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Biomedical subjects

A Brown

Publications and source records attributed to A Brown.

At least 163 records · Page 9Linked to original sources
PubMed1999

Microbiological and radioactive contamination from radioaerosol ventilation scanning: is there a problem?

Radioaerosol lung imaging may result in (a) microbiological contamination of nebulizer circuits (a potential hazard to patients if the circuit is re-used), and (b) radioaerosol contamination of the atmosphere (a hazard to staff, particularly if inhaled, ingested or both). Altogether, 138 circuits were assessed for bacteriological contamination, 93 of which had been used for ventilation perfusion studies and 45 for lung permeability studies in human immunodeficiency virus (HIV) positive patients. The circuits used for ventilation/perfusion (V/Q) studies were re-used over a period of 1-5 days. The mouthpiece and Y-piece were changed between patients. The circuits used for permeability studies were changed in toto for each patient. Organisms belonging to normal respiratory flora were isolated from the Y-piece, mouthpiece or both in 9 of 138 cases. An additional case (from one of the HIV-positive patients) demonstrated a growth of methicillin-resistant Staphylococcus. We also demonstrated bacteriological growth, most likely of patient origin, in circuit tubing in 11 cases at the end of the first day's use and 9 cases by day 5. None of the circuits used for HIV-positive cases were culture-positive. Airborne radioactive contamination was assessed during radioaerosol inhalation with and without an air extractor device (Nederman) during 40 ventilation studies. The 20 studies with air extraction showed a large decrease in room air contamination. Nebulizer circuits can, and occasionally do, become contaminated with patients' organisms; this represents a potential infection control hazard and therefore re-use is contraindicated. The use of an air extractor will significantly reduce airborne radioaerosol contamination.

Aerosols↗
PubMed1999

A one-hour walk-in service for wrist trauma imaging.

We investigated the feasibility of rapid imaging of wrist trauma following casualty presentation and any subsequent effect on image quality and interpretability. All patients referred for wrist imaging were injected with 370 MBq 99Tcm-hydroxymethyl diphosphonate (HDP) and imaged 1, 2 and 3 h later. Palmar images were acquired on a 256 x 256 x 16 matrix using a high-resolution collimator, 140 keV photopeak and a 20% window. The images were scored qualitatively by four qualified observers in three categories: image quality, lesion detection and lesion localization. Statistical analysis indicated a significant improvement in scan quality with time, the mean difference (+/- standard error of the mean) between the 1 and 3 h scans being 0.81 +/- 0.07 (P = 0.001). No significant differences were seen in lesion detection (0.05 +/- 0.08; P = 0.51) or localization (0.14 +/- 0.08; P = 0.10). We conclude that imaging of wrist trauma is possible as early as 1 h post-injection of 99Tcm-HDP, although negative studies at 1 h require a 3 h image to maintain diagnostic accuracy.

Adolescent↗
PubMed1999

Impact of a modern firefighting protective uniform on the incidence and severity of burn injuries in New York City firefighters.

The New York City Fire Department (FDNY) is the largest fire department in the United States, with over 11,000 firefighters. In 1994, FDNY changed to a modern firefighting protective uniform. The major difference between traditional and modern uniforms is that modern uniforms include both protective over-coat and over-pant, whereas traditional uniforms include only the over-coat. Furthermore, modern uniforms are manufactured using improved thermal protective textiles that meet or exceed current National Fire Protection Association standards for structural firefighting. The purpose of this study was to determine the impact of the modern uniform on the incidence and severity of FDNY burn injuries. We also evaluated the incidence and severity of other non-burn injuries to determine whether there was serious adverse impact. The number of lower-extremity burns decreased by 85% when 2 years' experience while wearing the modern uniform was compared with 2 years while wearing the traditional uniform. Upper-extremity burns and head burns decreased by 65% and 40%, respectively. Severity indicators (days lost to medical leave, hospital admissions, and skin grafts) for lower- and upper-extremity burn injuries were all substantially reduced. This occurred without significant change in the incidence or severity of trunk burns, heat exhaustion, inhalation injuries (actually decreased), or cardiac events. The reduction in the incidence and severity of burn injuries, the major occupational injury affecting this workforce, has been so dramatic and without untoward effects that the introduction of the modern uniform must be characterized as a sentinel event in the history of firefighter health and safety.

Adult↗
PubMed1999

Distribution of B-cell epitopes on the pseudorabies virus glycoprotein B.

