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Biomedical subjects

M Bajpai

Publications and source records attributed to M Bajpai.

At least 19 recordsLinked to original sources

Prepubertal human chorionic gonadotropin injection affects postpubertal germ cell maturation and androgen production in rat testis.

OBJECTIVES: To examine the effects of varying doses of prepubertal human chorionic gonadotropin (hCG) administration on postpubertal germ cell status and androgen status in rats. The long-term effects of prepubertal hCG administration on postpubertal testicular function are still debated. METHODS: Forty male prepubertal Wistar rats, aged 20 days, were divided into four equal groups. Group 1 served as the controls. Each rat in groups 2, 3, and 4 received subcutaneous hCG injections of 5 IU, 10 IU, and 50 IU, respectively, on days 20 and 30 of life. Serum testosterone levels were estimated on days 33 and 70. On day 70, the left testis of each rat was harvested for DNA flow cytometric analysis. RESULTS: The testosterone levels on day 33 progressively increased from groups 1 through 4, and the difference between any two groups was statistically significant. In contrast, the testosterone levels on day 70 were greatest in group 1 and progressively decreased in groups 2 through 4, with the lowest value in group 4. On day 70, only group 4 rats had a significantly reduced haploid cell population compared with all other groups. CONCLUSIONS: Prepubertal hCG administration adversely affects testosterone levels, and a high dose of hCG has adverse effects on the germ cell haploid cell population. A critical reevaluation of the use of hCG is required in prepubertal boys, especially with respect to the dosage.

Androgens↗

Involvement of tyrosine kinase and cAMP-dependent kinase cross-talk in the regulation of human sperm motility.

Tyrosine phosphorylation and its upregulation by cAMP have been associated with capacitation and motility changes of spermatozoa. In the present study, washed spermatozoa were incubated for 6 h in protein-supplemented complete medium with or without kinase inhibitors to verify whether upstream activation of protein kinase A is indispensable for tyrosine phosphorylation and motility changes to occur in capacitating human spermatozoa. H89, a specific protein kinase A inhibitor, significantly inhibited the activity of sperm protein kinase A. However, this inhibition did not alter capacitation-related tyrosine kinase activation. Tyrosine phosphorylated proteins, motion parameters and the incidence of phosphotyrosine-immunoreactive spermatozoa were decreased only slightly. Conversely, genistein, a tyrosine kinase inhibitor which inhibited sperm tyrosine kinase but not protein kinase A, significantly reduced all the parameters studied. Spermatozoa incubated with cAMP and pentoxifylline showed a rapid enhancement of tyrosine phosphorylation and some of the sperm motion parameters, particularly hyperactivation. Inclusion of H89 reduced cAMP stimulation of tyrosine kinase, and tyrosine phosphorylation and motion parameters were reduced almost to basal values. Treatment with genistein reduced tyrosine kinase activity, especially in the soluble fraction of sperm extracts. A decrease in tyrosine phosphorylation of soluble proteins, 105, 81, 55 and 48 kDa, correlated with a significant reduction in sperm motion parameters. Hyperactivation was reduced by tenfold. Tyrosine phosphorylated proteins in the insoluble fraction and the incidence of tyrosine phosphorylated-positive spermatozoa were not reduced markedly. Upstream protein kinase A activation may be a facilitatory rather than an indispensable step in the capacitation-induced tyrosine phosphorylation mediating motility changes in human spermatozoa. Triton-x100 soluble tyrosine phosphorylated proteins, more than their insoluble counterparts, appear to be involved in the modulation of human sperm motion characteristics.

Cells, Cultured↗

Incarcerated diaphragmatic hernia secondary to plication for eventration of diaphragm.

Diaphragmatic plication is the procedure of choice for congenital diaphragmatic eventration. In the absence of complications, most newborns with eventration do well after plication and have normal long-term respiratory functions. However complications are rare. Recurrence, ipsilateral pneumothorax and rupture of the diaphragm have been reported in literature. We report a case of incarcerated diaphragmatic hernia in a two-year-old child who had undergone plication for eventration of the diaphragm at six months of age.

Diaphragmatic Eventration↗

AIIMS clinical score: a reliable aid to distinguish neonatal hepatitis from extra hepatic biliary atresia.

