Drug-Eluting Balloons-A New Tool in the Treatment of Cardiac Allograft Vasculopathy: A Case Series.

Percutaneous coronary intervention in patients with cardiac allograft vasculopathy is burdened with a lot of difficulties. Although they have allowed significant progress in comparison with plain balloon angioplasty and bare metal stents, drug-eluting stents have not fully overcome problems of diffuse lesions and small-vessel disease that are so common in transplant coronary artery disease. There is growing evidence that drug-eluting balloons might be a better choice for patients with small vessel atherosclerotic coronary disease and yet there is no experience with this technology in patients with cardiac allograft vasculopathy. Herein we report a case series of successful percutaneous coronary interventions in patients with cardiac allograft vasculopathy.

Incidental extraction of a temporary epicardial pacemaker wire with right ventricular perforation during endomyocardial biopsy: a case report.

INTRODUCTION: Right ventricular perforation during endomyocardial biopsy is an unusual, although potentially life-threatening, complication caused with the tip of the bioptome. The majority of perforations in heart transplant patients can be managed without surgery owing to adhesions nearly obliterating pericardial space. CASE REPORT: We report a case of heart transplant patient who suffered right ventricular perforation as a consequence of incidental extraction of a temporary epicardial pacemaker wire during a routine endomyocardial biopsy sampling. CONCLUSIONS: The patient suffered no clinical consequences.

The exclusion of high trauma fractures may underestimate the prevalence of bone fragility fractures in the community: the Geelong Osteoporosis Study.

Fractures associated with severe trauma are generally excluded from estimates of the prevalence of osteoporotic fractures in the community. Because the degree of trauma is difficult to quantitate, low bone mass may contribute to fractures following severe trauma. We ascertained all fractures in a defined population and compared the bone mineral density (BMD) of women who sustained fractures in either "low" or "high" trauma events with the BMD of a random sample of women from the same population. BMD was measured by dual-energy X-ray absorptiometry and expressed as a standardized deviation (Z score) adjusted for age. The BMD Z scores (mean +/- SEM) were reduced in both the low and high trauma groups, respectively: spine-posterior-anterior (-0.50 +/- 0.05 and -0.21 +/- 0.08), spine-lateral (-0.28 +/- 0.06 and -0.19 +/- 0.10), femoral neck (-0.42 +/- 0.04 and -0.26 +/- 0.09), Ward's triangle (-0.44 +/- 0.04 and -0.28 +/- 0.08), trochanter (-0.44 +/- 0.05 and -0.32 +/- 0.08), total body (-0.46 +/- 0.06 and -0.32 +/- 0.08), ultradistal radius (-0.47 +/- 0.05 and -0.42 +/- 0.07), and midradius (-0.52 +/- 0.06 and -0.33 +/- 0.09). Except at the PA spine, the deficits were no smaller in the high trauma group. Compared with the population, the age-adjusted odds ratio for osteoporosis (t-score < -2.5) at one or more scanning sites was 3.1 (95% confidence interval 1.9, 5.0) in the high trauma group and 2.7 (1.9, 3.8) in the low trauma group. The data suggest that the exclusion of high trauma fractures in women over 50 years of age may result in underestimation of the contribution of osteoporosis to fractures in the community. Bone density measurement of women over 50 years of age who sustain fractures may be warranted irrespective of the classification of trauma.

The effect of big endothelin-1 in the proximal tubule of the rat kidney.

1. An obligatory step in the biosynthesis of endothelin-1 (ET-1) is the conversion of its inactive precursor, big ET-1, into the mature form by the action of specific, phosphoramidon-sensitive, endothelin converting enzyme(s) (ECE). Disparate effects of big ET-1 and ET-1 on renal tubule function suggest that big ET-1 might directly influence renal tubule function. Therefore, the role of the enzymatic conversion of big ET-1 into ET-1 in eliciting the functional response (generation of 1,2-diacylglycerol) to big ET-1 was studied in the rat proximal tubules. 2. In renal cortical slices incubated with big ET-1, pretreatment with phosphoramidon (an ECE inhibitor) reduced tissue immunoreactive ET-1 to a level similar to that of cortical tissue not exposed to big ET-1. This confirms the presence and effectiveness of ECE inhibition by phosphoramidon. 3. In freshly isolated proximal tubule cells, big ET-1 stimulated the generation of 1,2-diacylglycerol (DAG) in a time- and dose-dependent manner. Neither phosphoramidon nor chymostatin, a chymase inhibitor, influenced the generation of DAG evoked by big ET-1. 4. Big ET-1-dependent synthesis of DAG was found in the brush-border membrane. It was unaffected by BQ123, an ETA receptor antagonist, but was blocked by bosentan, an ETA.B-nonselective endothelin receptor antagonist. 5. These results suggest that the proximal tubule is a site for the direct effect of big ET-1 in the rat kidney. The effect of big ET-1 is confined to the brush-border membrane of the proximal tubule, which may be the site of big ET-1 sensitive receptors.

