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Biomedical subjects

Raj Kumar

Publications and source records attributed to Raj Kumar.

At least 19 recordsLinked to original sources

Lhermitte-Duclos disease.

BACKGROUND: Lhermitte-Duclos disease (LDD; dysplastic gangliocytoma of the cerebellum) is a rare hamartoma of the cerebellum. It was first described by Lhermitte and Duclos in 1920 as "Sur un ganglioneurome diffus du cortex du cervelet" (Lhermitte and Duclos [Bull Assoc Fr Etude Cancer 9:99-107, 1920]). Since then, due to its rarity and the variability of its presentation, the diagnosis is often missed. It is not only important for the neurosurgeon and the pathologist to be aware of this entity so as to differentiate from malignant lesions but also to distinguish it from other cerebellar malformations, which may be hypoplastic or dysplastic, focal or diffuse in nature, with brain stem and cerebral involvement, and varied natural course. ILLUSTRATIVE CASE: We report a case of LDD in a 16-year-old boy. This case exemplifies the rarity of the disease leading to lack of awareness with which the diagnosis was easily missed. We also take this opportunity to discuss the clinical presentation, neuroradiological appearance, and a brief summary of histopathological findings, pathogenetic considerations, and neurogenetical aspects.

Adolescent↗

Primary spinal primitive neuroectodermal tumor: case series and review of the literature.

Primary spinal primitive neuroectodermal tumor (PSPNET) is extremely rare and only 25 cases have been reported in the world literature so far. Three patients of 8, 9 and 18 years of age, who presented with variable grades of neurological deficit were diagnosed as having a dorsal intramedullary lesion, a holocord lesion and cervical extradural tumor with extraspinal extension, respectively, and were operated at our institute. The histopathology of all 3 children revealed PNET. The clinical course, image characteristics and outcome of the 3 children are described, and the relevant literature is reviewed. The following conclusions were drawn from the present study and review of the literature. PNET may manifest itself as a primary lesion of the spine unlike the more common drop metastases from an intracranial lesion. PSPNET may be intramedullary, intradural and extradural with variable extraspinal extension. PSPNET may present as holocord intramedullary lesion, an entity which has not been described earlier. These lesions have a short history, significant neurological deficits and rapid course of illness. PSPNET, though an established entity, did not find a place in the WHO 2000 classification of CNS tumors. Hence its status has to be defined.

Adolescent↗

Outcome of meningomyelocele/lipomeningomyelocele in children of northern India.

OBJECTIVE: To evaluate the clinical profile, associated anomalies and surgical outcome of children with meningomyelocele (MMC)/lipomeningomyelocele. METHODS: Out of a total of 181 cases of spinal dysraphism treated at our Institute between 1996 and 2004, 102 (56.35%) cases of MMC/lipomeningomyelocele were analyzed retrospectively and prospectively. The clinical profile and radiological findings of these children were recorded. Craniospinal MRI was the essential investigation and was done as a management protocol at our Institute for these children. Eighty-two out of 102 (80.3%) cases had pure MMC/lipomeningomyelocele and 20/102 (19.6%) had associated split cord malformation (SCM; complex spina bifida). All these children underwent surgery for their primary and associated malformations as indicated. They were clinically assessed over a mean follow-up period of 3.6 years ranging from 1.5 months to 8 years. No urodynamic or evoked potential studies were done to assess the sphincteric outcome following surgery. RESULTS: Forty-six (45.1%) of children with MMC had other associated tethering lesions, including the presence of SCM. Craniospinal axis screening remained an important tool to understand the associated tethering lesions and malformations. Only 58.8% of children had hydrocephalus; thus the incidence was much lower compared with reports from the western literature (80-96%). 63.3% of children with overt hydrocephalus required shunt surgery prior to the definitive surgery; however, 23.3% of cases required a shunt after the MMC has been closed. Improvement in clinical profile following microneurosurgery was observed in 42.8% of cases with motor involvement, 46.8% of cases with sensory dysfunction and 39.5% of cases with sphincteric involvement. Motor improvement was seen in 43.6% of cases of pure MMC/lipomeningomyelocele as compared to only 40.0% of cases of complex spina bifida. Sensory improvement was also better in pure MMC/lipomeningomyelocele group being seen in 48.0% of cases as compared to only 42.9% of cases of complex spina bifida. CONCLUSION: Presence of SCM with MMC is referred to as complex spina bifida and is seen in a significant proportion (19.6%) of all cases of MMC. Thorough assessment of the craniospinal imaging needs to be done to look for the presence of multiple tethering lesions which could be present in the same case. Not all children with spinal dysraphism with hydrocephalus required shunt surgery or CSF diversion but a constant and vigilant follow up could avoid it in 13.3% of cases. Improvement in motor and sensory dysfunction was better in the pure MMC/lipomeningomyelocele group than in the complex spina bifida group. Improvement in sphincteric dysfunction, although seen in significant cases, was less compared with improvement in motor and sensory dysfunction. This probably represents a lack of definitive objective criteria for urodynamic improvement and a lack of proper rehabilitation. Electromyographic studies and uroflowmetry are required to asses the true sphincteric outcome following surgery.

