A Delphi study to determine the European core curriculum for Master programmes in genetic counselling

Genetic counsellors have been working in some European countries for at least 30 years. Although there are great disparities between the numbers, education, practice and acceptance of these professionals across Europe, it is evident that genetic counsellors and genetic nurses in Europe are working autonomously within teams to deliver patient care. The aim of this study was to use the Delphi research method to develop a core curriculum to guide the educational preparation of these professionals in Europe. The Delphi method enables the researcher to utilise the views and opinions of a group of recognised experts in the field of study; this study consisted of four phases. Phases 1 and 4 consisted of expert workshops, whereas data were collected in phases 2 and 3 (n=35) via online surveys. All participants in the study were considered experts in the field of genetic counselling. The topics considered essential for genetic counsellor training have been organised under the following headings: (1) counselling; (2) psychological issues; (3) medical genetics; (4) human genetics; (5) ethics, law and sociology; (6) professional practice; and (7) education and research. Each topic includes the knowledge, skills and attitudes required to enable genetic counsellors to develop competence. In addition, it was considered by the experts that clinical practice should comprise 50% of the educational programme. The core Master programme curriculum will enable current courses to be assessed and inform the design of future educational programmes for European genetic counsellors.     

Thalidomide in systemic mastocytosis: results from an open‐label,multicentre, phase II study

Mastocytosis can lead to organ failure as well as systemic symptoms that can be disabling, with considerable deterioration in quality of life. Beside symptomatic treatments, interferon‐α and purine analogues have been shown to be effective but complete or long‐term remission is rarely obtained with these drugs. We conducted a phase II, multicentre, study to investigate thalidomide in severely symptomatic indolent and aggressive systemic mastocytosis. Twenty patients were enrolled of whom 16 were analysed for response. The overall response rate was 56%. Responses were observed in the skin in 61% of patients with a significant decrease in the pruritus score. Mast cell mediator‐related symptoms responded in 71% of cases and 25% of aggressive systemic mastocytosis patients had a response in terms of B/C findings (borderline/cytoreduction needed). Bone marrow mast cell infiltration decreased in five of the eight evaluable patients. There was no significant improvement in the AFIRMM (Association Française pour les Initiatives de Recherche sur le Mastocyte et Les Mastocytoses), Quality of Life or Hamilton scores. Grade 3–4 toxicities consisted of peripheral neuropathy (11%) and myelosuppression (neutropenia: 5%; thrombocytopenia: 11%). In conclusion, thalidomide might be useful in mastocytosis and in the treatment of mast cell‐related symptoms. It might be considered in selected patients, taking into account the benefit/risk balance and the individual patient evaluation.     

Outcomes for Inpatients with Normal Findings on Whole-leg Ultrasonography: A Prospective Study

Background

Ultrasonography is used routinely for ruling out suspected deep vein thrombosis in hospitalized patients, although most evidence supporting this strategy is derived from the outpatient setting. This study aimed to estimate the rate of venous thromboembolism when anticoagulant therapy was withheld from inpatients with normal findings on whole-leg ultrasonography.

Methods

As part of a prospective multicenter cohort study, 1926 medical and surgical inpatients with clinically suspected deep vein thrombosis during their stay were enrolled. Ultrasonography of all lower extremities was performed by board-certified vascular medicine physicians using a standardized examination protocol. Deep vein thrombosis was detected in 395 patients (20%). Anticoagulant therapy was withheld from patients with normal findings, and 523 of them were randomly selected for follow-up. The main outcome measure was 3-month incidence of symptomatic venous thromboembolism.

Results

A total of 513 patients with normal findings on ultrasonography successfully completed 3 months of follow-up, 9 patients were lost to follow-up, and 1 patient received anticoagulant therapy during follow-up. Three patients (0.6%) experienced nonfatal symptomatic venous thromboembolic events confirmed by objective testing. The cause of death was judged to be possibly related to pulmonary embolism for 7 other patients (1.3%). Overall, the 3-month rate of venous thromboembolism was 1.9% (10/513; 95% confidence interval, 0.9-3.5).

