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Biomedical subjects

R Kane

Publications and source records attributed to R Kane.

At least 19 recordsLinked to original sources

Leaving the professional tennis circuit: exploratory study of experiences and reactions from elite female athletes.

In 2002, Tennis Australia commissioned a report into the experiences of elite female past players on leaving the professional tennis circuit. Australian players who were in the top 800 of the Women's Tennis Association (WTA) end of year rankings and who had left the professional circuit within the previous 15 years were asked by mail to respond to a questionnaire. The questionnaire asked players to describe their feelings about leaving the tour during the time leading up to leaving the tour to two years after retirement. The main findings of the study suggested that those who planned to leave the tour found the transition process easy, whereas those who did not plan to leave the tour found the process difficult. Most players (66%) did not regret leaving the tour, and, although the remaining players responded that they regretted leaving, none attempted a comeback. Tennis Australia has implemented strategies to assist current players on the professional tour based on the results of this study.

Australia↗

Gremlin gene expression in bovine retinal pericytes exposed to elevated glucose.

AIM: To assess the influence of high extracellular glucose on the expression of the bone morphogenetic protein (BMP) antagonist, gremlin, in cultured bovine retinal pericytes (BRPC). METHODS: BRPC were cultured under conditions of 5 mM and 30 mM d-glucose for 7 days and total RNA was isolated. Gremlin mRNA levels were correlated, by RT-PCR, with other genes implicated in the pathogenesis of diabetic retinopathy and the signalling pathways in high glucose induced gremlin expression were probed using physiological inhibitors. Gremlin expression was also examined in the retina of streptozotocin induced diabetic mice. RESULTS: High glucose stimulated a striking increase in BRPC gremlin mRNA levels in parallel with increases in mRNA for the growth factors vascular endothelial growth factor (VEGF), transforming growth factor beta (TGFbeta), and connective tissue growth factor (CTGF) and changes in other genes including fibronectin and plasminogen activator inhibitor-1 (PAI-1). High glucose triggered gremlin expression was modulated by anti-TGFbeta antibody, by the uncoupler of oxidative phosphorylation, CCCP, and by inhibition of MAP-kinase (MAPK) activation. Striking gremlin expression was observed in the outer retina of diabetic mice and also at the level of the vascular wall. CONCLUSIONS: Gremlin gene expression is induced in BRPC in response to elevated glucose and in the retina of the streptozotocin induced diabetic mouse. Its expression is modulated by hyperglycaemic induction of the MAPK, reactive oxygen species, and TGFbeta pathways, all of which are reported to have a role in diabetic fibrotic disease. This implicates a role for gremlin in the pathogenesis of diabetic retinopathy.

Animals↗

Combination therapy with ribavirin and interferon in a cohort of children with hepatitis C and haemophilia followed at a pediatric haemophilia treatment center.

Nearly all children with bleeding disorders who received factor concentrates prior to the late 1980s were infected with hepatitis C. Treatment of adults infected with hepatitis C with combination therapy consisting of ribavirin and interferon has shown sustained response rates of 30-60%. Little data is available on the response of children infected with hepatitis C treated with combination therapy, especially those with bleeding disorders. We wish to report a single paediatric haemophilia treatment center's results of treatment of adolescents with haemophilia and hepatitis C infection with combination therapy. All patients followed at the haemophilia treatment center with hepatitis C, who were human immunodeficiency virus (HIV) negative and had a measurable hepatitis C viral load were eligible. Study patients received at least 6 months of 3 MU interferon-alpha via subcutaneous injection three times per week and 1000 mg day(-1) of ribavirin. Eleven patients agreed to participate in the study. Three patients had an un measurable viral load after 6 months of combination therapy. All three completed 12 months of medication and continued to remain free of hepatitis C for 12 months after discontinuation of therapy. Side-effects of combination therapy were significant but tolerable. The sustained response rate in this study is similar to the historical response rate seen in adults but less than the other reported response rates seen in children treated with combination therapy. Given the toxicity of combination therapy, and natural history of hepatitis C infection in children, consideration of a liver biopsy to evaluate disease progression prior to considering antiviral medications is warranted.

Antiviral Agents↗

The utility of computerized neuropsychological assessment of cognitive dysfunction in patients with relapsing-remitting multiple sclerosis.

