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Biomedical subjects

L Brown

Publications and source records attributed to L Brown.

At least 163 records · Page 9Linked to original sources
PubMed1995

Saliva and serum as diagnostic media for antibody to hepatitis A virus in adults and in individuals who have received an inactivated hepatitis A vaccine.

Saliva was evaluated as a diagnostic fluid for screening individuals for evidence of previous hepatitis A virus (HAV) infection and for evidence of seroconversion after vaccination with inactivated hepatitis A vaccine. A new and simple saliva collection method and an assay for detection of HAV antibody were used; the assay used an antibody capture format. There was complete concordance between the results of saliva-based assays and those of serum-based assays, both of which were used for determining previous natural HAV exposure. However, for vaccine recipients, 100% concordance for saliva-based and serum-based assays occurred only at serum titers of > 9,000 mIU/mL, which were determined with use of the modified HAVAB assay. Saliva provides adequate sensitivity and specificity for determining naturally acquired HAV infection, although it is not useful in clinical trials for determining seroconversion after HAV vaccination.

Adult↗
PubMed1995

New drugs in the treatment of heart failure.

1. Current therapy of heart failure relies on diuretics, positive inotropic compounds and vasodilators. The short-term haemodynamic benefits, especially of the cAMP generators, may be compromised by long-term limitations leading to an increased mortality. In contrast, some vasodilators, especially angiotensin converting enzyme inhibitors, improve survival even in severe heart failure. 2. Modulation of Na(+)- or K(+)-channels and calcium sensitization are positive inotropic mechanisms whose promise in treatment of heart failure needs to be fully explored. 3. The introduction of vasodilator therapy has been a significant advance. Newer compounds act to inhibit the endogenous vasoconstrictors angiotensin II and endothelin, or to potentiate the endogenous vasodilators atrial natriuretic factor and nitric oxide. The full potential of these compounds is yet to be realised.

Cardiotonic Agents↗
PubMed1995

alpha 1-Adrenoceptors on rabbit aortic smooth muscle cells in culture and in experimental intimal thickening.

1. This study has defined alpha 1-adrenoceptors and their reactivity in rabbit aorta, following removal of the endothelium and formation of a myointimal thickening, and also in smooth muscle cells (SMC) in cell culture which had undergone serial passaging and changes in phenotype. 2. [3H]-prazosin binding to SMC from control aorta, vessels 2 weeks after endothelial denudation and sub-cultured SMC (passage 3-6) was specific (displaceable with 10 mumol/L phentolamine), and of high affinity to a single class of sites (KD range: 71-114 pmol/L). The maximum binding density (Bmax) of alpha 1-adrenoceptors on SMC from the neointima (11,105 +/- 771 sites/cell) was not significantly different to that of control medial SMC (14,014 +/- 2472 sites/cell). However, SMC cultured to passage 6, showed a 2-fold increase in Bmax (30,227 +/- 4349 sites/cell). 3. The production of inositol phosphates (IP1, IP2 and IP3) by SMC following 10 mumol/L phenylephrine was assayed. Both freshly-dispersed aortic SMC and sub-cultured SMC were stimulated to produce increased inositol phosphates by the addition of phenylephrine which was completely inhibited by pre-incubation with 10 mumol/L phentolamine, suggesting that the stimulation was via alpha 1-adrenoceptors. 4. Maximal contractile responses of isolated thoracic and abdominal aortic rings to KCl (100 mmol/L), 5-HT and phenylephrine were unchanged two weeks after endothelial denudation. However, phenylephrine was significantly less potent (2.7-fold) in both areas of the aorta, while the potency of 5-HT was significantly enhanced (2.7-fold) after endothelial denudation only in the abdominal aorta. 5. The decreased sensitivity of the rabbit aorta to alpha 1-adrenoceptor agonists following endothelial denudation and the formation of a myointimal thickening is not due to changes in affinity or density of alpha 1-adrenoceptors. However multiple passaging of SMC in culture leads to an increase in alpha 1-adrenoceptor density. This change can be related to the altered cytodifferentiation of irreversible synthetic state SMC which are similar to those in atherosclerotic lesions.

