Wernicke-encephalopathy in children with cancer

In the last 4 years, 24 cases of neuroblastoma were treated in the Pediatric Hematology-Oncology Unit at the Chaim Sheba Medical Center, 8 of whom were under 1 year of age. Four of them were the product of a pregnancy-induced or preserved by gonadotropins, clomiphene citrate, or progestational hormones. These drugs are known to produce a higher than normal level of estradiol or progestrone in the early stages of pregnancy. Our observation led to the hypothesis that high levels of progestational hormones given during pregnancy are a risk factor for neuroblastoma in infancy. © 1994 Wiley-Liss, Inc.     

Improving diagnostic accuracy of prostate carcinoma by systematic random map-biopsy

Systematic random rectal ultrasound directed map-biopsy of the prostate was performed in 77 RDE (rectal digital examination) positive and 25 RDE negative cases, if applicable. Hypoechoic areas were found in 30% of RDE positive and in 16% of RDE negative cases. The score for carcinoma in the hypoechoic areas was 6.5% in RDE positive and 0% in RDE negative cases, whereas systematic map biopsy detected 62% carcinomas in RDE positive, and 16% carcinomas in RDE negative patients. The probability of positive diagnosis of prostate carcinoma increased in parallel with the number of biopsy samples/case. The importance of systematic map biopsy is emphasized.     

The adaptor Grb7 is a novel calmodulin-binding protein: functional implications of the interaction of calmodulin with Grb7

We demonstrate using Ca2+-dependent calmodulin (CaM)-affinity chromatography and overlay with biotinylated CaM that the adaptor proteins growth factor receptor bound (Grb)7 and Grb7V (a naturally occurring variant lacking the Src homology 2 (SH2) domain) are CaM-binding proteins. Deletion of an amphiphilic basic amino-acid sequence (residues 243-256) predicted to form an alpha-helix located in the proximal region of its pleckstrin homology (PH) domain demonstrates the location of the CaM-binding domain. This site is identical in human and rodents Grb7, and shares great homology with similar regions of Grb10 and Grb14, and the Mig10 protein from Caenorhabditis elegans. We show that Grb7 and Grb7V are present in the cytosol and bound to membranes, while the deletion mutants (Grb7Delta and Grb7VDelta) have less capacity to be associated to membranes. Grb7Delta maintains in part the capacity to bind phosphoinositides, and CaM competes for phosphoinositide binding. Activation of ErbB2 by heregulin beta1 decreases the pool of Grb7 associated to membranes. The cell-permeable CaM antagonist W7 (N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide), but not the CaM-dependent protein kinase II inhibitor KN93, prevents this effect. Highly specific cell-permeable CaM inhibitory peptides decrease the association of Grb7 to membranes. This suggests that CaM regulates the intracellular mobilization of Grb7 in living cells. Direct interaction between enhanced yellow fluorescent protein (EYFP)-Grb7 and enhanced cyan fluorescent protein (ECFP)-CaM chimeras at the plasma membrane of living cells was demonstrated by fluorescence resonance energy transfer (FRET). The FRET signal dramatically decreased in cells loaded with a cell-permeable Ca2+ chelator, and was significantly attenuated when enhanced yellow fluorescent protein-Grb7 chimera (EYFP-Grb7)Delta instead of EYFP-Grb7 was used. Finally, we show that conditioned media from cells transiently transfected with Grb7Delta and Grb7VDelta lost its angiogenic activity, in contrast to those from cells transiently transfected with their wild-type counterparts.     

