Primary regimens in immunosuppression.
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Biomedical subjects
Publications and source records attributed to R W Johnson.
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Pain is the most common complication of herpes zoster, but much confusion and dissent exist regarding terminology. Established (chronic) herpetic pain is remarkably resistant to treatment, but its prevention is partly achievable. Prodromal and acute herpetic pain are predictors for chronic pain. If research programs and clinical management are to progress optimally, researchers and clinicians must agree on appropriate use of such terms as "zoster-associated pain" and "postherpetic neuralgia."
Axial magnetic resonance (MR) images of non-neoplastic spinal cord cavities were reviewed in 115 patients with otherwise complete neurological and neuroradiological findings. The variations in axial morphology revealed three distinct cavitary patterns. These patterns were as follows: 1) symmetrically enlarged central cavities (28 patients); 2) central cavities that expanded paracentrally in one or more focal areas (36 patients); and 3) eccentric cavities that were off-center, frequently irregular, and sometimes associated with myelomalacia (51 patients). The radiological patterns of spinal cord cavitation correlated well with recently reported histopathological findings that distinguish simple dilations of the central canal, dilations of the central canal that dissect paracentrally, and primary cavitations of the spinal cord parenchyma (extracanalicular syringes). Like histologically confirmed central canal syringes, MR-defined central cavities were associated with pathogenic factors that affect the dynamics of the cerebrospinal fluid, including hindbrain malformations, hydrocephalus, and extramedullary obstructive lesions. Eccentric cavities resembled extracanalicular syringes and occurred typically with disorders that damage spinal cord tissue (e.g., trauma, infarction, meningitis/arachnoiditis, spondylosis/disc herniation, radiation necrosis, and transverse myelitis). Analysis of clinical findings at the time of MR imaging established the following correlations. 1) Symmetrically enlarged central cavities were asymptomatic or produced nonspecific neurological signs. 2) Central cavities that expanded paracentrally were associated with segmental signs referable to the paracentral component. 3) Eccentric cavities produced various combinations of long tract and segmental signs that could usually be related to the level, side, and specific quadrant of spinal cord cavitation.(ABSTRACT TRUNCATED AT 250 WORDS)
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BACKGROUND: Acyclovir given for 7 to 10 days is of proved benefit in acute herpes zoster, but studies of its effectiveness in preventing postherpetic neuralgia have had conflicting results. The role of corticosteroids in the treatment of herpes zoster is also controversial. METHODS: We conducted a double-blind, controlled trial in patients with acute herpes zoster to determine whether either 21 days of acyclovir therapy or the addition of prednisolone offered any improvement over 7 days of acyclovir therapy. Patients with a rash of less than 72 hours' duration were assigned to receive acyclovir (800 mg orally, five times daily) for 7 days with either prednisolone or placebo, or acyclovir for 21 days with either prednisolone or placebo. Prednisolone therapy was initiated at a dose of 40 mg per day and tapered over a three-week period. Patients were assessed frequently through day 28 and then monthly through month 6 to assess postherpetic neuralgia. RESULTS: Of 400 patients recruited, 349 completed the study. No significant differences were detected between the four groups in the progression of the rash (P > 0.1). With steroid therapy, a significantly higher proportion of the rash area had healed on days 7 and 14 (P = 0.02). Pain reduction was greater during the acute phase of disease in patients treated with steroids or 21 days of acyclovir (P < 0.01 and P = 0.02, respectively, on day 7; P < 0.01 for steroid therapy on day 14). However, on follow-up there were no significant differences between any of the groups in the time to a first or a complete cessation of pain. The steroid recipients reported more adverse events. CONCLUSIONS: In acute herpes zoster, treatment with acyclovir for 21 days or the addition of prednisolone to acyclovir therapy confers only slight benefits over standard 7-day treatment with acyclovir. Neither additional treatment reduces the frequency of postherpetic neuralgia.
