Biomedical subjects
Publications and source records attributed to M Stern.
A fatal case of eosinophilic meningitis associated with a large cell bronchogenic carcinoma is reported. Neither a cerebral parasitic disease nor metastatic localizations were found at necropsy. It is the first reported case of an eosinophilic meningitis linked to a bronchogenic carcinoma as a paraneoplasic syndrome.
In treating severe respiratory infections due to Pseudomonas aeruginosa and in patients with cystic fibrosis, new anti-pseudomonal beta-lactams constitute a good alternative to the traditional aminoglycoside antibiotic therapy. Among several criteria for the choice of an antibiotic, estimation of intrabronchial levels is to be taken into account. The authors report the results of the study of a new semi-synthetic penicillin, apalcillin, and two cephalosporins (cefsulodin, ceftazidime), active in vitro against Pseudomonas; their penetration into respiratory secretions was evaluated in 48 patients, intubated, tracheostomized, or undergoing fiberoptic bronchoscopy. Antibiotic concentrations were measured by the microbiological procedure. Bronchial penetration of apalcillin was early and noticeable, reaching a bronchial peak representing 20% of the simultaneous seric concentration. The local levels of cefsulodin and of ceftazidime did not differ from those achieved with cephalosporins studied previously; the bronchial peak reached 5,6 micrograms/ml for both drugs 2 hours after administration; this bronchial level corresponded to 15 to 20% of the serum concentration. The clinical response could not be evaluated due to the severe underlying pathology which compromised the outcome of the disease in the patients of this study. However, at least for apalcillin, a significant correlation was noted between bronchial levels, susceptibility of bacteria isolated in patients, and eradication of susceptible organisms.
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We determined lactic acid levels by the lactic dehydrogenase method in synovial fluid of 41 patients with various rheumatic diseases, to test the concept that significantly elevated values were diagnostic of septic arthritis. Nine patients had septic arthritis, 15 rheumatoid arthritis (RA), and the remainder miscellaneous conditions. In another 9 patients with different rheumatic diseases, including 1 with septic arthritis, synovial fluid lactic acid was determined by both the lactic dehydrogenase and gas-liquid chromatography methods. There was a wide scatter of values among patients with septic and nonseptic inflammatory arthritis, and much overlap occurred. We could not differentiate septic arthritis from RA on the basis of synovial fluid lactic acid levels. Results were similar with both procedures for determining lactic acid levels.
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Azthreonam is a new completely synthetic, monocyclic beta-lactam antibiotic with potent activity in vitro against most gram-negative aerobic bacteria. Its renal handling was studied in six healthy men after an intravenous loading dose of 1200 mg over 2 min followed by a continuous infusion of 500 mg/hr for 4 hr with and without oral probenecid (1 gm b.i.d. for 2 days before azthreonam infusion and during the day of infusion). To assess glomerular filtration, each subject also received an intravenous loading dose and continuous infusion of inulin. Azthreonam was excreted in the urine by glomerular filtration and tubular secretion in essentially equal proportions. Probenecid reduced plasma clearance of azthreonam bY suppressing renal tubular secretion, without altering glomerular filtration rate or nonrenal elimination. Probenecid increased total and free azthreonam levels and the azthreonam plasma t1/2 while reducing plasma protein binding and the apparent steady-state volume of distribution.
Medical students were assessed by questionnaire in their third and fourth years regarding attitudes about sex role, medical school, and career plans and in the third year about fear of success. Nine percent of each sex were judged to fear success. Stereotypical responses were reported by the students. Males, anticipating that they would work more than 60 hours per week, looked forward to academic careers, while females more often desired the sharing of financial and child care responsibilities with spouses. Attitudes toward chores were egalitarian, but in reality women performed most routine household activities. Both sexes agreed upon the characteristics that are necessary to be a good student as well as to succeed in later life. Women were more inclined toward artistic and domestic interests and helping others, while men were more interested in scientific investigation, athletics, and adventure. The implications of these similarities and differences for the students' future careers are discussed.
To investigate the oral bioavailability of aztreonam (SQ 26,776), we administered single 500-mg doses of this monobactam as an oral solution, as two 250-mg capsules, and as a 3-min intravenous infusion to 15 healthy male subjects at 1-week intervals according to a three-way crossover study design. Serum and urine samples were assayed by microbiological methods. The absolute systemic bioavailability of each oral formulation, defined as the ratio of areas under the serum concentration-time curves after oral and intravenous administration, was less than 1%. Peak serum levels achieved with oral solution, capsule, and intravenous infusion were 0.15, 0.14, and 56.7 micrograms/ml, respectively, and cumulative urinary excretion was 0.7, 0.6, and 68% of the administered dose, respectively.