Animals↗
PubMed1995

Assessment of the effect of head and neck position on upper airway anatomy in sedated paediatric patients using magnetic resonance imaging.

Upper airway patency can be compromised when children (or adults) receive sedative medication. The study examines the effect of two different positioning techniques (use of the 'sniff position pillow' (SPP) and shoulder elevation (SE) on maintenance of upper airway patency using MRI in 21 children sedated with intravenous pentobarbital (5-8 mg.kg-1). Children positioned on the SPP had a significantly greater degree of atlanto-occipital extension (P < 0.05), and a significantly greater nasopharyngeal diameter (P < 0.05) than those with shoulder elevation. The degree of atlanto-occipital extension was not significantly correlated with pharyngeal diameter (R = -0.68). No clinical signs of upper airway obstruction were noted and oxygen desaturation did not occur. Both positioning techniques were consistently associated with upper airway patency under the study conditions described. In obligate nose breathers to whom sedative agents are administered, the SPP is more likely to maintain nasopharyngeal patency than shoulder elevation.

Adjuvants, Anesthesia↗
PubMed1994

A novel human protein serine/threonine phosphatase, which possesses four tetratricopeptide repeat motifs and localizes to the nucleus.

A novel human protein serine/threonine phosphatase, PP5, and a structurally related phosphatase in Saccharomyces cerevisiae, PPT1, have been identified from their cDNA and gene respectively. Their predicted molecular mass is 58 kDa and they comprise a C-terminal phosphatase catalytic domain and an N-terminal domain, which has four repeats of 34 amino acids, three of which are tandemly arranged. The phosphatase domain possesses all the invariant motifs of the PP1/PP2A/PP2B gene family, but is not closely related to any other known member (< or = 40% identity). Thus PP5 and PPT1 comprise a new subfamily. The repeats in the N-terminal domain are similar to the tetratricopeptide repeat (TPR) motifs which have been found in several proteins that are required for mitosis, transcription and RNA splicing. Bacterially expressed PP5 is able to dephosphorylate serine residues in proteins and is more sensitive than PP1 to the tumour promoter okadaic acid. A 2.3 kb mRNA encoding PP5 is present in all human tissues examined. Investigation of the intracellular distribution of PP5 by immunofluorescence, using two different antibodies raised against the TPR and phosphatase domains, localizes PP5 predominantly to the nucleus. This suggests that, like other nuclear TPR-containing proteins, it may play a role in the regulation of RNA biogenesis and/or mitosis.

Amino Acid Sequence↗
PubMed1994

Identification of a cDNA encoding a Drosophila calcium/calmodulin regulated protein phosphatase, which has its most abundant expression in the early embryo.

A 3.3 kb cDNA encoding the complete amino acid sequence of a calcium/calmodulin regulated protein phosphatase has been isolated from a Drosophila eye disc cDNA library. The predicted protein of 560 amino acids (molecular mass 62 kDa) is 73-78% identical to human PP2B isoforms. The cDNA hybridised to the X-chromosome at cytological position 14D1-4. Two transcripts of 3.5 kb and 3.0 kb were expressed during embryonic development, their levels being highest in the early embryo. The larger transcript was also clearly present in adult females. This pattern of expression indicates a role for calcium/calmodulin regulated protein phosphatase in embryonic development.

Amino Acid Sequence↗
PubMed1994

Adrenoceptor-mediated cardiac and vascular responses in hypothyroid rats.

