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Biomedical subjects

R W Johnson

Publications and source records attributed to R W Johnson.

At least 91 records · Page 5Linked to original sources
PubMed1997

Near continuous cardiac output by thermodilution.

A new thermodilution method for frequent (near continuous) estimation of cardiac output, without manual injection of fluid into the blood, was tested. The method utilizes a pulmonary artery catheter equipped with a fluid filled heat exchanger. The technique is based on cyclic cooling of the blood in the right atrium and measurement of the temperature changes in the pulmonary artery. Using this technique, a new estimate of cardiac output can be obtained every 32 s. Cardiac output estimates, obtained for a running mean of three measurements with this method, were compared to the mean of three conventional thermodilution measurements. The measurements were obtained during short periods of stable respiration and circulation. In six pigs, we made 46 paired measurements of conventional thermodilution (TD) and near continuous (TDc) thermodilution. The cardiac output (COTD) ranged from 2.4-13.7 l/min (mean 5.4 l/min). The best linear fit through the paired data points was COTDc = -0.57 + 1.01 COTD. The mean difference between the methods was -0.50 l/min (S.D. = 0.39). The mean coefficient of variation of repeated measurements with the near continuous thermodilution was 3.6%. Considering changes of more than 0.25 l/min to be significant, all changes in cardiac output measured by conventional thermodilution were followed by the running mean of three near continuous thermodilution estimates. This study demonstrates the feasibility of the new method to monitor cardiac output, and to detect all changes greater than 0.25 l/min.

Animals↗
PubMed1997

Central lipopolysaccharide elevates plasma IL-6 concentration by an alpha-adrenoreceptor-mediated mechanism.

High circulating levels of interleukin-6 (IL-6) are evident after intracerebroventricular injection of lipopolysaccharide (LPS). To investigate the pathway of centrally induced IL-6 production, in the present study we evaluated the effects of specific alpha-adrenergic receptor antagonists administered peripherally on IL-6 production and hypertriglyceridemia induced by LPS administered centrally. In the first study, adult male Wistar-Furth rats were injected intracerebroventricularly with LPS. Centrally injected LPS increased plasma IL-6 and triglycerides (TG) in a dose-dependent fashion. To determine if LPS increased plasma IL-6 and TG through an alpha-adrenoreceptor mechanism, rats were pretreated intraperitoneally with either vehicle, phentolamine (alpha 1- and alpha 2-receptor antagonist), prazosin (alpha 1-receptor antagonist), or yohimbine (alpha 2-receptor antagonist). Thirty minutes later, rats were injected intracerebroventricularly with LPS. Whereas prazosin and yohimbine attenuated the increases in plasma IL-6 caused by LPS, phentolamine completely blocked the peripheral effects of central LPS. These data suggest that increased sympathetic activity and subsequent activation of alpha 1- and alpha 2-adrenergic receptors are important for controlling peripheral metabolic and endocrine systems when inflammatory stimuli are present in the brain.

Adrenergic alpha-Antagonists↗
PubMed1997

Coincidental changes in behavior and plasma cortisol in unrestrained pigs after intracerebroventricular injection of tumor necrosis factor-alpha.

The coincidental behavioral and physiological responses to inflammatory stimuli administered either peripherally or centrally were evaluated. In the first study, twenty castrated male pigs were injected ip with 0, 0.5, 5, or 50 microg/kg BW lipopolysaccharide (LPS). Body temperature was monitored telemetrically, and serial blood samples were collected via an indwelling jugular catheter for determination of plasma cortisol and tumor necrosis factor-alpha (TNF-alpha) concentrations. Sickness behaviors were measured during 10-min tests at 0, 2, 4, 8, 12, and 24 h post injection. The 5 and 50 microg/kg doses of LPS increased plasma concentrations of cortisol and TNF-alpha, while inducing anorexia, hypersomnia, and fever. In contrast, although 0.5 microg/kg LPS induced acute anorexia, hypersomnia, and fever, it did not increase plasma TNF-alpha; and the cortisol response was small and transient, suggesting the behavioral system in pigs is more responsive to LPS than the hypothalamic-pituitary-adrenal (HPA) axis. Because LPS-induced behavior and activation of the HPA axis involve proinflammatory cytokines in the brain, in a second study, unrestrained pigs with jugular catheters were injected intracerebroventricularly (I.C.V.) with recombinant porcine TNF-alpha. Vehicle or TNF-alpha (0, 5, or 50 ng/kg) was injected I.C.V., and plasma cortisol and behavior were determined as before. Pigs injected I.C.V. with 50 ng/kg TNF-alpha showed anorexia, hypersomnia, and an abrupt increase in plasma cortisol concentration. Whereas 5 ng/kg TNF-alpha I.C.V. also induced marked sickness behavior, it failed to stimulate the HPA axis, as indicated by plasma cortisol levels. That there was a distinct difference in the magnitude of behavioral and endocrine responses to LPS and TNF-alpha suggests that different systems that are responsive to inflammatory stimuli exhibit different sensitivities.

