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Biomedical subjects

B A Cooper

Publications and source records attributed to B A Cooper.

At least 19 recordsLinked to original sources
PubMed1998

Responses to endothelium-dependent agonists in subcutaneous arteries excised from hypercholesterolaemic men.

1. Vasomotor function of the vascular endothelium was examined in human subcutaneous arteries excised from 8 hypercholesterolaemic and 7 normolipidaemic subjects. 2. Left gluteal skin biopsies were performed under local anaesthesia. Subcutaneous arteries were isolated and two vessels from each subject mounted in separate myographs. A 20 ml fasting blood sample was taken at the time of the biopsy. 3. Hypercholesterolaemic subjects had either never been treated with lipid lowering therapy or therapy had been stopped at least two weeks before the study (n = 2). At the time of the study total plasma cholesterol levels (control: 4.6+/-0.3 vs hypercholesterolaemic: 8.3+/-0.6 mmol l(-1): P < 0.01) were significantly elevated in hypercholesterolaemic subjects when compared with controls. 4. Full concentration-response curves to the vasoconstrictor noradrenaline and the vasodilators acetylcholine and substance P were constructed. A single point concentration-response to sodium nitroprusside (10 microM) was also obtained. Dilator responses were obtained in vessels pre-constricted with a submaximal concentration of noradrenaline. Vessels were then incubated for 30 min with either L- or D-arginine (10 microM) and the concentration-response curves to the three dilator agonists repeated in the presence of the amino acid. 5. Maximum relaxation responses to acetylcholine (control vs hypercholesterolaemic: 83.3+/-6.1% vs 47.4+/-13.5%; P < 0.05), but not to substance P or sodium nitroprusside, were dampened in the hypercholesterolaemic group when compared with controls. 6. Neither incubation with L-arginine nor D-arginine had any effect on maximum relaxation responses to acetylcholine in either the control group (pre L-arginine vs plus L-arginine: 83.3+/-6.1 vs 82.3+/-5.5%, pre D-arginine vs plus D-arginine: 98.9+/-1.2 vs 98.2+/-1.1%) or the hypercholesterolaemic group (pre L-arginine vs plus L-arginine: 47.4+/-13.5 vs 55.3+/-14.3%, pre D-arginine vs plus D-arginine: 43.3+/-13.6 vs 65.4+/-12.3%). 7. When results from the two study groups were pooled, the strongest predictor of maximum relaxation obtained to acetylcholine was apolipoprotein A1 (r = 0.67; P = 0.001). 8. In conclusion, relaxation responses mediated by the endothelium-dependent agonist acetylcholine, but not by substance P, are impaired in hypercholesterolaemic patients. L-Arginine did not improve the impaired relaxation responses to acetylcholine. We suggest that impaired endothelium-dependent relaxation is specific to acetylcholine and not to an abnormal L-arginine-nitric oxide pathway in subcutaneous arteries excised from this study group.

Acetylcholine↗
PubMed1998

Risk factors associated with infant death among very low birth weight infants after discharge from an intensive care nursery.

Low birth weight infants have an increased incidence of death after discharge from the intensive care nursery (ICN). To evaluate factors associated with death, and especially unexpected death, we conducted a study on 724 infants discharged from our ICN with a birth weight 1500 g or less. Twenty-four infants died during the 1st year after discharge. Univariate analyses and logistic regression analyses were used to examine the effects of birth weight, gestational age, race, gender, growth retardation, chronic lung disease (CLD), intracranial hemorrhage (ICH), and socioeconomic risk on postdischarge death. Of the risk factors studied, only CLD (p = .001) and ICH (p = .004) were independently associated with death, but ICH alone was the most worrisome risk factor associated with sudden, unexpected death in low birth weight infants after discharge from an ICN.

Child↗
PubMed1997

Outcome of infants born at 24-26 weeks' gestation: II. Neurodevelopmental outcome.

OBJECTIVE: To assess the neurodevelopmental outcome of infants born at 24-26 weeks' gestation. METHODS: One hundred thirty-eight nonanomalous infants were born at our hospital after pregnancies of 24-26 weeks' gestation between 1990 and 1994. Ninety-four infants survived to discharge and 86 were followed in a nursery follow-up program for outcome. Associations between gestational age and neurodevelopmental outcome and risk factors and outcome were analyzed. Mean age at follow-up was 32 months. RESULTS: The frequency of cerebral palsy did not differ significantly in the three groups (11, 20, and 11% at 24, 25, and 26 weeks, respectively). The incidence of normal cognitive outcome was associated significantly with gestational age at birth (28, 47, and 71% normal at 24, 25, and 26 weeks, respectively). Poor neurologic outcome was associated with the medical risk factor of intracranial hemorrhage grade 3 or 4 or periventricular leukomalacia. Poor cognitive outcome was correlated with both medical and social risk factors; however, there was an association between poor cognitive outcome and lower gestational age (P < .05), regardless of the relationships of any other risk factors to cognitive outcome. CONCLUSION: Although the incidence of cerebral palsy was low in these three groups, the high percentage of infants born at 24 and 25 weeks' gestation with cognitive deficits is concerning.

