Association between CUBN gene variants, type 2 diabetes and vitamin D concentrations in an elderly Greek population.

Accumulating evidence suggests a potential implication of vitamin D biological network in the pathogenesis of diabetes mellitus. The megalin-cubilin endocytotic system constitutes a key transport structure, with a modulating role in vitamin D metabolism. We aimed to assess the contribution of variants in the CUBN gene to the genetic risk of Type 2 Diabetes Mellitus (T2DM). 95 polymorphisms within CUBN were genotyped in 716 patients with T2DM and 542 controls of Greek origin. Samples were analyzed on Illumina Human PsychArray. Permutation test analysis was implemented to determine statistical significance. Twenty-five-hydroxy-vitamin-D [25(OH)D)] levels were measured in a sub-group of participants (n = 276). Permutation analysis associated rs11254375_G/T (pemp = 0.00049, OR = 1.482), rs6602175_G/T (pemp = 0.016, OR = 0.822), rs1801224_G/T (pemp = 0.025, OR = 0.830), rs4366393_A/G (pemp = 0.028, OR = 0.829) and rs7071576_A/G (pemp = 0.04, OR = 1.219) with T2DM. Mean 25(OH)D concentrations were significantly lower in patients with T2DM compared to controls (16.70 ±â€¯6.69 ng/ml vs 18.51 ±â€¯6.71 ng/ml, p < 0.001), although both groups were vitamin D deficient. In a further quantitative analysis, rs41301097 was strongly associated with higher 25(OH)D concentrations (p = 5.233e-6, beta = 15.95). Our results indicate a potential role of CUBN gene in T2DM genetic susceptibility in the Greek population. These findings may also denote an indirect effect of vitamin D metabolism dysregulation on the pathogenesis of T2DM. Further studies are required to replicate our findings and clarify the complex underlying mechanisms.

Natural history of chronic hepatitis B virus infection in children of different ethnic origins: a cohort study with up to 12 years' follow-up in northern Greece.

AIM: To investigate the mode of transmission and the natural history of chronic hepatitis B virus (HBV) infection in children of different ethnicities in Greece. This study was part of the Interreg I-II EC project. PATIENTS AND METHODS: One hundred seventy-three hepatitis B surface antigen (HBsAg)(+) carriers, median age 6.9 (5-12) y, were prospectively followed-up for a mean period of 5.3 (1-12) y for serological markers of HBV infection, serum alanine aminotransferase (ALT), HBV-DNA, alpha-fetoprotein levels and ultrasonography. RESULTS: Vertical transmission predominates (61.8%) in Moslem children and horizontal (44%) in those born in Russia. At entry, 73 of 173 (42%) HBsAg(+) genotype D children were hepatitis B e antigen (HBeAg)(+), ranging from 27% to 67% among ethnic groups; 55 of 173 (32%) had ALT > 2 x upper normal limit (UNL), ranging from 21% to 39%. Of 100 anti-HBe(+) children, 85 (85%) were inactive carriers. During the follow-up period, seroconversion to anti-HBe was observed in 40 of 73 (55%) children with an annual rate of 11%; 35 of 40 (87.5%) had biochemical remission, and 28 of 35 (80%) lost HBV-DNA. In the anti-HBe(+) group, 27 of 100 (27%) lost HBV-DNA and 9 of 100 (9%) lost HBsAg. The annual seroconversion rate for HBeAg was significantly lower: in children with vertical transmission compared with horizontal (7.7% vs 14.8%, respectively, P < 0.001) and in Muslim children compared with both Christian children and those born in Russia (8.6% vs 12%, respectively, P < 0.001). No differences were found among the ethnic groups after adjusting for the mode of infection. Two of 173 children had progression of liver disease. CONCLUSIONS: The differences in HBeAg(+) status and seroconversion rate among the ethnic groups are related to the time/mode of HBV infection. The majority of children who developed anti-HBe immunity had biochemical remission, and a substantial number of the inactive carriers lost viremia during the observation period of up to 12 y.

Gastroesophageal reflux disease and Helicobacter pylori: lack of influence of infection on oesophageal manometric, 3-hour postprandial pHmetric and endoscopic findings.

AIM: To investigate the relationship between Helicobacter pylori and gastro-oesophageal reflux disease according to manometric and pHmetric findings. METHOD: Fifty-nine consecutive patients with reflux symptoms and endoscopic evidence of mild oesophagitis, were recruited. Manometry and ambulatory pHmetry were performed in all patients, as well as the 3-hour postprandial pHmetry, as a more flexible and well tolerable test. RESULTS: There were no significant differences between Helicobacter pylori positive and negative patients regarding age, sex ratio and endoscopic severity of oesophagitis. There was no difference in prevalence of abnormal oesophageal peristalsis between the two groups (Fisher's exact test, p=NS). Differences were also not found regarding lower oesophageal sphincter pressure between the two groups (mean PLOS 12.86+/-4.39 mmHg and 13.1+/-4.61 mmHg respectively; p=0.840). Finally, the mean values of DeMeester score were 60.38+/-48.04 and 67.64+/-51.04 respectively (p=0.576). CONCLUSION: Helicobacter pylori infection does not influence oesophageal peristalsis, the lower oesophageal sphincter pressure and the acidity of refluxates into the oesophageal lumen, in patients with established gastro-oesophageal reflux disease (esophagitis grade A and B).

