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Biomedical subjects

L Brown

Publications and source records attributed to L Brown.

At least 55 records · Page 3Linked to original sources

Surveillance of depleted uranium exposed Gulf War veterans: health effects observed in an enlarged "friendly fire" cohort.

To determine clinical health effects in a small group of US Gulf War veterans (n = 50) who were victims of depleted uranium (DU) "friendly fire," we performed periodic medical surveillance examinations. We obtained urine uranium determinations, clinical laboratory values, reproductive health measures, neurocognitive assessments, and genotoxicity measures. DU-exposed Gulf War veterans with retained metal shrapnel fragments were excreting elevated levels of urine uranium 8 years after their first exposure (range, 0.018 to 39.1 micrograms/g creatinine for DU-exposed Gulf War veterans with retained fragments vs 0.002 to 0.231 microgram/g creatinine in DU exposed but without fragments). The persistence of the elevated urine uranium suggests ongoing mobilization from the DU fragments and results in chronic systemic exposure. Clinical laboratory outcomes, including renal functioning, were essentially normal. Neurocognitive measures showing subtle differences between high and low uranium exposure groups, seen previously, have since diminished. Sister chromatid exchange frequency, a measure of mutation in peripheral lymphocytes, was related to urine uranium level (6.35 sister chromatid exchanges/cell in the high uranium exposure group vs 5.52 sister chromatid exchanges/cell in the low uranium exposure group; P = 0.03). Observed health effects were related to subtle but biologically plausible perturbations in central nervous system function and a general measure of mutagen exposure. The findings related to uranium's chemical rather than radiologic toxicity. Observations in this group of veterans prompt speculation about the health effects of DU in other exposure scenarios.

Adult↗

Partners for NP education: the 1999 AANP preceptor and faculty survey.

PURPOSE: To increase understanding of national trends in nurse practitioner (NP) clinical education, the Education Committee of the American Academy of Nurse Practitioners (AANP) conducted a survey at the 1999 National AANP Conference in Atlanta. DATA SOURCES: A convenience sample of preceptors (n = 87) and faculty (n = 42) out of the total attendance of 1,744 responded to a written questionnaire. CONCLUSIONS: Preceptor respondents provided data concerning the number of NP students supervised, influence of student supervision on productivity, and availability of incentives for precepting. Faculty reported placement and supervision issues, the extent of precepting in their clinical practice site, and recognition and support for this role. Faculty and preceptors disagreed about the types and number of incentives offered for accepting students as well as the congruence of clinical teaching activities and national teaching guidelines. Precepting did not appear to strongly influence preceptor productivity. External funding did not influence opportunities for clinical education. IMPLICATIONS FOR PRACTICE: In 1998, the graduates of NP programs rose by 15.8% and over half of all nursing students enrolled in graduate nursing programs were seeking a NP education. This increase in students may compromise the ability of schools of nursing to insure quality clinical education of NP students by increasing faculty workload and placing greater demands on expert preceptors in the community. Clinical education is also changing in light of changes in the health care system.

Data Collection↗

Effect of manually assisted cough and mechanical insufflation on cough flow of normal subjects, patients with chronic obstructive pulmonary disease (COPD), and patients with respiratory muscle weakness.

BACKGROUND: It has been suggested that cough effectiveness can be improved by assisted techniques. The effects of manually assisted cough and mechanical insufflation on cough flow physiology are reported in this study. METHODS: The physiological actions and patient self-assessment of manually assisted cough and mechanical insufflation were investigated in 29 subjects (nine normal subjects, eight patients with chronic obstructive pulmonary disease (COPD), four subjects with respiratory muscle weakness (RMW) with scoliosis, and eight subjects with RMW without scoliosis). RESULTS: The peak cough expiratory flow rate and cough expiratory volume were not improved by manually assisted cough and mechanical insufflation alone or in combination in normal subjects. The median increase in peak cough expiratory flow in subjects with RMW without scoliosis with manually assisted cough alone or in combination with mechanical insufflation of 84 l/min (95% confidence interval (CI) 19 to 122) and 144 l/min (95% CI 14 to 195), respectively, reflects improvement in the expulsive phase of coughing by these techniques. Manually assisted cough and mechanical insufflation in combination raised peak expiratory flow rate more than either technique alone in this group. The abnormal chest shape in scoliotic subjects and the fixed inspiratory pressure used made effective manually assisted cough and mechanical insufflation difficult in this group and no improvements were found. In patients with COPD manually assisted cough alone and in combination with mechanical insufflation decreased peak expiratory flow rate by 144 l/min (95% CI 25 to 259) and 135 l/min (95% CI 30 to 312), respectively. CONCLUSIONS: Manually assisted cough and mechanical insufflation should be considered to assist expectoration of secretions in patients with RMW without scoliosis but not in those with scoliosis.