Abnormalities, Multiple↗

LC and LC-MS study of stress decomposition behaviour of isoniazid and establishment of validated stability-indicating assay method.

Isoniazid was subjected to different ICH prescribed stress conditions of thermal stress, hydrolysis, oxidation and photolysis. The drug was stable to dry heat (50 and 60 degrees C). It showed extensive decomposition under hydrolytic conditions, while it was only moderately sensitive to oxidation stress. The solid drug turned intense yellow on exposure to light under accelerated conditions of temperature (40 degrees C) and humidity (75% RH). In total, three major degradation products were detected by LC. For establishment of stability-indicating assay, the reaction solutions in which different degradation products were formed were mixed, and the separation was optimized by varying the LC conditions. An acceptable separation was achieved using a C-18 column and a mobile phase comprising of water:acetonitrile (96:4, v/v), with flow rate and detection wavelength being 0.5 ml min(-1) and 254 nm, respectively. The degradation products appeared at relative retention times (RR(T)) of 0.71, 1.34 and 4.22. The validation studies established a linear response of the drug at concentrations between 50 and 1000 microg ml(-1). The mean values (+/-R.S.D.) of slope, intercept and correlation coefficient were 35,199 (+/-0.88), 114,310 (+/-4.70) and 0.9998 (+/-0.01), respectively. The mean R.S.D. values for intra- and inter-day precision were 0.24 and 0.90, respectively. The recovery of the drug ranged between 99.42 and 100.58%, when it was spiked to a mixture of solutions in which sufficient degradation was observed. The specificity was established through peak purity testing using a photodiode array detector. The method worked well on application to marketed formulation of isoniazid, and a fixed-dose combination containing isoniazid and ethambutol HCl. It was even extendable to LC-MS studies, which were carried out to identify the three degradation products. The m/z values of the peaks at RR(T) 0.71 and RR(T) 1.34 matched with isonicotinic acid and isonicotinamide, respectively. The product appearing at RR(T) 4.22 was isolated using preparative LC-MS, and turned out to be a yellow compound that was identified as isonicotinic acid N'-(pyridyl-4-carbonyl)-hydrazide based on mass, FTIR and (1)H/(13)C NMR spectral data. The same was indicated to be responsible for discolouration of isoniazid bulk drug substance and formulations, which is a familiar problem. The mechanism of formation of the said compound is outlined.

Biological Assay↗

Unusual split cord with neurenteric cyst and cerebellar heterotopia over spinal cord.

