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Biomedical subjects

M Bajpai

Publications and source records attributed to M Bajpai.

At least 37 records · Page 2Linked to original sources

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↗

Somatic growth and renal function after unilateral nephrectomy for Wilms' tumor.

Solitary kidneys in renal donors and patients who have undergone unilateral nephrectomy for malignant disease have been reported to undergo hyperfiltration injury. This study was undertaken to evaluate the somatic growth and development of followed-up patient after Wilms' tumor to evaluate their renal function and identify any evidence of injury in the remaining kidney. The growth and development of all the children was found to be normal, as was DTPA clearance. Microalbuminuria in 24-h urinary collections was detected in 84% of the patients, indicating evidence of hyperfiltration injury. This study highlights the need for close monitoring of the renal function of long-term follow-up patients after Wilms' tumor in addition to the routine monitoring for tumor recurrence.

Albuminuria↗

Lipid metabolising enzymes in isolated rat testicular germ cells and changes associated with meiosis.

To assess the lipid metabolising potential of testicular germ cells undergoing meiosis, spermatocytes and spermatids were isolated from adult rat testis and purified by centrifugal elutriation followed by density gradient centrifugation. Seven key enzymes of lipid metabolism (namely beta-hydroxybutyrate dehydrogenase, carnitine acetyl transferase, ATP citrate lyase, hydroxyacyl-CoA dehydrogenase, glycerol 3-phosphate dehydrogenase, acetyl-CoA carboxylase and long chain acyl-CoA synthetase) were assayed in cell homogenates. The results indicated that germ cells possess the key enzymes for de novo synthesis and oxidation of fatty acids. The significant increase in activities of anabolic enzymes and decrease in activities of catabolic enzymes in post-meiotic germ cells indicated a shift in lipid metabolism towards fatty acid synthesis during meiosis. Long chain acyl-CoA synthetase activity was not detected in the two cell types. The study indicates a major reorganization of fatty acid turnover during meiosis with equilibrium shifting in favour of synthesis.

3-Hydroxyacyl CoA Dehydrogenases↗

Changes in carbohydrate metabolism of testicular germ cells during meiosis in the rat.

A study was undertaken to estimate the activities of the key enzymes of glycolysis, the pentose phosphate pathway and the tricarboxylic acid (TCA) cycle in purified rat spermatocytes and spermatids, which have been shown to die in glucose-containing medium and require lactate/pyruvate for maintaining normal ATP concentrations. The aim was to elucidate the changes in the glycolytic and oxidative potential of germ cells undergoing meiosis. Pachytene spermatocytes and round spermatids from adult rat testis were purified to approximately 90% purity by trypsin digestion followed by a combination of centrifugal elutriation and Percoll density gradient centrifugation. After the purity and viability of these cells had been established, their contents of hexokinase, phosphofructokinase, lactate dehydrogenase (LDH) and LDH-X of glycolysis, glucose 6-phosphate dehydrogenase of the pentose phosphate pathway and citrate synthase, aconitase, malate dehydrogenase and 2-oxoglutarate dehydrogenase of the TCA cycle were estimated. These enzymes were also estimated in epididymal spermatozoa for comparison with the testicular germ cells. The results indicate greater activity of glycolytic and pentose phosphate pathway enzymes in spermatocytes than in spermatids, which exhibited greater activity of TCA cycle enzymes than the former. The difference in activity was statistically significant for most of the enzymes studied. In contrast, spermatozoa exhibited markedly greater activity of glycolytic enzymes and significantly lower activity of pentose phosphate pathway and TCA cycle enzymes than did the testicular germ cells. We conclude that the unusual dependence of spermatids exclusively on lactate may be due to their lower glycolytic potential, whereas spermatocytes with comparatively greater glycolytic activity have an intermediate dependence on lactate and are therefore able to utilise lactate, pyruvate, or both, while retaining a better ability to utilise glucose. Spermatozoa with the greatest glycolytic potential and the lowest TCA cycle activity appear to be 'programmed' to utilise exclusively glucose/fructose for energy.

Animals↗

Bilateral Wilms tumor: an eleven year experience.

Over the last 11 years, 101 patients of Wilms tumor were treated at our hospital. Of these, 7 had bilateral Wilms tumors (BWT). The first two patients were referred in terminal stages and died. Of the latter five, three have survived while one is on treatment. One patient succumbed to liver metastasis, he had stage III disease on one side and was irregular in his chemotherapy protocol. Remarkably, one of the survivors was cured even after developing vertebral metastasis, retroperitoneal recurrence and bilateral lung metastasis. Part of the success was due to "salvage chemotherapy regimens" using Cis-plantinum, ifosphamide and VP-16. Flow cytometric analysis of DNA ploidy performed on only three of the five patients showed that two tumors were aneuploid and one was diploid. Spectacular cure rates can be achieved in BWT by renal conservation surgeries and effective chemotherapy. The use of "salvage chemotherapeutic regimes" and the study of DNA ploidy is being highlighted.

