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Biomedical subjects

M Klein

Publications and source records attributed to M Klein.

At least 559 records · Page 31Linked to original sources
PubMed1987

Preclinical safety evaluation of the benzodiazepine quazepam.

7-Chloro-5-(2-fluorophenyl)-1,3-dihydro-1-(2,2,2-trifluoroethyl)-2H-1,4- benzodiazepine-2-thione (quazepam, Sch 16134, Dormalin) was evaluated for evidence of systemic toxicity, carcinogenicity and reproductive toxicity in several laboratory animal species including the hamster. Mutagenic potential was also assessed in one in vivo and three in vitro assays. In some studies, diazepam was used as a comparative control. Oral LD50 values were greater than 5000 mg/kg in the mouse and rat while i.p. LD50 values were approximately 900 and 2900 mg/kg in the mouse and rat, respectively. Studies in hamsters for 4 weeks at doses up to 500 mg/kg/d and for 51 weeks at doses up to 120 mg/kg/d demonstrated that the liver was the principal target organ in this species with the effects upon the liver related to dose and duration of dosing. Studies in the squirrel monkey for 13 and 52 weeks at doses up to 50 mg/kg/d demonstrated a transient ataxia, hypoactivity and somnolence during the initial two weeks of dosing. No unusual necropsy or microscopic observations were noted in the 13-week study. Male reproductive organs of quazepam-dosed monkeys were reduced in weight after 52 weeks. Moderate to marked impairment of spermatogenesis and higher liver weights with moderate to marked fatty change in both sexes were observed in groups given diazepam. Abrupt withdrawal of quazepam or diazepam after 52 weeks of dosing was associated at all dose levels with excitability, hyperactivity and convulsions. Two quazepam- and all diazepam-dosed monkeys died.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

IgA related disorders in rheumatoid arthritis.

Serum monomeric and polymeric IgA, IgA rheumatoid factor (IgA-RF) and IgA containing circulating immune complexes (IgA-CIC) were studied in 192 patients with rheumatoid arthritis (RA) to explore the relationships among IgA related abnormalities and to investigate their potential associations with disease activity, immunoregulatory disorders and effect of treatments. Total serum IgA and polymeric IgA (p-IgA) levels were elevated in 23 and 11% of patients with RA, respectively. Their respective mean concentrations in serum were significantly elevated compared to normal values (p less than 0.001 and p less than 0.004). A preferential increase in polymeric rather than monomeric IgA was observed. IgA-RF, detected by a solid phase ELISA, was found in 71% and was associated with decreased grip strength (p less than 0.005), active disease (p less than 0.05), increased p-IgA level (p less than 0.001), elevated p-IgA:total IgA ratio (p less than 0.05), the presence of IgA-CIC (p less than 0.005) and IgM-RF (p less than 0.005). Complement fixing IgA-CIC were detected in 40% of patients by IgA specific conglutinin and anti-C3 binding solid phase ELISA. High molecular weight IgA species precipitated by 2.5% polyethylene glycol from RA sera positive for IgA-CIC were shown to be IgA-RF complexed to IgG. Taken together, our results suggest that IgA-RF are essentially polymeric in nature and circulate as IgA-RF-IgG immune complexes. Although the presence of IgA-CIC was not associated with disease activity, IgA-CIC activated C3 and thus are potentially pathogenic.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1987

Is maternity care different in family practice? A pilot matched pair study.

In this pilot study, 81 patients booked for delivery by family physicians were matched to patients booked for delivery by obstetricians. Patients in both groups were at low obstetric risk. They were matched by age, parity, blood pressure, gestational age at delivery, and socioeconomic status. Patients booked with family physicians experienced fewer artificial rupture of membranes, inductions of labor, episiotomies, and forceps deliveries than those booked with obstetricians. These patients also spent a shorter time in hospital in spite of longer second stages of labor. Infant outcomes were equivalent in the two groups. A simple method of audit of maternity care that permits comparisons of the care provided by family physicians and obstetricians for obstetrically similar patients is described. This methodology employs matching within a given institution and facilitates the multicentered studies required to obtain the large populations needed to compare the process and outcome of infant and maternal care provided by these two types of physicians.