Not so long ago, it was believed that the brain is totally devoid of immunologic reactions, that cytokines derived from activated leukocytes serve only as communication molecules between leukocytes and that the immune system is regulated solely by intrinsic mechanisms. One by one, these old-time, traditional views have fallen by the wayside as neuroscientists, endocrinologists and pharmacologists have begun to explore immunology. The old view was that the immune system is autonomous because it neither affects nor is it affected by other physiologic systems. The new view is that cells of the immune system are inextricably linked with other physiological systems, including the neuroendocrine, cardiovascular, reproductive and central nervous systems (CNS). Changes in one system evoke changes in the other, and it is likely that communication loops have evolved between cells of the immune system and those of other tissues to coordinate and regulate functional activities aimed at preserving homeostasis during inflammation. The integrated view of immunophysiologists that cells of the immune system interact with the entire body, rather than existing as a separate physiologic system that operates autonomously, should help to unravel a number of mysteries in immunoregulation, such as the well-recognized redundant and pleiotropic properties of cytokines. Unfortunately, very few of these ideas have been incorporated into studying immunity of domestic animals. A complete understanding of immunobiology will be achieved only after this new field of immunophysiology is integrated into current immunological thinking.(ABSTRACT TRUNCATED AT 250 WORDS)
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The graft and patient survivals following renal transplantation in all Type 1 diabetic patients transplanted within the North-West of England between 1981 and 1990 at Manchester Royal Infirmary were studied. Fifty-two Type 1 (insulin-dependent) diabetic patients with end-stage renal failure due to diabetic nephropathy were transplanted during this period. They were compared to controls matched for age, sex, and year of transplantation and also to all 904 patients transplanted during the same period. Graft survival rates at 1 and 5 years in the diabetic patients were lower (80.8% and 62.1%, respectively), compared to controls (88.9% and 77.9%, respectively, p = 0.02) but were similar to those seen in all grafts (80.4% and 59.0%, respectively, p = NS). Actuarial patient survival rate at 5 years was lower in diabetic patients (76.3%) compared to the control group (94.2%, p = 0.003). Myocardial infarction was the main cause (60%) of death in diabetic patients. The results of this large recent series indicate that good graft and patient survival rates can be obtained in Type 1 diabetic patients, although they remain poorer than those of patients with non-diabetic renal disease. More rigorous pretransplantation cardiac assessment and treatment before acceptance of Type 1 diabetic patients for renal transplantation may help to improve patient survival.
Corticotropin-releasing hormone (CRH) has been implicated as an important mediator of behavior, immune, and neuroendocrine systems in animals experiencing stress, but its effects on these systems have not been evaluated in an integrated whole animal model. In this experiment we injected porcine and rat CRH (pCRH and rCRH) intracerebroventricularly (icv) and simultaneously and chronologically monitored acute changes in behavior, endocrine, and immune function in the pig. PBS or CRH (15, 50, and 150 micrograms pCRH and 15 and 150 micrograms rCRH) was injected icv, and serial blood samples were collected via an indwelling jugular catheter so that behavior could be monitored simultaneously. The central administration of pCRH and rCRH induced immediate dose-dependent behavioral and physiological responses. Pigs receiving 15 micrograms of either pCRH or rCRH had increased plasma ACTH and were hyperactive and vocal. However, when higher doses (i.e. 50 or 150 micrograms) were administered icv, the endocrine and behavioral responses were accompanied by a profound suppression of Concanavalin-A-induced lymphocyte proliferation. For example, pigs receiving 150 micrograms pCRH had increased plasma ACTH and motor activity at 10 min (P < 0.01) and suppressed lymphocyte proliferation at 30 min (P < 0.001). Whereas ACTH secretion declined after 40 min, the lymphocyte suppression and increased motor activity were sustained, suggesting different control mechanisms. It is suggested that although ACTH and cortisol may have negative feedback effects on ACTH secretion, they did not have these effects on the behavioral action of CRH. Furthermore, although the lowest dose of CRH (15 micrograms) induced motor activity and ACTH secretion, higher doses (50 or 150 micrograms) were necessary for suppression of mitogen-induced lymphocyte proliferation. These findings demonstrate that CRH in the pig brain is active for inducing simultaneous changes in behavioral and physiological systems and are, therefore, consistent with the hypothesis that brain CRH is important in mediating the interaction among behavior, endocrine, and immune systems in animals experiencing stress.
