Pseudotumours in haemophilia: non‐adherence,under‐reporting bleeds or bad luck?

Pseudotumours are a rare, severe complication of haemophilia which can occur in a spectrum of bones and soft tissues. It consists of an encapsulated blood collection, and as the swelling increases causes compression and eventual slow destruction of surrounding structures. Presented here are two cases of patients with haemophilia and pseudotumours, which demonstrate the heterogeneity of presenting symptoms and of treatment options.     

Advances in hepatitis C: What is coming in the next 5 years?

Hepatitis C virus (HCV) is a leading cause of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. Numerous advances have been made in the understanding of HCV replication, including detailed molecular characterization of its viral proteins and genomic RNA. The inability to grow HCV in cell culture had impeded the development of antiviral agents against this virus. To overcome this obstacle, a number of unique tools have been prepared, such as molecular clones that are infectious in the chimpanzee animal model of infection, and the development of a subgenomic replicon system in Huh7 cells. In addition, the major non-structural proteins have been crystallized, thus enabling rational drug design directed to these targets. Current developments in antiviral agents are reviewed in the context of these potential new viral targets for the future treatment of HCV in chronically infected individuals.     

Heroin‐Related Deaths in Sydney,Australia. How Common Are They?

The objective of this article was to determine the number of recent deaths caused by accidental illicit drug overdoses seen at the NSW Institute of Forensic Medicine, Glebe (Sydney). All Forensic cases (3559) were reviewed during the period July 1995-February 1997. Any that were classified as accidental illicit drug overdose were followed up, and demographic and toxicological data were collected for analysis. Our results found that one hundred and forty three accidental illicit drug overdoses were identified from 3359 autopsies during the 20 month data collection period (4%). Male to female ratio was 5:1, but females predominated in the methadone toxicity group. Most of the cases were under 40 years of age. Toxicological results showed that 80% of the deaths were associated with morphine (heroin) levels in the toxic range, although 91% had morphine present at some level. Only 35% of cases had significant levels of bile morphine, suggesting "chronic" usage. In many cases, multiple illicit substances and/or alcohol were thought to be important contributing factors. Cocaine was found in 13% of cases, and all of these had morphine (heroin) in their blood. Methadone was found in 13% of cases, and 13/19 had toxic levels--9/19 also had morphine in their blood. Only two cases had amphetamines or methamphetamines in their blood. The authors conclude that Heroin overdose is by far the most common cause of accidental illicit drug overdose. Those at greatest risk are naive users and those who are not tolerant. There is an urgent need for increased awareness and further education concerning the dangers of heroin use, particularly of multiple drug use (including alcohol). Only about one-third of these cases appear to be "chronic" users.     

Pancreatic β‐cell imaging in humans: fiction or option?

Diabetes mellitus is a growing worldwide epidemic disease, currently affecting 1 in 12 adults. Treatment of disease complications typically consumes ～10% of healthcare budgets in developed societies. Whilst immune‐mediated destruction of insulin‐secreting pancreatic β cells is responsible for Type 1 diabetes, both the loss and dysfunction of these cells underly the more prevalent Type 2 diabetes. The establishment of robust drug development programmes aimed at β‐cell restoration is still hampered by the absence of means to measure β‐cell mass prospectively in vivo, an approach which would provide new opportunities for understanding disease mechanisms and ultimately assigning personalized treatments. In the present review, we describe the progress towards this goal achieved by the Innovative Medicines Initiative in Diabetes, a collaborative public–private consortium supported by the European Commission and by dedicated resources of pharmaceutical companies. We compare several of the available imaging methods and molecular targets and provide suggestions as to the likeliest to lead to tractable approaches. Furthermore, we discuss the simultaneous development of animal models that can be used to measure subtle changes in β‐cell mass, a prerequisite for validating the clinical potential of the different imaging tracers.     

Seafood‐borne parasitic diseases in Australia: are they rare or underdiagnosed?

