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Biomedical subjects

S Knox

Publications and source records attributed to S Knox.

At least 19 recordsLinked to original sources
PubMed2005

Perlecan from human epithelial cells is a hybrid heparan/chondroitin/keratan sulfate proteoglycan.

Perlecan is a multidomain proteoglycan, usually substituted with heparan sulphate (HS), and sometimes substituted with both HS and chondroitin sulphate (CS). In this paper, we describe perlecan purified from HEK-293 cells substituted with HS, CS and keratan sulphate (KS). KS substitution was confirmed by immunoreactivity with antibody 5D4, sensitivity to keratanase treatment, and fluorophore-assisted carbohydrate electrophoresis. HEK-293 perlecan failed to promote FGF-dependent cell growth in an in vitro assay. This study is the first to report perlecan containing KS, and makes perlecan one of only a very few proteoglycans substituted with three distinct types of glycosaminoglycan chains.

Cell Line↗
PubMed2005

The effect of gender on outcome in digitalis-treated heart failure patients.

BACKGROUND: The use of digitalis is recommended for the treatment of heart failure to reduce hospitalization. Recent data suggest that digitalis treatment may adversely affect survival in women but not in men. We studied patients with left ventricular dysfunction enrolled in the Studies of Left Ventricular Dysfunction (SOLVD) to determine whether there was a gender-based survival difference in patients treated with digitalis. METHODS AND RESULTS: Symptomatic (n = 2569) and asymptomatic (n = 4228) patients with left ventricular ejection fraction < or = 0.35 were studied. Digitalis use was assessed at baseline and baseline demographic variables were catalogued and compared. A multivariate analysis, incorporating known covariates of risk for adverse cardiovascular events, was used to examine the association of digitalis with all-cause mortality, cardiovascular death, death from heart failure, and arrhythmic death, with, or without, worsening heart failure in women compared with men. Analysis for an interaction between digitalis and gender on mortality was also performed. No interaction between gender and digitalis treatment on survival was found, and there was no significant difference in the hazard ratios for men and women on digitalis either with respect to all-cause mortality, cardiovascular mortality, heart failure mortality, or arrhythmic death with worsening heart failure. When mortality for arrhythmic death without worsening heart failure was adjusted for the probability of being treated with digitalis (propensity analysis), women fared better than men. CONCLUSION: Data from the SOLVD trials suggest that digitalis treatment of heart failure does not result in a difference in survival between men and women. Because a randomized trial to definitively answer the question is unlikely, and perhaps inappropriate, examination of other heart failure populations for a gender-digitalis interaction is indicated.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2004

Changes in asthma management in Australian general practice.

AIMS: To investigate changes in national prevalence, severity and management rates of asthma in Australian general practice from 1990 to 2003. METHODS: A comparative study of general practitioner (GP) encounters with asthma patients, in cross sectional surveys from 1990-91 and 1998-2003. Main outcome measures were relative rates of asthma management, prevalence and severity of asthma. RESULTS: The prevalence of asthma remained constant between 1999 and 2002. Prevalence in children was significantly higher (18.4%) than in adults (13.2%) (p < 0.0001). The asthma management rate fell by 0.5 (from 3.7 to 3.2) per 100 encounters between 1990-91 and 1998 (8 years), and by a further 0.5 (from 3.2 to 2.7) per 100 encounters between 1998 and 2003 (5 years) suggesting an accelerating rate of decrease in the general practice asthma management rate over time. CONCLUSIONS: These findings suggest that Australians attending general practice may be gaining better control of their asthma.

Journal Article↗
PubMed2004

General practice encounters for psychological problems in rural, remote and metropolitan areas in Australia.

