bluuebunny/crossref_metadata_2025 huggingface dataset:
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.
Radiofrequency ablation of idiopathic ventricular tachycardia
Authors: Vohra J. , Shah A. , Hua W. , Gerloff J. , Riters A.
Published: March 2008

Abstract Background: Radiofrequency ablation (RFA) has been shown to be very effective in the treatment of supraventricular tachycardias and has replaced surgical ablation. Only a few reports of RFA for idiopathic ventricular tachycardia (VT) have appeared in the literature during the last two years.

Aim: This paper presents our experience with RFA for idiopathic VT in 19 patients.

Material: The age range of patients was 22–60, with a mean of 37.9 years. Twelve out of 19 were females, two patients had cardiac failure due to almost incessant VT while the rest had normal left ventricular function. Twelve patients had VT arising from the right ventricle (RV); of these, nine were from the outflow tract, two from the RV apex, and one from the mid‐anterior RV. Seven patients had VT arising from the left ventricle (LV); of these, five were from the inferobasal portion of the septum and two were from the anterolateral area.

Methods: In all patients the diagnostic study and therapeutic RFA were combined in a single procedure. Pacemapping was used to guide die site of RFA in patients with VT arising from the RV. Local activation time (LAT), Purkinje potentials (PP) and pacemapping were used to guide RFA in those patients with LV septal tachycardias.

Results: A total of 21 RF procedures were performed in 19 patients and 15 out of 19 patients had successful VT ablation. Ten of the 12 patients with RV tachycardias and all five patients with LV septal (left axis, right bundle branch block) tachycardias were successfully ablated. One patient with mid anterior RV VT required two attempts for successful ablation. One patient with RV outflow tract (RVOT) VT could not be ablated despite two attempts. Two patients with LV tachycardias arising from the antero‐lateral LV could also not be ablated. During a follow up period of two to 16 months none of the successful patients had recurrence of VT The number of RF applications was one to 27, mean 10; fluoroscopy times were four to 75, mean 26.9 minutes.

Conclusion: Idiopathic VT frequently arises from the RVOT and inferobasal portion of the LV septum. These tachycardias can be diagnosed on clinical and ECG grounds. RFA for idiopathic VT arising from these areas has a high success rate and this mode of treatment should be considered as a nonpharmacological curative treatment for symptomatic patients. (Aust NZ J Med 1996; 26: 186–194.)
Predictive diagnosis of multiple endocrine neoplasia (MEN 1) in four Australian kindreds
Authors: Grimmond S. M. , Teh B. A. , Hii S. I. , Cardinal J. , Walters M. , Epstein M. , Edwards M. , Hockey A. , Pullan P. T. , Perry‐Keene D. , Boyages S. , Cameron D. , Hayward N. K.
Published: March 2008

Background: Multiple endocrine neoplasia type 1 (MEN 1) is a tumour predisposition syndrome that usually manifests in the first four decades of life. It has an autosomal dominant mode of inheritance which means that any new member of a MEN1 kindred has roughly a 50% chance of developing the disorder during their lifetime. The localisation of the MEN1 gene to a small region of chromosome band llql3 has led to the development of DNA‐based predictive diagnosis for this disease.

Aims: To establish a polymerase chain reaction (PCR)‐based system, using simple tandem repeat polymorphisms (STRPs), to predict gene carriers in four Australian MEN 1 kindreds.

Funding: This work was supported by the National Health and Medical Research Council of Australia and the Princess Alexandra Hospital Foundation.

Methods: Six STRP markers flanking the MEN1 region of chromosome band 11q13 were used to screen individuals for a common haplotype in order to determine carrier status.

Results: The accuracy of prediction was calculated to be >95% in informative individuals.

Conclusions: DNA‐based presymptomatic detection of affected members of MEN 1 kindreds could facilitate their care and reduce the inconvenience and expense of repeated testing of unaffected members. However, due to occasional recombination events or uninformativeness of markers in certain individuals, carrier status cannot always be predicted.
Hickman catheters: left‐sided insertion, male gender, and obesity are associated with an increased risk of complications
Authors: Craft P. S. , May J. , Dorigo A. , Hoy C. , Plant A.
Published: March 2008

Background: Semipermanent tunnelled silicone rubber Hickman catheters are widely used to provide durable central venous access for patients with cancer or haematological disease.

Aims: To document the frequency and severity of Hickman catheter related adverse events and to identify predisposing factors.

Methods: A retrospective review was undertaken of 153 sequential Hickman catheters inserted into patients receiving treatment for cancer or haematological disease. All Hickman catheters were inserted percutaneously in a radiology department under local anaesthesia and fluoroscopic control. The exact position of the catheter tip was determined by reviewing post‐insertion radiographs.

