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We have previously hypothesized that early miscarriage in women with Hashimoto thyroiditis might be the result of a cross-reactivity process, in which blocking autoantibodies against thyrotropin receptor (TSHr-Ab) antagonize hCG action on its receptor on the corpus luteum. To test this hypothesis from the clinical perspective, we investigated the presence of TSHr-Ab in Hashimoto thyroiditis patients with apparently unexplained, first-trimester recurrent miscarriages compared to that in Hashimoto thyroiditis patients with documented normal fertility. A total of 86 subjects (43 cases and 43 age-matched controls) were finally included in a case-control study. No difference in the prevalence of TSHr-Ab positivity was detected between cases and controls (Fisher's exact test, p value = 1.00). In patients with recurrent miscarriages, TSHr-Ab concentrations did not predict the number of miscarriages (univariate linear regression, p value = 0.08). These results were robust in sensitivity analyses, including only cases with full investigation or those with three or more miscarriages. We conclude that no role could be advocated for TSHr-Ab in the aetiology of recurrent miscarriages in women with Hashimoto thyroiditis.

Problem: A high percentage of women schoolteachers having fertility problems were observed by three independent teams., Method: Expected percentage of educators was calculated in 4650 sub-fertile women and 2,062,891 women at reproductive age. To explore the possibility that schoolteachers' contact with childhood viral infections results in alterations of peripheral blood natural killer (NK) cells, a multiple linear regression analysis for profession, age, difficulty to conceive, number of abortions/implantation failures (predictor variables) was performed in childless educators (210) and housewives (184)., Results: The difference between observed and expected percentage of sub-fertile schoolteachers was statistically significant (17.6% vs 6.86%, P < 0.0001). The mean percentage of PB NK cells was slightly higher in educators compared to housewives (12.48% vs 11.56%, P = 0.10), and the multiple linear regression analysis revealed that the profession (schoolteacher or not) was the only predictive variable for higher NK% values (P = 0.044)., Conclusion: Teachers' sub-fertility appears as an 'occupational disease'. Τhe possibility that results from their exposure to childhood viral infections has to be further explored., (© 2010 John Wiley & Sons A/S.)

Background and Purpose: Nasopharyngeal carcinoma (NPC) represents a seldom malignancy in most developed countries. Nevertheless, NPC receives an endemic form in concrete racial entities. The aims of this study were to detect the presence of Epstein-Barr virus DNA (EBV-DNA) in peripheral blood of NPC patients, to molecularly define human leukocyte antigens (HLA) DRB1*, DQA1* and DQB1* allele frequencies, and, finally, to determine whether the genetic predisposition of an individual to NPC depends on the liability to EBV infection., Patients and Methods: A total of 101 patients of Hellenic origin and nationality, with histologically proven NPC, participated in this study. EBV-DNA detection was also applied in 66 patients with EBV-related malignancies (Hodgkin's [HL] and non-Hodgkin's lymphoma [NHL]) and infectious mononucleosis (IM), as well as in 80 healthy EBV-seropositive controls., Results: 81% of the NPC patients, 77.8% with HL, 72.2% with NHL, and 66.7% with IM were EBV-DNA positive, whereas the EBV genome was detected only in 15% of the healthy controls. These differences were statistically significant in all cases. Analysis of HLA class II antigens showed decreased frequency of the DRB1*07 (p = 0.003), DQA1*0103 (p = 0.002), and DQA1*0201 (p = 0.003) alleles among NPC patients. A significant association between the HLA-DR/DQ alleles and the presence of EBV-DNA in peripheral whole blood was not established., Conclusion: Circulating EBV-DNA and specific HLA class II alleles may predispose to or protect from NPC. However, the results of this study suggest that the genetic predisposition of an individual to NPC is independent of the liability to EBV infection.