Clinical Trials as Topic↗
PubMed1986

Relief of sleep-related oropharyngeal airway obstruction by continuous insufflation of the pharynx.

Sleep-related upper airway obstruction was treated by continuous insufflation of the pharynx (CIP) in 20 children. All had symptoms but only 1 qualified for a diagnosis of the obstructive sleep apnoea syndrome. Passage of warm humidified air through a thin nasopharyngeal tube at 2-10 litres/min (mean 3.5) relieved obstruction immediately in all patients. Relief was always clinically apparent and accompanied by reduced pleural pressure excursions during breathing. An index of the work of breathing (the product of breathing frequency and pleural pressure change per breath) fell by nearly 60% while patients were on CIP. Transcutaneous oxygen tension was monitored in 5 patients and was improved by CIP in each instance. Side-effects of CIP were minor and preventable with up to 72 days of continuous use. CIP is thus a simple and safe method that rapidly relieves severe oropharyngeal airway obstruction in children during sleep. Whether CIP is useful in domiciliary care or for adults has still to be established.

Adenoidectomy↗
PubMed1986

Cryoglobulinemia and hepatitis B markers in North African Jews with Raynaud's disease.

Mixed cryoglobulinemia was discovered in 11 of 20 patients with Raynaud's disease. Hepatitis B surface markers were found in 10 of these patients with cryoglobulinemia. All patients with cryoglobulinemia were female, and 10 were of northern African origin. This study indicates that, in a population with a high prevalence of hepatitis B infection, mixed cryoglobulinemia is an important etiologic factor in Raynaud's disease.

Adult↗
PubMed1986

Dose pipecolic acid interact with the central GABA-ergic system?

Several previous studies have suggested a strong GABA-mimetic action of the endogenous brain imino acid, L-pipecolic acid (L-PA). In the present study, these observations were evaluated using electrophysiological and neurochemical methods. In contrast to published data our electrophysiological studies on rat cortical neurones in situ showed only a weak, but bicuculline-sensitive depressant action of L-PA on cortical neurones. Furthermore, L-PA proved to have no affinity for any of the three components of the GABA-benzodiazepine-chloride channel receptor complex. However, using a modification of published methods a weak affinity for the GABA-B receptor site was demonstrated (IC50 = 1.8 X 10(-3) M). L-PA showed no anticonvulsive activity in several tests; in particular, it did not protect mice from seizures induced by inhibition of L-glutamate-1-decarboxylase (EC 4.1.1.15: GAD). L-PA had a very weak action on brain GABA levels of mice, and did not modify the rate of GABA synthesis. In conclusion, these results are not compatible with a strong in vivo interaction between L-PA and GABA-mediated inhibitory transmission.

Animals↗
PubMed1986

Pulmonary hypertension postventricular septal defect repair treated by extracorporeal membrane oxygenation.

Severe pulmonary hypertension complicating the correction of congenital cardiac defects is an unusual cause of early postoperative mortality. We present a case of a nine-month-old infant who developed paroxysmal pulmonary hypertension associated with severe hypoxemia after the successful repair of a large perimembranous ventricular septal defect (VSD). The pulmonary hypertension was refractory to all medical and pharmacologic therapy but was successfully treated with extracorporeal membrane oxygenation (ECMO). On ECMO, pharmacologic support was removed, pulmonary artery pressure reduced, and ECMO support withdrawn. To date, ECMO has been applied to pulmonary hypertension of the newborn, neonatal respiratory insufficiency, and for primary cardiac pump failure. Our experience with this case leads us to believe it is an effective therapy for acute pulmonary hypertension occurring after the repair of congenital cardiac anomalies.

Heart Arrest↗
PubMed1986

Morphological and isoenzymatic differentiation of B-chronic lymphocytic leukaemia cells induced by phorbolester.