Antineoplastic Combined Chemotherapy Protocols↗

Gastric transposition for esophageal replacement in children--an Indian experience.

Most pediatric surgeons are wary of gastric transposition as a means for esophageal replacement in children, especially during infancy. We present our initial experience of this technique in five children followed up for an average 1.7 years postoperatively. Four of them were infants (age range 5 m to 10 m at the time of transposition) with wide-gap esophageal atresia, while one was operated upon for an extensive corrosive esophageal stricture at 4 years age. The stomach was placed transhiatally in 3 patients and through the retrosternal route in 2 patients. A gastric outlet drainage procedure was performed in all cases. The average age at transposition in the 4 infants with esophageal atresia was 8.5 months and the mean weight was 7.4 kg. Three of the four infants required postoperative ventilation (mean duration 40 hours) and the average duration of hospital stay was 24 days. Our first transposition in a chubby infant resulted in death (20% mortality for this series) due to difficult ventilation. Other complications included anastomotic leak and subsequent stricture (one patient), adhesive obstruction (one patient), transient Horner's syndrome and recurrent laryngeal nerve palsy (one patient), and poor weight gain (one patient). Postoperatively, while the pattern of liquid gastric emptying was variable, no duodenogastric reflux was demonstrable. Thus gastric transposition is a safe, relatively simple and physiologic procedure in infancy and childhood and has given good functional results.

Burns, Chemical↗

Seasonal variations in Sertoli and germ cell marker enzymes in testis of rhesus and bonnet monkeys.

Variations in specific activities of the marker enzymes of Sertoli and germ cells during breeding (November-December) and non-breeding (May-June) seasons were investigated in rhesus and bonnet monkeys maintained under laboratory conditions. The marker enzymes selected for testicular cells were-Sertoli cells: beta-glucuronidase, gamma-glutamyl transpeptidase; pre-meiotic germ cells: glucose 6-phosphate dehydrogenase, malate dehydrogenase, alpha-glycerophosphate dehydrogenase; mature germ cells: LDH-X, sorbitol dehydrogenase. Results have indicated significant seasonal variation in marker enzymes only in rhesus testis. Marker enzymes of Sertoli cell increased while those of germ cell decreased significantly during non-breeding season. Marker enzymes of mature germ cells were affected much more drastically than those of the pre-meiotic germ cells.

Animals↗

Differential effects of hypothyroidism on Na-K-ATPase mRNA alpha isoforms in the developing rat brain.

In the developing rat cerebrum, the level of different isoforms of Na-K-ATPase mRNA increases significantly during the first three postnatal weeks, which represent the critical period of synaptogenesis and myelination-the two thyroid hormone-sensitive maturational events. To determine the possible functional relationship of these isoforms with maturational events in the developing brain and their mode of regulation by T3, we have examined the effect of hypothyroidism on the expression of the different alpha-isoforms (alpha 1, alpha 2, and alpha 3) of Na-K-ATPase mRNA covering the first 3 wk of postnatal development. Quantitation of these mRNAs from cerebra of 1-, 5-, 10-, 15-, and 20-d-old normal and hypothyroid rats by Northern blot analysis indicate that alpha 3 mRNA is not only predominantly expressed throughout this entire period of study but also represents the species which is most severely affected in the hypothyroid brain. The relative sensitivity for the expression of these mRNAs to T3 were alpha 3 > alpha 1 > alpha 2. These results, together with the report of predominant expression of the alpha 3 isoform in neuronal cells, suggest specific functional involvement of this isoform with the decisive maturational events in the rat brain. Kinetic studies on in vivo induction of Na-K-ATPase alpha-mRNAs by T3 in the 15-d-old hypothyroid rat shows clear stimulation of all the isoforms within 1 h of the administration of the optimal dose (200 micrograms T3/100 g body wt) suggesting a direct, possibly transcriptional effect of the hormone on the expression of these genes.

Aging↗

Management of metastatic Wilms tumor: an eleven year experience.

During the last 11 years, 101 patients of Wilms tumor were seen. Of these, 13 patients had metastatic disease at onset while 24 patients presented with relapse at a latter date. Seven patients have been cured, all had favourable histology. The risk factors associated with relapse were found to be unfavourable histology, lymph node involvement, age more than 6 years, diffuse spill, capsular and vascular invasion, and aneuploidy. Of the 18 patients who had relapsed, 14 were found to be aneuploid. Judicious use of various therapeutic options like radiotherapy to metastatic sites, second look surgery, resection of pulmonary metastasis and use of cis-platinum, VP-16 and Ifosfamide as "alternative chemotherapy protocols" were used to achieve cure in these advance cases.

