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Biomedical subjects

Vinita Singh

Publications and source records attributed to Vinita Singh.

16 recordsLinked to original sources

Efficacy of caudal butorphanol.

OBJECTIVE: To evaluate the efficacy of butorphanol with or without bupivacaine for caudal epidural anesthesia in children undergoing infraumbilical surgery. METHODS: Sixty ASA physical status I and II patients of either sex aged 1-10 yr were randomized to one of three groups. Group L received 1 ml/kg of 0.25% bupivacaine; Group B received 1 ml/kg of 25 microg/kg butorphanol diluted in normal saline; and Group LB received 1 ml/kg of 25 microg/kg butorphanol in combination with 0.25% bupivacaine, in caudal epidural anesthesia. Hemodynamic variables (HR and MAP) and respiratory rate were monitored in all patients. Sedation score, pain score and requirement of rescue analgesia were recorded at preset time intervals alongwith post-operative complications. RESULTS: There was no difference among the groups regarding sedation scores, requirement of rescue analgesia and post-operative complications. Mean duration of analgesia was maximum in group BL (14.5 +/- 3.5 hr, P<0.001), than in group L (8.8 +/- 4.8 hr) and group B (6.8 +/- 2.9 hr). CONCLUSION: The addition of 25 microg/kg butorphanol to bupivacaine resulted in superior analgesia with a longer period compared with caudal bupivacaine and butorphanol alone, without an increase of side effects.

Analgesics, Opioid↗

Shunt revision in hydrocephalus.

OBJECTIVE: A retrospective analysis of 50 hydrocephalic children having a minimum follow-up of 6 months was carried out to see their etiology, clinical features, complications, incidence of shunt revisions, outcome and the variation from their Western counterparts. METHODS: Clinical features, image findings and treatment of all the cases were recorded from their discharge summaries. Record of shunt revision complications and outcome was maintained by the principal author. The data of all the cases were analyzed. RESULTS: The age of children varied from 1 month to 12 yr (mean 2.2 yr). The most common etiology of hydrocephalus was aqueductal stenosis in 18 (36%) children. Post infective hydrocephalus, either of post-tubercular meningitis (TBM) or following bacterial meningitis, remained the cause in 15 children (30%). Congenital TORCH infection was responsible for 3 cases of hydrocephalus making infective etiology as the cause in 18 (36%) cases. Intra 4th ventricular neurocysticercus cyst caused blockade of CSF pathway in 2 children. 15 out of 50 children required shunt revision, either due to infection (8,16%) or shunt obstruction (7, 14%). Multiple shunt revisions were required in 2 children only. These revisions were required due to infection, obstruction or malfunction of the shunt. CONCLUSIONS: Infective etiology is responsible for hydrocephalus in significant number of children (36%). The possibility of TORCH infection, as a cause of hydrocephalus should be considered even amongst the children of screened mothers during antenatal check-up. Pure intra 4th ventricular neurocysticercus cysts (without intraparenchymal cyst), though rare, can manifest with outlet obstruction. Incidence of shunt revision using Chhabra's medium pressure shunt is very high in children at an average follow up of 1.6 yr. Post infective hydrocephalus is a major cause of delayed milestones, contributing to mental retardation.

Cerebral Ventricles↗

Oral midazolam and oral butorphanol premedication.

OBJECTIVE: To evaluate the efficacy of oral midazolam and oral butorphanol for their sedative analgesic effects in children. METHODS: Sixty children, aged 2 to 10 yrs, of ASA physical status I and II, scheduled for surgical procedures of 1 to 2 hrs duration were randomized to one of the two groups. Group I: children received midazolam 0.5 mg/kg orally and Group II: children received butorphanol 0.2 mg/kg orally. Score of the children was assessed every 5 minutes till the induction of anesthesia. Intraoperative and postoperative analgesic requirement was recorded along with postoperative recovery and complications. RESULTS: The groups were identical regarding the patient's characteristics, hemodynamic variables, duration of surgery and awakening time. Less time was required for the onset and time of maximum sedation in the butorphanol group (p<0.05). Sedation scores were similar among the groups at all time intervals, while the scores were higher in the butorphanol group at the time of induction (p<0.05). Less number of children required intraoperative and postoperative rescue analgesia in the butorphanol group (p<0.05). Statistically significant difference was found among the groups in respect to complete amnesia (50% in group I vs 80% I group II, p<0.05) and recollection (40% in group I vs 10% in group II, p<0.05). CONCLUSION: Oral butorphanol is comparable to oral midazolam in children but analgesia along with sedation is an additional advantage which makes it better than midazolam without a significant increase in side effects.

