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Biomedical subjects

D J Gordon

Publications and source records attributed to D J Gordon.

At least 37 records · Page 2Linked to original sources
PubMed1997

Substance P binding to peripheral blood mononuclear leukocytes in atopic dermatitis.

Substance P has various immunomodulatory effects, including in vitro modification of lymphocyte proliferation and cytokine release. Elevated levels of substance P and increased staining of substance P-positive nerve fibres have been reported in atopic dermatitis patients. We examined fluoresceinated substance P binding to a range of lymphocyte subsets and compared the results in atopic dermatitis, non-atopic psoriasis patients and normal controls. Fluoresceinated substance P and phycoerythrin-labelled monoclonal antibodies to CD3, CD4, CD8, CD57, CD19 and CD14 were incubated in duplicate with Ficoll-Hypaque separated peripheral blood mononuclear leukocytes. With flow cytometry the fluoresceinated substance P-positive cells were identifiable as a peak of positively fluorescent cells, and the percentages of positive cells were measured. We have demonstrated binding of fluoresceinated substance P to all subsets examined, with significantly less binding to atopic dermatitis CD3-, CD8- and CD57-positive cells. This may affect cytokine release and hence be important in the pathogenesis of atopic dermatitis.

Adolescent↗
PubMed1997

Neuropeptide modulation of Th1 and Th2 cytokines in peripheral blood mononuclear leucocytes in atopic dermatitis and non-atopic controls.

The neuropeptides substance P (SP) and vasoactive intestinal peptide (VIP) are present in the nerve endings in the skin and SP is thought to be present at abnormal concentrations in atopic dermatitis (AD) patients. Th1 and Th2 imbalance in AD has been the focus of recent immunological investigations and a preferential Th2 response by atopic cells on stimulation has been proposed. We wished to establish whether neuropeptides acted on T cells to affect their cytokine profile directly, using an accessory cell-independent stimulus (anti-CD3 monoclonal antibody and neuropeptides at several concentrations. We found that interferon (IFN)-gamma and interleukin (IL)-4 release were lower in AD. SP had an enhancing effect on both IFN-gamma and IL-4 at physiological concentrations (10(-10)-10(-6) mol/L) in AD, which was significantly different from controls (P < 0.05). VIP had inhibitory effects over this range in AD and in controls. We conclude that these neuropeptides have a modest effect on T-cell cytokine release and that their action is not cytokine-specific.

Adult↗
PubMed1996

Rationale and design for the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). ALLHAT Research Group.

Are newer types of antihypertensive agents, which are currently more costly to purchase on average, as good or better than diuretics in reducing coronary heart disease incidence and progression? Will lowering LDL cholesterol in moderately hypercholesterolemic older individuals reduce the incidence of cardiovascular disease and total mortality? These important medical practice and public health questions are to be addressed by the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), a randomized, double-blind trial in 40,000 high-risk hypertensive patients. ALLHAT is designed to determine whether the combined incidence of fatal coronary heart disease (CHD) and nonfatal myocardial infarction differs between persons randomized to diuretic (chlorthalidone) treatment and each of three alternative treatments--a calcium antagonist (amlodipine), an angiotensin converting enzyme inhibitor (lisinopril), and an alpha-adrenergic blocker (doxazosin). ALLHAT also contains a randomized, open-label, lipid-lowering trial designed to determine whether lowering LDL cholesterol in 20,000 moderately hypercholesterolemic patients (a subset of the 40,000) with a 3-hydroxymethylglutaryl coenzyme A (HMG CoA) reductase inhibitor, pravastatin, will reduce all-cause mortality compared to a control group receiving "usual care." ALLHAT's main eligibility criteria are: 1) age 55 or older; 2) systolic or diastolic hypertension; and 3) one or more additional risk factors for heart attack (eg, evidence of atherosclerotic disease or type II diabetes). For the lipid-lowering trial, participants must have an LDL cholesterol of 120 to 189 mg/dL (100 to 129 mg/dL for those with known CHD) and a triglyceride level below 350 mg/dL. The mean duration of treatment and follow-up is planned to be 6 years. Further features of the rationale, design, objectives, treatment program, and study organization of ALLHAT are described in this article.

