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Biomedical subjects

K Clarke

Publications and source records attributed to K Clarke.

At least 127 records · Page 7Linked to original sources
PubMed1993

Microalbuminuria does not predict cardiovascular disease in a normal general practice population.

Recent studies have suggested that microalbuminuria is relatively common (9.4%) in non-diabetic subjects and that it is an excellent marker for increased cardiovascular risk. In an attempt to assess the prevalence of microalbuminuria in Northern Ireland where there is a high incidence of coronary heart disease, we studied 400 males, age 35-65 years, chosen at random from a Belfast general practice. There was a 73% response rate (n = 273). Sixteen per cent of the population has ischaemic heart disease. Microalbuminuria was defined as an increased urinary albumin excretion rate of 20-200 ug min-1. Thirteen subjects (4.7%) had an albumin excretion rate of 20 ug min-1 or more. After exclusion of subjects with diabetes mellitus or renal diseases, the group with microalbuminuria (n = 8), was compared to those without microalbuminuria (n = 256). There was no significant difference in the incidence of ischaemic heart disease between the two groups, nor did the group with microalbuminuria have a more adverse profile of vascular risk factors, apart from serum triglyceride (1.8 +/- 0.2 v 1.3 +/- 0.0 mmol l-1, p < 0.05) and plasma glucose (5.5 +/- 0.3 v 5.1 +/- 0.3 mmol l-1, p < 0.05) levels. We conclude that in a general practice from an area at high risk of ischaemic heart disease, the prevalence of microalbuminuria was low. Contrary to previous reports, microalbuminuria was not helpful in predicting subjects at risk of ischaemic heart disease.

Adult↗
PubMed1993

Characterization of anergy to the superantigen Staphylococcus enterotoxin B.

In vivo administration of superantigens leads to activation and subsequent depletion or anergy of T cells expressing defined V beta-T cell receptors (TCR). Superantigens have therefore become intensively studied tools for examining parameters of immunoregulation and they may represent model antigens for pathogenic agents. An HIV-encoded superantigen has for example been implicated in the dramatic loss of helper T cells in AIDS. We investigated the response of V beta 8+ T cells in mice after primary and secondary exposure to the superantigen Staphylococcus Enterotoxin B (SEB).

Animals↗
PubMed1993

Lipid accumulation in isolated perfused rat hearts has no apparent effect on mechanical function or energy metabolism as measured by 31P NMR.

Male Sprague-Dawley rats were fed diets that contained 20% by weight soybean oil or rapeseed oil (21% and 43% erucic acid) for 7 days. The rapeseed oil diets increased the cardiac triacylglycerol content 5-fold and 25-fold, respectively, above control values. Hearts were removed from the animals and perfused with modified Krebs-Henseleit buffer at 37 degrees C. The calculated rate-pressure product was used as a measure of contractile function. 31P NMR spectra were acquired throughout a protocol that consisted of 12 min control perfusion, followed by 12 min perfusion with 20 microM isoproterenol, 12 min washout, 12 min total global ischemia, and 28 min reperfusion. The steady state levels of creatine phosphate, ATP, intracellular pH, contractile function, and the free energy of ATP hydrolysis (delta GATP) were determined for all three groups of hearts. Isoproterenol more than doubled the rate-pressure product of the hearts on all diets and decreased the concentrations of creatine phosphate and ATP with a concomitant rise in Pi. After global ischemia, creatine phosphate levels recovered fully, ATP levels remained low, and most hearts developed ventricular fibrillation. Changes in intracellular pH were the same for all groups: pH was 7.1 throughout the equilibration and isoproterenol perfusion period, decreased to pH approximately 6.4 during ischemia, and returned to 7.0 during reperfusion. The results indicate that the fat accumulation that occurs in the hearts of rats fed diets rich in high erucic acid rapeseed oil does not interfere with the cardiac high energy phosphate metabolism or contractile function.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

A stimulatory Mls-1 superantigen is destroyed by ultraviolet light while other Mtv-7 antigens remain intact. Significance for Mls-1 unresponsiveness.

