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G G Allen

Publications and source records attributed to G G Allen.

9 recordsLinked to original sources

Results of an Aboriginal community-based renal disease management program incorporating point of care testing for urine albumin:creatinine ratio.

INTRODUCTION: There has been a significant increase in the burden of renal disease among Aboriginal Australians over the past 15 years. Urine albumin:creatinine ratio (ACR) is a well-established marker of microalbuminuria and can be conveniently performed on the DCA 2000 point-of-care testing (POCT) analyser (Bayer Australia; Melbourne, VIC, Australia) with an on-site result available in 7 min. The application of the urine ACR POCT for renal disease risk assessment was pioneered by our group in the Umoona Kidney Project. This article describes the results of the management arm of the Umoona Kidney Project, which used point-of-care urine ACR testing for the first time within a management framework to monitor albuminuria in patients at highest risk of renal disease. The article also examines the analytical quality of POCT results and overall community acceptance of the Umoona Kidney Project. METHODS: Adults clinically assessed by Flinders Medical Centre renal specialists as being at greatest risk for renal disease were offered the ACE inhibitor (ACEI) perindopril on a voluntary basis. Selected renal markers, including POCT urine ACR (conducted on-site by Umoona's Aboriginal health worker team), plasma electrolytes, urea, creatinine, calculated glomerular filtration rate and blood pressure were measured six monthly. Regular quality control testing was undertaken to monitor the analytical performance of the POCT analyser. A culturally appropriate questionnaire was designed and implemented to assess community satisfaction with the project. RESULTS: In all, 231 patient management consultations were conducted over a two year period, with over 70% of patients having four or more (up to a maximum of eight) consultations; 35 patients (mean age 49.2 [+/-2.3] years, 54% males) participated voluntarily in the management arm. All were overtly hypertensive, hypertensive with other risk factors or had diabetes. The renal status of these patients was followed for a mean of 63 +/- 4.5 weeks. In total, 111 POCT urine ACR tests were performed for patient management (mean 3.2 tests per patient). There was no significant difference in POCT urine ACR in the study period with a median (and inter-quartile range) of 5.7 mg/mmol (1.2-15.2) pre-ACEI and 4.3 mg/mmol (1.3-16.7) post-ACEI treatment (p = 0.50, Wilcoxon signed ranks test). The calculated glomerular filtration rate altered from 110 to 118 mL/min (p = 0.019, paired t-test). There was no change in the group plasma potassium, urea and creatinine. Collectively these results indicate a stabilisation in renal function among the management group. Blood pressure (both lying and standing) fell significantly in the study period. The imprecision for urine ACR quality control POCT conducted during the management program was within nationally and internationally accepted precision goals for urine albumin, creatinine and ACR. Fifty community members completed the satisfaction questionnaire. Three-quarters of respondents felt there were no cultural barriers in providing a urine sample for urine ACR POCT. CONCLUSIONS: The management arm of the Umoona Kidney Project was effective in stabilising the renal function and improving the blood pressure of community members identified to be at greatest risk of kidney disease. POCT urine ACR testing can be utilised, not only for community risk assessment, but also for patient management. The Umoona Kidney Project was well accepted by the health service and community members.

Albuminuria↗

Albuminuria in a remote South Australian Aboriginal community: results of a community-based screening program for renal disease.

