Demonstration of an indomethacin-sensitive mechanism regulating immune reactivity in Chagas' disease patients

We investigated some aspects of the regulation of the immune response that were sensitive to the effect of indomethacin, an inhibitor of prostaglandin synthesis, in two groups of patients in the chronic phase of Chagas' disease, and in normal controls. One group of patients was defined as being infected but with no clinical evidence of cardiac involvement, while the other showed electrocardiographic alterations that are characteristic of Chagasic cardiomyopathy. The in vitro responses to mitogens (phytohemagglutinin and concanavalin A) and Trypanosoma cruzi antigens were evaluated in the presence or absence of indomethacin. It was found that the in vitro mitogenic stimulation by both phytohemagglutinin and concanavalin A of peripheral blood mononuclear cells from normal controls and infected and cardiomyopathic patients was significantly increased by indomethacin. An inverse correlation was found between the initial response to concanavalin A and the subsequent increase caused by the presence of indomethacin, for both the patients and the controls. Considering specific responses to T. cruzi antigens, we showed that in the presence of indomethacin these were significantly increased in infected patients, but not in cases of cardiomyopathy. Again, a significant inverse correlation was found between the basal responsiveness and the indomethacin-induced change. In general, infected patients showed changes in the presence of indomethacin that were most comparable to those of normal individuals. It would appear, therefore, that normal indomethacin-sensitive (prostaglandin-dependent) suppressor mechanisms operate in Chagas' patients. In certain cardiomyopathy patients, however, these control mechanisms may not operate; a possible consequence of this could be tissue damage.     

Giant osteoma of the frontoethmoidal sinus associated with two cerebral abscesses

A 36-year-old woman presented with severe frontal headache, fever, left palpebral swelling, and proptosis. Radiographic studies showed a giant frontoethmoidal osteoma, that extended intracranially into the frontal lobe and was associated with two abscesses, one within the lesion and the other in the right frontal lobe. The tumour was excised and the abscesses drained.The patient made a full recovery.     

Low testosterone levels are common and associated with insulin resistance in men with diabetes

CONTEXT: Low testosterone levels are common in men with type 2 diabetes and may be associated with insulin resistance. OBJECTIVE: We investigated prevalence of testosterone deficiency and the relationship between testosterone and insulin resistance in a large cohort of men with type 2 and type 1 diabetes. DESIGN: The study was a cross-sectional survey of 580 men with type 2 diabetes and 69 men with type 1 diabetes. A subgroup of 262 men with type 2 diabetes was then reassessed after a median of 6 months. RESULTS: Forty-three percent of men with type 2 diabetes had a reduced total testosterone, and 57% had a reduced calculated free testosterone. Only 7% of men with type 1 diabetes had low total testosterone. By contrast, 20.3% of men with type 1 diabetes had low calculated free testosterone, similar to that observed in type 2 diabetes (age-body mass index adjusted odds ratio = 1.4; 95% confidence interval = 0.7-2.9). Low testosterone levels were independently associated with insulin resistance in men with type 1 diabetes as well as type 2 diabetes. Serial measurements also revealed an inverse relationship between changes in testosterone levels and insulin resistance. CONCLUSIONS: Testosterone deficiency is common in men with diabetes, regardless of the type. Testosterone levels are partly influenced by insulin resistance, which may represent an important avenue for intervention, whereas the utility of testosterone replacement remains to be established in prospective trials.     

Skewed X-chromosome inactivation is associated with primary but not secondary ovarian failure

Premature ovarian failure (POF) is the occurrence of menopause before the age of 40, and may present with either primary or secondary amenorrhea. Numerous cases of POF in women with X-chromosome deletions or translocations have been reported; thus, it is possible that smaller rearrangements undetectable by conventional cytogenetics may contribute to POF in some patients. In females with an abnormal X chromosome, cells with inactivation of the normal X may be selected against, causing skewed X-chromosome inactivation (XCI). We therefore assessed XCI by methylation sensitive restriction digestion and PCR amplification at the androgen receptor (AR) locus, in 4 primary and 55 secondary POF patients and 109 control women. In samples heterozygous at AR and therefore informative for the skewing assay, the frequency of skewed XCI among the women with secondary amenorrhea was identical to that in control women, with 4 out of 48 (8.3%) secondary ovarian failure patients and 8 out of 97 (8.2%) control women having > or =90% skewing. Notably, all three primary amenorrhea patients that were informative at AR had skewed XCI > or =90% (P = 0.001 vs. control women; Fisher's exact test). To investigate whether X-chromosome copy number alterations were responsible, DNA from selected patients with skewed XCI was examined by high resolution DNA microarray, however no potential regions of DNA addition or deletion were confirmed by FISH or PCR. X-chromosome abnormalities undetectable by array, or reduced follicular pool due to an early trisomic rescue event, may explain the skewed XCI observed in POF patients presenting with primary amenorrhea.     