OBJECTIVE: To report a case of splitting of a cord, which could neither be classified as type I nor type II according to Pang's classification. The child had associated neurenteric cyst and cerebellar tissue heterotopia. CASE REPORT: A 3-year-old girl presented with a tuft of hair and dermal sinus at her upper dorsal spine. She had splitting of cord into two halves by two intradural horny osseocartilaginous spurs leaving a gap of 3 mm in between (two spurs and two halves of cords). A neurenteric cyst was seen passing from the anterior to posterior aspect of the cords through this gap. An associated heterotopic cerebellar tissue mass was encountered over the dorsum of cord proximal to splitting. The dermal sinus, neurenteric cyst, and spurs were excised to detether the cord. The heterotopic tissue was biopsied. The child had no neurological deficit at 2.5 years follow-up. CONCLUSION: An unusual splitting of cord by unusual spurs may leave a gap between two spurs and two halves of cords to pass a neurenteric cyst. Rarely, heterotopic tissue may be associated with split cord syndrome. A dermal sinus may lead into underlying neurenteric cyst (rather than dermoid).

Cerebellar Diseases↗

Folding mirror schlieren diffraction interferometer.

We demonstrate the use of a mirror as a viewing diaphragm to generate a built-in diffracted reference beam in schlieren diffraction interferometry (SDI). The use of a mirror edge as a diffracting element instead of a conventional knife edge considerably enhances the contrast of the schlieren pattern, and it is shown to be equal to that of a phase knife edge. This increase in contrast is due to the fact that the otherwise unutilized diffracted beam in SDI is recombined in the described folding mirror geometry.

Journal Article↗

Zingiber officinale exhibits behavioral radioprotection against radiation-induced CTA in a gender-specific manner.

At the organismic level, exposure to radiation can produce taste aversion (CTA) learning and emesis, which have been proposed as behavioral endpoints that are mediated by harmful effects of radiations on peripheral systems, primarily the gastrointestinal system. Thus, the aim of the present investigation was to study the gastroprotective action of hydroalcoholic extract of zingiber rhizome (Zingiber officinale Rosc.) against radiation-induced conditioned taste aversion (CTA) in both male and female species of animals, for testing its potential as a behavioral radioprotector. Administration of zingiber extract 1 h before 2-Gy gamma-radiation was significantly effective in blocking the saccharin avoidance response, with 200 and 250 mg/kg b.wt. i.p., being the most effective doses for male and female rats, respectively. A comparison of the efficacy of zingiber extract with two antiemetic drugs, ondansteron and dexamethasone, revealed that the extract rendered comparable protection against radiation-induced CTA. Our experiments also confirmed the existence of sex dichotomy (i.e., the sex of animal greatly influenced response towards radiation exposure) in relation to behavioral responses (CTA) or differential metabolism. The observed gender variations were hypothesized to be a result of hormonal fluctuations and differences in pharmacological parameters in male and female rats. To correlate the mechanism of action, the free-radical-scavenging potential of zingiber extract to scavenge hydroxyl ion and nitric oxide was also tested, in cell-free system and a concentration of 1000 microg/ml, was found to be the most potent, which has been proposed as one the many activities assisting in its overall ability to modulate radiation-induced taste aversion. The results demonstrate that Z. officinale possesses antioxidant, radioprotective and neuromodulatory properties that can be effectively utilized for behavioral radioprotection and for efficiently mitigating radiation-induced CTA in both males and females species.

Animals↗

Catalyst-free conjugated addition of thiols to alpha,beta-unsaturated carbonyl compounds in water.

[reaction: see text] Catalyst-free conjugate addition of thiols to alpha,beta-unsaturated carbonyl compounds in water is reported. beta-Sulfido carbonyl compounds were formed at room temperature, in short times and with excellent chemoselectivity. Competitive dithiane/dithiolane formation, transesterification, and ester cleavage were not observed. Water played a dual role in simultaneously activating the alpha,beta-unsaturated carbonyl compound and the thiol. This new methodology constitutes an easy, highly efficient, and green synthesis of beta-sulfido carbonyl compounds.