OBJECTIVE: Previous Australian research suggests there is very little difference in the prevalence of mental health disorders across rural, remote and metropolitan areas. However, mental health specialists are particularly scarce in rural and remote areas and some researchers have argued that non-metropolitan residents rely heavily on general practitioners (GPs) for mental health care. This article investigated rates of GP services for psychological problems across rural, remote and metropolitan areas. METHOD: The Bettering the Evaluation and Care of Health (BEACH) program, Medicare and Pharmaceutical Benefits Scheme data were used in this report. Data included all psychological, depression and anxiety problems reported as managed by GPs and prescriptions for mental health medications (written and filled). Problem and medication rates are given per 100 patient encounters and per 1000 population. RESULTS: Only a few regional differences were evident in the rate of psychological problems and prescriptions for mental health medications per 100 GP-patient encounters. However, rural and remote residents visited GPs less frequently than their metropolitan counterparts. Lower rates of GP encounters for psychological problems were evident for residents of most non-metropolitan areas (per 1000 population). Additionally, GPs prescribed mental health medications at half the rate for residents of remote areas than capital cities. CONCLUSIONS: General practitioners provide fewer mental health services per capita in non-metropolitan areas. This difference could represent completely untreated psychological problems or fewer follow-up consultations. While non-metropolitan residents have limited access to specialists, rates of GP encounters for psychological problems are also very low.

Anti-Anxiety Agents↗
PubMed2001

Electrophoretic, biosensor, and bioactivity analyses of perlecans of different cellular origins.

Three cellular sources of perlecan were examined in this study, namely human umbilical arterial endothelial cells (HUAEC), a transformed human umbilical venous endothelial cell line (C 1 1 STH) and a human colon carcinoma cell line (WiDr). Perlecans were immunopurified from conditioned media of the above cells and the purity of the perlecan preparations was examined by composite agarose polyacrylamide gel electrophoresis (CAPAGE) and semi-dry immunoblotting with monoclonal antibodies directed to either the perlecan core protein (mAb A76) or heparan sulphate (HS) side-chain (mAb10E4). The ability of each perlecan species to bind fibroblast growth factor-l (FGF-1) was examined using a biosensor (BIAcore). The bioactivity of perlecan FGF-1 interactions was also analysed using BaF3 cells transfected with fibroblast growth factor receptors FGFR1b and 1c. CAPAGE demonstrated subtle differences between the perlecans, indicating they had differing charge to mass ratios with C 11 STH perlecan being slightly more mobile in CAPAGE than the HUAEC and WiDr sample. BIAcore biosensor analysis demonstrated distinct differences in the ability of perlecan preparations to bind FGF-1; HUAEC and C 11 STH perlecan showed similar high binding responses as compared to WiDr perlecan, which bound FGF-1 very poorly. Binding of FGF-1 to endothelial perlecans was shown to be HS-dependent. Interestingly, HUAEC perlecan stimulated the growth of FGFR1b and FGFR1c expressing cells in the presence of FGF-1 comparable to heparin, whereas C 11 STH perlecan showed only very limited stimulation of FGFR 1b cells and was incapable of stimulating FGFR1c cells. WiDr perlecan exhibited no stimulation of growth in either cell line. Collectively the data presented herein indicate that. different cell types express perlecans which vary in the growth factor binding capabilities, which may suggest differences in their HS chain substructure. This may represent a subtle mechanism whereby cells can modulate the responsiveness of perlecan to a range of biologically important ligands and thus in a broader context may have important implications for cell signalling.

Biosensing Techniques↗
PubMed2001

The nursing shortage--it's back!

Nursing shortages have been cyclic events during the 1970s, 1980s, and early 1990s. Recent downsizings and reengineerings have witnessed professional nurses in reduction of workforce actions. Acute-care settings, with goals of increased productivity and cost reduction, have decreased ratios of professional to nonlicensed staff frequently forcing nurses to practice with fewer resources and in diverse healthcare settings. As inpatient settings find a higher acuity level of patients receiving care from a "leaner" high-percentage agency workforce, many experts believe we are beginning to experience a new wave of shortages that will be more critical than those of the past. Hospitals and other healthcare practice sites will experience a shortage of professionals necessary to provide care to patients and will be competing for those scarce resources. This article presents a discussion of the important factors of supply and demand related to the shortage and possible strategies for hospitals to use when approaching the large and complex challenge.

