A prospective study of evaluation of operative duration as a predictor of mortality in pediatric emergency surgery: Concept of 100 minutes laparotomy in resource-limited setting.

INTRODUCTION: Operative duration is an important but under-studied predictor of mortality in emergency laparotomies. AIMS AND OBJECTIVES: The primary objective of this study was to quantify the effect of duration of emergency laparotomy in children on mortality; and to identify a rough cut-off duration of laparotomy to serve as a guide so that a laparotomy can be planned to optimize pediatric surgical patient outcome. MATERIALS AND METHODS: This is a prospective study conducted in a government tertiary teaching institution over a period of 24 months. All children in the age group of 5-10 years presenting in the emergency department with Pediatric Risk of Mortality III score ≤8, undergoing emergency laparotomy in emergency operation theater, were included. OBSERVATIONS AND RESULTS: In all, 213 children were included in the study. The mean time from presentation to shifting to the operating room was 3.7 h. The mean operative duration was 108 min. The mean operative time in survived patients was 102 min as compared to 135 min in expired patients (P < 0.05). The 30-day in-hospital mortality rate was 17.4%. After application of binary logistic regression analysis, it was found that time to laparotomy and operative duration were significant risk factors (<0.05) predicting post-operative mortality. Kaplan-Meier survival curve showed a decrease at a mean weighted operative duration of approximately 100 min. Receiver operating characteristic curve analysis yielded operative duration of 123.5 min at which Youden's index maximized. CONCLUSION: This 100-min duration of laparotomy might appear a long duration but in casualty setup of a government hospital with limited resources, there are so many hurdles for optimal working that completion of an emergency laparotomy in children in 100 min can be considered a realistic target for improving post-operative outcome. At an operative duration of <123.50 min, mortality rates within acceptable limits can be achieved.

Diagnostic value of ultrasonography in evaluation and management of acute abdominal conditions in the paediatric age group.

BACKGROUND: The aims of this study have been elaborated below: (1) to enumerate the common causes of acute abdominal emergencies by ultrasonography in paediatric patients; (2) to establish the diagnostic efficacy of ultrasonography in evaluation of acute abdominal conditions in children and to illustrate the associated ultrasonographic findings; (3) and, to discuss the role of ultrasonography in guiding the mode of intervention in these cases. PATIENTS AND METHODS: This prospective study of ultrasonographic examination in 146 paediatric patients presenting with acute onset abdominal pain at the emergency/paediatric outpatient department section of Jawaharlal Nehru Medical College & Hospital, Aligarh, between June 2006 and December 2007, using 3.75 MHz and 8 MHz transducers of the ADARA (Siemens) machine. RESULTS: Common causes of acute abdominal emergencies in pediatric patients as noted on ultrasonography included nonspecific pain (28%), abdominal abscess (21%), acute appendicitis (7%) and intussusception (7%). Ultrasonography was diagnostic in 45.2% cases and supportive in 12.3% of the cases. As for as the final outcome, ultrasonography prevented surgery in almost 20% cases and laparotomy was avoided in 7% of the patients as ultrasound guided interventions in the form of abscess aspiration were carried out. CONCLUSION: Ultrasonography evaluation of children with acute abdominal pain, helps in making significant changes in the management plan of the patients, and also reveals various clinically unsuspected diseases.

Albumin-induced epithelial mesenchymal transformation.

