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Biomedical subjects

M D Brown

Publications and source records attributed to M D Brown.

At least 109 records · Page 6Linked to original sources
PubMed1997

Multiple metabolic abnormalities in normal glucose tolerant relatives of NIDDM families.

Non-diabetic first degree relatives of non-insulin-dependent diabetic (NIDDM) families are at increased risk of developing diabetes mellitus, and have been studied to identify early metabolic abnormalities. Hormone concentrations measured by specific enzyme immunoassays were assessed in non-diabetic relatives of North European extraction, and control subjects with no family history of diabetes were matched for age, sex and ethnicity. A 75-g oral glucose tolerance test was conducted and those with newly diagnosed NIDDM were excluded. Basal insulin resistance was determined by homeostasis model assessment (HOMA), and hepatic insulin clearance by C-peptide:insulin molar ratio. Relatives (n = 150) were heavier (BMI: p < 0.0001) than the control subjects (n = 152), and had an increased prevalence of impaired glucose tolerance (15 vs 3%, p < 0.01). The relatives had increased fasting proinsulin levels and decreased C-peptide levels following the glucose load, while insulin levels were increased at all time points. To examine whether the differences in hormone levels were secondary to the differences in glucose tolerance and adiposity, we studied 100 normal glucose tolerant relatives and control subjects pair-matched for age, sex, waist-hip ratio and BMI. The differences in proinsulin levels were no longer apparent. However, the relatives remained more insulin resistant, and had decreased C-peptide levels and C-peptide:insulin ratios at all time points. In conclusion, we have identified several metabolic abnormalities in the normal glucose tolerant relatives, and propose that the decreased hepatic insulin clearance helps to maintain normoglycaemia in the face of combined insulin resistance and decreased insulin secretion.

Adult↗
PubMed1997

Arterial blood pressure and forearm vascular conductance responses to sustained and rhythmic isometric exercise and arterial occlusion in trained rock climbers and untrained sedentary subjects.

Cardiovascular responses to sustained and rhythmic (5 s on, 2 s off) forearm isometric exercise to fatigue at 40% maximal voluntary contraction (MVC) and to a period of arterial occlusion were investigated in elite rock climbers (CLIMB) as a trained population compared to non-climbing sedentary subjects (SED). Blood pressure (BP), monitored continuously by Finapres, and forearm blood flow, by venous occlusion plethysmography, were measured and used to calculate vascular conductance. During sustained exercise, times to fatigue were not different between CLIMB and SED. However, peak increases in systolic (S) BP were significantly lower in CLIMB [25 (13) mmHg; (3.3 (1.7) kPa] than in SED [48 (17) mmHg; (6.4 (2.3) kPa] (P < 0.05), with a similar trend for increases in diastolic (D) BP. Immediately after sustained exercise, forearm conductance was higher in CLIMB than SED (P < 0.05) for up to 2 min. During rhythmic exercise, times to fatigue were two fold longer in CLIMB than SED [853 (76) vs 420 (69) s, P < 0.05]. Increases in SBP were not different between groups except during the last quarter of exercise when they fell in CLIMB. Conductance both during and after rhythmic exercise was higher in CLIMB than in SED. Following a 10-min arterial occlusion, peak vascular conductance was significantly greater in CLIMB than SED [0.597 (0.084) vs 0.431 (0.035) ml x min(-1) x 100 ml(-1) x mmHg(-1); P < 0.05]. The attenuated BP response to sustained isometric exercise could be due in part to enhanced forearm vasodilatory capacity, which also supports greater endurance during rhythmic exercise by permitting greater functional hyperaemia in between contraction phases. Such adaptations would all facilitate the ability of rock climbers to perform their task of making repetitive sustained contractions.

Adaptation, Physiological↗
PubMed1997

Y chromosome polymorphisms in native American and Siberian populations: identification of native American Y chromosome haplotypes.

