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Biomedical subjects

R W Johnson

Publications and source records attributed to R W Johnson.

At least 19 recordsLinked to original sources
PubMed1997

Role of corticosterone in the behavioral effects of central interleukin-1 beta.

To investigate the role of the hypothalamic-pituitary-adrenal (HPA) axis in behavioral responses to infection, we studied the effects of corticosterone on depressed social behavior induced by peripheral and central interleukin-1 beta (IL-1 beta) in the rat. Intact and adrenalectomized (ADX) rats were injected i.p. with IL-1 beta (500 ng) and their motivation to investigate a juvenile conspecific was assessed. Whereas ADX rats showed a marked depression in social behavior following i.p. IL-1 beta, intact controls did not. To verify that corticosterone was responsible for inhibiting the effects of IL-1 beta, corticosterone pellets or placebos were implanted i.p. in ADX rats. Following i.p. injection of IL-1 beta, ADX rats with placebos experienced depressed social behavior. Corticosterone replacement, however, reversed this effect in ADX rats, confirming that corticosterone modulates the behavioral effects of peripheral IL-1 beta. To determine if corticosterone modulates sickness behavior directly in the CNS, intact and ADX rats were injected i.c.v. with IL-1 beta or lipopolysaccharide (LPS). Although centrally administered IL-1 beta depressed social behavior to a similar extent in intact and ADX rats, the depression was prolonged in ADX rats. However, social behavior of ADX rats injected i.c.v. with LPS was depressed more than in intact controls, and this effect was reversible by corticosterone replacement. These results are interpreted to indicate that corticosterone inhibits the behavioral effects of IL-1 beta in the periphery and, perhaps, in the CNS. That the behavioral effects of central LPS were inhibited by corticosterone suggests the HPA axis may modulate behavior by regulating cytokine synthesis in the CNS.

Animals↗
PubMed1997

Herpes zoster and postherpetic neuralgia. Optimal treatment.

Herpes zoster is a common disease primarily affecting the elderly. Although some individuals experience no symptoms beyond the duration of the acute infection, many develop chronic pain [postherpetic neuralgia (PHN)], which is the commonest complication of herpes zoster infection and remains notoriously difficult to treat once established. It may persist until death and has major implications for quality of life and use of healthcare resources. Predictors for the development of PHN are present during the acute disease and should indicate the need for the use of preventive therapy. At the present time, use of antiviral and certain tricyclic antidepressant drugs, combined with psychosocial support, seem most effective, but are far from perfect. Sympathetic nerve blocks reduce acute herpetic pain but it is uncertain whether they prevent PHN. In the future, vaccines may have an important place in reducing the incidence of chickenpox in the population or, through the vaccination of middle-aged individuals, in boosting immunity to varicella zoster virus, thus preventing or modifying the replication of the virus from its latent phase that results in herpes zoster. Developments in the understanding of the pathophysiology of PHN indicate possible directions for improved drug management of established PHN, although no evidence yet exists for efficacy of the drugs concerned. Such agents include new generation anticonvulsants and N-methyl-D-aspartate antagonists.

Aged↗
PubMed1996

Importance of minimizing HLA-DR mismatch and cold preservation time in cadaveric renal transplantation.

Univariate and multivariate analyses have been performed on donor an d recipient variables to determine possible effects on the outcome of 516 primary cadaveric renal transplants performed in our single center from 1989 until 1993. The overall actuarial patient survival at 1 year and 5 years was 94.4% and 87.4%, respectively; the 1 year and 5 year graft survival rates were 88.3% and 77.8%, respectively. A total of 95 grafts were lost; death with function (35%) and chronic rejection (22%) were the major causes. Three variables (HLA-DR mismatch, delayed graft function, and prolonged cold ischemia time) had a significant detrimental effect on both short- and long-term graft survival. Zero HLA-DR mismatched grafts showed significantly enhanced survival over those with 1 HLA-DR mismatch both at 1 year (92.8% vs. 84.5%) and at 5 years (88.3% vs. 73.9%) only if cold ischemia time was less than 26 hours (P=0.0009). Occurrence of delayed graft function significantly lowered graft survival at both 1 year and 5 years (P=0.002), and the incidence was significantly associated with prolonged cold ischemia time (P<0.0001). HLA-A or HLA-B matching, percentage panel reactive antibodies (PRA), and anastomosis time showed no independent effect on long-term survival. The small number of 2 HLA-DR mismatched grafts (n=6) precluded separate analysis of this group. Acute rejection accounted for 12% of losses but had no statistically significant effect on graft survival, even though an increased frequency of rejection episodes was significantly associated with HLA-DR mismatch (P<0.0001). These results would suggest that significant survival benefits may be achieved by prospective HLA matching if cold ischemia times are limited. The efficiency of organ sharing must he improved to make optimal use of a limited resource.

Adolescent↗
PubMed1996

Twenty-one years survival with systemic AL-amyloidosis.

AL-amyloidosis has a poor prognosis, typically with cardiac or renal failure ensuing some months after diagnosis. However, sporadically there have been reports of long-term survivors, either with unusual manifestations of amyloidosis, or after concerted chemotherapy to suppress the overt or occult pathological monoclonal plasma cell population responsible for the elaboration of immunoglobulin light chains. We report the case of a 46-year-old man who has survived 21 years after the histological diagnosis of renal amyloidosis was made, after he had presented with severe nephrotic syndrome. This patient was given intensive chemotherapy but came to end-stage renal failure some 10 years later, was dialysed for 1 year, and then was the successful recipient of a cadaveric renal transplant, which is working excellently some 10 years later, with little evidence of recurrent renal or systemic amyloidosis. There is renewed interest in therapy for systemic amyloidosis, and this case demonstrates that with this approach the prognosis can be more favorable than is commonly assumed.