In order to map antigenically important regions of glycoprotein B (gB) of pseudorabies virus (PrV), a panel of recombinant fragments of gB expressed in E. coli and truncated fragments of gB generated by cleavage of purified native gB with trypsin and cyanogen bromide was analysed by using 26 monoclonal antibodies directed against gB. Three continuous epitopes were localized in the vicinity of the N terminus of gB, between amino acids (aa) 59 and 126. One continuous epitope mapped between residues 214 and 279. The residues involved in the assembly of eight discontinuous epitopes were located between aa 540 and 734. The constituents of two discontinuous epitopes were harboured in a segment encompassing aa 540-646. The clustering of continuous epitopes at the extreme N terminus of PrV gB and the locations of residues involved in the assembly of discontinuous epitopes of PrV gB are in good agreement with data on epitope locations in gB homologues from other herpesviruses.

Antibodies, Monoclonal↗
PubMed1999

A study of the follow up patterns of women treated for CIN 2 and 3 before and after the introduction of the 1992 guidelines.

OBJECTIVE: To analyse the five year cytology follow up data after discharge on women treated for histologically proven cervical intraepithelial neoplasia (CIN) 2 and 3. To assess whether the introduction of the 1992 Guidelines for Clinical Practice and Programme Management affected follow up patterns. To identify who was lost to follow up and for what reasons. DESIGN: A retrospective cohort study of cervical cytological follow up data from 186 women treated for CIN 2 and 3. SETTING: Primary care services, West Midlands, United Kingdom. POPULATION: One hundred and eighty-six women with CIN 2 or 3 treated with large loop excision of the transformation zone at the City Hospital, Birmingham, in whom the first follow up smear at six months was normal. The women were divided into two groups: Group 1 consisted of women treated before the introduction of the Guidelines (1988-1990), and Group 2 consisted of women treated at the time of the introduction of the Guidelines in 1992. INTERVENTION: Introduction of the 1992 Guidelines for Clinical Practice and Programme Management. MAIN OUTCOME MEASURES: To determine the number of follow up smears each woman had over a five year period, to determine the number of women who had the recommended number of follow up smears, and to identify the number of women lost to follow up. RESULTS: The median (interquartile range) number of smears in Group 1 was five (four to six) and in Group 2 was four (four to five). A similar proportion of women in both groups subsequently had abnormal smears (15% and 13.6%). Only one woman required further treatment. 22% of women in Group 1 and 10.2% of women in Group 2 had the correct number of smears to fulfil the 1992 Guidelines. There were 21 women (11.3%) who only had one smear following discharge from the clinic in the five year follow up period. CONCLUSIONS: The data from both cohorts shows follow up to be poor, and the introduction of the 1992 Guidelines has yet to result in an improvement in follow up patterns. The absence of a national cervical cytology database means that surveys of cytology follow up data will continue to be difficult due to the problems of data collection from numerous health authorities and the mobility of women in this age group.

Adult↗
PubMed1999

Activation of the PAK-related kinase by human immunodeficiency virus type 1 Nef in primary human peripheral blood lymphocytes and macrophages leads to phosphorylation of a PIX-p95 complex.

Human immunodeficiency virus type 1 (HIV-1) Nef enhances virus replication in both primary T lymphocytes and monocyte-derived macrophages. This enhancement phenotype has been linked to the ability of Nef to modulate the activity of cellular kinases. We find that despite the reported high-affinity interaction between Nef and the Src kinase Hck in vitro, a Nef-Hck interaction in the context of HIV-1-infected primary macrophages is not detectable. However, Nef binding and activation of the PAK-related kinase and phosphorylation of its substrate could be readily detected in both infected primary T lymphocytes and macrophages. Furthermore, we show that this substrate is a complex composed of the recently characterized PAK interacting partner PIX (PAK-interacting guanine nucleotide exchange factor) and its tightly associated p95 protein. PAK and PIX-p95 appear to be differentially activated and phosphorylated depending on the intracellular environment in which nef is expressed. These results identify the PIX-p95 complex as a novel effector of Nef in primary cells and suggest that the regulation of the PAK signaling pathway may differ in T cells and macrophages.

Carrier Proteins↗
PubMed1999

Selection for neutralization resistance of the simian/human immunodeficiency virus SHIVSF33A variant in vivo by virtue of sequence changes in the extracellular envelope glycoprotein that modify N-linked glycosylation.