It is important to distinguish neonatal hepatitis (NH) from extra hepatic biliary atresia (EHBA) in a neonate presented with jaundice as the former is purely medical management and the latter requires surgical procedure at the earliest. The observations on the critical evaluation of the neonatal jaundice cases led us to propose AIIMS clinical score (ACS) and this retrospective study was designed to evaluate the reliability of the ACS in all the 120 babies with jaundice referred to the pediatric surgery department during the past 10 year period. The ACS described here is based on 5 clinical parameters--Age, Jaundice, Colour of urine and stool and Clinical examination of liver. The accuracy of the hepatobiliary scan (HBS) with respect to the diagnosis of EHBA in this series, as compared to per operative cholangiography (POC) which is considered as the gold standard to distinguish these conditions was only 68%. However, ACS showed a sensitivity of 91.5%, a specificity of 76.3%, positive predictive value of 89.2%, negative predictive value of 80.5% and an overall diagnostic accuracy of 86.6%. ACS is reliable to distinguish NH from EHBA at bedside.

Biliary Atresia↗

Epigastric heteropagus twins--a report of four cases.

Asymmetrical conjoined twinning is an extremely rare congenital anomaly constituting only 1%-2% of all conjoined twins. In epigastric heteropagus twins (EHT), the dependent portion (parasite) is smaller than the host (autosite). The embryopathy is related to incomplete cleavage of the embryo at 2 weeks of gestation. However, some form of ischaemic insult in early gestation leads to selective atrophy of the cranial part of one of the monozygous twins. We report our experience with four cases of EHT and a review of the literature with a discussion of possible embryopathy.

Abnormalities, Multiple↗

Factors affecting outcome in the management of posterior urethral valves.

Children with posterior urethral valves (PUV) are at high risk for renal failure (RF). The outcome of renal function is significantly influenced by early diagnosis and the choice of primary therapy. We reviewed the outcome of renal function in 58 children with PUV. The choice of therapy in each case primary valve fulguration, vesicostomy, or high ureterostomy--was individually decided on the basis of the response to initial catheter drainage of the bladder. Patient age at diagnosis varied from newborn to 5.5 years, and follow-up ranged from 1.6 to 6 years (mean 3.9 years). The most common procedure was primary endoscopic valve ablation, which was carried out in 56.8% of cases. The other procedures were vesicostomy in 32.75% and high ureterostomy in 10.45%. Most neonates (66.6%) had RF at presentation, but one-half of them had achieved normal serum creatinine values at last follow-up. The recovery of renal function was lowest (33%) in older children where the diagnosis was delayed. A comparison between two groups of neonates and infants who differed on the basis of creatinine concentrations at 1 year of age suggested a statistically significant trend: children with normal or near-normal serum creatinine (0.8 mg/dl or less) by 12 months of age maintained good renal function at the time of final evaluation (1.0 mg/dl or less). Children with higher creatinine values at 1 year of age continued to have progressive RF. Seventy-five percent of the patients who had undergone early high ureterostomy after failure to respond to initial catheter drainage had regained normal renal function. We conclude that: serum creatinine at presentation is not predictive of subsequent renal function, but the values after a period of urinary-tract decompression are prognostically more useful; delay in diagnosis results in a poor outcome of renal function; and for optimal recovery of renal function, the choice of the primary procedure varies from case to case and can be determined by a systematic, stepwise approach (stepladder protocol).

Child, Preschool↗

Percutaneous nephrostomy in children with ureteropelvic junction obstruction and poor renal function.

OBJECTIVES: To evaluate the results of performing percutaneous nephrostomy (PCN) in all patients with kidneys with ureteropelvic junction obstruction (UPJO) and split renal function (SRF) of less than 10%, because the management of such cases is still under debate. If SRF improves, we perform pyeloplasty, otherwise nephrectomy is done. METHODS: The records of all patients with UPJO (n = 20; 17 unilateral and 3 solitary kidney) with poor function who underwent PCN were analyzed. The PCN remained in situ for at least 4 weeks, during which patients received low-dose oral trimethoprim prophylaxis. Repeated renography was obtained after 4 weeks. If no improvement in the SRF had occurred, nephrectomy was performed, otherwise pyeloplasty was performed. The patients were followed up with renograms at 3 months, 1 year, 2 years, and 5 years. RESULTS: Twelve of 17 kidneys with unilateral UPJO improved after PCN drainage and underwent pyeloplasty. The 5 kidneys that did not show improvement in the SRF underwent nephrectomy. In the patients with unilateral UPJO who improved after PCN drainage, the SRF increased to 29.2% +/- 12.6% and pyeloplasty was performed. At a mean follow-up of 2.3 years, none of these patients had developed hypertension, and the most recent SRF value was 31.4% +/- 12.8%. CONCLUSIONS: Most of the poorly functioning UPJO kidneys show improvement in function and not all such kidneys should be removed without a trial of PCN.