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↗
PubMed1997

APA, science, and the Defense of Marriage Act.

This paper uses the APA position on the Defense of Marriage Act to demonstrate that APA's advocacy policy regarding homosexual marriage is not based on science. It shows that the politics of advocacy have led a purportedly scientific organization to misinterpret, overgeneralize, and distort the results of research and to ignore the original purpose of the organization.

Female↗
PubMed1997

Inhibition of growth by pro-inflammatory cytokines: an integrated view.

In response to antigenic stimuli, a variety of cells, including activated macrophages, secrete cytokines that are responsible for altering the host's metabolism. Three of these cytokines (tumor necrosis factor alpha [TNF-alpha], interleukin-1 [IL-1], and interleukin-6 [IL-6]) have profound behavioral, neuroendocrine, and metabolic effects. There is evidence that cytokines and their cognate receptors are present in the neuroendocrine system and brain. Moreover, in laboratory animal species, IL-1, IL-6, and TNF-alpha have been found to modulate intermediary metabolism of carbohydrate, fat, and protein substrates, regulate hypothalamic-pituitary outflow, and act in the brain to reduce food intake. Finally, many of the systemic acute-phase responses to inflammatory stimuli such as lipopolysaccharide are inhibited by treatment with cytokine receptor antagonists. In short, many findings converge to suggest that a major component of the growth inhibition observed in immunologically challenged animals is mediated by pro-inflammatory cytokines. The goal of this article is to provide an integrated view of how cytokines act systemically on disparate tissues to alter growth.

Acute-Phase Reaction↗
PubMed1997

Time course of increased plasma cytokines, cortisol, and urea nitrogen in pigs following intraperitoneal injection of lipopolysaccharide.

The emerging view is that reduced feed intake, lean muscle accretion, and growth in immunologically challenged pigs is the result of increased cytokine activity, but this has not been directly tested. To begin addressing this issue, 72 crossbred barrows and gilts (11.55 +/- .19 kg BW) were not fed for 12 h and then injected i.p. with 0, .5, or 5 micrograms/kg of Escherichia coli lipopolysaccharide (LPS). Blood was collected by jugular puncture at 0, 2, 4, 8, 12, and 24 h after injection. Plasma levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), cortisol, plasma urea nitrogen (PUN), NEFA, and triglycerides were determined. Immunological stress was induced by LPS as indicated by increased secretion of TNF-alpha, IL-6, and cortisol. In pigs receiving 5 micrograms/kg of LPS, plasma TNF-alpha was increased 10-fold at 2 h after injection and was still elevated (P < .01) at 4 h. In these same pigs, plasma concentration of IL-6 was increased at 2 h and peaked at 4 h with levels exceeding baseline values by 200-fold (P < .01). Cortisol was elevated at 2, 4, and 8 h after injection (P < .01). The increased secretion of cytokines and cortisol in pigs injected with 5 micrograms/kg of LPS was followed by an increase in protein degradation, as evidenced by PUN values that were increased two- and threefold at 8 and 12 h after injection, respectively. However, unlike previous reports in laboratory animal species, plasma glucose, NEFA, and triglycerides were not altered by LPS. Nonetheless, as the period of feed deprivation progressed from 12 to 36 h, plasma NEFA and triglycerides increased (P < .05) and plasma glucose tended to decrease. We believe that immunological challenge induces cytokine synthesis and secretion in swine which, in turn, may induce protein catabolism.

Animals↗
PubMed1997

Health insurance coverage at midlife: characteristics, costs, and dynamics.

Recent data from the first two waves of the Health and Retirement Study are analyzed to evaluate prevalence of different types of health insurance, characteristics of different plan types, and change sin coverage as individuals approach retirement age. Although overall rates of coverage are quite high among the middle-aged, the risk of noncoverage is high within many disadvantaged groups, including Hispanics, low-wage earners, and the recently disabled. Sixty percent of individuals with health benefits are enrolled in health maintenance organizations (HMOs) or preferred provider organizations (PPOs). In addition, one-fourth of enrollees in fee-for-service (FFS) plans report restrictions in their access to specialists.

Age Factors↗
PubMed1997

Factors influencing kidney transplantation in Manchester, UK: 1989-1996.

The Manchester renal transplant center has the highest single center activity in the UK at present and has managed to achieve high posttransplant survival rates. We believe that this success is due to a combination of factors including a conservative approach to patient management; changes in clinical practice are only made after the evidence base has been established. This center is committed to the philosophy of prolonged survival of all transplanted kidneys. We believe that transplanting kidneys into clinically high-risk patients is not the best use of available resources.

Adult↗
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↗