Search PubMed⌕ Search

Biomedical subjects

M D Brown

Publications and source records attributed to M D Brown.

At least 19 recordsLinked to original sources
PubMed1992

Capillary growth in the heart.

Experiments were performed to test the hypothesis that increased stretch and/or tension of myocytes in the absence of changes in blood flow could induce capillary growth in the heart. Chronic treatment with either dobutamine (rabbits) or alinidine (rats) which increased force of contraction and/or stroke volume respectively without increases in coronary blood flow led to enlargement of the anatomical size of the capillary bed, with no change in cardiac weight, thus supporting the role of external mechanical factors in angiogenesis.

Animals↗
PubMed1992

Diseases resulting from mitochondrial DNA point mutations.

A number of mitochondrial DNA (mtDNA) mutations have been identified which cause familial, late onset neuromuscular degenerative diseases. These include missense mutations in most of the mtDNA polypeptide genes as well as base substitutions in several tRNA genes. Missense mutations in the mitochondrial electron-transport genes cause Leber hereditary optic neuropathy. Ten mutations have been associated with this disease, but four at nps 11,178, 3460, 4160 and 15,257 appear sufficient in themselves to cause the disease. One missense mutation in the ATPase 6 gene at np 8993 causes a second phenotype, neurogenic muscle weakness, ataxia and retinitis pigmentosum. Transfer RNA mutations have been identified for myoclonic epilepsy and ragged-red fibre disease in the tRNA(Lys) gene at np 8344 and for the mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes syndrome and for maternal mitochondrial myopathy and cardiomyopathy syndrome in the tRNA(Leu)(UUR) gene at nps 3234 and 3260, respectively. Deficiencies in mitochondrial oxidative phosphorylation enzymes have been observed in several common neurodegenerative diseases such as Alzheimer and Parkinson diseases. Perhaps mtDNA mutations play a role in these as well.

Base Sequence↗
PubMed1992

Mitochondrial DNA complex I and III mutations associated with Leber's hereditary optic neuropathy.

Four new missense mutations have been identified through restriction analysis and sequencing of the mitochondrial DNAs (mtDNA) from Leber's hereditary optic neuropathy (LHON) patients who lacked the previously identified 11778 mutation. Each altered a conserved amino acid and correlated with the LHON phenotype in population and phylogenetic analyses. The nucleotide pair (np) 13708 mutation (G to A, ND5 gene) changed an alanine to a threonine and was found in 6/25 (24%) of non-11778 LHON pedigrees and in 5.0% of controls, the np 15257 mutation (G to A, cytochrome b gene) changed an aspartate to an asparagine and was found in 4 of the 13708-positive pedigrees and 0.3% of controls, the np 15812 mutation (G to A, cytochrome b gene) changed a valine to a methionine and was detected in two of the 15257-positive pedigrees and 0.1% of controls and the np 5244 mutation (G to A, ND2 gene) changed a glycine to a serine and was found in one of the 15812-positive patients and none of 2103 controls. The 15257 mutation altered a highly conserved amino acid in an extramembrane domain of cytochrome b that is associated with the ligation of the low potential b566 heme and the 5244 mutation altered a strongly evolutionarily conserved region of the ND2 polypeptide. The 13708 and 15812 mutations changed moderately conserved amino acids. Haplotype and phylogenetic analysis of the four np 15257 mtDNAs revealed that all harbored the same rare Caucasian haplotype and that the np 13708, np 15257, np 15812 and np 5244 mutations were added sequentially along this mtDNA lineage. Since the percentage of sighted controls decreases as these mutations accumulate, it appears that they interact synergistically, each increasing the probability of blindness. The involvement of both mitochondrial complex I (np 5244, 11778, 13708) and complex III (np 15257, 15812) mutations in LHON indicates that the clinical manifestations of this disease are the product of an overall decrease in mitochondrial energy production rather than a defect in a specific mitochondrial enzyme.

Base Sequence↗
PubMed1992

Laboratory evaluation of Brazilian Mesocyclops (Copepoda: Cyclopidae) for mosquito control.

In laboratory tests, four different strains of Mesocyclops aspericornis (Daday) collected in or near Fortaleza, Brazil, showed potential as biological control agents of Aedes aegypti (L.) mosquito larvae but were not as effective against Anopheles or Culex. In contrast, the larger M. longisetus (Thiebaud), collected at Fortaleza, killed 100% of Ae. aegypti and Anopheles farauti (Laveran) (No. 1) at larval densities of 200/liter and Culex quinquefasciatus (Say) at 25/liter. In cage simulations with Ae. aegypti and Mesocyclops, both copepod species eliminated all immatures in earthenware pots by week 3. Owing to the lack of replacement, all Ae. aegypti adults subsequently died by week 8 or 9. Although both M. longisetus and M. aspericornis showed maximum reproductive potential at 25 degrees C, breeding occurred from 20 to 35 degrees C. Based on these laboratory evaluations, M. longisetus has been selected for field trials in rural villages in Ceará to control Ae. aegypti.

