bluuebunny/crossref_metadata_2025 huggingface dataset:
Absence of alpha‐1‐antitrypsin (Pi Null Bellingham) and the early onset of emphysema
Authors: Cook L. , Janus E. D. , Brenton (néeWatts) S. , Tai E. , Burdon J.
Published: March 2008

Background: Alpha‐1‐antitrypsin is the body's major inhibitor of human neutrophil elastase, a powerful proteolytic enzyme capable of degrading the common tissue components. There are over 70 genetic variants of alpha‐1‐antitrypsin, with the Z allele being of greatest clinical relevance. Individuals homozygous for this allele (approximately one in 2500 in Caucasians) have low serum alpha‐1‐antitrypsin levels (10–20% of normal) and are predisposed to emphysema, especially if they smoke. Much rarer are mutations which result in the complete or almost complete absence of alpha‐1‐antitrypsin in the serum.

Aim: To determine the cause of complete absence of alpha‐1‐antitrypsin in a patient who at age 27 years had both emphysema and idiopathic cardiomyopathy.

Methods: Molecular biology techniques were used to sequence the alpha‐1‐antitrypsin gene. Allele specific amplification was used to show the presence of the mutations in other family members.

Results: Investigation showed that the proband was homozygous for the Pi Null Bellingham variant of alpha‐1‐antitrypsin due to the mutation Lys 217 (AAG) to Stop (TAG). His grandmother was heterozygous for Pi Null Bellingham and the additional rare variant P Lowell, Asp 256 (GAT) to Val (GTT), a variant that also results in alpha‐1‐antitrypsin deficiency.

Conclusion: Patients with complete absence of alpha‐1‐antitrypsin develop premature emphysema not having smoked or after only minimal exposure, and much earlier than the more common Pi Z individuals who have the usual form of alpha‐1‐antitrypsin deficiency.
Dose intensive therapy with autologous blood stem cell transplantation in breast cancer
Authors: Kotasek D. , Sage R. E. , Dale B. M. , Norman J. E. , Bolton A.
Published: March 2008

Background: Breast cancer is the commonest form of cancer in Australian women. Although approximately 50% of women with breast cancer achieve long term survival by current management methods, recurrent or metastatic disease is generally incurable. In addition, women with Stage II disease with > 10 positive axillary lymph nodes and also women with locally advanced disease (Stage III) have a poor survival even with adjuvant therapy.

Aims: To assess the toxicity and efficacy of high‐dose chemotherapy with autologous peripheral blood stem cell (PBSC) transplantation in women with both metastatic and poor prognosis primary breast cancer.

Methods: Twenty‐eight women with either metastatic (15) or poor prognosis (13) primary breast cancer were enrolled in the study between November 1988 to January 1993. PBSC were harvested using high‐dose cyclophosphamide (Cy) with or without granulocyte‐colony stimulating factor (G‐CSF) and a myeloablative regimen of Cy, melphalan and carboplatin (CMCp) was used in the transplantation phase.

Results: Optimum numbers of stem cells were harvested in 85% of patients. The use of five G/m2 Cy plus G‐CSF resulted in better PBSC yields and a significant reduction in haematologic morbidity when compared to mobilisation with Cy alone. Twenty‐two women underwent 23 PBSC transplants (PBSCT). There have been two early deaths due to sepsis. The predominant morbidities observed following high dose chemotherapy and transplantation have been nausea, mucositis and diarrhoea. The median number of days to discharge following infusion of PBSC was 15 (range 11–21). At a median follow up time of 1.1 years (range 0 months‐3.6 years), 8/22 (36%) evaluable patients remain alive and disease free while 14/22 (64%) have relapsed or progressed or died.

Conclusion: High‐dose chemotherapy and autologous PBSCT is a potentially highly effective treatment of women with metastatic and poor prognosis primary breast cancer. Randomised studies are required to compare this form of therapy to more standard forms of treatment in breast cancer.
Total hip arthroplasty in the young arthritic patient
Authors: Bleasel J. F. , York J. R. , Korber J. , Tyer H. D. D.
Published: March 2008

Background: Hip disease is a major cause of immobility and pain in children and young adults with inflammatory arthritides. Total hip arthroplasty (THA) has previously been avoided in young patients because of the concern about durability of the prosthesis and the need for multiple revisions. There are now, however, growing reports of the success of such procedures in improving mobility and relieving pain in the young patient with severe hip disease. In this study we aimed to determine the clinical and radiological results in patients with inflammatory arthritides who had undergone THA before the age of 35 years.

Methods: Twenty‐one patients who had undergone a total of 38 hip arthroplasties were identified. Patients' hips were scored both pre‐operatively and at follow‐up using the scoring system of the Hospital for Special Surgery, which allots a score for pain, walking, motion and muscle power, and function. Complications were noted and follow‐up X‐rays were compared to postoperative films to assess radiological loosening.

Results: The mean age at operation was 24 years, and the mean follow‐up was 8.6 years. The results in terms of pain relief, mobility, movement and functional capacity were good. Revision was required in 13 hips (34%). This was mostly due to the failure of resurfacing prostheses. Radiological loosening was evident in a further six hips, five of which were asymptomatic.