Adolescent↗

The spironolactone renaissance.

Until recently, spironolactone was considered only as an antagonist at the aldosterone receptors of the epithelial cells of the kidney and was used clinically in the treatment of hyperaldosteronism and, occasionally, as a K(+)-sparing diuretic. The spironolactone renaissance started with the experimental finding that spironolactone reversed aldosterone-induced cardiac fibrosis by a cardiac action. Experimentally, spironolactone also has direct effects on blood vessels. Spironolactone reduces vascular fibrosis and injury, inhibits angiogenesis, reduces vascular tone and reduces portal hypertension. The rationale for the Randomized Aldactone Evaluation Study (RALES) of spironolactone in heart failure was that 'aldosterone escape' occurred through non-angiotensin II mechanisms. The RALES clinical trial was stopped early when it was shown that there was a 30% reduction in risk of death among the spironolactone patients. In RALES, spironolactone also reduced hospitalisation for worsening heart failure and improved the symptoms of heart failure. Other recent clinical trials have shown that spironolactone reduces cardiac and vascular collagen turnover, improves heart variability, reduces ventricular arrhythmias, improves endothelial dysfunction and dilates blood vessels in human heart failure and these effects probably all contribute to the increased survival in heart failure. Spironolactone may also be useful in the treatment of left ventricular hypertrophy, portal hypertension and cirrhosis. There have also been some recent small clinical trials of spironolactone as an anti-androgen showing potential in acne, hirsutism and precocious puberty.

Aldosterone↗

"It's not what you know, but who you knew": examining the relationship between behavior change and AIDS mortality in Africa.

Until there is an effective vaccine, changing sexual behavior (e.g., use of condoms or fewer partners) is still the only course of action that can slow the spread of HIV for most Africans. But exactly which factors influence behavior change and how are still debated. This article examines the notion that as the HIV/AIDS epidemic strengthens and spreads through communities in Africa, and mortality mounts, behaviors that prevent transmission should be changing. We focus on men in three countries--Uganda, Kenya, and Zambia--examining determinants of their behavior change, and analyze the relative importance of knowing someone who has died of AIDS as compared with other factors such as age, education level, knowledge of HIV/AIDS, economic status, and marital status. Data from three DHS surveys in Uganda (1995), Zambia (1996), and Kenya (1998) are fitted to a model predicting behavior change. Results from this cross-sectional, multinational study suggest that married and working men aged 20-40 are significantly more likely to have changed their behavior. Personal experience of AIDS is a significant predictor of behavior change in Uganda and Zambia, and is marginally significant in Kenya. One implication in the context of the epidemic is that behavior change is partly determined by the high level of mortality experienced by African communities. A second implication is that higher levels of disclosure, or lower levels of denial of AIDS as a cause of death, may help individuals change their behavior.

Acquired Immunodeficiency Syndrome↗

Total cost comparison of 2 biopsy methods for nonpalpable breast lesions.

