Reardon KA, Mendelsohn FA, Chai SY
… +1 more, Horne MK
Aust N Z J Med
· 2000 Feb · PMID 10800878
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BACKGROUND: Animal studies have demonstrated an interaction within the striatum between the angiotensin and dopaminergic systems. In rats, the angiotensin converting enzyme (ACE) inhibitor, perindopril, crosses the blood...BACKGROUND: Animal studies have demonstrated an interaction within the striatum between the angiotensin and dopaminergic systems. In rats, the angiotensin converting enzyme (ACE) inhibitor, perindopril, crosses the blood brain barrier and increases striatal dopamine synthesis and release. In humans, angiotensin type 1 receptors have been found on dopaminergic neurons in the substantia nigra and striatum. In Parkinson's disease, there is a marked reduction of these receptors associated with the nigrostriatal dopaminergic neuron loss. AIMS: We performed a double blind placebo controlled crossover pilot study in seven patients to investigate the effect of the ACE inhibitor, perindopril on the clinical features of moderately severe Parkinson's disease. RESULTS: After a four week treatment period with perindopril, patients had a faster onset in their motor response to L-dopa and a reduction in 'on phase' peak dyskinesia, p=0.021 and p=0.014 respectively. Patients also reported more 'on' periods during their waking day in their movement diary, p=0.007. Perindopril was well tolerated without any significant postural hypotension or renal dysfunction. CONCLUSIONS: These results suggest that ACE inhibitors such as perindopril may have a place in the management of motor fluctuations and dyskinesia in Parkinson's disease and justify further study.
Aust N Z J Med
· 2000 Feb · PMID 10800877
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AIM: To confirm the hypothesis that upper normal plasma glucose levels in non-diabetic subjects are independently predictive of mortality and cardiovascular disease (CVD). METHODS: The study reports on 113 months' follow...AIM: To confirm the hypothesis that upper normal plasma glucose levels in non-diabetic subjects are independently predictive of mortality and cardiovascular disease (CVD). METHODS: The study reports on 113 months' follow-up in a prospective study of CVD in the Australian elderly, The Dubbo Study. The cohort, first examined in 1988-89, consisted of 2805 men and women 60 years and older. Of the cohort, 2419 (86%) were defined as non-diabetic. The prediction of outcomes by quartile of fasting plasma glucose was examined in a Cox proportional hazards model, after linkage to hospital and death records. RESULTS: All-causes mortality increased progressively across quartile of fasting plasma glucose in both sexes, reaching statistical significance only in women. Coronary heart disease (CHD) incidence increased similarly, the increases being proportionately greater in women. Ischaemic stroke did not show a consistent gradient with fasting plasma glucose. After adjustment for age and other risk factors, all-causes mortality, CHD and ischaemic stroke incidence were not significantly related to plasma glucose in men. In women, all-causes mortality and CHD incidence showed a significant gradient with glucose quartile. Hazard Ratio (95% confidence intervals) for death in glucose Quartile IV (5.3-6.0 mmol/L) was 1.49 (1.03-2.14) and for CHD incidence was 1.52 (1.08-2.15). Subjects in the upper quartiles of fasting plasma glucose showed a clustering of overweight, hypertension, elevated serum triglycerides, reduced high density lipoprotein cholesterol and excess of small dense low density lipoprotein, suggestive of the Insulin Resistance Syndrome. CONCLUSION: Fasting plasma glucose levels in the upper normal range in non-diabetic elderly subjects appear to be associated with increased all-causes mortality and CHD, especially in women.
Aust N Z J Med
· 2000 Feb · PMID 10800876
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BACKGROUND: To determine the effect of high dose ipratropium bromide, both alone or in combination with standard dose salbutamol, on pulmonary function in patients presenting to the Emergency Department (ED) with acute e...BACKGROUND: To determine the effect of high dose ipratropium bromide, both alone or in combination with standard dose salbutamol, on pulmonary function in patients presenting to the Emergency Department (ED) with acute exacerbation of chronic obstructive airways disease (COAD). METHOD: The trial was a prospective, randomised, double blind trial of adult patients with COAD. All patients received nebulised salbutamol 5 mg and 500 microg ipratropium and hydrocortisone 250 mg i.v. at time=0, then were randomised to receive further nebulisers at time=15 minutes and time=30 minutes of salbutamol 5 mg combined with ipratropium 500 microg or salbutamol 5 mg alone or ipratropium 500 microg alone. Pulmonary function tests were conducted at time=0 and time=90 minutes. The primary endpoints were absolute and percent change in FEV1. RESULTS: The group randomised to receive 5 mg salbutamol and 500 microg ipratropium (n=18) showed a mean percentage change of FEV1 of 6.4% with a mean absolute change of 0.06 L (SD 0.18 L). Those who received 5 mg salbutamol (n=16) had a mean percentage change of 18.6% with a mean absolute change of 0.13 L (SD of 0.21 L). Those who received 500 microg ipratropium (n=16) had a mean percentage change of 4.8% with a mean absolute change of 0.023 L (SD of 0.07 L). There was no significant difference between the groups in FEV1 (p=0.56 for percentage change; p=0.36 for absolute change). CONCLUSION: The addition of 500 microg ipratropium to 5 mg salbutamol in subsequent nebulisers adds no benefit to pulmonary function after the initial nebuliser of both bronchodilators in the treatment of COAD in the ED.