INTRODUCTION: The poverty, poor environmental living conditions and poor health standards experienced by Aboriginal Australians in some communities in rural and remote Australia have been described recently as 'fourth world'. For more than a century Aboriginal people have suffered the effects of dispossession of their land; destruction of their traditional culture and values; and exposure to infectious diseases, alcohol and the Western diet that is high in fat and sugar. Collectively these factors have contributed to the prevalence of chronic disease that afflicts Aboriginal people. In particular, renal disease has emerged during the last decade as a major contemporary health problem for Aboriginal Australians. According to the latest age- and sex-adjusted figures, Aboriginal people now have approximately nine-fold the risk of non-Aboriginal Australians of developing end-stage renal disease. In parts of Australia's Northern Territory, where Aboriginal people represent over 20% of the Territory's population, the rates of end-stage renal disease have been described as 'epidemic', reaching 2700 per million in the Tiwi Islands. In response to a request from the Umoona Tjutagku Health Service in mid 1997, the Renal Unit at Flinders Medical Centre, Adelaide, South Australia, formed a partnership with the health service to conduct a renal-disease screening program for adult members of the Umoona Community at Coober Pedy, a town 850 kilometres north of Adelaide. The partnership was later expanded to include screening for children (conducted by the Renal Unit at the Women's and Children's Hospital, Adelaide, South Australia). The community named the program 'The Umoona Kidney Project'. The Umoona community had recently experienced the dislocation of a number of its older people who suffered from advanced renal disease and were undergoing dialysis in a variety of centres in South Australia and the Northern Territory. As a result, the community had suffered social trauma. Consistent with the community's overall holistic approach to healthcare, the community wanted the renal program to provide a focus for community awareness of and knowledge about chronic disease, as well as to complement existing health programs. OBJECTIVES: The study objectives were to identify the prevalence of risk factors for renal disease, notably albuminuria, in adults from a remote Aboriginal community, and to examine the association of albuminuria with other risk factors; to empower Aboriginal health workers to self-manage a sustainable, community-controlled renal health program; and to assess the reliability and cultural acceptability of point-of-care technology for detecting renal disease. METHOD: The study was a three-year cross-sectional voluntary adult screening program (The Umoona Kidney Project). The study was performed as a partnership between the Flinders Medical Centre Renal Unit and the Umoona Tjutagku Health Service, and it involved nephrologists, medical scientists, Aboriginal health workers and clinical nurses. SETTING: Umoona Tjutagku Health Service, 850 km north of Adelaide. PARTICIPANTS: 158 adult members of the Umoona community: 58 males (37%; mean age = 43.8 years, range 23-78) and 100 females (63%; mean age = 39.6 years, range 18-72). MAIN OUTCOME MEASURES: First morning urine albumin : creatinine ratio measured by the Bayer DCA 2000 point-of-care analyser machine (Bayer Australia, Melbourne, Australia); lying and standing blood pressure; random blood glucose; body mass index; urinalysis. RESULTS: The study found that of screened adults, 29/149 (19%, 95% C.I. 13%-27%) had persistent microalbuminuria and 13/149 (9%, 95% C.I. 4%-14%) had persistent macroalbuminuria; 62/148 participants (42%, 95% C.I. 34%-50%) had overt hypertension; 35/145 participants (24%, 95% C.I. 17%-32%) had diabetes; 3 participants were newly diagnosed as having non-insulin dependent diabetes; 96/148 participants (65%, 95% C.I. 57%-73%) were either overweight or obese. Strong correlation was observed between the progression of albuminuria and age, all blood pressure categories, blood glucose, body mass index and an increasing number of risk factors. CONCLUSIONS: The Umoona Kidney Project identified a significant community burden of previously unknown incipient and established renal disease that required addressing via clinical- and community-based interventions. The DCA 2000 was a reliable instrument for detecting albuminuria on-site in the remote clinical location and was well accepted by Aboriginal health workers and community participants.

Journal Article↗

The Henrietta Banting Breast Centre database: a model for clinical research utilizing a hospital-based inception cohort.

The cohort study design has been used successfully in clinical cancer research. Cohorts, however, are valuable only if they produce results which are valid and generalizable. Some hospital-based inception cohorts satisfy both these requirements and may thus be useful research tools. The development of one such hospital-based cohort, the Henrietta Banting Breast Centre database, is described. This cohort is composed of 1097 women diagnosed with primary breast cancer at Women's College Hospital, Toronto, from January 1977 through December 1986. Details of diagnostic procedures, pathology, treatment, dates and sites of recurrence, and date of death are available on 96% of women. By comparison with published series and with the Ontario Cancer Registry, we have demonstrated validity and generalizability. A major advantage is the ready availability of paraffin tissue blocks on virtually all cases, facilitating analyses of the prognostic importance of specific biologic variables and immunocytochemical hormone assays. Other completed studies and future uses of the cohort are described.

Breast Neoplasms↗

Nerve growth factor: increased angiogenesis without improved nerve regeneration.

Nerve growth factor (NGF) and laminin are important factors for neural development and regeneration. We examined the effects of increasing the local concentration and duration of action of NGF and laminin on peripheral nerve regeneration in the adult mouse sciatic nerve. A Silastic (silicone rubber) channel with intraluminal NGF solution was secured between transected nerve ends. The second channel tested, formed from a polysaccharide called chitosan, was prepared with NGF and laminin in the channel walls and provided a sustained release of NGF. At six weeks post-implantation, no improvement in nerve regeneration was identified in those channels prepared with NGF when comparing electromyographic thresholds (microA), maximum potentials (mV), nerve diameter, myelin sheath thickness, myelinated axon counts, or diameter. However, increased angiogenesis was demonstrated within the chitosan and Silastic channels prepared with NGF compared to those channels without NGF. Silastic exhibited minimal inflammation. Chitosan was associated with inflammation in many nerve channels.

