Gastric intramucosal pH-guided therapy in patients after elective repair of infrarenal abdominal aneurysms: is it beneficial?

Objective: To determine if gastric intramucosal pH (pHi)-guided therapy reduces the number of complications and length of stay in the intensive care unit (ICU) or the hospital after elective repair of infrarenal abdominal aortic aneurysms. Design: Prospective, randomized study. Setting: Surgical intensive care unit (SICU) of a University Hospital. Patients: Fifty-five consecutive patients randomized to group 1 (pHi-guided therapy) or to group 2 (control). Interventions: Patients of group 1 with a pHi of lower than 7.32 were treated by means of a prospective protocol in order to increase their pHi to 7.32 or more. Measurements and results: pHi was determined in both groups on admission to the SICU and thereafter at 6-h intervals. In group 2, the treating physicians were blinded for the pHi values. Complications, APACHE II scores, duration of endotracheal intubation, fluid and vasoactive drug treatment, treatment with vasoactive drugs, length of stay in the SICU and in the hospital and hospital mortality were recorded. There were no differences between groups in terms of the incidence of complications. We found no differences in APACHE II scores on admission, the duration of intubation, SICU or hospital stay, or hospital mortality. In the two groups the incidence of pHi values lower than 7.32 on admission to the SICU was comparable (41 % and 42 % in groups 1 and 2, respectively). Patients with pHi lower than 7.32 had more major complications during SICU stay (p<0.05), and periods more than 10 h of persistently low pHi values (< 7.32) were associated with a higher incidence of SICU complications (p<0.01). Conclusions: Low pHi values (<7.32) and their persistence are predictors of major complications. Treatment to elevate low pHi values does not improve postoperative outcome. Based on these data, we cannot recommend the routine use of gastric tonometers for pHi-guided therapy in these patients. Further studies are warranted to determine adequate treatment of low pHi values that results in beneficial effects on the patient's postoperative course and outcom

Spinal anaesthesia in a patient with Takayasu's disease

We report the successful anaesthetic management of therapeutic abortion under spinal anaesthesia in a 32-yr-old woman with Takayasu's disease. The pathology and pathophysiology of this syndrome and their impact on anaesthesia are discussed. (Br. J. Anaesth. 1994; 72: 129-132

Insurer and Employer Views on Pediatric Obesity Treatment: a Qualitative Study

This is the peer reviewed version of the following article: Hampl, S.E., Davis, A.M., Sampilo, M.L., Stephens, K.L. and Dean, K. (2013), Insurer and employer views on pediatric obesity treatment: A qualitative study. Obesity, 21: 795–799. doi:10.1002/oby.20112, which has been published in final form at http://doi.org/10.1002/oby.20112. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.OBJECTIVE The effectiveness of group-based comprehensive, multidisciplinary (stage 3) pediatric weight management programs is backed by a growing body of literature, yet insurance coverage of these programs is scarce to nonexistent, limiting their reach and long-term survival. The objective of this study was to better understand the perspectives of insurers and large employers on the issue of group-based treatment coverage. DESIGN AND METHODS The authors performed a qualitative study utilizing structured interviews with these stakeholders, following accepted techniques. RESULTS Six major themes emerged: cost, program effectiveness, corporate social responsibility, secondary parental (employee) benefits, coverage options and new benefit determination. CONCLUSION Future efforts to secure payment for group-based pediatric weight management programs should address these key themes

Bupivacaine concentrations in lumbar cerebrospinal fluid in patients with failed spinal anaesthesia

Background Spinal anaesthesia (SA) has high success rates. However, inadequate block after SA has been reported even in the absence of technical problems. Various mechanisms for failed SA (FSA) have been proposed, but reports of cerebrospinal fluid (CSF) concentrations of local anaesthetics (LA) after FSA are scarce. We report lumbar CSF concentrations of bupivacaine in 20 patients in whom adequate block after subarachnoid injection failed to develop. Methods All patients with inadequate block after subarachnoid injection of plain bupivacaine 0.5% and in whom a second subarachnoid injection of LA was to be performed as a rescue technique were eligible for entry into this study. A CSF sample was withdrawn immediately before injection of the second dose of LA. Patients in whom failure was obviously due to technical problems or inadequate dosage were excluded. Bupivacaine concentrations were assessed with high-performance liquid chromatography. Results During the study period of 15 months, 2600 spinal anaesthetics were performed. The failure rate was 2.7% (71 patients). In 20 patients (0.77%), CSF concentrations of bupivacaine were determined, which ranged from 3.36 to 1020 µg ml−1. Conclusions Inadequate CSF concentration of LA is a common reason for FSA. However, in 12 of our 20 patients, concentrations were above 73 µg ml−1, a concentration that should lead to an adequate block. In these patients, maldistribution of bupivacaine could be responsible for FSA. In view of the absence of sufficient block, despite adequate lumbar CSF concentrations of bupivacaine, concerns about neurotoxicity with repeat injections may be warrante

Perioperative administration of fibrinogen does not increase adverse cardiac and thromboembolic events after cardiac surgery