We have initiated a study of ancient male migrations from Siberia to the Americas using Y chromosome polymorphisms. The first polymorphism examined, a C-->T transition at nucleotide position 181 of the DYS199 locus, was previously reported only in Native American populations. To investigate the origin of this DYS199 polymorphism, we screened Y chromosomes from a number of Siberian, Asian, and Native American populations for this and other markers. This survey detected the T allele in all five Native American populations studied at an average frequency of 61%, and in two of nine native Siberian populations, the Siberian Eskimo (21%) and the Chukchi (17%). This finding suggested that the DYS199 T allele may have originated in Beringia and was then spread throughout the New World by the founding populations of the major subgroups of modern Native Americans. We further characterized Native American Y chromosome variation by analyzing two additional Y chromosome polymorphisms, the DYS287 Y Alu polymorphic (YAP) element insertion and a YAP-associated A-->G transition at DYS271, both commonly found in Africans. We found neither African allele associated with the DYS199 T allele in any of the Native American or native Siberian populations. However, we did find DYS287 YAP+ individuals who harbored the DYS199 C allele in one Native American population, the Mixe, and in one Asian group, the Tibetans. A correlation of these Y chromosome alleles in Native Americans with those of the DYS1 locus, as detected by the p49a/p49f (p49a,f) probes on TaqI-digested genomic DNA, revealed a complete association of DYS1 alleles (p49a,f haplotypes) 13, 18, 66, 67 and 69 with the DYS199 T allele, while DYS1 alleles 8 and 63 were associated with both the DYS199 C and T allele.

Asia↗
PubMed1997

The sensitivity and specificity of pain response to activity and position in categorizing patients with low back pain.

BACKGROUND AND PURPOSE: The purposes of this study were to develop screening tests for four low back pain (LBP) diagnoses based on patient reports concerning the severity of pain in various positions and during activities and then to examine the accuracy of these tests in assigning subjects to one of four LBP diagnostic categories. The accuracy of screening tests is determined by calculating sensitivity and specificity and is well established in epidemiology. SUBJECTS: One hundred six consecutive patients who either were being treated for LBP for the first time or had not received medical care for LBP at the participating clinics within the 12 months prior to the study were recruited. METHODS: Subjects completed a Pain Response to Activity and Position Questionnaire at the time of their initial clinic visit. The diagnosis of LBP was obtained from the medical record after at least 1 month of follow-up and the completion of diagnostic testing. Data analysis yielded symptom clusters that were used to produce screening tests for each of the four categories of LBP. RESULTS: Sensitivity, specificity, and positive and negative predictive power of the screening tests were (1) benign back disease: .57,.71,.40, and .82, (2) disk disease: .65,.49,.35, and .77, (3) spinal stenosis: .52, .74, .36, and .85, and (4) disk disease with spinal stenosis: .81, .54, .24, and .94. CONCLUSION AND DISCUSSION: Although more than half of the subjects with a particular LBP diagnosis tested positive for that diagnosis, approximately two thirds of the subjects who tested positive for each of the diagnoses actually had another diagnosis. Negative tests may be more useful in that between 77% and 94% of the subjects without the diagnosis tested negative. Although patient reports of LBP response to position and activity are not sufficient for diagnosis, they may be useful in ruling out a particular diagnosis.

Activities of Daily Living↗
PubMed1997

Effectiveness of an organized follow-up system for elder patients released from the emergency department.

OBJECTIVES: To determine whether an effective telephone callback system can be successfully implemented in a busy ED and to quantify the benefits that can be obtained related to the follow-up care of elder patients. METHODS: This was a prospective, cohort study conducted at a community teaching hospital during a 6-month period. Consecutive patients > or = 60 years old and released from the ED were selected for telephone follow-up. Calls were made by a research nurse within 72 hours after the patient's ED visit. Follow-up information included current medical status, problems encountered during the ED visit, compliance, and impact of the illness on self-care capabilities. RESULTS: Seventy-nine percent (831/1,048) of the patients selected for telephone follow-up were successfully contacted. The calls lasted an average of 4 +/- 2.5 minutes. Although 94% (778/831) of these patients had a regular physician, 14% failed to make their recommended follow-up arrangements. Compliance was significantly improved when a follow-up physician was contacted during the patient's ED visit. Approximately 96% of the patients were either satisfied or very satisfied with their ED care. However, 13% (109/831) had moderate deterioration in their ability to care for themselves. Of the patients contacted, 333 (40%) required further clarification of their home care instructions, 31 were advised to return to the ED for reevaluation, and 26 were referred to a medical social worker for psychosocial concerns. CONCLUSION: A telephone callback system is a feasible and effective method to improve follow-up care of elder patients released from the ED.

Activities of Daily Living↗
PubMed1997

Capillary red blood cell flow and activation of white blood cells in chronic muscle ischemia in the rat.