Can a giant cervical osteophyte cause dysphagia and airway obstruction? A case report.

Cervical spondylosis is a common disorder mainly affecting elderly people. It frequently presents with excessive bone formation (osteophytes). These may lead to pain and neurological deficits due to root compression. Dysphagia and airway obstruction due to a giant anterior osteophyte of the cervical spine are extremely rare. We present the case of an 81-year-old patient suffering from dysphagia and slight dyspnoea due to a giant cervical osteophyte. Osteophyte resection was performed and the patient was relieved from symptoms. This case highlights that a large cervical osteophyte may, albeit rarely, be the cause of simultaneously presenting dysphagia and dyspnoea, and should, therefore, be included in the diagnostic workup in such cases.

Complete response after sorafenib therapy for hepatocellular carcinoma in an HIV-HBV co infected patient: Possible synergy with HAART ? A case report.

A significant proportion of HIV patients, ranging between 5-67%, are co-infected with hepatitis B virus (HBV). Several studies suggest an increasing incidence of hepatocellular carcinoma (HCC) in HIV infected individuals. We report the case of a 69 years old male co infected with HBV and HIV who developed HCC. The patient was unfit for curative approach and he underwent three sessions of transcatheter arterial chemoembolisation (TACE). After the last session the disease assessment showed progression and sorafenib therapy was initiated. Highly active antiretroviral therapy (HAART) was continued during sorafenib treatment. The patient achieved a radiological complete response (CR) after 6 months of therapy and remained with no sign of HCC progression at subsequent assessment. Meanwhile, patient's HIV and HBV infections remained stable. Regarding toxicity the patient developed grade 3 hand foot skin reaction (HFSR) that required 50% dose reduction of sorafenib, grade 3 hypertension and grade 2 diarrhea. In conclusion this is the first case of successful treatment of HCC in a HIV-HBV co-infected patient and only the second report of the co administration of sorafenib with HAART.

The role of serial measurement of serum HBV DNA levels in patients with chronic HBeAg(-) hepatitis B infection: association with liver disease progression. A prospective cohort study.

BACKGROUND/AIMS: To evaluate the fluctuating course of serum HBV-DNA levels during the natural history of chronic HBV infection in the general population of North-Eastern Greece, in association with liver disease progression. METHODS: Two hundred and sixty-three adults with chronic HBV, median 34 years of age, were randomly selected and prospectively followed-up for a maximum period of 12 years. Viral markers, liver biochemistry and physical examination were performed every 6 months, and liver biopsy/abdominal ultrasound every 2-4 years. RESULTS: At entry, 195/263 (76%) were HBeAg (-)/anti-HBe (+) inactive carriers: (a) almost all 195 individuals with undetectable or HBV-DNA levels <2000IU/ml had no liver disease at entry and at follow-up period by imaging or liver histology evaluation (b) only 4/195 (2%) showed HBV reactivation with HBV-DNA >2000IU/ml. At entry, 48/263 (18%) patients were chronic HBeAg(-); (a) 1/3 patients had intermittently HBV-DNA <2000IU/ml for at least one occasion and were misclassified as inactive carriers (b) 22/48 (46%) had moderate/severe histology at entry and 5/48 (10%) showed liver disease progression during follow-up. Logistic regression analysis was used to derive OR (95%CI) for factors associated with liver disease progression. CONCLUSIONS: Close monitoring of serum HBV-DNA levels is useful in the management of chronic HBeAg(-) patients, as associated with liver disease progression.

Maximal voluntary ventilation in myasthenia gravis.

Assessment of respiratory muscle weakness is important at all stages of myasthenia gravis. The maximal voluntary ventilation (MVV) is an objective dynamic method for measuring the working capacity of respiratory muscles. The clinical value of this method was studied in 24 newly diagnosed patients with myasthenia gravis, classified according to Osserman criteria (grades I, IIa, and IIb). The MVV values were normal in group I, whereas a characteristic "myasthenic pattern" of decremental respiratory volumes was demonstrated during MVV in group IIa and IIb patients, with or without dyspnea. Despite some limitations and lack of specificity, MVV may be a valuable tool in the assessment of respiratory dysfunction in patients with myasthenia gravis. Muscle Nerve, 27: 715-719, 2003