Activation of the PI3K/Akt pathway and chemotherapeutic resistance.

The resistance of many types of cancer to conventional chemotherapies is a major factor undermining successful cancer treatment. In this review, the role of a signal transduction pathway comprised of the lipid kinase, phosphatidylinositol 3-kinase (PI3K), and the serine/threonine kinase, Akt (or PKB), in chemotherapeutic resistance will be explored. Activation of this pathway plays a pivotal role in essential cellular functions such as survival, proliferation, migration and differentiation that underlie the biology of human cancer. Akt activation also contributes to tumorigenesis and tumor metastasis, and as shown most recently, resistance to chemotherapy. Modulating Akt activity is now a commonly observed endpoint of chemotherapy administration or administration of chemopreventive agents. Studies performed in vitro and in vivo combining small molecule inhibitors of the PI3K/Akt pathway with standard chemotherapy have been successful in attenuating chemotherapeutic resistance. As a result, small molecules designed to specifically target Akt and other components of the pathway are now being developed for clinical use as single agents and in combination with chemotherapy to overcome therapeutic resistance. Specifically inhibiting Akt activity may be a valid approach to treat cancer and increase the efficacy of chemotherapy.     

Prevalence of Raynaud's phenomenon in young Greek males

The aim of this paper is to study the prevalence of Raynaud's phenomenon in young males. Young males were examined prospectively in a district hospital, and laboratory tests were performed on the basis of the clinical history. Young males (3.912), age 18–28 years old, were examined. Raynaud's phenomenon was present in seven men (1,79 per 1.000, 95% CI 0.72–3.68). Three of them had at least one member in their family diagnosed with Raynaud's phenomenon. Three were smokers. All had negative immunological test. Five patients reported having severe attacks and two had only mild ischemic attacks. The treatment was conservative for all patients, two of them necessitated vasodilators. Very low prevalence of Raynaud's phenomenon was observed in this young male group compared with the previous studies.     

Spontaneous cerebellar hemorrhage—experience with 57 surgically treated patients and review of the literature

The treatment of spontaneous cerebellar hemorrhage is still discussed controversially. We analyzed a series of 57 patients who underwent surgical evacuation of a cerebellar hematoma at our department. Preoperative clinical and radiological parameters were assessed and correlated with the clinical outcome in order to identify factors with impact on outcome. The overall clinical outcome according to the Glasgow Outcome Scale at the last follow-up was good (GOS 4??) in 27 patients (47%) and poor (GOS 2??) in 16 patients (28%). Fourteen patients (25%) died. The initial neurological condition and the level of consciousness proved to be significant factors determining clinical outcome (p????.0032 and p????.0001, respectively). Among radiological parameters, brain stem compression and a tight posterior fossa solely showed to be predictive for clinical outcome (p????.0113 and p????.0167, respectively). Overall, our results emphasize the predictive impact of the initial neurological condition on clinical outcome confirming the grave outcome of patients in initially poor state as reported in previous studies. The hematoma size solely, in contrast to previous observations, showed not to be predictive for clinical outcome. Especially for the still disputed treatment of patients in good initial neurological condition, a suggestion can be derived from the present study. Based on the excellent outcome of patients with good initial clinical condition undergoing surgery due to secondary deterioration, we do not recommend preventive evacuation of a cerebellar hematoma in these patients.     

Persistence of West Nile virus immunoglobulin M antibodies, Greece

A major outbreak of West Nile virus (WNV) lineage 2 infections was observed in 2010 in Greece. In order to check the persistence of WNV IgM antibodies, a second serum sample taken 75-180 days after onset of the illness from 29 patients with WNV infection was tested. A third sample was obtained 181-270 days after onset of the illness from 8 of the 12 patients with IgM-positive second sample. Mixed effects linear regression analysis indicated that the approximate time at which IgM index became negative was 164 (95% confidence interval, 95% CI 99-236) days after the symptoms' onset. Persistence of IgM antibodies was observed in 12% of patients at 181-270 days of follow-up. A sharp decrease in the IgM levels was observed, mainly in patients who had high IgM index value in the acute phase. All patients were WNV IgG positive at the follow-up.