Management of heparin-induced thrombocytopenia with fondaparinux in a patient with left ventricular assist device.

Heparin-induced thrombocytopenia is an immune-mediated serious adverse effect of heparin therapy. It is a relatively frequent complication among patients with mechanical circulatory support. Herein, we present a patient with severe heart failure and sepsis who developed heparin-induced thrombocytopenia shortly after implantation of left ventricular assist device as a bridge to transplantation and who was successfully treated with fondaparinux.

How have we been managing chronic obstructive pulmonary disease in Australia?

AIM: Although chronic obstructive pulmonary disease (COPD) is a main cause of disability, hospital admissions and premature deaths in Australia, little is known about the community management of COPD in relation to recently published guidelines. The aim of the article was to report on COPD management in a community based cohort. METHODS: A random sample of adults aged between 45 and 70 years drawn from the electoral roll participated in the study. They completed a detailed respiratory questionnaire, spirometry, methacholine challenge and measurement of transfer factor. COPD was defined according to the Global initiative for Chronic Obstructive Lung Disease (GOLD) criteria. Current asthma was defined as wheeze during the last 12 months together with bronchial hyperreactivity. Subjects were classified as either COPD-only, asthma-only or both asthma and COPD. RESULTS: Of 1224 subjects completing spirometry, 39 (3.5%) met the GOLD criteria for stage 2 or 3 COPD, asthma-only was found in 99 (8.9%) subjects and 40 (3.6%) subjects had both asthma and COPD. The COPD-only group was significantly older than the other two groups. More than 40% of subjects with COPD did not have a diagnosis of COPD from their doctors. Only 48.7% of subjects with COPD had ever been prescribed medication for their breathing. More than two-thirds of all subjects had seen a doctor for breathing problems, but very few had seen a general practitioner in the last 12 months and even fewer had respiratory function tests. CONCLUSIONS: Most subjects with COPD are being undertreated. Diagnosis, monitoring and referral systems should be improved. Preventive activities such as influenza vaccination and smoking cessation should be intensified.

Different endothelin receptor subtypes are involved in phospholipid signalling in the proximal tubule of rat kidney.

Phospholipid signalling mediated by endothelin (ET) receptor subtypes was studied in the rat proximal tubule. In freshly isolated proximal tubule cells, ET-1, ET-2 and sarafotoxin S6c (S6c) evoked an increase in 1,2-diacylglycerol (DAG), inositol 1,4,5-trisphosphate (InsP3) and phosphocholine (PCho), suggesting stimulation of both phosphatidyl-inositol 4,5-bisphosphate- and phosphatidyl-choline-specific phospholipase C (PLC), while ET-3 increased only DAG and PCho, presumably via phosphatidyl-choline-dependent PLC. Renal cortical slices were also stimulated by the above-mentioned agonists, followed by isolation of either brush border (BBM) or basolateral (BLM) membranes for which mass measurements of inositol lipids and DAG were performed. In BBM, DAG increased in response to ET-1, ET-2 and ET-3, and was followed by protein kinase C (PKC) translocation to the BBM, while in BLM, DAG formation and translocation of PKC were observed only in response to ET-3, suggesting spatial segregation of signalling systems between two membane domains of proximal tubule cells. Tyrphostine, pertussis toxin (PTX) or cholera toxin (CTX) did not influence ET-mediated signalling in either of the membranes, suggesting involvement of PTX- and CTX-insensitive G-protein-mediated stimulation of PLCbeta by ET receptors. ET-dependent stimulation of PLC in BBM and BLM was used as a tool to examine the presence of different ET receptor subtypes in these two cell membrane domains. BQ123, an inhibitor of ETA receptors, did not prevent ET-1-mediated signalling in BBM, but an ETA,B antagonist, bosentan, inhibited ET-3-mediated signalling in BBM. In addition, an ETB agonist, S6c, stimulated PLC in BBM. Neither BQ123 nor bosentan inhibited ET-3 signalling in BLM. Therefore, these data strongly suggest the presence of ETB receptors coupled to phosphatidyl-inositol 4,5-bisphosphate- and phosphatidyl-choline-dependent PLC in BBM and ETC receptors linked to phosphatidyl-choline-dependent PLC in BLM.

