Response of Plasmodium falciparum to dihydrofolate reductase inhibitors in Malindi, Kenya

The response of Plasmodium falciparum isolates to dihydrofolate reductase inhibitors (DHFRI) was examined in Malindi, Kenya. All 20 infected children treated with pyrimethamine/sulphadoxine responded. In contrast, after treatment with pyrimethamine, parasitaemia in 9 of 14 infections failed to clear or recrudesced during the seven-day follow-up. In a 48-hour in vitro test, five of six isolates resistant to pyrimethamine in vivo had a minimal inhibitory concentration (MIC) to pyrimethamine greater than or equal to 300 nmoles/1 compared with less than or equal to 100 nmoles/1 for the four sensitive isolates; four isolates did not grow. MIC to M-B 35769, an experimental DHFRI structurally similar to pyrimethamine were the same (six isolates) or 10-fold lower (three isolates). In the laboratory four of five isolates adapted to in vitro culture had the same MICs as in the field while one isolate became less responsive to both drugs. Cycloguanil (the active metabolite of proguanil) was more active in vitro in the laboratory than pyrimethamine or M-B 35769.     

Ovarian and omental ependymomas in peritoneal washings: cytologic and immunocytochemical features

The cytologic findings in peritoneal washings of two women, one of whom had an ovarian ependymoma and the other a primary omental ependymoma, are reported. The ependymomas were characterized by the presence of numerous, isolated, spindle and stellate cells as well as groups of cells forming true rosettes. The tumor cells displayed slightly pleomorphic, round-to-oval eccentric nuclei and abundant fibrillary cytoplasm with tapering cytoplasmic processes. In addition, one of the patients had numerous papillae and cell clusters with associated psammoma bodies indistinguishable from those found in low-grade serous carcinoma. The demonstration of glial fibrillary acidic protein (GFAP) in both cases by immunocytochemical procedures indicates the usefulness of this method in cytologic preparations to confirm the diagnosis of these uncommon neoplasms.     

Rapid cation-exchange high-performance liquid chromatographic procedure for the separation and quantitation of hemoglobins S, C, and O Arab in cord blood samples

A rapid method for separating and quantitating hemoglobin (Hb) variants in cord blood samples using cation high-performance liquid chromatography (HPLC) is described. The procedure is a modification of a previously published method, and uses a weak cation-exchange Brownlee-3CM column and Bis-Tris-KCN-Na acetate developers. A chromatogram can be completed in 10 minutes. The slow-moving variants, Hbs S, C, and O Arab, can be completely separated from each other and are identified by their elution times relative to Hb A. Hb E elutes as a shoulder on the descending side of Hb A, which is characteristic for this variant in this procedure. Differentiation between heterozygous, homozygous, and Hb X-beta+-thalassemia conditions is easily made.     

Velocity discrimination in the cat

After considerable training (over 2 years) we measured the just noticeable differences (JNDs) in velocity as a function of reference velocity in three cats. The velocity discrimination curve plotting JNDs in velocity, expressed as Weber fractions as a function of reference velocity is U-shaped with optimal performance at reference speeds between 25 and 60 degrees/sec. The discrimination curve changed little with a tenfold change in slit width. Compared to the human velocity discrimination curve determined with the same test apparatus, the feline curve is narrower and shifted towards faster velocities and larger Weber fractions. These results support our specific linking hypothesis between velocity tuned cells as observed in cortical areas 17 and 18 of the cat, and velocity discrimination.     

Opioid-receptor blockade reduces nose-poke self-stimulation derived from medial entorhinal cortex

Rats were trained to nose-poke for intracranial self-stimulation (SS) with electrodes unilaterally implanted in the medial entorhinal cortex. The acute effects of naloxone (NX; 0.1-10 mg/kg, IP) on a continuous reinforcement schedule were determined. Reductions in the self-stimulation rates occurred only at moderate doses (median of individual changes = -36% at 1 and 5 mg/kg), whereas the high dose (10 mg/kg) was ineffective. None of the doses influenced operant behavior. These results are consistent with the hypothesis that endogenous opioid-opiate receptor mechanisms play a modulatory role in SS reward. Considering that NX was administered systemically the action of the drug on reinforcement levels may be mediated by a site distinct from the locus of stimulation.     

A method for evaluating antianginal drugs in experimental animals: assessment of myocardial ischemia by myocardial pH

This paper describes a method by which antianginal drugs can be evaluated in the dog heart in situ. Myocardial pH was measured continuously by a micro glass pH electrode inserted in the left ventricular endocardial layers of the dog anesthetized with pentobarbital. Occlusion of the left anterior descending coronary artery (LAD) decreased myocardial pH, and release of the LAD restored the pH. The myocardial acidosis induced by ischemia was metabolic in nature and accompanied by a decrease in the levels of adenosine triphosphate and creatine phosphate and an increase in the levels of lactate in the myocardium. Drugs were injected intravenously 30 min after incomplete (partial) occlusion ot the LAD, lasting until 60 min after drug injection. Propranolol, atenolol, and sotalol markedly attenuated the myocardial pH that had been decreased by LAD occlusion. Nitroglycerin, diltiazem, and nicorandil also attenuated the pH, but these drugs were less active in attenuating myocardial acidosis. Dipyridamole, nifedipine, and beta-2 adrenoceptor antagonists were least active in this regard. It is concluded that myocardial pH can be used as an indicator of myocardial regional ischemia and utilized for evaluation of antianginal drugs.     

Subjective ratings of sleepiness--the underlying circadian mechanisms

Previous field and laboratory studies have revealed that there is a diurnal variation in subjective sleepiness that is different in form to that of objective sleepiness and many measures of performance efficiency. The worst subjective sleepiness occurs at the trough in the circadian temperature rhythm, the least subjective sleepiness about 7 h before the peak in temperature. A series of forced desynchronization experiments, in which the endogenous circadian oscillator controlling the temperature rhythm ran at a different period to the sleep/wake cycle, revealed that these findings can be explained by postulating subjective sleepiness to be under the control of both factors, with minimum sleepiness occurring at the peak in temperature in terms of the temperature cycle and about 6 h after waking in terms of the sleep/wake cycle.