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Biomedical subjects

M J Brown

Publications and source records attributed to M J Brown.

At least 163 records · Page 9Linked to original sources
PubMed1994

Didanosine compared with continuation of zidovudine in HIV-infected patients with signs of clinical deterioration while receiving zidovudine. A randomized, double-blind clinical trial. The Bristol-Myers Squibb AI454-010 Study Group.

OBJECTIVE: To determine the benefits of switching to didanosine compared with continuing zidovudine among patients infected with human immunodeficiency virus (HIV) who have previously used zidovudine and have signs of clinical deterioration. DESIGN: Randomized, double-blind, two-armed, parallel, comparative clinical trial with a blinded, compassionate crossover provision at 12 weeks. SETTING: Outpatient clinics at 19 tertiary care medical centers. PATIENTS: 312 patients infected with HIV who had received zidovudine for 6 months or more, had CD4 cell counts of 300/mm3 or less, and had signs of clinical deterioration within 12 weeks before study entry. INTERVENTION: Peroral didanosine tablets (600 mg/d adjusted for weight, "high dose") or zidovudine capsules (600 mg/d). MEASUREMENTS: Primary study end points were death, a new acquired immunodeficiency syndrome (AIDS)--defining event, or the combination of two new or recurrent HIV-related diagnoses with a 50% decrease in CD4 cells. RESULTS: Switching to didanosine was associated with fewer end points than continuing zidovudine (relative risk [RR] for zidovudine:didanosine = 1.5; 95% Cl, 1.1 to 2.0). This benefit was consistent across subgroups of patients with either AIDS-related complex or AIDS and was most apparent among those with a CD4 count at entry of 100/mm3 or more (RR = 2.2; Cl, 1.1 to 4.4). CONCLUSIONS: This study shows a positive treatment effect for switching from zidovudine to didanosine among patients with either AIDS-related complex or AIDS and validates the common practice of using clinical signs or a decrease in the CD4 count as an indication for changing therapy.

AIDS-Related Complex↗
PubMed1994

The effects of hedges on spray deposition and on the biological impact of pesticide spray drift.

Two series of drift deposition measurements were carried out at different wind speeds using sodium fluorescein as a tracer dye sprayed over a grass field 6 m upwind of a hedge. Efficient receptors were placed below and above hedge height (1.6 m) between 1 and 20 m downwind from the sprayed area. Receptors below hedge height reflected a sudden decrease in deposition immediately behind the hedge, followed by a gradual increase again up to 15 m, i.e., nine times the height of the hedge. The sheltering effect of a hedge from the biological impact of spray drift was studied by bioassays using tomato and Lychnis flos-cuculi plants for the herbicide MCPA and young Pieris brassicae larvae for the insecticide cypermethrin. These demonstrated that the protection afforded to sensitive species in strong winds may be quite limited, and severe damage may be inflicted over considerable distances. In intermediate cases, a protected zone is followed by a zone of further significant damage before drift depositions cease to have further effect. In some cases, the sheltered zone may extend to a distance where drift deposition, even in the absence of a hedge, has minimal effect.

2-Methyl-4-chlorophenoxyacetic Acid↗
PubMed1994

In vitro expression of calcitonin gene-related peptide in human endothelial cells transfected with plasmid and retroviral vectors.

Introduction of cDNA encoding human alpha-calcitonin gene-related peptide (CGRP), a potent vasodilator, into cultured human umbilical vein endothelial cells (HUVEC) was undertaken by using plasmids and retroviral vectors. In order to improve expression, modification of context coding sequence for the initiation of CGRP translation and deletion of nontranslated regions of CGRP cDNA in the transfection vectors were tested. Stable transfer of neo in the HUVEC was achieved with both plasmid and retroviral vectors. Integration rates obtained by using retrovirus (approximately 1%), where higher than those achieved with plasmid-mediated transfection (< 1/1000). CGRP expressed in the transfected HUVEC was secreted into culture medium when a leading sequence was included in the expression vectors. CGRP was detected by enzyme-linked immunosorbent assay (ELISA) in the supernatants of both transiently transfected and stably transfected/infected HUVEC. Higher levels of expression were achieved by using plasmid (giving a maximum CGRP concentration of 6.5 +/- 0.5 pM in the supernatant) than retroviruses. Lipofectin-mediated transfer of CGRP cDNA also resulted in transient expression of CGRP in the HUVEC.

Calcitonin Gene-Related Peptide↗
PubMed1994

Poisoned landscapes: the epidemiology of environmental lead exposure in Massachusetts children 1990-1991.

This research models the geographic variation in lead poisoning among children living in Massachusetts between 1990 and 1991. Elevated levels of blood lead, which reduce educational performance, arise because children are exposed to unnaturally concentrated sources of lead in the built environment. A Poisson regression model indicates that a large number of children with lead poisoning may be detected in towns with a high proportion of older housing, female headed households, African-Americans, and an industrial heritage. Our results suggest links between the processes of urbanization and industrialization in Massachusetts and today's lead poisoned landscapes.

