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Biomedical subjects

D Thomas

Publications and source records attributed to D Thomas.

At least 541 records · Page 30Linked to original sources

Risk assessment for aflatoxin B1: a modeling approach.

The data generated by Yeh et al. on hepatitis B virus, aflatoxin, and primary hepatocellular carcinoma (PHC) in Southern Guangxi, China was used to evaluate the cancer potency of aflatoxin. We examined model fits to these data to explore whether hepatitis B virus (HBV) and aflatoxin intake act together to affect PHC rates in an additive, multiplicative, or interactive fashion, using relative and excess risk model forms. Purely additive models fit the data poorly. Fitted models were checked for plausibility by comparing predictions for the U.S. population with actual PHC incidence rates in the United States, and parameter stability was evaluated. The multiplicative relative risk and the interactive excess risk models provided satisfactory descriptions of the Yeh et al. data and U.S. PHC rates. There is about an eight-fold difference in the potency estimate for aflatoxin under the multiplicative relative risk (5.7 (mg/kg-day)-1) and interactive excess risk models (45.6 mg/kg-day)-1). The assumptions and limitations of the various models are discussed.

Aflatoxin B1↗

Comparison of skin changes induced on mice by either group A type 12 or group G streptococci.

Adult Swiss webster mice were injected with 3 x 10(6) colony-forming units (cfu) of group G or 2.5 x 10(6) cfu of group A streptococci at intradermal injection sites on the right and left paralumbar areas of the back. The mice were sacrificed at intervals between 4 hours and 14 days post-injection (p.i.) and full thickness biopsies of skin 10 mm in diameter encompassing the sites of injection were taken. One tissue specimen was homogenized in PBS and plated to determine the number of cfu, while another was used for histopathological studies. The number of viable group A and group G streptococci in the tissue increased to 3 x 10(9) cfu by 96 hours p.i.: after 192 hours p.i. the group A cells had declined to 2.7 x 10(6) cfu compared to 1.1 x 10(8) cfu for group G cells. No streptococci of either group were detected at 336 hours (14 days p.i.). Gross edematous lesions induced by either streptococcus group were evident on all animals at 24 hours (p.i.). Group G streptococci lesions were larger and persisted longer than lesions induced by group A. Histological examination consistently revealed more inflammation and necrosis in tissue sections from mice injected with group G streptococci.

Animals↗

The role of endogenous angiotensin II in the regulation of renal haemodynamics and proximal fluid reabsorption in the rat.

1. The influence of endogenous angiotensin II (AII) on renal haemodynamics and tubular function was examined by clearance and micropuncture methods in anaesthetized rats during AII receptor blockade with the non-peptide antagonist DuP 753 (50 micrograms kg-1 min-1 i.v.). 2. Mean arterial pressure was reduced slightly (-5 +/- 2 mmHg) while filtration fraction and glomerular filtration rate rose by 30% without changes in renal plasma flow (RPF) or renal vascular resistance (RVR). 3. Fractional proximal fluid reabsorption (calculated from lithium clearance) fell from 73 to 64% (P < 0.01) and fractional distal sodium reabsorption decreased from 98 to 94% (P < 0.01). 4. Urine flow rate more than doubled, sodium output increased 4-fold and plasma renin concentration rose 8-fold while potassium excretion remained unchanged. 5. Proximal tubular fluid reabsorption (Jv) as measured by shrinking split-droplet micropuncture decreased by 21% (P < 0.01) during infusion of DuP 753 compared with 22.5% (P < 0.01) during converting enzyme inhibition by enalaprilat (MK422). 6. Responses to DuP 753 were similar to those previously documented with converting enzyme inhibitors except that DuP 753 failed to raise RPF. It is concluded that generation of intrarenal vasodilator paracrines has confounded conclusions about the renal action of converting enzyme inhibitors and we propose that in anaesthetized rats, endogenous angiotensin II (AII) has its major renal influences on glomerular filtration and proximal fluid reabsorption with little effect on renal vascular resistance.

Absorption↗

MET4, a leucine zipper protein, and centromere-binding factor 1 are both required for transcriptional activation of sulfur metabolism in Saccharomyces cerevisiae.

