Constitutional mismatch repair deficiency and Lynch syndrome among consecutive Arab Bedouins with colorectal cancer in Israel.

We assessed the molecular characteristics and the frequency of mutations in mismatch-repair genes among Bedouin patients with colorectal cancer (CRC) in Israel. Bedouin patients with a diagnosis of CRC at a major hospital in the southern part of Israel were deemed eligible for this study. The primary screening method was immunohistochemical staining for mismatch-repair proteins (MLH1, MSH2, MSH6, and PMS2). For subjects with abnormal immunohistochemical staining, we performed microsatellite instability (MSI) analyses, and for tumors with a loss of MLH1 expression we also performed BRAF testing. In MSI high cases we searched further for germline mutations. Of the 24 patients enrolled, four subjects (16.7%) had MSI high tumors: one subject was found to harbor a biallelic PMS2 mutation, one subject had Lynch syndrome (LS) with MSH6 mutation and two subjects had a loss of MLH1/PMS2 proteins/BRAF wild type/normal MLH1 sequence. Ten patients (41.7%) were younger than 50 at the time of diagnosis and none had first degree relatives with CRC. In conclusion, in this cohort of 24 consecutive Arab Bedouins with CRC, one patient was found to harbor a constitutional mismatch repair deficiency, one patient had LS with MSH6 mutation, and two patients had unresolved loss of MLH1/PMS2 proteins/BRAF wild type phenotype.

Thiamine deficiency in infancy: long-term follow-up.

BACKGROUND: In 2003, several hundred Israeli infants risked thiamine deficiency after being fed a soy-based formula deficient in thiamine. Approximately 20 patients were seriously affected, and three of them died. We report the clinical presentation of acute encephalopathy in 11 children and the long-term sequelae of eight children who initially survived. PATIENTS: In the acute phase, six had bulbar signs, five had ophthalmologic signs and two had phrenic neuropathy. Three of the five patients with cardiac involvement had cardiomyopathy and died in the acute phase. One patient presented with a complete atrioventricular block. RESULTS: In the long-term, one patient, who was in a chronic vegetative state, died after 6 years. Seven children exhibited mental retardation and motor abnormalities, six developed severe epilepsy, two early kyphoscoliosis, and one patient remained with a complete atrioventricular block. CONCLUSIONS: Infants who survive severe infantile thiamine deficiency have serious residual motor and cognitive sequelae as well as epilepsy.

Erdheim Chester - a rare disease with unique endoscopic features.

Erdheim-Chester disease (ECD) is a rare inflammatory syndrome in which systemic infiltration of non-Langerhans cell histiocytes occurs in different sites. Both the etiology and pathophysiology of ECD are unknown, but CD68 positive CD 1a/S100 negative cells are characteristic. The presentation of ECD differs according to the involved organs. This case report describes a patient with ECD and the gastrointestinal manifestations and unique endoscopic appearance as seen in gastroscopy and colonoscopy with histological proof of histiocyte infiltration of the lamina propria. The clinical and endoscopic findings of this unique case, to our knowledge, were never described before, so were the features of the gastrointestinal involvement in this disease.

Toxic hepatitis induced by Gymnema sylvestre, a natural remedy for type 2 diabetes mellitus.

Toxic hepatitis or drug-induced liver injury (DILI) encompasses a spectrum of conditions ranging from mild biochemical abnormalities to acute liver failure. Recent studies report that 35% to 48% of patients with diabetes use some form of complementary and alternative medical therapy. Moreover, >800 plants have been traditionally used for the treatment of diabetes. Despite this widespread use, only few were supported by rigorous clinical evidence. Gymnema sylvestre, also known as gurmar (sugar destroyer in Hindi), is a plant considered to be with potent antidiabetic effects and, hence, widely used in folk, ayurvedic and homeopathic systems in medicine. The authors were unable to find previous reports associating G sylvestre to liver injury. Herein, the authors report a case of DILI in a patient who was treated with G sylvestre for diabetes mellitus and review the literature to suggest possible mechanisms that led to this acute condition.

Hodgkin's lymphoma cells exhibit high expression levels of the PICOT protein.

