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Biomedical subjects

W Brown

Publications and source records attributed to W Brown.

At least 55 records · Page 3Linked to original sources
PubMed1999

Leaking urine: prevalence and associated factors in Australian women.

The Women's Health Australia project provided the opportunity to examine the prevalence of leaking urine and associated variables in three large cohorts of Australian women 18-23 years of age ("young" N = 14,761), 45-50 ("mid-age" N = 14,070), and 70-75 ("older" N = 12, 893). The proportion of women reporting leaking urine was 12.8% (95% CI: 12.2-13.3), 36.1% (35.2- 37.0), and 35% (34.1- 35.9) in each of the three cohorts, respectively. Logistic regression analysis showed significant associations between leaking urine and parity in the young and mid-age women, and between leaking urine and constipation, other bowel symptoms, body mass index, and urine that burns or stings in all three groups. In the mid-age and older cohorts, women who reported having both hysterectomy and prolapse repair, or prolapse repair alone, were also more likely to report leaking urine. Lower scores on the physical and mental component summary scores of the medical outcomes survey short form (36 items) questionnaire suggest lower quality of life among women who report leaking urine, compared with those who do not. Neurourol. Urodynam. 18:567-577, 1999.

Adolescent↗
PubMed1999

Women drivers' behaviour, socio-demographic characteristics and accidents.

The purpose of this study was to examine factors which affect driving behaviour and accident rates in women in Australia. Two groups of women (aged 18-23 and 45-50 years) participating in the Australian Longitudinal Study on Women's Health, completed a mailed questionnaire on driver behaviour and road accidents. Self reported accident rates in the last 3 years were 1.87 per 100,000 km for the young drivers (n = 1199) and 0.59 per 100,000 km for the mid-age drivers (n = 1564); most accidents involved damage only, not injury. Mean scores for lapses obtained using the Driver Behaviour Questionnaire, were similar in the two age groups and similar to those found in other studies. In contrast, scores for errors and violations for the young women were higher than for the mid-age group and previous reports using the same instruments. Riskier driving behaviour among young women was associated with stress and habitual alcohol consumption. In the mid-age group, poorer driver behaviour scores were related to higher levels of education, feeling rushed, higher habitual alcohol consumption and lower life satisfaction scores. Accident rates in both groups were significantly related to lapses. Women born in non-English speaking countries had significantly higher risk of accidents compared to Australian-born women: relative risk = 3.40, 95% confidence interval (1.93, 5.98) for the young drivers; relative risk = 1.77, 95% confidence interval (1.11, 2.83) for mid-age drivers. These findings support the need for road safety campaigns targeted at young women to reduce dangerous driving practices, such as speeding, 'tail gating' and overtaking on the inside. There is also a need for further research to understand how lifestyle characteristics are associated with higher risk of accidents and to explore factors which might account for the higher risk for women drivers who were born overseas.

Accidents, Traffic↗
PubMed1999

Pyrido [1,2a] indole derivatives identified as novel non-nucleoside reverse transcriptase inhibitors of human immunodeficiency virus type 1.

Pyrido [1,2a] indole derivatives were identified as potent inhibitors of human immunodeficiency virus type 1 (HIV-1) replication during a random screening programme. The compounds showed no antiviral activity against HIV-2 or in cells chronically infected with HIV-1, but had good inhibitory effect against purified HIV-1 reverse transcriptase (RT) in an in vitro assay. They were therefore classified as non-nucleoside RT inhibitors (NNRTI). The synthesis of additional compounds of the same class revealed a structure-activity relationship. The most potent compound of the series, BCH-1, had similar antiviral activity to the licensed NNRTI nevirapine against laboratory strains of HIV-1 cultured in cell lines and primary clinical isolates of HIV-1 cultured in peripheral blood mononuclear cells. However, BCH-1 showed greater cytotoxicity, providing a narrow selectivity index in the order of 35. BCH-1 had equivalent antiviral activity against viruses resistant to the nucleoside RT inhibitors zidovudine, didanosine and lamivudine and maintained better activity (less than threefold change in IC50) than nevirapine against viruses resistant to a range of NNRTIs with the single amino acid changes L100I, K103N, E138K or Y181C in the RT. Viruses with single V106A or Y188C amino acid changes showed five- and 10-fold resistance to BCH-1, respectively, in contrast to nevirapine, which had a > 100-fold change in IC50. However, virus with both V106A and Y188C amino acid changes showed higher level resistance (> 15-fold) to BCH-1. Virus with > 10-fold resistance to BCH-1 was rapidly selected for after growth in increasing concentrations of compound and was shown to be cross-resistant to nevirapine. Sequencing of this virus revealed two amino acid changes at positions 179 (V to D) and 181 (Y to C) in the RT. BCH-1 represents a new class of NNRTI, which may act as a lead to identify more selective compounds.

