Endoscopic placement of pancreatic stent for "Deep" pancreatic enucleations operative technique and preliminary experience at two high-volume centers.

BACKGROUND: Pancreatic enucleation (PE) is a viable option for the removal of non-malignant pancreatic masses leading to complete preservation of organ function. Nevertheless, PE is associated with substantial rates of post-operative pancreatic fistula (POPF), particularly when the mass is close to the main pancreatic duct (MPD). Preoperative stenting of the MPD may prevent its injury when performing PE. This paper describes a novel technique of "deep" PE preceded by endoscopic stenting of the MPD. METHODS: From January 2017 to May 2019, patients with small pancreatic neuroendocrine tumors proximal to the MPD were candidates for PE with previous stenting of the MPD at the University of Verona, Italy, and at the UCLA Medical Center, Los Angeles, California. The endoscopic stenting was scheduled either the day before or 3 weeks before surgery, depending on the participating institute. RESULTS: Ten patients were included in this pilot study. The endoscopic procedure was successful and well tolerated in all cases. Open, laparoscopic and robotic PE were performed. Seven patients had surgical complications. Among these, six developed a post-operative pancreatic fistula (POPF), but neither grade C fistulas nor disruptions of the MPD were detected. At pathology, a low grade pancreatic neuroendocrine tumor was confirmed in all cases. CONCLUSION: In the setting of high-volume centers, this procedure is safe, and it is associated with acceptable short-term surgical morbidity. The preoperative stenting of the MPD might extend the surgical indications for PE.

The Clinical Utility of Evaluating the Luminal Upper Gastrointestinal Tract During Linear Endoscopic Ultrasonography.

BACKGROUND: The clinical utility of performing esophagogastroduodenoscopy (EGD) before linear endoscopic ultrasonography (L-EUS) to evaluate the luminal upper gastrointestinal (GI) tract is not well established. GOALS: The study was aimed to determine the prevalence of clinically meaningful luminal abnormalities (any luminal finding requiring further evaluation with mucosal biopsy or initiation of treatment) in patients undergoing L-EUS. The study also sought to compare the ability of the gastroscope and the linear echoendoscope in identifying these lesions. STUDY: A prospective, multicenter cohort study enrolled patients undergoing L-EUS for nonluminal indications. All patients underwent EGD followed by L-EUS by 2 different endoscopists. The second endoscopist was blinded to the results of the initial EGD. The identification of clinically meaningful luminal lesions and quality of endoscopic visualization of the upper GI tract were measured. RESULTS: In the cohort of 175 patients, 52 (29.7%) patients had clinically meaningful luminal findings seen in the upper GI tract. There was no significant difference in the number of clinically meaningful lesions identified on EGD and L-EUS (25.1% vs. 22.9%, P=0.39). No significant difference was found in the miss rate of clinically meaningful lesions between the 2 modalities (EGD: 4.5% vs. EUS: 6.9%, P=0.39). CONCLUSIONS: A substantial minority of patients undergoing L-EUS for nonluminal indications will have clinically meaningful luminal findings. The endoscopic evaluation of the luminal upper GI tract can be adequately achieved using the linear echoendoscope.

Effect of Bacillus coagulans Unique IS2 with Lactulose on Functional Constipation in Adults: a Double-Blind Placebo Controlled Study.