Conclusions: THA can dramatically improve the quality of life of the young patient with arthritis. The main concern is the likely need for multiple revisions, with progressive loss of bone stock.
Narcolepsy in Hong Kong Chinese ‐ a preliminary experience
Authors: Wing Y.‐K. , Chiu H.F.K. , Ho C. K. W. , Chen C.‐N.
Published: March 2008

Background: Narcolepsy is a sleep disorder of unknown aetiology. Despite the widely reported strong association with HLA DR2 among different ethnic groups and their varying prevalence rates, there has never been any series of laboratory documented narcolepsy in Chinese.

Aims: To report the preliminary experience with Chinese narcoleptic patients and their HLA typing.

Methods: The records of 342 patients who presented to our sleep laboratory for various sleep problems from 1986 to 1992 were examined. Both clinical and polysomnographic data were analysed. The criteria for a diagnosis of narcolepsy is based on shortened mean sleep latency of less than 5 minutes and presence of rapid eye movement (REM) sleep in two or more of the five 20‐minute naps during multiple sleep latency test (MSLT).

Results: There were five narcoleptic patients documented resulting in an overall laboratory prevalence of 1.5% or 2.3% of patients presenting with hypersomnia. All patients were HLA DR2 positive.

Conclusion: There is 100% association with HLA DR2 in Hong Kong Chinese narcoleptic patients. Based on the laboratory prevalence, the prevalence rate of narcolepsy among Hong Kong Chinese population is estimated to be within the range of four in 10,000 to one in 100,000.
The role of high dose 67‐gallium scintigraphy in staging untreated patients with lymphoma
Authors: Larcos G. , Farlow D. C. , Antico V. F. , Gruenewald S. M. , Boyages J.
Published: March 2008

Background: Gallium‐67 (67Ga) scintigraphy has been reported to be of limited value in staging lymphoma patients. However, recent technical advances in radionuclide imaging have potentially enhanced the usefulness of this method.

Aims: The purposes of this study were to determine the current: (1) sensitivity and specificity and (2) impact on clinicians' treatment decisions of 67Ga scans performed at a teaching hospital.

Methods: There were 46 newly presenting patients with lymphoma (13 with Hodgkin's disease (HD) and 33 with non‐Hodgkin's lymphoma [NHL]). Planar 67Ga scans were performed up to eight days following injection of 300 MBq (8 mCi) with images interpreted by consensus of two blinded observers; sensitivity and specificity were determined on a lesion by lesion basis in comparison to computed tomography (CT) scans, palpation of peripheral lymph nodes and abdominal lymphangiograms (n = 5). The contribution of 67Ga scans to clinicians' treatment decisions was also independently assessed by an experienced oncologist.

Results: Gallium‐67 scan sensitivity and specificity were 80% and 96% for HD and 59% and 98% for NHL. Initial treatment plans were modified in three individuals (7%; 95% confidence intervals = 3–10%) due to lesions on the 67Ga scan not prospectively detected or considered equivocal on other tests.

Conclusions: Only a small proportion of newly diagnosed lymphoma patients benefit from staging with state of the art planar high dose 67Ga imaging.
Efficacy of drug intervention for lipids in the prevention of coronary artery disease
Authors: Howes Laurence G. , Simons Leon A.
Published: March 2008

Meta‐analysis of the benefit of drug intervention in hypercholesterolemia has produced conflicting conclusions, dependent upon which studies were included or which outcomes were considered. We have approached this question by considering coronary artery disease (CAD) outcomes, fatal and non‐fatal, in studies considered to be pivotal ‐ those of sufficient size and duration and those achieving sufficient cholesterol reduction to be likely to have a statistically significant outcome. In parallel, we have reviewed all the published angiographic trials of adequate design (randomised and controlled). In four pivotal primary prevention studies, CAD morbidity was reduced in the range 19–45%. CAD mortality was reduced significantly in one of these studies. Women were included in only one study and they did not exhibit the favourable outcome observed in men. In four pivotal secondary prevention studies, CAD morbidity was reduced in the range 5–36%. CAD mortality was significantly reduced in two studies. In eight angiographic intervention studies, lipid intervention was associated with consistently more evidence of regression or stable coronary disease. These studies also yielded suggestive evidence of improved clinical outcome. We conclude that drug intervention to lower cholesterol levels effectively reduces CAD morbidity and mortality in men already suffering from CAD (and may do so in women). Treatment is similarly effective in men with hypercholesterolemia having no prior history of CAD. We lack evidence of the value of treatment in the elderly or in women having no prior CAD.
Cholesterol reduction and death from noncoronary causes: evidence from randomised controlled trials*
Authors: MacMahonf Stephen
Published: March 2008

An overview of randomised trials of cholesterol reduction (26 trials, 50,000 patients, net cholesterol reduction ˜10%) provides clear evidence of a reduction in the incidence of coronary heart disease (CHD) after just a few years of treatment. Overall, the observed reduction in CHD death (9%± 3) was only half as large as the reduction in non‐fatal myocardial infarction (19%±4), although both were statistically significant (2p <0.005). In these trials, 60% of all deaths were from CHD, and since treatment reduced these by about 9%, the expected reduction in total deaths was about 5–6%. This expected reduction falls within the 95% confidence interval of the observed effect of cholesterol reduction on total mortality in these trials. There were small excesses of deaths from cancer and deaths from trauma among patients allocated active treatment. However, in no single trial, nor in the trials collectively, were these increases individually statistically significant. Furthermore, the increases did not appear to be specific to any one agent nor were the increases consistent between trials of the same agent. These observations suggest that the small excesses of noncoronary deaths observed in the cholesterol reduction trials may have occurred by chance. Evidence from ongoing longer‐term studies of treatments producing larger cholesterol reductions will be useful in further delineating the effects, if any, of such treatments on non‐coronary mortality.
Application of the Poincaré plot to heart rate variability: a new measure of functional status in heart failure
Authors: Kamen P. W. , Tonkin A. M.
Published: March 2008

Background: Conventional methods of quantifying heart rate variability using summary statistics have shown that decreased variability is associated with increased mortality in heart failure. However, many patients with heart failure have arrhythmias which make the ‘raw’ heart rate variability data less suitable for the use of summary statistical measures.

