A qualitative study of the barriers to using blinding in in vivo experiments and suggestions for improvement.

In animal experiments, blinding (also known as masking) is a methodological strategy to reduce the risk that scientists, animal care staff, or other staff involved in the research may consciously or subconsciously influence the outcome. Lack of masking has been shown to correlate with an overestimation of treatment efficacy and false positive findings. We conducted exploratory interviews across academic and a commercial setting to discuss the implementation of masking at four stages of the experiment: during allocation and intervention, during the conduct of the experiment, during the outcome assessment, and during the data analysis.

Phenotypic screening reveals TNFR2 as a promising target for cancer immunotherapy.

Antibodies that target cell-surface molecules on T cells can enhance anti-tumor immune responses, resulting in sustained immune-mediated control of cancer. We set out to find new cancer immunotherapy targets by phenotypic screening on human regulatory T (Treg) cells and report the discovery of novel activators of tumor necrosis factor receptor 2 (TNFR2) and a potential role for this target in immunotherapy. A diverse phage display library was screened to find antibody mimetics with preferential binding to Treg cells, the most Treg-selective of which were all, without exception, found to bind specifically to TNFR2.

Phenobarbital versus diazepam for delirium tremens--a retrospective study.

Introduction: Delirium tremens (DT) is a severe and potentially fatal condition that may occur during withdrawal from chronic alcohol intoxication. The purpose of the present study was to compare the effects and the rates of complications of phenobarbital and diazepam treatment in DT.

Material And Methods: Data were collected retrospectively from the medical files of patients who had received DT treatment (n = 194) at two psychiatric departments located in the general Copenhagen area in the 1998-2006 period.

Linear correlation between phenobarbital dose and concentration in alcohol withdrawal patients.

Introduction: Barbiturates are potent drugs for treatment of alcohol withdrawal symptoms, but they entail a risk of over-dosage and respiratory depression. The purpose of the present study was to investigate the correlation between phenobarbital dose and phenobarbital blood concentration in patients withdrawing from long-term alcohol intoxication.

Material And Methods: A total of 497 patients who were hospitalized for treatment of alcohol withdrawal symptoms during an 18-month period were enrolled in the study.

[Wernicke's encephalopathy in patients with alcohol withdrawal symptoms].

Introduction: Wernicke's encephalopathy (WE) is caused by lack of thiamin. In Denmark, WE most often occurs in alcoholics. In the present study, we wanted to investigate the frequency of WE in patients hospitalized for treatment of alcohol withdrawal symptoms in a psychiatric emergency ward.

Disulfiram in severe alcoholism--an open controlled study.

Background: Disulfiram is used to a great extent in Denmark to treat alcoholism but the evidence is limited.

Aim: To study the effect of supervised disulfiram treatment in alcohol dependence. Subjects were recruited from a psychiatric emergency ward following alcohol withdrawal treatment.

Gene expression in the neuropeptide Y system during ethanol withdrawal kindling in rats.

Background: Multiple episodes of ethanol intoxication and withdrawal result in progressive, irreversible intensification of the withdrawal reaction, a process termed "ethanol withdrawal kindling." Previous studies show that a single episode of chronic ethanol intoxication and withdrawal causes prominent changes in neuropeptide Y (NPY) and its receptors that have been implicated in regulating withdrawal hyperexcitability. This study for the first time examined the NPY system during ethanol withdrawal kindling.

Complex plastic changes in the neuropeptide Y system during ethanol intoxication and withdrawal in the rat brain.

Previous studies show that chronic ethanol treatment induces prominent changes in brain neuropeptide Y (NPY). The purpose of the present study was to explore ethanol effects at a deeper NPY-system level, measuring expression of NPY and its receptors (Y1, Y2, Y5) as well as NPY receptor binding and NPY-stimulated [(35)S]GTPgammaS functional binding. Rats received intragastric ethanol repeatedly for 4 days, and the NPY system was studied in the hippocampal dentate gyrus (DG), CA3, CA1, and piriform cortex (PirCx) and neocortex (NeoCx) during intoxication, peak withdrawal (16 hr), late withdrawal (3 days), and 1 week after last ethanol administration.

[Respiratory depression in delirium tremens patients treated with phenobarbital. A retrospective study].

Introduction: Delirium tremens (DT) is the most severe manifestation of alcohol withdrawal which--if untreated--has a high rate of mortality. Barbiturates are the most effective drug but respiratory depression may occur. In the present study we investigated the frequency of respiratory problems in DT patients treated with phenobarbital.

Pain management practices for lumbar punctures: are we consistent?

