bluuebunny/crossref_metadata_2025 huggingface dataset:
Regional differences in cardiovascular risk factor prevalence in Tasmania: are they consistent with the increased cardiovascular mortality?
Authors: Thomson A. , Watts R. , Rundle S. , Sexton P. , Singh B. B. , Woodward D.
Published: March 2008

Background: The death rate from cardiovascular disease in Tasmania has been among the highest in Australian States for a number of years. The North‐West (NW) and Northern regions of Tasmania account for most of the increased mortality.

Aims: To determine the prevalence of cardiovascular risk factors in the North and NW regions of Tasmania and to ascertain whether any differences are consistent with the regional patterns of mortality for ischaemic heart disease (IHD) within the State.

Methods: The design of the study was almost identical to the previous National Heart Foundation (NHF) Risk Factor Prevalence Survey conducted in 1989. The subjects, aged 20–69 years, were randomly selected from the Electoral Roll with 1146 subjects participating in the North and 1219 in the NW. Subjects answered a detailed questionnaire and then underwent a brief physical examination with venipuncture for blood lipids. Hobart data from the NHF Risk Factor Prevalence Survey in 1989 were used as an estimate of risk factor prevalence in the Southern region.

Results: In both males and females, mean systolic blood pressure was significantly higher in the NW than the South which was in turn higher than the North. Mean serum cholesterol levels in males were higher in the NW than the North. Smoking behaviour was similar in males and females in all regions. Males and females in the NW and North were more inactive than those in the South. Similar proportions in all regions were on either ‘no specific’ or ‘fat modified’ diets. Body mass index in males and females was higher in the NW and North but waist to hip ratios failed to show a consistent trend.

Conclusions: While the NW has an unfavourable risk factor profile compared with the South, the North does not. The risk factor data are broadly consistent with, but unlikely to be sufficient to explain fully, the regional differences in mortality from IHD. (Aust NZ J Med 1995; 25: 290–296.)
Upper gastrointestinal haemorrhage following coronary artery bypass grafting
Authors: Norton I. D. , Pokorny C. S. , Baird D. K. , Selby W. S.
Published: March 2008

Background: Upper gastrointestinal (UGI) bleeding is a relatively common and potentially fatal complication of coronary artery bypass graft (CABG) surgery. However, little is known of this problem, including its incidence, predisposing factors and safety of endoscopy in these patients.

Aim: To document the incidence, site, predisposing factors and outcome of UGI bleeding following CABG surgery. Also, to assess the safety of UGI endoscopy in these patients.

Method: Retrospective study of UGI haemorrhage following CABG at one institution between 1976 and 1991.

Results: Fifty‐five of 10,573 patients (0.5%) suffered a major UGI haemorrhage (as defined by need for transfusion or presence of melaena or haematemesis associated with hypotension). Of 51 patients undergoing endoscopy or laparotomy, 42 (82%) bled from duodenal ulceration. Five patients bled from gastric ulcers and one each from oesophagitis and Mallory Weiss tear. Nine patients underwent endoscopic therapy, which initially arrested haemorrhage in eight patients. However, three patients rebled and required surgery. Eight patients underwent surgery as initial therapy, resulting in an overall surgical rate of 20%. One patient died due to multi system failure following surgery. There were no complications from endoscopy. Patients who bled were more likely to have received inotropic support post‐operatively prior to the haemorrhage (p < 0.05) and tended to be older than controls (mean age 65.6 years vs 58.7 years, p < 0.01). Twenty‐one of the patients (38%) who bled had a past history of peptic ulceration or dyspepsia compared with 9% of controls (p < 0.001). Seven (12.5%) had previously bled from peptic ulceration. Patients who bled were less likely to have received H2‐receptor antagonists in the perioperative period than controls (4%vs 20%, p< 0.05).

Conclusion: Upper GI haemorrhage following CABG is relatively frequent. It is usually secondary to duodenal ulceration. Endoscopy is a safe procedure in this patient group. Mortality did not differ between index patients who suffered a UGI haemorrhage and controls undergoing CABG who did not bleed.
Drug delivery in asthma: A comparison of spacers with a jet nebuliser
Authors: Gibson P. G. , Wlodarczyk J. H. , Borgas T.
Published: March 2008

Background: Although spacer devices are frequently used for aerosol therapy in asthma, the commonly used spacers have undergone little controlled evaluation, and their relation to nebuliser therapy is unclear.

Aims: The aims of this study were to compare three delivery methods (Breath‐A‐Tech spacer, Volumatic spacer and jet nebuliser) for the administration of salbutamol to reverse acute histamine induced airway narrowing in asthma (Study 1); and to assess asthma control during two weeks use of inhaled therapy via Volumatic or Breath‐A‐Tech spacer (Study 2).

Methods: A randomised double‐blind cross‐over comparison was conducted. In Study 1, 27 adults with stable asthma who were currently using pressurised metered dose inhaler therapy attended for three study days. On each study day subjects inhaled doubling doses of histamine and were randomised to receive: (a) salbutamol 200 μg via Breath‐A‐Tech spacer and placebo 200 μg via Volumatic spacer; (b) placebo two puffs via Breath‐A‐Tech spacer and salbutamol 200 μg via Volumatic spacer; or (c) salbutamol 1 mg in 2 mL saline via jet nebuliser. FEV and FEF 25–75% were measured at two minute intervals for 20 minutes. In Study 2, subjects were randomised to use regular asthma medication by Volumatic or Breath‐A‐Tech spacers and recorded symptoms and peak expiratory flow (PEF) in a daily diary.