Amyloidosis↗
PubMed1996

Investigation of the effects of solution composition and container material type on the loss of 11-nor-delta 9-THC-9-carboxylic acid.

The loss of 11-nor-delta 9-tetrahydrocannabinol-9-carboxylic acid (THC-COOH) from solution was studied using fluorescence polarization immunoassay (FPIA) technology and x-ray photoelectron spectroscopy (XPS). Several materials (glass, silylated glass, high density polyethylene, polypropylene, polystyrene, polymethylmethacrylate, Teflon, and Kynar) were studied along with three solvents (water, urine, and Abbott cannabinoids diluent). THC-COOH losses ranging from 0 to 9.7 ng/cm2 and concentration reductions to 46% of starting values were measured. XPS indicated the presence of fluorine-labeled THC-COOH at materials surfaces. A half-life of 10 min was calculated for THC-COOH loss from urine stored in high density polyethylene at room temperature. Sample handling losses during pipetting were determined and ranged from 1.1 to 7.9 ng per aliquot. The effects of sample volume and sample handling on the THC-COOH concentrations of controls were also investigated.

Dronabinol↗
PubMed1996

Transplantation in the elderly.

Studies show that at present fewer patients aged > 60 are on the waiting list for transplantation than would be predicted from their proportion on renal replacement therapy by dialysis. Evidence to date shows that in these older subjects loss of grafts by rejection is less common than it is in younger subjects; there is also absolutely a greater loss of grafts due to death of the patient while the graft still functions. Well-matched grafts should be available to older subjects in whom thorough clinical assessment makes unlikely early death, particularly from cardiovascular causes, following transplantation. If this is to be achieved, agreed approaches to the assessment of such patients and to their inclusion on transplant waiting lists must be established.

Aged↗
PubMed1996

Corticosterone modulates behavioral and metabolic effects of lipopolysaccharide.

The behavioral and neuroendocrine responses following infection are important mechanisms for maintaining homeostasis and promoting recovery. The purpose of this study was to determine if glucocorticoids modulate the behavioral and metabolic effects of lipopolysaccharide (LPS) in rats. A single injection of LPS (10 micrograms/kg ip) increased plasma corticosterone at 4 h, but had no effect on social behavior, body temperature, or body weight. To determine if behavioral and metabolic effects of LPS were precluded by the increase in corticosterone, adrenalectomized (ADX) and sham-operated rats were injected with LPS. Whereas ADX rats expressed symptoms of sickness, intact controls did not. To verify that corticosterone was the adrenal hormone responsible for inhibiting these effects of LPS, corticosterone pellets or placebos were implanted intraperitoneally in ADX rats. Following injection of LPS, ADX rats with placebos expressed behavioral symptoms characteristic of sickness, including depressed social behavior. Corticosterone pellets, however, entirely reversed these effects in ADX rats. These results indicate that corticosterone modulates the behavioral and metabolic effects of LPS, suggesting that the hypothalamic-pituitary-adrenal axis is important in preventing profound behavioral disturbances in response to low-grade immune stimulation by infectious and noninfectious agents.

Adrenalectomy↗
PubMed1996

Outcome of pediatric cadaveric renal transplantation: a 10 year study.

This report deals with 120 cadaveric renal transplants performed in 101 pediatric recipients in this Centre in two five-year periods, 1984 to 1988 (N = 65) and 1989 to 1993 (N = 55). In the first group transplants were allocated on the basis of best size (small donors for small recipients); in the second group priority was given to beneficial HLA matching. Initial immunosuppression was either cyclosporine (CsA) monotherapy (15 mg/kg/day), or triple therapy (CsA 5 mg/kg/day, prednisolone 1 mg/kg/day and azathioprine 1 mg/kg/day) if there was delayed graft function. Patient survival at one year and five years (97.5% and 92.3%, respectively) did not differ between the two groups, although there was an improvement in graft survival at one and five years in the second period relative to the first: 69.2% and 53.8% versus 78.6% and 65.6%. This did not achieve statistical significance. One year graft survival in recipients under five years did not differ significantly from older children (72%). There was a trend to improvement in one year graft survival in the < five years of age pediatric patients in Group 2, with beneficially matched kidneys and improved immunosuppressive management. Graft losses due to acute rejection were similar in both groups. Donor age < 4 years significantly reduced one year graft survival (63% vs. 85%, P = 0.01), while recipient age had no effect. Small donor kidneys were associated with a higher incidence of graft thrombosis. Transplantation resulted in the normalization or acceleration of growth velocity in (84%) of the pre-pubertal children who completed follow up. In conclusion, we have shown that excellent patient and graft survival can be achieved in children transplanted under the age of five years. Kidneys from donors under the age of four years are associated with an unacceptable rate of graft loss. Small children do not readily accept cyclosporine monotherapy. Successful early renal transplantation offers the best chance of normal growth and development.

Adolescent↗
PubMed1995

The future of predictors, prevention, and therapy in postherpetic neuralgia.

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."

Forecasting↗
PubMed1995

Clinicopathological correlations in syringomyelia using axial magnetic resonance imaging.

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)

Adolescent↗
PubMed1994

A randomized trial of acyclovir for 7 days or 21 days with and without prednisolone for treatment of acute herpes zoster.

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.

Acute Disease↗
PubMed1994

Immunology discovers physiology.

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)

Animals↗