Association of CTLA-4 gene polymorphism with Graves' disease and ophthalmopathy in Iranian patients

BackgroundThe cytotoxic T lymphocyte associated antigen-4 (CTLA-4) gene, is one of the candidate genes for susceptibility to Graves' disease. This study aimed to investigate the association of Graves' disease and Graves' ophthalmopathy with polymorphisms at position + 49 in exon 1 and positions ? 318 and ? 1147 in the promoter region of CTLA-4 gene in Iranian patients.MethodsA total of 205 unrelated Iranian patients with Graves' disease who were referred to the outpatient endocrine clinic of a large university general hospital and 103 sex-matched healthy controls were included in this study. Venous blood was obtained, genomic DNA was extracted by a salting out method, and the polymorphisms at positions + 49, ? 318 and ? 1147 of the CTLA-4 gene were determined using the PCR-restriction fragment length polymorphism method (PCR-RFLP). Genotype and allele frequencies were determined.ResultsThe frequency of the G allele at position + 49 was significantly higher in patients with Graves' disease than in the control group (27.1% vs. 15.1%, OR = 2.096, 95%CI = 1.350–3.253 and p < 0.01). Significant trends were not seen for the other two polymorphisms studied. In patients with ophthalmopathy, the frequency of the G allele at position + 49 was higher than in those without ophthalmopathy (33.8% vs. 20.0%, OR = 2.043, 95%CI = 1.304–3.202 and p < 0.01).ConclusionThe results of this study suggest that the G allele at position + 49 in exon1 of the CTLA-4 gene is associated with Graves' disease and Graves' ophthalmopathy in Iranian patients.     

Gastrointestinal stromal tumours in a single institute: is there an association to other gastrointestinal malignancies?

Our knowledge of Gastrointestinal Stromal Tumours (GIST) has been broadened in the last few years by the discovery of the key function of c-kit tyrosine kinase mutation in their pathogenesis. A single institution database is presented and a hypothesis is examined regarding probable connection between GIST and other gastrointestinal malignancies. Between 2000 and 2004 20 patients were admitted to our department with GIS tumour. With the addition of three cases detected between 1991 and 2000, and proved to be GIST retrospectively, 23 cases are followed. Mean age was 64.52 years, male to female ratio 11:12. Ten tumours originated from the stomach, ten from small bowel, one from rectum and two from mesenterium. All patients underwent surgery, 16 operations were completed with R0 radicality, one R1 and four R2 resections were performed. Follow-up ranged from 1 to 157 months. Five out of 23 patients died (21.7%), six patients live with metastatic disease, twelve are disease free. Amongst patient-, tumour- and treatment-related factors the prognostic significance of Fletcher's risk and radicality of resection was demonstrated (p<0.05). Significantly more synchronous or metachronous gastrointestinal malignancies were found is this population of GIST patients, when compared to the prevalence of malignancies in normal Hungarian population (p<0.001).     

Reverse two-stage procedure in the surgical treatment of esophageal cancer

Authors have performed 266 one-stage resections and 6 reversed two-stage operations for the treatment of esophageal cancer during a 10-year-period. In six cases first a substernal bypass with colon or stomach was carried out while the tumourous esophagus was removed only 3-4 weeks later from a right thoracic approach. All six patients recovered. The reverse two-stage operation for esophageal cancer can be suggested with rare indications (pulmonary abscess, previous abdominal operations, severe malnutrition, etc.) and it is only justified when the advantage gained by increased operability and decreased morbidity and/or mortality is higher than the disadvantage ensuing from oncological, financial and patient demanding considerations.     

Penta X syndrome: a case report with review of the literature

We describe a 6 month-old girl with a 49, XX-XXX chromosome constitution. The patient had a characteristic round face, a low hairline, hypertelorism, epicanthus, a long philtrum, high-arched palate, short and webbed neck, small hands and feet, clinodactyly of the fifth fingers, overlapping toes, and separation between the first and the second toes. She also had atrial septal defect and patent ductus arteriosus complicated by myocarditis which exacerbated the course of her congestive heart failure. Psychomotor development was retarded with opisthotonoid posture, axial hypotonia, and with a borderline abnormal EEG. A densitometric, transmission analysis on X-linked polymorphic DNA-fragments of the Southern blots of the patient and the parents, using P20/MspI and pERT87-1/XmnI as probe/enzyme combinations, showed that the pentasomy X had resulted from 3 successive nondisjunctions at maternal meiosis. Clinical manifestations among 22 previously reported penta X syndrome patients are also reviewed.     