Inactivation of the centromere-binding factor 1 (CBF1) gene results in yeast strains that require methionine for growth. This auxotrophy is due to the inability of such strains to concentrate and assimilate sulfate from the medium. Northern (RNA) blot experiments reveal that the CBF1 protein is required for full induction of MET25 and MET16 gene transcription. However, we show that induction of the sulfate assimilation pathway is not achieved solely by CBF1. This induction also requires the integrity of a positive trans-acting factor, encoded by the MET4 gene. The MET4 gene was cloned, and its sequence reveals that it encodes a protein related to the family of the bZIP transcriptional activators. Evidence that MET4 is a transcriptional activator was provided by demonstrating that DNA-bound LexA-MET4 fusion proteins stimulate expression of a nearby promoter. The use of LexA-MET4 fusion proteins also reveals that the leucine zipper of MET4 is required for the recognition of the MET25 promoter. Moreover, an 18-bp fragment of the MET25 5' upstream region was found to confer S-adenosylmethionine-dependent regulation of a fusion gene. This regulation was shown to depend on both MET4 and CBF1. The obtained results suggest that the binding of CBF1 to its cognate sequences increases the ability of MET4 to stimulate transcription of the MET genes.

Amino Acid Sequence↗

Computerised infrared thermography and isotopic bone scanning in tennis elbow.

Thirty five cases of tennis elbow (17 unilateral, nine bilateral) were studied with infrared thermography and isotopic bone scanning. A hot focus was visualised in 16 of 17 cases of unilateral tennis elbow (94%) and in all nine cases of bilateral tennis elbow (100%) on infrared thermography, and abnormal increased epicondylar activity seen in 12 of 17 (71%) and eight of 18 (44%) cases respectively with isotopic bone scanning. Unilateral visual cooling (somatosympathetic responses) occurred in seven of 13 cases of unilateral tennis elbow (54%) with infrared thermography, and reduced perfusion in seven of 12 (58%) of similar cases with blood pool isotopic bone scanning. Computerised temperature assessments showed statistically significant side to side temperature differences when 17 active tennis elbows were compared with the opposite normal elbows for spot temperatures, proximal and distal forearm gradients. Similar temperature assessments in 18 bilateral tennis elbows compared with 17 normal elbows showed significant temperature differences for elbow spot temperatures and distal forearm gradients, but not for proximal gradients.

Adult↗

The effect of hemiplegia on blood pressure measurement in the elderly.

The blood pressure in both arms of 103 unselected hemiplegic patients was measured using a random-zero sphygmomanometer. Although for the whole sample the mean blood pressure in the paretic and unaffected arm was similar, a significant difference was found when the patients were subdivided according to the tone of the arm. The blood pressure was higher in paretic arms of patients with a spastic stroke and lower in the affected arm if the tone was flaccid. No other characteristics were associated with significant blood pressure differences, so that the findings appear to be directly related to changes in muscle tone. After a stroke the blood pressure should always be measured in the unaffected arm because changes in tone make measurements unreliable.

Aged↗

Myocardial viability in patients with Q wave myocardial infarction and no residual ischemia.

BACKGROUND: Coronary revascularization in patients with persistent angina after myocardial infarction reduces the incidence of recurrent angina pectoris and myocardial infarction and improves left ventricular function. The results of revascularization after a Q wave myocardial infarction when there is no residual ischemia may depend on myocardial viability. METHODS AND RESULTS: To determine whether there was viable myocardium in the infarct area in the absence of clinical and scintigraphic evidence of myocardial ischemia, 15 asymptomatic patients with a Q wave myocardial infarction, no redistribution on stress 201Tl test, and single-vessel disease (greater than 70% stenosis) with persistent anterograde blood flow were randomized to percutaneous transluminal coronary artery angioplasty (PTCA) or conservative medical treatment. After 2 months of follow-up, mean coronary blood flow measured by Doppler catheter in the infarct-related artery was higher in the PTCA treatment group (33 +/- 6 ml/min, n = 8) than in the conservative treatment group (16 +/- 4 ml/min, n = 7; p less than 0.05 between groups). The 201Tl pathological-to-normal ratios measured on postexercise images did not change in patients treated conservatively during the follow-up period (delta = +1.1 +/- 2.2%; NS from baseline) but increased significantly in patients treated by PTCA (delta = +8.5 +/- 2.3%; p less than 0.01 from baseline; p less than 0.05 between groups). Segmental wall motion improved on left ventricular angiography 2 months after PTCA (delta = +11.5 +/- 2.2%; p less than 0.001 from baseline) significantly more than in the conservative treatment group (delta = +4.1 +/- 1.4%; p less than 0.05 between both groups). Improvements of 201Tl ratios and segmental wall motion indexes correlated significantly (r = 0.73, p = 0.002). The mild improvement of global left ventricular ejection fraction measured in the PTCA treatment group did not differ significantly from changes in the conservative treatment group. CONCLUSIONS: Successful angioplasty of the stenotic infarct artery in patients with a Q wave myocardial infarction and no residual ischemia improved coronary flow, 201Tl uptake in the infarct area, and regional wall motion. Therefore, myocardial viability may last several weeks, as long as residual blood flow persists in the infarct-related artery. Optimal assessment of viability by imaging techniques should identify patients who are most likely to benefit from revascularization.

