Virtual combinatorial libraries: Dynamic generation of molecular and supramolecular diversity by self-assembly

Molecular and supramolecular diversity may be generated, respectively, by reversible, covalent or noncovalent self-assembly of basic components whose various potential combinations in number and nature represent a virtual combinatorial library. This concept is applied to the induction of inhibitors of carbonic anhydrase (CA) by reversible recombination of aldehyde and amine components. It is found that the presence of CA favors the formation of those condensation compounds that may be expected to present the strongest binding to the CA active site. The virtual combinatorial library approach may represent a powerful methodology for the discovery of substrates, inhibitors, receptors, catalysts, and carriers for a variety of processes.     

The impact of introducing new vaccines on the health system: Case studies from six low- and middle-income countries

Objective

We aimed to explore the impacts of new vaccine introductions on immunization programmes and health systems in low- and middle-income countries.

Methods

We conducted case studies of seven vaccine introductions in six countries (Cameroon, PCV; Ethiopia, PCV; Guatemala, rotavirus; Kenya, PCV; Mali, Meningitis A; Mali, PCV; Rwanda, HPV). Interviews were conducted with 261 national, regional and district key informants and questionnaires were completed with staff from 196 health facilities. Routine data from districts and health facilities were gathered on vaccination and antenatal service use. Data collection and analysis were structured around the World Health Organisation health system building blocks.

Findings

The new vaccines were viewed positively and seemed to integrate well into existing health systems. The introductions were found to have had no impact on many elements within the building blocks framework. Despite many key informants and facility respondents perceiving that the new vaccine introductions had increased coverage of other vaccines, the routine data showed no change. Positive effects perceived included enhanced credibility of the immunisation programme and strengthened health workers’ skills through training. Negative effects reported included an increase in workload and stock outs of the new vaccine, which created a perception in the community that all vaccines were out of stock in a facility. Most effects were found within the vaccination programmes; very few were reported on the broader health systems. Effects were primarily reported to be temporary, around the time of introduction only.

Conclusion

Although the new vaccine introductions were viewed as intrinsically positive, on the whole there was no evidence that they had any major impact, positive or negative, on the broader health systems.     

Association of the thickness of carotid intima-media complex and ancle brachial index with coronary disease severity

Abstract

Our aim was to establish the association of carotid intima-media thickness (CIMT) and ankle-brachial index(ABI) with the severity of coronary artery dissease (CAD). The study enrolled 150 examinees and divided them into two groups. The patients with stenotic changes in the coronary artery, constituted the first group (CP)(n=100); the second group consisted of the examinees without CAD — control goup (CG) (n=50). The following methods were used in the study: Color Doppler sonography of the carotid arteries, ABI, calculation of SCORE risk and coronary angiography.

Results

The number of coronary blood vessels affected by atherosclerosis was significantly higher with the increase of CIMT, CV risk score, and waist-hip ratio by one measurement unit: CIMT by 0.729; p<0.05; CV risk score by 0.033; p<0.05; and waist-hip ratio by 3.182; p<0.01. With each increase of ABI value by one measurement unit, the number of involved blood vessels dropped by 0.844; p<0.05.

Conclusions

Our results demonstrated that reduced ABI value, increased CIMT and number of plaques in the carotid arteries were in correlation with the severity of coronary artery disease.     

Long-term effectiveness and safety of interleukin-1 receptor antagonist (anakinra) in Schnitzler's syndrome: A french multicenter study

The aim of this study is to assess the long-term effectiveness and safety of IL1Ra in Schnitzler syndrome (SchS). Between 2010 and 2012, we performed a nationwide survey among French internal medicine departments to identify SchS patients. We retrospectively analyzed the long-term efficacy and safety of IL1Ra and the outcome of patients that did not receive this treatment. Forty-two patients were included in the study, 29 of whom received IL1Ra. The mean age at disease onset was 59.9 years. Disease manifestations included urticaria (100%), fever (76%), bone/joint pain (86%), bone lesions (76%), anemia (67%), and weight loss (60%). The monoclonal gammopathy was overwhelmingly IgM kappa (83%). The mean follow-up was 9.5 years (range: 1.6-35). Two patients developed Waldenström's macroglobulinemia and one developed AA amyloidosis. All of the 29 patients who received IL1Ra responded dramatically. After a median follow-up of 36 months (range: 2-79), the effectiveness remained unchanged. All patients remained on anti-IL-1 therapy. Twenty-four patients (83%) went into complete remission and five (17%) into partial remission. Three patients experienced grade 3-4 neutropenia. Six patients developed severe infections. No lymphoproliferative diseases occurred while on IL1Ra. When last seen, all patients without anakinra had an active disease with variable impact on their quality of life. Their median corticosteroids dosage was 6 mg/d (range: 5-25). IL1Ra is effective in SchS, with a sharp corticosteroid-sparing effect. Treatment failures should lead to reconsider the diagnosis. Long-term follow-up revealed no loss of effectiveness and a favorable tolerance profile. The long-term effects on the risk of hemopathy remain unknown.     

