Is an Antireflux Procedure Necessary for a Successful Appendicostomy? The Simplified Malone Antegrade Continence Enema Procedure.

Aim: The aim of this study was to present the long-term institutional experience and outcomes of our Malone antegrade continence enema (MACE) procedure using the proximal appendix without any antireflux procedure. Materials and Methods: A single-center prospective study of 29 children undergoing a simplified Malone antegrade continence enema (SMACE) procedure from 2006 to 2017 was conducted using the appendix, whole or split. The mean follow-up period was 11.5 years (ranging from 5 to 16 years). Results: In 25 children, the proximal appendix was used, and in 4 cases, the whole appendix was used as a conduit. On follow-up, the MACE channel has been working well in 29/29 patients. Among the complications, seven patients had stomal stenosis, which was managed by home dilatation. There was no reflux of stools seen in any of the patients. Conclusion: The SMACE procedure, without incorporating an antireflux mechanism, is technically simpler and saves operative time. Most importantly, the results are satisfactory and comparable with procedures using antireflux techniques.

Quality by design (QbD) based development and validation of an HPLC method for amiodarone hydrochloride and its impurities in the drug substance.

The USP monograph describes an HPLC method for seven impurities in the amiodarone drug substance using a L1 column, 4.6mm×150mm, 5µm packing (PF listed ODS2 GL-Science, Inertsil column) at 30°C with detection at 240nm. The standard contains 0.01mg/mL of amiodarone, and USP specified impurities D and E with a resolution requirement of NLT 3.5 between peaks D and E. Impurities in a 5mg/mL sample are quantitated against the standard. Impurity A peak elutes just before peak D. We observed two problems with the method; the column lot-to-lot variability resulted in unresolved A, D, and E peaks, and peak D in the sample preparation eluted much later than that in the standard solution. Therefore, optimization experiments were conducted on the USP method following the QbD approach with Fusion AE™ software (S-Matrix Corporation). The resulting optimized conditions were within the allowable changes per USP 〈621〉. Lot-to-lot variability was negligible with the Atlantis T3 (Waters Corporation) L1 column. Peak D retention time remained constant from standard to sample. The optimized method was validated in terms of accuracy, precision, linearity, range, LOQ/LOD, specificity, robustness, equivalency to the USP method, and solution stability. The QbD based development helped in generating a design space and operating space with knowledge of all method performance characteristics and limitations and successful method robustness within the operating space.

Quality by design (QbD) based development of a stability indicating HPLC method for drug and impurities.

In this paper, an application of Quality by Design (QbD) concepts to the development of a stability indicating HPLC method for a complex pain management drug product containing drug substance, two preservatives, and their degradants is described. The QbD approach consisted of (i) developing a full understanding of the intended purpose, (ii) developing predictive solutions, (iii) designing a meaningful system suitability solution that helps to identify failure modes, and (iv) following design of experiments (DOE) approach. The starting method lacked any resolution among drug degradant and preservative oxidative degradant peaks, and peaks for preservative and another drug degradant. The method optimization was accomplished using Fusion AE™ software (S-Matrix Corporation, Eureka, CA) that follows a DOE approach. Column temperature (50 ± 5°C), mobile phase buffer pH (2.9 ± 0.2), initial % acetonitrile (ACN, 2 ± 1%), and initial hold time (2.5, 5, or 10 min) of the HPLC method were simultaneously studied to optimize separation of the unresolved peaks. The optimized HPLC conditions (column temperature of 50°C, buffer pH of 3.1, 3% initial ACN with 2.5 min initial hold) resulted in fully resolved peaks in the two critical pairs. The QbD based method development helped in generating a design space and operating space with knowledge of all method performance characteristics and limitations and successful method robustness within the operating space.

A study of acute febrile encephalopathy with special reference to viral etiology.