BACKGROUND: Progressive chronic kidney disease is often associated with albuminuria and renal fibrosis linked to the accumulation of myofibroblasts producing extracellular matrix. Renal myofibroblasts are derived from a number of cells including tubular epithelial cells (TECs) through epithelial mesenchymal transformation (EMT). This study explores the hypothesis that exposure of TECs to albumin induces EMT. METHODS: Normal rat TECs (NRK52E) were exposed in culture to de-lipidated bovine serum albumin (dBSA; 10 mg/ml) for 2, 4 and 6 days. Binding/uptake of fluoresceined albumin by PTCs was evaluated. Transformation into myofibroblasts was assessed by light and electron microscopy, immunofluorescence and Western blotting for α-smooth muscle actin (α-SMA), E-cadherin and transforming growth factor-ß1 (TGF-ß1). We also investigated the expression of fibroblast-specific protein-1 (FSP-1) and collagens I, III and IV. TGF-ß1 biological activity, mRNA and protein were measured. A neutralising anti-TGF-ß1 antibody was used to analyse the role of TGF-ß1 in albumin-induced EMT. RESULTS: Exposure of TECs to dBSA led to binding/uptake of albumin as well as fibroblastic morphological changes. Incubation of TECs with dBSA caused a reduction of TEC marker E-cadherin (ANOVA p = 0.0002) and de novo expression of fibroblast markers α-SMA and FSP-1 (ANOVA p = 0.0001) in a time-dependent manner. It also increased expression and activity of TGF-ß1. Neutralisation of TGF-ß1 significantly reduced EMT (p < 0.01). CONCLUSION: This study demonstrates that in vitro, albumin induces the transformation of TECs into cells with myofibroblast characteristics; a process that may be TGF-ß1 dependent.

The value of fine-needle aspiration cytology in the evaluation of pediatric head and neck tumors.

OBJECTIVE: To study the efficacy of fine-needle aspiration cytology (FNAC) of head and neck masses in pediatric patients. STUDY DESIGN: Of the 128 cases studied, FNAC was performed in 74 patients and their cyto-histological correlation done. Sensitivity and specificity of cytological diagnosis was then computed. RESULTS: Benign lesions were found to be more common than the malignant variety, the commonest being soft tissue tumors (46.87%). Lymphomas were the commonest tumors (22.6%) in the malignant category. Cytology was done in 74 patients of whom smears from 21 patients were unsatisfactory for diagnosis. There was one false positive and two false negative cases resulting in the specificity and sensitivity of FNAC in pediatric head and neck tumors to be 95.65% and 93.3% respectively. CONCLUSION: FNAC is a useful and reliable tool in the diagnosis of head and neck masses with no contraindications and minimal complications even in children.

A comparison between EMLA cream application versus lidocaine infiltration for postoperative analgesia after inguinal herniotomy in children.

BACKGROUND: EMLA cream (eutectic mixture of local anesthetics) has been shown to penetrate intact skin and provide analgesia of superficial layers. There are no studies on the effects of topical application of EMLA cream for postoperative pain relief after inguinal hernia repair. OBJECTIVE: : This randomized, double-blind, placebo-controlled study compared the efficacy of topical application of 5% EMLA cream before surgery, with wound infiltration with 1% lidocaine for postoperative analgesia in children. METHODS: Ninety children, aged 4 to 12 years, undergoing elective inguinal hernia repair under general anesthesia were enrolled in the study. Patients were randomly assigned to receive either placebo cream (group1), 5% EMLA cream (group 2), or placebo cream followed by 0.5 mL/kg 1% lidocaine (group 3) in the wound after induction of anesthesia. The anesthetic technique and monitoring were standardized, and postoperative pain was assessed using a 10-point objective pain scale. Fentanyl was used as rescue analgesic in immediate postoperative period, and acetaminophen was administered for postoperative pain in surgical ward. RESULTS: The number of patients requiring fentanyl in the immediate postoperative period was significantly less in the study groups compared with the placebo group. Sixty-seven percent of patients in the placebo group required more than 1 dose of acetaminophen in the first 6 hrs compared with 23% (EMLA group) and 20% (lidocaine group). Four patients (two in the lidocaine group, one in the EMLA group, and one in the control group) developed subcutaneous infection at the site of incision 10 to 15 days postoperatively. CONCLUSION: Topical application of EMLA (5%) provides postoperative analgesia comparable to infiltration with 1% lidocaine after inguinal hernia repair in children.

Children with significant cervical lymphadenopathy: clinicopathological analysis and role of fine-needle aspiration in Indian setup.