Traditional paper-and-pencil neuropsychological batteries used to document cognitive deficits in multiple sclerosis (MS) patients lack timing precision. This makes it difficult to accurately measure psychomotor slowing, a central cognitive symptom of MS. Additionally, traditional batteries lack multiple alternate forms necessary to control for practice effects when assessing cognition over time. Finally such batteries are lengthy and expensive. Computerized neuropsychological batteries address many of these shortcomings. They measure response time more precisely, require less administration time, include alternate forms, and are ideal for rapid screening/triage. Although there are normative data on the reliability and validity of computerized measures, there have been no controlled validation studies with MS patients. The current study was designed to validate a computerized neuropsychological battery (ANAM) for use with relapsing-remitting (RR) MS patients. Prior to initiation of interferon-beta-1a (Avonex) treatment, subjects participated in a neuropsychological evaluation consisting of traditional and computerized measures. Moderate-to-high correlations were found between computerized and traditional measures. Computerized tests accurately predicted performance on key traditional tests. The battery was also concordant with traditional measures in identifying RR MS patients with and without neurocognitive impairment. Findings are discussed with respect to increased accuracy and accessibility of neuropsychological evaluations for MS patients.

Adolescent↗

Fragmentation of care for frail older people--an international problem. Experience from three countries: Israel, Canada, and the United States.

Cross-national comparisons of healthcare systems can help us to better understand them and to offer possible solutions for problems identified within these jurisdictions. Because multiple discontinuities present in most healthcare systems interfere with the appropriate clinical care of frail older people, we were interested in comparing the situation in three countries with markedly different healthcare systems. At one end of the spectrum we find Canada, with an almost fully socialized system. At the other stands the United States, where market forces are allowed the freest rein in any developed nation. Israel offers an intermediate model with elements held in common with both the U.S. and Canadian systems. Although the problems outlined in this paper can be addressed at the "micro" level, it is through an improvement in the structuring and organization of national systems of care that the appropriate conditions for the care of frail older people can be truly bettered. This international comparison offers insights for policy makers in these three states in particular and other countries in general.

Aged↗

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↗

Clinical features of newly presenting cases of chronic otitis media.

The clinical features of 58 consecutive patients presenting with a new case of chronic otitis media were prospectively collected over a 15-month period. Twenty-three ears had a keratin filled marginal or attic defect (14 with cholesteatoma), 20 had a self-clearing marginal or attic defect, and 21 had a central tympanic membrane perforation (including one cholesteatoma). Twenty patients (35 per cent) had an abnormal finding in the opposite ear. The patients' ages were dispersed over a wide range of age groups with a mean age of 34 years. Hearing loss was the most common presenting symptom (78 per cent), followed by otorrhoea (64 per cent). A significant proportion of patients denied any history of otorrhoea. Our findings should alert the clinician to suspecting a new case of COM in patients with hearing loss of any age, with, or without, a history of otorrhoea, regardless of their background ear history or the duration of their symptoms.

Adolescent↗

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↗

Transcription factor NF 1 expression in involuting mammary gland.

Transcripts of each of the four NF1 genes (NF1 A, B, C (CTF/NF1) and X) are expressed in both lactating and involuting mouse mammary gland but there is an indication that increased expression of an NF1 C (CTF/NF1) transcript accompanies early involution. The involution-associated 74 kD NF1 and the 114 kD lactation-associated NF1 are recognised by an anti-NF1 C-specific antibody that does not cross-react with other NF1 proteins. It is most likely that this lactation/involution switch in NF1 factors represents a change in expression of NF1 C (CTF/NF1) proteins.

Animals↗

Managed care and multilevel long-term care providers: reluctant partners.

Managed care is reshaping our health care system, although long-term care is only beginning to feel its effects. We report on the managed care involvement of 492 multilevel, long-term care facilities (MLFs; including skilled nursing and assisted/independent living) nationally. Organizational structure and culture and especially environmental characteristics are associated with whether facilities have contracts with managed care organizations (MCOs), plan to have contracts, are only gathering information on MCOs, or intend to do nothing in the near future. Resource dependence theory best explains MCO contracting patterns with MLFs appearing to be responding more to survival than to growth.

Aged↗

Implementing the second generation social health maintenance organization.

