bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hormonal male contraception: progress and prospects for the 21st century
Authors: Handelsman DAVID J. 
Published: March 2008

Abstract: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

Abstract: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

Abstract 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

Abstract 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 (<i>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

Abstract 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

Abstract 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

Abstract 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

Abstract 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

Abstract 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

Abstract 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.)
Variable hyperhomocysteinaemia phenotype in heterozygotes for the Gly307Ser mutation in cystathionine β‐synthase
Authors: Dawson P. A. , Kraus J. P. , Cochran D. A. E. , Dudman N. P. B. , Emmerson B. T. , Gordon R. B. 
Published: March 2008

Abstract Background: A deficiency of cystathionine β‐synthase (CBS) activity is the most frequent cause of homocystinuria, an autosomal recessive disease with multiple clinical manifestations. Mutations in the CBS gene have been reported in several patients with homocystinuria. Aims: To establish the molecular basis of CBS deficiency in a female patient with pyri‐doxine non‐responsive homocystinuria, and to apply the findings to genetic screening of her family members. Methods: The entire coding region of the CBS cDNA was amplified by PCR and used for direct sequence analysis. Mutant alleles were confirmed by direct sequence analysis of PCR‐amplified genomic DNA, and by a combination of single strand conformation polymorphism and temperature gradient gel electrophoresis analysis. Results: The proband was homozygous for a G919A base transition which predicts the substitution of serine for glycine at codon 307 in the CBS protein (G307S). The parents (both of Irish background) were heterozygotes for the G307S allele, while an asymptomatic sibling had normal CBS sequence. Plasma homocysteine, assessed after an oral methionine load, indicated the mother clearly had moderate hyperhomocysteinaemia, whereas the father had normal concentrations of homocysteine. This is the first report of a normal methionine load test in a proven heterozygote for a CBS mutation which causes severe homocystinuria in the homozygote. Other factor(s) may have contributed to hyperhomocysteinaemia in the mother. The G307S allele has been reported in other patients and appears to be a common allele among families of Celtic origin.