Retrograde inspection vs standard forward view for the detection of colorectal adenomas during colonoscopy: A back-to-back randomized clinical trial

BACKGROUND The adenoma detection rate(ADR) is inversely associated with the incidence of interval colorectal cancer and serves as a benchmark quality criterion during screening colonoscopy. However, adenoma miss rates reach up to 26% and studies have shown that a second inspection of the right colon in retroflected view(RFV) can increase ADR.AIM To assess whether inspection of the whole colon in RFV compared to standard forward view(SFV) can increase ADR.METHODS Patients presenting for screening or surveillance colonoscopy were invited to participate in this randomized controlled trial and randomized into two arms. In RFV arm colonoscopy was initially performed with SFV, followed by a second inspection of the whole colon in RFV. In the SFV arm first withdrawal was performed with SFV, followed by a second inspection of the whole colon again with SFV. Number, size and morphology of polyps found during first and second inspection in each colonic segment were recorded and all polyps were removed and sent for histopathology in separate containers.RESULTS Two hundred and five patients were randomly assigned to the RFV(n = 101) and SFV(n = 104) arm. In the RFV arm, both polyp detection rate(PDR) and ADR were increased under second inspection in RFV(PDR 1~(st) SFV: 39.8%, PDR 2~(nd)RFV: 46.6%; ADR 1~(st) SFV: 35.2%, ADR 2~(nd) RFV: 42%). Likewise, in the SFV arm,PDR and ADR were increased under second inspection(PDR 1~(st) SFV: 37.5%, PDR 2~(nd) SFV: 46.6%; ADR 1~(st) SFV: 34.1%, ADR 2~(nd)SFV: 44.3%) with no significant differences in ADR and PDR between the SFV and RFV arm. Mean number of adenomas per patient(APP) was increased in the RFV and SFV(APP RFV arm: 1~(st) SFV: 1.71; 2~(nd) RFV: 2.38; APP SFV arm: 1~(st) SFV: 1.83, 2~(nd)SFV:2.2). The majority of adenomas additionally found during second inspection in RFV or in SFV were located in the transverse and left-sided colon and were 5 mm in size.CONCLUSION Second inspection of the whole colon leads to increased adenoma detection with no differences between SFV and RFV. Hence, increased detection is most likely a feature of the second inspection itself but not of the inspection mode.     

Inter-ictal assay of peripheral circulating inflammatory mediators in migraine patients under adjunctive cervical non-invasive vagus nerve stimulation (nVNS): A proof-of-concept study

Objective

To assay peripheral inter-ictal cytokine serum levels and possible relations with non-invasive vagus nerve stimulation (nVNS) responsiveness in migraineurs.

Tumor induction by ras and myc oncogenes in fetal and neonatal brain: modulating effects of developmental stage and retroviral dose

Introduction into fetal rat brain cells of a replication-defective retroviral vector harboring v-Ha-ras and v-gag-myc rapidly causes the induction of highly malignant undifferentiated neuroectodermal tumors following transplantation into the brains of syngeneic hosts [Wiestler, et al. (1992) Cancer Res. 52: 3760–3767]. In the present study, we have investigated the modulating effect of the developmental stage of neural target cells and of the dose of the retroviral vector used in the grafting experiments. Exposure of fetal cells from embryonic day (E)12 or E14 produced a 100% incidence of malignant neuroectodermal tumors which led to the death of recipient animals after a median latency period of 32 days. A 100-fold reduction of the virus dose from 2.062×10⁶ to 2.062×10⁴ focus-forming units/ml resulted in a lower tumor incidence of 25%. Of six neural grafts exposed to v-Ha-ras and v-myc at E16, only one showed evidence of tumorigenesis (low-grade astrocytoma and hemangioma). All other transplants were morphologically normal for observation periods of 26 weeks, indicating a marked loss of transforming activity of ras and myc in more advanced stages of brain development. In retrovirus-exposed donor cells which caused the development of neural tumors in recipient rats, malignant transformation was also evident during culture in vitro, usually after 9–12 days. Oncogene complementation was also studied in the newborn rat brain. After microinjection of the retroviral vector into the brain at postnatal day (P)0, P1 and P3, 5 out of 20 animals (25%) developed a total of seven brain tumors. Histopathologically, three of these neoplasms were malignant neuroectodermal tumors which, in contrast to those induced in fetal brain transplants showed evidence of focal glial and/or neuronal differentiation. In addition, we observed one oligodendroglioma, two hemangiomas and a malignant hemangioendothelioma. These data indicate that neural precursor cells and endothelia of the rat brain represent the major target cells for the complementary action of ras and myc and that the use of target cells from later developmental stages (E16 and postnatal) leads to the induction of both primitive and more differentiated neoplasms.These studies were supported by the Fonds zur Förderung der wissenschaftlichen Forschung in Österreich (Erwin Schrödinger fellowship, JO501-MED), by the Swiss National Science Foundation and by the Cancer League of the Kanton of Zürich     

