Christos Zois

Association of Polymorphisms of the Estrogen Receptor α Gene With Bone Mineral Density and Fracture Risk in Women: A Meta-Analysis†

The contribution of genetic polymorphisms to bone mineral density (BMD) and fracture risk in women is a controversial topic. We evaluated the effect of the XbaI and PvuII polymorphisms of the estrogen receptor α to BMD and fracture risk in a meta‐analysis, including published data and additional information from investigators. Five thousand eight hundred thirty‐four women from 30 study groups were analyzed with fixed and random effects models. The PvuII polymorphism was not associated with BMD at any skeletal site examined and 95% CIs exclude effects over 0.015 g/cm2 for both the femoral neck and the lumbar spine. Conversely, XX homozygotes (women carrying two copies of the gene variant without an XbaI restriction site) consistently had higher BMD than other subjects. The magnitude of the effect was similar in the femoral neck and lumbar spine (0.014 g/cm2 [95% CI, 0.003–0.025] and 0.015 g/cm2 [95% CI, 0.000–0.030], respectively; no between‐study heterogeneity for either). Total body BMD was also significantly higher in XX homozygotes (by 0.039 g/cm2 and 0.029 g/cm2 compared with Xx and xx, respectively). Available data on fractures suggested a protective effect for XX (odds ratio [OR], 0.66 [95% CI, 0.47–0.93] among 1591 women), but not PP (OR, 0.93 [95% CI, 0.72–1.18] among 2229 women). In summary, we have found that XX homozygotes may have higher BMD and also a decreased risk of fractures when compared with carriers of the x allele, whereas the PvuII polymorphism is not associated with either BMD or fracture risk.

High prevalence of autoimmune thyroiditis in schoolchildren after elimination of iodine deficiency in northwestern Greece.

The current iodine status and the impact of silent iodine prophylaxis on the prevalence of autoimmune thyroiditis among schoolchildren in a formerly iodine-deficient community in northwestern Greece, were investigated. The findings were compared to those obtained from a similar survey conducted 7 years previously in the same area. A total of 302 schoolchildren (12-18 years of age) from a mountainous area of northwestern Greece were examined for the presence of goiter, and blood and urine samples were collected for assessment of thyroid function, antithyroid antibodies and urinary iodine excretion. In those children (n = 42) with palpable goiter or positive antibodies and/or a thyrotropin (TSH) level greater than 5 mU/L, thyroid ultrasonography was performed to estimate thyroid gland size and morphology. Median urinary iodine concentration in the children was 20.21 microg/dL, indicating sufficient iodine intake. Thyroid function was normal in all but 7 children, who had subclinical hypothyroidism (2.5%). Antithyroid antibodies (antithyroid peroxidase [TPO] and/or antithyroglobulin [Tg]) were positive in 32 children, including those with subclinical hypothyroidism (10.6%). Twenty-nine of these children (9.6%) also had the characteristic echo pattern of thyroiditis on ultrasound and were diagnosed to have autoimmune thyroiditis. In comparison to data from our previous survey 7 years ago, there has been a threefold increase in the prevalence of autoimmune thyroiditis among schoolchildren. In conclusion, silent iodine prophylaxis has resulted in the elimination of iodine deficiency in Greece, and this has been accompanied by an increase in the prevalence of autoimmune thyroiditis.

Association of polymorphisms of the estrogen receptor alpha gene with bone mineral density and fracture risk in women

The contribution of genetic polymorphisms to bone mineral density (BMD) and fracture risk in women is a controversial topic. We evaluated the effect of the XbaI and PvuII polymorphisms of the estrogen receptor α to BMD and fracture risk in a meta‐analysis, including published data and additional information from investigators. Five thousand eight hundred thirty‐four women from 30 study groups were analyzed with fixed and random effects models. The PvuII polymorphism was not associated with BMD at any skeletal site examined and 95% CIs exclude effects over 0.015 g/cm2 for both the femoral neck and the lumbar spine. Conversely, XX homozygotes (women carrying two copies of the gene variant without an XbaI restriction site) consistently had higher BMD than other subjects. The magnitude of the effect was similar in the femoral neck and lumbar spine (0.014 g/cm2 [95% CI, 0.003–0.025] and 0.015 g/cm2 [95% CI, 0.000–0.030], respectively; no between‐study heterogeneity for either). Total body BMD was also significantly higher in XX homozygotes (by 0.039 g/cm2 and 0.029 g/cm2 compared with Xx and xx, respectively). Available data on fractures suggested a protective effect for XX (odds ratio [OR], 0.66 [95% CI, 0.47–0.93] among 1591 women), but not PP (OR, 0.93 [95% CI, 0.72–1.18] among 2229 women). In summary, we have found that XX homozygotes may have higher BMD and also a decreased risk of fractures when compared with carriers of the x allele, whereas the PvuII polymorphism is not associated with either BMD or fracture risk.