Cerebral Palsy↗
PubMed1997

Outcome of extremely low birth weight infants (500 to 999 grams) over a 12-year period.

OBJECTIVE: Advances in neonatology have contributed to improved survival for extremely low birth weight (ELBW) infants. Neurodevelopmental outcome is usually reported for a single large group of infants rather than according to smaller birth weight groups because of small numbers. Our purpose was to review the neurodevelopmental outcome of a large group of ELBW infants and examine differential outcome according to birth weight. STUDY DESIGN: A total of 446 infants born between 1979 and 1991, with a birth weight of 500 to 999 g, were followed to mean age 55 months +/- 33 standard deviation. Univariate analyses of medical risk factors of birth weight, gestational age, year of birth, growth retardation, gender, inborn/outborn status, days on oxygen, intracranial hemorrhage, and social risk in relation to outcome were conducted on the group as a whole. Neurologic/developmental outcome was also analyzed by 100-g weight groups. RESULTS: A total of 61% of all infants were completely normal, with no neurologic, neurosensory, or cognitive deficits. There was no association between outcome and birth weight. There was a strong association between intracranial hemorrhage (ICH) grade III or IV and/or cystic periventricular leukomalacia (PVL) and abnormal outcome (Somers' D = .17) and ICH III/IV and/or cystic PVL and cognitive outcome (Kendall's tau = .15). Mild to moderate cognitive delays were associated with chronic lung disease (oxygen >60 days) (Kruskal-Wallis chi2 = 17.53) or high social risk (Kruskal-Wallis chi2 = 22.17). CONCLUSION: In this study of ELBW infants, low birth weight was not associated with abnormal outcome. The risk factors of ICH III-IV/cystic PVL, chronic lung disease, and high social risk were associated with abnormal outcome.

Analysis of Variance↗
PubMed1996

Vitamin B-12 deficiency after gastric surgery for obesity.

Low serum vitamin B-12 concentrations after gastric bypass (GB) surgery for obesity were observed in 11 of 28 patients without detectable impairment of crystalline vitamin B-12 absorption. This was observed in 2 of 19 patients with vertical banded gastroplasty (VBG). In contrast, protein-bound vitamin B-12 absorption was markedly impaired, as demonstrated in eight of these patients after GB (n = 7) and VBG (n = 1). Correction of this impaired absorption occurred when protein-bound vitamin B-12 was incubated with an enzyme mixture before consumption. Simultaneous ingestion of the enzyme mixture with protein-bound vitamin B-12 did not improve absorption of the vitamin. In a separate experiment, 10 patients with a normal result from the Schilling test failed to correct low serum vitamin B-12 concentrations with a quantity of oral crystalline vitamin B-12 equal to the recommended dietary allowance of 2 micrograms, taken twice daily for 3 mo. Serum total homocysteine values declined during this interval. An oral daily dose of 350 micrograms crystalline vitamin B-12 raised the average serum vitamin B-12 concentration to an amount greater than the lower reference limit. A dose > 350 micrograms/d was required to raise all patients' vitamin B-12 concentrations above this concentration rather than just above the population mean. We conclude that because concentrations of oral crystalline vitamin B-12 were required to normalize serum vitamin B-12 concentrations, that a mechanism other than formation of a vitamin B-12 intrinsic factor complex is responsible for crystalline vitamin B-12 absorption after GB for obesity.

Adult↗
PubMed1995

Inhibition of the oncogene product p185erbB-2 in vitro and in vivo by geldanamycin and dihydrogeldanamycin derivatives.

The erbB-2 oncogene encodes a transmembrane protein tyrosine kinase which plays a pivotal role in signal transduction and has been implicated when overexpressed in breast, ovarian, and gastric cancers. Naturally occurring benzoquinoid ansamycin antibiotics herbimycin A, geldanamycin (GDM), and dihydrogeldanamycin were found to potently deplete p185, the erbB-2 oncoprotein, in human breast cancer SKBR-3 cells in culture. Chemistry efforts to modify selectively the quinoid moiety of GDM afforded derivatives with greater potency in vitro and in vivo. Analogs demonstrated inhibition of p185 phosphotyrosine in cell culture and in vivo after systemic drug administration to nu/nu nude mice bearing Fisher rat embryo cells transfected with human erbB-2 (FRE/erbB-2). Specifically, dosed intraperitoneally at 100 mg/kg, 17-(allylamino)-17-demethoxygeldanamycin and other 17-amino analogs were effective at reducing p185 phosphotyrosine in subcutaneous flank FRE/erbB-2 tumors. Modifications to the 17-19-positions of the quinone ring revealed a broad structure-activity relationship in vitro.