Animals↗

An in vivo study of voltage-dependent renal tubular acidosis induced by amiloride.

It has been proposed that most forms of hyperkalemic distal renal tubular acidosis (dRTA) result from a voltage-dependent acidification defect in the cortical collecting tubule (CCT) in which hydrogen and potassium secretion are decreased secondary to a reduced, transepithelial potential difference (PD) arising from impaired sodium reabsorption. The present in vivo study examines one model of hyperkalemic dRTA, induced by chronic amiloride administration, to examine the relationship between urinary excretion of hydrogen and potassium ions and CCT PD in the rat kidney. Chronic administration of amiloride produced a significant metabolic acidosis with a plasma bicarbonate of 21.3 mmol/liter compared to 25.9 mmol/liter in control rats. Plasma potassium was higher in experimental animals (4.9 mmol/liter vs. 3.3 mmol/liter in controls) and was associated with a significantly reduced fractional excretion of potassium of 11.2% versus 37.4% in controls. When animals were loaded with DOCA and infused with 4% sodium sulphate to maximize urine acidification, urine pH was significantly higher in the experimental group (6.35 vs. 5.55 in controls) while the mean PD in cortical collecting tubules was markedly lower at -21.1 mV versus -58.9 mV in controls. These results support a voltage dependent mechanism to explain the defect in hydrogen and potassium ion secretion induced by amiloride.

Acidosis, Renal Tubular↗

Origin of positive transepithelial potential difference in early distal segments of rat kidney.

Previous studies from our laboratory indicate that early distal segments of the rat kidney have a positive transepithelial potential difference (PD). The present study investigates the origin of the positive PD. PDs were measured in early distal segments using a technique which allowed simultaneous microperfusion and PD measurement through a single pipette (3 to 6 micron O.D.). Microperfusion with artificial plasma ultrafiltrate resulted in a significantly negative mean PD of -4.9 +/- 0.7 mV (N = 17), in contrast to a positive free-flow PD of +5.7 +/- 1.1 mV (N = 174) (P less than 0.001). Addition of amiloride 10(-4) M to plasma ultrafiltrate changed the PD to +1.7 +/- 0.2 mV (N = 25, P less than 0.001). In contrast, furosemide 10(-4) M had no effect on the perfusion PD. Removal of sodium from the luminal perfusate abolished any effect of amiloride on the perfusion PD. Perfusion with artificial early distal fluid yielded a positive PD of +4.2 +/- 0.2 mV (N = 19). Amiloride increased this PD to +8.3 +/- 0.7 mV (N = 21, P less than 0.001). Subsequent experiments in which the sodium and potassium concentrations of the perfusates were varied indicated that concentration gradients for these ions across the early distal tubule could generate substantial diffusion PDs and that potassium was much more permeant than sodium.(ABSTRACT TRUNCATED AT 250 WORDS)

Amiloride↗

Effect of cisplatin on the transepithelial potential difference of rat distal tubule.

Cisplatin, an effective anti-tumor agent, has significant effects on renal function including reduced glomerular filtration rate and potassium and magnesium wasting. It has been shown recently that cisplatin increases sodium conductance across the isolated frog skin, an effect which was inhibited by amiloride. The present study investigates the influence of cisplatin on the transepithelial potential difference (PD) of distal nephron segments of the rat kidney. Measurements were made under free-flow conditions and during distal microperfusion. When cisplatin was infused intravenously in a dose of 2 mg/kg/hr, the mean free-flow PD in late distal segments (cortical collecting tubules) increased from -18.5 +/- 1.4 mV (N = 37) to -31.2 +/- 1.4 mV (N = 36) (P less than 0.001). The large negative PD seen with cisplatin was abolished with intravenous amiloride, a mean PD of +0.9 +/- 1.5 mV (N = 22) (P less than 0.001) being obtained, similar to a PD of +1.9 +/- 1.5 mV (N = 39) found in control animals infused with amiloride. Perfusion of individual late distal segments with artificial plasma ultrafiltrate yielded a mean control PD of -12.4 +/- 1.2 mV (N = 21) and a significantly higher PD of -17.5 +/- 1.5 mV (N = 24) (P less than 0.01) when cisplatin (10(-3) M) was added to the perfusate. The addition of amiloride to these perfusates reduced the mean PDs to -3.2 +/- 0.5 mV (N = 19) and -3.6 +/- 0.7 mV (N = 17), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Amiloride↗