We previously reported on the in vivo adaptation of an infectious molecular simian/human immunodeficiency virus (SHIV) clone, SHIVSF33, into a pathogenic biologic viral variant, designated SHIVSF33A. In the present study, we show that SHIVSF33A is resistant to neutralization by human immunodeficiency virus (HIV) and SHIV antisera. Multiple amino acid substitutions accumulated over time throughout the env gene of SHIVSF33A; some of them coincided with the acquisition of the neutralization resistance of the virus. Of interest are changes that resulted in the removal, repositioning, and addition of potential glycosylation sites within the V1, V2, and V3 regions of envelope gp120. To determine whether potential glycosylation changes within these principal neutralization domains of HIV type 1 formed the basis for the resistance to serum neutralization of SHIVSF33A, mutant viruses were generated on the backbone of parental SHIVSF33 and tested for their neutralization sensitivity. The mutations generated did not alter the in vitro replication kinetics or cytopathicity of the mutant viruses in T-cell lines. However, the removal of a potential glycosylation site in the V1 domain or the creation of such a site in the V3 domain did allow the virus to escape serum neutralization antibodies that recognized parental SHIVSF33. The combination of the V1 and V3 mutations conferred an additive effect on neutralization resistance over that of the single mutations. Taken together, these data suggest that (i) SHIV variants with changes in the Env SU can be selected in vivo primarily by virtue of their ability to escape neutralizing antibody recognition and (ii) carbohydrates play an important role in conferring neutralization escape, possibly by altering the structure of envelope gp120 or by shielding principal neutralization sites.

Amino Acid Sequence↗
PubMed1999

Prenatal factors and adult mental and physical health.

OBJECTIVE: To review research on prenatal influences on adult mental and physical health and draw implications for future directions in psychiatric research. METHOD: Schizophrenia is selected as an example from mental health and cardiovascular disease as an example from physical health. For each of these disorders, empirical findings on prenatal influences are reviewed, and the methods used to demonstrate them are critiqued. RESULTS: Research on prenatal antecedents of these conditions has proceeded in parallel: intriguing findings have related fetal growth restriction or fetal insult to adult health; similar types of causal pathways have been proposed to explain the relationships; and research has been plagued by similar limitations, including lack of precise prenatal exposure data and difficulty of controlling confounding. The prevailing view of disease causation, which is not well-suited to investigation of prenatal antecedents, impedes research in both fields. Yet, there has been little interchange between researchers in the 2 fields. CONCLUSIONS: We propose a causal paradigm that could serve as a guide for future investigations on the prenatal antecedents of adult health and promote interchange between research on mental and physical health. The paradigm reflects current thinking in epidemiology by encompassing not only risk factors as traditionally conceived but also causal chains over time and causal influences at multiple levels of organization. Implications for the design of new research are illustrated with reference to an ongoing study.

Adult↗
PubMed1999

Krox-20 controls SCIP expression, cell cycle exit and susceptibility to apoptosis in developing myelinating Schwann cells.

The transcription factors Krox-20 and SCIP each play important roles in the differentiation of Schwann cells. However, the genes encoding these two proteins exhibit distinct time courses of expression and yield distinct cellular phenotypes upon mutation. SCIP is expressed prior to the initial appearance of Krox-20, and is transient in both the myelinating and non-myelinating Schwann cell lineages; while in contrast, Krox-20 appears approximately 24 hours after SCIP and then only within the myelinating lineage, where its expression is stably maintained into adulthood. Similarly, differentiation of SCIP-/- Schwann cells appears to transiently stall at the promyelinating stage that precedes myelination, whereas Krox-20(-/-) cells are, by morphological criteria, arrested at this stage. These observations led us to examine SCIP regulation and Schwann cell phenotype in Krox-20 mouse mutants. We find that in Krox-20(-/-) Schwann cells, SCIP expression is converted from transient to sustained. We further observe that both Schwann cell proliferation and apoptosis, which are normal features of SCIP+ cells, are also markedly increased late in postnatal development in Krox-20 mutants relative to wild type, and that the levels of cell division and apoptosis are balanced to yield a stable number of Schwann cells within peripheral nerves. These data demonstrate that the loss of Krox-20 in myelinating Schwann cells arrests differentiation at the promyelinating stage, as assessed by SCIP expression, mitotic activity and susceptibility to apoptosis.

Animals↗
PubMed1999

Microbial dynamics in oil-impacted prairie soil.