Increased activity of ischemic skeletal muscles in which functional hyperemia is impaired has been linked with capillary endothelial swelling postcapillary white blood cell (WBC) adherence. The perfusion pattern of capillaries under these conditions and time course of WBC activation is not known. Capillary microcirculation was studied by videomicroscopy at rest and after muscle contractions (1 Hz, 10 min) in extensor digi-torum longus muscles of pentobarbital sodium-anesthetized rat during the early stages of chronic ischemia (unilateral ligation of the common iliac artery for 3 days) and in ischemic muscles subjected to increased activity (7 days of ischemia or 3 days of ischemia plus indirect electrical stimulation via planted electrodes, 10 Hz, 7 x 10 min on-90 min off/day) to investigate how perfusion was affected. All ischemic muscles had more intermittently flowing capillaries than did unoperated control) muscles. Temporal heterogeneity of perfusion at rest, assessed by velocity, time spent stationary, and stop/start frequency of red blood cells, was similar to control values in ischemic muscles but greater in ischemic muscles subjected to additional activity. Hyperemic responses to contractions were severely blunted in all ischemic groups. The portion of morphologically nonspherical WBCs, taken to indicate activation, was 24 +/- 3% in venous blood after 3 days of ischemia vs. 14 +/- 1% in control muscles and increased further by 7 days (42 +/- 2%) when activated cells were also found in arterial blood. Thus increased muscular activity may exacerbate the adverse effects of ischemia on capillary perfusion, and WBC activation, evident before endothelial swelling is apparent, provides the potential as a circulating signal for capillary swelling in the ischemic and other muscles.

Animals↗
PubMed1997

Improvement of insulin sensitivity by short-term exercise training in hypertensive African American women.

African American women have a high prevalence of insulin resistance, non-insulin-dependent diabetes mellitus, obesity, and hypertension that may be linked to low levels of physical activity. We sought to determine whether 7 days of aerobic exercise improved glucose and insulin metabolism in 12 obese (body fat >35%), hypertensive (systolic blood pressure > or =140 and/or diastolic blood pressure > or =90 mmHg) African American women (mean age 51+/-8 years). Insulin-assisted frequently-sampled intravenous glucose tolerance tests were performed at baseline and 14 to 18 hours after the 7th exercise session. There was no significant change in maximal oxygen consumption, body composition, or body weight after the 7 days of aerobic exercise. The insulin sensitivity index increased (2.68+/-0.45 x 10[-5] to 4.23+/-0.10 x 10[-5] [min(-1)/pmol/L], P=.02). Fasting (73+/-9 to 50+/-9 pmol/L, P=.02) and glucose-stimulated (332+/-58 to 261+/-45 pmol/L, P=.05) plasma insulin levels decreased. Additional measures related to the insulin resistance syndrome also changed with the 7 days of exercise: basal plasma norepinephrine concentrations were reduced (2.46+/-0.27 to 1.81+/-0.27 nmol/L, P=.02) and sodium excretion rate increased from 100+/-13 to 137+/-7 mmol/d (P=.03); however, there was no change in potassium excretion or 24-hour ambulatory blood pressure. We conclude that a short-term aerobic exercise program improves insulin sensitivity in African American hypertensive women independent of changes in fitness levels, body composition, or body weight. The present study indicates that short-term exercise can improve insulin resistance in hypertensive, obese, sedentary African American women and confirms previous reports that a portion of the exercise-induced improvements in glucose and insulin metabolism may be the result of recent exercise.

Adult↗
PubMed1997

De novo 14484 mitochondrial DNA mutation in monozygotic twins discordant for Leber's hereditary optic neuropathy.

Monozygotic twin brothers, clinically discordant for Leber's hereditary optic neuropathy (LHON), had a heteroplasmic point mutation at position 14484 in the mitochondrial DNA that was not detected in their mother. Moreover, the mutation occurred on the rare European haplogroup X, rather than the haplogroup J commonly associated with the 14484 mutation. These data indicate that the 14484 mutation in this family was a new mutation, indicating that it was the de novo occurrence of a common, primary LHON mutation.

Adolescent↗
PubMed1997

Test-retest reliability of patient reports of low back pain.