Fresh leukaemia cells from the peripheral blood of 6 patients with B-chronic lymphocytic leukaemia (CLL) were cultured in the continuous presence of the phorbolester 12-O-tetradecanoylphorbol 13-acetate (TPA) for in vitro induction of differentiation. Upon treatment with TPA the cells showed distinct morphological changes consisting of cytoplasmic and nuclear enlargement, vacuolisation and protrusion of cytoplasm, eccentric location of nuclei with perinuclear clear zones, and oval to elongated cell forms. Isoenzyme profiles of the enzymes carboxylic esterase, acid phosphatase, hexosaminidase and lactate dehydrogenase (LDH) were analysed by isoelectric focusing on polyacrylamide gels. An increase in the number and in the staining intensity of isoenzymes were observed for all 4 enzymes in the TPA-exposed cells indicating a maturation along the B cell pathway. TPA triggered the new expression of the tartrate-resistant acid phosphatase isoenzyme, a marker of hairy cell leukaemia (HCL) cells, and of the hexosaminidase I isoenzyme, a marker of multiple myeloma cells. The induced phenotypic changes are suggestive of differentiation to stages corresponding to those of HCL cells or 'pre-plasma cells'.

Acid Phosphatase↗
PubMed1986

Facilitatory transmitters and cAMP can modulate accommodation as well as transmitter release in Aplysia sensory neurons: Evidence for parallel processing in a single cell.

Presynaptic facilitation of transmission from sensory to motor neurons contributes significantly to behavioral sensitization of defensive withdrawal reflexes in Aplysia. Presynaptic facilitation is associated with a decrease in the serotonin-sensitive K(+) conductance. This decrease broadens the presynaptic action potential. In addition, the procedures that cause facilitation-stimulation of the connective (the pathway from the tail and head), application of modulatory transmitters, or injection of cAMP-also increase the excitability of the sensory neurons as tested with intracellular depolarizing pulses injected into the cell body. The increased excitability is reflected in a decreased threshold for generating action potentials and a reduction in accommodation to prolonged constant current stimuli. By influencing the excitability of the peripheral processes of the sensory neurons, stimulation of the connectives or serotonin also produces a small enhancement of the response of the sensory neurons to a tactile stimulus applied to the siphon. The excitability changes appear to result, at least in part, from the same cellular mechanisms that lead to broadening of the action potential, a cAMP-mediated closure of K(+) channels. Therefore, these findings indicate that the same class of mechanisms can, in principle, have a dual action and provide further evidence for parallel processing in the modulation of transmitter release from a single neuron.

Journal Article↗
PubMed1986

Action-potential duration and the modulation of transmitter release from the sensory neurons of Aplysia in presynaptic facilitation and behavioral sensitization.

Presynaptic facilitation of transmitter release from Aplysia sensory neurons is an important contributor to behavioral sensitization of the gill and siphon withdrawal reflex. The enhanced release is accompanied by reduction of the serotonin-sensitive S current in the sensory neurons and a consequent increase in duration of the presynaptic action potential (ranging from 10% to 30%). We find that changes of similar magnitude in the duration of depolarizing voltage-clamp steps in sensory neurons in intact abdominal ganglia yield increases in synaptic potentials of 45-120%. In dissociated cell culture, these changes lead to increases of 25-60% in the synaptic potential. Prolongation of presynaptic depolarization using voltage clamp or prolongation of the duration of the action potential by K(+)-channel blockers leads to prolongation of the time-to-peak of the synaptic potentials; similar changes in time-to-peak occur during presynaptic facilitation. The time-to-peak is not changed by homosynaptic depression or by changing the Ca(2+) concentration, procedures that alter release without changing the duration of the action potential. Preventing the spike from broadening by voltage clamping the presynaptic neuron substantially reduces or blocks the facilitation. These results suggest that broadening of the action potential during facilitation is a causal factor in the enhancement of transmitter release.

Journal Article↗