Delivery of Health Care↗
PubMed2001

Increasing realism among gay men in Sydney about HIV treatments: changes in attitudes over time.

It is important to know if optimism about HIV treatments is widespread and whether it is growing. To this end, cross-sectional surveys of gay men were conducted 6-monthly in Sydney between February 1997 and February 1999 (n = 3012). Recruitment was consistent at 4 gay community venues. The participants responded True, False or Unsure to 5 statements about the effectiveness of HIV treatments (2 items), and transmission (2 items) and 'worry' (1 item) in the context of treatments. In terms of effectiveness, HIV-positive men were more likely than non-positive men to dismiss 'cure' (P < 0.05) and more likely to support 'treatments prevent serious illness' (P < 0.001). Uncertainty about effectiveness decreased over time (P < 0.001 for each item). In terms of transmission, HIV-positive men were more likely than non-positive men to reject notions of reduced infectivity (P < 0.001). Over time, there was less uncertainty among non-positive men about undetectable viral load and transmission possibilities (P < 0.001). Overall, HIV-positive men were less 'worried' than non-positive men (P < 0.001) but there were no changes over time. On the whole, gay men in Sydney are now less uncertain about highly active antiretroviral therapies (HAART) than at the time of their introduction. Most men remain sceptical that these treatments can cure HIV infection and prevent HIV transmission, but in regard to managing illness among those infected, some initial uncertainty is being replaced by a growing optimism about the efficacy of treatments.

Adolescent↗
PubMed2001

Low proliferative rate of invasive node-negative breast cancer predicts for a favorable outcome: a prospective evaluation of 669 patients.

This study was designed to compare outcome in terms of disease-free survival (DFS) in women with histologically negative axillary lymph nodes and documented low proliferative rate cancer to other well-defined prognostic factors including type of adjuvant treatment. Between 1988 and 1998, we studied 669 patients with invasive node-negative breast cancer up to 5 cm in size and low proliferative rate measured by flow cytometry to determine S-phase fraction (SPF) or by histochemistry (Ki67/MIB1). At a median follow-up of 53 months, 5-year DFS for the entire group was 94% and did not differ significantly by type of systemic adjuvant treatment: none (133 patients, 95% DFS), tamoxifen (441 patients, 94% DFS), or chemotherapy with doxorubicin and cyclophosphamide (95 patients, 92% DFS). In a multivariate prognostic factor analysis, only tumor size was significant; 5-year DFS was 96% for T1N0 cancer versus 89% for T2N0 cancer (P = 0.01). We have prospectively confirmed that a low rate of proliferation as measured by SPF or MIB1 determination confers an excellent prognosis in invasive node-negative breast cancer up to 5 cm in size, regardless of adjuvant treatment.

Adult↗
PubMed2000

A scale of optimism-scepticism in the context of HIV treatments.

The aim of this research was to develop a brief scale of gay men's optimism-scepticism in the context of new HIV treatments. Following comprehensive literature search and communication with other researchers, 34 items about viral load testing, HIV therapies and concern about HIV infection were generated. By way of anonymous, self-complete questionnaires, these items were put to 532 gay men recruited at the Sydney Gay and Lesbian Mardi Gras Fair Day in February 1999. Principal axes factor analysis and item refinement yielded an optimism-scepticism scale based on 12 items (range 12-48, with higher scores indicating greater optimism). The sample mean was 19.8 (SD = 4.7). The scale had high internal consistency reliability (Cronbach's alpha = 0.79). Providing preliminary evidence of validity, men who reported unprotected anal intercourse with a causal partner 'in the past six months' had a significantly higher mean score (21.3) than those who did not report this risk practice (19.5, p < 0.001). Similar validation was provided from separate samples of gay men in Queensland and Sydney. Our scale of optimism-scepticism in the context of new HIV therapies is a brief, reliable instrument which can be incorporated within broader questionnaires and interview schedules. It is a useful tool to monitor attitudes toward HIV therapies and possible associations with risk practices.