Journal Article↗

External hydrocephalus in small children.

OBJECTIVE: Confusion exists in literature regarding the entity of external hydrocephalus which has been addressed by different terms like subdural effusion, hygroma, benign infantile hydrocephalus, etc. In this report, the author has tried to define the clinical and radiological criteria for reaching the diagnosis of external hydrocephalus. METHODS: Five children 9 months to 2 years of age with subdural fluid collection were studied prospectively for a period of 8 years. The radiological and clinical criteria sparsely described in literature were followed to study the profile of suspected cases. RESULTS: Four children presented with craniomegaly; the fifth case had tense, wide, and bulging fontanelle. CT of all five children showed hemispheric extracerebral fluid collection with enlarged subarachnoid spaces. Three children had mild to moderate ventriculomegaly without significant periventricular lucency, while the other two had borderline ventricular enlargement. All were managed conservatively. All five children were asymptomatic at follow-up from 12 weeks to 2 years. CONCLUSION: The possible conclusions from this study of rare cases are: external hydrocephalus needs differentiation from other conditions of subdural fluid collections. The radiological criteria such as (a) extracerebral fluid collection (relatively more in anterior convexity than posterior convexity), (b) dilatation of subarachnoid spaces, and (c) mild to moderate ventriculomegaly without (or with questionable) periventricular lucency may be helpful in making a radiological diagnosis of external hydrocephalus. Conservative treatment with acetazolamide helped in ameliorating the clinical features of the cases studied.

Child, Preschool↗

Intracranial sinonasal undifferentiated carcinoma (SNUC) in a child.

INTRODUCTION: Sinonasal undifferentiated carcinoma (SNUC) is a rare and relatively newly described clinicopathological entity of the nasal cavity and paranasal sinuses. CASE REPORT: Authors report a 12-year-old male child with SNUC, who presented primarily with features of raised intracranial pressure without any feature pertaining to nasal cavity/orbit involvement. The large mass, however, was also predominantly intracranial resembling with solid intra-axial tumor, with its classical clinical profile. DISCUSSION: The authors highlight important diagnostic features, pathogenesis, and outcome of SNUC. The unique features of the only intracranial involvement are also discussed.

Brain Neoplasms↗

Activation function 1 of glucocorticoid receptor binds TATA-binding protein in vitro and in vivo.

The mechanism through which the glucocorticoid receptor (GR) stimulates transcription is still unclear, although it is clear that the GR affects assembly of the transcriptional machinery. The binding of the TATA-binding protein (TBP) to the TATA-box is accepted as essential in this process. It is known that the GR can interact in vitro with TBP, but the direct interaction of TBP with GR has not been previously characterized quantitatively and has not been appreciated as an important step in assembling the transcriptional complex. Herein, we demonstrate that the TBP-GR interaction is functionally significant by characterizing the association of TBP and GR in vitro by a combination of techniques and confirming the role of this interaction in vivo. Combined analysis, using native gel electrophoresis, sedimentation equilibrium, and isothermal microcalorimetry titrations, characterize the stoichiometry, affinity, and thermodynamics of the TBP-GR interaction. TBP binds recombinant GR activation function 1 (AF1) with a 1:2 stoichiometry and a dissociation constant in the nanomolar range. In vivo fluorescence resonance energy transfer experiments, using fluorescently labeled TBP and various GR constructs, transiently transfected into CV-1 cells, show GR-TBP interactions, dependent on AF1. AF1-deletion variants showed fluorescence resonance energy transfer efficiencies on the level of coexpressed cyan fluorescent protein and yellow fluorescent protein, indicating that the interaction is dependent on AF1 domain. To demonstrate the functional role of the in vivo GR-TBP interaction, increased amounts of TBP expressed in vivo stimulated expression of GR-driven reporters and endogenous genes, and the effect was also specifically dependent on AF1.

