Clinical and therapeutic studies in mesangial immunoglobulin a glomerulonephritis

A long-term clinical and therapeutic study was performed in 47 patients with mesangial IgA glomerulonephritis. The male to female ratio was 2.9∶1. An episode of gross haematuria or the incidental discovery of asymptomatic microscopic haematuria with associated mild proteinuria heralded the apparent onset of renal disease. At the onset of observation 18 patients (38.2%) had high blood pressure. Other 17 patients developed hypertension during observation. Anaemia was uncommon. No essential abnormalities in serum protein and lipid patterns were found. Twenty-nine patients (61.6%) had higher levels of serum immunoglobulins—most frequently of IgA (42.5%). Twenty-two patients had low serum C₃ levels (46.8%). The percentage of patients with renal failure increased from 21.2 to 36.1 during observation. Male sex, hypertension, proteinuria higher than 2 g/24 h, elevated ESR, high serum IgA levels, longer duration of the disease and older age of patients suggest an unfavourable outcome. Long-term treatment with a combination of azathioprine/acenocumarol, or indomethacin, or levamisole has no effect on the clinical manifestation and evolution.     

VECURONIUM AND ATRACURIUM IN PATIENTS WITH END-STAGE RENAL FAILURE: A Comparative Study

Twenty patients with end-stage renal failure, undergoing kidneytransplantation, were assigned randomly to receive either vecuroniumor atracurium under evoked twitch tension control. The cumulative-dosetechnique was used to obtain 95% twitch depression (vecuronium:initial bolus 15 µg kg^–1, increments 6 µgkg^–1; atracurium: initial bolus 100 µg kg^–1,increments 40 µg kg^–1). Using ED₉₅ values derivedfrom the log-probit dose-response curves, vecuronium was 4.6times more potent than atracurium. The durations of action ofthe initial cumulativedoses (from end of injection of the lastincrement to 25% recovery) were 11.1± 3.3 min for vecuroniumand 16.2±3.9 min for atracurium (P < 0.05). In termsof duration of action of the maintenance doses (vecuronium one-quarterof the total incremental dose; atracurium one-third) some cumulationwas observed with vecuronium (interaction time x treatment;cumulation ratio 1.46 ±0.31 v. 0.98±0.10 for atracurium,P< 0.001). After 2 h of surgery, the mean recovery times(25% to 75% twitch height) did not differ (18.5±2.8 minand 16.7±4.4 min). It is concluded that vecuronium mightbe less safe than atracurium in patients with end-stage renalfailure undergoing prolonged operations.     

Phase I study of high-dose cytosine arabinoside and etoposide in patients with advanced malignancies

Summary Cytosine arabinsodie (ara-C) and etoposide (VP-16) display synergy in the laboratory. Twenty-six patients participated in a phase I study of high-dose ara-C in combination with VP-16. The dose of VP-16 was held constant at 50 mg/m² as an intermittent infusion over 33 h; escalating doses of ara-C were given as infusions during hours 9–12 and 21–24. Myelosuppression was the dose-limiting toxicity and occurred with doses considerably less than those expected from studies of the two drugs as single agents. The suggested initial doses for phase II trials with this schedule are 750 mg/m²×2 doses of ara-C and 50 mg/m² of VP-16. Nonhematologic toxicity was minimal; therefore, further dose escalation is feasible in patients in whom myelosuppression is acceptable.Supported in part by grants from the National Cancer Institute (CA-12197 and CA-09422) and the American Cancer Society CF-85-182     

4-Aminopyridine affects synaptosomal protein phosphorylation in rat hippocampal slices

Rat brain hippocampal slices were incubated with or without the convulsant 4-aminopyridine (4-AP). From these slices a crude mitochondrial/synaptosomal membrane fraction was prepared and analyzed for endogenous protein phosphorylation. 4-AP (10(-5) M) stimulated the phosphorylation of a 50 kDa protein by 86%. The phosphorylation of this 50 kDa protein is Ca2+/calmodulin-dependent and we suggest that this protein is the lower molecular weight subunit of Ca2+/calmodulin-dependent protein kinase II (CaMK II).     

Levels of metals in hair of young children as an indicator of environmental pollution

In 1982 the levels of lead (Pb), cadmium (Cd), vanadium (V), copper (Cu), and selenium (Se) were determined in hair of 231 four- to five-year-old children. The objective was to explore the feasibility of using metal-in-hair levels in groups of children as an indicator of environmental pollution. The study was carried out in four areas, which were assumed to differ in ambient pollution by metals. A questionnaire on personal data, socioeconomic status, intake of beverages, and life-style was completed by the parents. The metal-in-hair levels covered a large range. The variables pertaining to location together with sex, presence of a garden, and drinking of coffee and/or tea explained 32% of the variance of Pb, 24% of the variance of Cd, and 21% of the variance of V. The total variance explained by all measured questionnaire items was at best 38%. The location was the most important factor. Cu and Se levels did not differ between the locations.     

Actions of phencyclidine on the action potential and membrane currents of single guinea-pig myocytes

The direct actions of phencyclidine (PCP) on mammalian sarcolemma were examined by determination of the drug's effects on the action potentials of isolated guinea-pig ventricular cells, and on the underlying ionic currents. PCP (10(-6) to 10(-4) M) did not alter the resting membrane potential but produced a dose-dependent prolongation of the duration of the action potential, and a reduction of the rate of depolarization of phase 0 (Vmax) of the action potential. Voltage clamp experiments revealed that PCP blocks both myocardial Ca++ channels and myocardial time-dependent K+ channels. The K+ channel blockade was shown to exhibit an apparent voltage-dependence. The effects of PCP on these ionic channels could explain previous reports of it prolonging myocardial action potentials and conflicting reports of positive and negative inotropism.