Erol Kismet

Mutations in SLC29A3, Encoding an Equilibrative Nucleoside Transporter ENT3, Cause a Familial Histiocytosis Syndrome (Faisalabad Histiocytosis) and Familial Rosai-Dorfman Disease

The histiocytoses are a heterogeneous group of disorders characterised by an excessive number of histiocytes. In most cases the pathophysiology is unclear and treatment is nonspecific. Faisalabad histiocytosis (FHC) (MIM 602782) has been classed as an autosomal recessively inherited form of histiocytosis with similarities to Rosai-Dorfman disease (RDD) (also known as sinus histiocytosis with massive lymphadenopathy (SHML)). To elucidate the molecular basis of FHC, we performed autozygosity mapping studies in a large consanguineous family and identified a novel locus at chromosome 10q22.1. Mutation analysis of candidate genes within the target interval identified biallelic germline mutations in SLC29A3 in the FHC kindred and in two families reported to have familial RDD. Analysis of SLC29A3 expression during mouse embryogenesis revealed widespread expression by e14.5 with prominent expression in the central nervous system, eye, inner ear, and epithelial tissues including the gastrointestinal tract. SLC29A3 encodes an intracellular equilibrative nucleoside transporter (hENT3) with affinity for adenosine. Recently germline mutations in SLC29A3 were also described in two rare autosomal recessive disorders with overlapping phenotypes: (a) H syndrome (MIM 612391) that is characterised by cutaneous hyperpigmentation and hypertrichosis, hepatomegaly, heart anomalies, hearing loss, and hypogonadism; and (b) PHID (pigmented hypertrichosis with insulin-dependent diabetes mellitus) syndrome. Our findings suggest that a variety of clinical diagnoses (H and PHID syndromes, FHC, and familial RDD) can be included in a new diagnostic category of SLC29A3 spectrum disorder.

Proanthocyanidin prevents methotrexate-induced intestinal damage and oxidative stress.

Mucositis is an important dose-limiting side effect of methotrexate for which there is no definitive prophylaxis or treatment. This study was designed to investigate whether proanthocyanidin had a protective effect on methotrexate-induced small intestine damage. Twenty-eight albino rats were randomized into four groups. To the first group, methotrexate was applied as a single dose (20mg/kg) intraperitoneally. To the second group, proanthocyanidin (100mg/kg) was given orally every day by gavage in addition to methotrexate application until the rats were killed. To the third group, only proanthocyanidin was administered. The fourth group was the control. All animals were sacrificed 4 days after the intraperitoneal injection of methotrexate for histopathological examination and the assay for tissue malondialdehyde, superoxide dismutase and glutathione peroxidase levels. Methotrexate caused jejunal injury and increased malondialdehyde levels. Administration of proanthocyanidin decreased the jejunal damage and malondialdehyde level, which were caused by methotrexate treatment and increased superoxide dismutase and glutathione peroxidase levels. These results suggest that proanthocyanidin may protect the small intestine of rats from methotrexate-induced damage. The effects of proanthocyanidin could result from its antioxidant properties.

Pediatric abdominal masses: diagnostic accuracy of diffusion weighted MRI.

PURPOSE To retrospectively identify apparent diffusion coefficient (ADC) values of pediatric abdominal mass lesions, to determine whether measured ADC of the lesions and signal intensity on diffusion-weighted (DW) images allow discrimination between benign and malignant mass lesions. MATERIALS AND METHODS Approval for this retrospective study was obtained from the institutional review board. Children with abdominal mass lesions, who were examined by DW magnetic resonance imaging (MRI) were included in this study. DW MR images were obtained in the axial plane by using a non breath-hold single-shot spin-echo sequence on a 1.5-T MR scanner. ADCs were calculated for each lesion. ADC values were compared with Mann-Whitney U test. Receiver operating characteristic curve analysis was performed to determine cut-off values for ADC. The results of visual assessment on b800 images and ADC map images were compared with chi-square test. RESULTS Thirty-one abdominal mass lesions (16 benign, 15 malignant) in 26 patients (15 girls, 11 boys, ranging from 2 days to 17 years with 6.9 years mean) underwent MRI. Benign lesions had significantly higher ADC values than malignant ones (P < .001). The mean ADCs of malignant lesions were 0.84 +/- 1.7x10(-3) mm2/s, while the mean ADCs of the benign ones were 2.28 +/- 1.00x10(-3) mm2/s. With respect to cutoff values of ADC: 1.11x10(-3) mm2/s, sensitivity and negative predictive values were 100%, specificity was 78.6% and positive predictive value was 83.3%. For b800 and ADC map images, there were statistically significant differences on visual assessment. All malignant lesions had variable degrees of high signal intensity whereas eight of the 16 benign ones had low signal intensities on b800 images (P < .001). On ADC map images, all malignant lesions were hypointense and most of the benign ones (n=11, 68.7%) were hyperintense (P < .001). CONCLUSION DW imaging can be used for reliable discrimination of benign and malignant pediatric abdominal mass lesions based on considerable differences in the ADC values and signal intensity changes.

Ozone ameliorates methotrexate-induced intestinal injury in rats.

