Biomedical subjects
Publications and source records attributed to J Saunders.
The synergistic cytotoxicity of iodinated radiologic contrast agents and x-radiation is discussed. Experiments are described illustrating the phenomenon and lending support to the view that it is mediated by energetic photoelectrons. Some of its practical implications are indicated.
Isolates of Streptococcus pneumoniae, Enterococcus faecalis, Enterococcus faecium, and coagulase-positive and -negative staphylococci were investigated for their abilities, in vitro, to develop resistance to LY146032. Exposure of the organisms to incremental concentrations of LY146032 resulted in MICs 8- to 32-fold higher than those for the original isolates. After three passages on antibiotic-free medium, the high MICs were maintained for the coagulase-negative staphylococci and pneumococci, with a twofold decrease observed for the enterococci and a fourfold decrease observed for Staphylococcus aureus. The frequency of spontaneous emergence of resistance was highest with S. pneumoniae (1.2 X 10(-6) at 16 times the original MIC) and lowest with S. aureus (7.0 X 10(-10) at 8 times the original MIC). For bacteria For bacteria surviving time-kill studies MICs were also higher than were those for the original isolates. Exposure to LY146032 in vitro selected for strains with decreased susceptibilities to the antimicrobial agent. However, the emergence of resistance in vivo is unpredictable and can be evaluated only after prolonged clinical use of the drug.
An assay for the steroid hormone progesterone is described based on the inhibition of the agglutination by progesterone-bovine serum albumin conjugate of red cells coupled with monoclonal antiprogesterone antibody (reverse passive haemagglutination). A low-affinity agglutination system produced the optimal sensitivity, capable of detecting less than 1 ng/ml steroid. This assay has the simplicity and sensitivity for a potential clinical test for placental or corpus luteum function. It also serves as a model for detection of other small ligands (drugs, hormones) by inhibition of reverse passive haemagglutination.
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Despite the advent of sophisticated diagnostic technology the diagnosis of the surgical abdomen in the Intensive Care Unit continues to pose a problem for the surgeon. A retrospective analysis was carried out to evaluate the utility of diagnostic peritoneal lavage to diagnose intra-abdominal surgical disease. Diagnostic peritoneal lavage was carried out in patients in whom the physical exam was deemed unreliable, such as in patients with cardiopulmonary instability or mental obtundation. Patients were included in the study if autopsy or laparotomy confirmation of the lavage data was available. Forty four patients met the inclusion criteria and formed the basis of this study. Of the twenty three patients with a positive lavage, three false-positive diagnostic peritoneal lavages were discovered, either at laparotomy or postmortem exam. Of the twenty one patients where diagnostic peritoneal lavage was negative, no false-negatives were discovered at autopsy or laparatomy. Therefore, this test is 100 per cent sensitive and 88 per cent specific. It is concluded that a negative diagnostic peritoneal lavage makes intra-abdominal surgical disease highly unlikely. However, a positive lavage may require further diagnostic work-up.
An in vitro comparison of the activities of 13 oral antimicrobial agents against clinical isolates of bacteria commonly responsible for causing upper respiratory tract infections was performed. With regard to Haemophilus influenzae, beta-lactamase-negative strains were susceptible to amoxycillin, augmentin, cefaclor, erythromycin, trimethoprim, cotrimoxazole and tetracycline, with CL 284,635 being the most active agent. With the exception of amoxycillin these drugs were also active against beta-lactamase-producing strains. CL 284,635 was also very active against Branhamella catarrhalis isolates, including beta-lactamase-producing strains, but was less active against the Gram-positive bacteria tested. Cefadroxil, cephradine and cephalexin were mainly active against Gram-positive pathogens. Based on minimum inhibitory concentration determinations, cefaclor, augmentin and co-trimoxazole would be appropriate drugs for the treatment of those cases of otitis media and sinusitis where H. influenzae and Streptococcus pneumoniae are important pathogens provided they are susceptible to these agents.