Administration, Oral↗

Comparative study of complex spina bifida and split cord malformation.

OBJECTIVE: To see the difference in clinical profiles, radiological findings and surgical outcome of the group 1 split cord malformation and meningomyelocele (SCM with MMC) from group 2 (SCM without MMC). METHODS: 46 patients of SCM were selected from a total of 138 cases of spinal dysraphism. They were divided into two groups, based on presence or absence of MMC. Group I (SCM with MMC) n =19 patients and Group II (SCM without MMC) n=27 patients. A detail clinical evaluation and MR screening of whole spine of all cases was performed. All patients underwent surgical detethering of cord. After an average follow-up of 1.7 years, the operative results were clinically assessed and statistical significance was calculated. RESULTS: Male to female ratio was 1:09. Mean age of presentation was 3.6 years. Cutaneous markers like tuft of hair, cutaneous haemangioma, etc, had a higher incidence in group II in comparison to group I (50% vs 10.5%). The incidence of motor deficits was significant in group I in comparison to group II (63% vs 40%). The incidences of sensory loss, trophic ulcers, sphincteric dysfunction and muscle atrophy were relatively more common in group I patients, while neuro-orthopedic deformities such as congenital telepes equinovarus (CTEV), scoliosis and limb shortening were more frequent (67%) in group II children as compared to group I (53%). Type I SCM has higher incidence in group I children. Low lying conus were found in 47% patient of group I, while in group II it was noticed in 69%. The associated cranial anomalies like hydrocephalus, ACM and syrinx, were slightly higher in group I patients. At surgery, dysgenetic nerve roots, neural placode, arachnoid bands and atrophic cord were seen mainly in group I. Postoperative complications like, CSF leak, pseudomeningocele and meningitis were more commonly encountered in group I patients. The patients of group II showed better operative outcome compared to group I cases. CONCLUSION: Incidence of SCM with MMC amount to 41% of total SCM cases. Progressive neurological deficit was higher in this group (SCM with MMC) in comparison to the group harboring SCM without MMC. In view of a significant association of SCM in MMC cases, associated with other craniospinal anomalies, a thorough screening of neuraxis (by MRI) is recommended to treat all treatable anomalies simultaneously for desired outcome.

Adolescent↗

DAL-1/4.1B tumor suppressor interacts with protein arginine N-methyltransferase 3 (PRMT3) and inhibits its ability to methylate substrates in vitro and in vivo.

DAL-1 (differentially expressed in adenocarcinoma of the lung)/4.1B is a tumor suppressor gene on human chromosome 18p11.3 whose expression is lost in >50% of primary non-small-cell lung carcinomas. Based on sequence similarity, DAL-1/4.1B has been assigned to the Protein 4.1 superfamily whose members interact with plasma membrane proteins through their N-terminal FERM (4.1/Ezrin/Radixin/Moesin) domain, and cytoskeletal components via their C-terminal SAB (spectrin-actin binding) region. Using the DAL-1/4.1B FERM domain as bait for yeast two-hybrid interaction cloning, we identified protein arginine N-methyltransferase 3 (PRMT3) as a specific DAL-1/4.1B-interacting protein. PRMT3 catalyses the post-translational transfer of methyl groups from S-adenosyl-L-methionine to arginine residues of proteins. Coimmunoprecipitation experiments using lung and breast cancer cell lines confirmed this interaction in mammalian cells in vivo. In vitro binding assays demonstrated that this was an interaction occurring via the C-terminal catalytic core domain of PRMT3. DAL-1/4.1B was determined not to be a substrate for PRMT3-mediated methylation but its presence inhibits the in vitro methylation of a glycine-rich and arginine-rich methyl-accepting protein, GST (glutathione-S-transferase-GAR (glycine- and arginine-rich), which contains 14 'RGG' consensus methylation sites. In addition, induced expression of DAL-1/4.1B in MCF-7 breast cancer cells showed that the DAL-1/4.1B protein significantly inhibits PRMT3 methylation of cellular substrates. These findings suggest that modulation of post-translational methylation may be an important mechanism through which DAL-1/4.1B affects tumor cell growth.

