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David Wilkinson

Publications and source records attributed to David Wilkinson.

At least 37 records · Page 2Linked to original sources
PubMed2004

Roles of erbB4, rhombomere-specific, and rhombomere-independent cues in maintaining neural crest-free zones in the embryonic head.

Within the developing vertebrate head, the migration of neural tube-derived neural crest cells (NCCs) through the cranial mesenchyme is patterned into three streams, with mesenchyme adjacent to rhombomeres (r)3 and r5 maintained NCC-free. The receptor tyrosine kinase erbB4 is expressed within r3 and r5 and is required to maintain the r3-adjacent NCC-free zone in mouse embryos. In this study, we demonstrate that the extent of r3 involvement in patterning mouse NCC migration is restricted to the same dorsolateral region regulated by erbB4. In chick embryos, we show that erbB4 signaling similarly maintains the r3-adjacent NCC-free zone. However, although r5 expresses erbB4, this is insufficient to maintain the r3-adjacent NCC-free zone in grafting experiments where r5 replaced r3, indicating that erbB4 requires additional factors at the A-P level of r3 to pattern NCC migration. Furthermore, we show that the r5-adjacent NCC-free zone is maintained independently of r5, but requires surface ectoderm. Finally, we demonstrate that avian cranial surface ectoderm is patterned molecularly, with dorsolateral surface ectoderm at the levels of r2/3 and r7 expressing the sulfatase QSulf1 in quail, or the orthologue CSulf1 in chick. Aberrant NCC migration into r3-adjacent mesenchyme correlated with more focused QSulf1 expression in r2/3 surface ectoderm.

Animals↗
PubMed2004

Hyperbaric oxygen treatment and survival from necrotizing soft tissue infection.

HYPOTHESIS: Necrotizing soft tissue infection (NSTI) refers to a spectrum of infective diseases characterized by necrosis of the deep soft tissues. Features of manifestation and medical management have been analyzed for association with outcome. The use of hyperbaric oxygen (HBO(2)) therapy has been recommended as an adjunctive treatment but remains controversial. DESIGN: Retrospective cohort study. SETTING: A major tertiary hospital. PATIENTS: All patients admitted with a diagnosis of NSTI across a 5-year period. INTERVENTION: Features of manifestation and medical management were analyzed for their association with survival to hospital discharge. Long-term survival was analyzed for the intervention of HBO(2) therapy. MAIN OUTCOME MEASURES: Primary outcome was survival to hospital discharge. Secondary outcomes were limb salvage and long-term survival after hospital discharge. RESULTS: Forty-four patients were reviewed, with 6 deaths (14%). Survival was less likely in those with increased age, renal dysfunction, and idiopathic etiology of infection and in those not receiving HBO(2) therapy. Logistic regression determined the strongest association with survival was the intervention of HBO(2) therapy (P = .02). Hyperbaric oxygen therapy increased survival with an odds ratio of 8.9 (95% confidence interval, 1.3-58.0) and a number needed to treat of 3. For NSTI involving an extremity, HBO(2) therapy significantly reduced the incidence of amputation (P = .05). Survival analysis revealed an improved long-term outcome for the HBO(2) group (P = .002). CONCLUSION: Hyperbaric oxygen therapy was associated with improved survival and limb salvage and should be considered in the setting of NSTI.

Adult↗
PubMed2004

Uncovering a hidden epidemic: a study of the current burden of heart failure in Australia.

BACKGROUND: Australia, like other countries, is experiencing an epidemic of heart failure (HF). However, given the lack of national and population-based datasets collating detailed cardiovascular-specific morbidity and mortality outcomes, quantifying the specific burden imposed by HF has been difficult. METHODS: Australian Bureau of Statistics (ABS data) for the year 2000 were used in combination with contemporary, well-validated population-based epidemiologic data to estimate the number of individuals with symptomatic and asymptomatic HF related to both preserved (diastolic dysfunction) and impaired left ventricular systolic (dys)function (LVSD) and rates of HF-related hospitalisation. RESULTS: In 2000, we estimate that around 325,000 Australians (58% male) had symptomatic HF associated with both LVSD and diastolic dysfunction and an additional 214,000 with asymptomatic LVSD. 140,000 (26%) live in rural and remote regions, distal to specialist health care services. There was an estimated 22,000 incidents of admissions for congestive heart failure and approximately 100,000 admissions associated with this syndrome overall. CONCLUSION: Australia is in the midst of a HF epidemic that continues to grow. Overall, it probably contributes to over 1.4 million days of hospitalization at a cost of more than 1 billion dollars. A national response to further quantify and address this enormous health problem is required.