Results: Lung function improved from a baseline FEV, of 51% predicted to 72% after salbutamol inhalation from each of the delivery systems. The spacers and nebulisers produced the same maximum improvement in FEVi, however, lung function improved more rapidly when salbutamol was delivered by spacer. There was no difference in asthma control comparing inhaler use via Breath‐A‐Tech with Volumatic spacer over two weeks use. Subject preference favoured the Breath‐A‐Tech spacer (72%vs 4%).

Conclusions: The Volumatic and Breath‐A‐Tech spacer devices are effective delivery systems in asthma and may offer a more rapid response than jet nebulisation at a lower cost.
Australasian multicentre phase II study of paclitaxel (Taxol*) in relapsed ovarian cancer
Authors: Phillips K. A. , Fitzharris B. , Friedlander M. , McCrystal M. , Olver I. , Joughin J. , Bishop J. , Evans B. , Smith J.
Published: March 2008

Background: Until recently there has been no effective therapy for patients with relapsed ovarian carcinoma following standard platinum based chemotherapy. Paclitaxel has recently been approved for clinical use in this malignancy.

Aims: To evaluate the objective response rate and toxicity of paclitaxel in patients with relapsed ovarian cancer.

Methods: Paclitaxel was given on an outpatient basis as a three hour infusion every 21 days for a maximum often cycles to 72 patients with advanced ovarian cancer previously treated with at least one platinum containing regimen. The starting dose was either 175 mg/m2 (patients with one or two prior chemotherapy regimens) or 135 mg/m2 (three previous regimens). Premedication was given because of the documented risk of hypersensitivity reactions to paclitaxel.

Results: The overall response rate was 22% (95% confidence interval [CI] 13% to 34%) in the 72 patients enrolled in the study: four patients had a complete response. Three patients (4%) ceased treatment due to hypersensitivity reactions. Other significant (WHO grade 3 or 4) toxicities included neutropenia (51%), myalgia (14%), neurological (3%), alopecia (93%) and nausea and vomiting (3%). The estimated median survival of all patients was 9.8 months (95% CI: 9.1–13.0 months) with 44% alive at one year (standard error [SE] 7%).

Conclusions: This study confirms that paclitaxel given as a three hour infusion has significant activity and acceptable toxicity in advanced ovarian carcinoma previously treated with platinum regimens.
The effete in the heat: heat‐related hospital presentations during a ten day heat wave
Authors: Faunt J. D. , Wilkinson T. J. , Aplin P. , Henschke P. , Webb M. , Penhall R. K.
Published: March 2008

Background: Severe heat‐related illness can result in hospitalisation and possibly death. These illnesses are potentially preventable; in Australia high environmental temperatures are common.

Aims: To identify (i) possible risk factors for hospital attendance with heat‐related illness during a heat wave, (ii) problems with diagnosis and therapy, (iii) issues in prevention, and (iv) areas for further study.

Methods: A retrospective descriptive survey from four major teaching hospitals in Adelaide, South Australia (SA), was conducted during a ten day period of exceptional heat in February 1993, in order to review all emergency department presentations (i.e. deaths, casualty treatment or hospital admissions) with a heat‐related illness as determined by attending doctors' documentation. Demographic, clinical, management and outcome data were collected.

Results: Ninety‐four patients were classified as having a heat‐related illness of whom 78% had heat exhaustion. Eighty‐five per cent were age 60 years or over; 20% came from institutional care; 48% lived alone; 30% had poor mobility. Peak presentation followed high daily temperatures for four consecutive days. Severity was related to pre‐existing cognitive impairment, diuretic use and presenting temperature, heart rate, blood pressure, plasma sodium and plasma creatinine. Treatment tended to be non‐standardised. Mortality was 12%. Seventeen per cent required a more dependent level of residential care upon discharge.

Conclusion: Problems were identified in accuracy of diagnosis and appropriate intervention. Awareness of the risk factor profile is needed among health workers, to ensure early preventative strategies. Populations to target for future prevention include elderly people (including those in institutional care), patients with cognitive impairment and patients taking diuretics, multiple medication and/or with other severe co‐existing illnesses. Treatment could be more standardised.
Renal transplantation in young children
Authors: Burren C. P. , Jones C. L. , Francis D. M. A. , Powell H. R. , Walker R. G.
Published: March 2008

Aims: To review the outcome of renal transplantation in small children treated with triple immunosuppression at a single Australian centre.

Methods: The medical records of all children under the age of five years undergoing renal transplantation from 1988 were reviewed. The duration of follow‐up was 30 months (range 18–36).