OBJECTIVE: To identify, quantify, and compare total facility costs for 2 breast biopsy methods: vacuum-assisted biopsy (VAB) and needle-wire-localized open surgical biopsy (OSB). STUDY DESIGN: A time-and-motion study was done to identify unit resources used in both procedures. Costs were imputed from published literature to value resources. A comparison of the total (fixed and variable) costs of the 2 procedures was done. PATIENTS AND METHOD: A convenience sample of 2 high-volume breast biopsy (both VAB and OSB) facilities was identified. A third facility (OSB only) and 8 other sites (VAB only) were used to capture variation. Staff interviews, patient medical records, and billing data were used to check observed data. One hundred and sixty-seven uncomplicated procedures (71 OSBs, 96 VABs) were observed. Available demographic and clinical data were analyzed to assess selection bias, and sensitivity analyses were done on the main assumptions. RESULTS: The total facility costs of the VAB procedure were lower than the costs of the OSB procedure. The overall cost advantage for using VAB ranges from $314 to $843 per procedure depending on the facility type. Variable cost comparison indicated little difference between the 2 procedures. The largest fixed cost difference was $763. CONCLUSIONS: Facilities must consider the cost of new technology, especially when the new technology is as effective as the present technology. The seemingly high cost of equipment might negatively influence a decision to adopt VAB, but when total facility costs were analyzed, the new technology was less costly.

Biopsy↗

Hemobilia: four case reports and review of the literature.

In this report, we present four cases of hemobilia. Hemobilia occurs when conditions produce an abnormal communication between blood vessels and bile ducts. Although iatrogenic procedures as causes of hemobilia have been reported with increasing frequency, non-iatrogenic etiologies are still quite rare. We, therefore, report 4 cases of hemobilia secondary to different etiologies found in our institution from 1996 to 1998, that are non-iatrogenic. The first patient was a case of congenital aneurysm, the second pseudoaneurysm from trauma, the third cholangiocarcinoma and the fourth hepatocellular carcinoma. The classical triad consists of melena, jaundice and abdominal pain. Direct observation of blood flowing from the Ampulla of Vater by endoscopy was the initial diagnostic procedure in all four cases. Diagnosis was confirmed by ultrasonography, computerized tomography, angiography or surgery. Transcatheter selective embolization as a noninvasive treatment for hepatic aneurysm/pseudoaneurysm is emphasized.

Adult↗

A randomized trial of nurse specialist home care for women with high-risk pregnancies: outcomes and costs.

OBJECTIVE: To examine prenatal, maternal, and infant outcomes and costs through 1 year after delivery using a model of prenatal care for women at high risk of delivering low-birth-weight infants in which half of the prenatal care was provided in women's homes by nurse specialists with master's degrees. STUDY DESIGN: Randomized clinical trial. PATIENTS AND METHODS: A sample of 173 women (and 194 infants) with high-risk pregnancies (gestational or pregestational diabetes mellitus, chronic hypertension, preterm labor, or high risk of preterm labor) were randomly assigned to the intervention group (85 women and 94 infants) or the control group (88 women and 100 infants). Control women received usual prenatal care. Intervention women received half of their prenatal care in their homes, with teaching, counseling, telephone outreach, daily telephone availability, and a postpartum home visit by nurse specialists with physician backup. RESULTS: For the full sample, mean maternal age was 27 years; 85.5% of women were single mothers, 36.4% had less than a high school education, 93.6% were African American, and 93.6% had public health insurance, with no differences between groups on these variables. The intervention group had lower fetal/infant mortality vs the control group (2 vs 9), 11 fewer preterm infants, more twin pregnancies carried to term (77.7% vs 33.3%), fewer prenatal hospitalizations (41 vs 49), fewer infant rehospitalizations (18 vs 24), and a savings of more than 750 total hospital days and $2,496,145 [corrected]. CONCLUSION: This model of care provides a reasoned solution to improving pregnancy and infant outcomes while reducing healthcare costs.

Adult↗

The excess incidence of squamous cell esophageal cancer among us black men. Role of social class and other risk factors.