Aims: To examine the clinical potential of a new measure of heart rate variability data, presented by the Poincare plot pattern, as an adjunct to the summary statistical measures of R‐R interval

Methods: We used the Poincaré plot pattern to display beat‐to‐beat heart rate variability data from a group of 23 patients with heart failure and compared them with data collected from 20 healthy age‐matched control subjects. The data, which consisted of 2000 consecutive R‐R intervals, were gathered over 20–40 minutes while the subjects rested supine in a quiet darkened room.

Results: The morphological classification scheme proposed reflected the functional status of patients in heart failure. There was a significant difference (chi‐square = 27.5, df = 6, ρ < 0.0001) in the different pattern types between patients with NYHA Class I and II compared to patients with NYHA Class III and IV. All healthy subjects displayed a ‘cluster’ type of pattern characterised by normally distributed data. Sixteen of the 23 patients in heart failure also produced data which were normally distributed but the remaining seven produced data which required careful filtering to make them suitable for analysis using summary statistics, but which could be analysed by the Poincare plot.

Conclusions: The Poincaréot pattern is a semi‐quantitative tool which can be applied to the analysis of R‐R interval data. It has potential advantages in that it allows assessment of data which are grossly non‐Gaussian in distribution, and is a simple and easily implemented method which can be used in a clinical setting to augment the standard electrocardiogram to provide ‘real time’ visualisation of data.
Writing to referring doctors after a new patient consultation
Authors: Tattersall M. H. N. , Monaghan H. , Griffin A. , Scatchard K. , Dunn S. M. , Butow P. N.
Published: March 2008

Abstract Background: There are no Australasian data on the preferred information content of letters from consultant physicians to referring doctors.

Aims: To survey referring general practitioners (GPs) and specialists concerning their preferences for letters from a consultant physician after a new patient consultation to include different categories of information. To investigate the information content of letters written by one medical oncologist to referring doctors after a new patient consultation and contrast with that of individualised letters written to patients.

Methods: Fifty‐five referring GPs and 53 specialists were sent a questionnaire seeking their views on the information content of letters from consultant physicians. Ninety‐four letters after a new patient consultation were selected at random and analysed for their information content, and compared with 182 individualised letters sent to patients.

Results: Referring doctors wanted letters to contain details of diagnosis, clinical findings, test results and recommended future tests, treatment options, side effects and prognosis. Letters to referring doctors contained 19 items of information (range 8–33), while letters to patients contained a mean of 5.6 ‘salient’ points (range 5–7). Both letters almost always stated the diagnosis, the presenting history and recommended treatment. Letters to patients more commonly presented information about prognosis, further tests, and explanation of symptoms than letters to doctors. In contrast, letters to referring doctors contained more information concerning the past medical, family, and drug history, clinical findings and test results.

Conclusions: Letters sent by a consultant oncologist are not well tailored to the information needs of the referring clinician. Summary letters sent to patients may be modified to include information required by referring doctors. (Aust NZ J Med 1995; 25; 479–482.)
Radiation exposure to patient and operator during radiofrequency ablation for supraventricular tachycardia
Authors: Kovoor P. , Uther J. B. , Ricciardello M. , Ross D. L. , Collins L.
Published: March 2008

Abstract Background: Radiofrequency (RF) ablation has become the primary method of treatment for supraventricular tachycardia and often requires prolonged fluoroscopy times.

Aim: To quantitate radiation exposure to patient and operator during RF ablation for supraventricular tachycardia.

Methods: Thermoluminescent dosemeters were used to monitor radiation at seven sites. Positions were: patient's thyroid, left scapula, T9 vertebra, right scapula and L4‐L5 vertebra and the operator's thyroid and left hand. Monitoring was performed during 22 procedures. Of the patients studied 10 (45%) had atrioventricular junctional re‐entry tachycardia (AVJRT) and 12 (55%) had accessory pathway tachycardia.

Results: The median fluoroscopy times (minutes) and inter‐quartile ranges were 46 (39–65) for AVJRT, 55 (52–60) for left free wall accessory pathway (LFW), 107 (89–140) for septal and 166 (128–176) for RFW pathways. The mean radiation doses (mGy) to the chest wall were 50 for AVJRT, 47 for LFW, 87 for septal and 151 for RFW pathways. The mean radiation to the chest wall of the patient per case was found to be 3.9 times that reported for diagnostic cardiac catheter‐isation and 1.5 times that reported for angioplasty.