Results: The median duration of catheter use was 55 days (range one‐650). Complications led to the removal of 32% of catheters. Exit site infection complicated 22% of catheters, septicaemia 7%, migration or dislodgment 7%, and venous thrombosis 8%. Complications were more common in male patients (exit site infection and catheter loss), in patients with acute leukaemia (septicaemia) and in obese patients (catheter migration). Left sided catheters caused more venous thrombosis and were more likely to malfunction or block. Left sided catheters required removal more frequently than right sided catheters. Termination of the Hickman catheter within the high superior vena cava (SVC) resulted in loss of function earlier when compared to termination with the low SVC or right atrium (RA).

Conclusions: Right‐sided Hickman catheters terminating in the low SVC/RA offer the best chance of durable function. The use of subcutaneously tunnelled catheters in obese patients poses unique problems with catheter migration. Vigilance in the placement and care of Hickman catheters remains essential.
Relationship of non‐specific airway hyper‐responsiveness (AHR) to measures of peak expiratory flow (PEF) variability
Authors: Kolbe J. , Mercer‐Fenwick J. , Richards G. , Rea H.
Published: March 2008

Background: The relationship between airway hyper‐responsiveness (AHR) and clinical asthma remains controversial and unclear.

Aims: To test the hypothesis that serial measures of variability of peak expiratory flow rate (PEF) correlate with serial measures of AHR, and to determine which mathematical expression of variability provides the best correlation.

Methods: A longitudinal study over 180 days of 20 atopic, moderately severe asthmatics was undertaken. A diary of medication use and morning and evening PEFR before and after (3 agonist was kept and AHR (PD20 histamine) was measured at three‐weekly intervals. Using group data (128 sets) In PD20 was correlated with various measures of PEF variability over 9 days.

Results:

Within the group there was a weak but highly statistically significant correlation between AHR and measures of PEF variability ‐ the strongest correlation being with mean morning PEF. Within individual subjects, however, the correlation was not a consistent finding and only four patients had a statistically significant relationship (p<0.05) between AHR and mean morning PEF.

Conclusions: These results suggest that while PEF variability may reflect AHR for the purposes of epidemiologic studies, it is unlikely to be useful as a simple ‘non‐invasive’ means of assessing AHR in individual patients. More complex measures of PEF variability do not have an advantage over simpler measures such as mean morning PEF.
Diabetes, mortality and coronary heart disease in the prospective Dubbo study of Australian elderly
Authors: Simons L. A. , Friedlander Y. , McCallum J. , Simons J.
Published: March 2008

Background: A prospective study of Australian elderly living in Dubbo has shown that diabetes is a significant predictor of all‐causes mortality and coronary heart disease (CHD).

Aim: To examine and contrast clinical and socio‐demographic predictors of these outcomes in those with and without diabetes.

Methods: The data are derived from a community‐based sample of subjects 60 years and older followed over 62 months since 1988. Of 1155 men and 1472 women, 9.2% and 6.9% respectively manifested diabetes at baseline, based on history or fasting hyper‐glycaemia.

Results: In the presence of diabetes, all‐causes mortality was increased twofold in both sexes, CHD incidence was increased twofold in men and threefold in women, stroke incidence was increased twofold in women but little changed in men. Proportional hazards models were derived separately for persons with and without diabetes and risk factors differentially predictive in diabetes were sought. Significant predictors of death in diabetes were old age and current smoking. Those factors differentially predictive were ‘being married’ (Relative Risk [RR] 1.60 with diabetes and 0.69 without diabetes) and higher body mass index (BMI) (RR 1.03 with diabetes and 0.79 without diabetes). Significant predictors of CHD in diabetes were old age, prior CHD, severe hypertension, low HDL cholesterol and self‐rated health. Those factors differentially predictive were higher body mass index (RR 1.14 vs 0.83) and physical disability (RR 0.69 vs 1.55). Differential predictions with regard to BMI may relate in part to excess CHD and mortality at low BMI in non‐diabetic subjects.

Conclusion: The vascular disease burden of diabetes in the elderly has been confirmed, especially in women. A number of conventional risk factors are contributing to this burden and may be amenable to treatment.
Transdiaphragmatic pressure in young adult Singaporean subjects ‐ normal values and a comparison between different respiratory manoeuvres
Authors: Chan CHOONG‐CHEE , Cheong TUCK‐HONG , Wang YEE‐TANG , Poh SOO‐CHUAN
Published: March 2008

Background: Most published normal values for transdiaphragmatic pressure (Pdi) have been from Caucasian subjects and there is no universal agreement regarding the most appropriate manoeuvre for assessing Pdi.

Aims: The aims of our study were to obtain normal values and to compare the different manoeuvres used to assess Pdi in normal young Singaporean adults.

Methods: Twenty‐four normal subjects (23 Chinese, one Indian) were studied by measuring Pdi during maximal sniffs from functional residual capacity (sniff Pdi), maximal inspiration to total lung capacity (Pdi TLC) and maximal static inspiratory efforts from residual volume (Pdi PImax).

