Uptake of genetic counselling and predictive DNA testing in hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy is a common autosomal dominant disease, associated with heart failure and arrhythmias predisposing to sudden cardiac death. After the detection of the causal mutation in the proband predictive DNA testing of relatives is possible (cascade screening). Prevention of sudden cardiac death in patients with a high risk by means of an implantable cardioverter defibrillator is effective. In 97 hypertrophic cardiomyopathy families with a sarcomere gene mutation we retrospectively determined uptake of genetic counselling and predictive DNA testing in relatives within 1 year after the detection of the causal mutation in the proband. Uptake of genetic counselling was 39% and did not differ significantly by proband's or relative's gender, nor by young age of the relative (< 18 years) or a family history positive for sudden cardiac death. In second-degree relatives, eligible for predictive DNA testing when the first-degree relative had died, uptake was 27.5% (P = 0.047). Uptake of predictive genetic testing was 39%; conditional uptake of predictive genetic testing was 99%. Uptake of genetic counselling in hypertrophic cardiomyopathy is comparable to uptake in oncogenetics. Conditional uptake of predictive DNA testing, however, is much higher. Because sudden cardiac death can be prevented uptake of genetic counselling in hypertrophic cardiomyopathy should be as high as possible. To achieve this research into the determinants of uptake is needed.     

The impact of ischemic lesions in the donor kidney,donor age,recipient age and HLA (A,B, C,DR, DQ) matching on clinical course after kidney grafting

It is generally accepted that HLA matching improves graft survival [1]. However, there is no consensus on whether this improvement is reflected on daily clinical course. Clinical course after renal transplantation depends on many factors, such as donor age, recipient age, ischemic score in the kidney [2], and HLA matching [3]. The relative contribution of these factors is unknown. Because management of the recipients in the various centers differs considerably, only a single centre study would reveal the relative contribution of all these factors. Therefore, in our centre we studied the influence of these parameters on the clinical course after renal allografting.     

Premature sudden death--consider serious familial heart rhythm disturbances

We describe 3 patients from a region in the centre of the Netherlands with several relatives who died prematurely from sudden cardiac arrest. These premature deaths appeared to be caused by a unique familial sudden death syndrome. These patients and their relatives did not present any distinguishable signs, symptoms or abnormalities on further examinations apart from premature cardiac arrest occurring in about 50% of the affected family members before the age of 60 years. Genetic analysis appeared to be the only means to identify family members at risk, carrying lethal changes in their DNA that presumably involve the DPP6-gene. Patients who survive a premature sudden cardiac arrest and relatives of patients who died prematurely from sudden cardiac arrest should be referred to a cardiogenetics outpatient clinic. Timely recognition of persons affected allows appropriate treatment and may implicate an implantable cardioverter defibrillator.     

A long-distance runner with a painful sesamoid bone in the forefoot

A 38-year-old long-distance runner presented with pain in the left medial forefoot. In the presence of such symptoms, consideration should be given to a disease of or injury to a sesamoid bone. Radiology revealed a fracture line through the medial sesamoid bone under the first metatarsophalangeal joint. Conservative treatment was initially ineffective. Ultimately, local injections of lidocaine-methylprednisolone at the site of the pain, in the metatarsophalangeal joint and in the fracture line brought relief. In the diagnosis of patients with pain in the medial forefoot, apart from the patient's history and a physical examination, a skyline X-ray can be helpful to reveal a fractured or bipartite sesamoid. Almost all conditions affecting the sesamoids improve in the long run with conservative treatment. Besides reduction of weight-bearing pressure on the affected sesamoid, NSAIDs and ice massage, special attention should be paid to the foot (postural deformities), the shoe (inlays, sesamoid pad, shock absorption, stiff sole) and running on a soft surface. Insufficient therapeutic results may be due to osteonecrosis or non-union. These and persistent pain may, as a last resort, require surgical intervention such as screw fixation in case of a fracture or sesamoidectomy.     

Tacrolimus and posttransplant diabetes mellitus in renal transplantation

The most prominent side effect of tacrolimus is the induction of posttransplant diabetes mellitus (PTDM). In this review, the authors discuss the incidence, mechanism, prevention, and treatment of tacrolimus-induced PTDM in renal patients.     

MR renography by semiautomated image analysis: performance in renal transplant recipients

We evaluated a method of semiautomated analysis of dynamic MR image series in renal transplants. Nine patients were studied twice, with an average time interval of 7 days. MR examination consisted of a run of 256 T1-weighted coronal scans (GE; TR/TE/flip: = 11/3.4/60 degrees; slice thickness = 6 mm; temporal resolution = 2 seconds). Gadolinium-DTPA (0.05 mmol/kg) was injected with an injector pump (5 ml/seconds). MR renographs of the cortex and medulla were obtained by segmentation of the renal transplant and placement of two regions of interest (ROIs) overlying the peripheral and central renal parenchyma. In the first 100 frames of the renographs, analysis of variance (ANOVA) demonstrated significant intraclass correlation coefficients with mean values for the cortex and medulla of 0.47 and 0.59, respectively. We conclude that the procedure is a robust technique that generates meaningful signal curves.     

Influence of tacrolimus on glucose metabolism before and after renal transplantation: a prospective study

Most studies concerning the influence of tacrolimus on glucose metabolism have been performed either in animals or after organ transplantation. These clinical studies have largely been transversal with patients who were using steroids. Therefore, this prospective, longitudinal study investigated the influence of tacrolimus on glucose metabolism before and after transplantation. Eighteen Caucasian dialysis patients underwent an intravenous glucose tolerance test before and 5 d after the start of tacrolimus. Insulin sensitivity index (k(G)), insulin resistance (insulin/glucose ratio and homeostasis model assessment), and C-peptide and insulin secretion were calculated. Trough levels of tacrolimus were measured. After transplantation, the occurrence of posttransplantation diabetes mellitus (PTDM) was prospectively monitored. Statistical analysis was performed using the Wilcoxon signed ranks test and Spearman's rho for correlation. Before tacrolimus, k(G) was indeterminate in three patients. During tacrolimus, k(G) decreased in 16 of 18 patients, from a median of 1.74 mmol/L per min to 1.08 mmol/L per min (P<0.0001). The correlation between C-peptide and insulin data was excellent. Insulin secretion decreased from 851.0 mU x min/L to 558.0 mU x min/L (P = 0.014), whereas insulin resistance did not change. Insulin sensitivity correlated negatively with tacrolimus trough level. After transplantation, three patients developed PTDM; before tacrolimus, two had an indeterminate and one a low normal k(G). During tacrolimus administration, k(G) decreased in almost all patients as a result of a diminished insulin secretion response to a glucose load, whereas insulin resistance did not change. Patients with an abnormal or indeterminate k(G) seem to be at risk of developing PTDM while on tacrolimus.