Adolescent↗
PubMed2000

Condom use and 'withdrawal': exploring gay men's practice of anal intercourse.

Some gay men who have unprotected anal intercourse avoid ejaculation-they practise 'withdrawal'. Using data collected in 1997 from a sample of Sydney gay men (n=625), we explored the relation between men's practice of ejaculation and their use of condoms. We also investigated whether men who had unprotected withdrawal but not unprotected ejaculation were more likely to think unprotected withdrawal was safe, liked condoms less, liked anal intercourse more, or were more sexually adventurous. Considering separately insertive and receptive anal intercourse with regular and with casual partners, we found that the majority of men who practised unprotected withdrawal also practised unprotected ejaculation. Of those whose only unprotected sex was withdrawal ('true withdrawers'), most never used condoms (they did not also have protected sex with ejaculation). True withdrawers were compared with men who had unprotected ejaculation, who always used condoms, who had no anal sex and who had no partners. Those who were true withdrawers with casual partners were more likely to believe withdrawal was safe; no group effects were found with regular partners. No significant differences in condom attitudes were found. True withdrawers with regular partners liked anal intercourse less than other men, but true withdrawers with casual partners were indistinguishable from those who had unprotected ejaculation. True withdrawers did not differ in sexual adventurousness from other men who had anal intercourse. Most withdrawers avoided anal sex with ejaculation rather than use condoms. Converting them into reliable condom users may be a considerable challenge for health promotion.

Adult↗
PubMed2000

Gay men in Australia who do not have HIV test results.

Whereas most gay men in Australia know their HIV test result, a consistent minority do not. From Gay Community Periodic Surveys (n=6831) conducted during 1998 in the 5 largest cities, those who did not have HIV test results (13.3% overall) comprised 10.0% in Sydney, 15.7% in Melbourne, 13.6% in Brisbane, 15.2% in Perth and 14.0% in Adelaide, representing a significant difference between cities (P < 0.001). Gay men who did not have HIV test results differed from those who did in several ways. They were on average younger (31 vs 35 years, P<0.001) and less likely to be in professional occupations (P<0.001). They were less likely to identify themselves as 'gay' (P<0.001), spent less time with other gay men (P<0.001) and had fewer gay friends (P<0.001). They had sex with fewer different men 'in the previous 6 months' (P<0.001) and were more likely to be in a monogamous relationship or without sexual partners at the time of the survey (P<0.001). With respect to both regular and casual partners, they were more likely (P<0.001) to have 'no such partner'/'no anal intercourse' rather than 'anal intercourse' (either always protected or sometimes unprotected). These differences between gay men who did and did not have HIV test results were confirmed in a logistic regression (apart from 'amount of free time spent with gay men' and 'relationship status' which were accounted for by closely correlated variables in the reduced logistic model). Social and sexual environment appears to exert an influence on HIV testing rather than sexual risk per se.

Adult↗
PubMed1999

HIV treatments optimism and sexual behaviour among gay men in Sydney and Melbourne.

OBJECTIVES: To investigate associations between gay men's optimism and sexual behaviour in the context of new HIV treatments. METHODS: Cross-sectional surveys (using anonymous, self-completed questionnaires) were conducted in Sydney during February 1998 (n = 2200) and in Melbourne during January 1998 (n = 1891). Gay men were recruited at social and sex-on-premises venues, clinics and fair days/carnivals. RESULTS: In a multivariate analysis, unprotected anal intercourse with casual partners (UAIC) was associated with being recruited at a sex-on-premises venue (rather than a clinic or fair day/carnival), HIV positivity, having been tested for HIV less than 6 months ago (rather than over 2 years ago or never having been tested), and not having a regular partner. Over and above these factors, UAIC was associated with agreement with the statements 'An HIV-positive person who is on combination therapy is unlikely to transmit HIV' and 'I'm less worried about HIV infection than I used to be'. CONCLUSIONS: The data reveal a significant relationship between UAIC and certain aspects of optimism in the context of new HIV treatments. Whereas the direction of causality cannot be specified, there is a clear need for HIV and sexual health education programmes to clarify issues of viral load, new and drug resistant strains of HIV, and other infectious agents.

