[
{
"path": ".gitignore",
"chars": 211,
"preview": "dataset/glove*\n.DS_Store\n.idea/*\n__pycache__/*\nconfig/__pycache__/*\nmodel/__pycache__/*\ncommon/__pycache__/*\ndataset/CON"
},
{
"path": "README.md",
"chars": 3262,
"preview": "# TriggerNER\nCode & Data for ACL 2020 paper: \n\n[TriggerNER: Learning with Entity Triggers as Explanations for Named Enti"
},
{
"path": "common/__init__.py",
"chars": 74,
"preview": "from common.instance import Instance\nfrom common.sentence import Sentence\n"
},
{
"path": "common/instance.py",
"chars": 1021,
"preview": "#\n# @author: Allan\n# edited by Dong-Ho Lee\n#\nfrom common.sentence import Sentence\nfrom typing import List\n\nclass Instan"
},
{
"path": "common/sentence.py",
"chars": 473,
"preview": "#\n# @author: Allan\n# edited by Dong-Ho Lee\n#\n\nfrom typing import List\n\nclass Sentence:\n \"\"\"\n The class for the inp"
},
{
"path": "config/__init__.py",
"chars": 275,
"preview": "from config.config import Config, ContextEmb, PAD, START, STOP\nfrom config.eval import Span, evaluate_batch_insts\nfrom c"
},
{
"path": "config/config.py",
"chars": 11460,
"preview": "# \n# @author: Allan\n# edited by Dong-Ho Lee\n#\n\nimport numpy as np\nfrom tqdm import tqdm\nfrom typing import List, Tuple, "
},
{
"path": "config/eval.py",
"chars": 3796,
"preview": "#\n# @author: Allan\n# edited by Dong-Ho Lee\n#\n\nimport numpy as np\nfrom overrides import overrides\nfrom typing import List"
},
{
"path": "config/reader.py",
"chars": 6104,
"preview": "#\n# @author: Allan\n# edited by Dong-Ho Lee\n#\n\nfrom tqdm import tqdm\nfrom common import Sentence, Instance\nfrom typing im"
},
{
"path": "config/utils.py",
"chars": 9328,
"preview": "#\n# @author: Allan\n# edited by Dong-Ho Lee\n#\n\nfrom typing import List\nfrom common import Instance\nimport torch.optim as "
},
{
"path": "dataset/BC5CDR/dev.txt",
"chars": 1031781,
"preview": "22\tB-Chemical\n-\tI-Chemical\noxacalcitriol\tI-Chemical\nsuppresses\tO\nsecondary\tB-Disease\nhyperparathyroidism\tI-Disease\nwitho"
},
{
"path": "dataset/BC5CDR/test.txt",
"chars": 1080717,
"preview": "Torsade\tB-Disease\nde\tI-Disease\npointes\tI-Disease\nventricular\tB-Disease\ntachycardia\tI-Disease\nduring\tO\nlow\tO\ndose\tO\ninter"
},
{
"path": "dataset/BC5CDR/train.txt",
"chars": 1039940,
"preview": "Selegiline\tB-Chemical\n-\tO\ninduced\tO\npostural\tB-Disease\nhypotension\tI-Disease\nin\tO\nParkinson\tB-Disease\n'\tI-Disease\ns\tI-Di"
},
{
"path": "dataset/BC5CDR/train_20.txt",
"chars": 191917,
"preview": "Selegiline\tB-Chemical\n-\tO\ninduced\tO\npostural\tB-Disease\nhypotension\tI-Disease\nin\tO\nParkinson\tB-Disease\n'\tI-Disease\ns\tI-Di"
},
{
"path": "dataset/BC5CDR/trigger_20.txt",
"chars": 529298,
"preview": "Selegiline\tB-Chemical\n-\tO\ninduced\tT-1\npostural\tO\nhypotension\tO\nin\tO\nParkinson\tO\n'\tO\ns\tO\ndisease\tO\n:\tO\na\tO\nlongitudinal\tO"
},
{
"path": "dataset/CONLL/dev.txt",
"chars": 420223,
"preview": "CRICKET O\n- O\nLEICESTERSHIRE B-ORG\nTAKE O\nOVER O\nAT O\nTOP O\nAFTER O\nINNINGS O\nVICTORY O\n. O\n\nLONDON B-LOC\n1996-08-30 O\n\n"
},
{
"path": "dataset/CONLL/test.txt",
"chars": 379456,
"preview": "SOCCER O\n- O\nJAPAN B-LOC\nGET O\nLUCKY O\nWIN O\n, O\nCHINA B-PER\nIN O\nSURPRISE O\nDEFEAT O\n. O\n\nNadim B-PER\nLadki I-PER\n\nAL-A"
},
{
"path": "dataset/CONLL/train.txt",
"chars": 1668941,
"preview": "EU B-ORG\nrejects O\nGerman B-MISC\ncall O\nto O\nboycott O\nBritish B-MISC\nlamb O\n. O\n\nPeter B-PER\nBlackburn I-PER\n\nBRUSSELS "
},
{
"path": "dataset/CONLL/train_20.txt",
"chars": 266836,
"preview": "EU\tB-ORG\nrejects\tO\nGerman\tB-MISC\ncall\tO\nto\tO\nboycott\tO\nBritish\tB-MISC\nlamb\tO\n.\tO\n\nThe\tO\nEuropean\tB-ORG\nCommission\tI-ORG\n"
},
{
"path": "dataset/CONLL/trigger_20.txt",
"chars": 768421,
"preview": "EU\tB-ORG\nrejects\tT-3\nGerman\tT-0\ncall\tT-4\nto\tO\nboycott\tT-1\nBritish\tT-2\nlamb\tT-2\n.\tO\n\nEU\tT-5\nrejects\tT-4\nGerman\tB-MISC\ncal"
},
{
"path": "dataset/Laptop-reviews/test.txt",
"chars": 93225,
