Shilpa Sharma

Morphine-induced degradation of the host defense barrier : Role of intestinal mucosal injury

The effect of morphine on intestinal ulcer formation and on the degradation of the host defense barrier was studied. Mice receiving morphine (MRM) showed mucosal ulcer formation in the ileum and in the upper third of the colon. In in vitro studies, morphine enhanced apoptosis of cultured human colonic cells (HCC). Nitric oxide synthase (NOS) inhibitors attenuated the proapoptotic effect of morphine. Moreover, morphine stimulated NO generation by HCCs. MRM also showed a breach in the host defense barrier as well as injury to peritoneal macrophages. Although NOS inhibitors completely prevented morphine-induced intestinal ulcer formation, it provided only partial protection against a breach in the host defense barrier and peritoneal macrophage injury. Propranolol did not inhibit the induction of intestinal ulcer formation in MRM; nevertheless, propranolol prevented a breach in the host defense barrier as well as macrophage injury in MRM, whereas hemin exacerbated macrophage injury as well as the breach in the host defense barrier of MRM. These findings suggest that morphine-induced intestinal injury is mediated through NO generation. However, the degradation of the host defense barrier correlates with macrophage injury, but not intestinal injury.

Esophageal atresia: the total care in a high-risk population.

The outcome of cases of esophageal atresia depends on many factors that affect the prognosis. These factors have been identified since Waterston aimed to classify the anomaly according to the risk factors. There are other factors that affect the outcome, and these differ in different parts of the globe. This comprehensive review attempts to incorporate all the factors--preoperative, operative, and postoperative--that can pose risks to the ultimate survival of the baby. Early detection for proper management of these cases is essential. Feasibility to perform early esophageal replacement has come as a boom for these high-risk cases. Total care in a high-risk population of esophageal atresia depends on the investigative modalities adopted, available neonatal ICU care, and the surgeons experience. An attempt continues to decrease the associated morbidity and mortality in high-risk babies born with esophageal atresia and tracheoesophageal fistula.

Gender assignment and hormonal treatment for disorders of sexual differentiation

PurposeTo study the gender assignment and hormonal treatment advocated for disorders of sexual differentiation (DSD).MethodsA study was done on patients who were reviewed in the Pediatric Intersex Clinic to evaluate the pattern of gender assignment and hormonal treatment advocated.Results and conclusionThe patients included male pseudohermaphrodite (MPH) 169; congenital adrenal hyperplasia (CAH) 91; mixed gonadal dysgenesis (MGD) 29; true hermaphrodite (TH) 25; pure gonadal dysgenesis (PGD) 2; persistent mullerian duct syndrome (PMDS) 2 and others (micropenis, severe hypospadias with cryptorchidism, 46XX male) 39. Out of 91 cases of CAH, 70 (76.9%) were on steroids (prednisolone, hydrocortisone) and/or mineralocorticoids (fluoricortisone) for adrenal suppression. Out of 146 cases of male pseudohermaphrodite and 21 cases of true hermaphrodite and 3 cases of mixed gonadal dysgenesis reared as males, testosterone was given for local application for phallic growth in 101 and/or as systemic injection for mental makeup after puberty in 41 cases. Systemic testosterone injection was also given for 7 cases of CAH reared as males. Out of 26, 15 cases with mixed gonadal dysgenesis and one out of 2 cases of pure gonadal dysgenesis that attained puberty after being reared as females, after female genitoplasty, were given conjugated oestrogen (Premarin) supplemented with progesterone, as the uterus was preserved. For 12 post-pubertal cases of complete androgen insensitivity syndrome (AIS), only premarin was given as there was no uterus. Growth hormone and Gn RH analogue was given in 2 patients with CAH to tide over the early bone maturation induced by hormones with equivocal results. Thus judicious hormonal supplementation based upon type of DSD and gender assigned can provide a psychological and cosmetic benefit to patients with DSD.

The endometrium in assisted reproductive technology: How thin is thin?