Amino Acid Substitution↗
PubMed1999

Psychological stress and disordered eating: an exploratory study with young Australian women.

An exploratory study was conducted to examine whether the relationships between psychological stress and disordered eating, reported in many studies using American samples, would be found in a sample of young Australian women. A total of 212 women aged 18-22 years completed a questionnaire assessing a number of women's health issues, including life events stress, perceived stress levels, psychological distress, disordered eating behaviours, and concerns about weight and eating. While results showed few strong relationships between stress and eating variables for the sample overall, those women with high psychological stress levels appeared to be more likely to engage in disordered eating behaviours than women with low levels of stress. Results suggest that further investigation, targeting subgroups of women scoring highly on measures of psychological stress or disordered eating, may help clarify our understanding of the relationships between these factors in young Australian women.

Adolescent↗
PubMed1999

Taltirelin. Tanabe Seiyaku.

Taltirelin is a synthetic thyrotropin-releasing hormone (TRH) analog, under development by Tanabe Seiyaku for the treatment of neurodegenerative diseases. A new drug application (NDA) has been filed in Japan for the treatment of spinocerebellar disease (SCD) and is under review. Data suggest that taltirelin enhances dopamine neurotransmission, although this has been questioned. Taltirelin potentiates acetylcholine (ACh)-induced neuronal excitation in rat cerebral cortex neurons and inhibits high concentration AChinduced desensitization of neuronal excitation. TRH receptors have been located in several parts of the rat brain, including the pituitary, hypothalamus, and brain stem. These data provide support for the claim that taltirelin may have a potential benefit in dementia, which is consistent with limited clinical data. Taltirelin has been shown to be more potent and longer acting than TRH in increasing the amplitude of spinal reflex potentials and withdrawal flexor reflexes in spinal rats after iv administration. The compound is also active after intraduodenal administration, in contrast to TRH, indicating its potential for the treatment of spinal functional disorders. Analysts at Yamaichi had predicted that taltirelin would be launched in Japan in 1998; this was optimistic, though the new drug application is currently under review. Additionally, their prediction was of peak annual sales of less than 5 billion Yen; however taltirelin has been designated as an orphan drug in Japan.

Journal Article↗
PubMed1999

Ariflo (SmithKline Beecham plc).

Ariflo (SB-207499) is a phosphodiesterase (PDE)4 inhibitor under development by SmithKline Beecham and in phase III and II clinical trials as a potential treatment for chronic obstructive pulmonary disease (COPD) and asthma, respectively [284490]. It has commenced phase II trials as a treatment for bronchial asthma in Japan [248285,300145]. In February 1999, Merrill Lynch predicted that Ariflo would be launched by the end of 2000 or early 2001 with first year sales of UK pounds sterling 25 million rising to UK pounds sterling 175 million in 2003 [300257,314372]. In February 1999 ABN Amro predicted sales of UK pounds sterling 52 million in 2001 rising to UK pounds sterling 254 million in 2005 [317577,328676].

Journal Article↗
PubMed1998

Cloning and evaluation of the role of rat GALR-2, a novel subtype of galanin receptor, in the control of pain perception.

