Mylotarg has potent anti-leukaemic effect: a systematic review and meta-analysis of anti-CD33 antibody treatment in acute myeloid leukaemia.

Conventional chemotherapy is ineffective in the majority of patients with acute myeloid leukaemia (AML), and monoclonal antibodies recognising CD33 expressed on myeloid progenitors (e.g. gemtuzumab ozogamicin (GO)) have been reported to improve outcome in patients with AML. Reports of excess toxicity have resulted in GO's licence being withdrawn. As a result, the role of these agents remains unclear. A systematic review and meta-analysis included studies of patients with AML who had entered a randomised control trial (RCT), where one arm included anti-CD33 antibody therapy. Fixed effect meta-analysis was used, involving calculation of observed minus expected number of events, and variance for each endpoint in each trial, with the overall treatment effect expressed as Peto's odds ratio with 95 % confidence interval. Meta-analysis of 11 RCTs with 13 randomisations involving GO was undertaken. Although GO increased induction deaths (p = 0.02), it led to a reduction in resistant disease (p = 0.0009); hence, there was no improvement in complete remission. Whilst GO improved relapse-free survival (hazard ratio (HR) = 0.90, 95 % confidence interval (CI) = 0.84-0.98, p = 0.01), there was no overall benefit of GO in overall survival (OS) (HR = 0.96, 95 % CI = 0.90-1.02, p = 0.2). GO improved OS in patients with favourable cytogenetics, with no evidence of benefit in patients with intermediate or adverse cytogenetics (test for heterogeneity between subtotals p = 0.01). GO has a potent clinically detectable anti-leukaemic effect. Further trials to investigate its optimum delivery and identification of patient populations who may benefit are needed.

Type 2 diabetes mellitus and obesity in young adults: the extreme phenotype with early cardiovascular dysfunction.

AIM: A pilot study to phenotype young adults (< 40 years) with Type 2 diabetes mellitus. METHODS: Twenty people with Type 2 diabetes (aged 18-40 years), 10 lean and 10 obese control subjects underwent detailed assessment, including tagged cardiac magnetic resonance imaging, inflammatory proteins, lipids, vitamin D and maximal oxygen uptake. Outcomes were compared between the group with Type 2 diabetes and the control group. RESULTS: Mean (standard deviation) age, Type 2 diabetes duration and BMI in the group with Type 2 diabetes were 31.8 (6.6) years, 4.7 (4.0) years and 33.9 (5.8) kg/m(2) respectively. Compared with lean control subjects, those with Type 2 diabetes had more deleterious profiles of hyperlipidaemia, vitamin D deficiency, inflammation and maximal oxygen uptake relative to body mass. However, there was no difference between the group with Type 2 diabetes and the obese control group. The group with Type 2 diabetes had a higher left ventricular mass and a trend towards concentric remodelling compared with the lean control group (P = 0.002, P = 0.052) but not the obese control group (P > 0.05). Peak early diastolic strain rate was reduced in the group with Type 2 diabetes [1.51 (0.24)/s] compared with the lean control [1.97 (0.34)/s, P = 0.001] and obese control [1.78 (0.39)/s, P = 0.042] group. CONCLUSIONS: Young adults with Type 2 diabetes and those with obesity have similar adverse cardiovascular risk profiles, higher left ventricular mass and a trend towards left ventricular concentric remodelling. In addition, those with Type 2 diabetes demonstrate diastolic dysfunction, a known risk marker for future heart failure and mortality.

Successful surgical treatment of Q fever endocarditis with mitral valve repair.

We report a case of successful surgical treatment of Q fever endocarditis with mitral valve repair in a 66-year old retired British soldier. Valve replacement is invariably undertaken in Q fever endocarditis due to the degree of valvular damage and concerns about eradicating the organism, Coxiella burnetii. Our unique case allowed valve repair since pre-existing myxomatous degeneration and subsequent posterior mitral valve leaflet prolapse resulted in significant excess valve tissue, allowing quadrangular resection of the damaged and perforated P2 portion of this leaflet. Follow-up at four years (including three years of antibiotic treatment) has confirmed excellent valve repair, with no echocardiographic, clinical or microbiological evidence of recurrence. We are only the second group to describe valve repair in a patient with chronic Q fever endocarditis. Valve repair is preferable to valve replacement for Q fever endocarditis, if technically possible.

Paradoxical coronary artery embolism causing acute myocardial infarction in a young woman with factor V Leiden thrombophillia.

Paradoxical coronary artery embolism is a rare but under-diagnosed cause of acute myocardial infarction (AMI) and requires a high level of clinical suspicion to make an early diagnosis. We describe the case of a young woman who presented with a severe cough and chest pain who was subsequently found to have a paradoxical embolus in the right coronary artery. Echocardiography showed a patent foramen ovale (PFO) and an atrial septal aneurysm (ASA). The patient was found to be a heterozygous carrier of the factor V Leiden mutation that increases the risk for venous-thromboembolism. The association between a PFO and an ASA is a risk factor for systemic embolisation. This is the first reported case of paradoxical coronary artery embolus causing AMI in a non-pregnant patient with factor Leiden thrombophilia. Identification of this clinical phenotype is vital as the risk of future embolic events can be reduced by anticoagulation and closure of anatomical cardiac defects.

The impact of therapeutic doses of paracetamol on serum total antioxidant capacity.

INTRODUCTION: A link between regular paracetamol intake and asthma in adults has recently been postulated. Detoxification of paracetamol may deplete stores of glutathione, which is one of the major antioxidants present in the lung. A reduced source of glutathione in the lung may lead to increased oxidative damage to the epithelium and hence increased frequency and severity of asthma attacks in susceptible individuals. AIM OF STUDY: This study aimed to determine whether regular intake of maximum therapeutic doses of paracetamol reduced serum antioxidant capacity in healthy volunteers. METHODS: Fifteen young healthy volunteers (nine men, six women, mean age 21.3 years, range 19-32) took maximum therapeutic doses of paracetamol (1 g four times a day) for 14 days. On days 0 and 14 blood samples were taken at baseline and hourly for a period of 4 h following ingestion of 1 g paracetamol. Single venous blood samples were collected 1 h after ingestion of 1 g paracetamol on days 4, 7 and 10. Blood samples were analysed for serum paracetamol concentration and total antioxidant capacity. RESULTS: Mean total antioxidant capacity was significantly reduced over the 3-h post-dosing on both days 0 and 14 (P < 0.01). The results from days 4, 7 and 10 showed a trend towards reduced antioxidant activity over time. On day 14 values were consistently lower compared with the corresponding times on day 0 (P < 0.01 at 0, 1, 3 and 4 h, P < 0.05 at 2 h). CONCLUSIONS: Chronic ingestion of maximum therapeutic doses of paracetamol depletes serum antioxidant capacity in healthy volunteers in as few as 14 days, possibly by a reduction in glutathione. This may have implications for analgesic use in asthmatic individuals. Further studies are now required to assess the impact of paracetamol on antioxidant defences in the lung.