Treatment of Raynaud's syndrome with calcium entry blockers

The authors have presented the results of a 14-day open randomized trial of the efficacy of 3 calcium inlet blocking agents: nifedipine, verapamil and phendilin in 61 patients with Raynaud's syndrome. In the group of patients receiving 30-80 mg of nifedipine (20) there was a significant decrease in the frequency and expression of Raynaud's syndrome attacks, a positive effect of varying degree was noted in 19 patients. The drug raised slightly the skin and muscular blood flow and skin temperature. The use of 120-360 mg of verapamil in 21 patients caused no significant inhibition of Raynaud's syndrome and rise of hemocirculation. Phendilin (150-300 mg) though being comparable with nifedipine in efficacy, often produced side-effects resulting in the drug cancellation (8 out of 20). The efficacy of the calcium inlet blocking agents, especially nifedipine, for therapy of Raynaud's syndrome was emphasized.     

Adrenergic Receptor Genotype but Not Perioperative Bisoprolol Therapy May Determine Cardiovascular Outcome in At-risk Patients Undergoing Surgery with Spinal Block: The Swiss Beta Blocker in Spinal Anesthesia (BBSA) Study: A Double-blinded, Placebo-controlled, Multicenter Trial with 1-Year Follow-up

Background: Neuraxial blockade is used as primary anesthetic technique in one third of surgical procedures. The authors tested whether bisoprolol would protect patients at risk for cardiovascular complications undergoing surgery with spinal block.

Methods: The authors performed a double-blinded, placebo-controlled, multicenter trial to compare the effect of bisoprolol with that of placebo on 1-yr composite outcome including cardiovascular mortality, nonfatal myocardial infarction, unstable angina, congestive heart failure, and cerebrovascular insult. Bisoprolol was given orally before and after surgery for a maximum of 10 days. Adrenergic receptor polymorphisms and safety outcome measures of bisoprolol therapy were also determined.

Results: A total of 224 patients were enrolled. Spinal block could not be established in 5 patients. One hundred ten patients were assigned to the bisoprolol group, and 109 patients were assigned to the placebo group. The mean duration of treatment was 4.9 days in the bisoprolol group and 5.1 days in the placebo group. Bisoprolol therapy reduced mean heart rate by 10 beats/min. The primary outcome was identical between treatment groups and occurred in 25 patients (22.7%) in the bisoprolol group and 24 patients (22.0%) in the placebo group during the 1-yr follow-up (hazard ratio, 0.97; 95% confidence interval, 0.55-1.69; P = 0.90). However, carriers of at least one Gly allele of the [beta]1-adrenergic receptor polymorphism Arg389Gly showed a higher number of adverse events than Arg homozygous (32.4% vs. 18.7%; hazard ratio, 1.87; 95% confidence interval, 1.04-3.35; P = 0.04).     

Importance of an acid milieu in the sucralfate-induced gastroprotection against ethanol damage

Sucralfate is known for its gastroprotective properties in humans and rats, but the importance of intragastric pH in this protection is a subject of controversy. This study, performed on healthy young volunteers and rats, was designed to compare the gastroprotective effects of sucralfate with those of sucralfate combined with ranitidine or of sucralfate adjusted to pHs varying from 1 to 7. In humans the mucosal damage induced by 40% ethanol spray after 4 days of pretreatment with placebo, sucralfate (1 g four times daily), ranitidine (150 mg three times daily), or the combination of sucralfate plus ranitidine was evaluated by means of endoscopy with mucosal biopsy and histologic examination. Sucralfate alone reduced the endoscopic score significantly (compared with placebo) and prevented deep necrotic lesions. Neither ranitidine alone nor its combination with sucralfate prevented ethanol-induced endoscopic and histologic mucosal changes. In rats acute gastric lesions were induced by 100% ethanol. Sucralfate was relatively more effective in mucosal protection against ethanol when given at lower pH (1 or 2) than at original pH (4.5) and failed to protect at neutral pH (7.0). Pretreatment with ranitidine, which by itself did not change ethanol damage, greatly reduced the protection afforded by sucralfate. We conclude that sucralfate protects the gastric mucosa against ethanol damage both in humans and in rats and that this protection is dependent on the presence of an acidic intragastric pH.     

Comparative evaluation of the treatment of Sj?gren's syndrome with anti-rheumatic preparations

The paper is devoted to comparative assessment of combined therapy of prednisolone, chlorambucil, chloroquine phosphate and ibuprofen at small doses and its effect on clinicolaboratory signs of Sjogren's disease in 80 patients in the course of 1 and 5 years. Patients of the control group received only local therapy of the parotid glands. The results have demonstrated that combined therapy at small doses of prednisolone and chlorambucil (5 mg + 4 mg) is an effective method of treatment of the stomatological, ophthalmological and articular manifestations of SD and is also capable of preventing the systemic signs of disease. Combined therapy with chloroquine phosphate and ibuprofen neither influenced the clinicolaboratory signs of disease nor prevented disease progression with the development of systemic signs of diseases of various degrees. Disease progression was observed in 80% of patients receiving no basic drugs or receiving chloroquine phosphate+ibuprofen while in groups of patients receiving small doses of prednisolone and chloambucil disease progression was observed in 20% only.