The common inversion of the Williams-Beuren syndrome region at 7q11.23 does not cause clinical symptoms

Williams-Beuren syndrome (WBS) is caused by a approximately 1.5 million base pair deletion at 7q11.23. A common inversion of the region, WBSinv-1, exists as a polymorphism but was also found in individuals with WBS-like features but no deletion, suggesting it could cause clinical symptoms. We performed a full clinical, developmental and genetic assessment of two previously reported individuals with clinical symptoms and WBSinv-1 but no 7q11.23 deletion. We also examined expression of genes at 7q11.23 in individuals in the general population who have WBSinv-1. We show that individuals with clinical symptoms and WBSinv-1 do not show significant clinical or psychological overlap with individuals with WBS. In addition, a 1.3 Mb duplication of part of the velocardiofacial syndrome region on chromosome 22q11.2 was found in one participant with WBSinv-1 and clinical symptoms. We also demonstrate that individuals with WBSinv-1 show normal expression of genes from the WBS region. These results suggest that WBSinv-1 does not cause clinical symptoms and we advise caution when diagnosing individuals with atypical presentation of rare syndromes. Whole genome analysis may reveal previously unidentified copy number variants that could contribute to syndromic features.     

Symptomatic peripheral arterial disease: the value of a validated questionnaire and a clinical decision rule

BACKGROUND: If a validated questionnaire, when applied to patients reporting with symptoms of intermittent claudication, could adequately discriminate between those with and without peripheral arterial disease, GPs could avoid the diagnostic measurement of the ankle brachial index. AIM: To investigate the Edinburgh Claudication Questionnaire (ECQ) in general practice and to develop a clinical decision rule based on risk factors to enable GPs to easily assess the likelihood of peripheral arterial disease. DESIGN OF STUDY: An observational study. SETTING: General practice in The Netherlands. METHOD: This observational study included patients of > or =55 years visiting their GP for symptoms suggestive of intermittent claudication or with one risk factor. The ECQ and the ankle brachial index were performed. The prevalence of peripheral arterial disease, defined as an ankle brachial index <0.9, was related to risk factors using logistic regression analyses, on which a clinical decision rule was developed and related to the presence of peripheral arterial disease. RESULTS: Of the 4790 included patients visiting their GP with symptoms suggestive of intermittent claudication, 4527 were eligible for analyses. The prevalence of peripheral arterial disease in this group was 48.3%. The sensitivity of the ECQ was only 56.2%. The prevalence of peripheral arterial disease in a clinical decision rule that included age, male sex, smoking, hypertension, hypercholesterolemia, and a positive ECQ, increased from 14% in the lowest to 76% in the highest category. CONCLUSION: This study indicates that the ECQ alone has an inadequate diagnostic value in detecting patients with peripheral arterial disease. The ankle brachial index should be performed to diagnose peripheral arterial disease in patients with complaints suggestive of intermittent claudication, although our clinical decision rule could help to differentiate between extremely high and lower prevalence of peripheral arterial disease.     

Reduction of interleukin-17-induced inhibition of chondrocyte proteoglycan synthesis in intact murine articular cartilage by interleukin-4

OBJECTIVE: To investigate the role of interleukin-4 (IL-4) and IL-10 in basal and IL-1- and IL-17-mediated inhibition of chondrocyte metabolism. METHODS: Cartilage explants of patellae from naive mice were incubated with IL-17 and/or IL-1 alone or were pretreated with IL-4 and IL-10. In addition, knee joints of naive mice were injected intraarticularly with IL-4 and IL-10 alone or were coinjected with IL-1. Chondrocyte proteoglycan (PG) synthesis was measured in intact murine articular cartilage. Levels of nitric oxide (NO) were measured using the Griess reagent. RESULTS: IL-17, a novel cytokine secreted by CD4+ activated memory T cells, inhibited chondrocyte PG synthesis in intact murine articular cartilage, although the suppressive effect was less potent than that of IL-1. The suppressive effect of IL-17 was completely abolished in the presence of L-NIO (L-NS-[1-iminoethyl]ornithine), an inhibitor of NO metabolism, and IL-17 only slightly induced inhibition of PG synthesis in cartilage explants of patellae from iNOS (inducible NO synthase) knockout mice. This indicates that the suppressive effect of IL-17 was mediated by NO. Pretreatment with IL-4, but not IL-10, significantly reduced the inhibition of chondrocyte PG synthesis induced by IL-1 or IL-17. The IL-4-induced reduction in the inhibitory effects of IL-1 and IL-17 on chondrocyte PG synthesis was accompanied by decreased NO formation in the culture supernatants. CONCLUSION: IL-17 plays a role in the inhibition of chondrocyte PG synthesis. IL-4 and IL-10 have no effect on basal chondrocyte metabolism. However, IL-4-pretreated cartilage is less sensitive to the suppressive effect of IL-1 as well as IL-17. This suggests that IL-4 is protective in T cell-driven cartilage disturbances, probably through reduction of iNOS.     