Antihypertensive Agents↗
PubMed1996

Recurrence of thin melanoma: how effective is follow-up?

In order to assess the benefit to patients with thin malignant melanoma (< 0.76 mm) of a 5-year clinical follow-up programme, we have studied 602 patients with a minimum time from primary surgery of 5 years. Tumour recurrence occurred in 24 patients (4% of all patients) but only five surgically treatable recurrences (< 1% of all patients) occurred within the 5-year period following primary surgery. After 5 years there were four surgically treatable recurrences, but their prognosis was generally poor. The remaining cases of tumour recurrence were not surgically treatable. In the face of an increasing incidence of melanoma, and the accompanying increase in demand for surgical treatment and outpatient review, we question the need for prolonged hospital follow-up of thin melanoma.

Adult↗
PubMed1996

Infantile haemangiopericytoma of the hand.

Infantile haemangiopericytomas (IHP) are rare subcutaneous tumours arising from pericytes. Clinically they are difficult to diagnose and pathologically they appear to be locally invasive, but they have a better prognosis than adult haemangiopericytomas. We report a case of IHP affecting the hand of a 7-week-old child that required urgent treatment.

Hand↗
PubMed1995

An empirical evaluation of the placebo run-in.

A prerandomization placebo run-in period is often used in an attempt to exclude potential clinical trial participants who are likely to be poor adheres. It is assumed that potential participants who are poor adherers during the run-in will be less likely to take medication during the trial. This assumption was tested in the Cholesterol Reduction in Seniors Program (CRISP), by prescribing placebo for a 3-week period, but not using the results of the run-in as an entry criterion. The CRISP study was a pilot study designed to compare the effects on lipids and the safety of two doses of lovastatin and placebo in persons 65 years of age and older. After general entry criteria were satisfied, each participant was prescribed placebo for a 3-week period. At the end of the 3-week period, all participants were randomized to one of the three treatment groups, regardless of their adherence to the placebo. Of the 431 participants in the study, 66 (15%) who took less than 80% of the prescribed placebo or who failed to return their unused placebo pills were classified as poor run-in adherers. Poor run-in adherence was associated with lower educational attainment. At 3 and 6 months of follow-up mean adherence was 89.3% and 83.4% among all participants. Exclusion of poor run-in adherers would have increased these means to 90.9% and 85.5%, respectively. Treatment effect as measured by fall in LDL cholesterol would have increased by 2.9 mg/dl in the 40 mg/day dose group at 3 months of follow-up with the addition of a placebo run-in. We conclude that a placebo run-in would have had little effect on the outcome of the CRISP study and would have substantially increased recruitment difficulties. Lower educated persons were more likely to be excluded by a placebo run-in, but the effect of the run-in on follow-up adherence was stronger in less educated participants. More research about the role of a placebo run-in is needed in order to determine the appropriate role of this method in clinical trials.

Aged↗
PubMed1994

Cholesterol lowering in the elderly. Results of the Cholesterol Reduction in Seniors Program (CRISP) pilot study.

