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Biomedical subjects

M D Brown

Publications and source records attributed to M D Brown.

At least 163 records · Page 9Linked to original sources

Toward the elimination of homologous blood use in elective lumbar spine surgery.

Two hundred twenty-four consecutive patients underwent elective posterior lumbar spinal surgery over a 3 1/2-year span at the University of Miami/Jackson Memorial Medical Center. Patients ranged in age from 17 to 87 years, and 58% were male. Fifty-eight patients underwent revision surgery, and 65 patients required fusions, including 35 necessitating internal fixation. One hundred seventy-four patients (78%) were requested to participate in a preoperatively donated autologous blood (PDAB) program. Six of these patients were excluded from participation, and 168 patients banked 425 U of autologous blood. Eighty percent of the patients participating in the PDAB program received some or all of their donated blood. Intraoperative blood salvage was used in 37% of cases. Seven patients received homologous blood: four in addition to salvaged and donated blood, two that were unable to donate blood due to positive hepatitis B serology, and one erroneously. The combined use of PDAB and intraoperative salvage program allowed autologous blood replacement to meet the total transfusion requirements of 96% of the patients who predeposited blood, including 94% of those undergoing spinal fusions. Autologous blood comprised 99% of the total blood replacement used in this series, and 95% of the patients requiring blood transfusions received only autologous blood. Establishment of a protocol judiciously using PDAB in conjunction with intraoperative blood salvage can result in virtual elimination of the need for homologous blood transfusion in elective lumbar spine surgery.

Adolescent↗

Initial-impression diagnosis using low-back pain patient pain drawings.

Patient pain drawings were blindly selected from five lumbar spine disorder categories. The drawings were classified by low-back physicians, discriminant analysis, and several computerized artificial neural network configurations. The purpose was to determine the reliability of the patient pain drawing when diagnosing low-back disorders and to delineate the pain mark patterns particular to each disorder by comparing physicians with computerized methods. The physicians averaged 51% accuracy with individual preferences for certain disorder groups. The computerized methods demonstrated comparable accuracy (48%) and more agreement in classification. Associations were found between the predicted pain patterns for each diagnostic group made by an expert and the patterns generated by computerized methods. Variances in these associations are instructive to clinicians for making accurate predictions of diagnosis from pain drawings.

Diagnosis, Computer-Assisted↗

Histology and physiology of tissue expansion.

BACKGROUND: Tissue expansion is a concept based on the skin's natural ability to stretch in response to an underlying force. OBJECTIVE: The purpose of this article is to review the histological and physiological changes that occur within the soft tissue and underlying structures during tissue expansion. METHODS: An extensive search of the literature reviewing these changes is summarized herein. RESULTS: Conventional tissue expansion may result in epidermal hypertrophy, decreased dermal, muscle, and adipose thickness, and bone resorption. A vascular capsule and angiogenesis provides a highly vascular flap and improves flap viability. Few soft tissue changes occur during rapid tissue expansion. The ability of the skin to increase in surface area during conventional tissue expansion is primarily because of biological tissue creep. Rapid expansion may result from mechanical tissue creep. CONCLUSION: Many soft tissue changes occur during tissue expansion. Most of these changes return to the pre-expansion state over time following discontinuation of the expansion process.

Animals↗

Asian affinities and continental radiation of the four founding Native American mtDNAs.

The mtDNA variation of 321 individuals from 17 Native American populations was examined by high-resolution restriction endonuclease analysis. All mtDNAs were amplified from a variety of sources by using PCR. The mtDNA of a subset of 38 of these individuals was also analyzed by D-loop sequencing. The resulting data were combined with previous mtDNA data from five other Native American tribes, as well as with data from a variety of Asian populations, and were used to deduce the phylogenetic relationships between mtDNAs and to estimate sequence divergences. This analysis revealed the presence of four haplotype groups (haplogroups A, B, C, and D) in the Amerind, but only one haplogroup (A) in the Na-Dene, and confirmed the independent origins of the Amerinds and the Na-Dene. Further, each haplogroup appeared to have been founded by a single mtDNA haplotype, a result which is consistent with a hypothesized founder effect. Most of the variation within haplogroups was tribal specific, that is, it occurred as tribal private polymorphisms. These observations suggest that the process of tribalization began early in the history of the Amerinds, with relatively little intertribal genetic exchange occurring subsequently. The sequencing of 341 nucleotides in the mtDNA D-loop revealed that the D-loop sequence variation correlated strongly with the four haplogroups defined by restriction analysis, and it indicated that the D-loop variation, like the haplotype variation, arose predominantly after the migration of the ancestral Amerinds across the Bering land bridge.

Americas↗

Estimates of insulin action in normal, obese and NIDDM man: comparison of insulin and glucose infusion test, CIGMA, minimal model and glucose clamp techniques.

Many methods of varying complexity are available for the measurement of insulin resistance (action) in man. No study has previously compared several of these in the same subjects to establish which is the most appropriate for routine use. We have, therefore, compared six methods: the hyperinsulinemic eu(iso)-glycaemic clamp (Eu), insulin glucose infusion test (IGI), hyperglycaemic clamp (Hy), continuous infusion of glucose with model assessment (CIGMA), minimal model (Min) and modified minimal model (Mod). Nineteen subjects with varying degrees of glucose tolerance were studied. Eight normal (BMI 22.5 +/- 1.5 kg/m2), six obese (BMI 38 +/- 5 kg/m2) and five NIDDM subjects (BMI 27 +/- 3 kg/m2) were investigated, in a randomized fashion, on separate days. The ratio of metabolic clearance rate of glucose (MCRG) and Insulin (I) was used as the measure of insulin action during Eu, Hy and IGI. Si was calculated as the index of insulin sensitivity from (Min) and (Mod) and CIGMA was obtained as previously described. MCRG was converted to Si to allow for direct comparison with (Min). Methods requiring incremental endogenous insulin secretion (which was highly variable) to calculate an index of insulin action (Si Min, Si Hy and CIGMA) failed to find an overall difference between groups. Only Si Eu (p = 0.007) and Si IGI (p = 0.001) demonstrated a significant overall group difference when Si was used. When MCRG/I was used, Eu, IGI and Hy were able to distinguish a significant overall group difference. With the exception of CIGMA and SiHy all other methods found a significant difference in insulin action between normals and NIDDM subjects. Only Eu and IGI could distinguish obese from normal, while only Si Min, could distinguish obese from NIDDM subjects. Eu and IGI were the only methods to be significantly correlated: normals Rs = 0.75, p < 0.05, obese Rs = 0.9, p < 0.05, and NIDDM Rs = 1.0, p < 0.05. In conclusion we have demonstrated that: 1) The insulin-glucose infusion test and the eu(iso)glycaemic clamp were significantly correlated in normals, obese and NIDDM subjects. 2) Only the eu(iso)glycaemic clamp and insulin glucose infusion test could significantly separate obese from normal subjects. 3) the IGI appears to be a practical, simple and precise method for measuring in vivo insulin action in man and gives results closely similar to those found with the hyperinsulinemic eu(iso)glycaemic clamp.

Adult↗

Ethical considerations and CPR in the elderly patient.

Cardiopulmonary resuscitation has become an increasingly common event in the terminal illness of hospitalized seriously ill elderly patients. Elderly patients, however, tend to respond poorly to the resuscitation procedure. The authors analyze the ethical and legal considerations in offering or withholding cardiopulmonary resuscitation. The central position of the physician in decision-making is emphasized.

Age Factors↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