Journal Article↗
PubMed2004

Cancer and cancer risk in South Australia: what evidence for a rural-urban health differential?

OBJECTIVE: To determine the extent of evidence for a rural-urban health differential in cancer and cancer risk in South Australia. DESIGN: Secondary analysis and synthesis of data available between 1977 and 2000 from the publications of the South Australian Cancer Registry and reports of population health surveys carried out by the South Australian Department of Human Services. RESULTS: The mean annual age-standardised incidence of all forms of cancer combined was about 4% lower for rural residents (265.2 per 100,000 cf. 274.9 per 100,000). Of 31 types of cancer listed, the incidence of three was significantly higher among rural residents, the incidence of eight was significantly higher among urban residents and for 20 types there was no significant difference. Five year case survival for all cancers combined was 52% in both urban and rural residents. Significant survival differences were identified for only 10 cancers and survival for each was higher among urban residents. Melanomas were diagnosed in situ more often in the country, but invasive cases tended to be thicker. There was no rural-urban difference in early detection rates for breast cancer or bladder cancer. There were no substantial reported differences in major risk factors and early detection experiences apart from higher rates of smoking in the country. CONCLUSIONS: There is little evidence for substantial or systematic differences in risk factors for, and incidence and early detection of cancers between urban and rural South Australia. However, the apparent consistently poorer survival among rural residents warrants further study. WHAT THIS PAPER ADDS: It is widely reported that the health status of rural Australians is worse than that of their urban counterparts. There is an apparent increasing gradient in mortality from urban to remote areas of Australia. However, this apparent gradient is not evident for all diseases. This paper seeks to answer the question: is there any difference in the cancer disease experience (incidence, survival and early detection) and cancer risk factors between residents of rural and urban South Australia. Cancer registry data indicate that overall, the incidence of cancer is similar in rural and urban South Australia. The findings on survival differentials are of concern. While overall survival rates are very similar in country and city, and this is encouraging, analysis of individual types of cancer raises some concerns. The registry reports that significant differences in survival were only measured for 10 cancers and for all of these rural residents experienced higher mortality rates.

Adolescent↗
PubMed2004

The safety and tolerability of donepezil in patients with Alzheimer's disease.

Cholinesterase (ChE) inhibitors, which prevent the hydrolysis of acetylcholine, have been approved for the symptomatic treatment of Alzheimer's disease (AD) for over a decade. However, the first ChE inhibitors were associated with a high incidence of side-effects and general tolerability concerns, including hepatotoxicity. Side-effects associated with increased cholinergic activity, particularly in the gastrointestinal (GI) system, can prevent patients from achieving effective doses of drug. In addition, the advanced age and frail nature of patients with AD mean that poor tolerability is a serious concern. The potential for drug-drug interactions is also an important consideration, due to the high prevalence of comorbid disease in these patients. Data both from clinical trials and studies in routine clinical practice have shown that donepezil is associated with a low incidence of GI adverse events (AEs) that is comparable with placebo. Donepezil is a potent, selective inhibitor of acetylcholinesterase, and selective inhibition of central as opposed to peripheral ChEs might be expected to reduce the incidence of AEs, thus this may explain the lower incidence of cholinergic AEs observed following treatment with donepezil, compared with nonselective ChE inhibitors. There are no differences in cardiovascular AEs, including bradycardia, between placebo and donepezil groups in the clinical trials published to date, even in a very sick vascular dementia population with high rates of comorbidity and concomitant medication use. Data from single- and multiple-dose studies of donepezil in patients with hepatic impairment and with moderately to severely impaired renal function indicate that donepezil is safe and well tolerated in these groups. Furthermore, both in vitro and clinical studies have shown that donepezil is not associated with drug-drug interactions. The incidence of weight loss is very similar between donepezil- and placebo-treated patients. Although insomnia and other sleep disorders have been reported following administration of donepezil, lengthening the time period before increasing the dose of donepezil from 5 to 10 mg day(-1) or switching to morning dosing can reduce these events to the levels of placebo-treated patients. Over 770 million days of patient use and an extensive publication database demonstrate that donepezil has a good tolerability and safety profile.

