Immunology of infective endocarditis.
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Biomedical subjects
Publications and source records attributed to J Clarke.
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Interferon-alpha (IFN-alpha), a cytokine acting as an endogenous pyrogen and a putative activator of the opioid system, binds to opiate receptors in vitro. The mu opioid receptor antagonist, naloxone hydrochloride (NLX), attenuates IFN-alpha-induced increases in the firing rate of cold-sensitive neurons within thermosensitive areas of the brain. The influence of NLX on fevers induced by central endogenous pyrogens was investigated in rats. Subcutaneous (SQ) injection of NLX (1 mg/kg) was made 30 min prior to intracerebroventricular (ICV) injection of IFN-alpha 2b (7900IU). Alternatively, NLX (10 or 80 micrograms) was microinjected ICV 30 min prior to administration of IFN-alpha 2b. Administered SQ, NLX attenuated the febrile response to IFN-alpha 2b. In contrast, central (ICV) NLX did not attenuate fevers induced by IFN-alpha 2b. Animals previously exposed to both IFN-alpha 2b and NLX (SQ or ICV) subsequently lost their sensitivity to this cytokine, and also showed diminished reactivity to human recombinant interleukin-1 beta (hrIL-1 beta; 10 ng) and prostaglandin E2 (PGE2; 250 ng). These results suggest that systemic and central elements of the opioid system may play differential roles in temperature regulation. Previous administration of NLX and IFN-alpha 2b may alter the sensitivity of the CNS to subsequent injections of different pyrogens.
Matrix metalloproteases are known to play an important role in tumor invasion by mediating degradation of extracellular matrix. In this study, we have investigated the expression of the matrix metalloprotease pump-1 gene (also referred to as MMP-7, Matrilysin) in 44 ovarian tumors (12 low malignant potential tumors, 32 carcinomas) and 10 normal ovaries using quantitative PCR. The PCR product was labelled with 32P and a phosphoimager was used to determine the relative expression of pump-1 compared to an internal control beta-tubulin. mRNA expression levels of pump-1 were significantly elevated in 9 of 12 low malignant potential tumors and 26 of 32 carcinomas. Northern blot hybridization showed that the 1. 1-kb pump-1 transcript was abundant in carcinoma but seldom expressed in normal adult tissues including normal ovary. Immunohistochemical localization of the pump-1 protein confirms its expression by ovarian tumor cells. Our results suggest that pump-1 is frequently overexpressed in ovarian tumors and may contribute to its invasive nature or growth capacity, therefore pump-1 may serve as a useful marker for early detection of disease and/or a target for therapeutic intervention in downregulation of tumor progression.
PURPOSE: A computerized decision analysis, based on the results of published clinical trials, assessed the risks, benefits, and costs of different thrombolytic regimens for suspected myocardial infarction (MI) throughout the likely range of clinical circumstances. DATA SOURCE: Medline search and articles' bibliographies. STUDY SELECTION: All studies reporting efficacy and side effects of thrombolysis. DATA ANALYSIS: Life-expectancy outcomes of thrombolytic therapies for possible MI modeled by decision analysis. RESULTS: The analysis allows a clinician to estimate the benefits, risks, and relative costs of thrombolytic therapies throughout the likely range of individual clinical circumstances. When applied, for example, to the average patient in ISIS-2, estimated gains are 150 quality-adjusted days of life (QALDs) from treatment with streptokinase (SK) and 255 QALDs with "accelerated" tPA (tPA). tPA costs $1,686 more than SK, taking into account the cost of lifelong care of the extra strokes incurred. Nevertheless, the chances of stroke above which thrombolysis is not preferred are 5.0% for SK and 8.0% for tPA, with tPA remaining the preferred treatment for six hours after symptom onset; thereafter, SK is marginally preferred, but at much lower cost. Both regimens are beneficial in older patients provided the chances of MI and death are "average" or greater. CONCLUSION: When the chances of MI and death are known, decision analysis can be a useful bedside tool to guide thrombolytic therapy and subsequently, if needed, to review and defend the treatment decisions made.
Respiratory tract papillomas are associated with human papillomavirus (HPV) types 6 and 11; these HPV types are also commonly associated with genital warts (condyloma acuminata). Although most commonly seen in young children, the incidence of respiratory tract papillomas in young adults is increasing. It has been postulated that orogenital contact is the means of transmission in this age group. We performed a survey of adults with genital warts to assess the prevalence of respiratory tract papillomatosis in relation to sexual behaviour and other factors. Fifty-three adult patients (35 male, 18 female) with genital warts attending a genitourinary medicine clinic agreed to examination of the mouth and throat, including indirect laryngoscopy. Seventy per cent of the group had participated in oral sex. Two patients (3.8%) had lesions attributable to HPV infection of the oropharynx and larynx (one with laryngeal keratosis, one with papilloma of the pharynx). There was no specific risk factor identified to predict respiratory tract disease. In view of the high infectivity of genital warts, it is interesting to note the low prevalence of oropharyngeal warts in adults indulging in orogenital contact. Since malignant transformation is known in respiratory tract papillomas, we would recommend that any patient with genital warts who develops unexplained hoarseness has a specialist examination of the upper respiratory tract.
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An audit of contact tracing activity for a range of common sexually transmitted diseases (STD) was performed prospectively on 100 consecutive referrals to the health advisers at the Genitourinary Medicine (GUM) clinic in Wakefield. Targets for contact attendance were set according to the initial index patient diagnosis. Health adviser contact tracing methods (telephone, letter, visit) were logged. A total of 119 contacts were identified; of these, 86 (73%) were seen and examined. Attendance within the target time of one working week was not achieved in gonorrhoea contacts, but 61% warts contacts attended within the target of 4 weeks. Tracing by patient-carried contact slips after interview with the health adviser was effective in the majority (68%) of notifications.
15,661 cord bloods from Jamaican infants were examined for abnormal hemoglobins using alkaline cellulose acetate electrophoresis for the initial screening, supplemented by acid agar gel electrophoresis for samples exhibiting abnormal hemoglobin bands. Of the 16 electrophoretic variants which were detected, six were fully characterized and found to be: four Hb F Port Royal (alpha2 Ggamma2 125 Glu replaced by Ala) and two Hb F Victoria Jubilee (alpha2Agamma2 80 Asp replaced by Tyr). The Hb F Port Royal samples each constituted about one eighth of the total Hb F as did seven additional samples presumed to be Hb F Port Royal. The infants with this variant exhibited no special hematological characteristics or other consistent associations. Both Hb F Victoria Jubilee samples occurred in somewhat lower proportions of the total Hb F compared with Hb F Port Royal and exhibited an apparent increase of free alpha chains in the whole hemolysate. The data available on detectable gamma chain variants suggest that a specific point mutation may occur in either a HbGgamma or a HbAgamma locus.
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As care moves away from hospital settings, continual re-evaluation of community nursing and health care is essential for the wellbeing of patients. With the approach of the year 2000, Jean Clarke examines World Health Organization objectives, particularly in light of the Health for All (1998) policy.
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Intestinal bypass surgery as a treatment for morbid obesity was quite popular from 1965 to 1975 in the United States. The procedure was successful in reducing body weight but was controversial because of a high rate of complications which included an arthritis-dermatitis syndrome. Herein we review the knowledge garnered from a study of the complications from intestinal bypass surgery. Emphasis is placed on an analysis of the clinical manifestations, and the pathogenesis of the arthritis-dermatitis bypass syndrome, and how bypass disease may serve as a model for immune complex-mediated disease and for extra-intestinal complications in other enteropathies.
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