This study has investigated adrenoceptor-mediated responses and beta-adrenoceptors in neonatal-onset hypothyroidism in rats. Four groups of adult rats were studied: controls, neonatal-onset uncorrected hypothyroidism (continuous oral methimazole treatment) and after chronic triiodothyronine (T3) replacement of these rats at either 25 or 100 micrograms/kg/day for 8 weeks beginning at 12 weeks of age. Hypothyroid rats were 61% smaller with an 18% decrease in heart rate; food and water intake were reduced to 43% and 52%, respectively; O2 consumption was reduced to 20% and rectal temperature was 2.9 degrees lower. T3 administration increased body weight to 60-62% of controls; metabolic changes were reversed; but tachycardia and cardiac hypertrophy (60-120% increases) resulted. The positive inotropic responses to the selective alpha 1-adrenoceptor agonist, phenylephrine, in left ventricular papillary muscles were abolished; the beta 1-adrenoceptor agonist, noradrenaline, was significantly less potent as an inotropic compound in isolated cardiac tissues from hypothyroid rats. The potency of phenylephrine to contract thoracic aortic rings was reduced in hypothyroid rats. These changes in alpha- and beta-adrenoceptor mediated responses were reversed by T3 administration. Both beta 1- and beta 2-adrenoceptor densities were increased in the hypothyroid left ventricle; T3 administration further increased beta 1-adrenoceptor density. We conclude that neonatal hypothyroidism produces pronounced physiological responses, changes in adrenoceptor-mediated responses and an increased ventricular beta 1-adrenoceptor density. T3 replacement reversed the changes in cardiac responses and metabolic parameters, except body weight, but produced cardiac symptoms of hyperthyroidism (tachycardia, hypertrophy as well as an increased beta 1-adrenoceptor density).

Animals↗
PubMed1994

Pseudochoreoathetosis. Movements associated with loss of proprioception.

OBJECTIVE: To describe seven patients with proprioceptive sensory loss and choreoathetoid movements. DESIGN: Case series. SETTING: Outpatient and inpatient university referral. PATIENTS: Patients with sensory loss and abnormal movements. INTERVENTION: None. MAIN OUTCOME MEASURE: None. RESULTS: One patient had a parietal cortex injury, one had a thalamic infarction, two had spinal cord lesions, two had dorsal root ganglion neuronopathies, and one had an ulnar neuropathy. In each case, the duration of abnormal movements correlated with the duration of proprioceptive sensory loss, and the abnormal movements were restricted to body parts with proprioceptive sensory loss. The movements varied from chorea and athetosis to dystonia. CONCLUSIONS: These cases suggest that proprioceptive sensory loss can lead to a movement disorder, termed pseudochoreoathetosis, which occurs following the appearance of lesions anywhere along proprioceptive sensory pathways, from peripheral nerves to the cerebral cortex. It is hypothesized that pseudochoreoathetosis occurs because of the failure to process limb proprioceptive information in the striatum. Therefore, both choreoathetosis and pseudochoreoathetosis may be manifestations of the failure of the striatum to properly integrate cortical motor and sensory inputs.

Adult↗
PubMed1994

Molecular characterization of Borna virus RNAs.

Borna disease virus is cell-associated in infected animals. Antibodies in animals are directed against BDV proteins of 38/39, 24, and 14.5 kD. cDNA clones that encode these proteins hybridize to five mRNAs of 10.5, 3.6, 2.1, 1.4, and 0.85 kb. The 10.5, 3.6, 2.1, and 0.85 kb RNAs are 3' co-terminal; the 1.4 kb RNA is contained within the 10.5, 3.6, and 2.1 kb species but is not 3' co-terminal. A negative strand 10 kb RNA is also present in infected cells. To determine which of the large 10 kb species represents the genomic RNA, strand-specific probes were used for Northern analyses of RNA from infectious particles isolated by Freon extraction of BDV-infected rat brain. RNA purified from these particles contained both positive and negative sense 10 kb species. Treatment of particles with RNaseA before isolation of RNA resulted in detection of only negative strand species, suggesting that BDV is a negative strand RNA virus. However, the genomic organization of BDV is unlike any known negative strand RNA virus.

Animals↗
PubMed1994

Mode of delivery and perinatal results in breech presentation.