BACKGROUND: In 1996 the Health Care Financing Administration implemented a second generation of the Social HMO demonstration. This model retained the chronic care benefits of the original Social HMOs while attempting to develop a geriatric service model integrated into primary care and a screening and assessment process focused directly on healthcare risk factors. Other refinements included risk-adjusted capitation payment, broadened eligibility for expanded care benefits, low co-payments for these benefits, and no caps on the expanded care benefits expenditures. OBJECTIVES: The geriatric approach is designed to facilitate integration among providers and levels of care. This includes timely application of primary care monitoring and treatment to reduce illness and disability as well as a geriatric education and consultation program to provide specialty support for complex cases. Care management is designed for those requiring home-based care, those discharged from hospitals or nursing homes, and those having difficulty with treatment regimens. DESIGN: A case study of the Social HMO implementation through the Fall of 1999. SETTING: Health Plan of Nevada (HPN), with locations in Las Vegas, Reno, and surrounding areas. PARTICIPANTS: More than 25,000 Medicare beneficiaries participated during the study period. MEASUREMENTS: Administrative reports, charts, and interviews with administrators and clinicians. RESULTS: Within 12 months of operation under this authority, HPN succeeded in putting in place most of the components of the planned geriatric approach: a screening program to identify patients "at risk" for high service costs and disability and timely application of primary care treatment to reduce illness and disability. Geriatric education and a consultation program for complex cases were available, but full implementation was delayed until the plan was able to hire a full time geriatrician. CONCLUSIONS: Health Plan of Nevada's Social HMO program reflects current perspectives on how to integrate chronic care into an HMO. The accomplishments affirm that the provision of risk-adjusted reimbursement, along with the 5 % supplement to the normal Medicare capitation payment, are sufficient incentives for a health plan to restructure itself so that it places a priority on retaining and serving populations at risk for high expenditures.

Aged↗

Long-term functional status and quality of life after lower extremity revascularization.

OBJECTIVE: The objective of this study was to assess the longer term (up to 7 years) functional status and quality of life outcomes from lower extremity revascularization. METHODS: This study was designed as a cross-sectional telephone survey and chart review at the University of Minnesota Hospital. The subjects were patients who underwent their first lower extremity revascularization procedure or a primary amputation for vascular disease between January 1, 1989, and January 31, 1995, who had granted consent or had died. The main outcome measures were ability to walk, SF-36 physical function, SF-12, subsequent amputation, and death. RESULTS: The medical records for all 329 subjects were reviewed after the qualifying procedures for details of the primary procedure (62.6% arterial bypass graft, 36.8% angioplasty, 0.6% atherectomy), comorbidities (64% diabetics), severity of disease, and other vascular risk factors. All 166 patients who were living were surveyed by telephone between June and August 1996. At 7 years after the qualifying procedure, 73% of the patients who were alive still had the qualifying limb, although 63% of the patients had died. Overall, at the time of the follow-up examination (1 to 7.5 years after the qualifying procedure), 65% of the patients who were living were able to walk independently and 43% had little or no limitation in walking several blocks. In a multiple regression model, patients with diabetes and patients who were older were less likely to be able to walk at follow-up examination and had a worse functional status on the SF-36 and a lower physical health on the SF-12. Number of years since the procedure was not a predictor in any of the analyses. CONCLUSION: Although the long-term mortality rate is high in the population that undergoes lower limb revascularization, the survivors are likely to retain their limb over time and have good functional status.

Activities of Daily Living↗

Pharmacokinetics and central nervous system toxicity of declopramide (3-chloroprocainamide) in rats and mice.

Declopramide (3-chloroprocainamide) has been identified in previous studies as a representative of a new class of chemosensitizers. In this study, the toxicity and pharmacokinetics of declopramide have been investigated and compared with a structural analog, metoclopramide (MCA). Declopramide has not induced central nervous system (CNS)-related side effects in rats at doses up to 200 mg/kg, whereas MCA does at 12.5 mg/kg. In addition, declopramide did not bind to dopamine D2 receptors in subcellular preparations at doses up to 100 microM, whereas MCA showed affinity at 1 microM. Declopramide bound with affinity to 5-hydroxytryptamine3 receptors which are important in controlling vomiting. In contrast to MCA, declopramide has a rapid clearance from serum, a lower tissue concentration (about 15-fold lower than MCA) and a lower oral bioavailability (about 6-fold lower than MCA). However, declopramide was shown in vitro to possess a higher tumor cell absorption rate. One of the main metabolites of declopramide was identified as N-acetyl declopramide. Taken together, these data suggest that the clinical development of declopramide as a sensitizer of radio- and chemotherapies is an improvement over MCA, because it can be administered in a high dose and is devoid of CNS side effects.