Results: Six children received seven renal allografts (five living‐related [LR] and two cadaveric [CD]). They had a median age of 3.75 years (range 1.5–4.9) and weight of 11.6 kg (9.1–14.5) at the time of transplantation. All patients received an immunosuppressive regime involving cyclosporin A, azathioprine and prednisolone. There were no deaths. The only graft lost was a CD graft (severe acute rejection within one week of transplantation). Hypertension occurred in all recipients and usually required more than one antihypertensive drug for treatment. Renal function measured by serum median creatinine concentration (range) was 0.05 mmol/L (0.03–0.11) at three months (n= 6) and 0.10 mmol/L (0.07–0.22) at 30 months (n= 4). Growth estimated from median (range) height standard deviation scores was ‐ 1.97 (‐1.36‐ ‐ 4.04) at three months (n= 6) and ‐ 1.90 (‐ 1.74–2.50) at 30 months (n= 4). No patient was entirely weaned from prednisolone. Cyclosporin A side effects included hirsutism (five patients), gingival hyperplasia (six patients) and nephrotoxicity (three patients).

Conclusions: Satisfactory patient and graft survival can be accomplished in this recipient age group. The results compare with other international experience and accumulating Australian experience. Hypertension and poor skeletal growth were consistent observations. The long‐term outcome of renal function using triple immunosuppression remains to be determined.
Bronchiolitis obliterans organising pneumonia: a clinical and radiological review
Authors: Boots R. J. , McEvoy J. D. S. , Mowat P. , Fevre I. LE
Published: March 2008

Background: The clinical presentation, course, and radiological spectrum of bronchiolitis obliterans organising pneumonia (BOOP) is still being characterised to aid differentiation from other causes of organising pneumonia.

Aims: To define the clinical presentation, response to therapy, and radiological spectrum of BOOP.

Methods: Fifteen cases of BOOP were retrospectively reviewed. The clinical presenting features, treatment and outcome of each patient were determined. Three independent readers and chest X‐rays (CXRs) were blinded. CXRs were scored by a semi‐quantitative method. Modal scores were calculated for type and profusion of opacification of each CXR.

Results: The mean age of presentation was 64 years and the median duration of follow‐up was 12.5 months. Thirteen patients received corticosteroid therapy. Outcome was varied. One patient had progressive loss of lung function, five had persisting symptoms with stable abnormal lung function, and nine were asymptomatic with near normal lung function. Five patients had a disease relapse. Symptom length prior to presentation, duration and intensity of treatment were not associated with outcome (ρ= 0.23–0.9). Radiological opacities were alveolar in 73%, large localised infiltrates in 13%, nodular in 20% and mobile in 33% of CXR series. There was no relationship between overall profusion, type of CXR opacities and patient outcome, treatment duration or treatment intensity (ρ= 0.42–1.0).

Caonclusions: The clinical spectrum of BOOP includes mild subacute, chronic progressive, and acute life threatening illness. Prognosis and response to treatment is variable. The diversity of radiological findings and clinical presentations should prompt consideration of the diagnosis in patients with undiagnosed respiratory tract symptoms and persisting or varying radiological abnormalities.
Activated protein c resistance (APC) and inherited factor V (FV) mis‐sense mutation in patients with venous and arterial thrombosis in a haematology clinic
Authors: Ma D. D. F. , Aboud M. R. , Williams B. G. , Isbister J. P.
Published: March 2008

Abstract Background: Inherited factor V (FV) mis‐sense point mutation has recently been identified as a major cause of familial venous thrombosis. The incidence of this congenital haemostatic disorder in Australia is unknown.

Aim: To examine the incidence of this congenital defect in patients with thrombosis attending a haematology clinic.

Methods: Individuals investigated or treated for venous and arterial thrombosis over a four month period, as well as those who were on anticoagulant for valvular replacement or arrhythmia were studied for the presence of FV mis‐sense point mutation, FV Q506 (G to A at nucleotide position 1691) by a polymerase chain reaction based test, and activated protein C (APC) resistance using an APTT based coagulation assay.

Results: Forty‐five patients with venous thromboembolism (VTE), 20 patients with coronary artery disease and 25 patients with valvular replacement or arrhythmia who were on anticoagulant were examined. The frequency of FV mis‐sense point mutation in these three groups was 26.7%, 15% and 4% respectively. In this study, patients with FV Q506 were of a younger age and had a higher incidence of extensive thrombosis or recurrence as compared to those with the normal factor V gene. This mutation was found in a diverse group of people (four of the 12 patients were of non‐European origin). Nearly 50% of these patients had other risk factors for VTE. The number of patients with a family history of VTE was similar for those with the FV mutation and the normal FV.

Conclusion: This study confirms the high incidence of FV Q506 mutation in patients with VTE reported overseas. Several clinical features, i.e young age of onset of VTE, high recurrence rate, diverse ethnic background and importance of associated risk factors are highlighted. The findings in this study also raise the possibility that this mutation may be a risk factor for arterial thrombosis. Large studies are required to substantiate these findings.
The effects of increasing doses of enalapril on insulin sensitivity in normotensive non‐insulin dependent diabetic subjects
Authors: Walker R. J. , Lewis‐Barned N. J. , Edwards E. A. , Robertson M. C.
Published: March 2008

Background: There are conflicting reports about the effects of ACE inhibitors (ACEI) on insulin sensitivity and glycaemic control. Most studies have used a standard high dose of an ACEI but there have been no studies reported to establish whether any changes in glycaemic control or insulin sensitivity associated with ACEI are dose‐related.