Angioplasty, Balloon, Coronary↗

Thermography.

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Humans↗

Tuberous sclerosis with gingival overgrowth.

A case of tuberous sclerosis with gingival overgrowth is presented. A brief literature review and diagnostic criteria of tuberous sclerosis are discussed. The patient had a full-mouth gingivectomy with frequent post-operative maintenance visits. After 6 months, the overgrowth in conjunction with the tuberous sclerosis returned.

Adult↗

Empirical Bayes methods for testing associations with large numbers of candidate genes in the presence of environmental risk factors, with applications to HLA associations in IDDM.

Standard regression models for disease incidence data can be used to test for associations between a disease and measured genetic and environmental factors and their interactions. Complications arise when the gene is not observed, requiring segregation and linkage analysis approaches, or when the candidate gene(s) are found to be highly polymorphic, as in the HLA region. We propose a Bayesian approach to the latter problem, in which the log relative risks for all alleles at a given locus are taken to be independent and exchangeable, assuming there is no preferential zygotic assortment and negligible recombination. Multi-locus problems can be addressed either by adding exchangeable interaction terms or by adopting a multivariate prior for haplotype effects. Some simulations based on our current work on family studies of IDDM are discussed.

Alleles↗

[Blood cholesterol and mortality].

Mortality rates vary with serum cholesterol levels: the causal nature of this relationship is studied by prospective studies (analysis of associations) and unifactorial primary prevention trials (experimentation to determine causality). In prospective studies all cause mortality is often increased at low and high cholesterol levels because of the inverse relationships of this factor with cardiovascular mortality (positive) and non-cardiovascular mortality (negative). Coronary death increases proportionally to serum cholesterol levels in all populations, including those with low cholesterol levels, in both sexes and at all ages. The relationship with cerebrovascular mortality seems to depend on the clinical feature: increased mortality rate due to cerebral haemorrhage in patients with low serum cholesterol and a positive correlation with cerebral thrombosis. Mortality due to cancers is generally negatively correlated to serum cholesterol levels with a significant increase in mortality in patients with a low serum cholesterol. This relationship often becomes less significant as the time between measurement and death increases. Mortality due to violent causes is not usually related to serum cholesterol. The multitude of possible causes of confusion makes any causal interpretation of data illusory. Experimentation by unifactorial primary prevention trials is essential for any etiological research but none of the trials performed to date was designed to analyse the effect of lowering serum cholesterol on global or coronary mortality.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

[Relations between HDL-cholesterol and cardiovascular diseases].

Many retrospective and prospective epidemiological studies have demonstrated an inverse relationship between HDL-cholesterol and coronary risk. The predictive value of HDL-cholesterol is observed both in asymptomatic subjects and those with a primary vascular event. Several genetic abnormalities may be responsible for low HDL cholesterol (under 100 mg/dl or 0.26 mmol/l) or for a less severe hypoalphalipoproteinaemia. Despite some very low values, these rare causes of HDL deficiency are not all atherogenic and serve to emphasize the complexity of HDL metabolism. The protective role of HDL is explained by a number of mechanisms such as their role in the reverse transport from the peripheral tissues to the liver, their anti-oxidant effect and the increase in prostacyclin levels. The correction of isolated hypoalphalipoproteinaemia by drugs is controversial, but associated hyperlipidaemic states would be an indication to use drugs which increase the HDl-cholesterol the most.

Apolipoprotein A-I↗

[Role of triglycerides in cardiovascular diseases].