Cystic Dysplasia of the Testis: A Report of Three Cases and Review of the Literature

We describe the clinical and pathologic findings in three cases of cystic dysplasia of the testis and compare our findings to others in the English literature. The condition is characterized by dilatation of the rete testis with or without similarly affected adjacent structures. It is important to recognize this lesion for two reasons. First, it is associated with a high frequency of ipsilateral renal anomalies. Second, it is important to consider this condition in the differential diagnosis of cystic testicular mass in a neonate or a child. The management of this condition is quite different from the management of other testicular masses such as a hydrocele, testicular germ cell tumor, or infiltrative disorder (e.g., lymphoma, inflammation, torsion, or hematoma). Testicular cystic dysplasia is benign and the lesion can be removed surgically, leaving the rest of the testis intact. A discussion of the lesion's possible pathogenesis is also presented.     

Translation of the Leisure Satisfaction Scale into French: a validation study

Few standardized instruments are available for clients who speak languages other than English. The purpose of the study was to present and describe the process of translating an English standardized assessment into another language. Using the translation/validation methodologies described by Haccoun (1987) and Vallerand (1989), the Leisure Satisfaction Scale (LSS) was translated into French and then statistically validated. All correlations between both language versions of the LSS were found to be significant at the 0.01 level. Confirmatory factor analysis results were positive. Study findings indicate that the Haccoun (1987) and Vallerand (1989) methodologies provide clinicians with another option for ensuring culturally sensitive and relevant evaluations. Further research is needed to globally assess the measurement properties of the French version of this instrument.     

Fatigue as an important aspect of quality of life in patients with acute myeloid leukemia

Quality of life (QL) was evaluated in 101 patients with AML undergoing intensive and prolonged treatment at 12 sequential time points by using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C 30 questionnaire and the profile of mood states scale (POMS). For those patients having completed the course of inpatient treatment (n=37), QL improved from the beginning of chemotherapy to the end of inpatient treatment. Patients who subsequently went off protocol did not differ significantly in their self-assessed QL when compared with patients who completed therapy. Fatigue was more closely related to QL than nausea/emesis or appetite loss, but did not correlate with hemoglobin levels.     

Correlation between clinical syndromes and neuropsychological tasks in unmedicated patients with recent onset schizophrenia

The aim of this study is to circumscribe the cognitive deficits according to schizophrenic syndromes in a population of sub-acute untreated patients. We have studied the cross-sectional correlation between cognitive deficits and schizophrenic symptoms, in a group of 24 untreated patients (including 17 neuroleptic-naive patients) with recent onset of the disease. A task of alertness, a working memory (WM) test (including two levels of difficulty) and an abbreviated version of the Wisconsin Card Sorting Test (WCST) were selected. WM deficits and poor performance on the WCST were highly correlated with disorganized symptoms, modestly with the positive syndrome and not with the negative syndrome. Thus, disorganized symptoms, more than any other, appear to be related to the impairment of executive function and WM in recent onset unmedicated patients with schizophrenia.     

Depression and panic disorder after heart transplantation--treatment with sertraline

This report focuses on a case of major depression and panic disorder after heart transplantation. Due to these disorders, the male patient's compliance with cardiological treatment became increasingly insufficient. There are no controlled studies on psychopharmacological opportunities in cases such as this one. The patient was treated with sertraline and the outcome was healthy, without cardiovascular adverse effects or drug-drug interactions.