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Biomedical subjects

R W Evans

Publications and source records attributed to R W Evans.

At least 19 recordsLinked to original sources

The prospective association between adiponectin and coronary artery disease among individuals with type 1 diabetes. The Pittsburgh Epidemiology of Diabetes Complications Study.

AIMS/HYPOTHESIS: Recent findings suggest the potential involvement of adiponectin in obesity, diabetes and cardiovascular disease. We assessed the prospective association between adiponectin concentration and coronary artery disease in individuals with type 1 diabetes. METHODS: Participants were identified from the Pittsburgh Epidemiology of Diabetes Complications cohort, a prospective follow-up study of childhood-onset type 1 diabetes. At baseline, subjects had a mean age of 28 years, and a mean diabetes duration of 19 years. Cases (determined by physician-diagnosed angina, confirmed myocardial infraction, stenosis >or=50%, ischemic ECG or revascularization) were matched to the control subjects with respect to sex, age and diabetes duration. Samples and risk factors for analyses were identified from the earliest exam prior to incidence in cases. Sera and information on all covariates were available for 28 cases and 34 control subjects. Proportional hazards models were constructed including matching variables. RESULTS: Compared with those in men, adiponectin concentrations were elevated in females (p=0.009) and among individuals with macroalbuminuria (p=0.04). In multivariable analyses (adjusting for standard risk factors as well as lipoprotein measurements determined by nuclear magnetic resonance spectroscopy, E-selectin or antioxidants), adiponectin inversely predicted the incidence of coronary artery disease (hazard ratio=0.37 per 1 SD increase, 95% CI 0.19-0.73, p=0.004). CONCLUSIONS/INTERPRETATION: The results suggest that increased adiponectin concentration is prospectively associated with a lower risk of coronary artery disease type 1 diabetes. The potential of adiponectin determination as a useful marker of, and potential therapeutic target for, coronary artery disease prevention in type 1 diabetes should be further explored.

Adiponectin↗

The plug domain of a neisserial TonB-dependent transporter retains structural integrity in the absence of its transmembrane beta-barrel.

Transferrin binding protein A (TbpA) is a TonB-dependent outer membrane protein expressed by pathogenic bacteria for iron acquisition from human transferrin. The N-terminal 160 residues (plug domain) of TbpA were overexpressed in both the periplasm and cytoplasm of Escherichia coli. We found this domain to be soluble and monodisperse in solution, exhibiting secondary structure elements found in plug domains of structurally characterized TonB-dependent transporters. Although the TbpA plug domain is apparently correctly folded, we were not able to observe an interaction with human transferrin by isothermal titration calorimetry or nitrocellulose binding assays. These experiments suggest that the plug domain may fold independently of the beta-barrel, but extracellular loops of the beta-barrel are required for ligand binding.

Animals↗

Lipoprotein subclass measurements by nuclear magnetic resonance spectroscopy improve the prediction of coronary artery disease in Type 1 diabetes. A prospective report from the Pittsburgh Epidemiology of Diabetes Complications Study.

AIM/HYPOTHESIS: To examine whether nuclear magnetic resonance lipoprotein spectroscopy improves the prediction of coronary artery disease in patients with Type 1 diabetes, independently of conventional lipid and other risk factors. METHODS: A prospective nested case-control design of subjects with childhood onset Type 1 diabetes from the Pittsburgh Epidemiology of Diabetes Complications Study was used. 59 controls were age-, sex- and duration-matched to 59 incident cases of coronary artery disease (fatal or non-fatal myocardial infarction, angina, coronary stenosis >50%) occurring during 10 years of follow-up. Lipid mass and particle concentrations of VLDL, LDL, and HDL subclasses, grouped into three size categories (large, medium, and small), were assessed prior to event with nuclear magnetic resonance spectroscopy. RESULTS: Univariate analyses showed that both lipid mass and particle concentrations of all three VLDL subclasses, small LDL, medium LDL, and medium HDL were increased in CAD cases compared to controls, while large HDL was decreased. Mean LDL and HDL particle sizes were lower in cases. In multivariate models using conventional lipid and non-lipid risk factors, triglycerides and overt nephropathy were the strongest predictors of CAD. Nuclear magnetic resonance measures further improved the prediction, i.e. large HDL particle concentration (OR=0.43, p=0.030), medium HDL mass (OR=3.79, p=0.026) and total VLDL particle concentration (OR=2.33, p=0.033). CONCLUSION/INTERPRETATION: While these results underscore the importance of triglycerides and overt nephropathy in CAD risk in Type 1 diabetic patients, they also suggest that nuclear magnetic resonance lipoprotein spectroscopy could further refine its prediction and show novel findings concerning HDL subclasses.

Adult↗

Maternal and fetal amino acid concentrations and fetal outcomes during pre-eclampsia.

The pathophysiology of pre-eclampsia is contested, but one hypothesis indicates that it is a heterogeneous condition in which only a subset of affected women bear small-for-gestational age (SGA) babies. In intrauterine growth-restricted (IUGR) infants, placental transport of amino acids is diminished and the resulting decrease in cord-blood amino acid concentrations is thought to contribute to their stunted growth. In contrast, the metabolic syndrome (dyslipidaemia, hyperinsulinaemia, hyperglycaemia, hypertension and obesity) which is associated with high amino acid concentrations is more prevalent in women with pre-eclampsia. The focus of this study was to compare maternal and fetal serum amino acid concentrations during normal pregnancy and pre-eclampsia and to evaluate the associations between the amino acid concentrations and fetal growth. The results indicate that maternal and cord-blood amino acid concentrations were significantly higher in women with pre-eclampsia compared with normal pregnant women and the concentrations were inversely associated with measures of infant growth. Maternal and cord-blood amino acid concentrations were also significantly higher in pre-eclamptic mothers with SGA infants compared with pre-eclamptic mothers whose babies were not SGA. These data indicate that, in contrast to IUGR, pre-eclampsia is associated with enhanced placental amino acid transport or reduced fetal amino acid utilization. Furthermore, the data are consistent with the hypothesis that pre-eclampsia is a heterogeneous disease associated with the metabolic syndrome.