Child↗

Identification of thyroid regulatory elements in the Na-K-ATPase alpha3 gene promoter.

A -1027 bp to + 108 bp region of Na-K-ATPase alpha3 gene promoter has been searched for the presence of thyroid response elements (TRE). Computer analysis of this sequence using a consensus TRE sequence revealed the presence of four putative TRE rich regions referred to as regions I (-636 to -457 bp), II (-218 to -106 bp), III (-106 to -6 bp) and IV (-6 to +108 bp). Cotransfection of the luciferase linked full length construct as well as constructs progressively devoid of the TRE rich regions in Cos1 cells revealed that regions I and III are positively regulated by T3 whereas there are some sequences in region II which can suppress the positive regulatory effect of region III but not of region I. TRE IV seems to have no functional role. EMSA of the three functional TRE rich regions (I, II and III) showed strong and specific interaction with thyroid hormone receptor (TR) cloned and expressed in baculovirus. The overall results suggest the regulation of Na-K-ATPase alpha3 gene by T3 is complex involving several thyroidal regulatory elements.

5' Flanking Region↗

Management of bladder exstrophy.

The exstrophy-epispadias complex is a severe anomaly of the lower urinary tract. While the surgical reconstruction of normal anatomy in patients with this disorder was once considered impossible, modern management has made possible a near-normal reconstruction of the bladder and lower abdominal wall. Early operation in the neonatal period along with closure of the pelvic ring has been shown to significantly improve results in terms of continence and achievement of adequate bladder capacity. With the possibility of prenatal diagnosis, it is important that the counseling obstetricians and neonatologists should understand the basis of the surgical management and the outcome that can be expected.

Bladder Exstrophy↗

Neonatal Hirschsprung's disease.

Since the classic description of this disease by Harold Hirschsprung's. In 1886 just over a century ago, there has been a marked evolution in the diagnostic modalities, understanding of the pathophysiology, unraveling of genetic association and the treatment approach of this disease. Recent research on the molecular biology of the disease has bestowed us with a clearer understanding of the pathogenesis of the disease. Genetic deletions have been identified which explain the familial incidence of 3.6%-7.8%, and in some kindreds the inheritance rate approaches 50%. Improvement in the diagnostic approaches has evolved from full thickness rectal biopsy (under GA) to suction rectal biopsy. The development of the histochemical staining for acetylcholinesterase, allows rapid identification in the lamina propria of hypertrophied extrinsic nerve fibers which have proliferated in the absence of intrinsic ganglion cells. Frozen sections now permit screening for normal ganglia in the myenteric plexus from seromuscular biopsies during the definitive pull-through procedures or leveling colostomy. This service, however, requires significant infrastructure and an expert pathologist, not widely available. Hirschsprung's disease (HD) variants like intestinal neuronal dysplasia(IND), hypoganglionosis are better identified and treated with availability of histochemical staining. The three-stage procedure till date remains the gold standard; however, increasingly, the world over, two stage and even single stage procedures are being tried. In the era of minimally invasive surgery, perineal pull through procedure has been attempted with or without laparoscopic assistance.

Digestive System Surgical Procedures↗

Congenital diaphragmatic hernia.

