Biomedical subjects
Publications and source records attributed to M Weiner.
A hemangioma of the urinary bladder occurring in a 66-year-old man is described. Although hemangioma is a common lesion in many parts of the body, it remains a very rare primary tumor in the bladder. Clinically the patient usually presents with recurrent hematuria, control of which may necessitate a segmental cystectomy.
A case of prostatic adenocarcinoma metastasizing to the epididymis is described, and the literature is reviewed.
Distinct differences between topical acid preparations can be detected by simple preclinical and clinical pharmacologic models designed to evaluate potential utility in the treatment of superficial skin tumors. The models distinguish a tissue-dissolving (ulcerating) effect from a tissue-fixation (mummifying) effect, as reflected by a distinct and lasting discoloration of hair in vitro or the skin surface in vivo. Double-blind clinical comparison of the response to different preparations of matched pairs of small superficial skin tumors in 33 subjects demonstrated for greater utility for nitric acid preparations of appropriate strength (6 to 7N), with added oxidizable organic acids, over the mineral acid alone. The nitrate reduction products generated in such preparations markedly speed up discoloration in the models and apparently contribute to the improved clinical utility of the topical treatment by enhancing the speed and intensity of tissue fixation, but not tissue erosion. The architecture of lesions eradicated by such mixtures is generally adequately preserved for histologic diagnosis of the extruded tissue.
The mean generation time of Haemophilus influenzae in simulated blood cultures is 103 to 107 min. With 0.56 to 0.58 doublings per h, even large inocula of 256 cells per ml reach only 2 X 10(6) cells per ml and produce no visible evidence of growth after 24 h of incubation. Hemin and NAD added to simulated blood cultures triple the rate of growth of H. influenzae, so that even small inocula produce visible turbidity after overnight incubation. With a mean generation time of 36 min, a single cell of H. influenzae in simulated blood culture supplemented with hemin and NAD undergoes 30 doublings in 18 h, producing 2(30) (1.07 X 10(9] cells and visible turbidity.
Alterations in brain tryptophan levels and the rate of hepatic tryptophan metabolism by tryptophan oxygenase (TPO) were studied in male Sprague-Dawley rats rendered diabetic by intravenous administration of streptozotocin (STZ), 65 mg/kg. Determinations were made at the early onset of diabetes (1-4 days of glucosuria) and 8-12 days following STZ injection. Rats were considered diabetic if their serum glucose exceeded 250 mg percent. Tryptophan brain levels decreased by 17% after four days of diabetes, decreased by 22% on day 5, and by 27% 8-12 days after STZ. Brain 5-hydroxyindoleacetic acid levels were significantly decreased by 27% on day 5, but returned to control levels by 8-12 days. Serotonin concentration in the brain remained at control values. The initial appearance of a significant increase in total TPO activity coincided with the onset of a change in brain tryptophan. Total TPO activity increased by 60% after 4 days of diabetes. The increase was caused by an increase in apoenzyme activity since holoenzyme activity remained unaltered. Holoenzyme activity was increased by 37% after 8-12 days, and accounted for the change in total TPO activity. Insulin treatment reversed the STZ-induced alterations. The results are compatible with the hypothesis that diabetes increases hepatic TPO activity that in turn results in decreased plasma tryptophan levels and decreased availability of tryptophan for brain uptake. However, compensatory changes appear to maintain a stable serotonin concentration in the brain. The early and later changes in TPO activity during diabetes are apparently caused by different regulatory events.
A young man with polycystic kidney disease was seen initially with an brain-stem infarction. Postmortem examination disclosed a dissecting aneurysm of the basilar artery and a saccular aneurysm of the right vertebral artery. Dissecting intracranial aneurysms rarely are associated with saccular aneurysms and, to our knowledge, have not been reported in association with polycystic kidney disease.
A retrospective study of factors influencing survival in 1,103 patients with systemic lupus erythematosus (SLE) was carried out at 9 university centers diverse in geographic, socioeconomic, and racial characteristics. The mortality and disease characteristics of the patients at study entry varied widely among centers. The survival rates from the time patients with a diagnosis of SLE were first evaluated at the participating center was 90% at 1 year, 77% at 5 years, and 71% at 10 years. Patients with a serum creatinine greater than 3 mg/dl at study entry had the lowest survival rates: 48%, 29%, and 12% at 1, 5, and 10 years, respectively. Survival rate also correlated independently with the entry hematocrit, degree of proteinuria, number of preliminary American Rheumatism Association criteria for SLE satisfied, and source of funding of medical care. When data were corrected for socioeconomic status, race/ethnic origin did not significantly influence survival. Survival rates varied widely at different participating institutions, generally due to differences in disease severity. Place of treatment was independently associated with survival only in the second year after study entry. Disease duration before study entry did not account for the differences in disease severity.
Causes of death were examined for 1,103 systemic lupus erythematosus patients who were followed from 1965 to 1978 at 9 centers that participated in the Lupus Survival Study Group. A total of 222 patients (20%) died. Lupus-related organ system involvement (mainly active nephritis) and infection were the most frequent primary causes of death. Causes of death were similar throughout the followup period. Hemodialysis had little impact on the length of survival for patients with nephritis. Active central nervous system disease and myocardial infarction were infrequent causes of death. There were no deaths from malignancy.