BACKGROUND: Total and lipoprotein cholesterol levels continue to be predictors of coronary heart disease risk in men and women over 65 years old. Cholesterol-lowering trials, however, while sometimes including such subjects, have not concentrated on this age group. The Cholesterol Reduction in Seniors Program was a five-center pilot study to assess feasibility of recruitment and efficacy of cholesterol lowering in this age group. METHODS: The study was a randomized, double-masked clinical trial with placebo, 20-mg lovastatin, and 40-mg lovastatin arms. Major efforts were made to recruit women and minorities. Participants were followed up for 1 year on a cholesterol-lowering diet plus placebo or study drug. End points were changes in blood lipid levels. Data on other blood chemistry values, as well as quality-of-life measures and coronary heart disease morbidity and mortality, were also collected. RESULTS: Four hundred thirty-one subjects with low-density lipoprotein cholesterol levels greater than 4.1 and less than 5.7 mmol/L (159 and 221 mg/dL) were randomized, of whom 71% were women and 21% were African Americans; the mean age was 71 years. In the 20- and 40-mg lovastatin groups, total cholesterol levels fell 17% and 20%; low-density lipoprotein cholesterol levels fell 24% and 28%; triglyceride levels fell 4.4% and 9.9%, respectively. High-density lipoprotein cholesterol levels rose 7.0% and 9.0%, respectively. No changes were observed in the placebo group. Gender, race, and age did not significantly affect responses. Coronary heart disease morbidity and mortality data were collected but not analyzed for this study. CONCLUSION: Older subjects of both genders and a variety of racial and ethnic groups can be successfully recruited into a cholesterol-lowering trial. Lovastatin has effects similar to those reported in younger subjects in previous controlled trials. There is little advantage to the higher lovastatin daily dose. Side effects were remarkably low in all groups.

Aged↗
PubMed1994

The sliding fasciocutaneous flap.

A sliding fasciocutaneous flap on the medial side of the lower third of the leg is described. Its application in the management of skin defects in this area is illustrated.

Adult↗
PubMed1993

Prevalence of high blood cholesterol among US adults. An update based on guidelines from the second report of the National Cholesterol Education Program Adult Treatment Panel.

OBJECTIVE: To estimate the current levels and trends in the proportion of US adults with high blood cholesterol based on guidelines from the second report of the National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP II). DESIGN: Nationally representative cross-sectional surveys. SETTING/PARTICIPANTS: Data for 7775 participants 20 years of age and older from phase 1 of the third National Health and Nutrition Examination Survey (NHANES III) (data collected from 1988 through 1991) and for 9797 participants 20 through 74 years of age from NHANES II (data collected from 1976 through 1980) were used. RESULTS: From the data collection period in NHANES II (1976 through 1980) to the period in NHANES III (1988 through 1991), the proportion of adults with high blood cholesterol levels (> or = 240 mg/dL [6.21 mmol bd) fell from 26% to 20%, while the proportion with desirable levels (< 200 mg/dL [5.17 mmol/L]) rose from 44% to 49%. Currently, using the ATP II guidelines and NHANES III data, 40% of all adults 20 years of age and older would require fasting lipoprotein analysis; and 29% of all adults would be candidates for dietary therapy (as compared with 36%, using NHANES II data). Based on 1990 population data, it is estimated that approximately 52 million Americans 20 years of age and older would be candidates for dietary therapy. Assuming that dietary intervention would reduce low-density lipoprotein (LDL) cholesterol levels by 10%, as many as 7% of all adult Americans (approximately 12.7 million) might be candidates for cholesterol-lowering drugs. This estimate reflects approximately 4 million adults with established coronary heart disease, of whom half are aged 65 years and older, and up to 8.7 million adults without established coronary heart disease, of whom up to 3.1 million are aged 65 years and older. CONCLUSIONS: Substantial progress has been made in reducing the prevalence of high blood cholesterol; yet a large proportion of all adults, approximately 29%, require dietary intervention for high blood cholesterol.

Adult↗
PubMed1993

Declining serum total cholesterol levels among US adults. The National Health and Nutrition Examination Surveys.