Breast Neoplasms↗

Subependymal giant cell astrocytoma: a report of five cases.

Five cases of intraventricular subependymal giant cell astrocytomas (SEGCA) were retrospectively reviewed. Records and detailed work-up of all five cases were well maintained in view of rare occurrence of these tumors. The five patients were males aged 10, 12 (2 cases), 14 and 18 years. The 18-year-old aged male had no stigmata of tuberous sclerosis (TSC) on examination, while the rest presented with features of TSC, intraventricular tumors and hydrocephalus. None of the five cases had renal tumors and did not reveal cardiac tumors. Skin manifestations like shagreen patches were present in two, facial angiofibromas in three, periungal fibromas in two, hypopigmented macules in two and ash-leaf spot in two patients. Fundoscopic examination revealed retinal astrocytomas in two cases only. Two of the five children did not have mental compromise. A child who started throwing seizures early (at 5 months of age) had severe mental retardation. Although SEGCA is a less vascular tumor, one tumor bled profusely intraoperatively; it was excised rapidly via the transcortical route to salvage the life of the child, though he was planned for the transcallosal route like the other cases. The tumor of another child was also very vascular. Four children survived surgery and required no shunt CSF diversion, while one died of severe ventriculitis and septicemia 3 weeks after surgery.

Adolescent↗

Ascites in ventriculoperitoneal shunt.

OBJECTIVE: To fetch out the factors responsible for ascites, following shunt CSF diversion in cases of intracarnial lesions. Four children developing ascites/abdominal psuedocyst following ventriculoperitoneal shunt were analyzed to see the factors responsible for such complication. METHODS: Records of 4 cases developing ascites were studied retrospectively. These children developed ascites at 8 months, 6 months, 1 year and 1 year 2 months interval following their shunt installation. RESULTS: The primary etiology of hydrocephalus was demonstrated as thalamic glioblastoma, choroid plexus papillomas of third ventricle, post tubercular meningitis hydrocephalus and suprasellar craniopharyngioma. CONCLUSION: The proposed etiology of ascites in these cases was peritoneal metastasis from thalamic glioblastoma through ventriculoperitoneal shunt in first case, excessive production of CSF by choroid plexus papilloma in second, infection in the third case and craniopharyngioma causing excessive production of CSF in the fourth child. All the children were treated by reasonable laparotomy and fenestration of cyst along with the repositioning of shunt tip at another site.

Ascites↗

The 4.1/ezrin/radixin/moesin domain of the DAL-1/Protein 4.1B tumour suppressor interacts with 14-3-3 proteins.

The Protein 4.1 family contains at least two members that function as tumour suppressors, the neurofibromatosis 2 gene product merlin and the recently identified differentially expressed in adenocarcinoma of the lung (DAL-1)/Protein 4.1B molecule. DAL-1/Protein 4.1B loss is observed in a variety of tumours, including breast and lung cancers as well as meningiomas. We have previously demonstrated that DAL-1/Protein 4.1B interacts with some but not all merlin-binding proteins, raising the possibility that DAL-1/Protein 4.1B associates with additional unique proteins specific to its function as a negative growth regulator. Using yeast two-hybrid interaction cloning, we identified three 14-3-3 isoforms, beta, gamma and eta, to be DAL-1/Protein 4.1B-binding proteins. These interactions were verified by using glutathione S-transferase affinity chromatography in vitro and co-immunoprecipitation in vivo. The interaction of 14-3-3 with DAL-1/Protein 4.1B was specific, as 14-3-3 did not bind to the related Protein 4.1 family members merlin, ezrin or radixin. The DAL-1/Protein 4.1B domain that mediates 14-3-3 binding was mapped to residues Pro(244) and Leu(280) within the 4.1/ezrin/radixin/moesin domain. The identification of this novel DAL-1/Protein 4.1B-interacting protein represents the first step towards elucidating its potentially unique mechanism of action.