Australia is a multicultural country surrounded by water where seafood is regularly consumed. Literature suggests that some popular edible fish sold in fish markets may be infected with parasites transmissible to humans (notably, anisakids and other helminths); however the number of reported human cases due to these parasites is low. In this article we critically review topical publications to understand whether the low number of human infection is due to lack of expertise in Australia to identify and diagnose accurately seafood‐borne parasitic infections. The risk these parasites pose to humans may be underestimated due to: (i) errors or inability of diagnosing these infections, primarily due to less sensitive and specific serological tests and misidentifying parasites without a taxonomist in the diagnostic team; and (ii) medical practitioners not being aware of these parasites or not considering them in the differential diagnosis even in patients with history of regular raw or undercooked seafood consumption.     

Thyroid papillary cancers: microcarcinoma and carcinoma,incidental cancers and non‐incidental cancers – are they different diseases?

OBJECTIVE: Tumour size represents a much-debated prognostic factor in papillary cancer, and the necessity to perform a fine-needle aspiration (FNA) on small nodules is a frequent matter of discussion. We compared some prognostic histological features for various sizes of papillary cancers (PCs) and, with regard to these prognostic features, we compared non-incidental with incidental PCs. We also considered the possibility that ultrasonography could detect nodules harbouring the most aggressive cancers. DESIGN AND PATIENTS: We have studied patients with a histological diagnosis of PC from 1999 to 2003. FNA was performed on all nodules > 1.0 cm and on hypoechoic nodules with irregular margins or microcalcification when the size was < 1.0 cm (3321 FNAs in total). We were able to consider several different types of patients: those with PC diagnosed by FNA before surgery; those with large goitre and PC of small size diagnosed after histological examination and in whom a careful examination of the presurgical ultrasonography could show a distinct highly suspicious nodule that was not subjected to FNA, and patients with real incidental PC (that is, those with nodular goitre who correctly underwent FNA on suspicious nodules but in whom thyroid cancer was discovered only at histological examination). We considered two groups of patients with PC. Group 1 PCs were diagnosed before surgery with FNA (128 cases); in this group we also considered the two cases that were not correctly diagnosed before surgery. Group 2 real incidental PCs (12 cases) were found in goitres at histological examination after thyroidectomy for goitre (282 thyroidectomies). Group 1 was divided into three subgroups according to the maximum size of the PC at histological examination: (a) 44 PCs with maximum size < 10 mm, (b) 47 PCs with maximum size between 10 mm and 20 mm, and (c) 39 PCs with maximum size 20 mm. In all subgroups 1 as well as in group 2, the following four histological features were considered separately: multifocality, extracapsular extension, lymph-node involvement and its extent, and special aggressive features (dedifferentiation and/or insular aspects, tall and columnar variants). RESULTS: In subgroups 1a, 1b and 1c the results were, respectively: multifocality 56.8, 57.4 and 51.2%; extracapsular extension 27.2, 23.4 and 46.3% (P = 0.01, subgroups 1a and 1b vs. subgroup 1c); lymph-node metastasis 13.5, 23.3 and 46.1% (P = 0.003 subgroup 1a vs. 1c; P = 0.04, subgroup 1b vs. 1c); special aggressive features 11.3, 25.5 and 28.2% (P = ns). Group 2 showed one case of multifocality (8.3%) in a patient with prior exposure to radiotherapy in childhood, while no case was found of extracapsular invasion or lymph-node involvement, and only one patient had a PC with features of dedifferentiation. CONCLUSIONS: Non-incidental cancer, apart from multifocality, showed a classical progression for all prognostic factors from microcarcinoma to larger cancers. However, real incidental PC seemed to be different from non-incidental PC microcarcinoma regarding the main prognostic features. We conclude that ultrasonography is useful not only in terms of revealing the presence of cancer but also in identifying the most aggressive cancers.     

Low‐grade systolic murmurs in healthy middle‐aged individuals: innocent or clinically significant? A 35‐year follow‐up study of 2014 Norwegian men

