MAO-A inhibition in brain after dosing with esuprone, moclobemide and placebo in healthy volunteers: in vivo studies with positron emission tomography

Objective: The aim of the study was to investigate whether or not esuprone binds substantially to MAO-A in the human brain. Methods: In a randomised double-blind placebo-controlled study 16 male healthy volunteers were examined␣with positron emission tomography (PET) with [¹¹C]harmine. Eight of the volunteers were given daily doses of 800 mg esuprone, four were given bi-daily doses of 300 mg moclobemide, and four volunteers were given placebo tablets. PET was performed before initiation of a 7-day treatment period. On day 7, one investigation was made immediately before administration of the drug, representing 23 h after the previous day's treatment for esuprone and 11 h after the last tablets of moclobemide. Further investigations were made 4 h and 8 h after the morning dose on day 7. Results: PET showed a high degree of binding of [¹¹C]harmine, a high-affinity ligand for MAO-A, before the start of treatment, and a marked and similar reduction after treatment with esuprone and moclobemide. A slight tendency for normalisation of enzyme binding was observed at the last time point. In the placebo group no change was observed. Plasma kinetics of esuprone showed a rapid elimination with a half-life of about 4 h. Conclusion: The study demonstrates that esuprone was comparable to moclobemide in its effect on MAO-A inhibition in the brain at the doses given. This is an illustration of the potential of PET to monitor drug effects directly on target biochemical systems in the brain in human volunteers, and the possibility of using these data, rather than pharmacokinetic data, for the determination of dosing intervals. Received: 21 August 1996 / Accepted in revised form: 22 November 1996     

Prospective study of antigenemia,plasma viremia and lymphocytic viremia in HIV-infected hemophiliacs

A total of 186 blood samples from 24 HIV-1 seropositive hemophiliac patients, monitored every four months for 29 months, were investigated for the presence of viral antigen in plasma. In addition, peripheral blood mononuclear cells (PBMC) were cultured for HIV-1, using normal PBMC as a target for replication. Antigenemia was detected in 51 % of the patients and from PBMC in 87.5 % of the patients. The incidence of HIV isolation in asymptomatic patients (42.8 %) was similar to that found in symptomatic patients (51.4 %). Patients with opportunistic infections had a higher incidence of lymphocytic viremia (p<0.05). Plasma viremia was closely associated (p<0.05) with low CD4+ counts and infection progression. The persistence of antigenemia was also a marker of a poor clinical course. In treated patients, plasma viremia was the marker that better correlated with the clinical course, and it did not appear during the first nine months of therapy. Zidovudine doses of >500 mg/day significantly lowered the appearance of antigenemia and lymphocytic viremia (p<0.05).     

Nerve agent poisoning in primates: antilethal, anti-epileptic and neuroprotective effects of GK-11

 Organophosphorus nerve agents are still in use today in warfare and as terrorism compounds. Classical emergency treatment of organophosphate poisoning includes the combined administration of a cholinesterase reactivator (an oxime), a muscarinic cholinergic receptor antagonist (atropine) and a benzodiazepine anticonvulsant (diazepam). However, recent experiments with primates have demonstrated that such treatment, even when administered immediately after organophosphate exposure, does not rapidly restore normal electroencephalographic (EEG) activity and fails to totally prevent neuronal brain damage. The objective of this study was to evaluate, in a realistic setting, the therapeutic benefit of administration of GK-11 (gacyclidine), an antiglutamatergic compound, as a complement to the available emergency therapy against organophosphate poisoning. GK-11 was injected at a dose of 0.1 mg/kg (i.v) after a 45-min latency period to heavily intoxicated (8 LD₅₀) primates. Just after intoxication, man-equivalent doses of one autoinjector containing atropine/pralidoxime/diazepam were administered. The effects of GK-11 were examined on survival, EEG activity, signs of toxicity, recovery after challenge and central nervous system histology. The present data demonstrate that treatment with GK-11 prevents the mortality observed after early administration of classical emergency medication alone. EEG recordings and clinical observations also revealed that GK-11 prevented soman-induced seizures and motor convulsions. EEG analysis within the classical frequency bands (beta, theta, alpha, delta) demonstrated that central activity was totally restored to normal after GK-11 treatment, but remained profoundly altered in animals receiving atropine/pralidoxime/diazepam alone. GK-11 also markedly accelerated clinical recovery of soman-challenged primates. Lastly, this drug totally prevented the neuropathology observed 3 weeks after soman exposure in animals treated with classical emergency treatment alone. GK-11 represents a promising adjuvant therapy to the currently available emergency polymedication to ensure optimal management of organophosphate poisoning in man. This drug is presently being evaluated in a human clinical trial for a different neuroprotective indication. Received: 16 June 1997 / Accepted: 23 September 1997     