Child, Preschool↗
PubMed1994

Effects of physiological increments in human alpha-atrial natriuretic peptide and human brain natriuretic peptide in normal male subjects.

1. Brain natriuretic peptide, closely related to atrial natriuretic peptide in structure, may be an important circulating hormone. Its physiological role is unclear. First, we studied the effects of incremental infusions of brain natriuretic peptide in six healthy men on plasma brain natriuretic peptide levels and the pharmacokinetics of brain natriuretic peptide. Synthetic human brain natriuretic peptide-32 was infused intravenously, at an initial rate of 0.4 pmol min-1 kg-1, doubling every 15 min until the dose rate reached 6.4 pmol min-1 kg-1, at which rate the infusion was maintained for 30 min. 2. The brain natriuretic peptide infusion raised the brain natriuretic peptide-like immunoreactivity from 1.4 +/- 0.5 pmol/l to 21.4 +/- 7.6 pmol/l. Brain natriuretic peptide-like immunoreactivity after the end of infusion was consistent with a bi-exponential decay, with half-lives of 2.1 min and 37 min. 3. Next, we studied the effects of low-dose infusion of brain natriuretic peptide to mimic physiological increments in the circulating levels in comparison with atrial natriuretic peptide. Six dehydrated male subjects received intravenous infusions of atrial natriuretic peptide and brain natriuretic peptide, separately and in combination, in a randomized double-blind, placebo-controlled, four-part cross-over design. Atrial natriuretic peptide and brain natriuretic peptide were given at the rate of 0.75 and 0.4 pmol min-1 kg-1, respectively, for 3 h. The control infusion consisted of the vehicle. 4. Analysis of variance showed that atrial natriuretic peptide and atrial natriuretic peptide plus brain natriuretic peptide, but not brain natriuretic peptide alone, increased urinary flow and decreased urinary osmolality significantly.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Electric field-directed fibroblast locomotion involves cell surface molecular reorganization and is calcium independent.

Directional cellular locomotion is thought to involve localized intracellular calcium changes and the lateral transport of cell surface molecules. We have examined the roles of both calcium and cell surface glycoprotein redistribution in the directional migration of two murine fibroblastic cell lines, NIH 3T3 and SV101. These cell types exhibit persistent, cathode directed motility when exposed to direct current electric fields. Using time lapse phase contrast microscopy and image analysis, we have determined that electric field-directed locomotion in each cell type is a calcium independent process. Both exhibit cathode directed motility in the absence of extracellular calcium, and electric fields cause no detectable elevations or gradients of cytosolic free calcium. We find evidence suggesting that galvanotaxis in these cells involves the lateral redistribution of plasma membrane glycoproteins. Electric fields cause the lateral migration of plasma membrane concanavalin A receptors toward the cathode in both NIH 3T3 and SV101 fibroblasts. Exposure of directionally migrating cells to Con A inhibits the normal change of cell direction following a reversal of electric field polarity. Additionally, when cells are plated on Con A-coated substrata so that Con A receptors mediate cell-substratum adhesion, cathode-directed locomotion and a cathodal accumulation of Con A receptors are observed. Immunofluorescent labeling of the fibronectin receptor in NIH 3T3 fibroblasts suggests the recruitment of integrins from large clusters to form a more diffuse distribution toward the cathode in field-treated cells. Our results indicate that the mechanism of electric field directed locomotion in NIH 3T3 and SV101 fibroblasts involves the lateral redistribution of plasma membrane glycoproteins involved in cell-substratum adhesion.

Animals↗
PubMed1994

Demonstration of the neurotransmitter role of calcitonin gene-related peptides (CGRP) by immunoblockade with anti-CGRP monoclonal antibodies.

1. Monoclonal antibodies (MAbs) against rat alpha-calcitonin gene-related peptide (alpha CGRP) were produced. Those which bound CGRP in a radioimmunoassay and inhibited the binding of 2-[125I]-iodohistidyl10-CGRP in a receptor binding assay were selected for immunoblockade experiments. 2. The effect of MAbs on CGRP inhibition of electrically stimulated contractions of the rat isolated vas deferens was characterized. Four out of 11 MAbs tested shifted the concentration-response curve of CGRP to the right compared with vehicle or irrelevant MAb control. MAb C4.19 produced equipotent blockade of rat alpha CGRP and rat beta CGRP and was chosen for further studies. MAb C4.19 had no pharmacologically significant effect on the concentration-response relationship of isoprenaline, rat beta-endorphin or somatostatin. 3. We demonstrated that the pharmacological response to CGRP in the presence of MAb C4.19 could be predicted when the dissociation constant and concentration of binding sites of the antibody were known. Comparison of experimental and computer simulated data showed good agreement for EC50 and maximum effect of CGRP in the presence of MAb C4.19. 4. Capsaicin at 1 microM inhibited the electrically stimulated contractions by 60.8% (95% confidence interval 51.8% to 69.9%). This effect was significantly attenuated by MAb C4.19 to 26.0% (95% confidence interval 15.2% to 36.8%; P < 0.003). 5. The immunoblockade of exogenous and endogenous CGRP described here, together with complementary evidence from other studies, strongly suggest that CGRP has a major neurotransmitter role at the neuroeffector junction of the rat vas deferens.