A remote site in the Tallgrass Prairie Preserve (Osage County, OK) was contaminated with crude oil by a pipeline break in 1992. In 1996, the contaminated soil was bioremediated by blending with uncontaminated soil, prairie hay, buffalo manure, and commercial fertilizers, and spreading in a shallow layer over uncontaminated soil to create a landfarm. The landfarm was monitored for two years for aerobic and anaerobic bacteria, soil gases indicative of microbial activity, and for changes in the concentration of total petroleum hydrocarbons (TPH). Levels of hydrocarbon degraders and soil gas indicators of aerobic degradation were stimulated in the landfarm during the first warm season relative to uncontaminated prairie soil. However, these same indicators were less conclusive during the second warm season, indicating depletion of the more easily degradable hydrocarbons, although the landfarm still contained 6,800 mg/kg TPH on the average at the beginning of the second warm season. Methane formation and methanogen counts were clearly stimulated in the first warm season relative to uncontaminated prairie soil, indicating that methanogenesis plays an important role in the mineralization of hydrocarbons even in these shallow soils.

Journal Article↗
PubMed1999

Automated system for capture and detection of nucleic acids.

A fully automated nucleic acid analysis system is described, which offers positive sample identification, improved sensitivity and reduced user interaction compared to conventional techniques. The system relies on the sequence-specific capture of DNA onto solid-phase particles, confirming product identity without the problems of interpretation and lack of sequence information inherent in gel-based analyses. The system can be used for sequence confirmation, mutation analysis and semiquantitative detection of PCR products.

Automation↗
PubMed1999

Necator americanus (human hookworm) aspartyl proteinases and digestion of skin macromolecules during skin penetration.

The infective larvae of Necator americanus were shown to secrete all mechanistic classes of proteolytic enzymes with two overall pH optima of 6.5 and 8.5 using fluorescein isothiocyanate-labeled casein as the substrate. Since infective larvae are obligate skin penetrators, the effect of each of these enzyme classes against macromolecules derived from human skin was examined. Larval secretions were shown to degrade collagen types I, III, IV, and V, fibronectin, laminin, and elastin. All the skin macromolecules tested were hydrolyzed by aspartyl proteinase activity, which was inhibitable by pepstatin A. Collagen and elastin was also hydrolyzed by metalloproteinase activity, while the serine proteinase activity hydrolyzed only elastin. As a consequence of these experiments, the effect of proteinase inhibitors on the penetration of live larvae through hamster skin was tested. Larval penetration was significantly inhibited only by pepstatin A, confirming the importance of the aspartyl proteinase activity during the skin penetration process.

Animals↗
PubMed1999

Treatment costs of directly observed therapy and traditional therapy for Mycobacterium tuberculosis: a comparative analysis.

OBJECTIVE: Treatment of tuberculosis is a time-consuming and expensive process, often complicated by patient non-adherence. Directly observed therapy (DOT), an out-patient management strategy designed to ensure adherence, is not widely used because it is perceived to be too expensive. This study compared costs of tuberculosis treatment in DOT to the same factors in traditional therapy. DESIGN: A retrospective economic evaluation of 659 tuberculosis cases was reported to a major metropolitan county public health department between 1980 and 1994. Out-patient costs, in-patient costs and the cost impact of relapse and acquired resistance were estimated in 1995 dollars. RESULTS: Treatment costs were lower with DOT: $15,670 per case for in-patient care and $700 per case for out-patient care (P < 0.001). These cost differences resulted from shorter therapy duration (334 vs 550 days), fewer patient hospitalizations (58 vs 75%) and shorter hospital stays (26 vs 55 days per hospitalized patient). Relapse or acquired resistance occurred in 10.9% of patients and accounted for 35.7% of cost with traditional therapy, as compared to 1.2% of patients and 6.0% of cost with observed therapy. CONCLUSIONS: Directly observed therapy is less costly than traditional therapy.

Adolescent↗
PubMed1999

Relative effectiveness and cost-effectiveness of methods of androgen suppression in the treatment of advanced prostate cancer.