Aim: To examine the effect of increasing doses of enalapril on insulin sensitivity in normotensive non‐insulin dependent diabetic subjects.

Methods: The effects of increasing doses of enalapril on insulin sensitivity in ten normotensive non‐insulin dependent diabetic subjects were measured, using the hyperinsulinaemic isoglycaemic clamp technique. Following a baseline study, enalapril was commenced at 5 mg daily and increased to 10 mg daily then 20 mg daily at 14 day intervals. Repeat studies were undertaken after 14 days at each dosage.

Results: There was a significant dose‐related reduction of systolic blood pressure with enalapril. In contrast enalapril at 5‐20 mg daily produced no significant changes in insulin mediated glucose uptake (M‐value) or insulin sensitivity index (ISI).

Conclusions: These findings indicate that in this insulin resistant population of normotensive non‐insulin dependent diabetics, angiotensin converting enzyme inhibition with enalapril has no significant effect on insulin mediated glucose uptake.
Genetic analysis of disease susceptibility (disease susceptibility)
Authors: Foote SIMON
Published: March 2008

The human Genome Project has provided valuable took for the analysis of genetic traits in both humans and experimental mammals. A discussion of these tools and of some of the applications underway at the Hall Institute is provided.
Role of macrophages in the pathogenesis of human immunodeficiency virus (HIV) infection
Authors: Crowe SUZANNE M.
Published: March 2008

There are a number of mechanisms by which HIV‐infected macrophages contribute to the pathogenesis of the Acquired Immunodeficiency Syndrome (AIDS). Macrophage‐tropic strains of HIV are present at the time of infection, and persist throughout the course of infection, despite the emergence of T cell tropic quasispecies. As HIV causes chronic infection of macrophages with only minimal cytopathology, these cells can provide an important viral reservoir in HIV‐infected persons. Macrophages are more susceptible to HIV infection than freshly isolated monocytes. HIV‐infected macrophages can contribute to CD4 T lymphocyte depletion through a gp!20‐CD4 dependent fusion process with uninfected CD4‐expressing T cells. Increasing data support the role of HIV‐infected macrophages and microglia in the pathogenesis of HIV‐related encephalopathy and AIDS‐related dementia through the production of neurotoxins. HIV infection of macrophages in vitro results in impairment of many aspects of their function. Reduced phagocytic capacity for certain opportunistic pathogens, including Toxoplasma gondii and Candida albicans, may be responsible for reactivation of these pathogens in persons with advanced HIV infection, although the mechanisms underlying reactivation of infections and susceptibility to disease from new infections are likely to be multifactorial. Our studies showing defective phagocytosis and killing provide additional information that contribute to our understanding of the pathogenesis of AIDS. Studies of in vitro efficacy of potential antiretroviral therapies should be performed in both primary lymphocyte and monocyte cultures, given the importance of both of these cell populations to HIV pathogenesis and their differing biology.
Second messenger pathways in the modulation of neurotransmitter release
Authors: Majeuiski HENRYK K. , Musgrave IAN F.
Published: March 2008

Activation of receptors on postganglionic sympathetic nerve endings can alter the amount of noradrenaline release during a train of nerve impulses. These changes may be produced by the enzyme‐linked synthesis of second messenger molecules within the nerve terminal. Cyclic AMP analogues enhance noradrenaline release and two hormones adrenaline and ACTH appear to enhance noradrenaline release through activation of adenylate cyclase. Activation of the phospholipase C/protein kinase C pathway also elevates stimulation‐induced noradrenaline release and angiotensin enhancement of noradrenaline release appears to act through this pathway. On the other hand, receptors which inhibit noradrenaline release (α2‐adrenoceptors, muscarinic Mi receptors and neuropeptide Y receptors) do not act through either of these signal transduction pathways. Since these inhibitory systems are neurotransmitter activated and relay information on a nerve pulse to nerve pulse time scale back to the nerve ending a fast activation and deactivation rate of modulation is required. This may be better served by direct modulation of ion channels without a slow intervening enzyme step.

Activation of protein kinase C by phorbol esters produces relatively large increases (two‐threefold) in stimulation‐induced noradrenaline release and this enzyme may also have a physiological role. Protein kinase C may be an appropriate target for drugs to manipulate transmitter release and development of selective activators and inhibitors of the many protein kinase C isoenzymes may prove clinically useful in diseases with inappropriate transmitter release profiles.
The molecular mechanism of platelet adhesion
Authors: Berndt MICHAEL C. , Ward CHRISTOPHER M. , Luca MARIAGRAZIA DE , Facey DAVID A. , Costaldi PETER A. , Harris SIMON J. , Andrews R. K.
Published: March 2008