In the present double-blind randomised study, the efficacy of combination of Bacillus coagulans Unique IS2 and lactulose was evaluated in the treatment of functional constipation in adults. One-fifty participants diagnosed with functional constipation (Rome III criteria) were randomised (1:1:1) and supplemented daily with 15 mL suspension of probiotic (B. coagulans Unique IS2, 2 × 109 spores) with lactulose (10 g) (group 1) or lactulose (10 g) (group 2) or placebo (water) (group 3) for 4 weeks. The primary (stool frequency) and secondary outome measures (stool consistency, sensation of incomplete evacuation, defecation- and abdominal-pain) were recorded weekly for up to 4 weeks. Bacillus coagulans Unique IS2 with lactulose showed significant changes in stool frequency as compared to lactulose treatment; however, at the end of the trial, it was found insignificant due to the gradual increase of stool frequency score of lactulose treatment. The changes observed in stool consistency were early (2nd week) and remained consistent up to end of the trial. The significant reduction of sensation of incomplete evacuation, defecation-, and abdominal-pain correlated with the strains ability to produce short-chain fatty acids. No adverse events were observed in any of the groups, and all the vital parameters were normal during the course of the study. Overall, results indicated that B. coagulans Unique IS2 addition to lactulose reduced time required to relieve constipation as compared to lactulose alone. In conclusion, B. coagulans Unique IS2 with lactulose is more effective than lactulose alone to relieve symptoms of constipation in a shorter period. Trial registration: CTRI/2018/11/016399, dated 22/11/2018.

Self-perceived health-related quality of life of Indian children with specific learning disability.

BACKGROUND: Specific learning disability (SpLD) often remains undetected, resulting in the afflicted child experiencing chronic poor school performance. AIMS: To measure and analyze the self-perceived health-related quality of life (HRQoL) of children with newly-diagnosed SpLD. SETTINGS AND DESIGN: Cross-sectional questionnaire-based study in our clinic. MATERIALS AND METHODS: From February to December 2008, 150 children consecutively diagnosed as having SpLD were enrolled and their HRQoL documented using the DISABKIDS chronic generic module self-report version instrument. STATISTICAL ANALYSIS: Multiple regression analysis was carried out for determining the 'independent' impact that each of the clinical and socio-demographic variables had on a poor facet score outcome and on a poor total score outcome. RESULTS: Clinically significant deficits were detected in all 6 facets, namely: 'large deficits (effect size ≥-0.8)' in "social exclusion", "emotion", "limitation", "treatment", and "independence"; and 'medium deficit (effect size -0.5 to <-0.8)' in "social inclusion"; and 'large deficit' in "total score". Multivariate analysis revealed that: (i) not belonging to the upper socio-economic strata of society was an independent predictor of a poor "independence" facet outcome (P=0.010, OR=1.99, 95% CI: 1.18 to 3.37); (ii) not having experienced class detainment was an independent predictor of a poor "emotion" facet outcome (P=0.008, OR=3.04, 95% CI: 1.34 to 6.85); (iii) first-born status was an independent predictor of a poor "limitation" facet outcome (P=0.022, OR=2.60, 95% CI: 1.15 to 5.90); and (iv) female gender was an independent predictor of a poor "social exclusion" facet outcome (P=0.024, OR=0.28, 95% CI: 0.09 to 0.85) and a poor "overall health" outcome (P=0.025, OR=0.32, 95% CI: 0.12 to 0.87). CONCLUSIONS: Children with newly-diagnosed SpLD perceive their psychosocial, physical, and overall HRQoL to be significantly compromised.

Achieving synaptically relevant pulses of neurotransmitter using PDMS microfluidics.

Fast synaptic transmission is mediated by post-synaptic ligand-gated ion channels (LGICs) transiently activated by neurotransmitter released from pre-synaptic vesicles. Although disruption of synaptic transmission has been implicated in numerous neurological and psychiatric disorders, effective and practical methods for studying LGICs in vitro under synaptically relevant conditions are unavailable. Here, we describe a novel microfluidic approach to solution switching that allows for precise temporal control over the neurotransmitter transient while substantially increasing experimental throughput, flexibility, reproducibility, and cost-effectiveness. When this system was used to apply ultra-brief ( approximately 400micros) GABA pulses to recombinant GABA(A) receptors, members of the cys-loop family of LGICs, the resulting currents resembled hippocampal inhibitory post-synaptic currents (IPSCs) and differed from currents evoked by longer, conventional pulses, illustrating the importance of evaluating LGICs on a synaptic timescale. This methodology should therefore allow the effects of disease-causing mutations and allosteric modulators to be evaluated in vitro under physiologically relevant conditions.