In most pediatric oncology centers across Canada, it is now standard practice for children to be sedated for lumbar punctures (LPs). Although the use of sedation for LPs is well established in the pediatric oncology population, its use in other hospital units is not well documented. A patient record audit was completed to understand the types of pain management strategies used for LPs performed throughout a pediatric hospital.

Decreased gene expression of neuropeptide Y and its receptors in hippocampal regions during ethanol withdrawal in rats.

Ethanol withdrawal is associated with neuronal hyperexcitability and increased hippocampal glutamate release. Neuropeptide Y (NPY) appears to play an important role in regulation of hippocampal neuronal excitability by inhibiting glutamate release. Expression of NPY and its receptors Y1, Y2, and Y5 was studied in hippocampal areas of rats during ethanol withdrawal after repeated intragastric ethanol administration for 2 or 4 days using in situ hybridization.

Upregulation of glutamate receptor subtypes during alcohol withdrawal in rats.

Aims: To investigate glutamate receptor subtypes during alcohol withdrawal.

Methods: Rats were exposed to severe alcohol intoxication for 84 h and then decapitated at 0, 12 and 36 h after the last alcohol dose (n = 7 per group). Alcohol was administered five times a day by intragastric intubation.

Ethanol withdrawal in rats is attenuated by intracerebroventricular administration of neuropeptide Y.

Aims: The effects of intracerebroventricular administration of neuropeptide Y (NPY) on ethanol withdrawal were studied in rats.

Methods: Ethanol was administered intragastrically five times daily for 4 days. At 16-17 h after the last infusion of ethanol, rats were rated for withdrawal using a score based on three signs: irritability, tremor and rigidity.

Electrical amygdala kindling in alcohol-withdrawal kindled rats.

Repeated alcohol withdrawal has been shown to kindle seizure activity. The purpose of the present investigation was to study electrical amygdala kindling in rats previously exposed to alcohol-withdrawal kindling. In three independent experiments, male Wistar rats were subjected to multiple episodes each consisting of 2 days of severe alcohol intoxication and 5 days of alcohol withdrawal.

Irreversibility of kindled alcohol-withdrawal behaviour in rats.

In order to investigate whether alcohol-withdrawal kindling is an irreversible process, male Wistar rats were exposed to 12 episodes, each consisting of 2 days of severe alcohol intoxication and 5 days of alcohol withdrawal. Spontaneous withdrawal seizures were found in 15% of the animals during episodes 10-12. After an alcohol-free period of 26 days, the animals were subjected to three more episodes of alcohol dependence (i.

Serotonin1A receptor autoradiography during alcohol-withdrawal kindling.

A series of autoradiography experiments were conducted in order to test the theory that the serotonin (5-HT) receptor subtype 5-HT(1a) is involved in alcohol-withdrawal kindled convulsive behaviour. Alcohol-withdrawal kindling was performed by subjecting male Wistar rats to multiple episodes consisting of 2 days of alcohol intoxication and 5 days of alcohol withdrawal. In the first episode alcohol intoxication led to focal downregulation of [3H]-8-hydroxy-2-(di-n-propylamino)tetralin ([3H]-8-OH-DPAT) binding sites in septum and subregions of frontal cortex, hippocampus, and entorhinal cortex.

No loss of somatostatin-immunoreactive neurons in the hippocampal dentate hilus of alcohol-withdrawal-kindled rats.

The neuropeptide somatostatin has been suggested to play a role in seizure genesis, electrical kindling and the neurotoxic effects of alcohol. The purpose of the present experiment was to study somatostatin-immunoreactive (SS-IR) neurons in hippocampus during alcohol-withdrawal kindling. Alcohol-withdrawal kindling was performed by subjecting male Wistar rats to seven weekly episodes consisting of 2 days of severe alcohol intoxication and 5 days of alcohol withdrawal.

Glutamate and benzodiazepine receptor autoradiography in rat brain after repetition of alcohol dependence.

During repeated alcohol withdrawal, convulsive withdrawal behavior has been shown to be increased in a kindling-like manner in both clinical and experimental studies. In the present experiment, quantitative autoradiography was used to investigate binding of tritiated ligands to glutamate receptor subtypes and the benzodiazepine/GABA (BZ/GABA) receptor complex in rats exposed to 14 episodes of alcohol withdrawal. Seizures were detected in 25% of the animals during withdrawal episode 10-13.

Diazepam prevents progression of kindled alcohol withdrawal behaviour.

The purpose of the present experiment was to study the "kindling" hypothesis of alcohol withdrawal stating that exposure to repeated episodes of alcohol withdrawal results in an increased severity of subsequent withdrawal reactions. Two groups of male Wistar rats were subjected to 13 episodes of 2 days severe alcohol intoxication and 5 days alcohol withdrawal. Animals in the control group (n = 80) developed clinical withdrawal signs following each intoxication episode.