We have identified a novel subtype of galanin receptor (GALR-2) in rat dorsal root ganglia and spinal cord. The open reading frame of GALR-2 is 1116 nucleotides long, encoding a protein of 372 amino acids with a theoretical molecular mass of 40.7 kD. Membranes prepared from stable pools of 293 cells expressing GALR-2, but not wild-type 293 cells, demonstrated high affinity galanin binding sites. Rat galanin and galanin-related peptides M40, C7, M15, and galanin effectively competed for binding; peptide C7 demonstrated a lower affinity for rGALR-2, and all these peptides were agonists at rGALR-2 when assessed on a microphysiometer. Studies on the expression of GALR-2 in various tissues by Northern and in situ hybridization analyses suggest a low abundance but wide distribution of GALR-2 mRNA, including several discrete areas in brain and spinal cord and a high abundance in the dorsal root ganglia.

Amino Acid Sequence↗
PubMed1998

Differential induction of apoptosis by fludarabine monophosphate in leukemic B and normal T cells in chronic lymphocytic leukemia.

Fludarabine (F-ara-A), an adenine nucleoside analog with efficacy in B-cell chronic lymphocytic leukemia (B-CLL), has also been shown to have a long-lasting suppressive effect on T lymphocytes. In heterogeneous clinical samples, apoptosis cannot be detected by standard methods in small cellular subsets. We developed, therefore, a combined assay of in situ end-labeling of nicked DNA by terminal deoxynucleotide transferase, with measurements of cellular DNA content and surface antigens (CD3, CD4, CD8, and CD19) by multiparametric flow cytometry. This assay was used to determine F-ara-A-induced apoptosis in different lymphocyte subsets from CLL patients and normal controls treated with F-ara-A in vitro. Apoptosis was also correlated to bcl-2 protein levels. We observed a direct effect of F-ara-A on both B-CLL and T lymphocytes. The response to F-ara-A in B-CLL lymphocytes in vitro was Rai stage-dependent, the early-stages being more responsive (P = .01). Higher levels of spontaneous apoptosis were observed in B-CLL lymphocytes from early stage patients (P = .02). No difference was observed in spontaneous apoptosis of normal T cells in B-CLL, although T lymphocytes in late-stage disease were more sensitive to F-ara-A-induced apoptosis. Incubation with cyclosporin A did not affect B-CLL and T-lymphocyte survival compared with control cultures. Results suggested a direct apoptotic effect of F-ara-A on B-CLL lymphocytes that decreases with increasing clinical stage. No correlation was found between bcl-2 and spontaneous or F-ara-A-induced apoptosis. Apoptosis occurred at all cell-cycle stages and was not restricted to cells in S phase. The mechanisms of this stage-dependent apoptosis in CLL remain to be elucidated.

Antigens, CD19↗
PubMed1998

A multicenter study of the prevalence and susceptibility patterns of isolates of Streptococcus pneumoniae with reduced susceptibility to penicillin G in Louisiana.

Because of increasing reports of multiple-antibiotic-resistant strains of Streptococcus pneumoniae and associated clinical failures, this study was performed to determine the prevalence of multiresistance among strains from nine Louisiana medical centers. Using a National Committee for Laboratory Standards broth microdilution method, 481 strains were tested. Of these, 70% were penicillin-susceptible (PS), 23% had intermediate minimum inhibitory concentration values to penicillin (I), and 7% were fully resistant to penicillin (PR). The isolation rates (15% to 40% for I strains and 0% to 33% for PR strains) at the various medical centers varied appreciably. The prevalence of penicillin resistance was highest among upper respiratory isolates, while cross-resistance to other antimicrobials varied. The least cross-resistance was noted among PS strains. However, strains with reduced penicillin susceptibility had high levels of cross-resistance. Among I strains, the prevalence of cross-resistance (%) was noted for amoxicillin/clavulanate (6%), cefuroxime (71%), cefaclor (91%), ceftriaxone (13%), cefotaxime (34%), erythromycin (67%), azithromycin (32%), and clarithromycin (32%). For PR strains, the prevalence of cross-resistance was 97% for amoxicillin/clavulanate, cefuroxime, and cefaclor; 67% for ceftriaxone and erythromycin; 89% for cefotaxime; and 69% for azithromycin and clarithromycin. These data emphasize the high prevalence of multiple-antimicrobial-resistance among strains of S pneumoniae with reduced penicillin susceptibility in this geographic area.

Anti-Bacterial Agents↗
PubMed1998

Detection of genital human papillomavirus and associated cytological abnormalities among college women.