Accessory cells present Ag together with costimulatory signals as immunogens and without costimulatory signals as tolerogens. Responsiveness and unresponsiveness are thus alternatives of T cell immune reactions to Ag. Superantigens appear to make an exception; being presented by accessory cells capable of providing costimulatory signals, these Ag induce a strong T cell response but leave T cells unresponsive to a secondary challenge (anergy). We show here that T cell anergy is not a mandatory consequence of superantigen-induced activation. Mls-1- BALB/c recipients of DBA/2 spleen cells mount vigorous Mls-1 responses in vivo but their T cells retain the ability to respond to a subsequent Mls-1 challenge in vitro. We tested the possibility that the inability of DBA/2 spleen cells to inactivate Mls-1-reactive BALB/c T cells was the result of excessive costimulatory activity provided by Mls-1+ DBA/2 B cells. Costimulatory accessory cell activity has been reported to be destroyed by UV light. We exposed superantigen-presenting cells to UV radiation and found that they had lost the ability to stimulate an Mls-1 response without, however, gaining the capacity to render Mls-1-specific T cells anergic. Despite their inability to noticeably stimulate Mls-1-reactive T cells, UV-treated Mls-1+ lymphocytes induced an absolute unresponsiveness in Mls-1- recipients to a second challenge with the superantigen. Our data are in agreement with previous evidence, confirmed here, that BALB/c mice establish immunity against Mls-1+ cells, which causes the accelerated rejection of superantigen-bearing lymphocytes. Thus, our data imply that, whereas it takes stimulatory superantigenic Mtv-7 gene products to induce the activation of superantigen-reactive T cells, nonsuperantigenic Mtv-7 gene products may induce an immune response leading to the elimination of Mtv-7+ lymphoid cells.

Animals↗
PubMed1992

Assessment of value of calibrated lyophilised plasmas to determine International Sensitivity Index for coagulometers.

An attempt was made to correct for the effects of coagulometers on the International Sensitivity Index (ISI) in a series of collaborative studies. Modified ISI were derived from the prothrombin time results with coagulometer systems using a range of calibrated plasmas. Two alternative approaches to correction of the ISI were evaluated. The first relied on the consensus orthogonal regression slopes of the prothrombin times for each coagulometer system plotted against the consensus manual results; the second depended on the local individual slope of the prothrombin times for each instrument. The two procedures were compared with the currently recommended method where International Normalised Ratios (INR) are derived from the manual ISI of the thromboplastin. The recommended method gave a significant bias from the manual results with most coagulometers. In contrast, the local correction procedure gave no significant biases, whereas the consensus method did so in a few instances. Both these correction procedures seem more reliable than the recommended method of INR derivation, but the local correction is more accurate and offers a more practical solution by allowing laboratories to determine their own corrected ISI on a range of calibrated plasmas.

Calibration↗
PubMed1991

Analysis of 23Na NMR spectra from isolated perfused hearts.

The 23Na NMR spectra obtained from isolated hearts perfused with buffer containing the paramagnetic shift reagent dysprosium triethylenetetraminehexaacetic acid, Dy(TTHA)3-, are complex and contain a number of overlapping peaks of different intensities. Spectra from rat, rabbit, guinea pig, and ferret hearts obtained during periods of control perfusion are similar and undergo similar changes when the hearts are subjected to periods of ischemia and reflow. The contributions from the intracellular, interstitial, vascular, and bath compartments to the multiple peaks in the spectra of rats hearts have been assigned. The significant contributions to these spectra of bulk magnetic susceptibility effects and incomplete mixing have been demonstrated through a series of modeling experiments. Since the spectra from hearts of different species are so similar, the peak assignments made for the rat are applicable to spectra from rabbit, guinea pig, and ferret hearts as well. This work provides a framework for quantitative analysis of the spectral changes which occur during conditions such as ischemia and reflow.

Animals↗
PubMed1991

Nosocomial legionnaires' disease: lessons from a four-year prospective study.

We studied all cases of nosocomial pneumonia at our 800-bed tertiary care hospital from September 1983 to September 1987. Of the 813 cases of nosocomial pneumonia, 31 (3.8%) were definite (isolation of organism or fourfold rise in titer) and 21 (2.5%) were possible cases (single or stable antibody titer of greater than or equal to 1:256) of legionnaires' disease. The definite cases involved a more severe form of pneumonia and a significantly higher mortality rate--64% versus 14% (p less than 0.0009) compared with the possible cases. Despite attempted comprehensive surveillance, only four (13%) of the definite cases of legionnaires' disease were found that would not have been diagnosed if the study were not ongoing. The yield from adequate (4- to 6-week convalescent serum samples) serologic testing was 5%, whereas the yield from sputum culture was 11%. We conclude that targeted surveillance of immunosuppressed patients with nosocomial pneumonia by culture of respiratory tract secretions for Legionella pneumophila is adequate for monitoring for the presence of legionnaires' disease in a hospital.

Cross Infection↗
PubMed1991

Control of endemic nosocomial legionnaires' disease by using sterile potable water for high risk patients.