On-pump vs. off-pump coronary artery bypass surgery at a non-academic community hospital: have biocompatibility improvements eliminated the superiority of off-pump surgery?

OBJECTIVES: Standard coronary artery bypass grafting (CABG) surgery involves cardiopulmonary bypass (CPB) but given concerns over neurological and inflammatory complications related to CPB, many patients receive so-called off-pump procedures (OPCABG). Our objective is to determine if the recent improvements in the biocompatibility of CPB circuitry have improved post-operative outcomes at the community hospital level, particularly in terms of hospital length of stay (LOS), stroke and post-operative infection. METHODS: We analyzed hospital LOS, incidence of stroke, infection, and mortality along with several clinical variables in 209 patients (38% underwent OPCABG) at a single, non academic community hospital. We constructed a series of forward, stepwise, multiple-variable regression models using mediastinal infection, hospital LOS, and stroke as dependant variables. RESULTS: OPCABG was associated with a shorter median hospital LOS (3 days vs. 4 days; p=0.0001) and a reduced occurrence of stroke (0% vs. 7.6%; p=0.03). However, mediastinal infections occurred more commonly in OPCABG cases (10% vs. 2.2%; p=0.02). CABG and pre-existing renal disease were predictors of increased hospital LOS (p< 0.0001) whereas CABG was the only factor associated with decreased risk of mediastinal infection (OR=0.21 (0.05-0.80); p=0.02). CONCLUSIONS: At the community level, OPCABG appears to be superior in terms of LOS and incidence of stroke. Paradoxically, CABG surgery demonstrates a reduced rate of mediastinal infection.

Noncovalent interactions from electron density topology and solvent effects on spectral properties of Schiff bases.

Two Schiff bases were prepared by the condensation of o-allyl substituted 2,4-dihydroxy acetophenone with 1,2-diaminopropane (L1) and ethanediamine (L2) and characterized by elemental analysis, and ESI-MS, IR, UV-Vis, 1H and 13C NMR spectral techniques. The effect of solvents with respect to different polarities on UV-Vis and emission spectra of L1 and L2 was investigated at room temperature show that the compounds exist in keto and enol forms in solution and may be attributed to the intramolecular proton transfer in the ground state. The solute-solvent interactions, change in dipole moment and solvatochromic properties of the compounds were studied based on the solvent polarity parameters. For L1 and L2, the ground and excited state electronic structure calculations were carried out by DFT and TD-DFT at B3LYP/6-311G (d,p) level, respectively. The IR, NMR and electronic absorption spectra computed were compared with the experimental observations. The intramolecular charge transfer within the molecule is evidenced from the HOMO and LUMO energy levels and surface analysis. The noncovalent interactions like hydrogen bonding and van der Waals interactions were identified from the molecular geometry and electron localization function. These interactions in molecules have been studied by using reduced density gradient and graphed by Multiwfn.

Mechanism of action of Escherichia coli formamidopyrimidine N-glycosylase: role of K155 in substrate binding and product release.

Escherichia coli formamidopyrimidine N-glycosylase (fpg) is a DNA glycosylase with an associated beta,delta-lyase activity. We have recently shown that the highly conserved lysine residue K155 is important for base recognition. Incubation of a double-stranded DNA containing an abasic site with the wild-type fpg protein generated only beta,delta-product. However, incubation of a double-stranded DNA containing an abasic site opposite a small gap with fpg protein generated predominantly beta-product. These data suggested that the induction of a double-strand break by fpg led to the destabilization of the protein-DNA covalent intermediate, causing the fpg protein to prematurely dissociate from the DNA substrate. Furthermore, when a double-stranded DNA containing an abasic site opposite an A was used as a substrate, K155A mutant fpg protein yielded a mixture of beta- and beta,delta-products. These data suggested that K155 is essential for maintaining the stability of the intermediary protein-DNA covalent complex. Pre-steady-state burst kinetics showed that mutation in K155 led to the apparent disappearance of the initial burst, suggesting that the rate of product release from K155A is much greater than the rate of chemical reaction catalyzed by the mutant enzyme. This is consistent with the idea that K155A dissociates prematurely from the covalent complex, leading to a higher turnover number observed for K155A for DNA substrate containing an AP site.