Animals↗
PubMed1994

Review of neuropsychological functioning in treated phenylketonuria: an information processing approach.

Phenylketonuria is no longer associated with mental retardation and other devastating neurological effects. Nonetheless, learning disabilities and IQ loss are common, even in early-treated individuals. Until recently, IQ was used as the sole measure of mental functioning in this population. As specific academic deficits were recognized and as a greater variety of tests became available, evaluation of children with phenylketonuria has included neuropsychological testing. A review of the 21 published reports highlights the areas of consensus and the need for additional well designed studies in the future. Problem solving, particularly abstract reasoning and executive functions, appears to be impaired in children with phenylketonuria. Reaction time, or speed of mental processing, appears to be the other important area affected in PKU. An information processing model is presented as a paradigm for further research and development of remedial strategies for children with phenylketonuria.

Age Factors↗
PubMed1994

Acute lung disease in the immunocompromised host: CT and pathologic examination findings.

PURPOSE: To compare findings at computed tomography (CT) and pathologic examination in immuno-compromised patients with acute lung disease. MATERIALS AND METHODS: Findings in 33 chest CT scans were compared with findings in pathologic specimens obtained at open lung biopsy (n = 29) or autopsy (n = 4) in 32 patients, aged 17-64 years. RESULTS: Nodules were the main abnormality at CT in 14 cases. Pathologically, the 14 nodules were due to infection (n = 10), bronchiolitis obliterans organizing pneumonia (BOOP) (n = 3), or lymphoma (n = 1). Areas of ground-glass attenuation were the main finding in 15 patients. These areas were a result of BOOP (n = 4), cytotoxic drug reaction (n = 4), infection (n = 4), lymphoma (n = 2), or nondiagnostic biopsy (n = 1). Consolidation was the main finding in four cases, being seen with BOOP (n = 2), infarction due to fungal infection (n = 1), and diffuse pulmonary hemorrhage (n = 1). CONCLUSION: The pattern at CT accurately reflected the gross morphologic features seen in the pathologic specimens. Nodules were usually inflammatory lesions, often infections, and open lung biopsy usually revealed their specific origin.

Acute Disease↗
PubMed1994

Home abatement and blood lead changes in children with class III lead poisoning.

We studied the effect of home abatement on blood lead (PbB) levels in children from central Massachusetts who had not undergone chelation therapy and whose homes were abated between 1987 and 1990, when stricter abatement guidelines were enacted. One hundred and thirty-two children with a mean preabatement PbB of 25.9 micrograms/dL (1.25 mumol/L) were studied: their mean postabatement PbB (up to 1 year later) was 21.1 micrograms/dL (1.02 mumol/L) (P < .001). This reduction correlated with preabatement PbB; 32 of 33 (97%) with preabatement PbB > or = 30 micrograms/dL (> or = 1.45 mumol/L) were lower postabatement, and 64 of 79 (81%) with PbB 20 to 29 micrograms/dL (0.97-1.40 mumol/L) were lower. However, in children with preabatement PbB < 20 micrograms/dL (< 0.97 mumol/L), only seven of 20 (35%) were lower postabatement and, in fact, there was a significant rise in PbB from 16.8 to 19.3 micrograms/dL (0.81 to 0.93 mumol/L) (P = 0.05). Continued improvement in home abatement technology is needed if that strategy is to be effective in achieving the lower PbB levels now mandated in the 1991 Centers for Disease Control guidelines. Primary prevention of the initial blood lead level elevation remains the most desirable strategy.

Age Factors↗
PubMed1994

Plasma brain natriuretic peptide and C-type natriuretic peptide in essential hypertension.

OBJECTIVES: To study the relationship between hypertension and the plasma levels of brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP), and to determine whether the plasma levels of BNP and CNP are correlated. DESIGN: A cross-sectional study of the plasma levels of BNP and CNP in hypertensive patients and normotensive controls matched for age and sex was performed. SETTING: The hypertension research clinic in a teaching hospital and well-person risk factor screening clinics in general practice health centres. PARTICIPANTS: Fifty-four subjects (29 hypertensive, 25 normotensive controls) took part in the study after giving their informed consent. Hypertensive patients (n = 19) were paired with normotensive controls (n = 19) matched for age and sex to form a subgroup before analysis of the plasma. METHODS: The plasma levels of BNP and CNP were determined by specific radioimmunoassays. RESULTS: The mean plasma concentration of BNP was significantly higher in the hypertensive group than in the paired controls. In contrast, the mean plasma concentration of CNP was not significantly different in the hypertensive group than in the paired controls. Multiple regression analysis of all 54 subjects showed that the plasma level of BNP correlated significantly with age and systolic blood pressure, whereas the plasma level of CNP correlated significantly with sex, heart rate and alcohol intake. The CNP levels did not correlate significantly with either systolic or diastolic blood pressure, or with plasma brain natriuretic levels. CONCLUSIONS: Hypertension is associated with raised BNP but not CNP plasma levels.

Aging↗