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A battery of sophisticated studies of central nervous system function in man, including electroencephalogram (EEG) analyses in several laboratories, confirm the numerous clinical reports that alpha-[4-(1,1-dimethylethyl)-phenyl]-4-(hydroxydiphenylmethyl)-1- piperidinebutanol (terfenadine, RMI 9918, Triludan, Teldane, resp.) is devoid of the sedating action characteristic of other antihistamines. No basis has been uncovered for concern about inadvertent overdosage or the operation of machinery while under antihistaminic treatment with terfenadine. Full antihistaminic action is achieved with daily doses totaling 60 to 120 mg. Doses 10 times greater have been shown to be well tolerated in man, indicating a uniquely favorable therapeutic index for an effective H1-inhibitor. In evaluating comparative clinical studies, it is essential to consider whether sedation is factored into the study design as a desired or undesired action.
alpha-[4-(1,1-Dimethylethyl)phenyl]-4-(hydroxydiphenylmethyl)-1- piperidinebutanol (terfenadine, RMI 9918, Triludan, Teldane, resp.) was evaluated in groups of at least 30 patients per drug for relief of symptoms of active allergic pollinosis on a double-blind basis during the pollen season for 3 successive years. Terfenadine 20 mg 3 times a day was as effective as chlorpheniramine maleate 4 mg 3 times a day. In each study chlorpheniramine consistently showed a higher incidence of sedation than placebo. None of the terfenadine dosage schedules up to 200 mg 3 times a day caused sedation significantly different from that of placebo or efficacy greater than that seen with 20 mg 3 times a day. The incidence of central nervous system stimulation in the terfenadine group was also not different from that of placebo.
Low oxygen affinity red cells were prepared by incorporating inositol hexaphosphate (IHP) into red blood cells (rbc) by means of a liposomal transport system. The effect of in vitro simulated exchange transfusions on sickling was studied with buffered red cell suspensions containing 50% SS cells and 50% test cells. Test rbc were either stored cells with high oxygen affinity, fresh cells with normal affinity or IHP-loaded cells with decreased affinity. Oxygen equilibrium curves and percentage sickling as a function of PO2 were determined and the data analyzed in terms of percentage sickling as a function of oxygen delivery. Our simplified analysis shows that simulated exchange transfusion with stored and, to a lesser extent even with fresh blood, results in a decreased venous PO2 and increased sickling of the remaining SS cells. In contrast, transfusion with IHP-loaded cells results in higher venous PO2 values and less sickling throughout the range of oxygen delivery. Thus, the transfusion of IHP-loaded cells may result in less sickling of the remaining SS cells in addition to the normal dilutional effect.
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We have studied 50 Caucasoid children under 7 years of age with Haemophilus influenzae b disease. Half of the patients (Group A) had invasive disease shown by positive blood and/or spinal fluid culture. The other half (Group B) had noninvasive disease characterized by fever, nasopharyngitis, negative blood culture, and positive throat culture. Age, number of other siblings under 12 years old in the family, immune response, antibody production and genetic markers were compared in the two groups. Significant difference between the two groups was only seen in their genetic markers. HLA-B12 was present in 52% of Group A patients as opposed to 16% in Group B patients (P less than .01). HLA-Bw40 was present in 24% of group B patients and absent in all Group A patients (P less than .01). These findings would suggest that susceptibility and resistance towards developing invasive type b disease may be genetically determined.
The conjugative metabolism of p-nitroanisole (pNA) and p-nitrophenol (pNP) was studied in isolated hepatocytes of male and female rats rendered diabetic with streptozotocin. Hepatocytes of male diabetic rats formed more of the glucuronide conjugate from pNA than controls and a tendency toward higher sulfate conjugate production was observed. By summation of conjugated metabolites and unconjugated phenol, it was determined that O-demethylation of pNA was also increased, possibly accounting for the increased production of conjugated metabolites. Production of the sulfate conjugate directly from pNP was inhibited in male diabetic hepatocytes when the substrate concentration was 50 microM but was not altered at other substrate concentrations. Glucuronidation was increased in hepatocytes of diabetic rats when pNP was used as substrate at concentrations of 50 and 100 microM, whereas there was no difference from control at 25 microM pNP. Treatment of diabetic rats with insulin returned glucuronidation to control values. The effect of diabetes on glucuronidation in hepatocytes was not due to increases in microsomal glucuronyltransferase activity. In contrast to males, no differences were observed between hepatocytes of control and diabetic female rats in the capacity to form conjugated metabolites from pNA or pNP. It is consistent with previous reports that alterations in carbohydrate metabolism in hepatocytes of male diabetic rats led to accelerated formation of uridine diphosphate glucuronic acid, resulting in greater rates of glucuronidation.
Counterimmunoelectrophortesis was shown to be a sensitive method for rapid detection of pneumococcal and Haemophilus influenzae type b antigens in blood cultures.