Conclusion

Although withholding anticoagulant therapy after a single negative whole-leg ultrasonography seems to be safe, up to 3.5% of inpatients may nevertheless develop venous thromboembolism in the next 3 months. Further study is warranted to determine whether this strategy is equivalent to serial compression ultrasonography limited to proximal veins.     

Chronic foot‐shock stress potentiates the influx of bone marrow‐derived microglia into hippocampus

For several years, a new population of microglia derived from bone marrow has been described in multiple settings such as infection, trauma, and neurodegenerative disease. The aim of this study was to investigate the migration of bone marrow‐derived cells to the brain parenchyma after stress exposure. Stress exposure was performed in mice that had received bone marrow transplantation from GFP mice, allowing identification of blood‐derived elements within the brain. Electric foot‐shock exposure was chosen because of its ability to serve as fundamental and physical stress in mice. Bone marrow‐derived GFP⁺ cells migrated to the ventral part of the hippocampus and acquired a ramified microglia‐like morphology. Microglia marker Iba1 was expressed by 100% of the ramified cells, whereas ramified cells were negative for the astrocyte marker GFAP. Compared with the case in the control group, ramified cells significantly increased after chronic exposure to stress (5 days). One month after 5 days of stress exposure, ramified cells significantly decreased in ventral hippocampus compared with the group examined immediately after the last stress exposure. We report for the first time the migration of bone marrow‐derived cells to the ventral hippocampus after stress exposure. These cells have the characteristics of microglia. Mechanisms responsible for this migration and their roles in the brain remain to be determined. © 2010 Wiley‐Liss, Inc.     

Painful sciatic rubbing caused by benign synovioma of the spinal joints. Apropos of 4 cases

Synovioma, a benign neoplasm arising from pigmented villonodular synovium or synovitis, is uncommon. It involves the tendons and joints of the finger, ankle and foot. In this study four cases of villonodular synovioma of spinal joints are reported. The authors studied 555 cases of patients operated for sciatica due to herniated disk. Histopathology showed that in four out of 555 cases sciatica was found to be due to synoviomas of the spinal joints. The patients, three women and one man, were between 54 and 70 years of age and each had had a long history of low back pain with episodes of sciatica. Clinical evaluation at the time of surgery showed moderate severity of signs and symptoms. Roentgenographic studies of all four cases revealed osteoarthritic changes of vertebral apophyses, with two cases of spondylolisthesis. The pathogenesis of synovioma remains controversial and its histopathological characterization -hyperplasia VS/true tumours- has not yet been determined. It is possible that the number of recorded cases of sciatica due to synoviomas is small because surgical and pathological studies in patients with sciatica associated with osteoarthritic changes have not been adequately performed. Surgery consists of a large resection of the capsule and ligament including resection of intraspinal extension. Because this study involves only four cases, the first of which occurred in 1977, the possibility of recurrence cannot be evaluated.     

In vivo effects of fenoldopam on autonomic nervous system after inhibition or activation of ganglionic transmission

The study investigated the effects of dopamine D1-like receptor stimulation on the autonomic nervous system. Fenoldopam (20 microg/kg) was injected i.v. in conscious sinoaortic denervated dogs, that is, surgically deprived of baroreflex pathways. In barodenervated dogs, fenoldopam (20 microg/kg) induced arterial hypotension as well as bradycardia and reduced noradrenaline plasma levels. Pentolinium (0.1 mg/kg i.v.), used to induce partial blockade of nicotinic ganglionic receptors, suppressed the fenoldopam-induced decrease in sympathetic tone, suggesting a ganglionic location for the dopamine D1-like receptor. Moreover, the inability of fenoldopam to reduce the nicotine-induced increase in sympathetic tone suggests that a postsynaptic ganglionic location can be excluded for the dopamine D1-like receptor. The results of these "in vivo" experiments strongly suggest a presynaptic location for the ganglionic dopamine D1-like receptor, stimulation of which results in a reduction of sympathetic tone.