The role of triglycerides in cardiovascular disease is a controversial subject. Despite differences of opinion, present data allow a certain number of conclusions to be drawn. Hyperchylomicronemia is not associated with atherosclerosis, whereas type III hyperlipidemia is very atherogenic. These two abnormalities are, however, rare, and the majority of hypertriglyceridemias are, in practice, associated with increased very low density lipoproteins. Many epidemiological trials do not identify hypertriglyceridemia as an independent risk factor when the cholesterol and, in particular, the HDL cholesterol levels, are taken into consideration. Nevertheless, these results must be interpreted with caution as hypertriglyceridemia represents a very heterogeneous entity which is closely related to many factors which affect coronary risk (hypertension, insulin resistance, sedentarity, and even tobacco consumption). Therefore, hypertriglyceridemia and hypo-HDL-emia may be the result of the same primary abnormality; as the HDL-cholesterol level is more stable, it is the parameter which will be identified as a protective factor in epidemiological trials. The available data is insufficient to affirm that therapeutic lowering of triglycerides is accompanied by a reduced coronary risk because none of the large scale trials were designed to analyse this problem. Despite these epidemiological data, the measurement of serum triglyceride levels remains important in patients with hyperlipidemia.

Cholesterol, HDL↗

[Serum cholesterol and cancer. Is there a causal relationship?].

Several studies have reported an inverse relationship between serum cholesterol levels and the risk of cancer, especially of the colon (Seven Countries, Framingham, Chicago studies, London Whitehall Study, Paris prospective study, New Zealand Maori, Honolulu Heart Study, Hypertension Detection and Follow-Up Program, ...). For example, in the Multiple Risk Factor Intervention Trial (361 662 men), the global mortality graph was J-shaped, higher at either side of the 4.6-5.1 mmol/l value of serum cholesterol. This increased mortality with lower serum cholesterol levels was due to increased numbers of death from cancer. However, when the relationship is studied with respect to the time elapsed between the cholesterol measurement and death from cancer, the relative risk of death in the lowest decile with respect to the average of the following deciles, decreases with the period between measurement of the serum cholesterol and time of death. The negative relationship between serum cholesterol and death by cancer, very significant for deaths occurring within the first 5 years, disappeared almost completely for deaths occurring after 5 years. Other trials designed mainly to examine cardiovascular risk, and concerning smaller numbers, have not demonstrated this inverse relationship between serum cholesterol and cancer. This negative relationship between serum cholesterol and cancer must be acknowledged. It is weak and concerns mainly colonic cancer, especially in men in the elderly age groups. Several explanations have been put forward: influence of the combination of factors, competition of risk of death by other causes, chance, alteration of normal biological function of the cell membrane.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Is regression of atherosclerosis possible?].

Experimental studies have shown the regression of atherosclerosis in animals given a cholesterol-rich diet and then given a normal diet or hypolipidemic therapy. Despite favourable results of clinical trials of primary prevention modifying the lipid profile, the concept of atherosclerosis regression in man remains very controversial. The methodological approach is difficult: this is based on angiographic data and requires strict standardisation of angiographic views and reliable quantitative techniques of analysis which are available with image processing. Several methodologically acceptable clinical coronary studies have shown not only stabilisation but also regression of atherosclerotic lesions with reductions of about 25% in total cholesterol levels and of about 40% in LDL cholesterol levels. These reductions were obtained either by drugs as in CLAS (Cholesterol Lowering Atherosclerosis Study), FATS (Familial Atherosclerosis Treatment Study) and SCOR (Specialized Center of Research Intervention Trial), by profound modifications in dietary habits as in the Lifestyle Heart Trial, or by surgery (ileo-caecal bypass) as in POSCH (Program On the Surgical Control of the Hyperlipidemias). On the other hand, trials with non-lipid lowering drugs such as the calcium antagonists (INTACT, MHIS) have not shown significant regression of existing atherosclerotic lesions but only a decrease on the number of new lesions. The clinical benefits of these regression studies are difficult to demonstrate given the limited period of observation, relatively small population numbers and the fact that in some cases the subjects were asymptomatic. The decrease in the number of cardiovascular events therefore seems relatively modest and concerns essentially subjects who were symptomatic initially. The clinical repercussion of studies of prevention involving a single lipid factor is probably partially due to the reduction in progression and anatomical regression of the atherosclerotic plaque.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