Introduction lecture. The prostaglandins and their practical applications.
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Biomedical subjects
Publications and source records attributed to S Bergström.
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The recently confirmed value of amniotic fluid cytology as a tool in the determination of fetal maturity constitutes the background of the present study, in which the exfoliative capacity of human fetal skin was investigated with correlate ultrastructural methods. By transmission and scanning electron microscopy, detachment mechanisms are elucidated in the fetal periderm. It is concluded that the exfoliative capacity prevailing in early pregnancy fetal skin is different from the maturity-related exfoliative capacity in the third trimester. Both kinds of exfoliated cell material constitute antenatally available fetal tissue, the utilisation of which in antenatal diagnosis may be extended.
A patient who contracted urethritis from a beta-lactamase-producing strain of Neisseria gonorrhoeae was successfully treated with the cephalosporin derivative cefuroxime. As expected, neither cefuroxime nor cefamandole was hydrolysed by plasmid-coded gonococcal beta-lactamase. Cefuroxime ought to be a valuable and efficacious substitute for penicillins in the treatment of gonhorrhoea due to beta-lactamase-producing gonococcal strains.
The genetic and physiological mechanisms for affecting the amount of chromosomally mediated beta-lactamase of Escherichia coli K 12 was reviewed. The presence of clinical E. coli isolates with elevated beta-lactamase production was assessed. Among cephalothin resistant isolates from patients with urinary tract infections, six E. coli strains were found to produce elevated amounts of a beta-lactamase indistinguishable from that coded by the ampC gene of E. coli K 12. The resistance levels displayed by these isolates towards a number of beta-lactams was very high as compared to E. coli strains being wild type for chromosomal beta-lactamase production. Cefuroxime and to lesser extent cefamandole were stable to hydrolysis by E. coli chromosomal beta-lactamase but acted as inhibitors of the enzyme. Nevertheless increased beta-lactamase production mediated an increased resistance towards these drugs.
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Nonsteroidal antiinflammatory drugs (NSAID) induce the formation of bleeding gastric and intestinal ulcers in experimental animals. The damage can be prevented by prior local administration of prostaglandins, indicating that prostaglandins have protective properties on the gastrointestinal mucosa. The protective effect was studied in humans by measuring the fecal blood loss during indomethacin treatment of 18 patients with rheumatic diseases with and without concomitant oral supplementation with 1 mg prostaglandin E2 three times daily. The study had a randomized double-blind crossover design using 51Cr-labeled erythrocytes as marker of gastrointestinal bleeding. Indomethacin increased the daily fecal blood loss from 1.0 +/- 0.3 to 2.8 +/- 0.6 ml (P less than 0.005). When oral PGE2 was taken concomitantly, the blood loss was reduced to 1.1 +/- 0.2 ml daily (P less than 0.01), i.e., to the control level. Side effects of prostaglandin E2 were negligible, and the beneficial effect of indomethacin on joint status and symptoms was not interfered with. No changes were recorded in repeated blood tests except for a slightly reduced hemoglobin and a small but statistically significant reduction of serum-calcium during indomethacin treatment, an effect hitherto not described in normocalcemic human subjects. A protective effect on the gastrointestinal mucosa by oral prostaglandin E2 has by the present study been demonstrated also in humans. The protection is unrelated to the gastric acid secretion, which is not inhibited by oral prostaglandin E2. The finding may have clinical application, as gastrointestinal side effects and bleeding are common reasons for discontinuation of NSAID in patients with rheumatic diseases.
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Among cephalothin-resistant isolates from patients with urinary tract infections, six Escherichia coli strains were found to produce elevated amounts of a beta-lactamase indistinguishable from that coded by the ampC gene of E. coli K-12. The resistance levels displayed by these isolates toward a number of beta-lactams were, for five of them, considerably higher as compared with E. coli K-12 with the same amount of beta-lactamase, implying the importance of intrinsic resistance in these isolates. Cefuroxime, and to a lesser extent cefamandole, were stable to hydrolysis by E. coli chromosomal beta-lactamase but acted as inhibitors of the enzyme. Nevertheless, increased beta-lactamase production mediated an increased resistance toward these drugs. No plasmids were found in the isolates, suggesting a chromosomal location for the respective ampC locus.
An ultrasctructural study of amniotic epithelium and fetal periderm was undertaken in order to investigate the exfoliative capacity in these tissue surfaces in early human pregnancy. Contrary to earlier reports, no exfoliation could be detected from amniotic epithelium, while a heavy detachment of cells and cell fragments was observed from fetal skin. The importance of meticulous tissue preparation is obvious; detachment phenomena are easily produced artifactually by tissue scrapings and improper tissue preparation for morphological investigations.
In the present epidemiologic study, 53 workers with a long-term (more than five years) exposure to the electric field of 400 kV substations were examined and compared with a matched reference group of 53 nonexposed workers from the same power companies. Matching variables included age, geographic location and employment time. The aim of the study was to investigate the possibility of persistent, chronic health effects in the exposed group as a consequence of exposure. The investigation indluded the nervous system (neurasthenic symptoms, psychological tests, electroencephalography), the cardiovascular system (symptoms, blood pressure, electrocardiography), and the blood (hemoglobin, red blood cells, reticulocytes, white blood cells including differential count, thrombocytes, sedimentation rate). Fertility was also assessed. The results showed no differences between the exposed and reference groups as a consequence of the long-term exposure to the electric fields. The groups differed, however, in that the exposed group had (a) consistently better results on the psychological performance tests, (b) a fewer number of children, especially boys, and (c) somewhat higher education. The differences in test results were due to the higher education among the exposed. The difference in number of children was also thought to be related to factors other than exposure since it was found to be present already 10--15 years before the work in 400 kV substations began.
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Two beta-lactamase-producing strains of Neisseria gonorrhoeae were studied. The substrate profile, molecular weight, and isoelectric point of their beta-lactamases were similar to those of the TEM-1 enzyme produced by many gram-negative bacilli. The gonococcal beta-lactamase was cell bound during exponential growth and was most likely located in the periplasm. Penicillin hydrolysis was efficient in intact cells, suggesting that the cell-bound beta-lactamase was freely accessible to benzylpenicillin. Both beta-lactamase-producing strains of N. gonorrhoeae contained an additional multicopy plasmid with a mass of 3.3 megadaltons (Mdal). A spontaneous penicillin-susceptible revertant lacked both beta-lactamase activity and the 3.3-Mdal plasmid, providing evidence for plasmid-mediated penicillin resistance. During a shift from GC medium to rich MOPS medium, growth of the penicillin-susceptible revertant in contrast to that of the plasmid-carrying strain was markedly impaired, suggesting a physiological effect due to the presence of the 3.3-Mdal plasmid.
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