Low back pain is, in large part, a subjective illness. Clinicians must use patient descriptions of the severity and location of low back pain and how it responds to various activities and positions to make diagnostic and treatment decisions. Therefore, it is important to understand how reliably patients describe these aspects of low back pain. The purpose of this study was to determine the test-retest reliability of a visual analogue scale measure of pain intensity, a pain drawing measure of pain location, and the pain response to activity and position questionnaire. Fifty-three subjects (28 men and 25 women) with a mean age of 54.2 years were recruited from an outpatient orthopaedic clinic. They completed the visual analogue scale, pain drawing, and pain response to activity and position questionnaire before and again immediately after seeing their physician. Thirty-three subjects also completed the visual analogue scale and pain drawing measure that evening and the next morning. Test-retest reliability of the visual analogue scale and pain drawing measure was examined using an intraclass correlation coefficient. Reliability of each item on the pain response to activity and position questionnaire was examined by calculating an unweighted Cohen's kappa. Overall, the three pain measures demonstrated fair to good test-retest reliability: 1) visual analogue scale = .66-.93, 2) pain drawing = .58-.94, and 3) pain response to activity and position questionnaire = .46-.89. The results of this study suggest that, although there is some variability in how consistently patients report various aspects of low back pain, the reliability of these pain measures is sufficient to permit their use in making clinical decisions and measuring treatment outcomes.

Female↗
PubMed1997

Clustering of Caucasian Leber hereditary optic neuropathy patients containing the 11778 or 14484 mutations on an mtDNA lineage.

Leber hereditary optic neuropathy (LHON) is a type of blindness caused by mtDNA mutations. Three LHON mtDNA mutations at nucleotide positions 3460, 11778, and 14484 are specific for LHON and account for 90% of worldwide cases and are thus designated as "primary" LHON mutations. Fifteen other "secondary" LHON mtDNA mutations have been identified, but their pathogenicity is unclear. mtDNA haplotype and phylogenetic analysis of the primary LHON mutations in North American Caucasian patients and controls has shown that, unlike the 3460 and 11778 mutations, which are distributed throughout the European-derived (Caucasian) mtDNA phylogeny, patients containing the 14484 mutation tended to be associated with European mtDNA haplotype J. To investigate this apparent clustering, we performed chi2-based statistical analyses to compare the distribution of LHON patients on the Caucasian phylogenetic tree. Our results indicate that, unlike the 3460 and 11778 mutations, the 14484 mutation was not distributed on the phylogeny in proportion to the frequencies of the major Caucasian mtDNA haplogroups found in North America. The 14484 mutation was next shown to occur on the haplogroup J background more frequently that expected, consistent with the observation that approximately 75% of worldwide 14484-positive LHON patients occur in association with haplogroup J. The 11778 mutation also exhibited a moderate clustering on haplogroup J. These observations were supported by statistical analysis using all available mutation frequencies reported in the literature. This paper thus illustrates the potential importance of genetic background in certain mtDNA-based diseases, speculates on a pathogenic role for a subset of LHON secondary mutations and their interaction with primary mutations, and provides support for a polygenic model for LHON expression in some cases.

Chi-Square Distribution↗
PubMed1996

Update on chemonucleolysis.

A review of the world medical literature on chemonucleolysis with an emphasis on recent studies, meta-analyses, and the history of the procedure in North America from a regulatory, social, and medicolegal perspective was performed to determine the current status of chemonucleolysis in the management of disc displacement. The world literature supports the use of chymopapain for chemonucleolysis as a safe and effective alternative to surgical disc excision. The efficacy of chymopapain has been shown by prospective, randomized, placebo-controlled, double-blind trials with a minimum 10-year follow-up period. The safety of chymopapain injection compared with surgery has been demonstrated in meta-analyses and in extensive post-marketing surveillance in the United States and Europe. Clinical studies with collagenase and laboratory studies with chondroitinase ABC have shown that chemonucleolysis can be performed with enzymes other than chymopapain. Clinical trials have been performed with collagenase for chemonucleolysis, but all of the results have not been published. Preclinical research with chondroitinase ABC has demonstrated its usefulness for chemonucleolysis in the animal model, but human trials have not begun.

Animals↗
PubMed1996

Consensus summary of the diagnosis and treatment of lumbar disc herniation.

Clinicians must not simply decide that a patient with symptoms and a positive diagnostic test has a reason for a specific treatment, and likewise clinicians must not decide that a patient with symptoms and a negative test does not have a clinically important problem. We must also consider the sensitivity, specificity and predictive value of the diagnostic test and the individual characteristics of the patient. Treatment outcome depends on many factors. Point of service decisions vs population based decisions are obviously different. Each patient presents to the treating practitioner on a given day, at a given time, and it is this picture upon which a plan of care is formulated.

Humans↗
PubMed1996

Mitochondrial DNA sequence analysis of four Alzheimer's and Parkinson's disease patients.