One of the most primitive of host‐defence mechanisms is haemostasis, the ability to control blood loss. In response to vascular trauma, platelets rapidly adhere to the exposed subendothelial matrix, a process that ultimately results in the sealing of the vessel by a plug of platelets stabilised by fibrin. Paradoxically, it is the same cascade of events that leads to thrombosis and vessel occlusion, resulting in heart attack and stroke. The molecular events involved in platelet adhesion have therefore been the subject of intense investigation. In all but the largest blood vessels, the initial contact adhesion of platelets is mediated by subendothelial matrix bound von Willebrand Factor (v WF) and a specific v WF receptor on platelets, the glycoprotein (GP) Ib‐ V‐IX complex. Our understanding of this process arose from analysis of two congenital bleeding disorders, von Willebrand's disease and the Bernard‐Soulier syndrome, in which v WF or the GP Ib‐ V‐IX, respectively, are either absent or dysfunctional. This overview discusses our current molecular understanding of platelet adhesion and how engagement of v WF by the GP lb‐ V‐IX complex on platelets initiates the subsequent events in platelet activation leading to either haemostasis or thrombosis.
Interaction of the GTP‐binding protein Gi2 with a protein kinase A‐like kinase in mouse fibroblasts
Authors: Crouch MICHAEL F. , Jans DAVID A. , Simson LJUBOV , Hendry IAN A.
Published: March 2008

We have previously shown that the GTP‐binding protein, Gi2 of mouse Balb/c3T3 cells is linked to a serine kinase which phosphorylates the a‐subunit of Gi itself. In this report we show that Gi, is coupled to a second protein kinase. This kinase does not phosphorylate G, but phosphorylates another protein bound non‐covalently to Gi‐. Phosphorylation of the Gi‐linked protein induces its release from Gi. Kinase activity is slightly enhanced by G TPγS, suggesting that this kinase may be physiologically regulated by Gi. In an attempt to identify the kinase we have, examined the effect of peptide substrates and inhibitors on kinase activity. We found that the protein kinase A inhibitory peptide, PKI5‐24, inhibited the kinase activity, but at concentrations above those usually required to block protein kinase A. The protein kinase A substrate peptide, kemptide, acted as a substrate of the kinase, and was an inhibitor of the phosphorylation of the G‐linked protein. However, a protein kinase A, catalytic subunit antibody failed to react with any proteins linked to Gi. A protein kinase C inhibitory peptide had no effect on phosphorylation of the Gi‐linked protein. Thus, the identity of this kinase has not been resolved, but it may form part of the signalling system of activated Gi in fibroblasts.
Protein crystallography in Australia
Authors: Parker MICHAEL W.
Published: March 2008

Protein crystallography is the study of the three‐dimensional shapes of proteins at near atomic resolution. The field has provided a tremendous insight into the workings of numerous biological processes over the last few decades. The field is presently undergoing a massive worldwide expansion, not only in academic laboratories but also in the pharmaceutical industry. The main driving force for this expansion is the possibility of using the three‐dimensional atomic structures of proteins to design lead drugs and to improve the action of existing drugs. This expansion in the field has been mirrored in Australia where the number of protein crystallography groups has more than trebled in the last five years. The work in the Protein Crystallography Unit at St Vincent's Institute of Medical Research has centred on the structural elucidation of membrane proteins and structure‐based inhibitor studies of a protein family that attack certain anticancer drugs.
The Elite Seniors Study
Authors: Nair B. , Hughes J. , Basta M. , Hardy D. , Crooks R. , Finucane P. , Fletcher P. , Silberberg J.
Published: March 2008

Background: A descriptive study of self‐reported healthy elderly in Newcastle was undertaken for an adequate understanding of the normal characteristics of the elderly.

Aims: We sought to determine the frequency of abnormal clinical, laboratory and echocardiographic findings in a self‐reported healthy elderly population.

Methods: Volunteers aged greater than 75 years were recruited from active members of the region's bowling clubs. Forty‐five subjects with no self‐reported vascular or cardiac disease underwent clinical, laboratory and echocardiography assessment.

Results: Minor cardiovascular abnormalities were frequently detected. Echocardiography correspondingly found a high frequency of haemodynamically insignificant degenerative valvular lesions. Doppler left ventricular filling pattern of abnormal relaxation was a universal finding.

Conclusion: There is a high prevalence of age‐related echo‐Doppler abnormalities in the self‐reported healthy elderly with important implications for the interpretation of echo‐Doppler studies.
Bile acid malabsorption in HIV infected patients with chronic diarrhoea
Authors: Cramp M. E. , Hing M. C. , Marriott D. J. , Freund J. , Cooper D. A.
Published: March 2008

Aims: To look for the presence of bile acid malabsorption in HIV infected patients with chronic diarrhoea and determine whether bile sequestering agents may have a role in palliating this common problem.

Methods: Nineteen HIV infected patients with chronic diarrhoea (duration >one month) poorly controlled on conventional treatment were investigated using the seven day retention of 75seleno‐23‐homocholic acid taurine (SeHCAT) as a measure of bile acid loss from the enterohepatic circulation. Patients with evidence of bile acid malabsorption were offered cholestyramine.

Results: Sixteen (84%) had evidence of bile acid malabsorption (<15% retention at seven days). Ten of the 16 patients with bile acid malabsorption had terminal ileal biopsies ‐six had ileitis and four normal histology, suggesting that malabsorption is not always related to terminal ileitis. Thirteen patients with bile acid malabsorption have been treated with cholestyramine and 11 have reported a symptomatic response.

