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.     

Pharmacokinetics, metabolism and renal excretion of sulfatroxazole and its 5-hydroxy- and N4-acetyl-metabolites in man

Hydroxylation is the predominant pathway of metabolism for sulfatroxazole in the body, accounting for 70 per cent of the dose. Fifteen per cent of the dose is acetylated unimodally and 10 per cent is excreted unchanged. The half-lives of sulfatroxazole and its metabolites 5-hydroxysulfatroxazole and N4-acetylsulfatroxazole are approximately 22 h after administration of sulfatroxazole. N4-acetylsulfatroxazole, taken as parent drug, is eliminated by renal excretion (92 per cent of the dose). The initial elimination half-life of N4-acetylsulfatroxazole is 4.5 h, which later increases to 70 h as the result of the acetylation-deacetylation equilibrium. Probenecid inhibits the renal excretion of the metabolites 5-hydroxy- and N4-acetylsulfatroxazole. Inhibition of the N4-acetyl metabolite favours the deacetylation, which results in an increase of the T 1/2 of sulfatroxazole from 20 to 30 h. The protein binding value of sulfatroxazole is 84 per cent, that of N4-acetylsulfatroxazole is 37 per cent. Sulfatroxazole is excreted renally by passive processes, while the metabolites are excreted by both passive and active processes.     

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.     

Various problems in the diagnosis and treatment of the broncho-obstructive syndrome

Clinico-x-ray-laboratory investigation, bronchoscopy were performed, respiratory function and ECG were studied in 212 patients with different forms of chronic bronchitis. Six groups of patients were defined with relation to the presence or absence of obstruction, its nature (permanent, transient), prevalence (small, medium and large bronchi), genesis of disease (inflammatory, allergic). The characteristics of the groups and their clinico-x-ray, functional and immunological features were presented. Treatment including methods of climatotherapy, exercise therapy, pharmacological agents (antibacterial, broncholithic and antihistaminic), physiotherapy and administered with relation to the defined groups, proved to be effective. The improvement of bronchial permeability was noted in 49.5% (ranging from 40.0 to 68.7% in different groups).     

Immunological mechanisms giving rise to latency of herpes simplex virus in the spinal ganglia of the mouse

In the model of genital herpes simplex virus (HSV)-infection of mice, early latency could be induced by passive immunization with HSV-specific antibodies and, to a lesser degree, by adoptive transfer of immune lymphocytes prepared from spleen and draining lymph nodes of genitally infected syngeneic mice. Conversely, spontaneously occurring latency was inhibited by treatment of the animals with cyclophosphamide (Cph) and, to a lesser degree, with cyclosporin A (CyA). Whereas the effect of CyA could be compensated by passively administered HSV-specific antibodies, that of Cph could not. Apparently specific antibodies cooperate with a non-specific proliferating cell type, probably macrophages and/or NK-cells, as could be demonstrated by significantly reduced antibody effect in silica-treated mice. Moreover, F(ab)₂ fragments, in contrast to complete antibody molecules, were inactive. HSV-specific antibodies and also immune lymphocytes had little effect on virus production in the mucous membranes, immune lymphocytes being at least as active as antibodies. It is therefore not probable that latency is induced by attenuation of the peripheral disease. It can rather be concluded that the neuron itself is the target for the action of specific antibodies, cooperating in turn with macrophages and/or NK cells.With support of the Deutsche Forschungsgemeinschaft, Schn 174/6-3     

Intra-arterial thrombolysis for acute limb ischemia: a three-year experience

Peripheral arterial thromboembolism and thrombosis of arterial grafts continue to threaten viability of extremities. Percutaneous intra-arterial thrombolysis (IAT) and angiodilatation have afforded limb salvage in some of these patients. Proper patient selection appears to be the hallmark of success with IAT. During a recent three-year period, we used IAT in 32 extremities in 28 patients who had acute arterial insufficiency. Before IAT, 16 extremities were painful at rest, and 16 had incapacitating claudication. The overall success rate was 38%, but some degree of thrombolysis occurred in 88%. Limb salvage was achieved in 27 of 32 extremities (84%). Only five of 17 limbs (29%) with arterial graft thrombosis required no operation or an operation of lesser magnitude than predicted before IAT. Of six extremities with native arterial embolism, four (67%) were completely cleared with IAT. Major complications occurred in eight cases (25%), with two IAT-related deaths (6%). This study suggests that IAT is best reserved for individuals with acute limb ischemia caused by arterial embolus, those whose degree of ischemia would tolerate a 24-hour trial of IAT, and those whose femoral or tibial runoff is not likely to require remedial operation.