Results: Mean values±SD for sniff Pdi, Pdi TLC and Pdi PImax were 101.8±31.7, 46.8±26.4 and 83.5±35.5 cm H20 respectively. Sniff Pdi was significantly higher than Pdi TLC (p<0.001) and Pdi PImax (p=0.005). Pdi PImax was significantly higher than Pdi TLC (p<0.001). Males had significantly higher values for sniff Pdi (p=0.026) and Pdi PImax (p=0.022) than females. There was a significant correlation between the different methods of recording Pdi. Sniff Pdi had the highest values, least between‐ and within‐subject variation and most consistent pattern of respiratory muscle recruitment with the lowest proportion of negative gastric pressure (Pg) values (p<0.001).

Conclusions: Therefore, sniff Pdi may be better than Pdi TLC and Pdi PImax in assessing diaphragm function. Also, our subjects seemed to have lower sniff Pdi and Pdi PImax, and higher Pdi TLC compared with Caucasian subjects.
Assessment of left ventricular function after radiofrequency and direct current atrioventricular node ablation
Authors: Wong J. , Vohra J. , Chan W. , Mond H. G. , Lichtenstein M. , Kritharides L. , Warren R. J.
Published: March 2008

Background: There is limited information available regarding the effect of catheter ablation of the antioventricular (AV) junction on left ventricular (LV) function. Both deterioration and improvement in LV function have been reported following direct current (DC) ablation of the AV junction. The deterioration of LV function following DC ablation of the AV junction may be due to the ccompanying barotrauma, DC arcing and direct coagulation, or even the effects of chronic ventricular pacing. If this deterioration of LV function was a result of the accompanying effects of DC shock, the use of radiofrequency ablation (RF) should not result in deterioration of LV function.

Aim: To study LV function before and after different methods of AV junction ablation and in patients with chronic ventricular pacing without AV junction ablation.

Material: This study assessed LV function in patients following RF ablation, low energy DC ablation of the AV junction and compared the results with our previously reported finding in patients who had AV junction ablation using high energy DC shock. A group of patients undergoing permanent single chamber ventricular pacemaker implantation without AV junction ablation were selected as controls.

Methods: All patients were paced in the ventricle at 110 beats/minute during LV function assessment by radionuclide angiography. Global LV function and segmental wall motion abnormalities were assessed before, immediately following and three months after ablation.

Results: In the high energy DC ablation group, a fall in global LV function (50±3.0% to 43±3.0%, p=0.02) and impairment of segmental wall motion were detected. Low energy DC ablation resulted in segmental wall motion impairment similar to high energy DC but without affecting global ejection fraction (47.0%±6.7 to 45.5%±3.1, p>0.05). Neither RF ablation (44.0%±3.3 to 45.3%±3.5, p>0.05), nor chronic pacing (46.7%±4.9 to 47.0%±2.9 p>0.05) had any effect on global or segmental LV function.

Conclusions: Low energy DC or RF ablation of the AV junction does not affect global LV ejection fraction. The deterioration of global LV function after high energy DC shock ablation appears to be related to the accompanying effects of DC energy and not to the effects of chronic ventricular pacing.
Maternal selenium levels and Sudden Infant Death Syndrome (SIDS)
Authors: McGlashan N. D. , Cook S. J. , Melrose W. , Martin P. L. , Chelkowska E. , von Witt R. J.
Published: March 2008

Background: The possibility is tested that low anti‐oxidant status and/or low levels of selenium (Se) might predispose to Sudden Infant Death Syndrome (SIDS).

Aim: This study was undertaken to collect evidence on the Se status of pregnant and non‐pregnant women and newborn babies and to establish whether babies who later died of cot death had significantly divergent levels of blood Se at birth.

Methodology: Aliquots of blood were collected from all newly pregnant mothers in Tasmania and from the cords of all newborn babies. These were analysed for Se and glutathione peroxidase (GPx) content and compared by season and with non‐pregnant, age standardised blood donors in three areas of Tasmania and three mainland Australian States.

Results: Cot death babies' cordbloods were not significantly different in Se or GPx‐status, in this small sample, from those of other babies, nor was a seasonal variation in these parameters demonstrated among 390 randomly selected Tasmanian mothers. Mothers‐to‐be showed a decrease in enzyme levels during pregnancy and Tasmanian blood donors had significantly lower levels than donors from other States.

Conclusion: While no evidence can safely be drawn about a relationship between Se or GPx‐status and SIDS, this study provides base level measures for populations showing that Tasmanian residents have low levels of these anti‐oxidants.
The clinical spectrum of necrotising fasciitis. A review of 15 cases
Authors: Jarrett P. , Rademaker M. , Duffill M.
Published: March 2008

Abstract Background: Necrotising fasciitis represents a spectrum of disease which ranges from fulminant through acute to subacute varieties. While fulminating necrotising fasciitis is a well recognised entity the subacute variety is not.

Aim: To assess six years' experience of necrotising fasciitis at Waikato Hospital.

Method: Cases of necrotising fasciitis were identified from discharge statistics for the period 1990–1995. Records were reviewed for clinical features, predisposing factors, microbiology, histology, treatment and outcome.

