DQB1*0602 confers genetic susceptibility to multiple sclerosis in Afro-Brazilians

We studied the distribution of the HLA-DRB1, -DQA1 and -DQB1 alleles in 44 Afro-Brazilian patients with multiple sclerosis and 88 controls. Although no significant differences were found between the patients and controls for the DRB1 and DQA1 alleles, the HLA-DQB1*0602 allele was positively associated with multiple sclerosis (45.0% vs. 17.0%, Pc=0.024, RR=3.31). The positive extended haplotypes for DQB1*0602 were more frequent in patients than controls, although the differences were not statistically significant in any of them. These results in Afro-Brazilians are in line with other studies which have found DQB1*0602 to be associated with the disease in the absence of the DRB1*1501 allele. We therefore think that the association with the disease in this ethnic group is more allelic than haplotypic.     

Cross-reactivity between IgE-binding proteins from Anisakis German cockroach, and chironomids

Pascual CY, Crespo JF, San Martin S, Ornia N, Ortega N, Caballero T, Munoz-Pereira M, Martin-Estaban M. Cross-reactivity between IgE-binding proteins from Anisakis German cockroach, and chironomids. Anisakis simplex larvae parasitize animals used as seafood and can produce a specific immune response in man. The ingestion of seafood contaminated with stage three of A. simplex larvae can induce a specific IgE response with clinical symptoms, usually urticaria, even if the fish is cooked before ingestion and the invasive infestation power destroyed by heating. Our preliminary studies showed a strong association of A. simplex sensitization with Ascaris lumbricoides, Daphnia chironomid spp., Atlantic shrimp ‘Pandalus borealis’ and German cockroach ‘Blattella germanica’. We conducted the cross-reactivity study with cockroach, a ubiquitous insect, and Chironomidae ‘red mosquito larvae’, a work-related allergen, without any possibility of Anisakis contamination. Serum samples were collected from 60 pediatric patients, with serum specific IgE to A. simplex. Both specific-IgE and immunoblot-inhibition studies, with a serum pool from 18 patients, were performed to determine whether the association of sensitizations to nematodes and arthropods was due to immunologic cross-reactivity. In addition, serum samples from 21 of 60 patients who showed also sensitization to German cockroach were used for individual immunoblot studies. In the serum pool, dose-dependent inhibition of B. germanica and Chironomus spp. was observed after preincubation with the A. simplex extract. Immunoblot of Anisakis inhibited with Chironomus and German cockroach, yielded a partial blot inhibition but mainly on bands below 41 kDa. Blot inhibition of German cockroach and Chironomus with Anisakis was dose related. The band patterns in individual blots were heterogeneous, but most of them had bands of 30–43 kDa. None of these sera recognized allergens in the 14–kDa area. In our study, CAP-inhibition and immunoblot-inhibition analysis of Anisakis showed that several IgE-binding components could be shared by the three allergens.     

Nonmyeloablative stem cell transplantation is an effective therapy for refractory or relapsed hodgkin lymphoma: results of a spanish prospective cooperative protocol.

We report the results of reduced-intensity conditioning allogeneic stem cell transplantation (allo-RIC) in patients with advanced Hodgkin lymphoma (HL). Forty patients with relapsed or refractory HL were homogeneously treated with an RIC protocol (fludarabine 150 mg/m(2) intravenously plus melphalan 140 mg/m(2) intravenously) and cyclosporin A and methotrexate as graft-versus-host disease (GVHD) prophylaxis. Twenty-one patients (53%) had received >2 lines of chemotherapy, 23 patients (58%) had received radiotherapy, and 29 patients (73%) had experienced treatment failure with a previous autologous stem cell transplantation. Twenty patients (50%) were allografted in resistant relapse, and 38 patients received hematopoietic cells from an HLA-identical sibling. Five patients (12%) died from early transplant-related mortality (before day +100 after allo-RIC). One-year transplant-related mortality was 25%. Acute GVHD developed in 18 patients (45%). Chronic GVHD developed in 17 (45%) of the 31 evaluable patients. The response rate 3 months after the allo-RIC was 67% (21 [52%] complete remissions and 6 [15%] partial remissions). Eleven patients received donor lymphocyte infusions (DLIs) for disease relapse. The response rate after DLI was 54% (3 complete remissions and 3 partial remissions). Overall survival (OS) and progression-free survival (PFS) were 48% +/- 10% and 32% +/- 10% at 2 years, respectively. Refractoriness to chemotherapy was the only adverse prognostic factor for both OS (63% +/- 12% versus 35% +/- 13%; P = .05) and PFS (55% +/- 16% versus 10% +/- 9%; P = .006). For patients with failure of a prior autologous hematopoietic stem cell transplantation, results were especially good for those who experienced late relapses (>/=12 months: 2-year OS and PFS were 75% +/- 16% and 70% +/- 18%, respectively). These data suggest that allo-RIC is feasible in heavily pretreated HL patients and has an acceptable early transplant-related mortality. Results are better in patients allografted in sensitive disease. Both responses observed after the development of GVHD and DLI may suggest a graft-versus-HL effect. Allo-RIC has to be considered an effective therapeutic approach for patients who have had treatment failure with a previous autologous hematopoietic stem cell transplantation.     