Conclusions: Bile acid malabsorption can be demonstrated in some cases of HIV associated chronic diarrhoea and we suggest a therapeutic trial of a bile sequestering agent in patients whose symptoms are not well controlled using conventional anti‐diarrhoeal agents.
Carboplatin dosing based on measurement of renal function — experience at the Peter MacCallum Cancer Institute
Authors: Millward M. J. , Webster L. K. , Toner G. C. , Bishop J. F. , Rischin D. , Stokes K. H. , Johnston V. K. , Hicks R.
Published: March 2008

Background: Carboplatin is used in treating many types of cancer. Because renal excretion is the major variable determining the pharmacokinetics of this drug, a dosing formula based on glomerular filtration rate (GFR) has been proposed and is being increasingly used in carboplatin dosing. This method of dosing is critically dependent on accurate measurement of GFR.

Aims: To report the experience at a single major oncology centre of carboplatin dosing based on GFR, and comparisons of different methods of measuring renal function for use in this dosing method.

Methods: An initial group of patients (n=24) was studied where GFR was measured by Cr51EDTA clearance and compared to Tc99mDTPA clearance, measured 24 hour urine creatinine clearance and the Cockcroft and Gault formula. The carboplatin area under the plasma concentration versus time curve (AUC) was calculated using total platinum measured in a single blood sample assayed by flameless atomic absorption spectrophotometry. A subsequent patient group (n=16) was then studied using Tc99mDTPA clearance to measure GFR.

Results: Carboplatin dosing using Cr51EDTA clearance to measure GFR was accurate (<25% difference between planned and measured AUC) in 87% of samples. Estimation of renal function using the Cockcroft and Gault formula correlated with Cr51EDTA clearance only in patients with GFR <100 mL/minute. The measured 24 hour urine creatinine clearance did not correlate with Cr51EDTA clearance. Using Tc99mDTPA clearance to measure GFR, carboplatin dosing was accurate in 81% of samples. Across a GFR range of 42–239 mL/minute, the Cr51EDTA and Tc99mDTPA clearances were closely correlated (r=0.98, slope of regression line=1.02).

Conclusions: Carboplatin dosing using a pharmacological formula based on GFR produces accurate targeting of the carboplatin AUC. Tc99mDTPA clearance can be used to measure GFR instead of Cr51EDTA clearance, which is both more convenient and has potential cost savings. Estimates of renal function using the Cockcroft and Gault formula or measured 24 hour creatinine clearance are insufficiently accurate to use for carboplatin dosing.
Radiofrequency catheter ablation of left ventricular tachycardia in the normal heart
Authors: Hellestrand K. J. , Whalley D. W.
Published: March 2008

Background: Radiofrequency (RF) catheter ablation is a safe and effective cure for many forms of supraventricular tachycardia. Its efficacy in the cure of right ventricular outflow tract tachycardia, and some forms of left ventricular tachycardia in patients with left ventricular dysfunction, has also been shown. In contrast limited data are available to assess the role of RF catheter ablation in treating idiopathic left ventricular tachycardia (ILVT), an unusual form of tachycardia occurring in patients without demonstrable heart disease.

Aim: To examine the efficacy and safety of RF catheter ablation in patients with ILVT.

Methods: Three patients without structural heart disease and with recurrent drug‐refractory ILVT (right bundle branch block and left axis morphology) underwent electrophysiologic study (EPS) to initiate and localise the site of origin of their VT. RF catheter ablation of the VT focus was performed, with success being defined as failure to reinduce VT during incremental infusion of isoprenaline.

Results: In all three patients VT was inducible by rapid right atrial pacing and/or programmed ventricular stimulation, and could be terminated by intravenous verapamil. RF catheter ablation was successful in all patients. The site of successful ablation was common to each patient and was localised to the infero‐apical aspect of the left ventricular septum. It was characterised by the recording of the earliest presystolic ‘P’ potential during both sinus rhythm and induced ILVT. No complications occurred during the procedure. During follow‐up periods ranging from six to 12 months there were no symptomatic or documented episodes of recurrent ILVT.

Conclusions: We conclude that ILVT can be safely and effectively cured by RF catheter ablation.
An audit of third generation cephalosporin prescribing in a tertiary care hospital
Authors: LeMire M. , Wing L. , Gordon D. L.
Published: March 2008

Background: There is increasing resistance to commonly used antibiotics, including third generation cephalosporins, and an increasing cost burden.

Aims: To assess the appropriateness of prescribing of third generation cephalosporin antibiotics in a tertiary teaching hospital.

Methods: Prescriptions of third generation cephalosporins (ceftriaxone, cefotaxime and ceftazidime) to inpatients were identified prospectively by the Hospital Pharmacy Department for a six week period during May‐June 1994. Clinical data and indications were obtained from patient records and, when necessary, by interviewing the prescriber and by patient assessment. Criteria for appropriate prescribing were according to nationally accepted criteria outlined in the 1994–95 Antibiotic Guidelines handbook.

All inpatients who were prescribed a third generation cephalosporin at Flinders Medical Centre for the duration of the audit period were eligible. This included medical, surgical, paediatric, obstetric and gynaecology inpatients.

Results: Sixty‐five per cent of prescriptions for third generation cephalosporins were judged appropriate, 31% inappropriate and 4% doubtful. Inappropriate use was found particularly in the treatment of respiratory tract infections and abdominal sepsis, and in surgical prophylactic use.