Background/aims: High doses of iron are recommended intravenously in iron-depleted hemodialysis (HD) patients receiving recombinant erythropoietin (EPO). Iron deficiency and mainly iron overload impair cellular and humoral immune response mechanisms. Imbalances in T cell subsets are common findings in disorders of iron metabolism. The aim of this study was to evaluate the effect of iron load on peripheral blood lymphocytes subsets and on circulating cytokine levels in HD iron depleted patients, treated with EPO., Methods: We studied 19 stable adult HD patients, 12 males, with a mean age 59 +/- 11 years and mean HD duration 24 +/- 14 months. All patients were iron deficient and were treated with unchanged EPO dose for the last 4 months before entering the study. The administered dose of iron was infused intravenously (1,000 mg iron sucrose) in 10 doses, during 10 consecutive HD sessions. Patients were screened before the commencement of the HD session on two occasions, once prior to the first dose of iron and 2 days after the 10th dose. Hematocrit (Ht), hemoglobin (Hb), iron, serum ferritin, transferrin saturation, interleukin (IL)-2, IL-4, IL-10, interferon-gamma and tumor necrosis factor-alpha were measured. Major lymphocyte subsets (CD3+, CD19+, CD4+, CD8+, CD16+/56+, CD3+CD16+CD56+) and the ratio CD4+/CD8+ were also determined by two-color immunofluorescent analysis using flow cytometry., Results: Hb, transferrin saturation and ferritin increased significantly at the end of the study 11.2 +/- 0.9 to 11.6 +/- 0.8 g/dl, p < 0.005, 17.5 +/- 6.9 to 23.0 +/- 10.8 %, p < 0.05, and 70 +/- 43 to 349 +/- 194 microg/l, p < 0.005, respectively. IL-2 also increased significantly 27.8 +/- 15.2 to 38.9 +/- 12.8 pg/ml, p < 0.05. After iron load there was no significant change to the major lymphocyte subsets examined but a significant increase of the percentage and number of T lymphocytes with positive natural killer receptors (NKR+ T) cells was observed, 5.1 +/- 3.7% to 6.3 +/- 3.46%, p < 0.05, and 76.4 +/- 40 to 101.5 +/- 48 cells/microl, p < 0.005, respectively., Conclusion: Iron load in iron-deficient EPO-treated HD patients did not produce any changes in major lymphocyte subsets in peripheral blood, but it resulted in a significant increase of NKR+ T cells, a subpopulation important for local immune responses. Iron load for a relatively short period improved anemia of HD patients and influenced the levels of the circulating IL-2, which may regulate factors affecting the survival of patients., ((c) 2007 S. Karger AG, Basel.)

Primary manifestation of Wegener's granulomatosis in the mucosa of the middle ear is rather rare, and has been reported as presenting with serous otitis media, chronic otitis media, sensorineural hearing loss, and, in rare instances, unilateral facial palsy. Bilateral facial palsy has never been reported. This last fact constitutes the interest in our report of a 23-year-old female patient who presented with symptoms of recurrent bilateral otitis media, eventually developing sensorineural hearing loss and bilateral facial palsy. Soon thereafter neurological symptoms appeared and lung extension was noted. Histological examination of repeated biopsies taken from the nasal and middle ear mucosa was not conclusive for the suspected disease, and c-ANCA titers were also initially repeatedly negative. Eventually, positive lung biopsy and elevated c-ANCA titers when the patient had developed pulmonary granulomas confirmed the diagnosis of Wegener's granulomatosis. Mastoid surgery with facial nerve decompression of the most severely afflicted side did not result in the recovery of facial nerve function. Medical therapy with corticosteroids and cyclophosphamide improved the clinical picture but were ineffective in improving the bilateral sensorineural hearing loss and the facial paralysis on the operated side. We would contribute to the literature a unique case of bilateral facial nerve palsy due to Wegener's granulomatosis.

The concept that the major histocompatibility complex (MHC) plays an important role in the pathogenesis of nasopharyngeal cancer (NPC) in several ethnic groups has gained increased attention during the last 15 years. Earlier studies have suggested that an increased risk of NPC is associated with specific phenotypes of human leukocyte antigens (HLA). The present study was performed to examine the association of HLA specificities and haplotypes with NPC in a Greek population. In a genotypical study of 53 patients, a significant association between the haplotype HLA-B5DR11 and NPC was found, mainly in patients > 45 years. Also, the above haplotype was significantly associated with longer disease-free interval. HLA-B5 and HLA-B5DR11 were more often seen among patients with squamous cell histology than among those with the undifferentiated type. These results suggest that MHC loci are probably implicated in the pathogenesis and outcome of NPC in Greek patients.

The differentiation between cyclosporine nephrotoxicity (CyN) and acute rejection (AR) still remains a matter of intensive research. In a retrospective study over the last 2 years, we assessed the clinical and histopathological data of 43 episodes of renal dysfunction in 39 renal transplant recipients immunosuppressed with cyclosporine (CyA). Ten episodes (23.2%) were identified as AR and 10 (23.2%) as acute CyN; in six cases (13.9%), signs of both AR and CyN were found. Fever (80%), oliguria (50%), and edema (50%) were prominent features in AR, but not in CyN. Renal blood flow was higher in the nephrotoxicity group and for corresponding degree of renal dysfunction. Significant hyperuricemia (greater than 8 mg/dL) was a prominent finding in CyN (80%) and to a lesser extent in AR (20%). The helper to suppressor cell ratio in the peripheral blood remained stable or slightly decreased in all cases with CyN, but increased in 70% of the cases with AR. CyN was associated with significantly higher whole blood CyA levels (P less than 0.005) and there was a positive correlation between plasma creatinine and CyA levels during the nephrotoxicity episodes (P less than 0.02). Diffuse mononuclear cell infiltrate was observed in 90% of the biopsies with AR and only in 20% with CyN (P less than 0.005). Concerning the extent of the tubular lesions, no significant differences were observed between the two groups. In contrast, vascular lesions such as arterial endothelial proliferation (P less than 0.05), hyalinosis (P less than 0.05), and glomerular capillary thrombi (P less than 0.05) were more commonly seen in nephrotoxicity biopsies.(ABSTRACT TRUNCATED AT 250 WORDS)