BACKGROUND AND OBJECTIVES: Human papillomavirus (HPV) is strongly implicated in the etiology of cervical neoplasia; however, the frequency, rate, and predictors of neoplastic progression are unknown. GOAL: To measure the type-specific prevalence of cervical HPV and the rate of development of cytological abnormalities among a cohort of college women and to elucidate factors associated with acquisition of HPV DNA and progression to cytological abnormalities. STUDY DESIGN: Women 18 to 40 years of age seeking routine gynecologic care at a university health center were enrolled in a cross-sectional study with prospective, longitudinal follow-up of a subset of women. Demographic and behavioral data were collected using a written questionnaire. HPV DNA was detected in cervical scrapes by polymerase chain reaction using L1 consensus primers and a generic and 25 type-specific probes, and cervical cytological abnormalities were identified by Papanicolaou's (Pap) smear. RESULTS: HPV DNA was detected in 35% of the 414 women in the cross-sectional study; 66% of infections were with intermediate or high cancer risk HPV types. Multiple lifetime sex partners was an independent predictor of prevalent infection. Longitudinal analysis of 205 women showed that detection was transient (HPV DNA absent at follow-up) in 38% of the 84 women who were HPV-positive at enrollment. Persistent detection of the same HPV type at > or = 2 visits occurred in 14% of women and was significantly more common when intermediate or high cancer risk types were present. After 16 months of observation, 9% of HPV-infected women developed low-grade squamous intraepithelial lesions (SIL) and 5% developed high-grade SIL; the risk of incident SIL was 7.8-fold higher among women who had persistent HPV detection with the same type. CONCLUSIONS: It was concluded that cervical HPV infection is highly prevalent among college women. Although most infections are caused by intermediate of high cancer risk types, few women (5%) developed high-grade SIL during 16 months of observation.

Adolescent↗
PubMed1998

Sickle cell disease: problem solving/coping methods among affected children and their non-affected siblings.

A small group of children with sickle cell disease and their non-affected siblings served as participants in a descriptive research project designed to describe how these children problem-solve and cope with social and academic stress at school. Data collection involved pictorial stimuli to evoke story telling. The study's results indicate that both problem-solving and coping methods were identical between affected and non-affected children in the sample: both groups utilized direct action in dealing with stressful situations. The study's generalizability is limited on account of small sample size.

Adaptation, Psychological↗
PubMed1998

Trends in the incidence of upper extremity soft tissue malignancies: a 40-year review of the Connecticut State Tumor Registry.

BACKGROUND: Although soft tissue malignancies of the upper extremity are rare, the management of these lesions has been controversial and the etiologic factors associated with the occurrence of these tumors are not well understood. The purpose of this study was to identify possible epidemiologic factors related to a recently noted rise in the occurrence of these tumors in the state of Connecticut. METHODS: The occurrence of upper extremity soft tissue tumors over the past 40 years was reviewed in the Connecticut State Tumor Registry. Demographic data collected included occupational history, residence, and presence of concomitant malignancies. Tumor histology, the extent of resection, and the incidence of recurrences were also noted. Factors associated with recurrence were identified using linear regression analysis. RESULTS: During the 40-year study period, 359 patients having upper extremity soft tissue tumors were entered into the Connecticut State Tumor Registry. An increasing trend in the number of upper extremity soft tissue tumors was evident. Many patients were involved in heavy industry or related fields. Fibrosarcoma and liposarcoma were the most common tumor types, occurring in 111 (30.3%) and 48 patients (13.2%), respectively. Sixty-seven patients presented with a synchronous second primary malignancy of the breast (49 patients), lung (seven patients), or gastrointestinal tract (five patients). Most patients (69.9%) underwent local excision of the soft tissue tumors, with fewer undergoing wide excision (20.3%) or radical excision (9.7%). Recurrence, which occurred in 144 patients, was found to be associated with extent of resection, occupational history, and concomitant malignancy. Delineation of such risk factors may be helpful in identifying patients in whom aggressive management may decrease recurrence and improve survival.

Adolescent↗
PubMed1997

An in vitro model to assess mucosal immune function and bacterial translocation.