OBJECTIVES: Our purpose was to evaluate the outcome of deliveries with fetuses in breech presentation at labor and to compare the results by route of delivery. Specially reviewed were fetuses weighing > or = 1500 gm. STUDY DESIGN: An observational study of consecutive cases of all singleton pregnancies and twin pregnancies with the first fetus presenting in breech delivered at Chicago Lying-In Hospital from July 1980 to December 1987 was performed. Crude perinatal mortality and effect of mode of delivery (cesarean vs vaginal) by weight were compared after correction for nonpreventable causes. A further correction was made for fetuses weighing > or = 1500 gm by excluding all cases of fetal distress from the cesarean section group. All clinically relevant factors were evaluated. Statistical methods included comparison of frequencies in the two groups by chi 2 and Fisher exact tests and comparison of means by two-sample t tests. RESULTS: Of 21,380 deliveries, 843 (3.9%) presented by the breech. Forty-four percent were delivered vaginally; 8.4% were first twins. There were 51% preterm infants, and 24% had clinical distress. Crude perinatal mortality was 24%; 8% stillborns, 10% from prematurity, and 6% from other causes, including lethal congenital malformations. The corrected perinatal mortality was 15%. Vaginal deliveries had a higher 5-minute depression rate (32% vs 24%) and corrected perinatal mortality (23% vs 9.6%); however, fetal weights were significantly lower. There were no differences in outcomes for newborns weighing > or = 1500 gm by route of delivery; all five neonatal deaths in this subgroup occurred among the abdominal deliveries. CONCLUSIONS: The very poor perinatal outcomes in breeches are primarily related to factors other than breech presentation. Route of delivery for infants weighing > or = 1500 gm does not influence neonatal outcome; thus cesarean section solely for breech presentation in this subgroup does not appear to be justified.

Adolescent↗
PubMed1994

Factors influencing neonatal outcomes in the very-low-birth-weight fetus (< 1500 grams) with a breech presentation.

OBJECTIVES: Our purpose was to evaluate factors that may influence perinatal outcomes in the very-low-birth-weight infant with breech presentation. STUDY DESIGN: An observational study that included all consecutive singletons and twins with the first fetus with breech presentation weighing between 500 and 1500 gm delivered at Chicago Lying-In Hospital from July 1980 to December 1987 was performed. Uncorrected and corrected perinatal mortality and morbidity were calculated. After correction, the effect of mode of delivery (vaginal versus cesarean section) was studied. A further correction was made by excluding cesarean sections performed for fetal distress. Statistical methods included chi 2 and Fisher exact tests and logistic regression analyses to calculate unadjusted and adjusted odds ratios. RESULTS: Of the 262 fetuses studied, nearly 60% were delivered vaginally and were of younger gestational age and lower fetal weight (300 gm) than those delivered abdominally. Forty-four percent weighed < or = 800 gm, and the perinatal mortality rate was 64.5% (53.3% after correction). Vaginal delivery had higher rates of depression, respiratory distress syndrome, and death. Prematurity was the most frequent cause of neonatal death. The corrected neonatal mortality was similar to the total inborn population of our neonatal intensive care unit for the same years. Logistic regression analyses revealed that the differences in outcomes between the two groups were primarily related to effects of gestational age, fetal weight, and year of delivery. After these factors were adjusted for, the odds of neonatal death for vaginal delivery compared with cesarean delivery were not significantly different (odds ratio 1.4, 95% confidence interval 0.6 to 3.5, p = 0.48). However, in the subgroup in footling attitude the differences were much greater, with an adjusted odds ratio of 3.2 (95% confidence interval 0.7 to 14.9, p = 0.13). CONCLUSION: The exceedingly poor perinatal outcomes of very-low-birth-weight breech infants are mainly related to antenatal deaths (22%), extremely low birth weight (44%), congenital malformations, and premature labor, not to the breech presentation. The route of delivery did not significantly influence outcome among complete and frank attitudes; abdominal delivery may offer some benefit for footlings. Prematurity is the primary cause of death of normal very-low-birth-weight breech-delivered infants.