Alzheimer Disease↗
PubMed2004

Treatment of maternal syphilis in rural South Africa: effect of multiple doses of benzathine penicillin on pregnancy loss.

OBJECTIVES: Despite few data, the treatment of syphilis in pregnant women using a single dose of benzathine penicillin is the standard of care in many resource-poor settings. We examined the effect of various doses of benzathine penicillin on pregnancy loss among women with a positive Rapid Plasma Reagin (RPR) test result in a rural South African district. METHODS: All pregnant women making their first antenatal care visit during pregnancy were screened for syphilis using the RPR test. Those testing positive were counselled to receive three weekly doses of benzathine penicillin, and received a partner notification card. Pregnancy outcomes were determined from facility records or home visits where necessary. RESULTS: Of 8917 women screened, 1043 (12%) had reactive syphilis serology; of those with titre data available, 30% had titres of 1:8 or greater. While 41% (n = 430) of women received all three doses as counselled, 30% (n = 312) received only one dose, and 20% (n = 207) did not return to the clinic to receive treatment. Among the 947 women with pregnancy outcome data available, there were 17 miscarriages and 48 perinatal deaths observed. There was a strong trend towards reduced risk of pregnancy loss among women receiving multiple doses of penicillin (adjusted OR for perinatal mortality for each additional dose received, 0.63; 95% CI, 0.48-0.84). CONCLUSIONS: While this association requires further investigation, these results suggest that there may be substantial benefit to providing multiple doses of benzathine penicillin to treat maternal syphilis in this setting.

Abortion, Spontaneous↗
PubMed2004

Does health service utilisation vary by remoteness? South Australian population data and the Accessibility and Remoteness Index of Australia.

OBJECTIVE: To compare rates of self-reported use of health services between rural, remote and urban South Australians. METHODS: Secondary data analysis from a population-based survey to assess health and well-being, conducted in South Australia in 2000. In all, 2,454 adults were randomly selected and interviewed using the computer-assisted telephone interview (CATI) system. We analysed health service use by Accessibility and Remoteness Index of Australia (ARIA) category. RESULTS: There was no statistically significant difference in the median number of uses of the four types of health services studied across ARIA categories. Significantly fewer residents of highly accessible areas reported never using primary care services (14.4% vs. 22.2% in very remote areas), and significantly more reported high use (> or =6 visits, 29.3% vs. 21.5%). Fewer residents of remote areas reported never attending hospital (65.6% vs. 73.8% in highly accessible areas). Frequency of use of mental health services was not statistically significantly different across ARIA categories. Very remote residents were more likely to spend at least one night in a public hospital (15.8%) than were residents of other areas (e.g. 5.9% for highly accessible areas). CONCLUSION: The self-reported frequency of use of a range of health services in South Australia was broadly similar across ARIA categories. However, use of primary care services was higher among residents of highly accessible areas and public hospital use increased with increasing remoteness. There is no evidence for systematic rural disadvantage in terms of self-reported health service utilisation in this State.

Adolescent↗
PubMed2004

Electronic medical records may be inadequate for improving population health status through general practice: cervical smears as a case study.

OBJECTIVE: [corrected] To determine whether routine electronic records are an accurate source of population health data in general practice through reviewing cervical smears rates in four South Australian practices. METHODS: The cervical screening rate in a purposive sample of four general practices (three rural and one urban) was obtained using an audit of medical records and a telephone follow-up. RESULTS: The cervical screening rate using only immediately available electronic medical records indicated an overall low rate for the participating practices (44.9%). However, telephone follow-up and adjustments to the denominator indicated the real rate to be 85.7%. The offer of appointments during the telephone follow-up further improved this rate for eligible women (93.8%). CONCLUSIONS AND IMPLICATIONS: Electronic medical records may be inadequate in preventive screening in general practice, without ensuring their accuracy. Updating records by telephone or personal follow-up produces a much more accurate denominator.

Adolescent↗
PubMed2003

Uterine cavity matrix metalloproteinases and cytokines in patients with leiomyoma, adenomyosis or endometrial polyp.