Conclusions: Radiofrequency ablation is associated with significant irradiation of the patient and operator. All precautions should be taken to decrease this exposure. If eye irradiation is assumed to be equal to that to the thyroid, more than 45 procedures per month by a single operator (using ceiling‐suspended lead glass shielding) may result in exceeding the recommended dose limit to the eye. (Aust NZ J Med 1995; 25; 490–495.)
Clinico‐pathological study of cytomegalovirus (CMV) in AIDS autopsies: under‐recognition of CMV pneumonitis and CMV adrenalitis
Authors: Dore G. J. , Marriott D. J. , Duflou J. A.
Published: March 2008

Abstract Background: Cytomegalovirus (CMV) is a common cause of morbidity in human immunodeficiency virus (HIV) infected patients, predominantly when severe immunosuppression has occurred. Although CMV infection of the retina and gastrointestinal tract is well recognised as causing substantial morbidity, the significance of infection at other sites, in particular the lungs and adrenal glands is unclear.

Aims: To assess the extent of CMV infection in postmortem examinations performed on HIV‐infected patients. To estimate the degree of concordance between clinical and postmortem findings and the effect of prior diagnosis and/or treatment of CMV infection.

Methods: The postmortem examination findings and clinical records of 25 consecutive HIV‐infected patients who underwent a complete autopsy were examined.

Results: CMV infection was demonstrated in 19 patients (76%) at postmortem examination, with the most common sites of infection being the adrenal glands (56%) and lungs (44%). Concordance between clinical diagnosis of CMV infection and postmortem findings was low with only five of 19 patients (26%) having an antemortem diagnosis. No patient with CMV infection of the lungs or adrenal glands had a clinical diagnosis made, despite four patients having florid CMV pneumonitis at postmortem examination; in three the probable cause of death.

Conclusion: CMV infection is a common postmortem finding in HIV‐infected patients but the concordance between clinical diagnosis and autopsy findings is low. CMV appears to be a significant pathogen in HIV‐related respiratory disease. (Aust NZ J Med 1995; 25: 503–506.)
Determinants of severity of left ventricular dysfunction in Australian men and women with coronary disease aged 65 years or less
Authors: Wang X. L. , McCredie R. M. , Tam C. , Wilcken D. E. L.
Published: March 2008

Background: The degree of left ventricular (LV) impairment is an important determinant of long term outcome in patients with coronary artery disease (CAD).

Aim: We aimed to determine variables predictive of the severity of LV dysfunction in men and women aged 65 years or less with CAD, and to quantitate their contributions.

Methods: We documented atherogenic variables and extent of LV impairment and CAD severity at angiography in 521 consecutively studied men and women aged 65 years or less (381 males and 140 females). We assessed severity from an LV impairment score (Green Lane) and the ejection fraction. We related severity to quantitative and categorical variables which included the severity of angina (no angina, stable and unstable angina).

Results: The LV impairment score correlated closely (negatively) with the ejection fraction (r = ‐0.783, p= 0.0001). There were eight variables independently predictive of the severity of LV impairment assessed by the LV score. The variables in descending order of relative importance in predicting the LV scores were past history of myocardial infarction (MI), number of significantly diseased vessels (> 50% luminal obstruction), life‐time smoking dose, log‐triglycerides, total cholesterol to HDL‐C ratio, hypertension, age and Body Mass Index (BMI). They were all positive relationships. Together they correctly classified the LV scores of 52.6% of the patients. Gender was not an independent contributor to the LV score when other variables were controlled. When the contributions to the variance in LV scores of past history of MI (15.4%) and number of significantly diseased vessels (2.6%) were controlled, life‐time smoking dose independently explained 2.1% (p0.01) of the variance. The LV impairment score was 55% higher in heavy smokers than in non‐smokers (p = 0.01). When we compared patients with stable and unstable angina, LV scores are higher and ejection fraction lower in the unstable angina patients consistent with them having a greater degree of LV dysfunction.

Conclusion: We conclude that variables other than a history of MI and CAD severity contribute significantly to the variance of the degree in LV impairment in CAD patients among which the life‐time smoking dose, triglycerides, TC/HDL‐C, hypertension and increased BMI are all relevant to prevention, and that patients with unstable vs stable angina usually have more impaired LV function. (Aust NZ J Med 1995; 25; 309–315.)
The role of bronchoscopy in the diagnosis and treatment of pulmonary disease in HIV‐infected patients
Authors: Lewin S. R. , Hoy J. , Crowe S. M. , McDonald C. F.
Published: March 2008

Background: Pulmonary disease is the most common reason for presentation and the major cause of death in HIV‐infected patients. There has been an evolution in the optimal approach to the investigation of a pulmonary infiltrate in HIV‐infected patients since the introduction of induced sputum for the diagnosis of Pneumocystis carinii pneumonia (PCP).

Aims: To evaluate the usefulness of flexible fibreoptic bronchoscopy (FFB), bronchoalveolar lavage (BAL), transbronchial biopsy (TBB) and bronchial brushings (BB) in the diagnosis of pulmonary disease in HIV‐infected patients and to examine the effect of FFB on changes in therapy and survival.

Methods: The histories of all HIV‐infected patients referred to Fairfield Hospital for FFB between January 1990 and June 1993 were examined retrospectively.

Results: Forty‐two FFB were performed on 41 patients (40 male and one female). Definitive diagnoses made at FFB included Kaposi's sarcoma (KS) (n= 9), invasive aspergillosis (n= 5), PCP (n= 4), Mycobacterium avium complex (MAC) pneumonia (n= 2), cytomegalovirus (CMV) pneumonia (n= 1), Cryptococcus neoformans pneumonia (n= 1), microsporidium (n= 1) and Pseudomonas aeruginosa pneumonia (n= 1). TBB and BB did not provide a diagnosis for diseases not seen macro‐scopically at FFB or diagnosed by BAL. FFB findings altered diagnosis in 21/42 (50%) presentations and changed therapy in 26/42 (62%) cases.