Attitude↗
PubMed1999

Effects of similarities in lifestyle habits on familial aggregation of high density lipoprotein and low density lipoprotein cholesterol: the NHLBI Family Heart Study.

It is generally assumed that familial aggregation of lipids relates to both genetic and shared environmental factors. To determine the degree to which familial similarities in lifestyle habits explain familial aggregation of high density lipoprotein (HDL) and low density lipoprotein (LDL) cholesterol, the authors analyzed 1994-1996 data from 2,284 US adult participants in the National Heart, Lung, and Blood Institute Family Heart Study. For men and women, respectively, HDL cholesterol correlated with alcohol consumption (r = 0.27, p < 0.001; r = 0.21, p < 0.001), exercise (r = 0.06, p = 0.05; r = 0.10, p = 0.002), and smoking (r = -0.09, p = 0.005; r = -0.13, p < 0.001). There was strong familial aggregation of HDL cholesterol (parent-child, r = 0.32; sibling-sibling, r = 0.29), but less than 10% was explained by lifestyle habits. For LDL cholesterol, weak correlations were found for intake of total fat (r = 0.06, p = 0.07) and fruits/vegetables (r = -0.09, p = 0.005) among men and for smoking (r = 0.10, p = 0.002) among women. LDL cholesterol correlated strongly among family members (parent-child, r = 0.24; sibling-sibling, r = 0.31), but essentially none of this aggregation related to the lifestyle factors studied. This study suggests that lifestyle factors have little effect on the familial aggregation of HDL and LDL cholesterol.

Adult↗
PubMed1999

Radiation absorbed dose estimation for 90Y-DOTA-biotin with pretargeted NR-LU-10/streptavidin.

UNLABELLED: Pretargeted radioimmunotherapy permits the administration of doses of 90Y five times higher than is possible with antibodies directly labeled with 90Yttrium (90Y). These high doses of 90Y introduced new issues for dosimetry that were not encountered in prior studies using conventional radioimmunotherapy. We have addressed these issues here and correlated dosimetry estimates with observed toxicity and tumor responses. METHODS: The pretargeted radioimmunotherapy (PRIT) system employed the antibody NR-LU-10 conjugated with streptavidin, a glycoprotein clearing agent and 90Y-DOTA-biotin. A single dose of 90Y was escalated to 140 mCi/m2. Indium-111(111In) (3-5 mCi) DOTA-biotin was co-injected for gamma camera imaging and dosimetry assessment. The effect of bremsstrahlung radiation from increasing 90Y activity levels with a constant dose of 111In was studied using a phantom. Patient images identified the intestinal tract and the kidneys as potential organs at risk of clinically significant radiation toxicity. A method of measuring the activity localized in the intestinal tract was developed, and S values were calculated to estimate intestinal wall dose from radioactivity present in the intestine. Intestinal, bone marrow and renal toxicity were observed. Coefficients were derived for correlating the relationships between observed intestinal and marrow toxicity and the estimated radiation absorbed doses. RESULTS: At an 90Y:111In ratio of 50:1, bremsstrahlung radiation accounted for 12% of the counts in the images. Grade IV diarrhea was observed in patients estimated to have received 6850-14,000 cGy to the large intestinal wall. The correlation coefficient of intestinal toxicity with absorbed dose was 0.64. Myelotoxicity (measured as grade of suppression of absolute neutrophil count) correlated better with marrow dose (r = 0.72) than with the whole body dose, (r = 0.44). Delayed renal toxicity was observed in two patients 8 and 11 months following therapy. Tumor response was seen in the two patients with the highest estimated dose to tumor, 4,000-6,000 cGy. CONCLUSION: Dosimetry is feasible using 111In as a tracer in the presence of high 90Y activity. The absorbed dose estimates derived in the PRIT schema correlated moderately well with clinically observed toxicity and response.