Results: Fifteen cases were identified of which ten were female. The average age was 55 years (range of 15–92 years). One patient presented with fulminant, eight with acute and six with subacute necrotising fasciitis. Significant blister formation was noted in eight cases. Risk factors were identified in 14 patients including trauma, renal impairment, diabetes mellitus, and various drugs including diclofenac (four patients), naproxen (one patient) and prednisone (two patients).

Group A beta haemolytic streptococcus (GABHS) was identified in ten cases. Swab or tissue cultures had the highest yield for isolating the organism. Blood cultures grew GABHS in only three of 12 cases.

Eight patients (53%) died. Of the survivors all but one patient required debridement and skin grafting.

Conclusions: Necrotising fasciitis is a clinical spectrum of disease. It affects a wide age group and can have associated morbidities. It is often a fatal disease. Early recognition, high dose antibiotics and surgical debridement are important in the management of the entire spectrum of necrotising fasciitis.
The decline in asthma hospitalisations in persons aged 0–34 years in New Zealand
Authors: Kemp T. , Pearce N.
Published: March 2008

Abstract Aims: Hospitalisation rates for asthma for the 0–14 year and five‐34 year age ranges have been examined from 1969 to 1993 to determine whether the rise observed between the 1960s and 1980s has continued into the 1990s.

Results: In the 0–14 age range, hospitalisations peaked in 1986 then fell by 18.7% by 1993. There was a corresponding rise in hospitalisation rates for acute bronchitis/ bronchiolitis and it is possible that the fall in asthma hospitalisations in this age range is at least partly explained by diagnostic transfer. On the other hand, the trends in the five‐34 age range appear unlikely to be explained by diagnostic transfer. The rate peaked in 1986 and fell by 34.7% by 1993, with most of the decline occurring after 1989. This in part parallels the trends in mortality in this age range, which saw a sudden fall in the death rate in 1989.

Conclusions: New Zealand is not only benefiting from a marked fall in asthma deaths, but is also benefiting from a marked decline in asthma hospitalisations in young adults, and probably also in children.
Orthostatic blood pressure control and ageing*
Authors: Wing Lindon M. H. , Tonkin Anne L.
Published: March 2008

Reflex haemodynamic responses to orthostatic stress are attenuated with ageing, the extent of attenuation increasing with advancing age. In 15–20% of individuals aged >65 years, the attenuation may be so marked that there is an excessive fall of blood pressure (BP) on assumption of the upright posture, sufficient on occasions to cause symptomatic cerebral hypoperfusion ‐ this is known as ‘ageing‐related’ orthostatic hypotension (AOH), a major risk factor for morbidity and mortality. Comparison of the cardiovascular responses to a variety of physiological and pharmacological stresses in healthy young and elderly subjects and in those with AOH suggests that the predominant site of the ageing‐related change in cardiovascular reflex function is in the central connections of the arterial baroreflex, affecting particularly the BP buffering response. There is no evidence for ageing‐related impairment of the efferent limb of the baroreflex, i. e. there is no significant ageing change in sympathetic vasomotor function or cardiac drive. Ageing‐related impairment of baroreflex function also does not appear to result from either attenuation of arterial compliance or the presence of systolic hypertension, despite the epidemiological association between systolic hypertension and AOH. Better understanding of this important problem has the potential to improve the health of all elderly people.
The current status of thrombolytic therapy
Authors: Aylward Philip
Published: March 2008

Fibrinolytic therapy substantially reduces mortality from acute myocardial infarction. Patient selection is, however, important. The patient must present within 12 hours of the onset ofischaemic symptoms, have definite ECG changes of ST elevation or left bundle branch block and no contraindications. The major contraindications are those for risk of an intracerebral bleed, recent stroke, intracranial tumour or risk of a major systemic bleed. Age and hypertension are not contraindications but may modify the regimen used.

Heparin is required with recombinant tissue plasminogen activator but is optional with streptokinase.

The recent COBALT trial suggests that the accelerated weight related t‐PA regimen given over 90 minutes is more satisfactory than double bolus t‐PA. However, inpatients under 75 years of age, the two regimens were equivalent.

For patients suffering acute myocardial infarction, practitioners should now individualise choice of therapy, rather than give the same cocktail to all patients. The choice of regimen will depend on the cardiac risk, the stroke risk, the bleeding risk and the cost.
Idiopathic steroid responsive chronic lymphocytic meningitis—clinical features and long‐term outcome in 17 patients
Authors: Charleston A. J. , Anderson N. E. , Willoughby E. W.
Published: March 2008

Background: Some patients with chronic lymphocytic meningitis appear to respond to corticosteroid treatment, but investigations fail to identify the cause. The use of corticosteroids in patients with chronic meningitis is controversial and the long term outcome is unclear.

Aim: To review the long term outcome in 17 patients with the syndrome of idiopathic steroid responsive chronic lymphocytic meningitis.

Methods: Review of patients' records and examination of surviving patients 1.5 to 17.5 years (median 8.8 years) after presentation.