OBJECTIVE: To study the clinicopathological profile of children from India with cervical lymphadenopathy and the role of fine-needle aspiration cytology with special emphasis on tuberculosis as a cause. METHODS: A total of 89 children in the age group of 10 months to 12 years, presenting to our hospital from April 2004 to March 2005, were included. All the patients underwent thorough clinical and investigational assessment vis-à-vis cervical lymphadenopathy. Outcome measurements included clinical status and ability of conventional tests to categorize different types of lymphadenopathy and their utility in diagnosing tubercular lymphadenitis. Interobserver variability was analyzed measuring kappa test and was found to be in agreement. RESULTS: Reactive hyperplasia was the most common type of lymphadenitis, followed by granulomatous involvement. Unilateral posterior triangle lymph nodes were the most commonly affected in the tubercular cervical lymphadenopathy group. Fine-needle aspiration followed by Ziehl-Neelsen staining, histopathology and culture in combination were able to perform the diagnosis in 85.7% of cases affected with tubercular etiology. CONCLUSIONS: Fine-needle aspiration is a valuable diagnostic tool in the management of children with the clinical presentation of enlarged cervical lymph nodes. The technique reduces the need for more invasive and costly procedures, especially in a Third World country. Culture and histopathology, however, should be considered in cases where repeated fine-needle aspiration cytology is non-diagnostic.

Crianças com linfadenopatia cervical significativa: análise clínico-patológica e papel da aspiração por agulha fina no contexto indiano / Children with significant cervical lymphadenopathy: clinicopathological analysis and role of fine-needle aspiration in Indian setup

OBJETIVO: Estudar o perfil clínico-patológico de crianças indianas com linfadenopatia cervical e o papel da citologia aspirativa por agulha fina com ênfase especial na tuberculose como causa. MÉTODOS: Foram incluídas 89 crianças com faixa etária de 10 meses a 12 anos, admitidas em nosso hospital de abril de 2004 a março de 2005. Todos os pacientes foram submetidos a completa avaliação clínica e investigativa em relação à linfadenopatia cervical. Medidas de desfecho incluíram estado clínico e a capacidade de testes convencionais em categorizar tipos diferentes de linfadenopatia e sua utilidade no diagnóstico de linfadenite tuberculosa. A variabilidade interobservador foi analisada através do teste de kappa, tendo boa concordância. RESULTADOS: A hiperplasia reativa foi o tipo mais comum de linfadenite, seguida da granulomatosa. Os linfonodos do triângulo posterior unilateral foram o grupo afetado com maior freqüência no grupo de linfadenopatia cervical tuberculosa. A aspiração por agulha fina, seguida da coloração de Ziehl-Neelsen, histopatologia e cultura em associação, obteve sucesso em realizar o diagnóstico em 85,7 por cento dos casos de etiologia tuberculosa. CONCLUSÕES: A aspiração por agulha fina é uma ferramenta diagnóstica valiosa no tratamento de crianças com apresentação clínica de linfonodos cervicais aumentados. A técnica reduz a necessidade de procedimentos mais invasivos e dispendiosos, principalmente em países em desenvolvimento.Cultura e histopatologia, entretanto, devem ser consideradas em casos nos quais a citologia aspirativa por agulha fina não é diagnóstica.

OBJECTIVE: To study the clinicopathological profile of children from India with cervical lymphadenopathy and the role of fine-needle aspiration cytology with special emphasis on tuberculosis as a cause. METHODS: A total of 89 children in the age group of 10 months to 12 years, presenting to our hospital from April 2004 to March 2005, were included. All the patients underwent thorough clinical and investigational assessment vis-à-vis cervical lymphadenopathy. Outcome measurements included clinical status and ability of conventional tests to categorize different types of lymphadenopathy and their utility in diagnosing tubercular lymphadenitis. Interobserver variability was analyzed measuring kappa test and was found to be in agreement. RESULTS: Reactive hyperplasia was the most common type of lymphadenitis, followed by granulomatous involvement. Unilateral posterior triangle lymph nodes were the most commonly affected in the tubercular cervical lymphadenopathy group. Fine-needle aspiration followed by Ziehl-Neelsen staining, histopathology and culture in combination were able to perform the diagnosis in 85.7 percent of cases affected with tubercular etiology. CONCLUSIONS: Fine-needle aspiration is a valuable diagnostic tool in the management of children with the clinical presentation of enlarged cervical lymph nodes. The technique reduces the need for more invasive and costly procedures, especially in a Third World country. Culture and histopathology, however, should be considered in cases where repeated fine-needle aspiration cytology is non-diagnostic.