Conclusions: FFB together with BAL altered the working diagnosis and changed therapy in a significant number of patients. TBB and BB should not be routinely performed in all patients as these procedures are of limited value in this setting.
Validation of the Banff criteria for acute rejection in renal transplant biopsies
Authors: Dittmer I. D. , Zwi L. J. , Collins J. F.
Published: March 2008

Background: The histological criteria for the diagnosis of mild acute rejection in renal transplant biopsies have not been well defined.

Aim: To ascertain the value of the Banff criteria for transplant biopsy reporting, particularly for the diagnosis of acute rejection, and the ‘borderline’ category.

Methods: We compared two systems of histological assessment in 23 transplant biopsy specimens and compared histological diagnoses to separately defined clinical diagnoses. The histological criteria applied were those of the recently described Banff criteria which were compared with our traditional diagnostic method for each specimen.

Results: We found the Banff diagnoses more closely related to the clinical outcome than the system of histological diagnosis that we had previously been using.

Conclusions: We conclude that the Banff criteria more accurately reflect the clinical situation.
Comparison of Chemcard Cholesterol test and laboratory cholesterol measurements
Authors: Gan I. E. T. , Schier G. M.
Published: March 2008

Background: The Chemcard cholesterol test has been designed to estimate cholesterol levels in patients in General Practitioners' surgeries. The patients displaying elevated cholesterol levels may then be referred for a more accurate test at a recognised laboratory.

Aims: To compare the accuracy of the Chemcard cholesterol procedure with a standardised laboratory procedure for estimating cholesterol levels.

Methods: The Chemcard cholesterol procedure was applied to 200 subjects from the community, who were enrolled in a cardiovascular risk assessment programme.

Results: The correlation coefficient between the paired measurements was 0.83. The Chemcard cholesterol procedure gave slightly higher results than did the laboratory procedure as shown by the mean (± standard deviation) difference between the two methods of 0.16 ± 0.58 mmol/L.

Conclusions: The poor agreement between the two methods and the potential misclassi‐fication by Chemcard suggests that the Chemcard is not a reliable test system. The high level of risk group misclassification found in this study refutes the manufacturer's claims and does not eliminate the need for formal laboratory cholesterol measurement.
Aldosterone and its mechanism of action: more questions than answers
Authors: Fuller PETER J.
Published: March 2008

The physiology of the steroid hormone, aldosterone is well defined. The molecular events that mediate this response remain to be elucidated. Aldosterone binds to a specific mineralocorticoid receptor (MR) in sodium transporting epithelia. The structural determinants of ligand‐binding have been explored through the analysis of steroid resistance syndromes, however, the molecular basis of resistance to aldosterone, pseudo‐hypoaldosteronism remains an enigma. Cortisol also binds MR, access is however restricted by the enzyme 11β‐hydroxysteroid dehydrogenase. The MR induces specific genes which regulate apical amiloride‐sensitive epithelial sodium channels; the finding of activating mutations in Liddles syndrome (pseudoaldosteronism) has emphasised their key role. Such mechanisms may apply not only to the peripheral effects of aldosterone but also to the central regulation of blood pressure.
Hormonal male contraception: progress and prospects for the 21st century
Authors: Handelsman DAVID J.
Published: March 2008

During the second half of the 20 th century, progress in developing novel, practical contraceptive methods for men has lagged significantly behind developments for women. Despite the lack of reliable, reversible methods, men throughout the world continue to be strongly involved in family planning but a greater involvement will require more attractive and reliable contraceptive options for men. The closest to fruition are hormonal methods the features of which are reviewed. Landmark WHO contraceptive efficacy studies have established that hormonally‐induced azoospermia provides highly effective and reversible contraception for at least 12 months with minimal short‐term side effects. Even among the small subgroup of men who remain oligozoospermic during hormonal suppression, good contraceptive efficacy is achieved. The present goals are to develop improved second generation hormonal regimens which provide more uniform azoospermia to obviate the need for monitoring of sperm output and to develop long‐acting depot testosterone formulations used alone or with additional gonadotrophin suppressive agents such as progestins or GnRH antagonists. Significant obstacles to progress are the flight of industry from contraceptive R&D due to the financial deterrent posed by the product liability crisis as well as the low priority accorded male reproductive health. Together these will determine whether the range of contraceptive options available to our children in the 21st century will improve, or whether the historically recent unbalanced increase in reliance on women for family planning will continue.
A combined genetic and biochemical approach to mammalian signal transduction
Authors: Della NEIL G. , Hu YINLING , Holloway ANDREW J. , Wang DENNIS , Bowtell DAVID D. L.
Published: March 2008