Aust N Z J Med
· 2000 Feb · PMID 10800875
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BACKGROUND: Asthma management plans and asthma education have been incorporated into recent guidelines, and implementation of these reduces asthma morbidity. Junior doctors are frequently involved in asthma management, b...BACKGROUND: Asthma management plans and asthma education have been incorporated into recent guidelines, and implementation of these reduces asthma morbidity. Junior doctors are frequently involved in asthma management, but teaching about asthma in medical school is seldom assessed. We studied asthma knowledge, confidence in practical asthma management, and the effectiveness of an interactive asthma education workshop in final year medical students. Thirty-five students attended the workshop, with 26 returning questionnaires on both of the two sessions. METHODS: Students attended a two hour asthma workshop comprising interactive teaching sessions on management of acute and stable asthma, and a practical session using asthma devices. Theoretical knowledge was assessed by a 20 item questionnaire, completed immediately prior to the workshop and after two weeks, at a feedback session. Practical knowledge was assessed by confidence scores in use of asthma devices on a five point scale (not at all confident to very confident), before, immediately after the workshop, and after two weeks. RESULTS: Students scored poorly in questions on: predictors of asthma mortality, nebuliser and Turbuhaler use, asthma management plans, and physical signs in acute asthma. Mean (SE) knowledge score increased significantly from 64.4% (6.1) to 74.2% (5.6) (p<0.05; paired t-test) at two weeks. Confidence scores rose significantly for all practical aspects of asthma management (p<0.01; Wilcoxon matched pairs test), and declined at two weeks, but still remained significantly higher than at baseline (p<0.05). CONCLUSIONS: Medical students had poor knowledge about several important features of asthma care. The asthma workshop was effective in increasing knowledge and confidence in management of asthma in the short term, and could be useful in optimising implementation of asthma guidelines in clinical practice and potentially later in training of junior medical officers.
Aust N Z J Med
· 2000 Feb · PMID 10800874
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BACKGROUND: Reactive arthritis (ReA) is an inflammatory arthritis triggered by certain gastrointestinal and genitourinary infections. Single source outbreaks of triggering infections provide an opportunity to elucidate h...BACKGROUND: Reactive arthritis (ReA) is an inflammatory arthritis triggered by certain gastrointestinal and genitourinary infections. Single source outbreaks of triggering infections provide an opportunity to elucidate host susceptibility factors in this disease. AIM: To determine the role of Major Histocompatibility Complex (MHC) Class I alleles in ReA susceptibility after two large single source outbreaks of Salmonella Typhimurium gastroenteritis. METHODS: A questionnaire screening for features of ReA and a request for HLA class I typing were sent to all patients affected by two single source outbreaks of S. Typhimurium gastroenteritis. Individuals with arthritis of recent onset were interviewed, examined and diagnostic criteria for ReA applied. RESULTS: Nineteen cases of reactive arthritis, 11 female, were diagnosed in the 424 respondents with S. Typhimurium gastroenteritis from both outbreaks. Clinical features of the arthritis were similar to those described after other large single source outbreaks of Salmonella infection. HLA-B27 was expressed by only two of the 19 ReA patients and therefore did not predict susceptibility to this form of arthritis. Caucasians were, however, more likely to develop reactive arthritis than Asians. CONCLUSIONS: In this study, susceptibility to ReA was not increased in HLA-B27 positive individuals or males but was greater in those of Caucasian descent.