Cytodiagnosis of yolk sac tumor.

To analyze cytomorphologic features of yolk sac tumors of childhood. Four cases of pediatric yolk sac tumor (YST), diagnosed by fine needle aspiration cytology were reviewed (1998-2002). Age of patients ranged from 1(1/2) to 5 years. Three cases presented clinically with an intra-abdominal mass while one case presented with a testicular mass. Fine needle aspirates had been obtained directly as well as under radiologic (USG/CT) guidance. Smears were stained with H & E and Papanicolaou stain. In all cases values of serum alpha-fetoprotein and hCG were available preoperatively. Histopathologic diagnosis was correlated with cytologic findings in all the cases. Cytologic examination showed richly cellular smears with a combination of morphological patterns. Characteristically, tumor cells were arranged in papillary groups, tight cell clusters and formed acinar structures. Cells showed enlarged, moderately pleomorphic, hyperchromatic nuclei and moderate amount of cytoplasm, some of which displayed cytoplasmic vacuolation, displacing the nuclei eccentrically. Preoperatively, serum alpha-fetoprotein level was raised in all cases. Histopathology confirmed the cytologic diagnosis. Yolk sac tumor is common among the germ cell tumors of pediatric age group which presents a spectrum of cytomorphologic features having important differences with other germ cell neoplasm, e.g. embryonal carcinoma. Clinicoradiologic features and tumor markers are additionally helpful for an accurate cytologic diagnosis.

Head and neck masses in children: A clinicopathological study.

Fifty children with head and neck masses were evaluated clinically and pathologically. Inflammatory swellings constituted the majority (54%). Congenital - developmental malformations were the next common lesions (30%) and neoplastic masses constituted the rest (16%). Tuberculous lymphadenitis was found to be the single most common etiology (28%). Among congenital-developmental malformations, cystic hygroma was the most frequent lesion. The incidence of branchial cleft abnormalities was found to be low and no thyroglossal duct cyst was observed in this series. Among the neoplastic masses malignant lesions were more common than benign tumours and lymphoma was the most common head and neck malignancy observed.

Serum cortisol and prolactin response to surgical stress in infants and children.

In a prospective study on 40 infants and children undergoing elective surgery under general anaesthesia, serum cortisol and prolactin levels were compared to assess hormonal response to stress as regards to age, sex, length of surgery and anaesthetic techniques. The rise in serum cortisol was independent of age, sex, length of surgery and anaesthetic techniques while percentage rise in serum prolactin were more in females compared to males and significant post-induction surge irrespective of sex.

Low-density lipoprotein stimulates mesangial cell proteoglycan and hyaluronan synthesis.

BACKGROUND: Hyperlipidaemia leads to glomerulosclerosis in small mammals and may contribute to progressive renal disease in man. One prominent feature of lipid-induced glomerular injury in animal models is the accumulation of mesangial matrix. These studies were designed to investigate whether low-density lipoprotein (LDL) enhanced mesangial cell (MC) matrix deposition by modulating the production of proteoglycans (PG) and hyaluronan (HA). METHODS: Growth arrested human MC were metabolically labelled with either 50 microCi/ml Na(2)[(35)S]sulphate or 25 microCi/ml [(3)H]glucosamine and stimulated with LDL (10-100 microg/ml). The radiolabelled PG and HA extracted from the cell layer and the culture medium were isolated, quantified and characterized. Comparison of the PG core proteins synthesized by MC was carried out using Western blot analysis. RESULTS: LDL stimulation led to a dose- and time-dependent increase in [(35)S]sulphate incorporation into PG in the culture medium and to a lesser extent in the cell layer. Analysis of the glycosaminoglycan (GAG) chains showed no difference in either their size or charge. Enzyme digestion studies demonstrated that the synthesis of both chondroitin sulphate PG (CSPG) and heparan sulphate PG (HSPG) was enhanced as was the production of the core proteins of versican (a large CSPG), perlecan (a basement membrane HSPG) and to a lesser extent decorin (a small dermatan sulphate PG (DSPG)). An increase in HA synthesis was also demonstrated in [(3)H]glucosamine labelled cells following LDL stimulation. CONCLUSION: LDL selectively enhances the synthesis of specific PG and HA by mesangial cells. Such effects may contribute to the expansion of the mesangial matrix and modify cell-matrix interactions in lipid-induced renal damage.