The last five years have seen a rapid increase in interest and understanding of signal transduction pathways. While the description of such pathways has become more detailed and complex, a number of consistent findings have emerged. Modular domains, such as SH2 and SH3 domains, are present on a wide variety of proteins and mediate specific protein‐protein interactions. By defining the interaction mediated by such domains, a ‘language’ of interaction between proteins in signalling pathways is emerging. As more signalling proteins are identified it has become apparent that most oncogenes and tumour suppressor genes are components of major signalling pathways. Therefore, studies on the basic biology of signal transduction are having a direct impact on our understanding of cell transformation. With the characterisation of signalling pathways in a range of organisms, it has also become obvious that signalling pathways are ancient and have been highly conserved over the last billion years of evolution. A practical result of this finding has been the ability to exploit results obtained in genetically tractable invertebrate species such as C. elegans and Drosophila melanogaster to investigate signal transduction in mammals. This is an approach we have emphasised in our investigation of signal transduction by tyrosine kinase receptors in human and mouse cells. Results obtained in these studies with the Sos and Siah proteins are reviewed.
What dose of vitamin E is required to reduce susceptibility of LDL to oxidation?
Authors: Simons L. A. , Von Konigsmark M. , Balasubramaniam S.
Published: March 2008

Background: Oxidative modification of low density lipoprotein (LDL) may play a role in the pathogenesis of atherosclerosis. Ingestion of vitamin E in high dosage has been shown to reduce the susceptibility of LDL to copper‐induced oxidation, as assessed ex vivo.

Aim: To determine a minimum dose of supplementary vitamin E which will significantly reduce the susceptibility of LDL to oxidation.

Methods: A single centre, double‐blind, parallel placebo‐controlled trial. Healthy volunteers (total n=42) were randomised to receive placebo, 500, 1000 or 1500 IU/day of vitamin E (D‐α‐tocopherol) for a period of six weeks. Primary outcomes were change in lag time or oxidation rate to copper‐induced LDL oxidation. Secondary outcomes were changes in plasma vitamin E levels and clinical tolerance.

Results: Lag time to LDL oxidation was significantly prolonged and oxidation rate significantly slowed at all dose levels of vitamin E, indicating a threshold effect from 500 IU/day. Compared to placebo, the median prolongation in lag time on 500 IU/day was 26%, on 1000 IU/day 24% and on 1500 IU/day 35%. The corresponding slowing in oxidation rates was 14%, 19% and 25% respectively. The per cent change in plasma vitamin E concentration was highly correlated with the change in lag time (r=0.61, p<0.001) and oxidation rate (r=−0.55, p<0.001). Vitamin E was generally well tolerated.

Conclusions: Vitamin E in a dose of 500 IU/day will significantly reduce the susceptibility of LDL to oxidation. Whether or not this treatment will consistently reduce the future incidence of coronary artery disease will only be answered by further clinical trials.
Sidestream smoke inhalation decreases respiratory clearance of 99mTc‐DTPA acutely
Authors: Yates D. H. , Havill K. , Thompson M. M. , Rittano A. B. , Chu J. , Glanville A. R.
Published: March 2008

Background: The permeability of the alveolar‐capillary barrier to an inhaled aerosol of technetium 99m labelled diethylenetriamine penta‐acetate (99mTc‐DTPA) is used as an index of alveolar epithelial injury. Permeability is greatly increased in active smokers.

Aims: To determine the effect of sidestream smoke inhalation on permeability as this has not been described previously.

Methods: We measured lung clearance of inhaled 99mTc‐DTPA aerosol in 20 normal nonsmoking subjects before and after exposure to one hour's sidestream smoke inhalation.

Results: Measured carbon monoxide (CO) levels rose to a maximum of 23.5±6.2 ppm (mean ±D) from baseline values of 0.6± 1.3 (p<0.001) and plasma cotinine levels to a maximum of 9.5± 4.5 nmol/L (mean ± SD). The half time (T1/2 in minutes) for 99mTc‐DTPA clearance rose from baseline 69.1± 15.6 (mean ± SD) to 77.4± 17.8 (p<0.05) after smoke exposure. No effect of 99mTc‐DTPA scanning or of sidestream smoke was demonstrated on lung function.

Conclusions: We conclude that low level sidestream smoke inhalation decreases 99mTc‐DTPA clearance acutely in humans. The mechanism of this unexpected result is not established but may include differences in constituents between sidestream and mainstream smoke, alterations in pulmonary microvascular blood flow, or changes in surfactant due to an acute phase irritant response.
Meningococcal disease in urban south western Sydney, 1990–1994
Authors: Munro R. , Kociuba K. , Jelfs J. , Brown J. , Crone S. , Chant K.
Published: March 2008

Background: There has been a sustained increase in incidence of meningococcal disease throughout Australia since 1987. In south western Sydney the incidence is higher than the national rate and a cluster of cases occurred in 1991 resulting in a widespread vaccination programme.

Aims: To investigate the clinical demographics of patients with meningococcal disease treated in south western Sydney, and to differentiate meningococcal strains to understand better the epidemiology in this urban setting. In addition, to investigate whether delays in diagnosis of meningococcal disease and institution of appropriate treatment were occurring.

Methods: Retrospective classification of notified cases as meningitis, septicaemia, meningitis/septicaemia, and other syndromes. Clinical information recorded to establish patterns of disease, delays in diagnosis and appropriate treatment, and outcome. Microbiological classification of organisms isolated by serogroup, serotype and subtype.

Results: Meningococcal disease primarily affects young children in winter months in south western Sydney, with a secondary peak of incidence in the 15–20 year old age group. 20.7% presented with meningitis only, 22.4% with septicaemia only, and 53.4% with meningitis/septicaemia. There was a delay in diagnosis and institution of appropriate treatment of more than two hours in 21/58 (36.2%) patients including three of the six who died. No patient had received a parenteral antibiotic prior to coming to hospital ‐ 18.9% had received an oral antibiotic. The use of antibiotics before diagnostic lumbar puncture decreased the number of positive CSF cultures. However, in all but one patient with negative cultures there was other microbiological evidence of meningococcal disease. The mortality rate was highest (30.8%) in patients with septicaemia only, 6.5% in patients with meningitis/septicaemia and 0% in patients with meningitis only.