Short-term therapy for recurrent abortion using intravenous immunoglobulins: results of a double-blind placebo-controlled Italian study

It is still unclear whether i.v. immunoglobulins (Ig) can facilitate the reproductive prognosis of women who have suffered recurrent pregnancy loss. We report the results of a multicentre placebo- controlled study on the effect of Ig administration on pregnancy outcome in 46 women who had suffered at least three recurrent miscarriages. All were screened to exclude chromosomal or Mullerian abnormalities, the presence of antinuclear antibodies, lupus anticoagulant (LA) or elevated titres of anticardiolipin antibodies which may have revealed an underlying autoimmune problem. To avoid a selection bias towards ongoing pregnancies, i.v. Ig or placebo were administered between weeks 5 and 7 of gestation for 2 consecutive days as soon as each woman knew she was pregnant and before embryonic heart activity could be detected. A further infusion was administered at week 8 when ultrasonography confirmed an ongoing embryonic development. In all, 68% of the women who received Ig went to term versus 79% of those who received a placebo (not significant), with no significant differences in the pregnancy course or the perinatal outcome. These results suggest either that women with recurrent miscarriages who have no recognized cause of pregnancy loss have a good reproductive prognosis without any treatment or that the emotional care associated with the administration of a placebo can indirectly facilitate the progression of pregnancy.      

Specific IgE determination to Ani s 1, a major allergen from Anisakis simplex, is a useful tool for diagnosis.

BACKGROUND: The most serious limitation of the serodiagnosis of parasitoses is the occurrence of cross-reactions. OBJECTIVE: The possible use of Anisakis simplex major allergen Ani s 1 for diagnosis. PATIENTS AND METHODS: Forty-nine non-fish-allergic patients with Anisakis simplex hypersensitivity, 21 patients without allergic episodes suffering intestinal anisakiasis with obstruction of the intestinal lumen, and 10 unrelated sera as a control were included in this study to determine specific immunoglobulin (Ig)E and IgG to Anisakis simplex major allergen Ani s 1 by immunoblotting. RESULTS: Eighty-six percent of patients with Anisakis simplex hypersensitivity showed specific IgE directed to Ani s 1. Identical result was obtained for IgG detection in this group. Among patients with intestinal anisakiasis, 86% showed specific IgE, but only 29% had specific IgG (P < 0.001, two-tailed Fisher exact test). One of the 10 control subjects was positive both for IgE and IgG (P < 0.001). CONCLUSIONS: Determination of specific IgE directed to Anisakis simplex major allergen Ani s 1 is a useful tool for the diagnosis of hypersensitivity and intestinal anisakiasis. Further, measurement of specific IgG directed to Anisakis simplex major allergen Ani s 1 is only valid for Anisakis simplex allergy.     

Iron metabolism and fungal infections in patients with haematological malignancies.

AIM--To determine whether iron metabolism influences the incidence of systemic fungal infection in patients with haematological malignancies. METHODS--The study population comprised 74 patients who had undergone myeloablative chemotherapy. Systemic fungal infections were classified as confirmed (histological confirmation or characteristic septate hyphae) or possible (antibiotic resistant fever which resolved following administration of intravenous amphotericin B, together with either typical radiographic lesions or massive oropharyngeal candidiasis). Parameters of iron metabolism included serum iron concentrations, total iron binding capacity, serum transferrin, and ferritin concentrations and transferrin saturation values. RESULTS--Patients who developed a fungal infection had substantially increased transferrin saturation values and ferritin concentrations at diagnosis together with low serum transferrin and high serum iron concentrations. This profile was present in patients with a fungal infection regardless of the underlying haematological disorder. CONCLUSION--Increased transferrin saturation values and high ferritin concentrations may be additional risk factors for the development of systemic fungal infection in patients with haematological malignancies.     

The ileoanal J pouch: radiographic evaluation

Endorectal ileoanal pull-through offers an attractive alternative to proctocolectomy and ileostomy for patients with ulcerative colitis, Gardner syndrome, and familial polyposis. To our knowledge, a careful radiographic analysis of the ileum, ileal pouch, and ileoanal anastomosis after ileoanal pull-through has not been reported. Thirty-two patients with ulcerative colitis, Gardner syndrome, and familial polyposis underwent colectomy, mucosal proctectomy, and endorectal ileoanal pull-through of a 15-cm ileal "J" pouch and loop ileostomy. Twenty-five (78%) of 32 of all the pouches radiographically demonstrated spiral folds extending from the middle of the pouch to the pectinate line. Other radiographic features included a mesenteric mass effect, pseudopolyps, and a central lucency that indicated intrapouch sutures. Radiographs provide useful information in the postoperative management of the ileal pull-through.     

A Randomized Study of Nutritional Supplementation in Patients with Unilateral Wet Age-Related Macular Degeneration

The purpose of this study is evaluate the efficacy and safety of medicinal products containing the original Age-Related Eye Disease group (AREDS) formulation at doses approved in Europe (EU, control group; n = 59) with a product that adds DHA, lutein, zeaxanthin, resveratrol and hydroxytyrosol to the formula (intervention group; n = 50). This was a multicenter, randomized, observer-blinded trial conducted in patients aged 50 years or older diagnosed with unilateral exudative Age related Macular Degeneration AMD. At month 12, the intervention did not have a significant differential effect on visual acuity compared with the control group, with an estimated treatment difference in Early Treatment Diabetic Retinopathy Study (ETDRS) of −1.63 (95% CI −0.83 to 4.09; p = 0.192). The intervention exhibited a significant and, in most cases, relevant effect in terms of a reduction in some inflammatory cytokines and a greater improvement in the fatty acid profile and serum lutein and zeaxantin concentration. In patients with unilateral wet AMD, the addition of lutein, zeaxanthin, resveratrol, hydroxytyrosol and DHA to the AREDS EU recommended doses in the short-term did not have a differential effect on visual acuity compared to a standard AREDS EU formula but, in addition to improving the fatty acid profile and increasing carotenoid serum levels, may provide a beneficial effect in improving the proinflammatory and proangiogenic profile of patients with AMD.