Birth Weight↗
PubMed1994

Prevalence and differentials of low birth weight in Niamey, Niger.

This study provides population representative data on live births occurring in Niamey, Niger during the period 1980 to 1985. A total of 5097 live births were systematically sampled from maternity registers over the study period. Due to legislation and incentives to register all live births, between 90 and 95 per cent of all live births are represented in this study. The data here suggest that low birth weight (LBW) prevalence may be lower in this urban area than it is in the region as a whole; and that the demographic risk factors are similar to those found in other developing countries. Finally, in many developing countries, maternity coverage of attended births may be quite high, suggesting that record or prospective studies examining trends in LBW and risk factors for perinatal outcomes might be convenient and implemented at very low cost.

Adult↗
PubMed1994

Calcium sensitization as a positive inotropic mechanism in diseased rat and human heart.

The two isomers of the positive inotropic compound EMD 53998, (+)EMD 57033 and (-)EMD 57439, possess selective calcium sensitizing and phosphodiesterase (PDE) inhibitory properties, respectively. We measured the pharmacological responses to both enantiomers in isolated rat cardiac and vascular tissues and in muscles from severely failing human hearts. We also measured positive inotropic and chronotropic responses to EMD 57033 in cardiac tissues from rats with thyroid dysfunction, diabetes, or hypertension. Both compounds increased force of contraction in isolated rat cardiac tissues, although the ventricular response to EMD 57439 was only approximately 10% that of calcium chloride. Forskolin pretreatment potentiated responses to both compounds in atria but only to EMD 57439 in ventricles. Hyperthyroidism increased ventricular responses to EMD 57033 relative to calcium chloride; hypothyroidism and diabetes decreased these responses. Ventricular responses were unchanged in hypertensive rats. Both enantiomers produced positive inotropy in human isolated right atrial trabeculae, although the maximal increases were only 14% (EMD 57033) and 26% (EMD 57439) that of calcium chloride. In rat thoracic aortic rings, both enantiomers produced relaxation; the responses due to EMD 57033 were endothelium dependent. Thus, calcium sensitization produces positive inotropy and vascular relaxation in rats. Positive chronotropic responses to EMD 57033 are most likely due to PDE inhibition. The limited inotropic response in severely failing human myocardium, together with possible vasorelaxation, may provide cardiac support in heart failure without an excessive increase in cardiac O2 demand.

Animals↗
PubMed1994

Immunogenicity, safety and tolerability of varying doses and regimens of inactivated hepatitis A virus vaccine in Navajo children.

The Navajo are known to be at high risk for hepatitis A virus (HAV) infection. This study investigated the safety and immunogenicity of an investigational, alum-adjuvanted, formalin-inactivated HAV vaccine (VAQTA) developed by Merck Research Laboratories in Navajo children. One hundred two of 212 children, ages 4 to 12 years, were HAV-seronegative (< 10 mIU/ml by an enhanced sensitivity modification of the HAVAB; Abbott). Ninety of these children received the HAV vaccine. Study participants were given vaccines containing various viral protein concentrations: Group A (n = 18), 6 units; Group B (n = 36), 13 units; and Group C (n = 36), 25 units HAV protein (1 unit approximately 1 ng viral protein antigen). Three-dose (0, 8, 24 weeks) and two-dose (0, 24 weeks) regimens were compared in subgroups within B and C. The vaccine was well-tolerated and there were no serious adverse reactions; no vaccinee developed hepatitis A. After 1 dose 82 to 100% of children seroconverted (> or = 10 mIU/ml, modified HAVAB; Abbott) and 100% seroconverted after 2 doses. After 1 dose the geometric mean titer for antibody was: Group A, 22 mIU/ml; Group B, 18 mIU/ml; and Group C, 38 mIU/ml. After 3 doses geometric mean titers increased to 10,106 mIU/ml in Group A, 7258 mIU/ml in Group B and 11,856 mIU/ml in Group C. Further field studies are indicated to evaluate its use in high risk populations, such as the Navajo.

Age Factors↗