Clinical utility of urine neutrophil gelatinase-associated lipocalin measured at admission to predict outcomes in heterogeneous population of critically ill patients.

Urine neutrophil gelatinase-associated lipocalin (uNGAL) is a reliable early biomarker of acute kidney injury (AKI) in a homogeneous patient population. However, its utility in a heterogeneous population of critically ill, in whom the time of onset of renal insult is often unclear, is not clearly established. We evaluated the ability of a single measurement of uNGAL in a heterogeneous adult population, on admission to intensive care unit (ICU), to predict the occurrence of AKI and hospital mortality. One hundred and two consecutive adult patients had uNGAL measured within 8 h of admission to ICU. The demographic and laboratory data were collected at admission. The diagnosis of AKI was based on AKI Network (AKIN) criteria. The primary outcome was the development of AKI, and the secondary outcome was hospital mortality. The mean age was 54 ± 16.4 years and 65% were males. Urine NGAL (ng/ml) was 69 ± 42 in patients with AKI (n = 42) and 30.4 ± 41.7 in those without AKI (P < 0.001). The area under the receiver operating characteristic (ROC) curve for prediction of AKI was 0.79 and for serum creatinine (SCr) was 0.88. The sensitivity and specificity for a cut-off value of uNGAL of 75 ng/ml to predict AKI were 0.5 and 0.85 respectively. uNGAL > 75 ng/ml was a strong (odd ratio = 5.17, 95% confidence interval: 1.39-19.3) and independent predictor of hospital mortality. A single measurement of uNGAL at admission to ICU exhibited good predictive ability for AKI though the sensitivity was low. The predictive ability of uNGAL was inferior to simultaneously measured SCr at admission, hence limited its clinical utility to predict AKI. However, admission uNGAL was a strong, independent predictor of hospital mortality.

Mechanism-based inhibition of human leukocyte elastase and cathepsin G by substituted dihydrouracils.

A series of dihydrouracil derivatives has been synthesized and investigated for their in vitro inhibitory activity toward human leukocyte elastase (HLE) and cathepsin G (Cath G). Alkyl [sulfonyl(oxy)] uracils 1-2 were found to be efficient, time-dependent inhibitors of elastase (kobs/[I] M-1 s-1 values ranged between 480 and 8110). These compounds formed acyl enzymes that exhibited variable hydrolytic stability which appeared to be dependent on the nature of the R1 group (believed to be accommodated at the primary specificity site, S1). The acyl enzymes formed with cathepsin G deacylated rapidly, leading to a significant regain of enzymatic activity. In sharp contrast, the corresponding phosphorus compounds 3-4 were found to be potent, time-dependent irreversible inhibitors of HLE. Furthermore, the results of the structure-activity relationship studies suggest that the binding modes of compounds 1-2 and 3-4 may be different.

3-(Alkylthio)-N-hydroxysuccinimide derivatives: potent inhibitors of human leukocyte elastase.

A series of 3-(alkylthio)-N-hydroxysuccinimide derivatives was synthesized and their inhibitory activity towards human leukocyte elastase (HLE) was investigated. The interaction of the compounds having a 3-alkylthioether side chain (compounds 1 and 2) with HLE was found to involve rapid acylation of the enzyme, followed by total regain of enzymatic activity within 3 h. Interestingly, compounds 3-8, having an oxidized thioether side chain, were found to be highly effective, time-dependent, irreversible inhibitors of the enzyme. The k(obs)/I values for compounds 3-8 ranged between 890 and 24,000 M-1 s-1. These findings demonstrate that, unlike the physiological inhibitor of HLE (alpha-1-proteinase inhibitor), which is inactivated upon oxidation, low-molecular-weight compounds retain and/or show enhanced inhibitory activity towards HLE upon oxidation of the thioether side chain and lay the groundwork for the development of compounds that embody proteinase inhibitory and antioxidant activity.

