Polyarteritis nodosa associated with hepatitis B virus infection. The role of antiviral treatment and mutations in the hepatitis B virus genome

Polyarteritis nodosa (PAN) is a systemic inflammatory disease causing vasculitis of medium sized and small arteries. Circulating immune complexes containing viral proteins have been implicated in the pathogenesis of hepatitis B virus (HBV) related PAN and several immunosuppressive and antiviral regimens have been used with varying success. In our hospital seven HBV positive patients with a confirmed diagnosis of PAN could be identified between 1984 and 2001. Most patients had an acute HBV infection and all patients were treated with prednisone. A combination of prednisone and antiviral therapy with alpha-interferon (IFN) was used only in the last four patients. HBV DNA was isolated from serum samples obtained before treatment from the four IFN treated patients and amplified by using the polymerase chain reaction technique. None of the patients without, but two of four with antiviral therapy exhibited HBsAg seroconversion. In three out of four patients HBV DNA decreased rapidly after starting IFN therapy. Clinical remission of PAN was observed in three of the four treated patients, but in none of the three patients who were not receiving antiviral medication. Analysis of the HBV genome revealed no mutations that could be associated with PAN. In one patient a stop codon in the pre-core region and a double mutation A1762T-G1764A were found during antiviral therapy. We did not find HBV heterogeneity predisposing to the development of PAN. In our group of patients it appeared that clinical remission of PAN was primarily related to spontaneous or therapy induced loss of HBV DNA replication. The combined administration of a priming steroid course and IFN appears to be an improvement over prednisone monotherapy and should be considered for every patient with HBV related PAN. The efficacy of new generation nucleoside analogues should be further elucidated in future studies.     

Ileal patch duodenoplasty after right colectomy extended to the duodenal wall

After radical resection of cancer of the right colonic flexure, a parietal defect can be created in case of duodenal invasion. In this paper the authors describe an "easy and safe" duodenoplasty surgical technique using an ileal patch.     

Comparison between bacillus Calmette-Guérin and the A60 mycobacterial antigen complex used as cancer-preventive immunotherapies

Preparations of live or lysates ofMycobacterium bovis strain Calmette-Guérin (BCG) have long been used as treatments for a variety of cancer types, especially those involving the urinary tract, with varying success. This study was conducted to compare the antitumoral activity of BCG and the thermostable macromolecular antigen complex of BCG (A60) when used as preventive treatments, in conjunction with or without tumor antigens, against growth and dissemination of the EMT6 murine tumor cell line. It was demonstrated that tumor antigens alone did not significantly alter the oncological indexes, although a slight increase in both T lymphocyte and macrophage activations was found. It was further demonstrated that A60 induces a protective activity up to 40% greater than that of live BCG and that this protection was not accompanied by any of the adverse effects sometimes observed during BCG immunotherapy.Abbreviations BCGMycobacterium bovis strain Calmette-Guérin - A60 the thermostable macromolecular antigen complex ofM. bovis BCG - EMT6 murine transplantable mammary adenocarcinoma - ELISA enzyme-linked immunosorbent assay     

Four-week low-glycemic index breakfast with a modest amount of soluble fibers in type 2 diabetic men

Low-glycemic index diets are associated with a wide range of benefits when followed on a chronic basis. The chronic effects, however, of the substitution of 1 meal per day are not well known in diabetic subjects. Therefore, we aimed to evaluate whether the chronic use of a low-glycemic index breakfast (low-GIB) rich in low-GI carbohydrates and a modest amount of soluble fibers could have an effect on lipemia at a subsequent lunch, and improve glucose and lipid metabolism in men with type 2 diabetes. A total of 13 men with type 2 diabetes were randomly allocated in a double-blind cross-over design to a 4-week daily intake of a low-GI versus a high-GI breakfast separated by a 15-day washout interval. The low-GI breakfast was composed of whole grain bread and muesli containing 3 g beta-glucan from oats. Low-GIB induced lower postprandial plasma glucose peaks than the high-GIB at the beginning (baseline, P <.001) and after the 4-week intake (P <.001). The incremental area under the plasma glucose curve was also lower (P <.001, P <.01, baseline, and 4 weeks, respectively). There was no effect on fasting plasma glucose, insulin, fructosamine, or glycosylated hemoglobin (HbA(1c)). Fasting plasma cholesterol, as well as the incremental area under the cholesterol curve, were lower (P <.03, P <.02) after the 4-week low-GIB period than after the high-GIB period. Apolipoprotein B (apo B) was also decreased by the 4-week low-GIB. There was no effect of the low-GI breakfast on triacylglycerol excursions or glucose and insulin responses at the second meal. The high-GIB, however, tended to decrease the amount of mRNA of leptin in abdominal adipose tissue, but had no effect on peroxisome proliferator-activated receptor gamma (PPARgamma) and cholesterylester transfer protein (CETP) mRNA amounts. In conclusion, the intake of a low-GI breakfast containing a modest amount (3 g) of beta-glucan for 4 weeks allowed good glycemic control and induced low plasma cholesterol levels in men with type 2 diabetes. The decrease in plasma cholesterol associated with low-GI breakfast intake may reduce the risk of developing cardiovascular complications in subjects with type 2 diabetes.     