Neurologic manifestations in inflammatory bowel diseases: Current knowledge and novel insights

BACKGROUND Crohns disease (CD) and ulcerative colitis (UC), widely known as inflammatory bowel diseases (IBD), are thought to result from an inappropriate activation of the mucosal immune system driven by intestinal bacterial flora. METHODS Although the extraintestinal manifestations of IBD are well documented, the association of IBD with neurologic and neuromuscular involvement is rare and often controversial, with sporadic and conflicting data on its prevalence and spectrum. In addition, a serious number of the latter manifestations may become life-threatening, playing a very important role in disease morbidity. To define the pattern of neurologic involvement in IBD, the most important manifestations in these patients have been reviewed, exploring also their clinical significance. RESULTS There is evidence that UC and CD can manifest both in the PNS and CNS. Thrombotic complications are common in IBD patients, but cerebral vascular involvement is rare. CONCLUSIONS Neurologic manifestations in IBD patients are more common than previously estimated and may follow a different pattern of involvement in CD and UC. Small numbers of patients currently preclude a better characterization of the clinical spectrum and a better understanding of pathogenesis.

Systematic review: hepatic fibrosis – regression with therapy

Background  Hepatic fibrosis occurs in response to chronic liver injury, regardless of the cause. An impressive amount of knowledge concerning the pathogenesis and treatment of liver fibrosis has emerged over the past few years. The hallmark of this event is the activation of the hepatic stellate cell. The latter event causes accumulation of extracellular matrix and formation of scar, leading to deterioration in hepatic function.

Inflammatory bowel disease and hepatitis B and C in Western Balkans: A referral centre study and review of the literature

BACKGROUND AND AIMS There is limited data on IBD patients diagnosed with viral hepatitis B and C. The aim of the study was to assess the prevalence of chronic HBV or HCV infection in IBD patients followed by our centre and to describe and review the course of bowel and liver disease during therapy. METHODS Single centre retrospective study on 482 consecutive IBD patients. Laboratory investigation for HBV and HCV was performed with routine methods. Treatment protocols for HBV included IFNa and nucleot(s)ide administration and for HCV combined IFNa and ribavirin. RESULTS We diagnosed 15 patients (15/482, 3.1%) with HBV or HCV. Of these, 11 were HBV (11/482, 2.3%) and 4 were HCV (4/482, 0.8%). Nine of eleven HBV patients received antiviral therapy (8 lamivudine, 1 IFNa). Five lamivudine patients were switched to tenofovir and in another one adefovir dipivoxil were added. Bowel disease was in remission in ten of the eleven HBV patients. One patient was diagnosed with carcinoid tumor. Two HCV patients received IFNa that was well tolerated. One HCV patient denied therapy and one died from hepatocellular cancer. Of the seven patients on azathioprine only one achieved sustained response. Four patients on Infliximab achieved bowel disease remission but experienced biochemical or virological flare. CONCLUSIONS This study demonstrates that prevalence of HBV and HCV infection in a large IBD cohort from Western Balkans is compared to that of the background population. IBD patients under immunosuppressants may apparently be treated with safety if preventive antiviral treatment is administered.

Anterior ischemic optic neuropathy in a patient with Crohn's disease and aberrant MTHFR and GPIIIa gene variants

Large spectrums of ophthalmic manifestations from the anterior to the posterior segment have been so far reported in patients with inflammatory bowel disease. Anterior ischemic optic neuropathy is caused by acute ischemic infarction of the optic nerve head and is distinguished in two different types, non-arteritic anterior ischemic optic neuroparhy (NAION) which is the most frequent type and arteritic anterior ischemic optic neuropathy. Non-arteritic anterior ischemic optic neuroparhy may result in severe visual field loss. We present the case of a 69 year-old man with known history of Crohns disease that was referred to the Department of Ophthalmology after noticing sudden blurred vision of his left eye. Ophthalmologic examination revealed a corrected visual acuity of 8/10 OS and 10/10 OD. Pupil examination showed a relative afferent pupillary defect of the left pupil and fluoroangiography revealed hyperfluorescence of the left optic disc, indicating edema and NAION attack on his left eye. Genetic analysis showed that the patient was homozygous for MTHFR C677T genetic polymorphism and A1/A2 heterozygous for GPIIIa polymorphism.