Animals↗

A truncated derivative of nmt 1 promoter exhibits temperature-dependent induction of gene expression in Schizosaccharomyces pombe.

Despite increasing exploitation of Schizosaccharomyces pombe as a model system there is a lack of convenient vectors for research and application. Expression with the commonly used promoter, nmt 1, requires a laborious regime involving the removal of repressor, thiamine, from a growing culture and further growth for 18 h to achieve maximum expression, thus underlining the need for more user-friendly promoters. We report here the isolation and characterization of a truncated derivative of the nmt 1 promoter having novel induction characteristics: it is induced by shift of growth temperature from 36 degrees C to 25 degrees C, achieving maximum expression within 3 h. Similar features of expression were observed with the reporter genes GFP and beta-galactosidase, a native gene, cdc 18, and a commercially important foreign therapeutic protein, streptokinase. The new promoter element offers additional advantages, such as lack of deleterious effect on cell viability and potential ability to express toxic proteins. These features make the new promoter a potentially better alternative to nmt 1, both as a research tool and for expression of commercially important proteins in Sz. pombe, and suggest the possibility of using similar approaches to design promoters with novel and useful properties.

Base Sequence↗

Purely intra-articular versus general anesthesia for proposed arthroscopic partial meniscectomy of the knee: a randomized controlled trial.

PURPOSE: The aim of this study was to compare intra-articular anesthesia alone versus general anesthesia with regard to ease of the procedure, level of postoperative pain, and patient satisfaction when partial meniscectomy is anticipated. METHODS: We prospectively randomized to general anesthesia or to intra-articular anesthesia 107 patients who were about to undergo knee arthroscopy, in whom partial meniscal resection was anticipated on the basis of clinical or radiologic grounds. Technical difficulty of the procedure, level of postoperative pain and nausea, and overall patient satisfaction were assessed. RESULTS: The ease of obtaining arthroscopic views, the adequacy of these views, and the ease of performing partial meniscal resection or another procedure were similar in both groups according to scores assigned by the operating surgeon. Pain at 6 hours postoperatively was significantly less in the intra-articular anesthesia group but was similar in the 2 groups at 24 and 48 hours. Patients who were given intra-articular anesthesia reported higher satisfaction rates in understanding the underlying disease of the knee. CONCLUSIONS: We propose that intra-articular anesthesia alone can be effectively used in knee arthroscopies in which partial meniscal resection is anticipated. LEVEL OF EVIDENCE: Level I, high-quality randomized controlled therapeutic trial.

Adult↗

Protection of the hemopoietic system by Podophyllum hexandrum against gamma radiation-induced damage.

A semi-purified extract of low-altitude Podophyllum hexandrum (REC-2001) containing a relatively low content of podophyllotoxin (3.25 %) exhibited potent antioxidant ability in lipid media (at 1000 microg/mLagainst 0.25 kGy) and significant (p < 0.05) hydroxyl ion scavenging potential (78.83 % at 500 microg/mL). In vitro investigations revealed the ability of REC-2001 to significantly (p < 0.05) reduce radiation-induced hemolysis (2 microg/mL; 46.184 %) and nitric oxide scavenging levels (IC (50): 792 +/- 1.25 microg/mL). Protection of the hemopoietic system of Strain 'A' mice administered 20 mg/kg BW REC-2001 30 min prior to lethal irradiation (10 Gy) was recorded and was mediated by free radical scavenging and lowering of lipid oxidation. Further studies investigating the effects of REC-2001 on stem cell modulation are warranted.

Animals↗

Unusual tumors of the posterior fossa skull base.