Background Although infusion of fibrinogen concentrate is increasingly used in bleeding patients after cardiac surgery, safety data are scarce. We aimed to evaluate the effect of perioperative administration of fibrinogen concentrate on postoperative morbidity and mortality in patients undergoing cardiac surgery. Methods During a 2 yr study period, 991 patients underwent cardiac surgery at a single university centre and were eligible for propensity score (PS) matching. We matched 190 patients with perioperative infusion of fibrinogen concentrate (median dose 2 g) with 190 controls without fibrinogen administration. After PS matching, crude outcome was analysed. Further, a multivariate logistic regression including additional risk factors for adverse outcome was performed. The primary endpoint was a composite of mortality and the occurrence of major cardiac and thromboembolic events within 1 yr. Secondary outcomes included mortality after 30 days and 1 yr and the composite of mortality and adverse events after 30 days. Results The administration of fibrinogen concentrate was not associated with an increased risk for mortality and thromboembolic or cardiac events within 1 yr after cardiac surgery [unadjusted hazard ratio (HR) 0.91; 95% confidence interval (CI) 0.55-1.49; P=0.697]. When using multivariate logistic regression model, the HR for adverse outcome in patients with administration of fibrinogen concentrate was 0.57 (95% CI 0.25-1.17; P=0.101). Similarly, the administration of fibrinogen concentrate did not adversely affect the secondary outcomes when applying unadjusted and multivariate regression analyses. Conclusions Our study strongly suggests that the administration of fibrinogen concentrates at low dose is not associated with thromboembolic complications or adverse outcomes after cardiac surger

The CHK1 inhibitor MU380 significantly increases the sensitivity of human docetaxel-resistant prostate cancer cells to gemcitabine through the induction of mitotic catastrophe.

As treatment options for patients with incurable metastatic castration-resistant prostate cancer (mCRPC) are considerably limited, novel effective therapeutic options are needed. Checkpoint kinase 1 (CHK1) is a highly conserved protein kinase implicated in the DNA damage response (DDR) pathway that prevents the accumulation of DNA damage and controls regular genome duplication. CHK1 has been associated with prostate cancer (PCa) induction, progression, and lethality; hence, CHK1 inhibitors SCH900776 (also known as MK-8776) and the more effective SCH900776 analog MU380 may have clinical applications in the therapy of PCa. Synergistic induction of DNA damage with CHK1 inhibition represents a promising therapeutic approach that has been tested in many types of malignancies, but not in chemoresistant mCRPC. Here, we report that such therapeutic approach may be exploited using the synergistic action of the antimetabolite gemcitabine (GEM) and CHK1 inhibitors SCH900776 and MU380 in docetaxel-resistant (DR) mCRPC. Given the results, both CHK1 inhibitors significantly potentiated the sensitivity to GEM in a panel of chemo-naïve and matched DR PCa cell lines under 2D conditions. MU380 exhibited a stronger synergistic effect with GEM than clinical candidate SCH900776. MU380 alone or in combination with GEM significantly reduced spheroid size and increased apoptosis in all patient-derived xenograft 3D cultures, with a higher impact in DR models. Combined treatment induced premature mitosis from G1 phase resulting in the mitotic catastrophe as a prestage of apoptosis. Finally, treatment by MU380 alone, or in combination with GEM, significantly inhibited tumor growth of both PC339-DOC and PC346C-DOC xenograft models in mice. Taken together, our data suggest that metabolically robust and selective CHK1 inhibitor MU380 can bypass docetaxel resistance and improve the effectiveness of GEM in DR mCRPC models. This approach might allow for dose reduction of GEM and thereby minimize undesired toxicity and may represent a therapeutic option for patients with incurable DR mCRPC

No association between islet cell antibodies and coxsackie B, mumps, rubella and cytomegalovirus antibodies in non-diabetic individuals aged 7–19 years

Viral antibodies were tested in a cohort of 44 isletcell antibody-positive individuals age 7–19 years, and 44 of their islet cell antibody-negative age and sex-matched classmates selected from a population study of 4208 pupils who had been screened for islet cell antibodies. Anti-coxsackie B1-5 IgM responses were detected in 14 of 44 (32%) of the islet cell antibody-positive subjects and in 7 of 44 (16%) control subjects. This difference did not reach the level of statistical significance. None of the islet cell antibody-positive subjects had specific IgM antibodies to mumps, rubella, or cytomegalovirus. There was also no increase in the prevalence or the mean titres of anti-mumps-IgG or IgA and anti-cytomegalovirus-IgG in islet cell antibody-positive subjects compared to control subjects. These results do not suggest any association between islet cell antibodies, and possibly insulitis, with recent mumps, rubella or cytomegalo virus infection. Further studies are required to clarify the relationship between islet cell antibodies and coxsackie B virus infections

Extensive molecular tinkering in the evolution of the membrane attachment mode of the Rheb GTPase

Rheb is a conserved and widespread Ras-like GTPase involved in cell growth regulation mediated by the (m)TORC1 kinase complex and implicated in tumourigenesis in humans. Rheb function depends on its association with membranes via prenylated C-terminus, a mechanism shared with many other eukaryotic GTPases. Strikingly, our analysis of a phylogenetically rich sample of Rheb sequences revealed that in multiple lineages this canonical and ancestral membrane attachment mode has been variously altered. The modifications include: (1) accretion to the N-terminus of two different phosphatidylinositol 3-phosphate-binding domains, PX in Cryptista (the fusion being the first proposed synapomorphy of this clade), and FYVE in Euglenozoa and the related undescribed flagellate SRT308; (2) acquisition of lipidic modifications of the N-terminal region, namely myristoylation and/or S-palmitoylation in seven different protist lineages; (3) acquisition of S-palmitoylation in the hypervariable C-terminal region of Rheb in apusomonads, convergently to some other Ras family proteins; (4) replacement of the C-terminal prenylation motif with four transmembrane segments in a novel Rheb paralog in the SAR clade; (5) loss of an evident C-terminal membrane attachment mechanism in Tremellomycetes and some Rheb paralogs of Euglenozoa. Rheb evolution is thus surprisingly dynamic and presents a spectacular example of molecular tinkering

Does High BMI Influence Hospital Charges in Children Undergoing Adenotonsillectomy?

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/93757/1/oby.2008.234.pd