A thin endometrium is encountered infrequently (2.4%) in assisted reproductive technology cycles. When it does occur it is a cause of concern as it is associated with lower implantation rate and pregnancy rate. Though pregnancies have been reported at 4 and 5 mm it is apparent that an endometrial thickness <6 mm is associated with a trend toward lower probability of pregnancy. Hormone replacement therapy – frozen embryo transfer (FET) cycles appear to give better results due to an improvement in endometrial receptivity (ER). The etiology of thin endometrium plays a significant part in its receptivity. A number of treatments have been tried to improve endometrial growth, but none has been validated so far. Confirming ER of a thin endometrium by an ER array test before FET offers reassurance.

Male Genitoplasty for Intersex Disorders

Aim. To evaluate surgical procedures adopted for male genitoplasty in intersex disorders. Patients and Methods. Case records of intersex patients undergoing male genitoplasty from Pediatric Intersex clinic were studied. Results. Of 356 intersex cases undergoing urethroplasty from 1989–2007, the hypospadias was penoscrotal (68%), scrotal (17%) and perineal (15%). 351 patients underwent chordee correction for mild: moderate: severe chordee in 24 : 136 : 191 cases. Byars flaps were fixed upto the corona in 267 cases. Urethroplasty performed was Theirsch duplay in 335 cases, Snodgrass in 16 cases and Ducketts onlay graft in 5 cases that did not require chordee correction. Age at urethroplasty was 2.5 years—22 years (mean 11.5 years, median—5.6 years). Penoscrotal transposition correction and testicular prosthesis insertion were performed independently. Complications included fistula (45), recurrent fistula (11), stricture (12), baggy urethra (8) and recurrent infection due to persistent vaginal pouch (5). Additional distal urethroplasty was required in 15 patients for previous urethroplasty done upto the corona 5–15 years earlier. Conclusion. Hypospadias in intersex disorders is associated with severe chordee in most cases and requires an early chordee correction to allow phallic growth, staged urethroplasty and multiple surgeries to achieve good cosmetic and functional results.

Therapeutic use of stem cells in congenital anomalies: A pilot study

Introduction: Stem cells with potential to transform into healthy cells and repair damaged cells may prove beneficial in various congenital malformations. Aim: To explore the use of stem cells in liver cirrhosis and meningomyelocele. Materials and Methods: During July 2005 to July 2006, stem cells were used in 27 patients; 12 with liver cirrhosis and 15 with meningomyelocele. Autologous stem cells were injected during definite surgery into hepatic artery and portal vein or hepatobiliary radicles for liver cirrhosis or spinal cord and caudal space for meningomyelocele. The pre-operative status of the patient served as control for that patient. Results: The patients with liver cirrhosis were between 1.5 and 9 months (mean 4.12 months). Liver cirrhosis was due to extra hepatic biliary atresia (EHBA); neonatal hepatitis and choledochal cyst in 8; 2 and 2 patients, respectively. About five patients expired due to late presentation and ongoing cirrhosis. Follow up results evaluated at 3-12 months (n=7) showed absence of cholangitis (4/7); yellow stools (5/7); decreased liver firmness (3/7); improved liver functions (6/7) and improved appetite (6/7). Hepatobiliary scan was excretory in 6/7 with improved uptake in 4/7. Histopathology repeated after stem cells demonstrated comparative improvement in fibrosis in three. The meningomyelocele patients were between 0 and 1 month; 1-5 months, and 1-4 years in 5; 8 and 2 cases, respectively. 5 had history of rupture. 3 had undergone meningocele repair in past with neurological deficits. Redo surgery for tethered cord was done in 1. Follow up (3-11 months) in 14 cases showed improved power in 4 (28%), dramatic recovery in 3 (22%), and status quo in 7 (50%). One patient is still under observation. Conclusion: Initial use of stem cells in EHBA and meningomyelocele has shown beneficial results. However, long-term evaluation with randomized-controlled trials is essential to draw further conclusions.

Parapagus conjoined twins: Complicated anatomy precludes separation

A parapagus set of male conjoined twins was brought to our institution at 12 h after birth. An extensive sharing of the abdominal viscera (single liver, hindgut), abdominal aorta, pelvis (single rectum and anus), genitalia (one set) and vertebral column was found. The surgical separation was not considered due to medical and ethical issues.

