Plague--perspectives on a rare disease.
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Biomedical subjects
Publications and source records attributed to J Mann.
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The introduction of an open access general practitioner endoscopy service may result in many unnecessary examinations being performed. In an attempt to prevent this, 235 patients attending for endoscopy were interviewed and the results analysed to determine which factors best discriminated between those with major disease (ulcers, cancers, oesophageal strictures; n = 48) and those without (n = 187). The six characteristics which best discriminated between the two groups were increasing age, history of vomiting, male sex, smoking, and a past history of peptic ulcer or hiatus hernia. With the use of these six features a scoring system was devised, designed to give an indication of the likelihood of finding such disease in an individual patient. This was assessed prospectively in a further 356 patients. The results showed that by utilising this scoring system it would be possible to reduce the number of examinations performed by 30% yet still detect 98% of serious disease. If confirmed in further prospective studies, this scoring system (or a modification) could more accurately assess individual priority for endoscopy and enable optimum use to be made of limited resources.
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Challenge of rat peritoneal mast cells with anti-rat IgE induces a similar pattern of protein phosphorylation to that already reported for compound 48/80. Rapid phosphorylation of a mast cell protein, mol. wt 78,000, is induced by sodium cromoglycate and several chemically related anti-allergic agents in the absence of any challenge. Phosphorylation of this protein reflects their potency in inhibiting anti-IgE-induced histamine release. Compounds which inhibit histamine release by elevating intracellular cAMP levels do not induce phosphorylation. However, dibutyryl-cGMP induces phosphorylation of the 78,000 mol. wt protein in the absence of any challenge, at concns which inhibit IgE-dependent histamine release. Sodium cromoglycate appears to activate an endogenous control mechanism for switching off mediator release using a mechanism mediated by cGMP.
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The synergism between endogenous regulators of proliferation (protors), alkylating agents and hormones in vitro was studied. The effects were monitored by the incorporation of 3H-TdR into human and rat short term bone marrow cultures and by the formation of mouse granulocyte-macrophage colonies in semisolid agar capillaries. An additive and/or slight potentiating synergism was demonstrated between different types of inhibitory protors (GI-3S2, GI-3S3 and GI-3B), between GI-3 and hydrocortisone, and between GI-3 and the alkylating agents (adriamycin, dianhydrogalactitol) examined. The results offer a real possibility of strengthening the inhibition of neoplastic proliferation without increasing cytotoxicity of the drugs used.
Sexual function and the effects thereon of testosterone enanthate were studied in six hypogonadal men with the objective of delineating the specific components of male sexuality affected by androgen. To obtain a detailed picture of these components, prospective self-report data (from daily logs) of sexual activity and feelings, recordings of all night penile tumescence, and laboratory psychophysiological data were assessed. Double blind placebo experiments with cross-over design were used to compare the effects of placebo and 200- and 400-mg doses of testosterone enanthate. Erectile responses to erotic film and fantasy were not lower in the hypogonadal patients than in normal men and, in fact, were higher on some parameters, especially prolongation of detumescence time after exposure to film or fantasy. Three subjects who kept consistent daily logs had increased frequencies of sexual acts and feelings, orgasms, and spontaneous erections after testosterone administration. Nocturnal penile tumescence and spontaneous daytime erections were reduced in untreated hypogonadal men and were significantly increased after testosterone treatment, but the laboratory-tested erectile responses to film and fantasy were not affected by testosterone. These data and previous findings lead to the conclusion that the major androgen action on male sexuality involves libido factors (i.e. sexual motivation/interest). Though stimulus-bound erections elicited in the laboratory were not reduced in hypogonadal men, spontaneous (sleep or waking) erections were clearly testosterone dependent.
GI-3, an endogenous inhibitory fraction isolated from leukocytes, selectively inhibits the proliferation of granuloid precursor cells in a non-toxic manner. Its active principle was determined as an acidic chlor-tolidine positive decapeptide [ 3 ]. The in vitro effect on normal and acute leukaemic human bone marrow and blood cells was examined. A dose dependent inhibition by GI-3 of 3H-TdR incorporation into myeloid cells of normal bone marrow was found, the sensitivity of human cells being higher than that of rat cells. The proliferation of the target leukaemic bone marrow and blood cells (AML, AMMoL) was also decreased by the endogenous inhibitor in a dose dependent manner in untreated subjects as well as in patients in remission or relapse. The rate of inhibition of leukaemic of well-known cytostatics (adriamycin hydrochloride, dianhydrogalactitol) applied for comparison. Beyond its direct cytostatic effect, GI-3 could be used in the differential diagnosis of blastic leukaemias, complementing the routine cytochemical methods.
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In acutely uremic animals, the contractile force of the heart is consistently increased; such an increase can be dissociated from changes of afterload or catecholaminergic drive. It is associated with diminished sarcolemmal Na,K-ATPase activity in the heart which, in turn, may be related to increased levels of endogenous digitalis-like substances (endigens) that have been postulated to represent a natriuretic factor. In patients with chronic uremia, myocardial contractility is usually normal, but occasionally there may be heart failure unrelated to pre-existing hypertension, coronary heart disease, anemia, fluid overload, or other recognizable factors. So far, the experimental basis for this clinical observation is uncertain. Possible causes for the clinical syndrome include an excess of parathyroid hormone or cardiodepressor substances. There is experimental evidence of impaired cardiac response to beta adrenergic agonists, e.g., decreased isoproterenol-dependent calcium uptake, diminished inotropic and chronotropic responses. In acutely uremic rats, cardiac cyclic AMP levels are high but can be reversed by beta blockers. Heart calcium content is variable and heart weight is constantly increased in acutely uremic rats, despite decreased skeletal muscle mass. The change in heart weight is not related to anemia, to an excess of parathyroid hormone, or to sympathetic activity; its cause remains unknown. Experimental studies to date have shown a variety of abnormalities, but do not provide a uniform concept of the mechanisms or an explanation for the cardiac dysfunction so often observed in patients with uremia.
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Elderly depressed patients who met the research diagnostic criteria (RDC) for major depressive illness, resistant to other types of treatment, were treated with phenelzine, a nonselective monoamine oxidase (MAO) inhibitor, for a period of 2 to 7 weeks, following 2 weeks of placebo washout period. Dosage ranged from 15-75 mg daily. Clinical status of patients as well as vital signs, EKG, and platelet MAO inhibition were measured weekly. All responders at the end of this period were followed for 1 to 2 years. Analysis of the results showed a 65% response rate as measured by Hamilton, Global, and Self-rating Scales. No significant drug effect in cognitive functioning, as measured by objective cognitive tests, was observed. Clinical improvement was sustained for all participants throughout the follow-up period with no side effects. A direct relationship between platelet MAO inhibition and clinical response was found. The majority of the responders (70%) had achieved high platelet MAO inhibition values (greater than 80%), while most of the nonresponders had platelet MAO inhibition values of less than 80%. These findings have potential clinical and research implications for treating geriatric depression, especially the ones resistant to other forms of treatment.
A series of 8009 genetic amniocenteses were retrospectively examined to evaluate the relationship of the procedure to Rh isoimmunization. Of the 615 Rh negative women giving birth to Rh positive infants and estimated to be at risk, thirteen (2.1 per cent) were sensitized subsequently to the amniocentesis. Eleven of the sensitizations occurred early in the programs, and a combination of experience and ultrasound performed concurrently with the amniocentesis appear to have reduced the risk of isoimmunization to that of control data from the literature.