Adenocarcinoma↗
PubMed1998

Determination of SK&F 108566 (Teveten) in human plasma by reversed-phase high-performance liquid chromatography.

A sensitive, selective and rugged analytical method was developed for the determination of SK&F 108566 (eprosartan, Teveten) in human plasma. The new method employs a simple solid-phase extraction procedure to isolate the drug and its internal standard (SB-200062) from plasma samples. The assay is based on analysis by reversed-phase high-performance liquid chromatography with ultraviolet absorbance detection. The dynamic range of the assay is from 10.0 to 5000 ng/ml, based on 0.5-ml aliquots of plasma. No interference from the endogenous components of plasma, the anticoagulant, or sample collection devices have been noted. The assay has been fully validated. The mean within-run precision (6.5%), between-run precision (4.0%), accuracy (106%) and recovery (71.8%) of the method were considered acceptable. Additionally, SK&F 108566 was found to be stable in plasma under the storage and sample preparation conditions used. This assay has been successfully employed to provide pharmacokinetic data from clinical trials.

Acrylates↗
PubMed1998

Cultures of sexual adventurism as markers of HIV seroconversion: a case control study in a cohort of Sydney gay men.

A case control analysis within an ongoing cohort study was used to examine differences between seroconverters and men who remained HIV-negative. The cases were interviewed within one to 13 months prior to their seroconversion. Their responses to a structured questionnaire were compared with those of HIV-negative controls drawn from the same time period and from the same longitudinal study, Sydney Men and Sexual Health. Data collected from both cases and controls included: demographic and contextual variables, knowledge of HIV transmission, sexual practices, drug and alcohol use and attitudinal factors. The aim was to compare the sexual behaviours, and the social and cultural contexts of such behaviours, of men prior to their HIV seroconversion with men who did not seroconvert. Twenty-three men had seroconverted within the cohort. Cases were identified by a positive HIV antibody test or self-report of positive HIV status following a previous negative HIV test. Three-hundred-and-sixty-nine controls were selected on the basis of being HIV negative at interview in 1994, and having at least one subsequent medically-confirmed negative HIV antibody test. Univariate predictors of seroconversion were: being in a regular relationship with a known HIV-positive partner, drug use, and engaging in a range of anal and esoteric sexual practices. Practices commonly used to enhance sexual pleasure, such as group sex, watching and being watched having sex, the use of sex toys and dressing up/fantasy, were engaged in more frequently by seroconverters. Engaging in these esoteric sexual practices was highly correlated with drug use, involvement in the gay community and engagement in a wide range of anal practices. In the multivariate analysis independent predictors of seroconversion were: younger age; being in a regular relationship with a known HIV-positive partner; believing withdrawal to be safe with regard to HIV transmission; and range of esoteric practices. These results indicate the importance of the social and cultural contexts of particular sexual practices and consequent HIV transmission. Sexually adventurous men may be at increased risk for HIV because they seek sex within particular sexual sub-cultures.

Adult↗
PubMed1998

Increase in unprotected anal intercourse with casual partners among Sydney gay men in 1996-98.

We examined differences over time in Sydney gay men's unprotected anal intercourse, particularly with a view to investigating any behavioural changes after the recent improvements in antiretroviral therapies. Trends in unprotected anal intercourse were monitored through the Sydney Gay Community Periodic (cross-sectional) Surveys which were conducted at six-monthly intervals between February 1996 and February 1998. Gay men (n = 2,863) were recruited and self-completed a short questionnaire at three gay venues and a sexual health clinic. There was a significant increase in unprotected anal intercourse with casual partners (but not with regular partners), applicable to both HIV positive and HIV negative men. Sexual practice was generally unrelated to ideas about recent advances in viral load testing and combination therapies.

Adult↗