Differences in enhancing effects of zolpidem and benzodiazepine drugs on recurrent inhibition in rat hippocampal slices

It has been reported that the clinical and electroencephalographic profiles of zolpidem, a non-benzodiazepine drug which binds preferentially to the ω₁ benzodiazepine recognition sites located within the GABA_A receptor complex, are different from those of benzodiazepine drugs, which bind non-selectively to the ω₁ and ω₂ sites. In order to clarify the electrophysiological mechanism underlying the unique profile of zolpidem, the present study compared the enhancing effects of zolpidem and two benzodiazepine drugs, triazolam and diazepam, on recurrent inhibition. This inhibition was expressed as suppression of the orthodromically induced population spikes by the preceding antidromic stimulation of the alveus in the CA1 region of rat hippocampal slices. The rank order of potency for enhancing recurrent inhibition was triazolam > diazepam > zolpidem. From the present results and previously reported findings that zolpidem has a lower affinity for the ω₂ sites than diazepam while both have the same affinity for the ω₁ sites, we concluded that the hippocampal recurrent inhibition appears to be enhanced mainly by activation of the ω₂ sites, but not by that of the ω₁ sites. Furthermore, the lower potency of zolpidem for enhancing recurrent inhibition may underlie its unique profile in terms of its clinical and electroencephalographic effects. Received: 1 November 1996/Final version: 22 January 1997     

Natural antibodies against the immunoglobulin F(ab′)2 fragment cause elimination of antigens recognized by the F(ab′)2 from the circulation

A humanized monoclonal IgG1 antibody, designated hC4G1, recognizes the fibrinogen receptor glycoprotein (GP)IIb/IIIa on platelets and inhibits platelet aggregation. When the F(ab′)₂ fragment of hC4G1 (F(ab′)₂ hC4G1) was administered to cynomolgus monkeys, all the monkeys showed inhibition of platelet aggregation ex vivo. Unexpectedly, a significant decrease in platelet count was observed in 5 of 18 monkeys. Antibodies against F(ab′)₂ hC4G1 were detected in the plasma of these monkeys by ELISA. Antibody activity in the plasma of these monkeys was significantly correlated with the intensity of platelet decrease (r = 0.84). The natural monkey antibodies to F(ab′)₂ hC4G1 were directed against the C-terminal region of F(ab′)₂ fragment common to all human and humanized IgG antibodies. Natural homo-reactive antibodies were also detected in human plasma from 15 of 40 healthy volunteers. Specificity was closely similar to that of the monkey antibodies. Affinity-purified human homo-reactive antibodies enhanced phagocytosis of platelets treated with the F(ab′)₂ hC4G1. Monkey plasma with high homo-reactive antibody activity was confirmed to decrease platelet count when administered together with F(ab′)₂ hC4G1 to a monkey with low antibody activity. These results suggest that F(ab′)₂ of humanized and human antibodies causes elimination of the corresponding antigens from the circulation by homo-reactive antibodies.     

A case report of pleural empyema treated by video-assisted thoracoscopic surgery in an elder patient receiving hemodialysis

A 79-year-old male who had the treatment of renal failure with hemodialysis was admitted to our hospital for the management of right pleural empyema. We performed thoracoscopic débridement and pleural irrigation in the management of empyema thoracis, because both chest tube drainage and antibiotic therapy had failed. Postoperatively pleural irrigation was performed for three weeks and the chest drains were removed after four weeks. He was successfully transferred to our department of internal medicine at four weeks after the operation. Thoracoscopic débridement and pleural irrigation for the elder patient with pleural empyema is safe, effective and minimally invasive surgical procedure.     