Aedes↗
PubMed1992

Leber's hereditary optic neuropathy: a model for mitochondrial neurodegenerative diseases.

A number of human diseases have been attributed to defects in oxidative phosphorylation (OXPHOS) resulting from mutations in the mitochondrial DNA (mtDNA). One such disease is Leber's hereditary optic neuropathy (LHON), a neurodegenerative disease of young adults that results in blindness due to atrophy of the optic nerve. The etiology of LHON is genetically heterogeneous and in some cases multifactorial. Eleven mtDNA mutations have been associated with LHON, all of which are missense mutations in the subunit genes for the subunits of the electron transport chain complexes I, III, and IV. Molecular, biochemical, and population genetic studies have categorized these mutations as high risk (class I), low risk (class II), or intermediate risk (class I/II). Class I mutations appear to be primary genetic causes of LHON, while class II mutations are frequently found associated with class I genotypes and may serve as exacerbating genetic factors. Different LHON pedigrees can harbor different combinations of class I, II, or I/II mtDNA mutations, as shown by the complete sequence analysis of the mtDNAs of four LHON probands. The various mtDNA genotypes included an isolated class I mutation, combined class I+II mutations, and combined class I/II+II mutations. The occurrence of such genotypes supports the hypothesis that LHON may result from the additive effects of various genetic and environmental insults to OXPHOS, each of which increases the probability of blindness.

Adolescent↗
PubMed1992

Expert performance in low-back disorder recognition using patient pain drawings.

Eight low-back-pain experts who regularly include pain drawings in their clinical workup were asked to classify 25 drawings. The experts used only the drawings to place cases into one of five broadly defined diagnostic categories: benign disorder, herniated disc, spinal stenosis, underlying disorder, or psychogenic disturbance. The physicians demonstrated adequate accuracy--51% correct--when compared with change (20% correct). Classification accuracy was greatest for psychogenic disorders (85%), followed by spinal stenosis (58%), herniated discs (52%), and benign disorders (50%). Predictions were comparatively poor for the underlying disorder category (10%). The individual physician accuracies varied from 44 to 60%. "Classic" pain patterns for each disorder group were identified by determining which drawings were correctly classified by most physicians. Physicians may wish to impart greater significance to pain drawings close to one of our "classic" patterns than to others.

Back Pain↗
PubMed1992

Chronotropic and inotropic responses to adrenoceptor agonists in vitro after chronic dobutamine treatment in the rabbit.

1. Effects of long-term administration of the inotropic agent dobutamine (beta-and alpha 1-adrenoceptor agonist) on cardiac adrenoceptor function were studied in the rabbit. 2. After 2 weeks' continuous i.v. infusion of dobutamine (Dobutrex, 20 micrograms kg-1 min-1), spontaneous atrial rates in vitro were similar to controls, as were maximal rates in response to isoprenaline (262 +/- 17 vs 268 +/- 21 b.p.m., P greater than 0.05) but the chronotropic potency of isoprenaline was reduced, as shown by a nine-fold increase in EC50. 3. Basal developed tension of papillary muscles was greater after chronic dobutamine treatment and increases in contraction force in response to beta-activation by isoprenaline and noradrenaline were significantly higher. Maximal developed tensions were 93 +/- 14% (P less than 0.02) and 94 +/- 25% (P less than 0.05) respectively greater than those of control muscles. 4. The inotropic potency of isoprenaline, but not noradrenaline, was reduced significantly after chronic dobutamine with a two-fold increase in EC50. 5. Responses to alpha 1-adrenoceptor activation by phenylephrine were unchanged after dobutamine treatment. 6. These changes are consistent with functional desensitization of the myocardium by the prolonged beta- but not alpha 1-agonist activity of dobutamine. In contrast, there was an enhanced effectiveness of beta-adrenoceptor activation.

Animals↗
PubMed1992

Effects of human insulin on insulin binding antibody production in nondiabetic subjects.