Animals↗
PubMed1995

erbB-2 oncogene inhibition by geldanamycin derivatives: synthesis, mechanism of action, and structure-activity relationships.

Overexpression of the erbB-2 oncogene has been linked to poor prognosis in breast, ovarian, and gastric cancers. Naturally occurring benzoquinoid ansamycin antibiotics herbimycin A, geldanamycin (GDM), and dihydrogeldanamycin were found to potently deplete p185, the erbB-2 oncoprotein, in human breast cancer SKBR-3 cells in culture. Chemistry efforts to modify selectively the ansa ring of GDM afforded derivatives with greater potency in vitro and in vivo. Analogs demonstrated inhibition of p185 phosphotyrosine in cell culture and in vivo after systemic drug administration to nu/nu nude mice bearing Fisher rat embryo cells transfected with human erbB-2. Functional group modification in the ansa ring was performed stereoselectively and regiospecifically without the need for protection strategies. Essential functional groups that were required for anti-erbB-2 activity were the 7-carbamate and the 2,3-double bond. Modification of the functional groups at the other positions was permitted. Structure-activity relationships are described for 1-5-, 7-9-, 11-, 15-, and 22-substituted geldanamycins.

Animals↗
PubMed1994

Outcome of very low birth weight infants: multiple gestation versus singletons.

OBJECTIVE: Multiple gestation infants are overrepresented in intensive care nurseries, and have been reported to have greater morbidity than singletons. A cohort of very low birth weight infants was examined to determine outcome of premature infants based on gestation type (multiple or single) and hypothesized that at this low birth weight, the outcome of the groups would be similar. METHOD: The sample was composed of all infants with birth weights < or = 1250 g born in a 10-year period (September 1977 through September 1987). Ninety-two percent (n = 364) of the infants discharged were seen at 1 year of age, and 73% (n = 249) were observed to school age. Morbidity was assessed by neurodevelopmental examinations and standard developmental tests. RESULTS: At 1 year of age and at school age, there were no differences in neurologic or neurosensory outcome between multiple gestation and single gestation infants. Logistic regression analyses were performed on the school age data, using cognitive outcome as the dependent variable and gestation type, birth weight, gestational age, intracranial hemorrhage, chronic lung disease, and a social risk factor as predictor variables. Gestation type was not associated with cognitive outcome at school age. Social risk factors and chronic lung disease showed an association with cognitive outcome at school age. CONCLUSIONS: Multiple gestation was not related to increased morbidity in this very low birth weight group. The developmental outcome of all infants with birth weights < or = 1250 g in this study was related to medical and social risk factors. These findings were consistent for a large group of infants over a 10-year period.

Developmental Disabilities↗
PubMed1994

Homocysteine: relationship to serum cobalamin, serum folate, erythrocyte folate, and lobation of neutrophils.

Serum levels of total homocysteine were studied in the following: 26 healthy adults; 79 hospitalised patients in whom serum cobalamin, serum folate, and erythrocyte folate were greater than 230 pmol/L, 12 nmol/L, and 600 nmol/L, respectively; 32 hospitalised patients whose serum cobalamin was less than 147 pmol/L, compared to 25 patients whose serum cobalamin was greater than 147 pmol/L but unmatched in any other parameter; and 194 patients in whom samples were sent for determination of cobalamin and folate from a neurological service. None of this last group had megaloblastic anaemia. There was a relationship between the elevated concentrations of total homocysteine in serum and low concentrations of serum cobalamin and of erythrocyte folate. This relationship was most evident in samples with serum cobalamin < 86 pmol/L and erythrocyte folate < 335 nmol/L, although elevated homocysteine levels were found in some samples where serum cobalamin and erythrocyte folate levels were greater than these. Serum folate correlated poorly with serum total homocysteine. There was only a poor-to-fair correlation of neutrophil lobe counts to total serum homocysteine.

Adult↗
PubMed1993

Neonatal complications after the administration of indomethacin for preterm labor.