In vitro studies on the new beta-adrenoceptor antagonist, cetamolol (Betacor), have demonstrated that the compound is a potent antagonist of the chronotropic effects of isoproterenol on guinea pig atria. The pA2 value (8.05) of cetamolol was slightly lower than that of propranolol (8.44). The compound was shown to possess a moderate degree of cardioselectivity as indicated by a lower pA2 value for the antagonism of isoproterenol-induced relaxation of the isolated guinea pig trachea (pA2 = 7.67) compared with that derived from atrial experiments (pA2 = 8.05). Up to concentrations of 10(-4) M, cetamolol displayed negligible negative inotropic activity relative to propranolol in the electrically stimulated guinea pig left atrial preparation. When applied to isolated right atria from reserpinized rats, cetamolol had a positive chronotropic effect (approximately 75% of that displayed by practolol) which was antagonized by pretreatment with propranolol, thus indicating intrinsic sympathomimetic activity. Specificity experiments in a number of isolated tissues indicated that cetamolol had very little antihistaminic, anticholinergic, alpha 1-adrenergic blocking, or calcium antagonistic properties. Biochemical receptor binding studies are in general agreement with the observations from the isolated tissue experiments.
Activities of lactase, sucrase, and maltase were determined in small intestinal biopsies of 125 children with coeliac disease, cow's milk protein intolerance, transient gluten intolerance, nonspecific enteropathies, and controls. Four cases of primary disaccharidase deficiencies could be identified. In the enteropathies, morphometric data were more closely correlated to the degree of the mucosal lesion (r = -0.92 for crypt depth) than were disaccharidase activities (r = 0.61 for lactase). In a stepwise discriminant analysis of the patient groups, based upon immunological, morphometric, and biochemical variables, lactase activity was a valuable secondary criterion, ranking third among the variables used.
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Our previous findings show that cancer patients' plasma lacks a factor (LCMEF) which is characterized by its ability to enhance lymphocytic cortisol metabolism. In the present study, using the dialysis method, we tried to evaluate the size of that factor. Plasma of healthy donors (HP) was dialyzed against water. Human lymphocytes from healthy donors were incubated with cortisol in media containing buffer (PBS) and one of the following additions: 1) dialyzate, 2) dialyzed HP (DP), 3) reconstituted HP (DP + P). The cortisol conversion rates were compared with that obtained with untreated HP and with PBS. The results showed no significant differences among the conversion rates obtained with HP, dialyzate, and reconstituted HP. Dialyzed plasma, however, showed a significantly lower rate, which was equal to that obtained with PBS. This implies that the factors are smaller than 10,000 daltons.
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The effects of topical 0.5% Timoptic on the reepithelialization of rabbit corneas were compared to the effects observed in rabbits receiving either vehicle, phosphate-buffered saline (PBS), PBS containing 0.5% timolol maleate, or no treatment. The rate of epithelial wound closure was slowed, and epithelial DNA content was less in both Timoptic- and vehicle-treated corneas. Light microscopy showed that the epithelium of animals treated with either Timoptic or vehicle processed fewer cellular layers in the wounded areas as well as considerable disruption of the epithelial layer. The rate of DNA synthesis and the cyclic adenosine monophosphate content of the epithelial cells from all treatment groups were statistically the same. The impaired wound closure observed during Timoptic and vehicle treatment was probably due to the sloughing of cells caused by the 0.01% benzalkonium chloride in the vehicle and not to impaired healing caused by the metabolic effects of timolol meleate.
One hundred and twenty-five small intestinal biopsies from children with coeliac disease (CD), cow's milk protein intolerance (CMPI) and controls were compared by morphometric analysis, by counting intraepithelial lymphocytes (IEL) and by quantitative evaluation of immunoglobulin-containing cells of lamina propria. The double-stain immunofluorescent technique of Brandtzaeg and Baklien [2] was used, based on defined mucosal tissue units. A patchy enteropathy was found in 60% of CMPI, and in 14% of nonspecific changes, but never in CD. There was a significant difference in crypt depth between CD (360 +/- 80 microns) and CMPI (217 +/- 92 microns), even when lesions of equal grade were compared (P less than 0.015). IEL counts per 1000 epithelial cells showed even better discrimination between the groups (CD: 793 +/- 173, CMPI: 320 +/- 143, P less than 0.001). In CD, there was a relatively greater increase of IgM-cells (X 4.9) and of IgG-cells (X 4.2) than of IgA-cells (X 2.6). Ig-cell changes outlasted the morphological lesion in CD on a gluten-free diet. In CMPI, IgM-cells (X 2.3), IgG-cells (X 2.5), and IgA-cells (X 1.7) were proportionately increased, compared to controls. A special increase of IgE-cells in CMPI could not be substantiated. By computerized stepwise discriminant analysis based upon crypt depth, villus/crypt-ratio, IEL-count, and counts of IgM-, IgG-, IgA-containing cells of lamina propria, accurate classification of patient groups was accomplished, even when only the initial biopsy data were analysed.
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When a preliminary analysis suggested that treatment with HBO might cause an increased mortality due to HBO, a paired control study of 36 patients treated with HBO and 36 matched controls was carried out. While mortality, mean day of death, and total hospital days were the same between the two groups, the HBO group suffered more kidney damage, had more positive blood cultures. The paired control method showed that the increased mortality observed in both groups of patients studied was not due to HBO treatment but to some other undetected selection factor. The findings that the HBO-treated patients had increased sepsis and renal damage warrants further investigation.