OBJECTIVE: To study the etiological profile of patients with acute febrile encephalopathy syndrome focusing chiefly on the viral etiology, and to correlate clinical and radiological features of patients with viral encephalitis. METHODS: A prospective hospital based study conducted on the consecutive patients admitted in a pediatric unit during the period of 1(st) February 2004 to 31st January 2005 based on the following inclusion criteria: (1) Age more than 1 month and less than 18 years and (2) A diagnoses of acute febrile encephalopathy, based on the following criteria: (i) fever (ii) acute depression of consciousness or mental deterioration for more than 12 hours with or without motor or sensory deficit and (iii) Total duration of illness at the time of admission 1 week or less. RESULTS: The final study group comprised of 151 patients with mean age of 3.21 +/- 2.9 (range of mth-13 years) and male: female ratio of 1.71: 1. A diagnosis other than viral encephalitis was reached in 94 patients (62.3 %). Pyogenic meningitis was the most frequent diagnosis 51(33.8 %) followed by tubercular meningitis 12 (7.9 %), and cerebral malaria 8 (5.2 %) in the patient group of non-viral causes. Fifty-seven cases (37.3%) were suspected as viral encephalitis and mean age of the cases suspected as viral encephalitis was 2.8 +/- 2.9 (Range 1 mth-10 yrs) with male: female ratio of 1.28: 1. Etiological diagnosis was reached or considered probable in 41 (72%) cases out of the suspected patients. The most common etiological agent identified was enterovirus 71 in 20 patients (35.1 %). The other viruses identified were mumps in 6 (10.5%), Japanese encephalitis in 5 (8.7%), and measles in 4 (7%) cases. MRI brain was done in 39 patients and was abnormal in 14 patients. Out of 57 cases of suspected viral encephalitis 10 patients expired within 48 hours, 2 > 48 hours and 19 atients had significant neurological sequels at discharge. CONCLUSION: The etiology of acute febrile encephalopathy varies from infectious etiologies to noninfectious metabolic disorders. There are no distinguishing clinical or radiological features to differentiate the various causes of viral encephalitis. The clinical and the radiological findings in encephalitis should be interpreted in the geographical and other epidemiological background.

Gel permeation chromatography of dextrans in parenteral solutions: calibration procedure development and method validation.

We describe development and validation of a gel permeation chromatographic (GPC) method for dextrans in parenteral solutions. The GPC method was adopted from USP monographs on Dextran 40 and Dextran 70 raw materials. The method was optimized with a mobile phase flow rate of 1 mL/min and column temperature of 40 degrees C, to sharpen dextran and dextrose peaks. An easy-to-use, curve-fitting program capable of non-linear regression was developed in-house, using Microsoft Excel and its Solver add-in to successfully meet the GPC calibration requirements for dextrans and dextrose, i.e., the experimental molecular weights within 100+/-5% of the known molecular weights for dextrans and molecular weight of dextrose within 180+/-2 Da. The GPC method was validated in terms of its stability indicating nature, robustness (column temperature of 40+/-3 degrees C), accuracy (lack of effects of pH and concentration of dextrans or matrix components), and precision (repeatability and intermediate). Molecular weight distribution of dextrans were unchanged when the dextran containing test solutions were subjected to forced degradation using heat, light (daylight and UV light), extreme alkaline conditions or oxidative conditions. The method was capable of detecting changes in molecular weight distribution caused by degradation under extreme acidic conditions and heat, thereby confirming the stability indicating nature of the method. The concentration of Dextran 40 and Dextran 70 (75-125% of the nominal assay concentration), matrix components (108-111% of their nominal concentrations), and solution pH (pH 3-7 for Dextran 40 solutions and pH 4-7 for Dextran 70 solutions) did not affect the measured molecular weight distribution of Dextran 40 or Dextran 70. The method was precise with %R.S.D. of less than 1% for M (W) values of Dextran 40 or Dextran 70.

Isolated liver tuberculosis: a case report.

A case of liver tuberculosis resembling a hemangioendothelioma on computed tomography and clinically masquerading as a tumor is reported. The cause of isolated liver tuberculosis and the importance of an open liver biopsy is discussed, with a review of the literature.