OBJECTIVE: To test the hypothesis that human insulin may have a low immunogenicity and that short-term exposure may not cause endogenous insulin antibody production. RESEARCH DESIGN AND METHODS: Randomized double-blind prospective study. Serum samples collected for insulin binding antibodies and measured by a sensitive immunochemical assay. Subjects were seven healthy nondiabetic patients who had never received exogenous insulin. Each subject received 6 separate monthly injections of human insulin. On four occasions, both regular and NPH insulin were administered. On the other two occasions, either NPH or regular insulin was administered alone. RESULTS: Mean +/- SE basal insulin antibody levels (1.2 +/- 0.2 micrograms/L) increased to a maximal level of 4.5 +/- 0.8 micrograms/L after four injections. Thereafter, antibody levels declined to an end-of-study value of 2.5 +/- 0.3 micrograms/L. This represented a highly significant overall increase (P less than 0.001). A control group of six insulin-dependent diabetic subjects treated with human insulin over the same period as the test subjects demonstrated no change in insulin antibody concentrations (2.8 +/- 0.7-2.7 +/- 0.6 micrograms/L). CONCLUSIONS: These results suggest that human insulin preparations, when administered subcutaneously, may be more immunogenic than previously considered. The antigenic response was rapid, because only four subcutaneous injections were sufficient to produce insulin antibody levels in nondiabetic patients similar to those observed in insulin-dependent diabetic patients receiving chronic insulin replacement therapy.

Adult↗
PubMed1992

A comparison of four methods for assessing in vivo beta-cell function in normal, obese and non-insulin-dependent diabetic man.

Several methods of varying complexity are available for the measurement of in vivo insulin secretion in man. No study has previously compared these in the same subjects to establish which is the most appropriate for routine use. We have, therefore, compared four methods for measuring insulin secretion in man: Hyperglycaemic clamp (Hy), Minimal model (MIN), shortened intravenous glucose tolerance test (IVGTT) and continuous infusion of glucose with model assessment (C.I.G.M.A.). Seventeen subjects with varying degrees of insulin sensitivity were studied. Seven normal (BMI 22.5 +/- 1.5 kg/m2), five obese (BMI 38 +/- 5 kg/m2) and five NIDDM subjects (BMI 27 +/- 3 kg/m2) were investigated, in a randomised fashion, on separate days. First (PSI) and second phase (PSII) rate constants (MIN); incremental insulin secretion 0-10 mins (Hy delta I) and steady state insulin levels from the last 30 minutes (Hy120-150) from the hyperglycaemic clamp; 3 minute insulin concentration and incremental area under insulin secretion curve 0-10 min (IVGTT) and beta-cell function (%) from C.I.G.M.A. were used as indicators of insulin secretion. Each index of insulin secretion could detect an overall difference between the groups. Insulin secretion in normals and obese was similar but significantly increased compared to NIDDM. In normals PSI correlated with C.I.G.M.A. (Rs = 0.92, p < 0.02) and Hy120-150 (Rs = 0.82, p < 0.05). IVGTT0-10 correlated with PSII (Rs = 0.83, p < 0.05), HY delta I (Rs = 0.84, p < 0.05) and IVGTT3 min (Rs = 1.0, p < 0.001). In obese PSII correlated with C.I.G.M.A. (Rs = 0.91, p < 0.05), Hy delta I (Rs = 1.0, p < 0.02) Hy120-150 (Rs = 0.92, p < 0.05) and IVGTT3 min Rs = 1.0, p < 0.02). In addition Hy delta I also correlated with C.I.G.M.A. (Rs = 0.92, p < 0.05) and IVGTT3 min (Rs = 1.0, p < 0.02). In NIDDM Hy delta I correlated with C.I.G.M.A. (Rs = 0.91, p < 0.005). When all subjects from the three groups were combined, significant positive correlations were obtained between each index of insulin secretion. In conclusion we have demonstrated that: (a) C.I.G.M.A., IVGTT, Minimal model and hyperglycaemic clamp can provide similar overall results for, in vivo, beta-cell function in man. (b) Significant positive correlations were obtained between each index of insulin secretion when all subjects were combined. (c) Using the above methodologies insulin secretion in normal and obese appears similar but significantly increased compared to NIDDM subjects.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1992

A mitochondrial DNA variant, identified in Leber hereditary optic neuropathy patients, which extends the amino acid sequence of cytochrome c oxidase subunit I.

A G-to-A transition at nucleotide pair (np) 7444 in the mtDNA was found to correlate with Leber hereditary optic neuropathy (LHON). The mutation eliminates the termination codon of the cytochrome c oxidase subunit I (COI) gene, extending the COI polypeptide by three amino acids. The mutation was discovered as an XbaI restriction-endonuclease-site loss present in 2 (9.1%) of 22 LHON patients who lacked the np 11778 LHON mutation and in 6 (1.1%) of 545 unaffected controls. The mutant polypeptide has an altered mobility on SDS-PAGE, suggesting a structural alteration, and the cytochrome c oxidase enzyme activity of patient lymphocytes is reduced approximately 40% relative to that in controls. These data suggest that the np 7444 mutation results in partial respiratory deficiency and thus contributes to the onset of LHON.

