A case series study of therapeutic implications of type IIIb4: a rare variant of esophageal atresia and distal tracheoesophageal fistula.

BACKGROUND: A wide spectrum of variations can occur in type IIIb esophageal atresia and distal tracheoesophageal fistula [EA-TEF] (Kluth D. Atlas of esophageal atresia. J Pediatr Surg 1976; 11 (6):901-19). The aim of this study was to evaluate the variant anatomy of subtype IIIb4 EA-TEF and its therapeutic implications. METHODS: We performed a retrospective review of 4 patients of this variant subtype within a series of 259 esophageal atresias, managed over a study period of three years, at our institution. The diagnosis was made at thoracotomy. The overlapping upper and lower esophageal pouches, initially, gave a false impression of esophageal continuity. The long TEF coursed parallel in proximity to the upper pouch (UP) and the trachea needing meticulous dissection. The TEF measured 8-10mm in diameter and was ligated and divided high on the trachea near the thoracic inlet. The patients were followed up by a contrast swallow, radioactive technetium-99m- sulfur colloid scan, echocardiography and bronchoscopy (if indicated). RESULTS: The mean birth weight and gestational age was 2250 g and 38 weeks respectively. The mean follow up was eighteen months (range 5-42 months). An associated anorectal malformation was present in two patients while none had associated congenital heart disease. The Waterston grading was A and B in one patient each and C in two patients. All the patients had muscular UP extending up-to the level of arch of azygous vein (T(3-4)). The lower esophageal pouch (LP) and the fistula extended high, near the thoracic inlet. Tracheal injury occurred in one patient, with thin LP, warranting postoperative elective ventilation. A postoperative barium swallow did not reveal anastomotic leak or stricture in any patient. Follow-up barium swallow showed long LP extending high up in the chest, up to clavicles in all four patients and redundancy of UP in case 1. Severe gastroesophageal reflux was present in two patients. Bronchoscopy revealed tracheomalacia in case 1. Three patients were thriving well at the last follow-up. One patient died at five months of age due to aspiration pneumonia. CONCLUSIONS: The knowledge of diagnostic and therapeutic implications of the variant subtype IIIb4 EA-TEF should be in the armamentarium of the treating surgeon to reduce pitfalls in its management.

A psychological profile of a serial killer: a case report.

Serial killers have always fascinated society. A serial killer is typically defined as a perpetrator who murders three or more people over a period of time. Most reported cases of serial killers come from the United States and Canada. In India, there are few reported cases. We present, to the best of our knowledge, the first Indian case in the literature. The present case is of a 28-year-old man, Surinder Koli. The Department of Forensic Medicine & Toxicology, All India Institute of Medical Sciences, New Delphi handled the forensic study. We present a most unique psychological investigation into the mind of a serial killer.

Pleuropulmonary blastoma with cervical lymph node metastasis at presentation.

Pleuropulmonary blastoma is a rare childhood neoplasm accounting for less than one percent of all primary malignant lung tumors of children less than six years of age. Metastasis to CNS, orbit and iris, bone, contralateral lung and rarely adrenal glands, liver, kidney and pancreas has been described. This report presents a rare case of pleuropulmonary blastoma with cervical lymph node metastasis at the time of presentation.

Characterization, thermodynamic parameters and in vivo antimalarial activity of inclusion complexes of artemether.