Conclusion: Third generation cephalosporin prescribing in a tertiary care teaching hospital is frequently inappropriate, as judged against widely available Australian guidelines.
Five year leukaemia‐free survival of 72% and 77% for early stage acute and chronic myeloid leukaemia treated by HLA‐identical sibling bone marrow transplantation
Authors: Atkinson K. , Downs K. , Dodds A. , Concannon A. , Milliken S.
Published: March 2008

Background: HLA‐identical sibling bone marrow transplantation is an accepted treatment for patients with acute myeloid leukaemia (AML) and chronic myeloid leukaemia (CML). We have recently reported improving results in HLA‐identical sibling transplant over the ten year period 1981‐1990. In this report we described the outcome in patients transplanted at St Vincent's Hospital, Sydney between 1989 and 1993.

Aims: To determine the leukaemia‐free survival, transplant‐related mortality rate, and relapse rate for patients with AML or CML given HLA‐identical sibling marrow transplants between 1989 and 1993.

Methods: Sixty‐two patients with AML or CML received high dose busulphan/cyclophos‐phamide chemotherapy followed by infusion of T replete, HLA‐identical sibling bone marrow. Cyclosporin/short methotrexate was utilised as prophylaxis for graft‐versus‐host disease, ganciclovir as prophylaxis for cytomegalovirus disease and cotrimoxazole as prophylaxis for Pneumocystis carinii pneumonia. Low dose intravenous heparin was used as prophylaxis for hepatic veno‐occlusive disease.

Results: The five year disease‐free survival for patients with AML transplanted in first complete remission was 72% and for those with CML transplanted in first chronic phase was 77%. The relapse rate for AML transplanted in first complete remission was 15% and for CML in first chronic phase 0%. The transplant‐related mortality for AML transplanted in first complete remission was 16% and for CML transplanted in first chronic phase 23%. In contrast, the disease‐free survival, relapse rate and transplant‐related mortality for patients with AML transplanted outside first complete remission and for CML transplanted beyond first chronic phase was 17%, 57% and 57% respectively.

Conclusions: The outcome for patients transplanted for early AML or early CML continues to improve and exceeds that obtainable by conventional therapy. The salvage rate is so low for patients transplanted in later stages of AML or CML that all patients less than 55 years of age with these diseases, who have a HLA‐identical sibling donor, should be offered bone marrow transplantation early in their disease course.
A cost‐effectiveness analysis of enalapril maleate in the management of congestive heart failure in Australia
Authors: Butler J. R. G. , Fletcher P. J.
Published: March 2008

Background: This study is motivated by the results of the SOLVD treatment trial (N Engl J Med 1991; 325: 293‐302) which demonstrated the clinical efficacy of enalapril in the treatment of congestive heart failure but did not undertake an economic evaluation of enalapril therapy.

Aims: To undertake a cost‐effectiveness analysis of enalapril maleate versus placebo, in conjunction with conventional treatment, in the management of congestive heart failure in Australia.

Methods: The published results from the SOLVD treatment trial are used to estimate the increase in survival, and the reduction in the number of hospitalisations, arising from the use of enalapril in the management of congestive heart failure. The costs of enalapril therapy are estimated using Australian data on the drug and non‐drug costs of enalapril therapy and the costs of hospitalisation.

Results: Enalapril therapy increases mean survival in heart failure patients by 1.68 to 1.80 months. The average additional drug and non‐drug cost of enalapril therapy is estimated to be $1890 over a four year period, against which must be offset cost savings from a reduction in hospitalisations of $2060 to $2140. On balance, therefore, enalapril is cost saving, reducing health care costs for a congestive heart failure patient on average by SI70 to $250 over a four year period. This value is sensitive to estimates of cost offsets and of improved survival which can result in either a net cost saving with enalapril of approximately $1200 per patient or a net additional cost of up to $3000 per patient (over four years) or greater than $20,000 per life‐year saved.

Conclusions: The addition of enalapril to conventional management of congestive heart failure in Australia should improve survival and may provide a net reduction in treatment costs compared with conventional management alone.
Prevalence of Helicobacter pylori infection in different ethnic groups in New Zealand children and adults
Authors: Fraser A. G. , Scragg R. , Metcalf P. , McCullough S. , Yeates N. J.
Published: March 2008

Background: Helicobacter pylori infection is a major risk factor for peptic ulcer disease and gastric cancer. A study of patients with dyspepsia attending for gastroscopy showed significant differences in H.pylori seropositivity between ethnic groups.

Aims: To determine the prevalence of H.pylori in children and adults in the community in different ethnic groups and to identify risk factors for infection.

Methods: Serum samples (324) were randomly selected from a cross‐sectional survey of 11–12 year old school children with a high proportion of Maori and Pacific Island groups. Serum samples (579) were randomly selected from a cross‐sectional workforce survey of 5677 participants aged 40–64 years. Serum samples were tested for H.pylori IgG.

Results: The percentage seropositivity in 11–12 year old children was European 7%, Maori/part Maori 21%, all Pacific Island groups 48% and for the workforce survey 35.8%, 57.4% and 73.2% respectively. Compared with Europeans the increased relative risk of seropositivity for H.pylori in Maori and Pacific Island participants was significant after adjusting for age and socio‐economic status (1.43 [1.13, 1.80] and 1.76 [1.43, 2.18]) respectively. The relative risk of H.pylori infection significantly increased with age, lower socio‐economic status and lower household income, but was not significantly associated with gender, alcohol or cigarette use.