Methotrexate (Mtx) is an effective chemotherapeutic agent used in various cancer treatments. Gastrointestinal toxicity is the drug’s major limiting factor, arising mainly from oxidative damage. It has been proposed that ozone (O3) is an activator of antioxidant enzymes. Thus, this study was designed to investigate the efficacy of ozone therapy in the prevention of Mtx-induced intestinal injury in rats. Twenty rats were allocated into three groups: sham, Mtx alone (untreated) and Mtx+O3 (treated with ozone). Ozone was administered at a dose of 0.72 mg/kg daily via an intraperitoneal route for 15 days. On day 16, Mtx was applied via an intraperitoneal injection at a dose of 6 mg/kg for 5 days. All rats were sacrificed at day 21. Efficacy of the treatment was assessed by measuring the histopathologic injury score (HIS), and biochemically by determining tissue superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA) in ileum, liver and kidney homogenates. Although two rats (25%) died in the untreated group, all rats in the sham and treatment groups survived the study. The HIS, antioxidant enzyme and MDA levels of the ileal tissue were significantly lower in the ozone treated group than the untreated group (p

Sinus histiocytosis with massive lymphadenopathy in three brothers

Rosai-Dorfman disease (Sinus Histiocytosis with Massive Lymphadenopathy; SHML), is a rare cause of lymph node enlargement in children. 1 It consists of chronic massive enlargement of cervical lymph nodes frequently accompanied by fever, leukocytosis, elevated erythrocyte sedimentation rate (ESR), and hyperglobulinemia. 2,3 Extranodal sites are involved in approximately 25% of patients. 3 Although elevated antibody titers to some viruses have been found, evidence to incriminate these as etiologic agents is lacking. 4–6 To date, neither a definite etiologic agent nor a genetic inheritance has been identified in cases of SHML. It is known as a nonfamilial disease of the lymphoreticuloendothelial system. This report describes three brothers with SHML and this is the first report of three cases in one family.

Hematopoietic stem cell transplantation in Langerhans cell histiocytosis: case report and review of the literature.

Abstract:  The prognosis in children with LCH who do not respond to the conventional therapies is very poor. SCT may be a new approach. However, there are limited data about the results of the transplantations. Herein we report a patient with refractory multisystem LCH who underwent allogeneic bone marrow transplantation and is disease and treatment free 54 months after transplantation. Further studies are required to establish the role of SCT in refractory LCH.

Transfusion-related acute lung injury in a child with neuroblastoma during a late engraftment period of autologous stem cell transplantation.

Abstract:  TRALI is a rare and serious complication of blood product transfusion characterized by acute respiratory distress, non‐cardiogenic pulmonary edema, hypoxia, fever, and hypotension developing during or up to six h following transfusion. The disease can be life‐threatening and should be considered whenever complications occur after a transfusion in stem cell transplant recipients. Caution should be exercised as the symptoms of TRALI are similar to diseases such as pulmonary hemorrhage, pulmonary edema, and engraftment syndrome. The neutrophil engraftment generally occurs after 14 days following allogeneic stem cell transplants. The diagnosis of TRALI becomes very difficult with late engraftments. Herein, we report TRALI in a pediatric recipient whose neutrophil engraftment occurred on day 67.

Bone mineral density in children with nocturnal enuresis.

In enuretic children there is a significantly higher incidence of fine and gross motor clumsiness, delayed developmental milestones, slower and poor linear growth, and these patients are shorter than normal children. Skeletal maturation of enuretic children has been determined with bone age in only two studies before, but to our knowledge bone mineral content of enuretic children has not previously been determined by bone mineral density measurement. Bone mineral density was measured by the dual-energy x-ray absorptiometry method in children with nocturnal enuresis and compared with that of a control group to detect whether there were any delay in bone development and any decrease in bone mass. Thirty enuretic children were compared with a control group of 40 healthy children with respect to body height and weight measurements, daily calcium intake, serum calcium, phosphorus and ALP levels, chronological and bone ages, and bone mineral density measurements. Of the parameters compared, bone age was significantly retarded, and bone mineral density was significantly reduced in children with enuresis (8.3 ± 1.9 vs 9.7 ± 2.3 years; p = 0.01, and 0.5476 ± 0.07 vs 0.6077 ± 0.05 g/cm2; p = 0.001, respectively). Chronological ages demonstrated a significant correlation with the bone ages in both the study and control groups (r = 0.852, p < 0.001, and r = 0.844, p < 0.001, respectively). However, the mean chronological age was significantly greater than the mean bone age in the study group (p < 0.001), whereas the mean chronological age was not significantly different from the mean bone age in the control group (p = 0.514). To clarify the exact mechanism responsible for these manifestations of skeletal maturation retardation, the relationship between the maturational delay of the central nervous system connections or the effect of any perinatal insult and the retardation in skeletal maturation remains to be determined.

Primary gastric burkitt lymphoma: a rare cause of intraabdominal mass in childhood

Primary gastric lymphoma in the pediatric population is rare and the role of Helicobacter Pylori (H. Pylori) in its pathogenesis is unclear. In this report, we describe a case of non-Hodgkin’s lymphoma (Burkitt’s type) coexisting with H. pylori and discuss the potential relationship between H. Pylori and gastric Burkitt lymphoma.

Adrenomedullin worsens skin necrosis in rats subjected to vincristine‐induced extravasation

Background.  Extravasation of vesiccant drugs such as vinca alkaloids causes severe injury, which may range from erythema to skin necrosis or ulceration. The skin necrosis may not be fully evident until several weeks or months after the initial damage, and may require surgical intervention. The main treatments for vincristine extravasation are hyaluronidase injection and topical warming, and the aim of treatment is to increase the clearance of the drug from the extravasation site.