Validated ion-exclusion chromatographic method for citrate and acetate in medical fluids.

In this paper we describe the development and validation of a solid-phase extraction procedure, followed by ion-exclusion chromatographic determination of citrate and acetate in medical fluids. The medical fluids contained trace levels of non-polar compounds, which were not of interest for the purposes of assay requirements, but due to their strong affinity towards the ion-exclusion chromatography column necessitated a 180-min long runtime to elute. The developed SPE procedure, based on trapping the hydrophobic compounds, on a reversed-phase material, while allowing analytes of interest elute off unretained, shortened the runtime to 35 min. The procedure is simple since it has only two steps, conditioning of the SPE cartridge with acetonitrile and treating the sample. The SPE procedure followed by ion-exclusion chromatographic determination was successfully validated per the International Conference on Harmonization (ICH) guidelines in terms of specificity, accuracy as recovery versus untreated sample, precision, range, linearity of response, ruggedness, stability of treated samples, and robustness. The validation data showed that the method is specific, accurate, precise, rugged, and robust. The validated method has been routinely used in the manufacturing environment.

A novel PI index and its applications to QSPR/QSAR studies.

A novel topological index, PI (Padmakar-Ivan index), is derived in this paper. The index is very simple to calculate and has disseminating power similar to that of the Wiener (W) and the Szeged (Sz) indices. The comprehensive studies show that the proposed PI index correlates highly with W and Sz as well as with physicochemical properties and biological activities of a large number of diversified and complex compounds. The proposed PI index promises to be a useful parameter in the QSPR/QSAR studies. The stability of each model is demonstrated by applying cross-validation test. Furthermore, more favorable comparison with other representative indices such as the Randic index is also made in order to establish the predictive ability of the PI index. The results have shown that in several cases the PI index gave better results.

Long-term results of surgery for posterior urethral valves: a review.

Although the techniques for valve resection have been refined and the short-term management of patients with posterior valves has improved remarkably, there is growing concern about long-term outcome. Prenatal diagnosis has added to the urgency of predicting long-term outcome. This paper reviews all the important long-term data available with the aim of providing a concise picture for the reader, vis-a-vis long-term renal function, the role of proximal diversion in long-term outcome, bladder function and incontinence, the place of renal transplantation, prenatal diagnosis, intervention and prediction of renal function and sexual function and fertility.

Genetic transformation and hairy root induction in Holostemma ada-kodien K. Schum--a vulnerable medicinal plant.

Hairy roots were induced from shoot buds and seedling hypocotyls of Holostemma by infection with agropine type Agrobacterium rhizogenes strains. Type of explant, Agrobacterium rhizogenes strain used for infection, co-culture time and photoperiod influenced the transformation frequencies. Hairy roots were induced from seedling hypocotyls and shoot bud explants upon infection with agropine type Agrobacterium rhizogenes strains. The hairy roots were thin, whitish in colour and showed negatively geotropic growth. The transformed nature of hairy roots was confirmed by opine analysis.

QSAR study on binding affinity of PATs (rodenticides) to the [3H]-mepyramine-labelled H1 receptor in rat and guinea pig brain.

The binding of a series of PAT analogues (rodenticides) to the [3H]-mepyramine-labelled H1 receptor in rat and guinea pig brain was investigated topologically using negentropy (N), molecular redundancy (MRI), first-order molecular connectivity (1chi(v)), Wiener (W), and Szeged (Sz) indices. Multiple regression analyses showed that MRI provided excellent results upon introduction of indicator parameters. Predictive ability of the proposed models was discussed using cross-validation parameters.