Activity of luxabendazole against liver flukes,gastrointestinal roundworms,and lungworms in naturally infected sheep

The anthelmintic potential of luxabendazolc was investigated in sheep harboring mixed naturally acquired helminth infections. Results were assessed by comparing worm counts of the treated groups (seven animals each) on days 7–8 posttreatment with those of the nontreated control group, except for protostrongylid lungworms, for which the changes in pre-and posttreatment group mean larval counts/g feces were assessed for intensity effect. A single oral treatment at doses of 10.0 or 12.5 mg/kg body wt removed 97.6% of the adultFasciola hepatica and 63.2%–83.8% of theDicrocoelium dendriticum. Luxabendazole at 7.5, 10.0, and 12.5 mg/kg proved 100% effective in removing adult worms of the generaHaemonchus, Ostertagia, Trichostrongylus, Cooperia andNematodirus as well as tissue-associated larval stages of gastrointestinal nematodes of the abomasal mucosa. The drug showed an intensity effect of 79.7%–87.6% againstStrongyloides papillosus. Luxabendazole removed allDictyocaulus filaria and reduced the fecal excretion of larvae of protostrongylus species (Protostrongylus rufescens, Neostrongylus linearis, Cystocaulus ocreatus, Muellerius capillaris) by 97.8%–99.6%. The efficacy of luxabendazole compared favorably with that of Diplin Kombi (oxyclozanide and levamisole), which was used as a reference drug.     

Swiss Haemovigilance Data and Implementation of Measures for the Prevention of Transfusion Associated Acute Lung Injury (TRALI)

SUMMARY: In Switzerland, blood donations are collected exclusively from healthy non-remunerated voluntary blood donors mainly by 13 regional Blood Transfusion Services throughout the country. Thereby, self-sufficient blood supply for a population of about 7.5 million is achieved, and approximately 300,000 units of red cells, 75,000 therapeutic units of fresh plasma, and 20,000 therapeutic units of platelets are transfused annually. Reporting to Swissmedic (the Swiss agency for therapeutic products) of all suspected adverse transfusion events on a standardised form is mandatory. Data are then analysed to estimate the risks of the most serious transfusion events. Together with transfusion of an incorrect blood component and bacterial contamination of platelet concentrates, TRALI is a significant risk of transfusion in Switzerland and occurs in approximately every 8,000-20,000 FFP transfusions according to current haemovigilance data. Among 25 reported cases between 2002 and November 2007, 4 are proven immune TRALI, 2 are highly likely immune TRALI, 10 are possibly immune TRALI, 8 are non-immune TRALI, and 1 is a suspected case which could not be confirmed as TRALI. Based on the hypothesis of an immunological trigger of TRALI, an exclusion of the transfusion of plasma from female donors can be considered as a precautionary measure which might have prevented 4 cases of proven immune TRALI, 2 cases of highly likely immune TRALI, and an unknown number of the 10 cases of possibly immune TRALI. Based on these data and encouraging preliminary reports of the effects of comparable measures in other countries, the decision was made that starting with January 1st 2007 the production of quarantined FFP is restricted to donations from men or from women confirming that they have never been pregnant (to their knowledge) or with negative tests for antibodies against HLA class I and II. The analysis of further vigilance data is needed to elucidate the efficacy of this preventive measure.     

Severe transfusion-related acute lung injury

A 46-yr-old man developed severe hypoxemia, pulmonary infiltrates, and an acute decrease in his leukocyte count shortly after transfusion of fresh-frozen plasma (FFP) during recovery from cardiac surgery. Cardiogenic pulmonary edema was excluded. Granulocyte-reactive and agglutinating alloantibodies were detected in the serum of the fresh-frozen plasma donor. The cross-match with the patient's granulocytes revealed antibodies specific for HLA class I. Transfusion-related acute lung injury (TRALI) is a potentially life-threatening, under-recognized and under-reported complication of transfusion. Conservative transfusion strategies and preclusion of the implicated blood donors with granulocyte-reactive antibodies from future blood donation may prevent TRALI and could save lives. IMPLICATIONS: Transfusion-related acute lung injury (TRALI) is a potentially life-threatening, probably under-recognized and under-reported complication of transfusing blood products. Conservative transfusion strategies and preclusion of the implicated blood donors with granulocyte-reactive antibodies from future blood donation may prevent TRALI and potentially save lives.     

Results of 300 kidney transplantations

Kidney transplantation is a widely used method for the treatment o fend-stage renal disease. Between September 3, 1993 and December 2002 a total of 300 kidney transplantations were performed at the Department of Surgery at the Medical University of Pécs. In 24 patients simultaneous kidney and pancreas transplantation was performed. The mean age of the 189 male and 111 female patients was 42 years. The HLA B, Dr tissue antigen mismatches was 1.63. The average cold ischemic time was 1199 minutes whereas the average anastomotic time was 43 minutes. Early surgical complications happened to 16 patients. In spite of the immunosuppressive treatment 26 acute steroid resistant rejection have occurred, 9 of which were irreversible. In our opinion the meticulous surgical technique is as important as the postoperative care is. The early and late complications of 300 renal transplants are reviewed by the authors.