OBJECTIVE: To examine the secular trend in serum total cholesterol levels of the US adult population. DESIGN: Nationally representative cross-sectional surveys with both an in person interview and a medical examination that included the measurement of blood lipid levels. SETTING/PARTICIPANTS: Between 6000 and 13,000 adults aged 20 through 74 years examined in each of four separate national surveys during 1960 through 1962, 1971 through 1974, 1976 through 1980, and 1988 through 1991. RESULTS: Mean serum total cholesterol levels in US adults aged 20 through 74 years have consistently declined over the time period 1960 through 1991. More than half of the decline occurred during the time period 1976 through 1991. This decline occurred across the entire distribution of serum cholesterol levels and in all age-sex groups. High-density lipoprotein cholesterol and very low-density lipoprotein cholesterol levels have not changed, suggesting that the decline in total cholesterol levels is due to a decline in low-density lipoprotein cholesterol levels. CONCLUSIONS: These results document a continuing and substantial decline in serum cholesterol levels among US adults. They suggest that public health programs, designed to reduce cholesterol levels, are proving successful. The observed downward trend in serum cholesterol levels has coincided with a continuing decline in coronary heart disease mortality. These observations suggest that the Healthy People 2000 goal of reducing the mean serum cholesterol level of US adults to no more than 200 mg/dL (5.17 mmol/L) is attainable.

Adult↗
PubMed1993

Rationale and design of the Department of Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial (HIT) for secondary prevention of coronary artery disease in men with low high-density lipoprotein cholesterol and desirable low-density lipoprotein cholesterol.

Although a large body of epidemiologic evidence suggests that low levels of high-density lipoprotein (HDL) cholesterol are strongly associated with an increased risk of coronary artery disease (CAD), no large-scale clinical trials focusing on this association have been reported. This report describes the rationale and design of the Department of Veterans Affairs HDL Intervention Trial (HIT), a multicenter, randomized, controlled clinical trial designed to determine whether lipid therapy reduces the combined incidence of CAD death and nonfatal myocardial infarction in men with established CAD who have low levels of HDL cholesterol with "desirable" levels of low-density lipoprotein (LDL) cholesterol. Twenty-five hundred men with CAD and HDL cholesterol < or = 40 mg/dl, LDL cholesterol < or = 140 mg/dl, and triglycerides < or = 300 mg/dl are being recruited at 20 Department of Veterans Affairs medical centers, randomized to either gemfibrozil or placebo, and followed in a double-blind manner for an average of 6 years. In this population, gemfibrozil is expected to increase HDL cholesterol by 10 to 15%, have a negligible effect on LDL cholesterol, and lower triglycerides by 30 to 40%. Because an estimated 20 to 30% of patients with CAD have a low HDL cholesterol as their primary lipid abnormality, the results of this trial are expected to have far-reaching clinical implications.

Adult↗
PubMed1993

A correlation between DNA-nuclear matrix binding and relative radiosensitivity in two human squamous cell carcinoma cell lines.

Three aspects of DNA topology were examined in two human squamous cell carcinoma lines of differing radiosensitivity (SQ-9G, D0 = 1.46 Gy; and SQ-20B, D0 = 2.36 Gy). High-salt-extracted nuclei (nucleoids) were taken from gamma-irradiated cells, stained with ethidium bromide and examined by flow cytometry. After 5 Gy, nucleoids from SQ-9G cells became 30% less efficient at adopting positive DNA supercoils than were unirradiated controls. In contrast, only a 4% difference was found with the radioresistant SQ-20B line. Both lines produced positive supercoils more efficiently after irradiation if first exposed to the topoisomerase II inhibitor VP16. Ethidium bromide titration of nucleoids was consistent with each containing similar numbers and sizes of DNA loops. In each line approximately 30-35% of DNA was accessible to trioxsalen, as shown by inter-strand crosslinking after UV photo-activation. Exhaustive digestion of nuclear DNA by DNase I removed more DNA from the radiosensitive than from the radioresistant cell line (12% vs 28% remaining). This difference was thought to be due to the increased accessibility of SQ-9G DNA in vitro. We suggest that a looser association of SQ-9G DNA with the nuclear matrix both promotes DNase I digestion and affects the ability of SQ-9G nucleoids to maintain positive DNA supercoils after irradiation. These data implicate the DNA matrix attachment region in the expression of radiation sensitivity in the cell lines studied.

Carcinoma, Squamous Cell↗
PubMed1993

Investigation of possible adverse allergic reactions to mycoprotein ('Quorn').