Results: The cause of the steroid responsive chronic meningitis was found during follow up in two of the 17 patients: Wegener's granulomatosis and multiple sclerosis in one patient each. A cause was not found in the other 15 patients. Seven of these patients eventually recovered and corticosteroids were withdrawn after six weeks to six years without a recurrence of symptoms. Four patients improved transiently, but died six months to 26 years after starting treatment; in two, steroids were withdrawn a few weeks before death. Four patients had active chronic meningitis and reduction in the dose of corticosteroids was associated with a recurrence of symptoms. Leptomeningeal and brain biopsy in eight patients showed non‐specific abnormalities which were not helpful in the diagnosis.

Conclusions: A subgroup of patients with idiopathic chronic lymphocytic meningitis responds to corticosteroids. Leptomeningeal biopsy and long term follow up seldom identify the underlying cause in these patients. Steroid treatment must be undertaken with caution, even after infective causes of chronic meningitis have been excluded.
The causes of sporadic and ‘senile’ chorea
Authors: Warren J. D. , Firgaira F. , Thompson E. M. , Kneebone C. S. , Blumbergs P. C. , Thompson P. D.
Published: March 2008

Background: Although ‘senile’ chorea is commonly listed in the differential diagnosis of chorea, the condition is poorly defined. Indeed, the existence of such an entity is debated. There are few contemporary prospective studies of sporadic chorea in the elderly.

Methods: Detailed prospective study of patients presenting with undiagnosed chorea over a three year period to a Movement Disorder Clinic.

Results: Twelve patients, aged 50 to 89 years, were identified. The final diagnoses were Huntington's disease, confirmed on genetic testing in six, antiphospholipid antibody syndrome in two, and hypocalcaemia, tardive dyskinaesia and basal ganglia calcification in each of the three remaining cases. Only one patient remained undiagnosed despite extensive investigation.

Conclusions: The majority of patients with ‘senile’ chorea actually have Huntington's disease even in the absence of a family history. Rarer causes of chorea still need to be considered in the elderly when Huntington's disease has been excluded by DNA analysis.
Smoking habits and cessation programme in an Australian teaching hospital
Authors: Jones T. E. , Crocker H. , Ruffin R. E.
Published: March 2008

Background: Data on prevalence of cigarette smoking by hospital employees are limited in Australia, but anecdotal evidence suggests that many health sector employees continue to smoke despite abundant evidence regarding the harmful effects of this habit. Nicotine is an addictive drug and arguably this should be known better in the health industry than in any other industry. Despite having this knowledge at their disposal, health sector employers rarely provide assistance to employees, relying instead on restrictive policies to reduce smoking in the workplace.

Methods: To assist employees to quit smoking, we instituted a medium intensity Stop Smoking Programme, run by a clinical pharmacist offering nicotine patches and support on a weekly basis. A principal aim of the service was to redress the imbalance between the availability of cigarettes and the most effective nicotine replacement therapy, the trandermal nicotine patch. Following 18 months operation of this service, we surveyed hospital employees to ascertain smoking rates and views on smoking cessation in this South Australian teaching hospital.

Results: In the first 18 months of operation, 111 staff members availed themselves of the service. At the first follow up period (three months), 21 were not contactable, 29 were successful in not smoking and 61 were still smoking. Six of the 29 who were not smoking at three months resumed smoking by six months, and a further four resumed smoking by 12 months. At the time of this report, 12 of the remaining 19 non smokers had completed two years since quitting and a further three of these had resumed regular smoking by this time. The cost of providing the service was modest at approximately $180.00 per known successful quitter. Results from the survey showed that 12.4% of hospital employees were regular smokers. Smoking prevalence was not equally distributed with female employees being twice as likely to smoke as their male counterparts and employees in the catering department having the highest smoking prevalence (23.8%).

Conclusions: Although the prevalence of cigarette smoking by employees of this teaching hospital is lower than for the general community, health sector employers can reduce smoking prevalence further by providing assistance to their employees to quit smoking. The Stop Smoking Programme we describe is effective and could be replicated by other hospitals and similar organisations.
Mycobacterial lymphadenitis in eastern Sydney
Authors: Wark P. , Goldberg H. , Ferson M. , Mckenzie D. , Lau E. , Rivas K.
Published: March 2008

Background: There has been a resurgence of tuberculosis (TB) in the developed world, especially extrapulmonary manifestations, of which lymphadenitis is the most common. We reviewed all cases of mycobacterial lymphadenitis notified in the eastern suburbs of Sydney from 1989 to 1996.

Aims: To review all cases of mycobacterial adenitis in eastern Sydney.

Methods: This was a retrospective review of the medical records of 54 patients (aged 1.2 to 84 years), recruited from all notifications of TB presenting as lymphadenitis at Prince of Wales, Sydney Children's and St Vincent's Hospitals.