BACKGROUND: The use of indomethacin as a tocolytic agent in pregnant women appears to be accompanied by a low incidence of neonatal complications. However, the neonatal effects of indomethacin have been studied primarily in infants born after 32 weeks' gestation. This study was designed to examine the incidence of neonatal complications in very premature infants. METHODS: We identified 57 infants delivered at or before 30 weeks' gestation whose mothers had been treated with indomethacin for preterm labor and matched them with 57 infants whose mothers had not received indomethacin. The infants in the two groups were matched for sex, gestational age at delivery (mean [+/- SD], 27.6 +/- 2.0 weeks), exposure to betamethasone for 24 hours or more before delivery, and rupture of membranes 24 hours or more before delivery. RESULTS: There were no significant differences between the two groups in birth weight, Apgar scores, cord-blood gas values, frequency of multiple gestation, or incidence of respiratory distress syndrome. The proportion of infants who required exogenous surfactant was similar, as were ventilator settings at 24 hours, the incidence of chronic lung disease, and the incidence of sepsis. The infants exposed to indomethacin had a lower urine output and higher serum creatinine concentrations during the first three days after delivery. More indomethacin-exposed infants had necrotizing enterocolitis (29 percent vs. 8 percent, P = 0.005), intracranial hemorrhage grade II to IV (28 percent vs. 9 percent, P = 0.02), and patent ductus arteriosus (62 percent, vs. 44 percent, P = 0.05). More indomethacin-exposed infants with a patent ductus arteriosus required surgical ligation because of either a lack of initial response or a reopening of the duct after postnatal indomethacin therapy (50 percent vs. 20 percent of the unexposed infants, P = 0.05). CONCLUSIONS: Antenatal indomethacin therapy for preterm labor appears to increase the risk of serious neonatal complications in infants born at or before 30 weeks' gestation.

Cerebral Hemorrhage↗
PubMed1993

Symptomatic and asymptomatic methylenetetrahydrofolate reductase deficiency in two adult brothers.

We describe two brothers with 5,10-methylene tetrahydrofolate reductase (MTHFR) deficiency. The younger patient first developed limb weakness, incoordination, paresthesiae, and memory lapses at age 15 years, and by his early twenties he was wheelchair bound. His older brother remains asymptomatic at age 37 years. Both had homocystinuria and homocystinemia and low plasma levels of methionine. MTHFR activities in cultured skin fibroblasts of both patients were < 10% control and residual enzyme activities were markedly reduced on heating. The parents had intermediate enzyme activities and the reductase in the father (who had unexplained paraparesis and homocystinemia), but not in the mother, was also thermolabile. Both patients were treated with oral folate and betaine which improved, but did not totally correct, their biochemical abnormality. MTHFR deficiency should be considered in the differential diagnosis of unexplained neurologic disease in adolescents and adults.

Adult↗
PubMed1991

Lysosomal cobalamin accumulation in fibroblasts from a patient with an inborn error of cobalamin metabolism (cblF complementation group): visualization by electron microscope radioautography.

Cobalamin (Cbl, vitamin B12) bound to transcobalamin II (TCII) enters cultured fibroblasts by receptor-mediated endocytosis. Following degradation of the TCII, Cbl is subsequently found in either the cytoplasm bound to methionine synthase or in the mitochondria bound to methylmalonyl CoA mutase. In fibroblasts from patients belonging to the cblF complementation group, Cbl is found free in the cell and is not transferred to the above two target enzymes. Quantitative EM radioautography was utilized to visualize intracellular Cbl in fibroblasts from cblF patients and from normal subjects. In cblF cells, 60% of all silver grains were assigned to lysosomes, with only 12.6% over cytoplasm and 1.2% over mitochondria. In contrast, in control cells, only 4.7% were assigned to lysosomes, with 47% to cytoplasm and 23.4% to mitochondria. Subcellular fractionation showed that in cblF cells, the majority of label was associated with clearly recognizable lysosomes. These studies conclusively demonstrate that secondary lysosomes accumulate Cbl in cblF disease.

Autoradiography↗
PubMed1991

The use of the Lanthony New Color Test in determining the effects of aging on color vision.

The primary purpose of this study was to collect data on the loss of color vision as a function of age. The Lanthony New Color Test (NCT), which measures acquired losses of color vision in the dimensions of hue, saturation, and brightness, was used to compile data on 68 subjects. The minimum number of subjects were 10 per decade from age 30 to 90 years. An age gradient of selective loss of discrimination of saturation beginning at age 50 was demonstrated, with rapid change noted after age 60. Similar findings were seen for hue but were not evident for brightness. By age 70, a neutral zone emerged at blue/purple, Munsell chroma level 2. The instrument was shown to be reliable and valid in comparison to the Farnsworth Dichotomous Panel D.15. It is seen that this information will provide a basis for planning safer, more functional environments for elderly people.

Adult↗
PubMed1991

Barrier-free design: a review and critique of the occupational therapy perspective.

This review of the occupational therapy literature on barrier-free design identifies both a paucity of related occupational therapy research on the topic and a lack of a common conceptual base with which to guide the development and use of environmental assessments. Nonetheless, two fledgling themes can be extrapolated: the consistent reference to the concepts of accessibility, mobility, function, and safety and an increased awareness among occupational therapists regarding the accessibility standards developed by the American National Standards Institute (ANSI) (ANSI, 1971, 1980). A problem-solving model suggested by designers for the 1979 revision of ANSI standards that incorporates these conceptual themes is described and discussed.

Activities of Daily Living↗