Conclusions: The high seroprevalence of H.pylori in Maori and Pacific Island groups is consistent with the differences in incidence of gastric cancer. H.pylori continues to be a common infection in Maori and Pacific Island school children. Ethnicity appears to be a risk factor for H.pylori independent of socio‐economic status.
Apolipoprotein E genotyping in Alzheimer's disease in an Australian sample
Authors: Yang J. G. , Poropat R. A. , Brooks W. S. , Broe G. A. , Nicholson G. A.
Published: March 2008

Background: Several previous studies have reported an increased frequency of the E4 allele of the gene for Apolipoprotein (APOE4) in both familial and sporadic Alzheimer's disease (AD). We report the results of a study of this association in an Australian clinic‐based sample.

Aim: To investigate the relationship between APOE4 frequency and AD in an Australian clinic‐based sample and compare the results with previous studies.

Methods: Subject DNA was PCR amplified, enzymatically digested with Hhal and the resulting fragments electrophoretically separated. The genotypes were ascertained according to the resulting fragment sizes and the resulting allele frequencies analysed by calculating a z‐statistic for comparison of two proportions.

Results: The frequency of the APOE4 allele was 53% in the AD group and 11% in the control group. This difference is statistically significant. There was no significant difference in E4 allele frequencies between AD subjects with a family history and those without. At least one E4 allele was found in 26/30 (87%) of AD patients and 10/50 (20%) of controls. The allele frequencies of the control subjects used in this study were found to be consistent with those of several previous studies.

Conclusion: The frequency of the APOE4 allele was significantly higher in AD subjects than in unaffected controls. This provides further evidence of an association between APOE4 and both familial and sporadic AD.
Home and hospital intravenous therapy for two acute infections: an early study
Authors: Montalto M. , Dunt D.
Published: March 2008

Abstract Aim: To study the severity, treatment and outcome of patients with cellulitis and pyelonephritis treated with intravenous antibiotics in either a hospital in the home unit (HHU) or traditional inpatient beds.

Method: Retrospective case reviews were used. All patients with cellulitis and pyelonephritis from January 1995 until January 1996 who were assessed as appropriate for HHU care were included. Each HHU case was included. The traditional in‐hospital group was defined as patients who had been assessed as suitable for HHU, but who did not enter the HHU for non‐clinical reasons. Background variables were: patient age; patient gender; prior treatment with antibiotics; temperature on presentation; creatinine on presentation; leucocyte count on presentation; parenteral medication used; and pre‐existent conditions. Outcome variables were: number of days until febrifuge; total duration of stay; duration of in‐hospital stay; duration of HHU stay; patient incidents; and status at discharge.

Results: The two groups exhibited similarities on patient and condition characteristics, although differences in the types of antibiotics used were found. A positive clinical outcome was achieved in every patient. In‐hospital duration of stay was briefer in the HHU groups.

Discussion: These early results are encouraging for home intravenous therapy. Further studies, controlled trials if possible, are now required to establish these findings more definitively.
Activity and toxicity of docetaxel (Taxotere®) in women with previously treated metastatic breast cancer
Authors: Shapiro J. D. , Millward M. J. , Rischin D. , Davison J. D. , Michael M. , Francis P. A. , Ganju V. , Toner G. C.
Published: March 2008

Abstract Background: Metastatic breast cancer is a major cause of cancer death in Australian women. Docetaxel is a new cytotoxic drug that has shown promise in the treatment of metastatic breast cancer in patients who have previously received other chemotherapy, particularly an anthracycline, and has recently been approved for marketing in Australia.

Aim: To report the first Australian experience with docetaxel in a group of women with metastatic breast cancer.

Methods: Patients with progressive metastatic breast cancer who had previously received other chemotherapy were treated with docetaxel 75 mg/m2 or 100 mg/m2 given as a one hour infusion every three weeks. All patients received oral dexamethasone for five days starting 24 hours prior to docetaxel as prophylaxis against fluid retention. The patients' response to docetaxel and toxicity were assessed by standard criteria.

Results: Twenty‐six patients were treated. The major toxicity was neutropenia with 92% of patients experiencing at least one episode of grade 4 (absolute neutrophil count <0.5X109/L) neutropenia. Hospital admission for febrile neutropenia occurred in 44% of patients with one death from sepsis. Cumulative fluid retention was observed but in only one patient was it dose‐limiting. Apart from alopecia, other toxicities were infrequent and rarely serious. In 23 patients assessable for response, there were 11 partial responses (48%). Three other patients whose disease could not be assessed for response had clinical improvement. The median survival of all patients treated was eight months.

Conclusions: The response rate observed with docetaxel is comparable to that seen in trials in the United States and Europe and confirms the high activity of this new cytotoxic agent. Neutropenia is the major toxicity, and consideration should be given to the use of prophylactic oral antibiotics or colony stimulating factors to try and prevent febrile episodes. Clinicians will need to balance the benefits, toxicities, and cost of docetaxel in determining the appropriateness of its use in their patients.