The importance of secretory immunoglobulin A (IgA) on intestinal barrier function has gained increasing acceptance. However, due to the complexity of the intestinal microenvironment, the relative role of secretory IgA (sIgA) in mucosal defense has been difficult to study in vivo. Polarized Madin-Darby canine kidney (MDCK) epithelial cells expressing the complementary DNA (cDNA) for the polymeric Ig receptor were grown as monolayers in an in vitro two-chamber cell culture system to study the impact of sIgA on bacterial translocation (BT). Polymeric sIgA or media alone was added to the apical chambers of cell monolayers followed by apical inoculation with bacteria. The basal compartment was sampled at timed intervals thereafter to determine BT. Bacterial passage across the MDCK epithelial cell monolayers occurred in a time and bacterial inoculum concentration gradient. Addition of sIgA led to significant reductions in BT across the epithelial cell monolayers. This is a useful model for further investigation on the role of sIgA in intestinal barrier function.

Animals↗
PubMed1997

Microbial production of a novel trihydroxy unsaturated fatty acid from linoleic acid.

A bacterium isolated from a dry soil sample collected from McCalla, AL, USA, converted linoleic acid to a novel compound, 12,13,17-trihydroxy-9 (Z)-octadecenoic acid (THOA). The organism is a Gram-positive, non-motile rod (0.5 microns x 2 microns). It was identified as a species of Clavibacter ALA2. The product was purified by high pressure liquid chromatography, and its structure was determined by 1H and 13C nuclear magnetic resonance and Fourier transform infrared spectroscopies, and by mass spectrometer. Maximum production of THOA with 25% conversion of the substrate was reached after 5-6 days of reaction. THOA was not further metabolized by strain ALA2. This is the first report of a 12,13,17-trihydroxy unsaturated fatty acid and its production by microbial transformation. Some dihydroxy intermediates were also detected. THOA has a structure similar to those of known plant self-defense substances.

Bacteria↗
PubMed1997

A comparison study of children with sickle cell disease and their non-diseased siblings on hopelessness, depression, and perceived competence.

The purpose of this comparison study was to explore the extent to which hopelessness and self-perceptions of competence are associated with depression in a community population of children with sickle cell disease compared to their non-diseased siblings. Subjects were African-American children drawn randomly from the case management programme at the L.D. Barksdale Sickle Cell Anemia Foundation. Depression scores were higher for the non-diseased siblings. The children with sickle cell disease scored lower on the perceived physical competence scale. Recommendations for practice include increasing hope, improving relationships, monitoring depression in patients and their siblings, and monitoring perceptions of cognitive, social, physical, and general self-worth.

Adaptation, Psychological↗
PubMed1997

Human mini-chromosomes in mouse embryonal stem cells.

We have introduced human mini-chromosomes of 4 Mb and approximately 15 Mb in size into mouse embryonal stem cells. Although these human mini-chromosomes are stable in hamster and chicken cells, they re-arrange or segregate aberrantly in the embryonal stem cells and are rapidly lost in the absence of selection. However, one of the mini-chromosomes re-arranged, acquired mouse centromeric sequences and was then stably maintained for at least 60 population doublings in culture. This mini-chromosome, which is 4 Mb in size, is a candidate for a mouse germ line chromosome vector.

Animals↗
PubMed1997

Food habits of young and middle-aged women living outside the capital cities of Australia.

Young (18-22 years) and middle-aged (45-49 years) women living in urban and rural areas of New South Wales completed a brief food frequency questionnaire as part of a wider health survey. Urban women in both age groups consumed meat less frequently than women in rural areas, and women in the less populated rural areas were more likely to eat green and yellow vegetables and least likely to eat dried beans. There were few other geographic differences in food habits. Middle-aged women consumed reduced-fat milk, fruit, vegetables, fish, biscuits and cakes significantly more frequently, and rice, pasta, full-cream milk, fried food and take-away food less frequently than younger women. Smokers in both age groups consumed fresh fruit, vegetables and breakfast cereals significantly less frequently than non-smokers, and women with low levels of habitual physical activity consumed fresh fruit and cereals less frequently than more active women. The findings suggest that strategies aimed at changing eating behaviours should be age-group-specific and targeted specifically to smokers and less active women.

Adolescent↗