OBJECTIVE: To determine whether leiomyoma, adenomyosis and endometrial polyps are associated with changes in uterine cavity matrix metalloproteinases (MMP-2 and MMP-9) and cytokines. STUDY DESIGN: Uterine cavity irrigation was performed in women with leiomyoma, adenomyosis and endometrial polyps, and in women with a normal uterus. MMP-2 and MMP-9 were assayed in the uterine washings by gelatin zymography. For individual subjects, the total MMP level was obtained by adding the semi-quantitative scores of band densities related to gelatinases in the zymograms. Interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma) and transforming growth factor-beta1 (TGF-beta1) were measured using enzyme-linked immunosorbant assay (ELISA) kits. RESULTS: The uterine cavity of patients with leiomyoma, adenomyosis and endometrial polyps had significantly higher MMP scores than controls. Although the mean IL-1beta levels were elevated in uteri harboring a pathology compared with the normal uteri, the cytokine was significantly elevated only in the adenomyotic group. Significantly elevated levels of IFN-gamma were found in uteri with leiomyoma and endometrial polyps. Uterine washings from leiomyoma and adenomyosis contained significantly elevated mean levels of TGF-beta1 compared with controls, while TNF-alpha was significantly higher only in leiomyoma. When uterine cytokine levels were compared in relation to individual MMP levels a significant relationship was found between TGF-beta1 and elevated levels of MMP-9 and total MMPs in leiomyoma. A significant relationship was also found between IL-1beta and elevated levels of MMP-2, MMP-9 and total MMPs in the endometrial polyp group. CONCLUSION: The uterine cavity in leiomyoma, adenomyosis and endometrial polyps contains elevated levels of MMPs and cytokines compared with the normal uterus. In some pathologies elevated cytokines are associated with elevated MMPs.

Cytokines↗
PubMed2003

Factors associated with rural practice among Australian-trained general practitioners.

OBJECTIVE: To determine the factors associated with general practitioners' current practice location, with particular emphasis on rural location. DESIGN: Observational, retrospective, case-control study using a self-administered questionnaire. SETTING: Australian general practices in December 2000. PARTICIPANTS: 2414 Australian-trained rural and urban GPs. MAIN OUTCOME MEASURE: Current urban or rural practice location. RESULTS: For Australia as a whole, rural GPs were more likely to be male (odds ratio [OR], 1.42; 95% CI, 1.17-1.73), Australian-born (OR, 1.95; 95% CI, 1.55-2.45), and to report attending a rural primary school for "some" (OR, 2.21; 95% CI, 1.69-2.89) or "all" (OR, 2.79; 95% CI, 1.94-4.00) of their primary schooling. Rural GPs' partners or spouses were also more likely to report "some" (OR, 2.75; 95% CI, 2.07-3.66) or "all" (OR, 2.86; 95% CI, 2.02-4.05) rural primary schooling. A rural background in both GP and partner produced the highest likelihood of rural practice (OR, 6.28; 95% CI, 4.26-9.25). For individual jurisdictions, a trend towards more rural GPs being men was only significant in Tasmania. In all jurisdictions except Tasmania and the Northern Territory, rural GPs were more likely to be Australian-born. CONCLUSIONS: GPs' and their partners' rural background (residence and primary and secondary schooling) influences choice of practice location, with partners' background appearing to exert more influence.

Adult↗
PubMed2003

Prevalence of asthma and asthma action plans in South Australia: population surveys from 1990 to 2001.

OBJECTIVES: To assess trends in the prevalence of self-reported doctor-diagnosed asthma, associated asthma related morbidity, and the uptake of written asthma action plans in South Australia, 1990-2001. DESIGN, SETTING AND PARTICIPANTS: Surveys by telephone interview of the South Australian population between 1990 and 2001, and interview of participants in their own homes by trained health interviewers. MAIN OUTCOME MEASURES: Asthma prevalence, percentage of patients with written action plans, and asthma associated morbidity. RESULTS: The reported prevalence of doctor-diagnosed asthma has increased from 8% (95% CI, 6.4%-9.6%) in 1990 to 12.8% (95% CI, 11.4%-14.2%) in 2001. Morbidity, as measured by wakening at night (daily or weekly) and days lost from normal activities because of asthma, has remained constant over the decade. The percentage of patients with written asthma action plans increased to a peak of 42.3% (95% CI, 40.3%-44.3%) in 1995, but then declined to 22.2% (95% CI, 20.7%-23.7%) in 2001. CONCLUSIONS: The prevalence of asthma has increased while morbidity has remained constant, indicating that the burden of asthma has increased. The associated decline in the percentage of patients with asthma action plans in recent years is cause for concern.

