Biological perspectives in chronic pain, depression, and organic mental disorders.
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Biomedical subjects
Publications and source records attributed to M F Murphy.
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We report a case of meningitis and perceptive deafness caused by Streptococcus suis type II (Group R beta-haemolytic streptococcus). The illness is known to be an occupational hazard of pigmeat handlers and our patient worked in a pet food factory processing pig meat. His hearing loss was very severe and showed no improvement despite adequate antibiotic treatment. The organism that was isolated is the first to show penicillin resistance. The implications of this for antibiotic treatment are discussed.
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Streptomyces antibioticus possesses a tryptophan-inhibitable 3-deoxy-D-arabino-heptulosonic acid 7-phosphate (DAHP) synthetase whose synthesis is also repressed by L-tryptophan. Studies of the DAHP synthetase obtained by ammonium sulfate fractionation of a crude extract derived from S. Antibioticus revealed that the enzymic activity was only partially inhibited by tryptophan. Inhibition of the DAHP synthetase activity was strongly pH dependent at values below 7.0. A number of tryptophan analogues was noted to inhibit the enzyme; by contrast, other aromatic amino acid end products failed to affect DAHP synthetase activity. Chorismic acid, a key intermediate in aromatic amino acid biosynthesis, was ineffective as an inhibitor when used alone; however, if supplied with L-tryptophan, a further reduction of DAHP synthetase activity (15--25%) was routinely observed.
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The multiplication in tissue cultures of three isolates of subacute sclerosing panencephalitis virus as well as the Edmonston strain of measles virus was observed to be inhibited by various concentrations of the antiviral agent ribavirin (1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide). The blockage of viral replication by ribavirin could be reversed by the simultaneous addition of equimolar concentrations of either guanosine or adenosine. Expression of virus-specific antigens was greatly reduced in the presence of the antiviral drug.
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This study evaluated Cobe Trima for donor and operational acceptability, the quality and storage stability of the blood components collected, and the clinical responses to transfusion. The study was carried out in 2 phases; phase 1 assessed the efficiency of red cells and platelet collection, and the characteristics of the components collected before and after storage. Phase 2 was an evaluation of operational issues and the in vitro characteristics of the red cells and platelet concentrates at the time of transfusion in respect to their cellular content, and leucocyte (interleukin IL-6 and IL-8) and platelet-derived (Rantes) cytokine levels. Cytokine levels were also measured in the donors before and after the collection procedure and in patients both before and after transfusion. The clinical responses to a small number of transfusions were assessed. The Cobe Trima was found to be straightforward to use by the operators, although additional operator training was required to manage occasional uncertainty with alarm messages. It was acceptable to the donors except for the occurrence of citrate reactions in 3/6 donors in phase 1; this problem persisted in phase 2 (6/15 donors), and needs to be addressed in the future. All blood components met UK product specifications apart from 2 platelet concentrates, 2 red cell concentrates, and one unit of FFP; the red cell and platelet concentrates had good storage characteristics. The 2 procedures, which resulted in low platelet yields, were due to occlusion of the plasma line; the method for installation of the harness has been subsequently modified to prevent this. 2 red cell concentrates showed haemolysis; the reason for this was not established. The Factor VIII level was satisfactory in plasma and the cellular content was low. The responses to 12 platelet transfusions were expected as in a group of haematology patients, and no immediate adverse effects were reported with any of the transfusions. Leucocyte-associated (IL-8 and IL-6) and platelet-associated (Rantes) cytokine levels were not elevated in donor samples taken before or after the collection procedure, or in the red cell and platelet concentrates at the time of issue. Pre- and post-transfusion IL-8 levels were raised in one patient with non-immune platelet refractoriness, and normal in 2 patients with excellent or almost satisfactory responses to platelet transfusions raising the question as whether IL-8 could be used as a laboratory marker for non-immune platelet refractoriness due to infection.
This study examined the hormonal differences between premenopausal mothers of twins and other premenopausal parous women during and after pregnancy. Serum concentrations of oestradiol and testosterone between 6 and 20 weeks of gestation were measured for 11 mothers of twins and 115 mothers of singletons selected from the controls in a case-control study of cryptorchidism. Serum concentrations of oestradiol, progesterone, testosterone, follicle stimulating hormone and sex hormone-binding globulin during the menstrual cycle were measured for 25 mothers of twins and 38 mothers of singletons recruited as a part of a prospective study of breast cancer risk. During pregnancy, women carrying twins had a 58% higher geometric mean oestradiol concentration (p = 0.02) and a 50% higher testosterone concentration (p = 0.03) than women carrying singletons. Women who had previously had twins demonstrated a 49% higher mean concentration of follicle stimulating hormone (p = 0.02) and a 42% higher concentration of sex hormone-binding globulin (p = 0.03) than women who had singletons only, but no significant differences in oestradiol, progesterone and testosterone concentrations. The increased concentrations of follicle stimulating hormone during the menstrual cycle of mothers of twins, which has also been reported in two previous studies suggests that follicle stimulating hormone level may be an important determinant of dizygotic twinning.
Dosage and tolerance are critical issues in successful drug therapy for patients with Alzheimer's disease (AD). A clear distinction among patient populations and AD patient subpopulations is necessary to ensure a thorough assessment of new central nervous system-active compounds. Phase I inpatient trials, in which tolerance and safety are evaluated under double-blind conditions in the target population, provide valuable information for use in planning multicenter outpatient trials. In similar studies, even those involving the elderly, tolerance and safety outcomes in healthy volunteers are not always predictable. An early trial of the effects of velnacrine in healthy, elderly, male volunteers was followed by a trial in the target population. A group of volunteers, aged 60 to 74 years who did not have AD, received 300 mg of velnacrine each day. This dosage was well tolerated for 28 days. Diarrhea, generally of moderate severity, was the only reported adverse effect. No subjects were required to discontinue taking velnacrine. In contrast, a similar trial showed a dosage of 300 mg of velnacrine each day intolerable among patients with AD. Adverse reactions to dosages greater than 225 mg/day included dizziness, fainting, nausea and/or vomiting, headache, and severe diarrhea. A velnacrine dosage of 225 mg/day appeared to be safe and well tolerated in a small population of healthy patients with AD. Based on the inpatient experience with AD subjects, a maximum dose of 225 mg/day was adopted for outpatient studies. Although factors that may contribute to drug sensitivity in patients with AD vary beyond conclusive parameters, the observed sensitivity within the target AD group may indicate a safety/tolerance study as a worthwhile antecedent to multicenter efficacy trials.
Because only those patients receiving treatment are included in a study, it is difficult to determine the true incidence of infection in human bite wounds. Many undoubtedly never receive treatment since patients normally are reluctant to appear in the emergency department as a result of embarrasing circumstances. However, it is known that infection rates and resulting morbidity can be substantially reduced if the bite wound victim comes to the emergency department promptly after wounding. In addition, a meticulous wound care regimen should be standard for all human bite wounds, rather than relying solely on antibiotics, which is a common practice.