PURPOSE: To investigate the relationship between social class factors and squamous cell esophageal cancer and the extent to which alcohol, tobacco, diet, and social class contribute to the five-fold higher incidence among black than white men in the United States.METHODS: Interviews were conducted with 347 incident cases of squamous cell esophageal cancer (119 white males and 228 black males) and 1354 population-based controls (743 white males and 611 black males) from Atlanta, Detroit, and New Jersey. Risks were estimated using unconditional logistic regression controlling for potential confounders.RESULTS: Elevated risks of squamous cell esophageal cancer were associated with indicators of low social class, especially low annual income. The adjusted odds ratios (ORs) for subjects with incomes < $10,000 versus incomes of $25,000 or more were 4.3 (95% CI = 2.1-8.7) for whites and 8.0 (95% CI = 4.3-15.0) for blacks. The combination of all four major risk factors: annual income less than $25,000, moderate/heavy use of alcohol, use of tobacco for six months or longer, and consumption of less than 2.5 servings of raw fruits and vegetables per day accounted for almost all of the squamous cell esophageal cancers in whites (98%) and blacks (99%), and for 99% of the excess incidence among black men.CONCLUSIONS: Lifestyle modifications, especially a lower intake of alcoholic beverages, would markedly decrease the incidence of this cancer in both races and narrow the racial disparity in risk. Further studies into the determinants of social class may help identify a new set of exposures for this tumor that are amendable to intervention.

Journal Article↗

Drosophila protein phosphatase 5 is encoded by a single gene that is most highly expressed during embryonic development.

A putative Drosophila melanogaster homologue of mammalian PP5, termed Dm PP5, was identified from cDNA. Dm PP5 comprises a phosphatase catalytic domain preceded by an amino terminal domain containing three tetratricopeptide repeat motifs and shares 60% overall amino acid identity with human PP5. Genomic restriction analysis identified a single Dm PP5 gene that was mapped to the third chromosome at locus 85E10-12 and a strain carrying a deletion that encompasses this gene was identified. Dm PP5 mRNA and protein are more highly expressed in the embryo than at later developmental stages, but their expression levels do not always change synchronously. Dm PP5 protein localises to both the nucleus and the cytoplasm of cells at the periphery of newly cellularized embryos.

Amino Acid Sequence↗

The design and synthesis of thrombin inhibitors: analogues of MD805 containing non-polar surrogates for arginine at the P1 position.

A series of monocyclic and bicyclic amino acids have been synthesised and incorporated into thrombin inhibitors based on CGH728, an analogue of the Mitsubishi compound MD805. Benzthiazolylalanine (Bta) was found to be a good non-polar substitute for arginine at the P1 position, yielding compounds with low nanomolar potency and good selectivity for thrombin.

Alanine↗

PDEF, a novel prostate epithelium-specific ets transcription factor, interacts with the androgen receptor and activates prostate-specific antigen gene expression.

Prostate cancer, the most frequent solid cancer in older men, is a leading cause of cancer deaths. Although proliferation and differentiation of normal prostate epithelia and the initial growth of prostate cancer cells are androgen-dependent, prostate cancers ultimately become androgen-independent and refractory to hormone therapy. The prostate-specific antigen (PSA) gene has been widely used as a diagnostic indicator for androgen-dependent and -independent prostate cancer. Androgen-induced and prostate epithelium-specific PSA expression is regulated by a proximal promoter and an upstream enhancer via several androgen receptor binding sites. However, little progress has been made in identifying androgen-independent regulatory elements involved in PSA gene regulation. We report the isolation of a novel, prostate epithelium-specific Ets transcription factor, PDEF (prostate-derived Ets factor), that among the Ets family uniquely prefers binding to a GGAT rather than a GGAA core. PDEF acts as an androgen-independent transcriptional activator of the PSA promoter. PDEF also directly interacts with the DNA binding domain of androgen receptor and enhances androgen-mediated activation of the PSA promoter. Our results, as well as the critical roles of other Ets factors in cellular differentiation and tumorigenesis, strongly suggest that PDEF is an important regulator of prostate gland and/or prostate cancer development.

Amino Acid Sequence↗

Health effects of depleted uranium on exposed Gulf War veterans.