Asthma↗
PubMed2003

Neuropathology of human Alzheimer disease after immunization with amyloid-beta peptide: a case report.

Amyloid-beta peptide (Abeta) has a key role in the pathogenesis of Alzheimer disease (AD). Immunization with Abeta in a transgenic mouse model of AD reduces both age-related accumulation of Abeta in the brain and associated cognitive impairment. Here we present the first analysis of human neuropathology after immunization with Abeta (AN-1792). Comparison with unimmunized cases of AD (n = 7) revealed the following unusual features in the immunized case, despite diagnostic neuropathological features of AD: (i) there were extensive areas of neocortex with very few Abeta plaques; (ii) those areas of cortex that were devoid of Abeta plaques contained densities of tangles, neuropil threads and cerebral amyloid angiopathy (CAA) similar to unimmunized AD, but lacked plaque-associated dystrophic neurites and astrocyte clusters; (iii) in some regions devoid of plaques, Abeta-immunoreactivity was associated with microglia; (iv) T-lymphocyte meningoencephalitis was present; and (v) cerebral white matter showed infiltration by macrophages. Findings (i)-(iii) strongly resemble the changes seen after Abeta immunotherapy in mouse models of AD and suggest that the immune response generated against the peptide elicited clearance of Abeta plaques in this patient. The T-lymphocyte meningoencephalitis is likely to correspond to the side effect seen in some other patients who received AN-1792 (refs. 7-9).

Aged↗
PubMed2003

Impact of undergraduate and postgraduate rural training, and medical school entry criteria on rural practice among Australian general practitioners: national study of 2414 doctors.

OBJECTIVE: To determine the association between rural undergraduate training, rural postgraduate training and medical school entry criteria favouring rural students, on likelihood of working in rural Australian general practice. METHODS: National case-control study of 2414 rural and urban general practitioners (GPs) sampled from the Health Insurance Commission database. Participants completed a questionnaire providing information on demographics, current practice location and rural undergraduate and postgraduate experience. RESULTS: Rural GPs were more likely to report having had any rural undergraduate training [odds ratio (OR) 1.61, 95% confidence interval (CI) 1.32-1.95] than were urban GPs. Rural GPs were much more likely to report having had rural postgraduate training (OR 3.14, 95% CI 2.57-3.83). As the duration of rural postgraduate training increased so did the likelihood of working as a rural GP: those reporting that more than half their postgraduate training was rural were most likely to be rural GPs (OR 10.52, 95% CI 5.39-20.51). South Australians whose final high school year was rural were more likely to be rural GPs (OR 3.18, 95% CI 0.99-10.22). CONCLUSIONS: Undergraduate rural training, postgraduate training and medical school entry criteria favouring rural students, all are associated with an increased likelihood of being a rural GP. Longer rural postgraduate training is more strongly associated with rural practice. These findings argue for continuation of rural undergraduate training opportunities and rural entry schemes, and an expansion in postgraduate training opportunities for GPs.

Australia↗
PubMed2003

Self-reported patterns of health services utilisation: an urban-rural comparison in South Australia.

OBJECTIVE: To compare self-reported patterns of health service utilisation among residents of urban and rural South Australia. DESIGN, SETTING AND MAIN OUTCOME MEASURES: Secondary analysis of data generated by computer-assisted telephone interviews of 7377 adults done in 1995-6. Respondents were asked if they had used each of 18 different health services during the previous 12 months. Residence was classified in three ways: (1) capital city versus rest of the state, (2) by the Rural, Remote and Metropolitan Areas classification (RRMA) and (3) by the Accessibility and Remoteness Index for Australia classification (ARIA). RESULTS: General practitioner services were most frequently used, by approximately 89% of respondents. Only 4% reported not using any service. Comparing capital city with rest of the state, modest but statistically significant differences in utilisation (P < 0.01) were measured for nine services. In eight of these nine, utilisation was higher among rural residents. Analysing by RRMA, eight services were reportedly used differently and seven of these were the same as those identified from the capital city versus rest of state comparison. Across the five ARIA categories, six previously identified services were reported as being used differentially. Overall, rural residents had a higher than expected rate of moderate and high level of health service use. CONCLUSIONS: Self-reported use of a range of health services was broadly similar across urban and rural South Australia, with most cases of higher use were reported from rural areas rather than urban areas. Similar results were obtained when residence was classified in the three different ways.