Serogroup C was the predominant organism in all age groups. The predominant serotype was 2b (80% of serogroup C isolates). Subtypes were more variable but P1.2 occurred in 66.7% of serogroup C strains.

Conclusions: There is a need for more education in our Health Area to improve the time taken to diagnose and institute appropriate treatment. The predominance of serogroup C is unusual in urban Australia where national data show serogroup B organisms predominate. Meningococci of phenotype C:2b:Pl.2 have continued to cause disease in our Health Area for the past five years. This phenotype is uncommon in other areas of Australia.
The use of thrombolytic therapy in patients presenting to a peripheral metropolitan Emergency Department with acute myocardial infarction
Authors: Jacobs I. G. , Fatovich D. M.
Published: March 2008

Background: While use of thrombolytic therapy in the management of acute myocardial infarction has become accepted practice in major teaching hospitals, its use in peripheral metropolitan hospitals has not been well accepted.

Aim: To evaluate the use of thrombolytic therapy in the management of acute myocardial infarction in the Emergency Department (ED) of a peripheral metropolitan hospital.

Methods: A mixed prospective and retrospective observational study of 69 patients with acute myocardial infarction, who received thrombolytic therapy during a three year period, was conducted in a community based ED.

Results: Demographic data, door to drug interval, complications occurring during administration of thrombolytics and subsequent interhospital transfer were recorded. The mean door to drug interval in 1992 was 79.7 minutes (95% CI: 50.7 to 109.1) and by 1994 this had fallen to 25.6 minutes (95% CI: 18.9 to 32.3). Hypotension (22%) was the most common complication of therapy observed and cardiac arrest occurred in two cases (3.2%). A single episode of hypotension and vomiting were the only complications that occurred during interhospital transfer. There were no deaths during therapy or transfer.

Conclusion: Thrombolytic therapy can be undertaken in the EDs of peripheral metropolitan hospitals in a safe and timely manner. There is little justification for routine medical escorts in the clinically stable post thrombolysis patient.
Survey of cyclosporin‐sparing agent use in Australasian transplant centres
Authors: Jones T. E.
Published: March 2008

Background: The coprescription of drugs which elevate cyclosporin blood concentration has been advocated to reduce the costs associated with use of this expensive immunosuppressive drug. This is the first time that drugs have been widely prescribed for an economic purpose and while it is thought to be widespread, there are little published data on the extent of this practice in Australia and New Zealand.

Aims: To determine the extent to which cyclosporin sparing agents are used by Australian and New Zealand organ transplant centres, to determine which agents are used and why these agents are used by some but not all centres.

Methods: Organ transplant centres were surveyed via a questionnaire.

Results: Considerable variation in use of cyclosporin sparing agents exists both within and across organ transplant types by Australian and New Zealand transplant centres. Diltiazem use is more widespread than ketoconazole.

Conclusions: Little of the variability in use of cyclosporin sparing agents can be explained by scientific considerations. While the central government benefits from the significant cost savings achieved by the use of cyclosporin sparing agents, individual transplant units may not. Transplant units may however be the major target in the event of litigation arising as a result of adverse effects. The availability of generic brands and improved formulations of cyclosporin may affect the viability of using cyclosporin sparing agents
Epidemiological study of angioedema and ACE inhibitors
Authors: Gabb G. M. , Ryan P. , Wing L. M. H. , Hutchinson K. A.
Published: March 2008

Background: Angioedema is an uncommon and poorly recognised adverse reaction to angiotensin converting enzyme inhibitors (ACE‐Is). The epidemiology of this association has not been described.

Aims: To examine the epidemiology of angioedema and its relation to ACE inhibitor prescribing. To examine the characteristics of angioedema occurring in patients taking ACE inhibitors.

Methods: A retrospective case control study and a case note audit were conducted of 40 patients who presented to a teaching hospital Accident and Emergency Department with angioedema on 48 occasions. One hundred and sixty control subjects presenting to the same Accident and Emergency Department but without angioedema were matched to cases by age, sex and presentation date. An ecological study comparing the numbers of angioedema admissions by age cohorts to South Australian (SA) public hospitals with the prescription volumes of ACE‐Is in Australia was also undertaken.

Results: Case control study: In patients presenting with angioedema compared with controls, the exposure odds ratio for ACE‐Is was 5.1 (95% CI 2.03–12.89) and for nonsteroidal anti‐inflammatory drugs (NSAIDs) was 4.13 (95% CI 1.28–13.39).

Case note audit: 15/40 (38%) patients presenting with angioedema on 19/48 (40%) occasions were taking an ACE‐I. These patients were older and less likely to have an atopic history than those not taking an ACE‐I. The onset of angioedema after starting an ACE‐I was delayed for greater than six months in nine patients. ACE‐I therapy was continued after 53% of presentations.

Ecological study: The number of admissions with angioedema to SA public hospitals increased between 1985–86 and 1994–95, predominantly in older patients, and paralleled the increasing prescription volumes of ACE‐Is.