Mycoprotein ('Quorn') is a food produced for human consumption from Fusarium graminearum. Crossreactivity studies showed that mycoprotein shared multiple common allergenic determinants with Aspergillus fumigatus and Cladosporium herbarum and some with Alternaria alternata. There is, therefore, a potential for mould allergic patients to react adversely to inhaled or ingested mycoprotein. Mycoprotein RAST screening of mycoprotein production workers was made during a 2 year period. Two of the production workers had specific RAST binding > or = 2% but none reported symptoms. Two of 10 patients referred to hospital following vomiting and diarrhoea after ingestion of mycoprotein had a mycoprotein skin-prick test weal > or = 2 mm but none had a significantly raised RAST. These largely negative results are important and reassuring because consumption of the product in the U.K. is now widespread and increasing.

Adult↗
PubMed1992

Hydrogen peroxide lethality is associated with a decreased ability to maintain positive DNA supercoiling.

Hydrogen peroxide is more toxic to mammalian cells at 37 degrees C than 0 degree C at all concentrations studied. Histone-free nuclei (nucleoids) extracted from treated cells have a reduced ability to maintain positive DNA supercoiling, with the maximum effect at the higher temperature. Prior exposure of cells to sodium ascorbate at 0 degree C increased both toxicity and the inhibition of nuclear supercoil rewinding. After exposure at 0 degrees C, normal levels of supercoiling returned with both a fast and a slow component, kinetics characteristic of DNA single-strand break repair; the fast component was eliminated when cells were exposed at 37 degrees C due to in situ rejoining. At least a portion of the lethal lesions induced by hydrogen peroxide are DNA double-strand breaks (dsb) because the dsb repair-deficient mutant, xrs-5, is approximately two to three times more sensitive than wild-type cells over the initial portion of the survival curve. However, the increased toxicity found after exposure at 37 degrees C is observed equally in both cell lines, indicating that temperature-dependent cell killing is not directly linked to DNA dsb. It is suggested that cell killing at 37 degrees C is mediated through two linked processes. First, hydrogen peroxide may disrupt cation-stabilized nuclear supercoiling by direct ion oxidation. Second, as a part of the oxidation process, hydrogen peroxide will produce potentially cytotoxic free radicals close to the DNA-linked metal site, limited in extent only by the presence of chemicals capable of reducing metal ions prior to reoxidation.

Animals↗
PubMed1992

The addition of muscle to the lateral arm and radial forearm flaps for wound coverage.

There is good evidence of the benefit of transferring vascularized muscle into wounds that are contaminated or have been infected previously. This benefit particularly applies in cavities around bones and joints. We present two patients in whom the inclusion of a portion of muscle in the lateral arm and radial forearm flaps allowed the effective combination of good-quality skin cover with the properties of vascularized muscle.

Adult↗
PubMed1992

Comparison of allergic responses to dust mites in U.K. bakery workers and Swedish farmers.

The IgE RAST response to Dermatophagoides pteronyssinus and four storage mites (Lepidoglyphus destructor, Tyrophagus putrescentiae, Glycyphaghus domesticus, and Acarus siro) was examined in 251 U.K. bakery workers and compared with that previously found in 440 Swedish farmers. Storage mites are found commonly in stored hay and grain so both these groups potentially encounter them in their work. In neither group of workers was a positive RAST (greater than or equal to 0.35 PRU) to D. pteronyssinus correlated with a positive RAST to a single storage mite. As in the Swedish farmers, significant though not strong correlations were found in the U.K. bakers between positive RAST responses to G. domesticus and L. destructor and to T. putrescentiae and L. destructor (P less than 0.05). Homologous and heterologous RAST inhibition studies showed there was low cross-reactivity between storage mites and D. pteronyssinus. L. destructor showed the least inhibition by the other antigens, suggesting it possessed the fewest common allergens. The most important difference in the IgE responses between the two groups was the much higher response to D. pteronyssinus in the U.K. bakers, which was not found in the Swedish farmers whose highest IgE response was to L. destructor.

Agriculture↗