A small group of Gulf War veterans possess retained fragments of depleted uranium (DU) shrapnel, the long-term health consequences of which are undetermined. We evaluated the clinical health effects of DU exposure in Gulf War veterans compared with nonexposed Gulf War veterans. History and follow-up medical examination were performed on 29 exposed veterans and 38 nonexposed veterans. Outcome measures employed were urinary uranium determinations, clinical laboratory values, and psychiatric and neurocognitive assessment. DU-exposed Gulf War veterans with retained metal shrapnel fragments are excreting elevated levels of urinary uranium 7 years after first exposure (range 0.01-30.7 microg/g creatinine vs 0.01- 0.05 microg/g creatinine in the nonexposed). The persistence of the elevated urine uranium suggests on-going mobilization from a storage depot which results in a chronic systemic exposure. Adverse effects in the kidney, a presumed target organ, are not present at this time, though other effects are observed. Neurocognitive examinations demonstrated a statistical relationship between urine uranium levels and lowered performance on computerized tests assessing performance efficiency. Elevated urinary uranium was statistically related to a high prolactin level (>1.6 ng/ml; P=0.04). More than 7 years after first exposure, DU-exposed Gulf War veterans with retained metal fragments continue to excrete elevated concentrations of urinary uranium. Effects related to this are subtle perturbations in the reproductive and central nervous systems.

Adult↗

Progress on strain differentiation of Citrus tristeza virus and its application to the epidemiology of citrus tristeza disease.

Citrus tristeza virus (CTV) occurs in most citrus producing regions of the world, and it is the most serious viral pathogen of citrus. With the recent establishment of the brown citrus aphid, Toxoptera citricida, its most efficient vector, on Madeira Island (Portugal) and in Florida (USA) and the countries of the Caribbean Basin, the impact of CTV is likely to increase in these regions. Since there are many strains of CTV and CTV infections frequently occur as mixtures of several strains, it is necessary to be able to distinguish the strains for regulatory purposes, disease management and epidemiology. We describe the evolution of techniques developed to detect CTV and to differentiate the individual strains, and present the results of tests using these latest methods on CTV isolates from mainland Portugal, Madeira Island and Florida. Mild and decline-inducing strains of CTV were detected in mainland Portugal and mild, decline-inducing and severe stem pitting strains on Madeira Island. In Florida we demonstrated the presence of infections that reacted with probes made against stem pitting strains not previously detected there. It is concluded that CTV presents a significant threat to citrus production in mainland Portugal, on Madeira Island and in the neighbouring countries of the Mediterranean Basin, as well as in Florida, elsewhere in the USA and throughout the Caribbean Basin, especially following the widespread establishment of T. citricida throughout the region.

Amino Acid Sequence↗

Corneal abrasions associated with pepper spray exposure.

Pepper spray containing oleoresin capsicum is used by law enforcement and the public as a form of nonlethal deterrent. Stimulated by the identification of a case of a corneal abrasion associated with pepper spray exposure, a descriptive retrospective review of a physician-maintained log of patients presenting to a jail ward emergency area over a 3-year period was performed. The objective was to give some quantification to the frequency with which an emergency physician could expect to see corneal abrasions associated with pepper spray exposure. Of 100 cases of pepper spray exposure identified, seven patients had sustained corneal abrasions. We conclude that corneal abrasions are not rare events when patients are exposed to pepper spray and that fluorescein staining and slit lamp or Wood's lamp examination should be performed on all exposed patients in whom corneal abrasions cannot be excluded on clinical grounds.

Adolescent↗

Psychological adjustment to familial genetic risk assessment: differences in two longitudinal samples.

Heritable cancer risk assessment is an increasingly common method of deriving valuable information relevant to deciding on appropriate screening regimens and preventive treatments. Assessments of heritable risk typically include familial-genetic evaluation, where analyses relate family pedigree to cancer risk, and DNA testing, where analyses indicate genetic mutations associated with cancer risk (e.g., BRCA1/BRCA2 mutations) or their absence. In this paper we report on the psychological responses of women given familial-genetic evaluations for ovarian cancer risk. The baseline and 6 to 12 follow-up assessments of an initial clinic-attending cohort of 65 women are compared with the baseline and 9 to 12 follow-up assessments of a second clinic-attending cohort of 60 women. Sizeable differences were found in the prevalence of clinically significant depression in these two physician or self-referred populations, as assessed by the Center for Epidemiological Studies Depression scale and in the mean scores. Hypotheses accounting for these differences are discussed.

Adaptation, Psychological↗