Administration, Oral↗

Transjugular intrahepatic portosystemic shunt (TIPS) for Budd-Chiari syndrome or portal vein thrombosis: review of indications and problems.

OBJECTIVE: The aim of this study was to evaluate the role of transjugular intrahepatic portosystemic shunt (TIPS) in patients who present with portal vein thrombosis (PVT) or Budd-Chiari Syndrome (BCS). METHODS: Nine patients with recent PVT and four patients with BCS underwent TIPS. The diagnosis was confirmed by color Doppler ultrasound and by angiogram in most patients. Patients were followed clinically and had TIPS checked periodically for patency. The end point was mortality, subsequent surgical shunting or orthotopic liver transplantation (OLT). RESULTS: TIPS was placed in 13 of 15 (87%) patients with BCS or PVT. The mean decrease in pressure gradient was 56%. Median and mean follow-up were 14 months and 16.9 months. Procedure related complications occurred in two of 13 (15%), both in the PVT group. Direct procedural mortality was one of 13 (8%). The majority of patients with PVT (five of eight) underwent OLT. Of the remaining three, one patient subsequently developed a cavernous transformation of portal vein but is stable, one patient is stable, without further variceal bleeding, and one patient died because of multiple organ failure. In patients with BCS, three of four (75%) did well with TIPS, but one patient required immediate surgical shunting after occlusion of the TIPS. Two patients underwent OLT and the fourth patient is stable 2 yr later but has cirrhosis on biopsy. CONCLUSIONS: In patients with BCS, TIPS placement is effective and can be used as a bridge to liver transplantation. TIPS in the noncavernous PVT group should only be recommended when cirrhosis and uncontrollable variceal bleeding are present.

Adult↗

Trends in teenage pregnancy in England and Wales: how can we explain them?

Teenage pregnancy is associated with adverse social and physical outcomes for both mother and child. We drew on various sources--birth and abortion statistics from the Office for National Statistics, data from the National Survey of Sexual Attitudes and Lifestyles, and routinely collected data from family planning clinics--to identify trends in England and Wales and their possible determinants. The rate of teenage sexual activity has increased steadily and consistently over the past four decades, whilst the rate of teenage fertility has shown greater variation. When the teenage fertility rate is calculated against the denominator of sexually active women, rather than the total sample of teenage women, the underlying trend in teenage fertility over the past four decades has been downwards, though not consistently so. Fluctuations in the teenage fertility rate seem to track intervention-related factors such as access to, and use of, contraceptive services and the general climate surrounding the sexual health of young people.

Abortion, Induced↗

The effects of clinical pathways for renal transplant on patient outcomes and length of stay.

OBJECTIVES: Clinical pathways have been implemented nationwide but little is understood about their effects on efficiency of care and patient outcomes. The present study examined the effects of both development and implementation of two renal transplant pathways. METHODS: Cohorts of patients at a university hospital were compared before, during, and after the development and implementation of two renal transplant clinical pathways: isolated renal transplant from cadaveric donors (n = 170) or from living donors (n = 178). Clinical pathways for cadaveric and living related donor renal transplants were developed and implemented. Hospital length of stay and complications and infections after renal transplant were determined. RESULTS: Mean length of hospital stay decreased after development and implementation of the cadaveric donor pathway (11.8 days after implementation versus 17.5 days before development). Cadaveric kidney recipients also had statistically fewer complications and infections after both guideline development and guideline implementation (57.1% before, 24.5% during, 18.5% after), but the greatest effect occurred during development. All of these findings persisted after control for demographic and comorbid factors. There were no changes in hospital stay, complications, or infections in the patients who received kidneys from living donors. CONCLUSIONS: The development and use of a clinical pathway for cadaveric donor renal transplant patients was associated with a significant decline in length of stay, complications, and infections, but much of the effect was seen during development rather than during implementation, and a closely related pathway for living related donor patients had no effect. Further understanding of what factors predict an effective pathway and what elements (ie, development or implementation) have an effect should be undertaken.

Adult↗