Results: There were two distinct groups: Group 1, patients with Mycobacterium tuberculosis (MTB), n=37 (68.5%), Group 2, patients with atypical mycobacteria, n=17 (31.5%). For Group 1, 83.3% were foreign born and 18.9% were positive for the human immunodeficiency virus (HIV). Disease involved single node groups in 73% (the cervical chain was involved in 70.1%). Complete resolution of lymphadenopathy at conclusion of treatment occurred in 73.1%. Outcome was not documented in 13.5%, of the rest; 83.8% completed treatment; 2.7% were lost to follow up before treatment concluded; 2.7% were still being seen at the time of writing and 10.8% died within six months of treatment starting (all were HIV positive). HIV positive patients had more diffuse disease. Group 2 were all Australian born. They comprised children less than six years who were all HIV negative and adults (aged 30–55 years) who were all HIV positive. The children were all treated surgically with 80% having complete resolution of their modes. Those adults with HIV had a mortality of 83.3% during treatment.

Conclusions: In eastern Sydney lymphadenitis caused by MTB in the HIV negative population is mostly seen in those who are immigrants. Our large proportion of HIV positive patients tended to have diffuse disease and a high mortality. The reporting of outcomes was poor and in a greater than expected number of outcome and follow up were inadequately documented.
The corrected TIMI frame count. The new gold standard?
Authors: French John K. , Ellis Christopher J. , White Harvey D.
Published: March 2008

Over the last decade Thrombolysis in Myocardial Infarction (TIMI) flow grades have been the gold standard for the assessment of efficacy of infarct‐artery reperfusion. However, with the introduction of core angiographic laboratories, the reproducibility of TIMI flow grades has been questioned. The corrected TIMI frame count (CTFC) has been developed as a more reproducible method of quantifying infarct artery blood flow after myocardial infarction (MI). We have utilised the CTFC in two studies to examine infarct‐artery blood flow.

In the Hirulog in Early Reperfusion and Occlusion (HERO 1) study, the CTFC was measured at 90–120 minutes after administration of aspirin, streptokinase and either Hirulog or heparin. Only 27% of patients had a normal CTFC (≥27) in the infarct‐related artery. Patients with a prolonged CTFC (>27) had more abnormal left ventricular function (LVF) as measured by the mean chord score in the ‘area at risk’ (‐2.51 vs ‐2.06, p=0.02), on left ventriculography.

In a second study, infarct‐artery flow was examined four weeks and one year after MI. At four weeks, only 43% of patients with patent infarct‐related arteries had a ‘normal’ CTFC of ≥27. A prolonged CTFC at four weeks was a univariate predictor of increased reocclusion at one year (p=0.001).

CTFCs are frequently abnormal in patent infarct‐related arteries, and predict reocclusion. Whether frame counting is a better predictor of late clinical outcomes than the TIMI flow grade needs to be prospectively examined in large clinical trials.
Pregnancy outcome in systemic lupus erythematosus (SLE): a review of 54 cases
Authors: Johns K. R. , Morand E. F. , Littlejohn G. O.
Published: March 2008

Aim: To compare the pregnancy outcome, in particular gestational age and birth weight in women with systemic lupus erythematosus (SLE) diagnosed before and after pregnancy, and to review data on presence or absence of the antiphospholipid (aPL) antibody and flares of disease activity.

Method: Case histories were reviewed of women with a diagnosis of SLE and an obstetric event attending Monash Medical Centre (MMC) over an eight year period (1988–96). Fifty‐four pregnancies in 28 women were studied, with 44 occurring after the diagnosis of SLE (Group 1) and ten prior to the diagnosis of SLE (Group 2).

Results: In Group 1 there were 25 live births (63%) with 16 full term and nine premature deliveries, 12 spontaneous abortions, three foetal deaths in utero and four elective terminations. In Group 2 there were seven live births (70%), two spontaneous abortions and one foetal death in utero. The mean gestational age of live births was 35.8 weeks and 39.2 weeks respectively (p<0.001). The mean birth weight of live births was 2448 g and 3030 g respectively (p=0.023). a PL antibodies were positive in eight of 26 women tested with three live births and were negative in 18 of 26 women with 12 live births. Flares of disease activity occurred in 17 of 28 pregnancies.

Conclusion: Pregnancy in women with a predisposition to SLE have a high risk of an adverse outcome. Clinical disease confers an additional risk. The mean gestational age and birth weight were significantly less in women with established disease. Mild flares in disease activity resulted in a favourable outcome while renal flares had a worse outcome.
The economic cost of asthma in Singapore
Authors: Chew F‐T. , Goh D. Y‐T. , Lee B‐W.
Published: March 2008

Background: Asthma is a common chronic disorder. In Singapore, it is estimated that 140,000 individuals have current asthma and more than 100 individuals die of this disease annually.

Objective: This study estimates the economic cost of asthma, both direct and indirect, to the patient and community.

Method: Direct cost estimates were based on all levels of medical care, which included inpatient care, emergency room visits, specialist outpatient and primary healthcare, and medication costs. Indirect costs were estimated from cost of time lost by patients and their families attending to medical needs and the loss of productivity due to absenteeism. These estimates were calculated to the 1992/93 US dollar.