Fibronectin augments monocyte adhesion to low-density lipoprotein-stimulated mesangial cells.

BACKGROUND: Glomerular monocyte infiltration is an early feature of lipid-mediated renal injury in animal models. Interactions between mesangial and infiltrating mononuclear cells may contribute to the development of glomerular scarring. METHODS: Adherence of U-937 monocytes to low-density lipoprotein (LDL)- or tumor necrosis factor alpha (TNFalpha)-prestimulated human mesangial cells was assessed by colorimetry of nuclear staining with crystal violet. Blocking antibodies were added to examine the mechanisms of binding. Adhesion molecule expression and fibronectin synthesis were measured by ELISA. RESULTS: Preincubation of mesangial cells for 24 hours with LDL (100 micrograms/ml) or mildly oxidized (minimally modified) LDL (MM-LDL) increased monocyte adhesion by 207% and 240%, respectively, compared with control nonstimulated cells (100%). TNFalpha (100 U/ml) enhanced binding by 335% and up-regulated intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) expression by 505% and 179%, respectively, as compared with MM-LDL (120% and 116%) and LDL, which had no effect. Blocking antibodies to these adhesion molecules inhibited monocyte binding to TNFalpha- and, to a lesser extent, MM-LDL-primed mesangial cells, but had no effect after LDL pretreatment. In contrast to TNFalpha, MM-LDL and LDL increased mesangial cell-associated fibronectin, whereas antibodies to fibronectin inhibited monocyte binding to lipoprotein-stimulated but not TNFalpha-stimulated cells. CONCLUSIONS: Although enhanced monocyte adhesion to TNFalpha- and, to a lesser extent, MM-LDL-stimulated mesangial cells is mediated by changes in ICAM-1 and VCAM-1 expression, both LDL and MM-LDL promote similar cellular interactions as a result of increased fibronectin production.

Oxidation of low density lipoprotein by mesangial cells may promote glomerular injury.

Low density lipoprotein (LDL) deposition and local oxidation play a key role in the pathogenesis of atherosclerosis and may likewise contribute to glomerular injury. These studies were designed to determine whether cultured human mesangial cells oxidize homologous LDL and to compare the effects of unmodified and oxidized lipoprotein on cell proliferation, viability and eicosanoid production. Cell-mediated lipoprotein oxidation was demonstrated and could be suppressed by oxygen free radical scavengers and inhibitors of arachidonic acid metabolism. When incubated with cells, oxidized LDL (Ox-LDL) at concentrations up to and including 100 micrograms/ml reduced 3H-thymidine incorporation without causing cytotoxicity as assessed by lactate dehydrogenase release. Under the same conditions there was a concentration-dependent increase in the synthesis of prostaglandins E2,6-keto-PGF1 alpha and thromboxane B2. In contrast, unmodified LDL enhanced DNA synthesis at concentrations less than 40 micrograms/ml and had little effect on eicosanoid production. These results demonstrate that exogenous oxidized LDL inhibits mesangial cell proliferation and increases eicosanoid synthesis. Unmodified lipoprotein can be directly oxidized by these cells through mechanisms that involve generation of oxygen free radicals.

A prospective study of closure techniques of abdominal incisions in infants and children.

In a prospective study of layered versus mass closure of abdominal incisions in infants and children, 34 cases underwent wound closure by layered and mass closure technique on an alternate basis. All the patients were assessed for their nutritional status and haemoglobin level pre-operatively, and wound complications were compared with respect to closure technique, nutritional status and normal haemoglobin level. Presence of protein energy malnutrition and anaemia did not increase the risk of wound complications with either of the technique.

Interactions between lipoproteins, glomerular cells and matrix.