Organization of gallbladder lithotripsy with the MPL-9000 at the Zurich university hospital. Initial results

Gallstone shock wave therapy at the University Hospital of Zurich is a joint venture between the Medical Clinic, Medical Policlinic and Surgical Clinic. Patients with symptomatic cholecystolithiasis willing to submit themselves to a long period of treatment, were accepted for ESWL, should no contraindications be present. From October 1988 through May 1989 we treated 48 patients. In approximately two thirds of our patients we were successful with one ESWL alone, in one third 2 sessions and in two patients even 3 sessions were needed. In 42 patients course after therapy was as planned. Six had to be cholecystectomized later on. Best results were achieved in patients with single gallstones. In 2 of 5 cases there was disagreement between the number of gallstones found sonographically and the intraoperative findings. Histologic examination of gallbladders after ESWL showed no pathologic changes.     

Biodisponibilité de la glutamine et réponse du métabolisme protéique à l'apport de glutamine chez l'homme

Glutamine is synthetized in most tissue and accounts for two-thirds of the free amino acid pool in skeletal muscle. Glutamine is not only an interorgan nitrogen shuttle but a precursor of urinary ammonium, and a favorite fuel of the immune system and the gut (which uses ≠ 17 g of glutamine per day). Because they were designed at a time when glutamine was considered both unstable and non-essential, « tradtionalparenteral nutrition (PN) solutions are devoid of glutamine. Although « classicPN is able to maintain normal rates of glutamine turnover in healthy subjects or unstressed patients, classic PN solutions are unable to correct the precipitous depletion of glutamine pool that accompagnies catabolic illness. Glutamine becomes a « conditionally essentialamino acid in these situations. Replenishment of glutamine pool seems to stimulate protein synthesis, and improve nitrogen balance in catabolic patients. Supplementation of PN with glutamine-containing dipeptides or α-ketoglutarate (at doses of 15–50 g/d) is as effective as glutamine itself. The enteral route represents an attractive alternative for the supply of glutamine since : 1) glutamine is efficiently absorbed ; 2) nearly 50 % of enterally infused glutamine reaches systemic blood ; 3) glutamine residues present in a bound form in peptides seem to be bioavailable ; and 4) in addition to its protein anabolic effect, glutamine affects intestinal absorption and trophicity.     

浅谈对传染科护士素质的要求与体会

根据笔者在传染科病房工作中的体会,从六个方面针对传染科工作的特殊性和存在的共性分别阐述了传染科护士在工作中如何高标准、严要求自己,如何对病人做到到位的护理,旨在提高传染科病房的整体护理质量,从而把更多的实惠让利于患者。     

Biomonitoring of genotoxic exposure of aluminium plant workers.

Humans are environmentally and occupationally exposed to polycyclic aromatic hydrocarbons (PAH). PAH's are a class of tumorigenic compounds which act through metabolic transformation to chemically reactive forms, epoxides, which covalently bind to DNA forming DNA adducts. To evaluate the genotoxic effects of PAH's, air and urine samples were analyzed for PAH. Blood samples were analyzed for benzo(a)pyrene-diol-epoxide-DNA (BPDE-DNA) adducts. New methods for analyzing DNA adducts in lymphocytes have been used to study the genotoxic effects of human exposure to carcinogens. BPDE-DNA adducts in lymphocytes have been used as internal dosimeters of exposure to PAH's and several studies have been conducted. We measured BPDE-DNA adducts in aluminium plant workers with immuno-assay and physico-chemical methods. PAH-DNA adducts were detectable to a lesser extent in subjects working in an aluminium plant compared to subjects working in a coke oven plant.