Over the last two decades there has been a constant improvement in the understanding of the pathophysiology of Congenital Diaphragmatic Hernia (CDH) and its management. However, the ideal treatment remains elusive. The earlier management strategy of immediate surgery is replaced by the principle of physiological stabilisation and delayed surgery. Conventional mechanical ventilatory techniques, with high pressures and hyperventilation to reverse ductal shunting and cause alkalinization, are being questioned because of the risks of barotrauma and consequent broncho-pulmonary dysplasia. It has also been shown that paralysis with pancuronium bromide for patients on conventional mechanical ventilation results in increased incidence of sensorineural hearing loss in childhood survivors of CDH. With the introduction of the concept of permissive hypercapnia and high frequency oscillation ventilation, the complications of pulmonary barotrauma are circumvented. Although ECMO therapy is invasive, yet has improved survival by about 15% independently, especially in critically ill infants who have the predictive mortality rate of more than 80%. Further insights into the pathophysiology of CDH and the introduction of less invasive therapeutic techniques in the form of high frequency oscillation ventilation, inhalation nitric oxide, surfactant, and perfluorocarbon liquid ventilation may even make the need for ECMO redundant.

Extracorporeal Membrane Oxygenation↗

Intestinal atresia.

Intestinal atresia accounts for about one third of all cases of neonatal intestinal obstruction. The survival rate has improved to 90% in most of the series with the operative mortality being < 1%. The survival rate improves with distal atresias. An increased mortality is observed in multiple atresias (57%), apple peel atresia (71%), and when atresia is associated with meconium ileus (65%), meconium peritonitis (50%) and gastroschisis (66%). Although appearance of echogenic bowel on prenatal ultrasonography is suggestive of GI, it is confirmed in only 27% cases. Prenatal ultrasonography is more reliable in detection of duodenal atresia than more distal lesions. Short bowel syndrome is the major impediment in the management of jejunoileal atresia. Although total parenteral nutrition (TPN) is the main adjunctive treatment, it delays intestinal adaptation and may cause cholestasia and subsequent liver damage. Graduated enteric feedings, use of growth hormone, glutamine and modified diets containing low fat, complex carbohydrates and protein supplements have been used in a adults with short bowel syndrome to successfully diminish TPN requirements and enhance nutrient absorption in nearly half of the patients. Utilization of growth factors to facilitate intestinal adaptation and advances in small bowel transplant may improve the long-term outcomes in future.

Diagnosis, Differential↗

Gastric teratoma in children.

Gastric teratoma (GT) comprises less than 1% of all teratomas in children. Though GT in the presence of immature neuroepithelial elements is regarded as malignant, the prognosis is excellent after complete excision of the tumor. Because of its rarity the world literature lacks a large study. Clinical experience with ten cases of GT is presented and discussed. Only one patient was female; the mean age at presentation was 3.2 months. Two cases were immature grade III GT; one of these had infiltrated the left lobe of the liver and the transverse colon while the other had metastasized to the regional lymph nodes and omentum. All the patients underwent complete excision. There were no deaths, and after a mean follow-up period of 4.2 years, all the patients had no recurrence and were healthy. Both the mature and immature types of GT have an excellent prognosis after complete excision of the tumor. Even when the immature type infiltrates surrounding structures, complete excision offers recurrence-free survival without requiring chemo- or radiotherapy.

Biopsy↗

High incidence of adriamycin cardiotoxicity in children even at low cumulative doses: role of radionuclide cardiac angiography.

BACKGROUND/PURPOSE: Adriamycin (doxorubicin), a chemotherapeutic agent commonly used in the treatment of pediatric solid tumors, is known to have a dose-related cardiotoxicity, which is reported to be more common in children. The clinical manifestation of this is congestive cardiac failure (CHF), and this is fatal in 50% of the cases. Various strategies, including prospective multiple gated acquisition (MUGA) scan for early detection of the onset of cardiac damage has been recommended to decrease this fatality caused by cardiotoxicity. METHODS: All children receiving Adriamycin for solid tumors, registered at our pediatric solid tumor clinic from January 1998 through June 1999, were included in the study. Cardiotoxicity was evaluated by using electrocardiogram (ECG)-gated radionuclide cardiac angiography (MUGA scan). RESULTS: MUGA scans were performed on 55 patients in the above-mentioned period of 18 months. Twenty-three patients had only 1 baseline MUGA scan done, 12 of these are awaiting further studies at appropriate time and 11 are either dead or lost to follow-up. Of the remaining 32 patients, 13 have shown evidence of cardiotoxicity on MUGA scan done at a cumulative dose of 180 to 200 mg/m(2), in the form of decrease in left ventricular ejection fraction (LVEF) or abnormality in myocardial movements. Three of these 13 patients had clinical evidence of CHF. In 10 patients, timely discontinuation of Adriamycin, based on the MUGA report, probably has helped avoid the development of CHF. CONCLUSION: Routine monitoring of all children receiving Adriamycin is required to avoid the mortality and morbidity of Adriamycin-related cardiotoxicity, which may develop at relatively low cumulative doses also.