Results: The total cost of asthma in Singapore was estimated to be US$33.93 million per annum. This was made up of US$17.22 million in direct costs and US$16.71 million in indirect costs. Inpatient hospitalisation accounted for the largest proportion of direct medical expenditure, approximately US$8.55 million. The loss of productivity from acute asthma accounted for the largest proportion of the indirect costs at US$12.70 million. The cost estimates did not include premature death due to disease. These estimates represent approximately US$238 per asthmatic person per year or US$11.90 per person per year.

Conclusion: This study shows that the economic cost of asthma is also considerable in populations outside the Western hemisphere, and justifies the need for a concerted effort to reduce asthma morbidity worldwide.
Influence of angiotensin converting enzyme (ACE) genotype on interpretation of diagnostic tests for serum ACE activity
Authors: Stokes G. S. , Monaghan J. C. , Schrader A. P. , Glenn C. L. , Ryan M. , Morris B. J.
Published: March 2008

Background: The discovery that an insertion/deletion (I/D) polymorphism of the angiotensin converting enzyme (ACE) gene influences the circulating concentration of ACE may have implications for the proper use of serum ACE activity measurements in screening for sarcoidosis.

Aim: To determine whether the sensitivity of the serum ACE test improves if ACE genotype is taken into account.

Methods: A retrospective determination of ACE genotype and clinical diagnosis was done in 54 patients with serum ACE activity above the upper limit of the reference range for the insertion (II) genotype. ACE was measured by radioenzymatic and spectrophotometric techniques, and genotype by PCR.

Results: When serum ACE values determined diagnostically were related to the appropriate genotype‐specific reference range, sensitivity and specificity for diagnosis of sarcoidosis were 65–70% and 58% respectively, compared to 47–57% and 77% with a reference range unsegregated for genotype.

Conclusion: ACE genotyping may be helpful in determining the diagnostic significance of mildly elevated serum ACE activity in patients with the II and ID genotypes.
Large animal models of heart failure
Authors: Power J. M. , Tonkin A. M.
Published: March 2008

Congestive heart failure (HF) is a major focus of medical research. Its incidence has greatly increased in recent decades because of an aging population base and the increasingly successful treatment of other forms of chronic cardiac disease. Relevant large animal models of HF should reflect the complex interactions of cardiac dysfunction, neurohumoral dynamics and peripheral vascular abnormalities found in human HF. A number of large animal models have been developed, especially in dogs, sheep and swine, using naturally occurring HF, or single or combinations of interventions, as instruments to trigger the development of HF.

Naturally occurring HF models are not commonly used because of ethical or perceived ethical grounds, however, King Charles Cavalier Spaniel and Yucatan Mini Pig models have been described. Tachycardia induced HF is the most commonly used HF model. Ventricular pacing at 220–240 bpm results in profound low output, biventricular, oedematous failure in two to three weeks. Lower pacing rates result in a more stable, sustainable, lesser degree of failure. Positive features of this model include ‘acceptance’, aetiological relevance to patient tachycardia induced HF, neurohumoral and functional profile similar to most human HF, relatively low cost simple preparation, ability to manipulate the degree of failure with pacing rate, reversibility, reliability and a large amount of published multi species data. Limitations to the use of the model are the rapid onset, the fact that reversibility is only relevant to the tachycardia induced patient HF, the absence of hypertrophy in failure, the diminished plasma atrial natriuretic peptide (ANP) levels, absence of ANP of ventricular origin, and the interference between rapid pacing and therapeutic interventions. Myocardial damage models of HF include those models induced by ischaemia, eg due to coronary occlusion (ligation or aneroid) or intracoronary microembolism, transmyocardial DC shock, toxic cardiomyopathy from adriamycin, doxorubicin or catecholamines. Overload models of HF may be induced by high pressure from aortic constriction, aortic regurgitation, renal artery constriction, pulmonary stenosis or aortocaval shunts, or by induction of mitral regurgitation from chordae or leaflet damage.

No single, all‐encompassing, large animal model of HF exists to date. Selection of the type of model to be used should be based primarily on the hypotheses to be tested and secondarily on the available resources and facilities.
Animal models of heart failure
Authors: Arnolda L. F. , Llewellyn‐Smith I. J. , Minson J. B.
Published: March 2008

Animal models of heart failure present homogenous groups of animals all with heart failure produced by a well defined lesion at a particular stage of evolution, in contrast to humans, who present with heart failure of uncertain duration from a wide variety of causes and with marked variation in age and pre‐morbid health and fitness. Animal models of heart failure provide diseased groups of animals in which experimental procedures, not possible in humans, can be evaluated and in which new treatments can be tested before their safety is established in humans. An ideal model should have a common human counterpart and should closely mimic heart failure in humans. Thus the haemodynamic changes should include increased cardiac filling pressures and low cardiac output. There should be evidence of activation of the sympathetic nervous system and increased secretion of hormones such os renin, angiotensin, aldosterone, vasopressin, atrial natriuretic factor and endothelin. The clinical features of the human syndrome such as cardiomegaly, lung and peripheral oedema and decreased exercise tolerance should be present. Lastly, the model should be inexpensive and technically simple to produce and study.