The present study aimed to improve solubility, dissolution and ultimate bioavailability of poorly soluble artemether, an antimalarial drug, by encapsulating it in ß-cyclodextrin (ß-CD) and its methyl and hydroxylpropyl derivatives. The effect of these complexes was confirmed by in vivo studies. Phase solubility studies indicated 1:1 stoichiometry and were supported by mass spectrometry and proton nuclear magnetic resonance ((1)H-NMR) spectroscopy. True inclusion of artemether into the cyclodextrin cavity was observed in lyophilized complexes by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and Fourier transform infrared spectroscopy (FT-IR) studies. The mode of inclusion was supported by two-dimensional (2D) NMR. Solution calorimetry was used to confirm 1:1 stiochiometry by determining the enthalpy of interaction between the drug and cyclodextrins. The stability constant (K) of inclusion and other thermodynamic parameters such as enthalpy (ΔH) as well as entropy (ΔS) of binding accompanying the encapsulation were determined. The calculated value of K indicated that M-ß-CD has maximum complexing efficiency. Dissolution studies indicated that the highest release rate was observed for lyophilized complexes. In vivo studies of lyophilized complexes of M-ß-CD showed a 3-fold increase in antimalarial activity compared to artemether and resulted in 100% eradication of parasite. However, 83% and 50% survival rates were achieved in 40 days using HP-ß-CD and ß-CD complexes respectively. The study concludes that encapsulation of artemether by cyclodextrins is a good alternative to enhance the bioavailability of the drug.

The rapid drift of the Indian tectonic plate.

The breakup of the supercontinent Gondwanaland into Africa, Antarctica, Australia and India about 140 million years ago, and consequently the opening of the Indian Ocean, is thought to have been caused by heating of the lithosphere from below by a large plume whose relicts are now the Marion, Kerguelen and Réunion plumes. Plate reconstructions based on palaeomagnetic data suggest that the Indian plate attained a very high speed (18-20 cm yr(-1) during the late Cretaceous period) subsequent to its breakup from Gondwanaland, and then slowed to approximately 5 cm yr(-1) after the continental collision with Asia approximately 50 Myr ago. The Australian and African plates moved comparatively less distance and at much lower speeds of 2-4 cm yr(-1) (refs 3-5). Antarctica remained almost stationary. This mobility makes India unique among the fragments of Gondwanaland. Here we propose that when the fragments of Gondwanaland were separated by the plume, the penetration of their lithospheric roots into the asthenosphere were important in determining their speed. We estimated the thickness of the lithospheric plates of the different fragments of Gondwanaland around the Indian Ocean by using the shear-wave receiver function technique. We found that the fragment of Gondwanaland with clearly the thinnest lithosphere is India. The lithospheric roots in South Africa, Australia and Antarctica are between 180 and 300 km deep, whereas the Indian lithosphere extends only about 100 km deep. We infer that the plume that partitioned Gondwanaland may have also melted the lower half of the Indian lithosphere, thus permitting faster motion due to ridge push or slab pull.

Quantitative analysis of in vitro compatibility of binary and ternary mixtures of nitroimidazole and macrolides in combination with omeprazole using a calorimetric technique.

In the present study, in vitro interactions between nitroimidazoles, macrolides and omeprazole in binary and ternary mixtures were examined by measuring their enthalpy of solution (delta(sol)H) using a calorimetric technique. A comparison of the enthalpy of solution of the pure drugs with those of binary and ternary mixtures at pH 2 and 6 was made to indicate the magnitude of interaction between them. The delta(sol)H for all the nitroimidazoles is endothermic at pH 2 and 6 but both the macrolides show exothermic behavior, whereas the enthalpy of solution of omeprazole changes from -40.52 to 4.35 kJmol(-1) as the pH changes from 2 to 6. The results have been quantified by determining the excess enthalpy of solution for both binary and ternary systems. The small deviations from ideality for all the binary systems are attributed to various non-bonding interactions between different functional groups on both the drug molecules. The results suggest compatibility of drug pairs in their binary mixtures. However, ternary mixtures show somewhat larger interactions. The magnitude of interaction enthalpy of a ternary mixture comprising tinidazole, clarithromycin and omeprazoles which are available as a marketed kitshas been calculated to be significant, suggesting that the three drugs cannot be co-formulated.