Child↗

Effect of treatment with phenobarbital and stiripentol on carbamazepine-induced teratogenicity and reactive metabolite formation.

A model using SWV mice was developed to investigate the mechanistic basis of carbamazepine (CBZ)-related fetotoxicity. Drug administration was initiated prior to conception and continued until day 18 of gestation. The incidence of malformation was 33% following CBZ exposure (1,500 mg/kg/day), compared with a 5% incidence in pair-fed control animals (P < 0.05). Coadministration of nonteratogenic doses of phenobarbital (PB; a cytochrome P-450 inducer) (45 mg/kg/day) and CBZ (1,000 mg/kg/day) increased the frequency of malformation from 10% to 26% (P < 0.05), compared with mice dosed with CBZ alone (1,000 mg/kg/day). Coadministration of stiripentol (STP; a cytochrome P-450 inhibitor) (300 mg/kg/day) decreased the incidence of malformations produced by CBZ (1,500 mg/kg/day) from 33% to 16.7% (P < 0.05). The effect of PB administration on the binding of 14C in maternal and fetal tissue was assessed in dams that received CBZ (1,000 mg/kg/day) with or without PB (45 mg/kg/day) or STP (300 mg/kg/day) chronically and a single i.p. dose of 14C-CBZ on day 12 of gestation. In all instances, binding was greatest in maternal liver, then in the placenta, fetal head and body, and maternal thigh muscle. In all tissues, PB caused a two-to threefold increase in binding, compared with binding in mice exposed to CBZ alone. STP administration decreased protein adduct formation only in maternal liver. The binding of 14C was also assessed in hepatic microsomes prepared from female mice exposed to CBZ and PB or STP as in the in vivo study of 14C binding. The extent of irreversible binding was 67% greater in microsomes prepared from mice pretreated with PB and CBZ than with CBZ alone, while STP resulted in only 21% inhibition of 14C adduct formation (P < 0.05). The results are consistent with the formation of a chemically reactive teratogenic metabolite of CBZ in mice by cytochrome(s) P-450.

Abnormalities, Drug-Induced↗

Technetium-99m-HMPAO SPECT cerebral blood flow study in children with craniosynostosis.

UNLABELLED: Premature closure of cranial sutures (primary craniosynostosis) in children leads to characteristic skull deformities and prevents the constricted brain from growing normally. Although the cause remains unknown, several etiological factors have been cited. Recently, hypovascularity has been reported as a possible cause of craniosynostosis. METHODS: In a prospective study regional cerebral blood flow studies were carried out with 99mTc-HMPAO SPECT in seven children with craniosynostoses. Five preoperative and six postoperative studies were conducted and the results correlated with radiological and surgical findings. RESULTS: Preoperative studies revealed regional hypovascularity in the underlying cerebral hemisphere, corresponding to the fused sutures. Postoperative studies revealed disappearance of these perfusion defects in most cases, indicating normalization of perfusion following surgical decompression. CONCLUSION: This study establishes the presence of cerebral hypovascularity in craniosynostoses and suggests that early surgery and release of craniostenosis is essential to achieve optimum perfusion and brain development.

Brain↗

Duplications of the alimentary tract: clues to the missing links.

This is a review of the past 10 years' experience with duplications of the alimentary tract at the All India Institute of Medical Sciences, New Delhi, during which 14 infants and children with a total of 15 duplications were treated. Esophageal duplications represented the majority of cases (55%). Certain unexplained associations in this malformation led the authors to perform (1) detailed histological studies of the duplication cysts to seek explanation for the high incidence of gastric mucosa in their walls and its presence in duplications even in the distal parts of the gut, and (2) myelography and postmyelography computerized axial tomography scans to substantiate the spinal pathology. Three of four myelograms in patients with esophageal duplications showed an intraspinal pathology, and all three had vertebral defects. Histological evaluation of the cyst wall showed that gastric mucosa was the most common ectopic tissue in the walls of the cysts, and the tissues were in various primitive stages of differentiation. On the basis of these data, the authors hypothesize that (1) the embryonic endoderm of the entire alimentary tract has the potential to develop into gastric mucosa at the time of inception of duplications, which explains the high incidence of gastric mucosa and its presence in duplications even in the distal parts of the gut, (2) persistence of the embryonic relationship of the esophagus with the vertebral column is responsible for the high incidence of vertebral defects in esophageal duplications. The results of myelography in this series also support the theory of split notochord syndrome.

Child↗