A comparative QSAR study using Wiener, Szeged, and molecular connectivity indices

In this study we have investigated the relative correlation potential of Wiener (W), Szeged (Sz), and molecular connectivity indices (0chiR, 1chiR and 2chiR) in developing quantitative structure-activity relationships, QSAR; log P values of benzoic acid and its nuclear-substituted derivatives were used for this purpose. The statistical analyses for univariate and multivariate correlations had indicated that both W and Sz are closely related to the connectivity indices (mchiR) and that the W, the Sz, and the 1chiR indices have similar modeling potentials. 1chiR gives slightly better results than both W and Sz. Other connectivity indices 0chiR and 2chiR correlate poorly with log P.

Analysis of wastewater for anionic and cationic nutrients by ion chromatography in a single run with sequential flow injection analysis.

To prevent nutrient enrichment and, hence the undesirable ecological impacts, the nutrients monitored in wastewater samples include two anionic species, i.e., nitrate and orthophosphate, and a cationic species, ammonium. Ion chromatography (IC) is one of the popularly used techniques for determinations of nitrate and phosphate in these samples, whereas determination of ammonium in wastewater samples is typically done using manual or automated wet chemistry, e.g., flow injection analysis (FIA). We have developed a sequential IC-FIA method, using Lachat's QC8000 IC system, which allows determinations of nitrate, phosphate and ammonia in a single injection. In this system, a QuickChem Small Suppressor cartridge is regenerated in between the samples. A sample is injected while leaving the suppressor off-line. Ammonium, a cation, elutes in the void volume of an anion-exchange column. The unsuppressed column effluent, exiting the conductivity flow cell, up to this point is used for FIA determination of ammonia. When ammonia exits the conductivity flow cell, a fully regenerated suppressor is brought in-line for conductometric detection of the anions. Analog data are simultaneously acquired from colorimetric and conductometric detectors, for the cationic and anionic nutrients, respectively. The method is accurate with spike recoveries in wastewater samples ranging from 91% for nitrate to 114% for chloride. It is precise with RSD values, for replicate analyses (n = 7) of a mid-range standard, ranging from 0.4% for phosphate to 1% for nitrate.

Primary anastomosis in esophageal atresia type I without a gap.

This paper reports the case of an infant born with type I esophageal atresia (EA) associated with duodenal atresia (DA). The critical condition of the patient necessitated an exploratory laparotomy, which revealed severe dilatation of the stomach and duodenum. The routine procedure for repairing type I EA is a delayed primary anastomosis after 10 weeks of age because of the long gap between the two esophageal segments. In our case, due to the concomitant DA, the lower pouch was long enough to allow primary neonatal anastomosis. A radiograph taken with a Hegar dilator in the lower segment via the gastrostomy confirmed this suspicion, and the baby underwent a thoracotomy and primary anastomosis between the esophageal pouches. The authors propose the possibility of primary esophageal anastomosis in similar cases.

Presacral teratoma presenting with congenital urinary ascites.

Congenital teratomas occur most frequently in the sacrococcygeal region. Most grown into a large perineo-sacral swelling that is conspicuous externally. Infrequently, the neoplasm is contained almost entirely within the pelvis in the presacral space. Congenital urinary ascites is observed in patients with obstructive uropathy; posterior urethral valves in a newborn is one of the most prominent causes of urinary ascites. We report a case of presacral teratoma leading to rupture of the urinary bladder due to outflow obstruction and causing urinary ascites. The ascites was drained, the bladder was repaired, and the teratoma was successfully excised. A review of the literature did not reveal any similar case.

Papillomatosis of the gallbladder in metachromatic leukodystrophy.

A 2-year-old boy who presented with a cystic gallbladder mass was found histologically to have metachromatic leukodystrophy. Diffuse hyperplasia of the gallbladder mucosa, multiple tendrillar fronds extending into the lumen, extensive papillomatosis, and the presence of large numbers of macrophages bearing metachromatic material confirmed the diagnosis. The child developed progressive degeneration of the central nervous system, refractory bronchopneumonia, and generalized muscular atrophy. A computed tomographic scan of the brain demonstrated hypodense areas of white matter suggestive of demyelination. This report describes the rare association of gallbladder papillomatosis with a storage disorder and reviews the relevant literature.