Treatment of neuroleptic induced tardive dyskinesia with cyproheptadine

Zusammenfassung Cyproheptadin ist seit Jahren als Antimetabolit des Serotonins verwendet worden. Es wurde über eine Wirksamkeit desselben bei extrapyramidalen Hyperkinesien (von den Angelsachsen als tardive dyskinesia bezeichnet) nach Neuroleptika-Medikation berichtet. Wir behandelten 11 Patienten, die wegen chronischer Schizophrenie behandelt wurden und schwere Dyskinesien aufwiesen, Cyproheptadin (Periactinol®, Periactin) verabreicht. In vier Fällen verschwand unter dieser Medikation das extrapyramidale hyperkinetische Syndrom vollständig, bei vier weiteren Fällen trat eine befriedigende Besserung auf. Im Verlaufe der Therapie wurden keine nennenswerten Nebenwirkungen beobachtet, die eindeutig auf das Cyproheptadin zurückzuführen gewesen wären.     

An unusual case of rhythmic movement disorder

Rhythmic movement disorder is one of the sleep-wake transition disorders listed in the International Classification of Sleep Disorders. According to this classification, the condition commonly occurs in infants and toddlers, and persistence beyond 4 years of age is unusual. Recently, we encountered a case in which rhythmic movement disorder persisted up until the age of 12 years with spikes registering on the sleep electroencephalogram. Epileptic seizure was ruled out because of the characteristic rolling movement, absence of any other epileptic symptoms (e.g. vocalization and tonic-clonic seizure) and cessation as a result of removal of the blanket.     

Arthroscopic synovectomy for rheumatoid arthritis using a holmium:YAG laser

OBJECTIVE: To determine the usefulness of the holmium:YAG laser system in arthroscopic synovectomy (ASSX) for treating rheumatoid arthritis (RA). METHODS: ASSX was performed on 15 knees (one Larsen Grade 1, 7 Grade 2, 7 Grade 3) and 8 ankles (6 Grade 2, 2 Grade 3) of 17 female patients with RA. The average age at ASSX was 50.6 years (25-70). The average followup period was 24.4 months (10-47). RESULTS: Seven out of 8 knees with grade 1 or 2 had reduced pain and swelling, as well as decreased average serum levels of C-reactive protein (CRP) (from 3.6+/-1.1 to 1.4+/-0.3 mg/dl). However, 4 out of 7 knees with grade 3 showed recurrence of pain and swelling along with persistent average serum level of CRP (from 4.3+/-1.0 to 3.8+/-1.0 mg/dl). All 8 ankles with Grade 2 or Grade 3 experienced reduced pain and swelling, while the average serum CRP levels did not change (from 3.2+/-0.9 to 2.9+/-1.0 mg/dl). CONCLUSION: The Holmium:YAG laser was useful in ASSX for treating RA knees and ankles.     

OP-1206, a prostaglandin E1 derivative. Effects of oral administration to patients with chronic lung disease

In order to assess the clinical effectiveness of an oral prostaglandin E1 derivative, OP-1206, five patients with chronic obstructive pulmonary disease and two with pulmonary fibrosis were studied from the standpoint of hemodynamics and nine others with chronic lung disease from the standpoint of respiratory function. Oral intake of OP-1206 resulted in a significant decrease in the pulmonary arterial pressure (p less than 0.01), total pulmonary vascular resistance (p less than 0.01), pulmonary arteriole resistance (p less than 0.01), and total systemic vascular resistance (p less than 0.05), and an increase in the cardiac index (p less than 0.05) and oxygen delivery (p less than 0.01) with insignificant changes of PaCO2, PaO2 and pH. There was no clinical improvement of lung function after OP-1206 intake. OP-1206 is a potent vasodilator, improving cardiac performance in patients with chronic lung disease and possibly preventing the progress of cor pulmonale in this kind of patient.     

Initial Evaluation of AF78: a Rationally Designed Fluorine-18-Labelled PET Radiotracer Targeting Norepinephrine Transporter

Molecular Imaging and Biology - Taking full advantage of positron emission tomography (PET) technology, fluorine-18-labelled radiotracers targeting norepinephrine transporter (NET) have potential...