Application of blood purification to non-renal organ failure.

The application of artificial organs to the task of blood purification in the setting of non-renal organ failure simultaneously presents important challenges and opportunities. Failures of cardiovascular, hepatic, coagulation and immune systems are all characterized by dysregulation leading to multi-organ failure. When sustained, these conditions result in multiple organ system dysfunction and death and are far too common in modern intensive care units (ICUs). While the pathogenesis of each of these organ failures is complex and variable, brought about by a variety of underlying conditions, the potential to improve patient outcomes by simultaneously targeting multiple pathways can perhaps best be realized by blood purification. Unlike drug strategies, which are usually limited to one component of these complex networks, blood purification is, by its very nature, broad spectrum and self regulating. For example, as the concentration of mediators or toxins increases, so does removal. Furthermore, given the many failed trials of specific therapy, the recent focus of immunomodulatory therapy in sepsis has shifted to non-specific methods of influencing the entire inflammatory response without suppressing it. In this issue of the journal, members of the Acute Dialysis Quality Initiative (ADQI) present systematic reviews on the application of hemofiltration, ultrafiltration, plasma therapies and liver-assist therapy for the treatment of non-renal organ failure. The focus of these reviews is on clinical evidence as well as recommendations for future research.

Uncertainty in rate loss corrections based on counting a periodic pulser.

Tomographic gamma scanning of waste produces three-dimensional transmission and emission images. These are used to derive item-specific attenuation correction factors that improve the accuracy of non-destructive waste assay. For each vertical layer, data grabs of short duration are acquired as the waste item is rotated and translated. The image reconstruction demands accurate rate loss corrections to minimize assay bias. For this application a pulser was used to perform the necessary rate loss corrections. In this work, we summarize the benefits of the pulser approach and review the basic principles on which the method is based. We extend the treatment to include a derivation of the expression for the uncertainty in the net pulser peak area in the presence of an underlying continuum. We report experimental results, taken using a Canberra model WM2900 Tomographic Gamma Scanner, over a broad range of count-rates and peak-to-continuum ratios. Repeat counts under controlled conditions allowed the correction factor and its variance to be determined and compared against expectations. These results confirm the validity of the correction factor formula and the corresponding expression for its uncertainty. The rate loss analysis has been built into a Monte Carlo Replicate engine to allow the uncertainty to be propagated into the total measurement uncertainty of the final assay.

Identification of a new noradrenaline induced gene in the rat heart by differential mRNA display.

OBJECTIVE: Noradrenaline treatment of animals results in postnatal hypertrophy of the heart. This process requires many qualitative and quantitative changes in gene expression; however, the identities of the key regulatory genes which modulate the process are not known. The aim of this study was to investigate whether a recently developed technique, differential display, could provide a new route to the identification and characterisation of these critical genes. METHODS: The technique of differential display was modified for use on cardiac RNA samples and the expression of clones identified by this approach was characterised by northern analysis. RESULTS: Differential display was successfully adapted to the study of noradrenaline induced cardiac gene expression. A previously unsuspected gene was identified, the expression of which appears to be strongly modified during the onset of this process. CONCLUSIONS: Differential display offers the potential to identify and clone many of the genes critically important in regulation of growth of the mammalian heart.

Efficient inhibition of human leukocyte elastase and cathepsin G by saccharin derivatives.