Clinical symptoms, diagnosis and treatment of multiple endocrine neoplasia type 1. Results of genetic screening in Hungarian patients

Multiple endocrine neoplasia type 1 syndrome is an autosomal dominant disorder characterized by endocrinopathies involving the parathyroid glands, anterior pituitary gland, and pancreas. Also, it may be associated with foregut carcinoid, adrenocortical tumors and non-endocrine tumors. After reviewing the prevalence, genetic background, clinical symptoms, diagnosis and treatment of the disorder, the authors present their genetic screening method used for the detection of mutations of the MEN1 gene (prescreening of polymerase chain reaction amplified exons using temporal temperature gradient gel electrophoresis followed by direct DNA sequencing). Using this method, the authors identified disease-causing MEN1 gene mutations in 9 probands (small deletions in 2 cases, insertion in 2 cases, nonsense mutations in 2 cases and missense mutations in 3 cases). Of the 9 mutations, 4 proved to be novel mutation not reported in the literature. Family screening indicated de novo mutations in 2 probands. In addition to mutations, several sequence polymorphisms were also detected. The authors conclude that one of the major advantages of genetic screening in families with MEN1 syndrome was the identification of family members carrying the mutation who should be regularly screened for disease manifestations and those not carrying the mutation in whom clinical screening is unnecessary. Also, genetic screening may be useful in cases when MEN1 syndrome is suspected, but the clinical manifestations do not fully establish the diagnosis of MEN1 syndrome.     

Interstitial lung disease in mixed connective tissue disease

INTRODUCTION: The authors analyzed the incidence of interstitial lung disease in mixed connective tissue disease. They were seeking an answer to the following problems: the nature of the pathological course of mixed connective tissue disease complicated by and the therapy to be used in interstitial lung disease. PATIENTS AND METHODS: 179 patients were followed up during a period of 15.9 +/- 6.1 years. Interstitial lung disease was diagnosed using high resolution computed tomography. The diagnosis of interstitial lung disease was not obvious in 5 patients thus open lung biopsy was performed, which confirmed common interstitial pneumonitis. The patients were followed-up, and the data of computed tomography and respiratory function tests were detected 6 months, and then 4 years after the acute lung disease complicated by mixed connective tissue disease. RESULTS: Out of the 179 mixed connective tissue disease patients 96 (53.6%) had interstitial lung disease. The onset of interstitial lung disease was the most frequent in the 2-4 years of the disease. Four years after the first appearance of interstitial lung disease severe fibrosis was diagnosed in 24 patients (25%). A honey comb formation in the lung developed only in one patient. For the treatment of interstitial lung disease, corticosteroid treatment had to be combined with cyclophosphamide in 51 cases. In 4 patients (24%), pulmonary arterial hypertension evolved 2-4 years following interstitial lung disease. The high pulmonary arterial pressure decreased using pulsed corticosteroid treatment, cyclophosphamide, prostacyclin analogue, anticoagulants therapy and the 4 patients stay alive. The pulmonary arterial hypertension was caused by obliterative vasculopathy. CONCLUSION: Pulmonary involvement is found in more than half of the patients with mixed connective tissue disease. Early diagnosis of interstitial lung disease is possible by computed tomography. Interstitial lung disease can be treated by the combination of corticosteroids and cyclophosphamide. The authors were the first to detect the coexistence of interstitial lung disease and pulmonary arterial hypertension in mixed connective tissue disease. Subsequent respiratory alterations in these patient necessitate regular patient follow up.     

Our experiences with nephrectomy with special emphasis on using biocompatible materials

We performed 43 open partial nephrectomies with different indications between 1996 and 2004, most of them (29) for renal cancer. We used different types of biocompatible materials for haemostasis. We describe our own recommendations and what is described in literature.     

Can the injured spleen be preserved? Results of 20-year experiments

Researches of different spleen salvaging techniques have begun in 1986 at our department. The early purpose was to develop new spleen preservation surgical techniques, such as spleen autotransplantation and spleen resection. Besides the morphological and radiological examinations we also performed different investigations including hemorheological, hemostaseological and immunological follow-up of the splenic function. From these parameters changes in red blood cell deformability and peripheral phagocyte activity could indicate the possible complications originated from the reduced splenic function. Recent paper takes a survey of these experiences.