OBJECTIVES: With 184,500 new cases and 39,200 deaths anticipated in 1998, prostate cancer is second only to lung cancer in cancer mortality for men. This report is a systematic review of the evidence from randomized controlled trials on the relative effectiveness of alternative strategies for androgen suppression as treatment of advanced prostate cancer. Three key issues are addressed: (1) the relative effectiveness of the available methods for monotherapy (orchiectomy, luteinizing hormone-releasing hormone [LHRH] agonists, and antiandrogens), (2) the effectiveness of combined androgen blockade compared to monotherapy, and (3) the effectiveness of immediate androgen suppression compared to androgen suppression deferred until clinical progression. Outcomes of interest are overall, cancer-specific, and progression-free survival; time to treatment failure; adverse effects; and quality of life. Two supplementary analyses were conducted for each key question: (1) meta-analysis of overall survival at 2 years (questions 1 and 2) and 5 years (questions 2 and 3), and (2) cost-effectiveness analysis. SEARCH STRATEGY: The MEDLINE, CANCERLIT, and EMBASE databases were searched from 1966 to March 1998, and Current Contents to August 24, 1998, for the terms: leuprolide (Lupron); goserelin (Zoladex); buserelin (Suprefact); flutamide (Eulexin); nilutamide (Anandron, Nilandron); bicalutamide (Casodex); cyproterone acetate (Androcur); diethylstilbestrol (DES); and orchiectomy (castration, orchidectomy). The search was then limited to human studies indexed under the MeSH term "prostatic neoplasms" and by the UK Cochrane Center search strategy for randomized controlled trials. Total yield was 1,477 references. SELECTION CRITERIA: We Reports of efficacy outcomes were limited to randomized controlled trials. Phase II studies that reported on withdrawals from therapy and all studies reporting on quality of life were also included. DATA COLLECTION AND ANALYSIS: The systematic review used a prospectively designed protocol conducted by two independent reviewers, with disagreements resolved by consensus. The meta-analysis combined data on overall survival using a random effects model. The cost-effectiveness analysis used a decision analysis model of advanced prostate cancer with health states and transitions derived from the literature and estimates of effectiveness derived from the meta-analysis. The cost-effectiveness analysis is conducted from a societal perspective, consistent with the guidelines of the U.S. Public Health Service Panel on Cost-Effectiveness in Health and Medicine. MAIN RESULTS: Survival after treatment with an LHRH agonist is equivalent to survival after orchiectomy. The available LHRH agonists are equally effective, and no LHRH agonist is superior to the other when adverse effects are considered. Survival may be somewhat lower with use of a nonsteroidal antiandrogen. There is no statistically significant difference in survival at 2 years between patients treated with combined androgen blockade or monotherapy. Meta-analysis of the limited data available shows a statistically significant difference in survival at 5 years that favors combined androgen blockade. However, the magnitude of this difference is of questionable clinical significance. For the subgroup of patients with good prognosis, there is no statistically significant difference in survival. Adverse effects leading to withdrawal from therapy occurred more often with combined androgen blockade. No evidence is yet available from randomized controlled trials of androgen suppression initiated at prostate-specific antigen (PSA) rise after definitive therapy for clinically localized disease. For patients who are newly diagnosed with locally advanced or asymptomatic metastatic disease, the evidence is insufficient to determine whether primary androgen suppression initiated at diagnosis improves outcomes. (ABSTRACT TRUNCATED)

Androgen Antagonists↗
PubMed1998

Enzymatically active papain preferentially induces an allergic response in mice.

Human exposure to papain, a cysteine proteinase, is associated with hypersensitivity reactions. We demonstrate in mice that enzymatically active papain preferentially induces an IgG1 response and results in mast cell degranulation, both features typical of an allergic reaction. Inactive papain, blocked with E-64, appears to desensitize mice to subsequent challenge by active enzyme. These results suggest that the enzymatic activity of papain is critical in inducing an allergic response and that the use of inactive allergens may be a possible strategy for desensitizing allergic individuals.

Animals↗
PubMed1998

Nigrostriatal dopaminergic activities in dementia with Lewy bodies in relation to neuroleptic sensitivity: comparisons with Parkinson's disease.

BACKGROUND: In dementia with Lewy bodies (DLB) mild extrapyramidal symptoms are associated with moderate reductions in substantia nigra neuron density and concentration of striatal dopamine. Many DLB patients treated with typical neuroleptics suffer severe adverse reactions, which result in decreased survival. METHODS: In a series of DLB cases, with and without neuroleptic sensitivity, substantia nigra neuron densities, striatal dopamine and homovanillic acid concentrations, and autoradiographic [3H]mazindol and [3H]raclopride binding (to the dopamine transporter and D2 receptor, respectively) were analyzed and compared to control and idiopathic Parkinson's disease cases. RESULTS: D2 receptors were up-regulated in neuroleptictolerant DLB and Parkinson's disease compared to DLB without neuroleptic exposure and controls. D2 receptors were not up-regulated in DLB cases with severe neuroleptic reactions. Dopamine uptake sites were reduced concomitantly with substantia nigra neuron density in Parkinson's disease compared to controls, but there was no significant correlation between substantia nigra neuron density and [3H]mazindol binding in DLB groups. There was no significant difference in substantia nigra neuron density, [3H]mazindol binding, and dopamine or homovanillic acid concentration between neuroleptic-tolerant and -sensitive groups. CONCLUSIONS: Failure to up-regulate D2 receptors in response to neuroleptic blockade or reduced dopaminergic innervation may be the critical factor responsible for neuroleptic sensitivity.

Adult↗