In a setting where potable water is contaminated with Legionella pneumophila serogroup 1, we performed two case control studies. The first case control study consisted of 17 cases of nosocomial Legionnaires' disease (LD) and 33 control (the patients who were admitted to the ward where the case was admitted immediately before and after the case) subjects. Cases had a higher mortality rate 65% vs 12% (P less than 0.004); were more likely to have received assisted ventilation (P less than 0.00001); to have nasogastric tubes (P less than 0.0004) and to be receiving corticosteroids or other immunosuppressive therapy (P less than 0.0001). Based on the results of this study, sterile water was used to flush nasogastric tubes and to dilute nasogastric feeds. Only 3 cases of nosocomial LD occurred during the next year compared with 12 the previous year (P less than 0.0001). Nine cases subsequently occurred and formed the basis for the second case-control study. Eighteen control subjects were those patients admitted to the same unit where the case developed LD, immediately before and after the case. The mortality rate for the cases was 89% vs 6% for controls (P less than 0.00003). The only other significant difference was that cases were more likely to be receiving corticosteroids or other immunosuppressive therapy 89% vs 39% (less than 0.01). We hypothesized that microaspiration of contaminated potable water by immunocompromised patients was a risk factor for nosocomial Legionnaires' disease. From 17 March 1989 onwards such patients were given only sterile potable water. Only two cases of nosocomial LD occurred from June 1989 to September 1990 and both occurred on units where the sterile water policy was not in effect. We conclude that aspiration of contaminated potable water is a possible route for acquisition of nosocomial LD in our hospital and that provision of sterile potable water to high risk patients (those who are receiving corticosteroids or other immunosuppressive drugs; organ transplant recipients or hospitalized in an intensive care unit) should be mandatory.

Case-Control Studies↗
PubMed1991

Indium-111-leukocyte imaging in acute cholecystitis.

Eleven patients with suspected acute cholecystitis underwent sequential 99mTc-iminodiacetic derivative (IDA) and 111In-white blood cell (WBC) imaging to determine if 111In-WBCs accumulate within an acutely inflamed hemorrhagic gallbladder wall and, thus, could be employed as a reasonable alternative to 99mTc-IDA scintigraphy in detecting acute cholecystitis. Seven patients had surgically confirmed acute cholecystitis. Of these cases, five had a true-positive 99mTc-IDA and 111In-WBC, one an indeterminate 111In-WBC and true-positive 99mTc-IDA, and one a true-positive 111In-WBC and false-negative 99mTc-IDA scan. The remaining four patients did not have acute cholecystitis. All visualized their gallbladder within 1 hr after 99mTc-IDA administration and none had 111In-WBC gallbladder wall uptake. Both 111In-WBC and 99mTc-IDA scintigraphy accurately detected acute cholecystitis: hepatobiliary scintigraphy demonstrated a cystic duct obstruction and 111In-WBC imaging detected the inflammatory infiltrate within the gallbladder wall. The sensitivity and specificity of each was 86% and 100%, respectively.

Acute Disease↗
PubMed1990

Evidence from population mixing in British New Towns 1946-85 of an infective basis for childhood leukaemia.

Mortality from leukaemia under age 25 was studied in British New Towns to test the hypothesis that leukaemia represents a rare response to a much commoner (but unrecognised) infection, the transmission of which is facilitated when large numbers of people come together. The density of children was higher in the rural, but lower in the overspill, New Towns than in the areas from which their incomers originated. Residents of the rural New Towns had greater diversity of origin than those of the overspill towns of London and Glasgow. These two factors would encourage a greater rise in the postulated underlying infection in the rural towns, and in these a significant excess of leukaemia at ages 0-4 was found in 1946-65. In both sets of towns there was a significant deficit in other age groups consistent with immunising effects of the relevant infection. There are parallels with feline leukaemia virus infection, in which contrasting leukaemogenic and immunising effects occur in different social settings owing mainly to differences in intensity of viral exposure.

Adolescent↗
PubMed1990

Energetic correlates of cardiac failure: changes in the creatine kinase system in the failing myocardium.

To address the hypothesis that impaired ATP synthesis rates caused by changes in the creatine kinase system is an important mechanism underlying cardiac failure, we measured total creatine kinase activity, isoenzyme composition and creatine content in two animal models of hypertrophy with cardiac dysfunction, the spontaneously hypertensive rat in the transition to failure and the creatine-depleted hyperthyroid rat heart challenged by hypoxia. During the transition from stable compensated hypertrophy to failure characterized by decreased functional capacity, we found that total creatine kinase activity and particularly mitochondrial creatine kinase activity decreased. The decrease in functional capacity, the further increase in heart size and the derangements in the creatine kinase system did not occur if these animals were treated for 6 months with the antihypertensive agents, guanethidine or hydralazine. These results suggest that changes in the creatine kinase system occur coordinately with the transition to failure. To assess whether the changes in the creatine system may be causally linked to decreased functional capacity, we used 31P NMR spectroscopy of isolated perfused hearts to define the high energy phosphate content and cardiac performance of creatine-depleted (approximately 50%) hypertrophied hearts challenged by hypoxia. These hearts displayed greater susceptibility to hypoxic injury with regard to both systolic and diastolic function during and following hypoxia. We also measured total creatine kinase activity in right ventricular biopsy specimens from patients with various forms of cardiomyopathy and low ejection fractions, and found a positive correlation between total creatine kinase activity and ejection fraction. Taken together, these results support the hypothesis that decreasing the energy reserve for ATP synthesis renders the heart more susceptible to systolic and diastolic failure.

Animals↗