Degradation kinetics of Metronidazole and its Mutual Prodrug with Ciprofloxacin : a Calorimetric Analysis

Calorimetric technique has aroused considerable interest as a versatile tool in pharmaceutical industry and academia to provide useful information about thermodynamic and kinetic aspects of drug molecules. The present paper utilizes this technique to monitor the hydrolytic degradation of metronidazole and its prodrug with ciprofloxacin; i.e. 2-(2-methyl-5-nitroimidazol-1-yl)ethyl-1-cyclopropyl-6-fluoro-1;4-dihydro-4-oxo-7-(1-piperazinyl)-quinoline-3-carboxylate. The synthesis of the present mutual prodrug was envisaged to combine the antiprotozoal and anaerobic antibacterial effects of metronidazole with antibacterial effects of ciprofloxacin. Heat flux microcalorimeter was used to determine the rate of heat evolved during the degradation of the drug and prodrug as a function of concentration; pH and temperature. In terms of enthalpy of hydrolysis the response is exothermic both for drug and prodrug. However; the absolute value of the enthalpy of reaction (?rH0) is low for the prodrug. The degradation followed pseudo first order kinetics; showed marked stability at pH 3-7 followed by accelerated hydrolysis at higher pH; characteristic of general acid-base catalysis. The catalytic rate constant for hydrogen ion (kH) and hydroxyl ion (kOH) were found to be 0.413 and 526.1 M-1h-1; respectively; at 318.15 K. The hydrolysis of the prodrug was found to be approximately 50-60 times faster than that of the drug. This may be attributed to the fact that hydrolysis of ester group in prodrug is assisted by keto group on the ciprofloxacin. However; there is no effect of protonation of nitrogen in piperazine ring in ciprofloxacin on the hydrolysis due to the distance from the ester moiety

The histopathology of congenital pouch colon associated with anorectal agenesis.

The colonic pouch excised during surgery in 17 patients with congenital pouch colon associated with anorectal agenesis (CPC) was subjected to detailed histological examination after staining with hematoxylin and eosin. The patients included 11 newborns, 3 infants, and 3 older children. The most frequently observed abnormalities were acute and chronic inflammation of the mucosa and submucosa, focal or generalized thinning of muscle layers, especially of the outer muscle coat, disorganized muscle layers, a decreased number of mature ganglion cells, and neuronal hyperplasia and hypertrophy in nerve plexuses. Ectopic heteroplastic tissues were identified in 2 patients. These findings suggest that the colonic pouch in CPC represents abnormally developed colonic tissue and points to the similarity with segmental dilatation of the colon. The neuromuscular abnormalities explain the physiological characteristics of the colonic pouch, namely weak peristalsis as well as the propensity to undergo marked dilatation even after tubularization.

Microcalorimetric evaluation of the in vitro compatibility of amoxicillin/clavulanic acid and ampicillin/sulbactam with ciprofloxacin.

Solution calorimetric technique has been used to determine the compatibility of binary and ternary systems of ampicillin trihydrate (AMP), sulbactam sodium (SS), amoxicillin trihydrate (AM), potassium clavulanate (PC) and ciprofloxacin hydrochloride (CP). The enthalpy of solution (DeltasolH) were obtained over a wide range of composition in the pH range 2-9. For all the pure drugs the DeltasolH is endothermic in nature. The molar enthalpies of interaction of binary (DeltaHbi.E) and ternary (DeltaHter.E) mixtures of the drugs in aqueous buffers have been determined. The DeltaHbi.E for all binary systems is negative and pH dependent (maximum pH 6-8) indicating the interaction among charged species of the drugs. In case of binary systems with CP the magnitude of DeltaHbi.E indicate strong interactions. The variation and magnitude of DeltaHbi.E for the systems is discussed in terms of hydrogen bonding and van der Waal's interaction in the solution. The interaction parameter for ternary systems (A) is positive indicating repulsive interaction among the drugs. The coefficients hi's calculated from Redlich-Kister equation for binary systems (DeltaHbi.E) and ternary interaction parameter (A) were used to predict the compatibility of the marketed formulations in pH range studied.

Kinetics of degradation of diclofenac sodium in aqueous solution determined by a calorimetric method.