14-3-3 Proteins↗

Suppression of growth and increased cellular attachment after expression of DAL-1 in MCF-7 breast cancer cells.

The differentially expressed in adenocarcinoma of the lung (DAL-1) gene, which shares significant homology with members of the 4.1/ezrin/radixin/moesin/neurofibromatosis 2 (ERM/NF2) protein family, has previously been shown to suppress growth in lung cancer cell lines. This gene localizes to chromosome band 18p11.3, which undergoes loss of heterozygosity (LOH) in nonsmall cell lung carcinomas and a significant proportion of ductal carcinomas in situ (DCIS) of the breast. This finding suggests that alteration of gene(s) (possibly DAL-1) within this chromosomal region may be important early in the progression of breast disease. We generated MCF-7 cell lines expressing DAL-1 constitutively or under the control of an inducible promoter and analyzed the effect of DAL-1 expression on growth. These investigations revealed that the DAL-1 protein suppresses the growth of MCF-7 cells and may do so in part through the induction of apoptosis. In addition, expression of DAL-1 increased attachment of these cells to a variety of extracellular matrices. This is the first evidence that the DAL-1 protein functions at the interface between cell adhesion and apoptosis in controlling cell growth.

Apoptosis↗

Prenatal diagnosis in two families with autosomal, p47(phox)-deficient chronic granulomatous disease due to a novel point mutation in NCF1.

OBJECTIVE: Prenatal diagnosis was required in two unrelated families with chronic granulomatous disease (CGD) patients who lacked expression of p47(phox) protein; thus a search for mutations in NCF1 was undertaken. METHODS: Gene scanning was applied to establish the relative number of coding and pseudo-NCF1 genes. PCRs specific for coding NCF1 cDNA and coding NCF1 exon-7 genomic DNA were devised. RESULTS: The normal 1:2 ratio of coding and pseudo-NCF1 genes was found in the patients. Sequencing of the RT-PCR product specific for mRNA from the coding NCF1 genes revealed a novel homozygous G579A mutation in both patients, changing the TGG codon for Trp193 into the TAG stop codon. This mutation was confirmed in genomic DNA. The parents of both patients were found to be heterozygotes for this mutation. In the chorionic villus DNA of the first family a heterozygous G579A mutation was found. Postpartum, functional NADPH oxidase tests were normal. In the second family, this mutation was present in homozygous form in the chorionic villus DNA. Following termination of the pregnancy, the diagnosis of p47(phox)-deficient CGD was confirmed on DNA extracted from fetal blood. CONCLUSION: This is the first report of prenatal diagnosis in p47(phox)-deficient CGD.

Adolescent↗

Connexin 36 in bovine retina: lack of phosphorylation but evidence for association with phosphorylated proteins.

In vertebrate retina interneuronal communication through gap junctions is involved in light adaptation and in the transfer of visual information from the rod pathway to the cone pathway. Reports over the last two decades have indicated that these gap junctions are regulated by cyclic nucleotide-dependent protein kinases suggesting that the gap junction proteins, connexins, are phosphorylated. Though all the connexins involved in light adaptation and information transfer from rod to cone pathway are not yet known, connexin 36 has been shown to be definitively involved in the latter process. We have therefore attempted to investigate the cyclic nucleotide-dependent phosphorylation of this connexin in bovine retina. We found several soluble and membrane proteins in bovine retina whose phosphorylation was regulated by cyclic nucleotides. However, no protein of about 36 kDa with cyclic nucleotide-regulated phosphorylation was found in gap junction-enriched membrane preparations. A 36-kDa phosphorylated protein was found in gap junction-enriched membranes phosphorylated in the presence of calcium. However, this protein was not immunoprecipitated by anti-connexin 36 antibodies indicating that it was not connexin 36 in spite of its similarity in molecular weight. Immunoprecipitation did reveal phosphorylated proteins coimmunoprecipitated with connexin 36. Two of these proteins were identified as beta and alpha tubulin subunits. Though cyclic GMP and calcium did not greatly influence the association of these proteins with connexin 36, the results suggest the possibility of connexin 36 associating with other proteins. Together, these observations indicate that interneuronal communication at gap junctions made by connexin 36 may not be regulated by direct phosphorylation of connexin 36, but possibly by phosphorylation of associated proteins.