Conclusion: A considerable proportion of patients presenting with angioedema will be taking an ACE‐I or a NSAID. The association of ACE‐Is and angioedema is not well recognised, partly because the onset of angioedema may be delayed for months or years after commencement of an ACE‐I. A persisting risk of angioedema is present in patients who have initially commenced an ACE‐I uneventfully. The epidemiology of angioedema is now changing in parallel with the increasing use of ACE‐Is.
Hepatitis C genotypes in Australian haemophilia patients
Authors: Baker R. I. , Smith J. , Eikelboom J. , Leahy B. , Kay I. , Lavis N. , Palladino S. , Cheng W. , Price J. , Mews C.
Published: March 2008

Background: Differences in the hepatitis C virus (HCV) genotype influence the severity of HCV related liver disease and response to interferon therapy. HCV infection is frequent in Australian haemophilia patients who have been exposed repeatedly to multiple HCV genotypes through non HCV virally inactivated clotting factor concentrates. The distribution of the various HCV genotypes in Australian haemophilia patients is unknown.

Aim: To examine the HCV genotype distribution and clinical features of HCV associated liver disease in Australian haemophilia patients.

Methods: Forty patients with bleeding disorders who were known to be both HCV antibody and polymerase chain reaction (PCR) positive were evaluated by direct sequencing of the PCR products for the HCV genotype.

Results: Genotype 1 was found in 65% of patients (26/40), type 2 in 5% (2/40) and type 3 in 30% (12/40). No genotypes 4 to 6 were found. There was no association between the HCV genotype and the severity of haemophilia, alanine transaminase levels, or the presence of portal hypertension. Unlike European, Asian and American studies where the majority of type 1 infection is subclass lb, in Australian haemophilia patients it is subclass la (73% ‐ 19/26) which may have a better prognosis and response to interferon.

Conclusions: Despite patients with haemophilia being exposed to multiple HCV genotypes, it appears that there is no selection advantage of one genotype over another. Australian haemophilia patients with HCV have a different genotype distribution to that reported in other countries and care should be observed in interpreting non Australian studies concerning HCV.
A comparison of the effects of oral prednisone and inhaled beclomethasone dipropionate on circulating leukocytes
Authors: Cameron R. G. , Black P. N. , Braan C. , Browett P. J.
Published: March 2008

Background: While the side effects of oral glucocorticoids are well recognised there is debate about the systemic effects of high doses of inhaled glucocorticoids such as beclomethasone dipropionate and how these compare with the effects of oral prednisone.

Aim: To compare the effects of different doses of oral prednisone and inhaled beclomethasone dipropionate (BDP) on changes in circulating leukocytes.

Methods: Changes in different subsets of circulating leukocytes were measured as an index of the systemic effects of inhaled BDP and oral prednisone. We compared the effects of inhaled placebo and 500 and 1000 μg of inhaled BDP with oral placebo and 2.5, 5 and 10 mg of prednisone in eight healthy volunteers. Leukocyte numbers were measured before and four hours after each dose of medicine.

Results: Compared with inhaled placebo, 1000 (xg of inhaled BDP led to a significant increase in neutrophils as a percentage of the total white count (ρ<0.05) and a significant decrease in the total lymphocyte number (ρ<0.05) and in the number of CD4 lymphocytes (ρ<0.05). For 1000 μg BDP the increase in the % neutrophil count was 8.55% (95% CI 5.17 to 11.93) and the fall in lymphocyte numbers was ‐0.14X107L (95% CI 0.06 to ‐0.34) while 2.5mg prednisone led to an increase in the % neutrophil count of 9.31% (95% CI 5.82 to 12.80) and a fall in lymphocyte numbers of ‐0.07X 107L (95% CI 0.05 to ‐0.19).

Conclusions: The systemic effects of 1000 μg inhaled BDP and 2.5 mg of prednisone are similar.
Clinical associations of anti‐lamin autoantibodies
Authors: Hill C. , Roberts‐Thomson P. , Pollard A. , Gillis D. , Kirkham B.
Published: March 2008

Abstract Background: The clinical associations of anti‐lamin autoantibodies were first described in 1973. Since then a number of individual case reports and two small series have been published. These have suggested an association with connective tissue disorders and autoimmune liver disease.

Aims: To identify the clinical and laboratory associations of anti‐lamin autoantibodies in an Australian population.

Methods: Retrospective review of routine antinuclear antibody testing between 1990–1994 for characteristic linear staining of nuclear envelope on indirect immunofluorescence on HEp‐2 cells with clinical status defined by retrospective review of case records.

Results: Twenty‐eight patients were identified and the clinical status of 27 patients defined. Eleven patients had associated IgG anti‐cardiolipin antibodies; anti‐phospholipid syndrome was present in nine. Seven further patients had liver disease; five had autoimmune liver disease, with associated autoantibodies. The remaining nine patients had a diverse group of diseases. There was no correlation between the titre of the autoantibody and clinical status. An association with anti‐cardiolipin antibodies was found although the cause remains obscure.

Conclusion: Anti‐lamin autoantibodies, as identified by indirect immunofluorescence, are associated with a diverse group of diseases but particularly with anti‐phospholipid syndrome and liver disease. Testing for anti‐phospholipid antibodies and more specific markers of systemic lupus erythematosus and autoimmune disease, for example anti‐dsDNA antibodies, anti‐smooth muscle antibodies and anti‐mitochondrial antibodies should be pursued when anti‐lamin autoantibodies are detected. (Aust NZ J Med 1996; 26: 162–166.)