This paper reviews some commonly used models of heart failure in relation to the criteria listed above. There is no perfect animal model of heart failure and in practice one should match the model to the purpose of the study.
Walking with its training effects on the fitness and activity patterns of 79–91 year old females
Authors: Hamdorf P. A. , Penhall R. K.
Published: March 2008

Background: Information is lacking about the physiological and psychosocial effects of exercise among very old persons.

Aim: To investigate the effect of a twice‐weekly, six‐month progressive walking programme on 38 healthy women in their ninth decade, for evidence of the benefits of exercise.

Methods: Aerobic fitness, blood pressure, skinfold thickness and habitual activity patterns were studied in a randomised controlled trial. Women were chosen, as this is a group of increasing demographic importance for which studies are lacking.

Results: The training group and control group were not significantly different at baseline. However, after six months of progressive exercise the training group showed lower resting (p<0.05) and working (p<0.005) heart rates compared with non‐exercising controls. ANCOVA analyses indicated higher scores for the training group compared with the control group for Maximum Current Activity and Normative Impairment Index (both p<0.001), which are both components of the Habitual Activity Profile. Morale also significantly improved within the training group (p<0.01).

Conclusions: These data show the trainability of very old women and the positive impact a low frequency, progressive exercise programme can have on cardiorespiratory fitness and daily living activity patterns. Such improvements are likely to be indicative of an enhanced outlook for independence.
Efficacy, safety and tolerability of anagrelide in the treatment of essential thrombocythaemia
Authors: Mills A. K. , Taylor K. M. , Wright S. J. , Bunce I. , Eliadis P. , Brigden M. C. , Seeley G. , Bashford J. , Olsen T. , Rentoul A. , Kelly C.
Published: March 2008

Background: Essential thrombocythaemia (ET) has an associated risk of thrombotic and haemorrhagic complications, which can be minimised by control of the platelet count. Anagrelide selectively lowers the platelet count, however, there is little Australasian experience with its use and scant data on symptom control.

Aims: To evaluate the efficacy of anagrelide for platelet reduction and symptom control in a broad cohort of patients with well‐defined ET, and to determine the safety and tolerability in such a population.

Methods: Seventeen patients with ET and a platelet count >600X109/L were prospectively enrolled. The evaluable four males and 12 females with a median age of 58 years (range 14–79) included ten patients (63%) previously treated with two or more agents and 12 patients (75%) who had failed other therapies. The median follow‐up was seven months (range 15 days to 36 months).

Results: Anagrelide, in an average dose of 1.9 mg/day, reduced the platelet count from a mean of 728X109/L (95% CI 611‐845X109/L) to 412X109/L (95% CI 319‐504X109/L) (p<0.001) and maintained it at this level. Fourteen patients (88%) had a platelet reduction to <600X109/L. All symptomatic patients had improvement in symptoms attributable to thrombocythaemia. There were three haemorrhagic and three thrombotic episodes in a total of three patients (19%), including one death from an intracerebral haemorrhage. Six patients (37%) were removed from therapy due to toxicity after a median of 151 days. Side effects included palpitations, abdominal pain and cough.

Conclusions: Anagrelide is efficacious and safe in ET, both for platelet and symptom control. Minor side effects are common, however, tend to occur early and resolve spontaneously in most cases.
Familial risk estimation in systemic sclerosis
Authors: Englert H. , Small‐McMahon J. , Chambers P. , O'Connor H. , Davis K. , Manolios N. , White R. , Dracos G. , Brooks P.
Published: March 2008

Background: Familial systemic sclerosis has been rarely reported. Assumptions have therefore been made implying no familial disease aggregation. This study critically challenges the assumption using a methodical population‐based epidemiological approach to quantify the prevalence and characteristics of familial systemic sclerosis.

Methods: In this retrospective cohort study the systemic sclerosis prevalence in first degree family members was compared between 715 systemic sclerosis patients (710 families) and 371 randomly ascertained age and gender group‐matched general practice controls (371 families). These data, obtained by telephone questionnaire (living patients) or medical records review (deceased patients and untraceable patients of unknown living status), were validated, where necessary, and expressed in terms of relative risk, absolute risk and population point prevalence.

Results: Systemic sclerosis affecting first degree members was validated in ten of 710 families. Reporting of systemic disease in another four more distant family members, and the co‐occurrence of systemic and localised disease in three families was also documented.

Observed and expected disease subtype concordance was 80% (44–97%) and 68% respectively and the female predominance among familial cases was similar to that for non‐familial disease. The risk of disease in a subsequent first degree relative was compared to the risk in an initial first degree family member. Its estimated magnitude was wide (11–158). However, use of population prevalence data to determine the expected number of systemic sclerosis patients in the negative cohorts' families suggests the higher estimate is more realistic. Despite the high magnitude, the absolute disease risk in first degree family members remained low – approximating 1%. The population prevalence of familial systemic sclerosis approximated 1.4/million.

Conclusions: This study substantially increases the otherwise small list of documented instances of familial systemic sclerosis. More importantly, it quantifies the risk for the first time, ranking it as the disease's most powerful determinant identified to date.