Animals↗

Intramedullary mass lesion of the spinal cord in children of a developing milieu.

A retrospective study of 22 children with intramedullary mass lesions (neoplastic and nonneoplastic) was performed to see the frequency of different histotypes of tumors/lesions and the functional outcome in Indian children. The age of the children varied from 1.5 to 16 years with a median of 8 years. The male to female ratio was 2.7:1. The children having a minimum follow-up of 3 months and a complete clinicopathological record were entered into this study. McCormick functional grading was applied retrospectively to assess the preoperative grade and postoperative functional outcome of the children. Histopathologically, these 22 cases were astrocytomas (n = 6, 27.3%), ependymomas (n = 3, 13.6%), dermoids (n = 3, 13.6%), epidermoids (n = 2, 9.1%), ependymal cysts (n = 2, 9.1%), and myxopapillary ependymoma, neurenteric cyst, ganglioglioma, teratoma, tuberculoma and anteriovenous malformation one each (4.55%). Near-total or gross-total resection was achieved in 13 (59%) and subtotal resection in 7 patients (32%), while complete excision of tuberculoma was achieved in 1 patient. Coagulation of perimedullary vessels was done in another single patient with anteriovenous malformations. Fourteen of the 22 cases having had functional grade IV or V preoperatively, improved to grade I or II (n = 7) and to grade III (n = 4, all astrocytomas) following surgery. Two patients died (1 within 2 days and 1 after 3 months due to recurrence of the tumor) and 1 case deteriorated at the follow-up of 4 months. Eight out of the 22 patients who had been admitted with functional grade II or III improved to grade I or II following surgery. The following conclusions were drawn after evaluation of these cases: (1) astrocytomas and ependymomas constituted only 50% of intramedullary tumors; (2) nonneoplastic, malformative tumors like dermoid and epidermoid showed a higher incidence (23%) in comparison with the Western World where all congenital intramedullary tumors (including dermoids and epidermoids) account for 5-8% only; (3) extremely rare cystic lesions like ependymal cyst and inflammatory granuloma may manifest as an intramedullary lesion; (4) even neurenteric cyst, though rare, may manifest as a pure intramedullary lesion without the stigmata of spinal dysraphism, and (5) delayed presentation was the cause of unfavorable outcome in a developing milieu.

Adolescent↗

Benign intradural extramedullary masses in children of northern India.

Twenty-five children with benign intradural extramedullary tumors/lesions were retrospectively analyzed to see the frequency of different histotypes in this location and their variation from the Western world. The duration of symptoms, clinical profile and surgical outcome of these cases were evaluated. The age of children ranged from 1.5 to 18 years, with a mean age of 7.5 years. Thirteen amongst them were male. Follow-up ranged from 3 months to 5 years with a mean of 19 months. McCormick functional grading was used retrospectively to find out the functional outcome in these children. Sixty-eight percent of these cases presented with functional grade IV or V. The mean duration from the appearance of the first symptoms to admission to our hospital in these children was 13 months. Improvement in the functional grade following surgical excision was noted amongst all, except one, who presented with schwannoma, and did not improve from grade III even after a 14-month follow-up. Reoperation/two-staged operation was required in 3 children. The following conclusions were drawn from this study: (1) approximately half (48%) of intradural extramedullary benign tumors are nerve sheath tumors, i.e. neurofibromas, neurilemomas and schwannomas. Giant neurofibromas with giant extraforaminal extension may rarely manifest with a large extraspinal mass; (2) meningioma is an infrequent tumor in this location; (3) developmental cystic dysraphic lesions (neurenteric cyst, arachnoid cysts), unassociated with the stigmata of spinal dysraphism, are significantly more frequent (28%) than reported in the literature; (4) the possibility of infective lesions (granuloma, abscess) causing compressive features cannot be denied even in intradural extramedullary tumors; (5) long-standing lesions, with a long segment involvement, also have a good outcome following a good microsurgical excision, and (6) more than half of the children (68%) present with a severe neurological compromise, either because of ignorance and poor education or due to the scanty diagnostic facilities available at the peripheral hospitals of the developing milieu.

Adolescent↗