Pasco JA, Sanders KM, Henry MJ
… +3 more, Nicholson GC, Seeman E, Kotowicz MA
Aust N Z J Med
· 2000 Feb · PMID 10800873
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BACKGROUND: Dietary calcium deficiency may be a risk factor for osteoporosis. AIMS: To estimate habitual calcium intakes and prevalence of calcium supplementation among free-living Australian women and validate a calcium...BACKGROUND: Dietary calcium deficiency may be a risk factor for osteoporosis. AIMS: To estimate habitual calcium intakes and prevalence of calcium supplementation among free-living Australian women and validate a calcium-specific food-frequency questionnaire. METHODS: Calcium intakes for 1045 randomly selected women (20-92 years) were estimated by questionnaire which was tested against estimates from four day weighed records kept by 32 randomly selected women. RESULTS: The mean difference between calcium estimates was not statistically significantly different from zero (mean difference=121 mg; standard deviation of differences=357 mg; p>0.05). There was moderate agreement (weighted kappa=0.4) between methods in ranking subjects into tertiles of calcium intake. Mean dietary calcium intakes were 615 mg/day for 20-54 years, 646 mg/day for 55-92 years and 782 mg/day for lactating women. Seventy-six per cent of women aged 20-54 years, 87% of older and 82% of lactating women had intakes below the recommended dietary intake (RDI). There was no association detected between calcium intake and age. Dairy foods provided 79.0% of dietary calcium intake. Calcium supplements were used by 6.6% and multivitamins by a further 4.3% of women. Supplementation was independent of dietary calcium intake and more likely used by postmenopausal women. CONCLUSIONS: Our results suggest that 76% of women consume less than the RDI even when supplemental calcium is included. Furthermore, 14% have less than the minimal requirement of 300 mg/day and would, therefore, be in negative calcium balance and at risk of bone loss. Despite advertising campaigns promoting better nutrition and increased awareness of osteoporosis, many women are failing to achieve an adequate calcium intake.
Phanuphak P, Grayson ML, Sirivichayakul S
… +8 more, Suwanagool S, Ruxrungtham K, Hanvanich M, Ratanasuwan W, Ubolyam S, Hughes MD, Wanke CA, Hammer SM
Aust N Z J Med
· 2000 Feb · PMID 10800872
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AIM: To compare the clinical and immunological efficacy, and tolerance of two dosage regimens of zidovudine (ZDV) in an adult Thai population with early symptomatic human immunodeficiency virus (HIV) disease and to ident...AIM: To compare the clinical and immunological efficacy, and tolerance of two dosage regimens of zidovudine (ZDV) in an adult Thai population with early symptomatic human immunodeficiency virus (HIV) disease and to identify important clinical issues associated with conducting HIV trials in South-East Asia. METHODS: HIV-infected Thai adults, with early symptomatic HIV disease and CD4 lymphocyte counts less than 400/mm3, who were managed in the infectious diseases clinics at two university teaching hospitals in Bangkok, Thailand, were enrolled in a randomised, open-label, dose-regimen comparison trial of ZDV. Two oral ZDV dosing regimens: regimen A, 100 mg tid+200 mg nocte (ZDV-A) vs regimen B, 250 mg bid (ZDV-B) were compared. The main outcome measures were: 1. Clinical efficacy: rate of progression to acquired immunodeficiency syndrome (AIDS) or death. 2. Immunologic efficacy: changes in CD4 lymphocyte numbers compared to baseline; rate of decline of CD4 lymphocyte numbers to less than 100/mm3. 3. Toxicity, as defined by clinical symptomatology and laboratory parameters. RESULTS: Two hundred and four patients were enrolled (103 ZDV-A; 101 ZDV-B) of whom 195 were followed beyond baseline. Patients were typical of those encountered with HIV in Thailand: mean age 33 years; 89% male; 88% heterosexual HIV acquisition; mean baseline CD4 lymphocyte count 241/mm3. Follow-up while on therapy was comparable for the two groups (mean+/-SD): 533+/-236 days (ZDV-A) vs 592+/-210 days (ZDV-B). One hundred and eleven patients (57%; 51 ZDV-A; 60 ZDV-B) were treated for at least 22 months (669+/-30 days). Clinical and immunological outcomes for ZDV-A and ZDV-B, including rate of progression to AIDS or death, development of non-AIDS-defining opportunistic infections, mean changes in CD4 lymphocyte numbers/mm3, difference in area under the CD4:time distribution curve and difference in the rate of decline of CD4 lymphocyte numbers to less than 100/mm3, were not significantly different. The presence of oral hairy leukoplakia or unintentional weight loss of 10-20% at enrollment were significantly associated with the later development of AIDS (p=0.03 and 0.04, respectively). ZDV-associated toxicity was similar for both regimens. Maintaining protocol adherence and appropriate clinical follow-up emerged as important practical issues. CONCLUSION: In Thai adults, ZDV 100 mg tid+200 mg nocte and ZDV 250 mg bid have similar clinical and immunological efficacy. Rates of ZDV toxicity are comparable to those reported in non-Asian populations. Despite limitations in medical care access and maintaining long-term follow-up, successful trials of antiretroviral agents are feasible in South-East Asia and multi-drug treatment trials should be pursued in appropriate institutions.