Antineoplastic Agents↗

Surgery in tuberculosis.

Tuberculosis in children involves many organs and systems including lymphatics, lungs, CNS, GIT and genitourinary. Although the mainstay of treatment is medical, surgery has a definite role under specific circumstances. It is important to differentiate atypical mycobacterial infection wherein surgery is the primary modality of treatment. The lung is most commonly involved in tuberculosis and besides bronchoscopy, thoracic procedures range from tube thoracostomy to decortication and lung resection. Neurotuberculosis constitutes almost half the cases of extrapulmonary tuberculosis and tuberculous meningitis (TBM) is the commonest type of CNS involvement. Hydrocephalus is a late complication of TBM and shunt surgery is indicated when signs and symptoms of raised intracranial pressure persist despite adequate medical therapy. Abdominal tuberculosis could be peritoneal or gastrointestinal. Either form can complicate the other and each can present in acute, subacute or chronic form. Surgical therapy is reserved for complications like strictures, fistulae and GI bleed. Genitourinary tuberculosis constitutes 15-20% of all extrapulmonary disease and epididymitis is the most common manifestation in the males. Surgery is generally reserved for management of complications such as ureteral strictures, perinephric abscesses and nonfunctioning kidneys.

Child↗

Transcriptional and post-transcriptional regulation of Na+,K(+)-ATPase alpha isoforms by thyroid hormone in the developing rat brain.

Transcriptional and post-transcriptional events involved in the induction of sodium potassium adenosine triphosphatase (Na+,K(+)-ATPase) by thyroid hormone (T3) were investigated. In vitro transcription of nuclei isolated from cerebra of 5- and 15-day-old normal and hypothyroid rats showed that transcription of all alpha mRNA isoforms (alpha 1, alpha 2 and alpha 3) of Na+,K(+)-ATPase are sensitive to T3. This is evidenced by a 50-70% reduction in the rates of transcription of alpha 1 and alpha 3 mRNA and 20-40% reduction of alpha 2 mRNA in nuclei from hypothyroid cerebra compared with those from normal controls. Preincubation of nuclei from hypothyroid cerebra with T3 prior to transcription also showed an increase in the rates of transcription of these mRNAs. At the post-transcriptional level, T3 enhanced the half life of alpha 3 mRNA by 1.5-fold with no discernible effect on alpha 1 and alpha 2 mRNA.

Aging↗

A common genetic basis for idiosyncratic toxicity of warfarin and phenytoin.

CYP2C9 is mainly responsible for the metabolic clearance of phenytoin and (S)-warfarin. We have shown previously that mutations in the CYP2C9 gene are associated with diminished metabolism of (S)-warfarin, and so we have now studied the metabolism of phenytoin to its primary inactive metabolite, (S)-pHPPH, by these mutant enzymes. Kinetic parameters were determined for (S)-pHPPH formation using recombinant CYP2C9 variants purified from insect cells. The data demonstrate that the CYP2C9*3 gene product retains only 4-6% of the metabolic efficiency of the wild-type protein, CYP2C9*1, towards phenytoin and (S)-warfarin. Consequently, we suggest that homozygous expression of CYP2C9*3 may represent a common genetic basis for (apparently) idiosyncratic toxicities that have been reported for these two low therapeutic index drugs.

Animals↗

Surgical aspects of chronic constipation in children.

Chronic constipation accounts for 3% of paediatric visits. These patients can be broadly classified into three groups: (a) medical group (60-70%), (b) surgical group (20-25%), (c) refractory constipation group (5-10%). The first two groups can be managed by dietary adjustments and surgery respectively. The recognition and management of refractory constipation is a slower process and needs close scrutiny and perseverance before a definite therapeutic option could be decided.

Adolescent↗