"preview": "Boot\tB-aspectTerm\ntime\tI-aspectTerm\nis\tO\nsuper\tO\nfast\tO\n,\tO\naround\tO\nanywhere\tO\nfrom\tO\n35\tO\nseconds\tO\nto\tO\n1\tO\nminute\tO\n"
},
{
"path": "dataset/Laptop-reviews/train.txt",
"chars": 391689,
"preview": "I\tO\ncharge\tO\nit\tO\nat\tO\nnight\tO\nand\tO\nskip\tO\ntaking\tO\nthe\tO\ncord\tB-aspectTerm\nwith\tO\nme\tO\nbecause\tO\nof\tO\nthe\tO\ngood\tO\nbat"
},
{
"path": "dataset/Laptop-reviews/train_20.txt",
"chars": 47592,
"preview": "I\tO\ncharge\tO\nit\tO\nat\tO\nnight\tO\nand\tO\nskip\tO\ntaking\tO\nthe\tO\ncord\tB-aspectTerm\nwith\tO\nme\tO\nbecause\tO\nof\tO\nthe\tO\ngood\tO\nbat"
},
{
"path": "dataset/Laptop-reviews/trigger_20.txt",
"chars": 81847,
"preview": "I\tO\ncharge\tT-1\nit\tT-1\nat\tO\nnight\tO\nand\tO\nskip\tT-0\ntaking\tT-0\nthe\tT-0\ncord\tB-aspectTerm\nwith\tO\nme\tO\nbecause\tO\nof\tO\nthe\tO\n"
},
{
"path": "dataset/Laptop-reviews/trigger_turk.txt",
"chars": 81847,
"preview": "I\tO\ncharge\tT-1\nit\tT-1\nat\tO\nnight\tO\nand\tO\nskip\tT-0\ntaking\tT-0\nthe\tT-0\ncord\tB-aspectTerm\nwith\tO\nme\tO\nbecause\tO\nof\tO\nthe\tO\n"
},
{
"path": "model/__init__.py",
"chars": 40,
"preview": "from model.charbilstm import CharBiLSTM\n"
},
{
"path": "model/charbilstm.py",
"chars": 2241,
"preview": "# \n# @author: Allan\n#\nimport torch\nimport torch.nn as nn\nfrom torch.nn.utils.rnn import pack_padded_sequence, pad_packed"
},
{
"path": "model/linear_crf_inferencer.py",
"chars": 9363,
"preview": "#\n# @author: Allan\n#\nimport torch.nn as nn\nimport torch\n\nfrom config import log_sum_exp_pytorch, START, STOP, PAD\nfrom t"
},
{
"path": "model/soft_attention.py",
"chars": 2901,
"preview": "\"\"\"soft_attention.py: Structured Self-attention layer.\nIt creates trigger representations, and sentence representation w"
},
{
"path": "model/soft_encoder.py",
"chars": 4360,
"preview": "\"\"\"soft_encoder.py: Encoding sentence with LSTM.\nIt encodes sentence with Bi-LSTM.\nAfter encoding, it uses all tokens fo"
},
{
"path": "model/soft_inferencer.py",
"chars": 13699,
"preview": "\"\"\"soft_inferencer.py: Inference on Unlabeled Sentences\ncompute the similarities between the self-attended sentence repr"
},
{
"path": "model/soft_inferencer_naive.py",
"chars": 5610,
"preview": "\"\"\"soft_inferencer_navie.py: Inference on Unlabeled Sentences (without trigger - baseline setting)\nBaseline setting infe"
},
{
"path": "model/soft_matcher.py",
"chars": 6564,
"preview": "\"\"\"soft_matcher.py: Joint training between trigger encoder and trigger matcher\nIt jointly trains the trigger encoder and"
},
{
"path": "naive.py",
"chars": 4148,
"preview": "\"\"\"naive.py: Testing baselines\n\nbaseline setting (Bi-LSTM / CRF)\nuse percentage argument to reproduce the results (20 %)"
},
{
"path": "requirments.txt",
"chars": 96,
"preview": "torch >= 0.4.1\nnumpy\noverrides == 2.0\ntqdm\ntermcolor\nsklearn\nmatplotlib\npytorch_pretrained_bert\n"
},
{
"path": "semi_supervised.py",
"chars": 5850,
"preview": "\"\"\"semi_supervised.py: semi_supervised learning with triggers (self training)\n\nusing 20% of the train data w/ triggers ("
},
{
"path": "supervised.py",
"chars": 4690,
"preview": "\"\"\"supervised.py: supervised learning with triggers\n\nusing 20% of the train data w/ triggers (already in trigger_20.txt "
},
{
"path": "util.py",
"chars": 1867,
"preview": "\"\"\"util.py: polishing trigger set to use.\n\n1. same trigger in different entity type -> delete\n2. multiple same triggers "
}
]
About this extraction
This page contains the full source code of the INK-USC/TriggerNER GitHub repository, extracted and formatted as plain text for AI agents and large language models (LLMs). The extraction includes 38 files (7.8 MB), approximately 2.0M tokens, and a symbol index with 88 extracted functions, classes, methods, constants, and types. Use this with OpenClaw, Claude, ChatGPT, Cursor, Windsurf, or any other AI tool that accepts text input. You can copy the full output to your clipboard or download it as a .txt file.
Extracted by GitExtract — free GitHub repo to text converter for AI. Built by Nikandr Surkov.