European Community Respiratory Health Survey calibration project of dosimeter driving pressures.

Two potential sources of systematic variation in output from Mefar dosimeters, the system used in the European Community Respiratory Health Survey (ECRHS) study have been evaluated: individual nebulizer characteristics and dosimeter driving pressure. Output variation from 366 new nebulizers produced in two batches for the second ECRHS were evaluated, using a solute tracer method, at a fixed driving pressure. The relationship between dosimeter driving pressure was then characterized and between-centre variation in dosimeter driving pressure was evaluated in an Internet-based survey. A systematic difference between nebulizers manufactured in the two batches was identified. Batch one had a mean+/-SD output of 7.0+/-0.8 mg x s(-1) and batch two, 6.3+/-0.7 mg x s(-1) (p<0.005). There was a wide range of driving pressures generated by Mefar dosimeters as set, ranging between 70-245 kPa, with most outside the quoted manufacturer's specification of 180+/-5%. Nebulizer output was confirmed as linearly related to dosimeter driving pressure (coefficient of determination (R2)=0.99, output=0.0377 x driving pressure-0.4151). The range in driving pressures observed was estimated as consistent with a variation of about one doubling in the provocative dose causing a 20% fall in forced expiratory volume in one second. Systematic variation has been identified that constitutes potentially significant confounders for between-centre comparisons of airway responsiveness in the European Community Respiratory Health Survey, with the dosimeter driving pressure representing the most serious issue. This work confirms the need for appropriate quality control of both nebulizer output and dosimeter driving pressure, in laboratories undertaking field measurements of airway responsiveness. In particular, appropriate data on driving pressures need to be collected and factored into between-centre comparisons. Comprehensive collection of such data to optimize quality control is practicable and has been instigated by the organizing committee for the European Community Respiratory Health Survey II.

Age- and gender-specific rate of fractures in Australia: a population-based study.

There is little population-based data concerning fracture rates in Australia. We ascertained all fractures occurring during 2 years in adults aged 35 years and over residing within a defined region (population 218 000), representative of the Australian population. The major strength of this study is the comprehensive ascertainment of fractures, which was ensured by regular searches of the only two radiologic providers in the Geelong Osteoporosis Study region. Nevertheless, vertebral fractures are likely to be underestimated since our ascertainment relied on a clinical indication for a medical imaging procedure. Among those aged 35-55 years, the fracture rate (persons per 10,000/year) in men was about double the rate in women (65 vs 35). The fracture rate was almost 7 times higher in women over 60 years versus women less than 55 years of age. In contrast, the fracture rate in men over 60 years was only 50% higher than in men less than 55 years of age (72 vs 104). Fracture rates in women and men were highest at the hip (28 and 10 respectively), spine (21 and 7), distal forearm (Colles') (18 and 4) and humerus (11 and 3), and were 3-4 times higher in women than men. These fractures accounted for 63% of all fractures in women and 32% in men. By contrast, the rate of lower leg and ankle fractures was less than 10 per 10,000 in both women and men and did not increase to the same extent with age. Hip fracture rates appear high, particularly among the older age strata, compared with retrospective ascertainment in other populations. In Australia, as in many other countries, there is an increasing longevity of the population. The number of women aged 90 years and over increased by 32% and the number of men of this age increased by 48% in the 5 years between the Australian national census of 1991 and 1996. Given stable fracture rates, the substantial health burden imposed by age-related fractures, particularly hip fractures, will continue to escalate in both women and men.