Many of the behavioral responses following acute bacterial or viral infection are now considered important for maintaining homeostasis during inflammation. In the present study, we extend this concept to pigs (16 crossbred barrows) by demonstrating that lipopolysaccharide (LPS, .5, 5, or 50 micrograms/kg BW) from Escherichia coli injected i.p. reduces feed intake, decreases activity, and elevates body temperature. To determine whether any of these effects could be mediated via a prostaglandin (PG)-dependent mechanism, a second experiment with 16 crossbred barrows was conducted. Barrows were pretreated with indomethacin (IND, 5 mg/kg BW [a cyclooxygenase inhibitor]), and their behavior and body temperature following a challenge i.p. injection of LPS (5 micrograms/kg BW) were assessed. Pretreatment with IND inhibited the anorexia and inactivity caused by LPS, suggesting that the behavioral effects of LPS are dependent on activation of a PG system. Lipopolysaccharide alone, however, did not elevate body temperature in this case; thus, the involvement of PGs in this response was not determined. Collectively, these data indicate that pigs respond to LPS by reducing feed intake, decreasing activity, and becoming febrile. The ability of IND to inhibit behavioral effects of LPS is consistent with the hypothesis that a PG system is involved in mediating sickness behavior. Perhaps, by altering the activity of cyclooxygenase it is possible to enhance or inhibit the behavioral symptoms of sickness in pigs.
Aloe vera at doses of 100 and 300 mg/kg daily for 4 days blocked the wound healing suppression of hydrocortisone acetate up to 100% using the wound tensile strength assay. This response was because of the growth factors present in A. vera masking the wound healing inhibitors such as sterols and certain amino acids. The sterols showed good anti-inflammatory activity (-36%) in reducing the croton oil-induced ear swelling. This activity displayed a dose-response relationship.
This article discusses the efforts of the Coalition of 100 Black Women and the City College of New York in influencing the retention rate of minority college students as one means of outreach.
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The changing treatment and outcome for children with chronic renal failure (CRF) requiring renal replacement therapy (RRT) was assessed in children referred to the only paediatric unit in the North West Region of England between 1968 and 1988. There were 108 children. Referrals in consecutive 5-year time periods increased from 9 to 41 over the 20 years with the overall incidence of new referrals less than 15 years old reaching 8.5 per million childhood population in 1983-87, whilst the proportion of children under 5-years increased from 0% to 22%. The survival rate was better in those commencing RRT in the later years: 5-year survival 56% for the 1968-72 cohort vs 88% for 1978-82. The increasing number of referrals particularly among young children, coupled with improved survival rates have considerable implications when determining the provision of care for children with ESRD.
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A method fo nonradioactive DNA sequencing, which has been marketed commercially, uses four different fluorescent tags to label DNA fragments and fixed-wavelength excitation/fluorescence detection of the labels. This study presents an alternative method of detection based on synchronous luminescence (SL), in which both excitation and emission wavelengths are scanned simultaneously. This approach has proven in the past to have significant advantages over fixed-wavelength luminescence in the analysis and identification of fluorescent analytes. In this paper, the utility of synchronous excitation was investigated as a method for DNA sequencing with fluorescent tags. A laser-based SL instrument, recently developed in this laboratory, was used to resolve the spectra of a mixture of the dyes used in the fluorescence-based sequencing scheme. A preliminary limit of detection of 720 zeptomoles (10(-21) M) of fluorescein isothiocyanate dye in solution was achieved with this instrument. The results presented here suggest that the SL technique could result in an increase in sensitivity and a decrease in error rate of identification during DNA sequencing.
In a study of the effects on renal allograft survival of HLA mismatching, mismatching for cytomegalovirus (CMV) antibody status, and post-transplant CMV infection, 148 cyclosporin-treated renal transplant recipients were given kidneys optimally matched for HLA-A, -B, and -DR antigens but not matched for CMV antibody status. Mismatching for HLA-B and -DR antigens was associated with a greater number of rejection episodes and a lower graft survival, but mismatching for CMV antibody status and posttransplant primary or recurrent CMV infection exerted no effect on graft survival. The role of matching of renal transplant recipients and donors for CMV antibody status in preference to HLA matching (proposed as a means of reducing the mortality associated with primary CMV infection) is discussed.