Lipid deposition, mononuclear cell infiltration and accumulation of mesangial matrix components are recognized as early events in the development of glomerulosclerosis whilst correction of plasma lipid abnormalities slows the progression of renal disease in experimental models. In vitro studies have demonstrated that low density lipoprotein (LDL) is bound and internalized by mesangial cells, acts synergistically with growth factors to stimulate cellular proliferation and modifies secretion of chemotactic mediators and matrix components. LDL incubated with mesangial cells becomes oxidized and in this modified from inhibits cell proliferation and causes cytotoxic injury. Oxidation of LDL also modulates its effects on cell secretory function. Since proteoglycans secreted by mesangial cells bind LDL particles, excess matrix accumulation may exacerbate lipoprotein-mediated injury. These findings suggest that lipoproteins deposited and oxidized in the glomerulus may promote inflammation, cell injury and sclerosis.

Peri-anesthetic management of tracheo-esophageal fistula.

During a 3-year period 11 neonates underwent general anesthesia for primary repair of tracheo-esophageal fistula (TEF). The age ranged from 1-10 days. Out of these patients, 8 (72.7%) had atresia of the esophagus with a blind upper pouch and lower segment communicating with a trachea. A total of 7 patients (63.6%) had aspiration pneumonitis pre-operatively. Intubation was difficult in 3 (27.3%). There was no intraoperative mortality. However, the incidence of post-operative mortality was 27.3% (3 cases). The cause of death in all these cases was severe non-resolving pneumonia.

Structure and motion of phospholipids in human plasma lipoproteins. A 31P NMR study.

The structure and motion of phospholipids in human plasma lipoproteins have been studied by using 31P NMR. Lateral diffusion coefficients, DT, obtained from the viscosity dependence of the 31P NMR line widths, were obtained for very low density lipoprotein (VLDL), low-density lipoprotein (LDL), high-density lipoproteins (HDL2, HDL3), and egg PC/TO microemulsions at 25 degrees C, for VLDL at 40 degrees C, and for LDL at 45 degrees C. At 25 degrees C, the rate of lateral diffusion in LDL (DT = 1.4 x 10(-9) cm2/s) is an order of magnitude slower than in the HDLs (DT = 2 x 10(-8) cm2/s). At 45 degrees C, DT for LDL increases to 1.1 x 10(-8) cm2/s. In contrast, DT for VLDL increases only slightly going from 25 to 40 degrees C. The large increase in diffusion rate observed in LDL occurs over the same temperature range as the smectic to disordered phase transition of the core cholesteryl esters, and provides evidence for direct interactions between the monolayer and core. In order to prove the orientation and/or order of the phospholipid head-group, estimates of the residual chemical shift anistropy, delta sigma, have been obtained for all the lipoproteins and the microemulsions from the viscosity and field dependence of the 31P NMR line widths. For VLDL and LDL, the anisotropy is 47-50 ppm at 25 degrees C, in agreement with data from phospholipid bilayers. For the HDLs, however, significantly larger values of 69-75 ppm (HDL2) and greater than 120 ppm (HDL3) were obtained.(ABSTRACT TRUNCATED AT 250 WORDS)

Dynamic structure of the lower density lipoproteins. I. Incorporation of high levels of labelled lipids into very low and low density lipoproteins.

Selectively labelled lipids have been incorporated into the surface monolayer of human serum low density lipoprotein (LDL) and very low density lipoprotein (VLDL). From 3 to 17 mol% of phosphatidylcholine, selectively deuterated at various positions along the sn-2-acyl chain, was transferred from unilamellar vesicles to VLDL using a partially purified phosphatidylcholine transfer protein. Selectively deuterated palmitic acids were incorporated into LDL (6-20 mol%) and into VLDL (7-10 mol%). Electron microscopy, light scattering, and 31P nuclear magnetic resonance indicated that particle size remained unchanged. Gel exclusion chromatography and chemical analysis showed no difference in hydrodynamic properties and only slight alteration to particle component ratios. Biological activity of labelled VLDL was measured from the rate of cholesterol esterification by cultured J774A.1 cells. Effect of labelling LDL was evaluated by monitoring LDL uptake and degradation by cultured human skin fibroblasts. In all cases the lipoproteins containing labels were indistinguishable from their native counterparts.