An isothermal heat conduction microcalorimeter has been used to study the stability of diclofenac sodium both alone and its inclusion complex with beta-cyclodextrin in aqueous solution. The rates of heat evolved during degradation of diclofenac sodium have been measured by a highly sensitive microcalorimetric technique as function of concentration, pH and temperature. The calorimetric accessible data have been incorporated in the equations for determination of rate constants, change in enthalpy and order of reaction. The decomposition of diclofenac sodium both alone and its inclusion complex with beta-cyclodextrin in solution corresponds to a pseudo-first order reaction. The values of rate constants, k's at 338.15 K, (calculated from the variation of heat evolution with the time) for the degradation of diclofenac sodium at pH 5, 6, 7, 8 and its inclusion complex with beta-cyclodextrin at pH 7 are found to be 4.71 x 10(-4), 5.69 x 10(-4), 6.12 x 10(-)4, 6.57 x 10(-4) and 4.26 x 10(-4) h(-1) respectively. There is good agreement between calorimetric determined t(0.5) and literature values. It has been found that beta-cyclodextrin retards the degradation of diclofenac sodium. The kinetic parameters have been calculated for the reaction. The negative entropy of activation suggests the formation of an ordered transition state.

Microcalorimetric studies to determine the enthalpy of solution of diclofenac sodium, paracetamol and their binary mixtures at 310.15 K.

A sensitive and selective microcalorimetric technique has been used to determine the enthalpy of solution of diclofenac sodium (DS), paracetamol (PC) and their binary mixtures over a wide range of composition in the pH range 4-12. The systems showed endothermic behavior. The molar enthalpies of solutions of DS vary between 42.26+/-0.16 and 50.48+/-0.03 kJ mol(-1) at pH 4-9 and for PC from 24.28+/-0.05 to 36.03+/-0.01 kJ mol(-1) at pH 5-12. The excess molar enthalpy of their mixtures has also been determined. The values of excess molar enthalpy of solutions are negative and very low in magnitude indicating no specific interaction between DS and PC in solution.

Kinetic studies of the degradation of an aminopenicillin antibiotic (amoxicillin trihydrate) in aqueous solution using heat conduction microcalorimetry.

Recent developments in isothermal microcalorimetry allow the direct determination of kinetic and thermodynamic parameters for slow reactions from studies conducted at appropriate temperatures and under designated environmental control. The degradation kinetics of amoxicillin trihydrate has been investigated as a function of pH (1-10) and temperature (303.15-318.15 K) at 0.5 M ionic strength using heat conduction microcalorimetry. Equations were developed incorporating calorimetric accessible data, rate constants and change in enthalpy, which showed that the degradation of amoxicillin trihydrate in aqueous solution followed pseudo-first-order kinetics under our experimental conditions. The enthalpy of degradation reaction was found to be exothermic in nature. The values of the rate constant k for individual steps were determined from the values of the overall rate constants at different pH. Energy of activation of overall reaction as a function of pH and for individual rate constants was determined. The log k-pH profiles indicated specific-acid and specific-base catalysis and there were inflection points near pH 3 and pH 7 corresponding to the pKa1 and pKa2 values. Quantitatively, there was good correlation between calorimetric determined half-life (t1/2) and the literature value in the acidic region determined by other methods at 310.15 K. The presence of a beta-lactam ring and of an alpha-amino group in the C-6 side chain played a critical role in the degradation of amoxicillin trihydrate and the zwitterionic form of the drug was found to be more stable.

Survey of bottled drinking waters sold in Canada for chlorate, bromide, bromate, lead, cadmium and other trace elements.