Calcium-sensing receptor autoantibodies are relevant markers of acquired hypoparathyroidism

We investigated the presence of autoantibodies (aAbs) directed against the parathyroid gland in 17 patients with spontaneous isolated acquired hypoparathyroidism. Fourteen patients with acquired hypoparathyroidism (AH) associated with type I or II autoimmune polyendocrinopathy syndrome were also tested in comparison with a control group of 68 subjects without AH, including patients with other autoimmune diseases and healthy blood donors. aAbs against parathyroid tissue were screened using an indirect immunofluorescence technique on primate parathyroid tissue and human parathyroid adenoma. aAbs against the calcium-sensing receptor (CaSR) were analyzed using an immunoblotting assay with the recombinant extracellular domain of the human CaSR as antigen. Seven of the 31 patients with AH were positive for CaSR aAbs. Five of the positive sera were obtained from the group with isolated AH. The two other positive sera were from patients with autoimmune polyendocrinopathy syndrome. The sensitivity of the immunoblotting technique was higher than that of both the radioimmunological test using the extracellular domain of the CaSR and the indirect immunofluorescence technique. There were no positive sera in the control group. In conclusion, using an immunoblotting assay, we demonstrate the presence of CaSR aAbs in about one third of the patients with isolated AH, pointing out the value of detecting such aAbs to assess the autoimmune origin of the disease.     

Altered thyroid and adrenal function in children born at term and preterm, small for gestational age

Intrauterine growth retardation may permanently influence the endocrine system by affecting its programming during development. The aim of this study was to evaluate thyroid and adrenal function together with insulin sensitivity in a group of children born small for gestational age (SGA). Forty SGA children (mean age, 6.7 +/- 1.7 yr) and 35 children born appropriate for gestational age (mean age, 6.5 +/- 2.2 yr) were selected for the study. TSH, free T4, free T3 (fT3), rT3, antithyroid antibodies, cortisol, and dehydroepiandrosterone sulfate (DHEAS) were assessed. Insulin sensitivity was evaluated with the quantitative insulin sensitivity check index (QUICKI). A thyroid ultrasound was also performed in the SGA children. We found that TSH was significantly higher in SGA than in children born appropriate for gestational age [2.9 +/- 1.1 vs. 1.7 +/- 0.7 microU/ml (mIU/liter); P < 0.001]; furthermore, eight SGA children (20%), seven born preterm and one at term, had TSH levels above the upper limit of normality. fT3 was also higher in SGA children (4.2 +/- 0.4 vs. 3.6 +/- 0.6 pg/ml; 6.4 +/- 0.6 vs. 5.5 +/- 0.9 pmol/liter; P < 0.0001), whereas no difference was found for free T4, rT3, and the fT3/rT3 ratio. Urinary iodine was normal, and antithyroid antibodies were absent. Thyroid ultrasound showed a normal echographic pattern with a normal volume in SGA children. Serum cortisol was similar in both groups, whereas DHEAS was significantly lower in SGA subjects (43 +/- 18 vs. 65 +/- 50 microg/dl; 1.1 +/- 0.4 vs. 1.7 +/- 1.3 micromol/liter; P < 0.05). There was no difference in insulin sensitivity between the two groups. Birth length and birth weight were the main determinants of TSH and DHEAS serum levels, respectively. In conclusion, functional thyroid and adrenal changes have been found in children who suffered from intrauterine growth retardation. A larger survey with an appropriate follow-up is, however, required to confirm these findings and to assess their natural evolution.     

Gains of Continuing Resuscitation in Refractory Out-of-hospital Cardiac Arrest: A Model-based Analysis to Identify Deaths Due to Intra-arrest Prognostication

Objective: Prognostication bias, in which a clinician predicts a negative outcome and terminates resuscitation (TR) thereby ensuring a poor outcome, is a rarely identified limitation of out-of-hospital cardiac arrest (OHCA) research. We sought to estimate the number of deaths due to intra-arrest prognostication in a cohort of OHCA's, and use this data to estimate the incremental benefit of continuing resuscitation. Methods: This study examined a cohort of consecutive non-traumatic EMS-treated OHCAs from a provincial ambulance service, between 2007 and 2011 inclusive. We used Cox and logistic regression modeling, adjusting for Utstein covariates, to estimate the probability of ROSC, survival, and favorable neurological outcomes as a function of resuscitation time, and applied these models to estimate the number of missed survivors in those who had TR (prior to 20, 30, or 40 minutes). We determined the time juncture at which (1) the likelihood of survival fell below 1%, and (2) the proportion of survivors who had achieved ROSC exceeded 99%. Results: Of 5674 adult EMS-treated cases, 46% achieved ROSC, and 12% survived. The median time of TR was 27.0 minutes (IQR 19.0–35.0). Continuing resuscitation until 40 minutes yielded an estimated 17 additional survivors (95% CI 13–21), 10 (95% CI 7–13) with favorable neurological outcomes. The probability of survival of those in refractory arrest decreased below 1% at 28 minutes (95% CI 24–30 minutes). At 36 minutes (95% CI 34–38 minutes) >99% of survivors had achieved ROSC. Conclusion: We identified possible deaths due to intra-arrest prognostication. Resuscitation should be continued for a minimum of 30 minutes in all patients, however for those with initial shockable rhythms 40 minutes appears to be warranted. Interventional trials and observational studies should standardize or adjust for duration of resuscitation prior to TR.