The mitochondrial DNA (mtDNA) sequence was determined on 3 patients with Alzheimer's disease (AD) exhibiting AD plus Parkinson's disease (PD) neuropathologic changes and one patient with PD. Patient mtDNA sequences were compared to the standard Cambridge sequence to identify base changes. In the first AD+PD patient, 2 of the 15 nucleotide substitutions may contribute to the neuropathology, a nucleotide pair (np) 4336 transition in the tRNA(Gln) gene found 7.4 times more frequently in patients than in controls, and a unique np 721 transition in the 12S rRNA gene which was not found in 70 other patients or 905 controls. In the second AD+PD patient, 27 nucleotide substitutions were detected, including an np 3397 transition in the ND1 gene which converts a conserved methionine to a valine. In the third AD+PD patient, 2 polymorphic base substitutions frequently found at increased frequency in Leber's hereditary optic neuropathy patients were observed, an np 4216 transition in ND1 and an np 13708 transition in the ND5 gene. For the PD patient, 2 novel variants were observed among 25 base substitutions, an np 1709 substitution in the 16S rRNA gene and an np 15851 missense mutation in the cytb gene. Further studies will be required to demonstrate a causal role for these base substitutions in neurodegenerative disease.

Alzheimer Disease↗
PubMed1996

MITOMAP: a human mitochondrial genome database.

We have developed a comprehensive database (MITOMAP) for the human mitochondrial DNA (mtDNA), the first component of the human genome to be completely sequenced [Anderson et al. (1981) Nature 290, 457-465]. MITOMAP uses the mtDNA sequence as the unifying element for bringing together information on mitochondrial genome structure and function, pathogenic mutations and their clinical characteristics, population associated variation, and gene- gene interactions. As increasingly larger regions of the human genome are sequenced and characterized, the need for integrating such information will grow. Consequently, MITOMAP not only provides a valuable reference for the mitochondrial biologist, it may also provide a model for the development of information storage and retrieval systems for other components of the human genome.

Amino Acid Sequence↗
PubMed1996

Fast capillary electrophoresis-laser induced fluorescence analysis of ligase chain reaction products: human mitochondrial DNA point mutations causing Leber's hereditary optic neuropathy.

High speed capillary electrophoresis-laser-induced fluorescence (CE-LIF) has been used to separate and detect point mutations using the ligase chain reaction (LCR). The method utilizes short capillary columns (7.5 cm effective length) and fields of 400 V/cm to analyze DNA-ethidium bromide complexes using an He/Ne laser. The method was first demonstrated with a commercially available kit for LCR based on a lacI gene fragment inserted in a Bluescript II phagemid. LCR-CE-LIF was then applied to detect point mutations in human mitochondrial DNA, resulting in Leber's hereditary optic neuropathy (LHON). Three severe mutations were analyzed in which the original base is substituted by a thymidine base at positions 3460, 11778 and 14459. Appropriate primers were designed with polyT tails for length discrimination of pooled samples. Successful detection of mutated samples was achieved, with appropriate correction for small amounts of nonspecific ligated product. The method is rapid, easy to implement, and automatable.

Base Sequence↗
PubMed1996

In vivo pericyte-endothelial cell interaction during angiogenesis in adult cardiac and skeletal muscle.

Pericytes (PC) exert an inhibitory effect on endothelial cell (EC) proliferation in vitro and withdrawal of PC occurs prior to EC proliferation during pathological capillary growth in vivo. Using stereological analyses of PC and capillary EC fine structure, we have studied their relationship during the early stages of physiological angiogenesis using two in vivo models. In rat skeletal muscle where capillary growth was induced by indirect electrical stimulation, there was a reduction in the relative area of contact between pericytes and the capillary abluminal surface (22% vs 30% for normal controls; P < 0.05) and pericyte surface: volume ratio (12.5 vs 14.9 microns-1 for normal controls; P < 0.05) after 3 days of stimulation, at a time prior to the appearance of new capillaries. Further withdrawal of pericyte processes was evident at the point where an actual increase in capillary numbers was observed (7 days stimulation; PC surface: volume ratio = 10.4 microns-1), although the degree of PC-EC interdigitation increased. Similar changes, but to a lesser extent, were observed in both left ventricular myocardium and papillary muscles of pigs following 4-5 weeks chronic heart rate reduction. Although PC coverage of capillaries in the heart was found to be less than that in skeletal muscle, the relative contact area between PC and capillaries also showed a reduction in paced vs sham-operated control heart (papillary: 15% vs 20%; ventricle: 12% vs 16%; P < 0.05). Interdigitation of PC and EC was absent in cardiac muscle. These data suggest that retraction of PC may play a permissive role in controlling angiogenesis in vivo in normal adult tissue.

Animals↗