Adult↗
PubMed2003

Are socio-economically disadvantaged Australians making more or less use of the Enhanced Primary Care Medicare Benefit Schedule item numbers?

We aimed to examine the relationship between levels of socio-economic disadvantage (measured by the Socio Economic Indexes for Areas [SEIFA] used by the Australian Bureau of Statistics) and uptake of the Enhanced Primary Care (EPC) item numbers on the Medicare Benefits Schedule. Health services are often less likely to reach those that most need them and so it is important to monitor whether disadvantaged communities are accessing EPC The rates of health assessments, care plans and case conferences are similar in each SEIFA quartile (from advantaged to disadvantaged populations), favouring the more disadvantaged quartiles in some cases. These national trends are not observed in each state and territory. For all EPC services combined, the lowest number of doctors that provide EPC services are found in the 2 most disadvantaged quartiles, yet more EPC services are provided in these quartiles, due to the higher mean and median number of services provided by general practitioners in these quartiles. Overall, populations living in the most disadvantaged quartiles have similar or higher levels of EPC uptake, apparently due, at least in part, to greater than average use of EPC services by general practitioners in these areas.

Australia↗
PubMed2003

Influence of HIV-1 coinfection on effective management of abnormal vaginal discharge.

BACKGROUND: Reports on microbiologic cure rates following syndromic management (SM) of women with nonulcerative sexually transmitted infections (STIs) are limited. GOAL: The goal of the study was to determine the effectiveness of the drugs used in SM of nonulcerative STIs and bacterial vaginosis in women and to compare the response among those with and without HIV-1 coinfection. STUDY DESIGN: This was a cohort study of women with nonulcerative STIs who were treated according to local SM protocols. RESULTS: Of 692 women recruited, 415 (80%) returned 8 to 10 days later, and 290 (70%) consented to a second examination, in which specimens were obtained. Clinical cure was reported by 67%, and microbiologic cure ranged from 80% to 89% for the three discharge-causing STIs and was independent of HIV-1 status. Only 38% of those with bacterial vaginosis were cured, and HIV-1-infected women were less likely to be cured (28% versus 52%; P < 0.001). CONCLUSIONS: Clinical and microbiologic response to SM of the nonulcerative STIs was not affected by HIV-1 coinfection, but cure rates for bacterial vaginosis were reduced.

Adolescent↗
PubMed2003

Association between HIV-1 infection, the etiology of genital ulcer disease, and response to syndromic management.

BACKGROUND: Reports on the effect of HIV-1 infection on healing rates of ulcers are conflicting. GOAL: The goal was to determine the etiology and response to treatment of genital ulcer disease (GUD) in relation to HIV-1 infection. STUDY DESIGN: This was a cohort study of patients with GUD treated with local syndromic management protocols. RESULTS: Among the 587 recruited, the prevalences of infections due to HSV, Treponema pallidum, Chlamydia trachomatis (lymphogranuloma venereum [LGV]), Haemophilus ducreyi, Calymmatobacterium granulomatis, and HIV-1 were 48%, 14%, 11%, 10%, 1%, and 75%, respectively. The prevalence T. pallidum of was higher among men (P = 0.03), and an association was seen among HIV-1-seronegatives on univariate and multivariate analyses (P < 0.001; = 0.01). The prevalence of C trachomatis (LGV) was higher among females (P = 0.004), and an association was seen among HIV-1-seropositives on univariate analysis (P = 0.04). At follow-up, 40/407 (10%) showed a decreased healing tendency, not associated with ulcer etiology or HIV-1 seropositivity. CONCLUSION: Response to syndromic management of GUD was acceptable and not associated with HIV-1 coinfection.

Adolescent↗