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Biomedical subjects

M Adams

Publications and source records attributed to M Adams.

At least 127 records · Page 7Linked to original sources
PubMed1996

Impaired vascular reactivity in insulin-dependent diabetes mellitus is related to disease duration and low density lipoprotein cholesterol levels.

OBJECTIVES: This study sought to examine whether endothelial function is impaired in the large vessels of asymptomatic young adults with insulin-dependent diabetes and whether endothelial dysfunction is related to duration or control of diabetes, small-vessel disease or other vascular risk factors. BACKGROUND: Endothelial dysfunction is an early event in atherosclerosis, and large-vessel atherosclerotic disease is the major cause of morbidity and mortality in diabetes. METHODS: We compared 80 young adults with insulin-dependent diabetes (15 to 40 years old; mean [+/- SD] diabetes duration 13 +/- 8 years) with 80 matched nondiabetic control subjects. Using high resolution vascular ultrasound, we measured brachial artery responses to reactive hyperemia (with increased flow causing endothelium-dependent dilation) and sublingual glyceryltrinitrate (causing endothelium-independent dilation). RESULTS: Flow-mediated dilation was significantly impaired in diabetic subjects (5.0 +/- 3.7% vs. 9.3 +/- 3.8% in control subjects, p < 0.001). The ratio of flow-mediated dilation to glyceryltrinitrate-induced dilation was significantly lower in the diabetic subjects (p < 0.02), indicating that impaired dilation to increased flow was out of proportion to the impairment of the glyceryltrinitrate response in these subjects (15.6 +/- 5.6% vs. 19.7 +/- 6.6% in control subjects, p < 0.001). On multivariate analysis, flow-mediated dilation was inversely related to both duration of diabetes (r = -0.26, p < 0.05) and low density lipoprotein (LDL) cholesterol levels (r = -0.38, p < 0.005). CONCLUSIONS: Vascular reactivity is impaired in the systemic arteries of asymptomatic young adults with insulin-dependent diabetes and may represent early large-vessel disease. The degree of impairment is related to the duration of diabetes, and these patients appear particularly vulnerable to damage from LDL cholesterol, even at levels considered acceptable in nondiabetic subjects.

Adolescent↗
PubMed1996

Low-molecular-weight heparin in pediatric patients with thrombotic disease: a dose finding study.

OBJECTIVE: To compare low-molecular-weight preparations of heparin (LMWH) with standard heparin in children requiring anticoagulant treatment for thromboembolic disease. METHODS: We treated 25 children who required heparin, but were at significant risk of bleeding, with LMWH (enoxaparin, Rhone-Poulenc Rorer). The median age was 4 years (range, newborn to 17 years), with nine infants less than 2 months of age. Fourteen children had a deep vein thrombosis or pulmonary embolism, nine had thrombotic complications in the central nervous system, and two had complex congenital heart disease, for which they received prophylaxis at a lower dosage (0.5 mg/kg given subcutaneously twice a day). The remaining 23 children received an initial dose of 1 mg/kg, every 12 hours subcutaneously, with subsequent doses adjusted to achieve a 4-hour anti-factor Xa level between 0.5 and 1.0 unit/ml. RESULTS: Newborn infants had increased dose requirements; an average of 1.60 units/kg was required to achieve therapeutic heparin levels. For the remaining children, the initial dose of 1.0 mg/kg was sufficient. After the initial dose adjustment, LMWH was administered with twice-weekly monitoring. The median duration of therapy with LMWH was 14 days. Two children with previously documented gastrointestinal ulcers bled and required transfusion therapy. Therapy with LMWH was continued without further events. There were no new thrombotic events during the treatment with LMWH. The cost of administering LMWH compared with heparin was reduced by 30% because of decreased laboratory monitoring, blood sampling times, intravenous starts, and nursing time. Needle punctures were reduced with LMWH therapy by the placement of a subcutaneous catheter. CONCLUSION: These results provide the basis for a randomized, controlled trial comparing LMWH with standard heparin in pediatric patients.

Adolescent↗
PubMed1996

In vitro hydrogen production by glucose dehydrogenase and hydrogenase.

A new in vitro enzymatic pathway for the generation of molecular hydrogen from glucose has been demonstrated. The reaction is based on the oxidation of glucose by Thermoplasma acidophilum glucose dehydrogenase with the concomitant oxidation of NADPH by Pyrococcus furiosus hydrogenase. Stoichiometric yields of hydrogen were produced from glucose with the continuous recycling of cofactor. This simple system may provide a method for the biological production of hydrogen from renewable sources. In addition, the other product of this reaction, gluconic acid, is a high-value chemical commodity.

Cloning, Molecular↗
PubMed1996

Genetic analysis of thermolabile methylenetetrahydrofolate reductase as a risk factor for myocardial infarction.