A series of saccharin derivatives I has been synthesized and evaluated for their inhibitory activity toward human leukocyte elastase and cathepsin G. Most of the compounds were found to be efficient and time-dependent inhibitors of elastase. Inactivated elastase was found to regain its activity almost fully after 24 h (80-90% activity) and the half-lives of reactivation ranged between 12-15 h. Addition of hydroxylamine to fully-inactivated enzyme led to rapid and complete recovery of enzymatic activity. A tentative mechanism of action is proposed on the basis of biochemical and model studies.

Novel approaches to the treatment of acute renal failure.

Acute renal failure (ARF) occurs frequently in hospitalised patients and is associated with significant morbidity and mortality. Many therapeutic strategies have been undertaken both to prevent acute renal injury and, once ARF occurs, to improve renal function and reduce mortality. Among the available pharmacological options, no specific therapy has been shown to alter the course of ARF. This article reviews the efficacy of several strategies in experimental renal disease and raises the possibility that similar interventions might be available to the clinician in the near future for the prevention and management of ARF. The prospect of these novel strategies together with the ever-increasing understanding of the complex pathophysiology of ARF, offers the promise of effective and more physiological therapeutic interventions in this new millennium.

A lignan from the root of Ecbolium linneanum Kurz.

From the chloroform extract of the root of Ecbolium linneanum Kurz., a furofuran type of unsymmetrical lignan named as Ecbolin A was isolated. The structure was established by spectroscopic methods and confirmed by single crystal X-ray diffraction studies.

Acute interstitial nephritis complicating Legionnaires' Disease.

An acute interstitial nephritis was found in a patient with sudden renal failure and lung infection caused by Legionella pneumophilia. Our patient regained and maintained normal renal function after a short period of dialysis support. The diagnosis should be considered in any patient with a chest infection complicated by acute renal failure especially if confusion is disproportionate to the degree of uremia.

Physiological dead space & arterial to end-tidal CO2 difference under controlled normocapnic ventilation in young anaesthetised subjects.

Physiological dead space and its components were determined in 27 young, otherwise healthy anaesthetised individuals before start of surgery. A squarewave inspiratory flow pattern and an end inspiratory pause (25 and 10% of cycle time respectively) were used at a respiratory rate of around 16 bpm with minute ventilation adjusted to maintain normocapnia. The physiological dead space was found to be 2.23 ml/kg with anatomical dead space forming 110.66 +/- 27.55 ml out of 125.55 +/- 27.06 ml. While VD alv was positively correlated to pause pressure, VD ant was correlated to age, weight, and body surface area. Mean arterial end tidal carbon dioxide difference was quite low (0.24 +/- 0.44 kPa).

Immunogenicity study of Haemophilus influenzae type B conjugate vaccine in Indian infants.

OBJECTIVE: To assess the immunogenicity in Indian infants to Haemophilus influenzae b oligosaccharide conjugate vaccine (HbOC). DESIGN: Prospective multicenter study. SETTING: Pediatric Out Patient Department of general hospitals in Pune and Mumbai. SUBJECTS: 124 full term healthy infants brought for routine DPT/OPV immunization. METHODS: Infants were administered 3 doses of 0.5 ml of HbOC, on the same day as their DPT/OPV immunization, injected intramuscularly on the limb opposite to that where DPT vaccine was administered. Data on local reactions and general symptoms was collected for three days after every dose. The children had their blood collected for assay of anti PRP (polyribosil ribitol phosphate) antibody titers, along with the first injection and one month after the third injection. One hundred and three infants completed the study protocol with two blood collections. RESULTS: The initial geometric mean titers (GMT) of 0.124 mcg/ml rose by 37 times to 4.552 mcg/ml. Ninety eight children (95.1%) had a final titer of > or = 0.15 mcg/ml, the minimum level associated with protection, and 77 children (74.8%) had a final level of > or = 1.0 mcg/ml, a level associated with long term protection. CONCLUSION: HbOC is immunogenic in Indian infants when used as per the locally recommended DPT/OPV immunization schedule.