Adult↗

Transferrin-mediated iron acquisition by pathogenic Neisseria.

The pathogenic Neisseria have a siderophore-independent iron-uptake system reliant on a direct interaction between the bacterial cell and transferrin. In the meningococcus this uptake system is dependent on two surface-exposed transferrin-binding proteins. This short account will review our current knowledge of the transferrin-mediated iron-acquisition system of pathogenic Neisseria.

Cell Membrane↗

Caries, bitewings, and treatment decisions.

BACKGROUND: The most common adjunct to the visual and tactile clinical examination for dental caries is the bitewing radiograph. The aim of this study was to report on treatment planning decisions made by Victorian dentists when given a range of predetermined radiographic scenarios. METHODS: A postal survey was conducted to obtain data from 550 dentists selected systematically (every fourth dentist) from the register of the Dental Board of Victoria (1996). RESULTS: The survey response rate was 64 per cent. Fifty per cent of responding dentists selected an operative intervention for radiographic lesions confined to enamel. CONCLUSIONS: A review of current dental literature does not support this approach because a large proportion of proximal tooth surfaces that have associated radiolucencies confined to enamel are not cavitated. This study supports the need for continuing education programmes on the management of dental caries; such programmes should follow an evidence-based model.

Attitude of Health Personnel↗

Diagnostic testing for headache.

A careful and complete headache history supplemented by a neurologic and general physical examination, as appropriate, enables the astute physician to diagnose most headaches correctly without diagnostic testing. When indications are present (see Box 1), some headache patients with a normal physical examination require testing even though the yield may be low. Failure to test may result in misdiagnosis of potentially serious and life-threatening causes of headaches, such as brain tumors, chronic meningitis, SAH, and temporal arteritis.

Acute Disease↗

Topics in migraine management: a survey of headache specialists highlights some controversies.

The authors' Survey of headache specialists highlights a number of controversial issues in migraine management including the following: acute treatment, focusing on use of triptans, and preventative medications; treatment of migraine with prolonged aura and basilar migraine; and the use of oral contraceptives in migraine. Interestingly, the prevalence of migraine among the headache specialists themselves is much higher than in the general population. Although triptans have revolutionized the acute treatment of migraine, treatment is still problematic for the sizable percentages of patients with an incomplete or no response and recurrence of headache. Triptans are generally very safe when the physician, aware of the potential for coronary artery vasoconstriction, appropriately screens patients before and during their use. Serotonin syndrome as a complication of triptan use is quite rare. Although there is no definite evidence of teratogenesis, triptans should not be taken during pregnancy unless the potential benefit justifies the potential risk to the fetus. Caution is also advised when using a triptan during breastfeeding. The United States Headache Consortium parameters, which consider indications for preventative treatment and propose general principles of management, are reviewed. Unfortunately, the experience of many migraineurs with preventative medications is less than satisfactory because of side effects or lack of efficacy. Treatment of both migraine with prolonged aura and basilar migraine is anecdotally based. Many headache specialists do not use beta blockers for prevention for those with prolonged aura and basilar migraines because of concerns over the potential limitation of compensatory vasodilatory capacitance. There are seven case reports in the literature of an association between stroke and the use of beta blockers in migraineurs. Prevention using divalproex sodium and verapamil is favored by many headache specialists. Triptans are contraindicated in the treatment of patients with hemiplegic or basilar migraine because of concern over the potential for cerebral vasoconstriction. The frequency of migraine is usually unchanged with the use of oral contraceptives although, occasionally, migraine may occur for the first time or increase in frequency. Studies have produced conflicting results as to whether low-dose estrogen oral contraception increases the risk of stroke. Migraine alone increases the risk of stroke, at least in women under the age of 45 years. Most women with migraine without aura and migraine with visual aura lasting less than 1 hour can safely use low-dose estrogen oral contraceptives when there are no other contraindications. Those with aura symptoms such as hemiparesis or dysphasia or prolonged focal neurologic symptoms and signs lasting more than 1 hour should avoid starting low-dose estrogen oral contraceptives and stop the medication if they are already taking it.

Contraceptives, Oral↗

Prospective association of lipoprotein(a) concentrations and apo(a) size with coronary heart disease among men in the Multiple Risk Factor Intervention Trial.

In this nested case-control study, lipoprotein (a) [Lp(a)] concentrations and apo(a) isoform size were measured in serum samples obtained from men participating in the prospective Multiple Risk Factor Intervention Trial (MRFIT). Serum from men aged 35 to 57 years and stored for up to 20 years were analyzed for Lp(a) levels (n=736) and isoform size (n=487), respectively. Cases involved nonfatal myocardial infarctions (MI; n=98), documented during the active phase of the study that ended on February 28, 1982 and coronary heart disease (CHD) deaths (n=148) monitored through 1990. Median Lp(a) levels did not differ between cases and controls and mean apo(a) size did not vary between cases and controls in the entire study population. When adjusted for age and Lp(a) concentration, logistic regression analysis indicated that small apo(a) isoforms were associated with CHD deaths among smokers (OR 3.31; 95% CI 1.07-10.28).

Adult↗