Five unusual cases of posterior skull base tumors were treated through different skull base approaches. Two or more staged operations were required to achieve total or near-total excision and decompression of two extensive tumors. Total excision of an extensive en plaque meningioma of the foramen magnum that encircled the brain stem and cervical spinal cord could not be achieved through the extreme lateral and suboccipital craniectomy approach. However, the vital structures were decompressed and the patient's postoperative morbidity was acceptable. An extended middle fossa approach was required to excise a hemangiopericytoma of the middle and posterior fossae in a 12-year-old. Extension of the tumor into the posterior fossa precluded a retromastoid approach because the mass draped the lower cranial nerves posteriorly. Two men had undifferentiated adenocarcinomas involving the jugular foramen and middle to posterior fossa, respectively. The origin of one was renal in a 37-year-old man. A 63-year-old man survived 1.5 years after a good decompression of his extensive tumor and irradiation. The histological diagnosis of paraganglioma of the occipital bone was a surprise in a 25-year-old man with pure bony involvement. These cases indicate that the appropriate selection of skull base approaches and their combination can provide the needed access to achieve adequate excision or decompression of masses located in challenging anatomical regions of the skull base. Furthermore, good surgical excision improves palliation in radioresistant metastatic tumors of the skull base.

Journal Article↗

Paradoxical response to chemotherapy in neurotuberculosis.

OBJECTIVE: Our objective was to investigate the paradoxical response and the factors responsible for such an uncommon (but known) response to chemotherapy in neurotuberculosis. MATERIAL AND METHODS: Ten children with intracranial tuberculomas/neurotuberculosis were retrospectively studied, who were on regular antituberculous chemotherapy. Any deterioration of the neurological condition, increase in the size of the lesion or appearance of new lesions was studied clinically and radiologically during the follow-up period. RESULTS: An atypical response to chemotherapy was observed from 3 weeks to 1 year of chemotherapy. Four of the 10 children, who were receiving chemotherapy for either post-tubercular meningitis (TBM), hydrocephalus (2) or TBM (2), developed multiple granulomas in 3 and hydrocephalus in 1 case. The remaining 6 children who were diagnosed to have granulomas at their presentation deteriorated at the follow-up despite regular chemotherapy. CT scans were repeated in 7 of 10 cases at the time of neurological deterioration, out of which 5 children showed appearance of new granulomas or abscess(es) and 2 showed an increase in the size of their preexisting granulomas. One patient with faintly enhancing granulomas in the posterior fossa responded to an additional use of steroids. The remaining 9 patients required surgical intervention on account of their neurological deterioration. CONCLUSIONS: (1) Paradoxical responses to intracranial tuberculoma/neurotuberculosis can occur at any time even up to 1 year during chemotherapy despite a regular standard antitubercular treatment. (2) New granuloma(s) or abscess(es) may appear in children receiving chemotherapy for TBM during the follow-up. (3) Hydrocephalus may also appear despite a regular chemotherapy in treated TBM cases. (4) Immature faintly enhancing tuberculomas have a more likely chance of resolution with antituberculous chemotherapy and glucocorticoids, while a well-formed and probably large-sized (>3 cm) granuloma may have a risk of paradoxical enlargement.

Adolescent↗

Unusual clinical and MRI features of a cerebellopontine angle medulloepithelioma. Case report and review of literature.

We describe for the first time an unusual location and clinical presentation of medulloepithelioma, a rare embryonal tumor. A 5-year-old child presented with sudden onset of bilateral hearing loss. On imaging, the lesion appeared to be extra axial and was located in the right cerebello-pontine (CP) angle, extending into middle fossa along the trigeminal ganglion and in front of the brain stem into the opposite CP angle. It did not show any enhancement following contrast administration and had restricted diffusion on diffusion-weighted imaging, simulating an epidermoid. However, in vivo localized proton MR spectroscopy revealed a creatine peak dominated by a large choline resonance, peak of glycine with lactate/lipid and invisible N-acetylaspartate suggestive of a neoplastic lesion and not an epidermoid. Only subtotal resection could be performed and the patient had a stormy post-operative course due to extensive dissemination of the disease.

Brain Chemistry↗