Amino Acid Sequence↗
PubMed1992

Complications of chemonucleolysis.

Complications in chemonucleolysis are inevitable. However, the incidence of these may be minimized with attention to detail. Proper patient selection, based on a knowledge of the natural history of lumbar disk herniation and elimination of patients with contraindications to diskolysis, will result in a higher success rate with lower incidence of complications in diskolysis. Once the proper patient has been selected, attention must be turned to technique with respect to the use of local anesthesia, appropriate patient positioning, good fluoroscopic control, and two-needle technique for appropriate needle positioning. Immunologic complications can be nearly eliminated with the use of a preoperative enzyme immunoassay test. Carefully considering all of these factors will allow chemonucleolysis to present a safe alternative to disk surgery.

Anaphylaxis↗
PubMed1992

Floppy eyelid syndrome: a case report and clinical review.

Floppy eyelid syndrome is a clinical entity associated with a chronic papillary conjunctivitis which is resistant to topical therapeutic agents. The disorder is usually found in older, obese males with upper eyelids which are loose, rubbery, and easily everted. This paper is a review of the clinical characteristics and treatment of the syndrome and includes a case of a 16-year-old male with floppy eyelid syndrome, one of the youngest reported.

Adolescent↗
PubMed1991

Cyclosporine for plaque-type psoriasis. Results of a multidose, double-blind trial.

BACKGROUND: Severe plaque-type psoriasis has been successfully treated with orally administered cyclosporine, but there has been no comparative, controlled evaluation of various dosages and their efficacy and side effects. METHODS: In a 16-week, double-blind trial, we randomly assigned 85 patients with severe psoriasis to receive 3, 5, or 7.5 mg of cyclosporine per kilogram of body weight per day or a placebo consisting of the vehicle for the drug. After eight weeks the dose could be adjusted to improve safety or efficacy while maintaining blinding. RESULTS: The psoriasis improved in a dose-dependent fashion. After eight weeks of fixed-dose therapy, 36, 65, and 80 percent of the patients receiving 3, 5, and 7.5 mg of cyclosporine per kilogram per day, respectively, were rated as being clear or almost clear of psoriasis; each group had significant improvement (P less than 0.0001) as compared with the group receiving vehicle, in which none of the patients were rated as clear or almost clear. The patients who received 5 mg per kilogram were the least likely to require dosage adjustments because of side effects or a lack of efficacy. The glomerular filtration rate, measured in a subgroup of 34 patients receiving cyclosporine, decreased by a median of 16 percent. Higher doses of cyclosporine had greater adverse effects on systolic blood pressure, glomerular filtration rate, and serum levels of creatinine, uric acid, bilirubin, and cholesterol. Delayed-type hypersensitivity reactions to skin-test antigens were reduced by cyclosporine administration. Cyclosporine appears to become concentrated in skin. CONCLUSIONS: Cyclosporine therapy leads to a rapid and thorough clearing of psoriasis; an initial dose of 5 mg per kilogram per day seems to be appropriate. However, the safety of cyclosporine for the long-term treatment of psoriasis remains to be determined.

Administration, Oral↗
PubMed1991

A new technique for the in vitro measurement of nucleus pulposus swelling pressure.

Swelling of the intervertebral disc nucleus pulposus may be a contributing factor in lower back pain syndromes. We have designed and tested a new osmometer for in vitro determination of nucleus pulposus swelling pressure. The functional principle of the osmometer involves compressing a sample of nucleus pulposus with nitrogen gas until saline pressure gradients across a 0.45-micron Millipore filter are eliminated. Swelling pressures of both pooled dog and pooled pig lumbar disc nucleus pulposus were measured on the new osmometer and were compared with swelling pressure determined using the equilibrium dialysis technique. The osmometer measured swelling pressures comparable to those obtained by the dialysis technique. This osmometer provides a rapid, direct, and accurate measurement of swelling pressure of the nucleus pulposus.

Animals↗
PubMed1991

Statistical diagnosis of lumbar spine disorders using computerized patient pain drawings.

Discriminant analysis is applied to 250 quantified low back patient pain drawings to study the ability of a computerized statistical method for classifying novel cases into one of five clinically-significant lumbar spine disorders. Tests on independent data were 46.2 percent (%) correct overall. Benign disorder (55.6%), herniated disc (51.7%), and psychogenic (56.3%) pain drawings were more accurately discriminated than the spinal stenosis (32.2%) and underlying disorder cases (35.2%). It is concluded that computerized patient pain drawings provide valid "initial impressions" of lumbar spine disorders. Further research is suggested to better distinguish between herniated disc and spinal stenosis pain descriptions, and for better recognition of serious underlying disorder pain drawings.

Back Pain↗