Hyperhomocyst(e)inemia is associated with an increased risk of coronary artery disease and myocardial infarction. Both genetic and environmental factors influence the plasma level of homocysteine. One of the metabolic pathways for homocysteine involves the enzyme methylenetetrahydrofolate reductase (MTHFR), which regulates the conversion of homocysteine to methionine. A thermolabile variant of MTHFR is associated with reduced enzyme activity and increased plasma homocysteine levels. Recently, the cause of this variant of MTFHR has been identified as a single base change altering an alanine to a valine residue in the protein. Using a PCR-based assay to distinguish the normal and thermolabile variants of MTHFR in this study, we investigated whether the thermolabile variant is a genetic risk factor for myocardial infarction. In a study of 532 subjects (310 myocardial infarction patients and 222 population-based controls), we found no difference in either MTHFR genotype distribution (p = 0.57) or allele frequencies (p = 0.68) between cases and controls. The allele frequencies of the thermolabile variant were 0.34 and 0.35 in cases and controls, respectively. The age- and sex-stratified odds ratio for risk of myocardial infarction associated with homozygosity for the thermolabile variant was 0.85 (95% CI 0.50-1.50, p = 0.57) and that with carriage of the thermolabile allele was 1.06 (95% CI 0.73-1.52, p = 0.76). The odds ratios remained non-significant when restricted to young subjects (< 60 years) or males, and were not influenced by several other risk factors for myocardial infarction considered either singly or in combination. Interestingly, in both cases and controls, there was a trend toward a higher prevalence of hypertension in subjects carrying the normal allele, although as this is a post-hoc finding it needs to be interpreted with caution. The thermolabile variant of MTHFR is not a major risk factor for myocardial infarction and is unlikely to explain a significant proportion of the reported association of hyperhomocyst(e)inemia with coronary artery disease.

Adult↗
PubMed1996

Diagnostic utility of endocrine and neuroimaging screening tests in first-onset adolescent psychosis.

OBJECTIVE: To determine the diagnostic utility of endocrine and neuroimaging screening tests in first-onset adolescent psychosis. METHOD: 111 consecutively admitted adolescents (aged 13 through 19 years) who presented with a first-onset psychosis and who had an unremarkable medical history and normal physical examination were given a battery of endocrine and neuroimaging screening tests. Diagnostic utility of a screening test was defined as an abnormal result (a positive test) that either led to a previously unknown or unsuspected medical diagnosis or played an important role in the clinical care of the patient. RESULTS: 15.4% of the endocrine screening tests and 11.0% of the neuroimaging screening tests were identified as positive. However, no endocrine and no neuroimaging tests met criteria for diagnostic utility. The direct cost of this screening battery was $636.95 per patient. CONCLUSION: Routine endocrine and neuroimaging screening tests in first-onset adolescent psychosis provide no diagnostic utility and are not cost-effective. Selective use of appropriate endocrine and neuroimaging diagnostic tests in populations with symptoms suggestive of organic disorders should replace routine screening procedures.

Adolescent↗
PubMed1996

The association among negative life events, perceived problem solving alternatives, depression, and suicidal ideation in adolescent psychiatric patients.

Previous research demonstrated that the combination of a negative life event (NLE) and less constructive perceived problem solving alternatives (PPSAs) was associated with more depression in unselected adolescents. This study investigated these variables and their association with suicidal ideation in 80 adolescent psychiatric patients. Depressed patients reported more negative effects from NLEs, particularly family conflict and academic failure, and were more likely to consider self-destructive PPSAs than their less depressed counterparts. The impacts of NLEs and negative PPSAs were independently associated with both depression and suicidal ideation for this population, in contrast to non-patients.

Adolescent↗
PubMed1996

Repeated intra-ventral tegmental area administration of SKF-38393 induces behavioral and neurochemical sensitization to a subsequent cocaine challenge.

To assess the role of dopamine receptor subtypes in the initiation of behavioral sensitization to cocaine, the partial D1 agonist SKF-38393 (0.01-1.0 microgram/side), the D2/3 agonist quinpirole (0.1-1.0 microgram/side) or saline was infused once daily over 3 days into either the ventral tegmental area (VTA) or the nucleus accumbens shell. Relative to saline controls, intra-VTA SKF-38393 administration did not influence behavior during the treatment regimen, whereas the higher dose of quinpirole produced a significant suppression of locomotor activity after the third daily administration. Infusion of 1.0 microgram/side SKF-38393 into the nucleus accumbens shell produced marked behavioral hyperactivity after both the first and last daily infusions, with no significant difference between the behavioral responses on these days. In contrast, quinpirole did not influence behavior after its infusion into the nucleus accumbens shell. Two weeks after the last daily intracranial drug infusion, all animals were administered cocaine (15 mg/kg, i.p.) and behavioral activity was monitored. The repeated administration of SKF-38393 into the VTA resulted in sensitization to the locomotor-activating effects of cocaine. No other drug pretreatment influenced the cocaine-induced behavioral response. To determine whether repeated D1 agonist administration influenced dopamine release in the nucleus accumbens shell, in vivo microdialysis was performed in this structure after three daily intra-VTA infusions of saline or 0.1 microgram/side SKF-38393. The increase in dopamine levels in the nucleus accumbens shell induced by cocaine was significantly greater among rats pretreated with repeated SKF-38393 administration. Taken together, these results indicate that the repeated intra-VTA administration of a D1 agonist mimics the sensitization process produced by repeated cocaine administration.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1996

The role of presenilin 1 in the genetics of Alzheimer's disease.

Approximately 75% of AD patients have an onset of the disease after the age of 60 years, and 60% of AD patients have no family history of the disease. Some cases of EOAD are clearly inherited in an autosomal-dominant manner. The beta APP gene on chromosome 21, the PS-1 gene on chromosome 14, and the PS-2 gene on chromosome 1 have all been characterized as genes in which mutations lead to familial EOAD. For LOAD, the work on ApoE indicates that the epsilon 4 allele is a risk factor for developing AD. However, 35-50% of all AD patients do not have an epsilon 4 allele. Other loci contributing to LOAD remain to be mapped and characterized. As in other complex disorders, these additional loci may involve genetic interactions with the known AD loci. Identification of all susceptibility loci for AD is a major goal in resolving the pathogenesis of AD.

Alternative Splicing↗