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The four separated isomers of the muscarinic agonist 1, previously known as AF30, have been synthesized by a route that has allowed the absolute stereochemistry of each isomer to be assigned. With the chirality of (-)-camphanic acid known, X-ray analysis of the more crystalline intermediate diastereomeric camphanate 5A allowed the absolute stereochemistry at the quinuclidine chiral center to be determined. Each diastereomer was separately transformed into the spirodioxolane with concomitant introduction of the second chiral center. Chromatographic separation followed by a second crystal structure determination revealed the absolute stereochemistry of all four isomers of 1. Detailed biological evaluation of each isomer indicated that while the 3(R),2'(S) isomer was the most active in binding studies, it was the 3(R),2'(R) isomer that displayed the largest functional selectivity between ganglion (M-1 site) and heart (M-2 site). With the same internal chiral standard, the absolute configuration of the more active enantiomer of 3 was shown to be S, confirming earlier literature reports.
A diagnosis of Epstein's syndrome was made in a young female with congenital macrothrombopathic thrombocytopenia, a nephropathy and mild sensorineural deafness. Previous case reports of this rare disorder are briefly reviewed and attention is drawn to the frequent association between inherited thrombocytopenia and renal disease.
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The in vitro activities of two new carboxyquinolones, A-56619 (difloxacin) and A-56620, were compared with those of ciprofloxacin, norfloxacin, and ofloxacin against genital tract pathogens. All the quinolones were highly active against Neisseria gonorrhoeae. A-56619 had the lowest MICs against Chlamydia trachomatis (MIC range, 0.125 to 0.25 micrograms/ml) and Haemophilus ducreyi (MIC for 90% of isolates tested, 0.1 micrograms/ml).
The effect of chronic oral administration of cimetidine (1 g per day) and ranitidine (300 mg per day) on plasma levels of prolactin (PRL), testosterone, dihydrotestosterone (DHT), luteinizing hormone (LH), follicle stimulating hormone (FSH), sex hormone binding globulin (SHBG) and human growth hormone was compared in 2 groups of male patients who presented with dyspeptic symptoms. Eight were treated with ranitidine and 9 with cimetidine for 4 weeks. The glucose and insulin response to a 100 g oral glucose load was also assessed. Cimetidine treatment resulted in a significant increase in plasma testosterone levels which was not found in the ranitidine group. No significant change occurred in PRL, LH, FSH, SHBG, DHT and growth hormone. There was no evidence of a significant alteration in carbohydrate metabolism.
Food was withheld from female rats for 0-72 h at various stages of the oestrous cycle. Withholding food for periods of 24 h ending at 12:00 h on the day of pro-oestrus reduced the mating rate from 61 to 25% (P less than 0.05) but not the pregnancy rate of those rats that mated. Fasting for 24 h ending at 18:00 h on the day of pro-oestrus reduced the pregnancy rate from 82 to 18% (P less than 0.05) without affecting the mating rate and a 48-h fast starting at 12:00 h on the day of pro-oestrus reduced the pregnancy rate from 82 to 25% (P less than 0.05). Withholding food for 23 h ending at 17:00 h on the day of pro-oestrus prevented the LH and prolactin surges normally present at 17:00 h on this day. The treatments had no apparent effect on the ability of the adenohypophysis to release LH in response to injections of GnRH. When ovariectomized female rats fasted for 0-72 h and given 2 injections of oestradiol dibenzoate to test the ability of the hypothalamus to respond to an increasing plasma oestradiol concentration by stimulating the release of LH, a fast for 24 h reduced and a fast for 72 h completely prevented LH release.
The results of this study demonstrate that passive transfer of immune serum containing high titres of treponemal antibody into normal guinea-pigs significantly lowered the percentage of animals developing chancre-like lesions, but did not prevent the dissemination of organisms into the draining lymph nodes after these recipients were challenged with virulent treponemes. Similar levels of partial protection against cutaneous syphilitic infection occurred in guinea-pigs receiving partially purified anti-treponemal immunoglobulins, while immune serum depleted of IgG by treatment with Protein A was totally unprotective. Western blotting analysis revealed the presence of several Treponema pallidum polypeptides detectable by immune guinea-pig IgG. These findings provide direct evidence to suggest that syphilitic infection induces the formation of serum factors, residing primarily in the IgG fraction of immune serum, that are capable of providing a limited form of resistance to symptomatic disease.