Abstract. Bodegard J, Skretteberg PT, Gjesdal K, Pyörälä K, Kjeldsen SE, Liestøl K, Erikssen G, Erikssen J (Oslo University Hospital, Oslo; University of Oslo, Oslo; University of Eastern Finland, Kuopio; University of Oslo, Oslo; Oslo University Hospital, Oslo). Low‐grade systolic murmurs in healthy middle‐aged individuals: innocent or clinically significant? A 35‐year follow‐up study of 2014 Norwegian men. J Intern Med 2012; 271 : 581–588. Objective. To determine whether a low‐grade systolic murmur, found at heart auscultation, in middle‐aged healthy men influences the long‐term risk of aortic valve replacement (AVR) and death from cardiovascular disease (CVD). Setting and subjects. During 1972–1975, 2014 apparently healthy men aged 40–59 years underwent an examination programme including case history, clinical examination, blood tests and a symptom‐limited exercise ECG test. Heart auscultation was performed under standardized conditions, and murmurs were graded on a scale from I to VI. No men were found to have grade V/VI murmurs. Participants were followed for up to 35 years. Results. A total of 1541 men had no systolic murmur; 441 had low‐grade murmurs (grade I/II) and 32 had moderate‐grade murmurs (grade III/IV). Men with low‐grade murmurs had a 4.7‐fold [95% confidence interval (CI) 2.1–11.1] increased age‐adjusted risk of AVR, but no increase in risk of CVD death. Men with moderate‐grade murmurs had an 89.3‐fold (95% CI 39.2–211.2) age‐adjusted risk of AVR and a 1.5‐fold (95% CI 0.8–2.5) age‐adjusted increased risk of CVD death. Conclusions. Low‐grade systolic murmur was detected at heart auscultation in 21.9% of apparently healthy middle‐aged men. Men with low‐grade murmur had an increased risk of AVR, but no increase in risk of CVD death. Only 1.6% of men had moderate‐grade murmur; these men had a very high risk of AVR and a 1.5‐fold albeit non‐significant increase in risk of CVD death.     

Successful treatment of idiopathic recurrent pericarditis in children with interleukin‐1β receptor antagonist (anakinra): An unrecognized autoinflammatory disease?

Recurrent pericarditis occurs in association with various medical conditions, but in most cases the condition appears to be idiopathic. Although high‐dose steroid treatment is often effective, it may have serious side effects. Herein we describe 3 children with recurrent pericarditis who were treated at our hospital, during flares, with the interleukin‐1β receptor antagonist anakinra, with immediate response. Pericarditis recurred when anakinra treatment was discontinued, and no further episodes occurred after it was resumed. Idiopathic recurrent pericarditis shares several features with autoinflammatory diseases, and anakinra has been efficacious in the treatment of the latter diseases. The findings in these patients suggest that idiopathic recurrent pericarditis may be a previously unrecognized autoinflammatory disease.     

Asthma‐specific quality of life questionnaires in children: Are they useful and feasible in routine clinical practice?

This study used well-validated quality of life (QOL) instruments to compare the QOL scores achieved by children aged 7-17 years with the views of their parents of the effects of their child's asthma on family life. Also, a comparison was made between the child's QOL scores and the judgment of the clinician in charge in regard to asthma control.There was poor correlation between the overall scores of the children and the overall caregiver's score (r = 0.19, P = 0.18), and no correlation between the child's score and assessment of control given by the clinician in charge of the case (r = 0.02, P = 0.98).It is important to recognize that there may be little relationship between the concerns of the child regarding his or her asthma, the effects on the family as reported by a parent, and the clinician's view of asthma control. This recognition may significantly affect treatment planning with the family. The administration of the QOL instrument used in this study was straightforward and quite quick, with a mean time to completion of about 8 min.     

Defining overweight and obesity in pre‐school children: IOTF reference or WHO standard?

Two international datasets are used to define overweight and obesity in pre‐school children: the International Obesity Task Force (IOTF) reference and the WHO standard. This study compares the performance of the two datasets in defining overweight and obesity in 24–60 months old children. This was done by plotting the IOTF cut‐offs against WHO curves and by comparing the prevalence of overweight and obesity, as defined by the IOTF reference and by the WHO standard, using 2001 data from the Czech Republic. The IOTF cut‐off for overweight in 24–60 months old children goes from 1.7 to 1.1 z‐scores on the WHO chart, and for obesity it shifts with age from 2.7 to 2.2 z‐scores. As a consequence, at 5 years of age the prevalence of overweight in Czech girls is 3.4% using the WHO and 15.3% using the IOTF definition. These discrepancies are due to the choice of cut‐offs and to the different criteria used to select the sample for the IOTF reference and the WHO standard. Research is urgently needed to identify, for the WHO standard, BMI cut‐offs associated with an increased risk of overweight and obesity, and associated health outcomes later in life.