The perineal midsagittal view in male fetuses — pivotal for assessing genitourinary disorders

A wide range of genitourinary pathologies can be diagnosed in utero, from a simple vesicoureteral reflux to a more complex disorder of sexual differentiation. The prognosis and neonatal management of these conditions differ significantly. Evaluation of the fetal perineal anatomy is paramount to making the right diagnosis. The aim of this pictorial essay is to show sonographers how to acquire a perineal midsagittal view in a male fetus, and to demonstrate how this specific view allows assessment of the urethra and penis, to differentiate various genitourinary pathologies.

     

Temporary fibrin glue occlusion of the main pancreatic duct in the prevention of intra-abdominal complications after pancreatic resection: prospective randomized trial

OBJECTIVE: To determine whether temporary occlusion of the main pancreatic duct with human fibrin glue decreases the incidence of intra-abdominal complications after pancreatoduodenectomy (PD) or distal pancreatectomy (DP). SUMMARY BACKGROUND DATA: To the authors' knowledge, there are no randomized studies comparing outcomes after pancreatic resection with or without main pancreatic duct occlusion by injection of fibrin glue. Of three nonrandomized studies, two reported no fistulas after intracanal injection and ductal occlusion with fibrin glue after PD with immediate pancreatodigestive anastomosis, while another study reported no protective effect of glue injection. METHODS: This prospective, randomized, single-blinded, multicenter study, conducted between January 1995 and January 1999, included 182 consecutive patients undergoing PD followed by immediate pancreatic anastomosis or DP, whether for benign or malignant tumor or for chronic pancreatitis. One hundred two underwent pancreatic resection followed by ductal occlusion with fibrin glue (made slowly resorbable by the addition of aprotinin); 80 underwent resection without ductal occlusion. The main end point was the number of patients with one or more of the following intra-abdominal complications: pancreatic or other digestive tract fistula, intra-abdominal collections (infected or not), acute pancreatitis, or intra-abdominal or digestive tract hemorrhage. Severity factors included postoperative mortality, repeat operations, and length of hospital stay. RESULTS: The two groups were similar in pre- and intraoperative characteristics except that there were significantly more patients in the ductal occlusion group who were receiving octreotide, who had reinforcement of their anastomosis by fibrin glue, and who had fibrotic pancreatic stumps. However, the rate of patients with one or more intra-abdominal complications, and notably with pancreatic fistula, did not differ significantly between the two groups. There was still no significant difference found after statistical adjustment for these patient characteristic discrepancies, confirming the inefficacy of fibrin glue. The rate of intra-abdominal complications was significantly higher in the presence of a normal, nonfibrotic pancreatic stump and main pancreatic duct diameter less than 3 mm, whereas reinforcement of the anastomosis with fibrin glue or use of octreotide did not influence outcome. In multivariate analysis, however, normal pancreatic parenchyma was the only independent risk factor for intra-abdominal complications. No significant differences were found in the severity of complications between the two groups. CONCLUSIONS: Ductal occlusion by intracanal injection of fibrin glue decreases neither the rate nor the severity of intra-abdominal complications after pancreatic resection.     

Laparoscopic surgery for benign lesions of the pancreas

Background: Minimally invasive pancreatic surgery, although known to be feasible and safe, is still not considered a standard procedure. We report our experience with laparoscopic pancreatic surgery in a retrospective case series. Materials and Methods: Fifteen consecutive patients (3 male, 12 female) underwent primarily laparoscopic pancreatic surgery from February 2000 to June 2005. Histologically confirmed diagnoses were: neuroendocrine pancreatic tumors (n = 11), adult nesidioblastosis (n = 1), serous cystadenoma (n = 1), and pseudocysts due to chronic pancreatitis (n = 2). Results: Enucleation (n = 3) or left pancreatic resection with spleen preservation (n = 6) was performed laparoscopically in 9 patients. The mean (+/-standard deviation) operative time was 173 +/- 48 minutes (range, 120-250 minutes) and the mean postoperative hospital stay was 5.5 +/- 1.2 days (range, 5-8 days) for the laparoscopic cases. Conversion to open surgery was necessary in 6 patients because of: closeness of the lesion to the portal/mesenteric vein (n = 3), inadequate intraoperative tumor localization (n = 2), or stapler device dysfunction (n = 1). In these patients, open enucleation (n = 1), middle segment pancreatectomy (n = 2), left pancreatic resection (n = 2), and pylorus-preserving Whipple resection (n = 1) were performed. The mean operative time was 268 +/- 74 minutes (range, 150-360 minutes) with a mean postoperative hospital stay of 8 +/- 2 days (range, 6-10 days). Both operative time and hospital stay were significantly longer in patients with secondary open surgery compared to patients with successful laparoscopic operations. Conclusion: Laparoscopic enucleation or distal pancreatectomy with spleen preservation for benign lesions located in the body or tail of the pancreas can be performed safely, with all the potential benefits of minimally invasive surgery. Preoperative tumor localization is of utmost importance to limit pancreatic mobilization and to avoid blind pancreatic resection and conversion to open surgery.