PICOT was originally discovered as a protein kinase C (PKC) binding protein in human Jurkat T-lymphocytes in which it was found to modulate PKCtheta-dependent functions. In addition, RT-PCR analysis suggested the expression of PICOT in a wide range of organs and cell types, including cells that are devoid of PKCtheta. We aimed at analyzing the expression of the PICOT protein in mouse lymphoid organs, and to compare them with those of Jurkat T-lymphocytes and other cell lines. We also analyzed whether PICOT expression in T-lymphocytes is dependent on the presence of PKCtheta, and whether it correlates with cell growth rate. Western blot analyses demonstrated PICOT expression in all lymphoid organs and cell lines tested. In addition, similar expression levels were observed in lymphoid organs of wild-type and PKCtheta-null mice, suggesting that PICOT expression in T-lymphocytes is independent of PKCtheta. However, PICOT expression levels were higher in Jurkat T-lymphocytes and other lymphoma cell lines compared to freshly isolated lymphocytes, while T-lymphocyte mitogens, such as concanavalin A, increased PICOT expression concomitantly with the induction of a faster T-lymphocyte growth rate. Finally, immunohistochemistry of freshly-isolated lymph nodes from Hodgkin's lymphoma patients revealed significantly higher levels of PICOT in Hodgkin's cells, compared to the normal surrounding lymphocytes. The present results show a direct correlation between PICOT expression levels and increased cell growth, both in vitro and in vivo, and suggest that immunostaining of PICOT might be useful for in situ identification of transformed cells, such as those of Hodgkin's lymphoma.

Mantle cell lymphoma in a tubular adenoma: unusual presentation with synchronous colonic carcinoma.

An 80-year-old man underwent sigmoidectomy for adenocarcinoma. Six months later, after a near-syncope incident, pancytopenia was detected in the absence of occult blood in the stools. A bone marrow biopsy showed malignant lymphoma, suggestive of mantle cell lymphoma (MCL). Colonoscopy at this time revealed 3 colonic tubular adenomas. Reassessment of the histology of the colonic polyps and appropriate immunohistochemical stains showed that the lamina propria of one of the tubular adenomas was infiltrated by MCL. Reexamination of the sections taken at the time of the original sigmoidectomy showed MCL in 2 of the regional lymph nodes removed at that time, but no evidence of lymphoma in the colon was found. To our knowledge, this is the fifth reported case of synchronous occurrence of intestinal MCL and colonic carcinoma and the first report of MCL presenting in a tubular adenoma of the colon.

Colitis cystica profunda and solitary rectal ulcer syndrome-polypoid variant: Two confusing clinical conditions.

Colitis cystica profunda and solitary rectal ulcer syndrome-polyoid variant are related chronic benign disorders with characteristic histological features. However, the clinical and endoscopic settings are confusing and misleading, suggesting other rectal conditions. We report a case of colitis cystica profunda and solitary rectal ulcer syndrome-polypoid variant that was misdiagnosed initially as an ulcerative proctitis. Since an occult malignancy could not be ruled out by superficial biopsies, the mass was removed by full-thickness transanal excision.

Psammomys obesus (sand rat), a new animal model of non-alcoholic fatty liver disease.

BACKGROUND/AIMS: Non-alcoholic fatty liver disease (NAFLD) is an increasingly recognized condition that includes a spectrum of clinicopathologic conditions ranging from steatotosis to cirrhosis and liver failure. NAFLD is usually associated with features of the metabolic syndrome. No established therapies can be offered to patients with NAFLD. An appropriate animal model of NAFLD would be of help in understanding the mechanisms of the disease and in testing novel therapeutic modalities. Available animal models, such as ob/ob and db/db mice, are unsatisfactory since they show only partial resemblance to human NAFLD. Psammomys obesus (sand rat) is a well-established model of type-2 diabetes and obesity, which shares most metabolic parameters of the human metabolic syndrome. In the present study, we hypothesized that P. obesus will also show features of non-alcoholic fatty liver disease. METHODS: Experimental and control animals were fed normal rat chow or either chow to which fiber (30% wheat straw) was added for 6-18 weeks. Body weight and capillary glucose were measured regularly. At sacrifice blood samples, liver and epididymal fat were obtained. Histology of the liver was blindly determined by a pathologist. RESULTS: The experimental group showed increased body weight, liver and abdominal fat pad mass, raised plasma glucose, insulin and lipids. Also, alanine-aminotransferase (189+/-76 IU versus 86+/-26 IU; p<0.0001) was significantly higher in the experimental than the control group. Microscopic examination of liver tissue demonstrated marked macrovesicular fat infiltration in the experimental group while it was histologicaly normal in the control animals (liver fat score 1.7+/-1.0 and 0.2+/-0.4; p<0.0001, respectively). CONCLUSIONS: Fed a calorie-rich diet P. obesus develops a syndrome, which shares metabolic, laboratory and histopathologic characteristics compatible with human NAFLD.