Mineral, spring and other bottled drinking waters sold in Canada in the winter of 1995-96 were surveyed for chlorate, bromide, bromate, Cr(VI), Li, B, Al, Mn, Cu, Zn, Sr, Ba, Be, V, Cr, Co, Ni, As, Se, Mo, Ag, Cd, Sb, Tl, Pb, Na, K, Ca and Mg. Chlorate and bromide were determined by ion chromatography (IC) with conductivity detection, Cr(VI) by IC with colorimetric detection, bromate by solvent extraction and gas chromatography (GC), trace elements by inductively coupled plasma mass spectrometry (ICPMS), and Na, K, Ca and Mg by flame atomic absorption spectrometry (FAA). Most chemicals in the 199 samples analysed were well within national and international drinking water guidelines. World Health Organization and/or Canadian drinking water guidelines were exceeded for B (22 samples), Al (9), Cr (1), Mn (5), Ni (1), As (10), Se (24) and Pb (1). Bromate levels are reported for information purposes and are considered as the maximum concentrations in the samples. In three distilled water products, unexpectedly high concentrations of Cu (88-147 micro g l(-1)) and Ni (16-35 micro g l(-1)) were found, and a comparison of distilled and non-distilled waters from two of the brands suggested the likely cause to be contamination during the distillation process. Li concentration in one sample was at a therapeutic dose and could pose an overdose risk to individuals on Li medication.

Calorimetric studies of diclofenac sodium in aqueous solution of cyclodextrin and water-ethanol mixtures.

The technique of solution calorimetry has been employed to study the interaction between diclofenac sodium and beta-cyclodextrin by determining the enthalpies of solution of the drug in water and in aqueous beta-cyclodextrin solution. Thermodynamic parameters characterizing the binding process such as enthalpy deltaH0, equilibrium constant K, free energy deltaG0 and entropy deltaS0 have been calculated to be 12.00 kJ mol(-1), 1670 dm3 mol(-1), -19.03kJ mol(-1) and 22.98 J K(-1) mol(-1), respectively. Enthalpies of solution of diclofenac sodium have also been determined in water-ethanol mixtures.

Congenital pouch colon associated with segmental dilatation of the colon.

A 1-day-old boy who presented with an anorectal malformation (ARM) was found to have a segmental dilatation of the colon (SDC) associated with a typical congenital pouch colon (CPC) malformation. The distal colonic pouch terminated in a high colovesical fistula. The posterior portion of the perineal raphé was duplicated and ended in 2 anal dimples. Both dilated segments of the colon were excised. The similarity between CPC and SDC is highlighted, and the possible embryogenesis of both conditions is discussed.

Two cases of pseudoduplication of the external genitalia.

In two newborn boys an accessory rudimentary phallus and scrotal sacs were present on the surface of a midline perineal swelling. Both boys had an associated high anorectal anomaly (ARA), a small phallus, and a bifid scrotum with absence of the scrotal raphé. One also had penile torsion with hypospadias and an accessory anal dimple. During definitive surgery for the ARA in one patient, excision of the perineal soft-tissue mass and overlying duplicated penoscrotal tissue was performed. The embryogenesis of this condition is discussed.

Female pseudohermaphroditism associated with cloacal anomalies: faulty differentiation in the caudal developmental field.

A 1(1/2)-year-old girl with a urogenital sinus defect associated with an enlarged phalluslike clitoris is described. The child had an anteriorly located anus, a single kidney with grade III vesicoureteric reflux, a 3.5-cm-long common urethrovaginal channel, a large vesical calculus, and a hamartoma in the pubic region. After a preliminary colostomy, definitive surgery consisted of urethral reconstruction, vaginal reconstruction using a colonic graft, and posterior relocation of the anus. The discussion centers on a review of the previously reported cases of female pseudohermaphroditism associated with cloacal or urogenital sinus defects (FPHCD). The likely embryogenesis of this condition is discussed, and the similarity of the features with those seen in some patients with complete penoscrotal transposition (CPST) is highlighted.

Complete diphallia associated with features of covered exstrophy.

This report describes a 1-day-old boy with complete true diphallia associated with features of covered or pseudo-exstrophy and an anorectal malformation. The urinary bladder and rectum were single. A divided sigmoid colostomy was constructed at birth for the anorectal anomaly. Complete diphallia and its likely embryogenesis are discussed.