bluuebunny/crossref_metadata_2025_split huggingface dataset:
Upper gastrointestinal haemorrhage following coronary artery bypass grafting
Authors: Norton I. D. , Pokorny C. S. , Baird D. K. , Selby W. S. 
Published: March 2008

Abstract 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

Abstract 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

Abstract 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

Abstract 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

Abstract 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

Abstract 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 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

Abstract 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.
Role of macrophages in the pathogenesis of human immunodeficiency virus (HIV) infection
Authors: Crowe SUZANNE M. 
Published: March 2008

Abstract: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

Abstract: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

Abstract: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

Abstract: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

Abstract: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.