Male genitoplasty for 46 XX congenital adrenal hyperplasia patients presenting late and reared as males

Aim: To evaluate the clinical profile and management of 46 XX Congenital Adrenal Hyperplasia (CAH) patients presenting with severe virilization and assigned a male gender. Materials and Methods: Of 173 children diagnosed with CAH at the Pediatric Intersex Clinic since 1980, seven children with CAH presented late with severe virilization and were reared as males. All of them were assigned the male sex with removal of the female adnexa. Six were treated with male genitoplasty. Appropriate hormonal supplementation was offered after puberty. Results: The mean age at presentation was 14.2 years (7 – 21). Six patients had presented after puberty, only one at seven years of age. Staged male genitoplasty comprising of chordee correction, male urethroplasty, and bilateral testicular prosthesis was performed. The female adnexa (uterus, ovaries, most of the upper vagina, and the fallopian tubes) were removed. The mental makeup was masculine in six and bigender in one. Bilateral mastectomy was performed at puberty in all. Hormonal treatment comprised of glucocorticoids and testosterone. Six patients were comfortable with the outcome of the masculinizing genitoplasty. One had a short-sized phallus. One had repeated attacks of urinary tract infection arising from the retained lower vaginal pouch. Social adjustments were good in all, except in one who had a bigender mental makeup. Conclusion: CAH patients with severe virilization presenting late and reared as males are extremely rare. However, the assigned gender can be retained adequately as males, meeting the socioeconomic compulsions of the society. The results are satisfactory following appropriate surgical procedures and hormonal supplementation.

Early onset ovarian hyperstimulation syndrome despite use of segmentation approach and ovarian hyperstimulation syndrome prophylaxis.

We report a case of early onset severe ovarian hyperstimulation syndrome (OHSS) presenting with oliguria in an antagonist cycle triggered with GnRH agonist and a freeze-all approach. Prophylactic measures in the form of GnRH antagonist, cabergolin and plasma expanders were given after oocyte retrieval. Twenty-four hours after oocyte retrieval patient developed oliguria and moderate ascites. She was managed in ICU with albumin and diuretics. She responded to conservative management and did not require paracentesis. Severe OHSS can occur in PCOS patients even after using a segmented approach i.e. GnRH agonist trigger with a ′freeze all′ policy. Patients at risk of OHSS should be closely monitored following ovum pickup even when an agonist trigger has been given, for early detection and management.

Transposed intrathoracic stomach: functional evaluation.

BACKGROUND To study the functional aspects of the transposed stomach in the thoracic cavity and its effects on other organ systems. PATIENTS AND METHODS Children who had undergone gastric transposition more than 5 years ago were evaluated for symptoms, anthropometry, anaemia, duodenogastric reflux, pulmonary function, gastric emptying, gastric pH, gastroesophageal reflux and stricture, gastric motility, and gastritis and atrophy on histological examination of gastric mucosa. RESULTS Ten children were evaluated at a median follow-up of 90.5 months. On evaluation of symptoms, nine children were satisfied with the overall outcome. All patients had their weight and 7 patients had height less than 3 rd percentile for their respective age. Anaemia was present in 7/10 children. On evaluation with hepatobiliary scintigraphy, duodenogastric reflux was present in only 1 patient. Mass contractions of the transposed stomach were present in two thirds of the children. The mean gastric emptying t1/2 was 39.1 minutes. Pulmonary function tests were suggestive of restrictive lung disease in all the patients. Forced vital capacity (FVC) and forced expiratory volume in 1 sec (FEV1) were worse in children who underwent transposition or diversion following oesophageal anastomotic leak. Acid secretion was preserved in most patients with episodes of high gastric pH during sleep in nearly half. Mild gastritis was present in all patients where as mild atrophy of the gastric mucosa was observed in only 1child. Helicobacter pylori were positive in 3/ 8 children. Barium swallow demonstrated reflux in 2 children. CONCLUSIONS Most children with transposed stomach remain asymptomatic on follow up. However, subclinical abnormalities are detected on investigations, which need close observation as they can manifest later in life.