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Biomedical subjects

T Krishnamoorthy

Publications and source records attributed to T Krishnamoorthy.

18 recordsLinked to original sources
PubMed2006

Reversible periictal MRI abnormalities: clinical correlates and long-term outcome in 12 patients.

Although a wide spectrum of reversible periictal magnetic resonance imaging (MRI) abnormalities (RPMA) are being increasingly identified, the clinicians are often in a dilemma about their localization significance. This prompted us to analyze the clinical, MRI, electroencephalographic (EEG) and follow-up data of 12 patients with RPMA seen in a tertiary referral epilepsy center. RPMA occurred after a single or a cluster of focal seizures with or without secondary generalization. The interictal and ictal EEG abnormalities were localized to the site of RPMA in nine patients. RPMA involved areas remote from the site of EEG abnormalities in four patients. We have developed a comprehensive classification to account for the wide spectrum of RPMA involving gray matter, white matter and leptomeninges with or without contrast enhancement or mass effect. Follow-up MRIs showed complete resolution of RPMA in all, except in four patients, who developed residual focal atrophy. During median follow-up period of 3 years, recurrence of RPMA was observed in two patients. Diffusion weighted MRI in two patients and histopathological finding in one patient favored causal role of hypoxia in the pathogenesis of RPMA. Our observations help to understand the electroclinical profile, radiological spectrum, localization significance and natural history of RPMA better.

Adolescent↗
PubMed2006

Endovascular treatment of direct carotid cavernous fistulae: a pictorial review.

INTRODUCTION: Direct carotid-cavernous fistulae (CCFs) are type A fistulae according to Barrow's classification. Endovascular treatment of these lesions is challenging. METHODS: The purpose of this review was to evaluate the endovascular treatment of direct CCFs. We also describe the technique, symptomatology and complications associated with the procedure and report on the long-term follow-up in our treated patients. RESULTS: A total of 89 patients with a direct CCF were treated. All patients had baseline brain CT or MR imaging. Treatment comprised transarterial balloon or coil embolizations. The patients were followed up at 1 month and then every 6 months thereafter. Detachable balloons were used in 79 fistulae. In 12 fistulae the balloon could not be negotiated through the fistula and these fistulae were treated with transarterial coil occlusion. Clinical outcomes of the treated patients evaluated at 1 month were: 79 patients (88.8%) cured, 9 (10.1%) significantly improved, 1 (1.1%) remaining static. CONCLUSION: Endovascular treatment of direct CCFs is safe and effective and results in long-term cure.

Adolescent↗
PubMed2006

Hemimegalencephalic appearance of normal hemisphere in unilateral heterotopia and absent corpus callosum.

We report two patients with medically refractory epilepsy who had MRI evidence of unilateral subcortical nodular heterotopia and agenesis of corpus callosum. The abnormal hemisphere was small, whereas the contralateral normal hemisphere appeared large and crossed the midline. Although the normal hemisphere was initially mistaken for hemimegalencephaly, there were no typical radiological features. Moreover, the electroencephalographic abnormalities lateralized to the hemisphere showing heterotopia. Because contralateral hemispheric abnormalities like heterotopia, hemimicrencephaly, and hemimegalencephaly can occur in patients with hemispheric heterotopias, we emphasize the importance of careful scrutiny of the contralateral hemisphere in patients with unilateral heterotopia. Absence of typical radiological features and appropriately lateralized electroencephalographic abnormalities will help differentiate the two. This is crucial when planning epilepsy surgery.

Adult↗
PubMed2006

Pyogenic cerebral abscess with discharging sinus complicating an embolized arteriovenous malformation.

Brain arteriovenous malformations (AVM) are treated with endovascular embolization either as a definitive treatment or as an adjunct to surgery or stereotactic radiotherapy. Complications of AVM embolization are well known but infection of the embolised AVM nidus is extremely rare. On Pubmed search we found only a single case report of an infected brain AVM after embolization. We report a case of pyogenic cerebral abscess with superior sagittal sinus extension complicating an embolised AVM and discuss the possible etiopathogenesis.

Adult↗
PubMed2006

Endovascular treatment of ruptured posterior circulation dissecting aneurysms.

BACKGROUND: and aim: Dissecting aneurysms of the posterior circulation constitute a relatively uncommon subgroup of aneurysms. They account for 3-7% of cases of nontraumatic subarachnoid hemorrhage. Because of high risk, in most cases the patients require surgical or endovascular therapy. In this study we discuss the clinical efficacy of endovascular treatment with long-term follow-up in ruptured dissecting aneurysms of the posterior circulation. MATERIALS AND METHODS: This retrospective study was conducted at our institution between January 1995 and June 2005. Eight patients (4 male; 4 females) ranging in age from 24 to 65 years (mean, 46.75 years), were included. All presented with SAH. Endovascular treatment was based on the configuration of the dissecting aneurysm. Attempt was made to occlude the dissecting aneurysm. RESULT: A total of 8 ruptured dissecting aneurysms in the posterior circulation were treated. Out of them 5 were in the intradural vertebral artery, 2 in the basilar trunk and one in the proximal PCA. All the cases were technically successful. We have seen only two complications. The pre and post procedure (at the time of discharge) mean modified Rankin scores in the patients were 4.6 (SD 0.51) and 1.7 (SD 1.98). This improvement in Rankin score after endovascular treatment was statistically significant (Wilcoxon signed rank test, P=.017). CONCLUSION: Endovascular management of these lesions is safe and effective mode of treatment and gives adequate protection from rebleed.

Adult↗
PubMed2006

Carotid artery stenting: results and long-term follow-up.

BACKGROUND AND PURPOSE: The role of carotid artery stenting (CAS) as an alternative to carotid endarterectomy in the treatment of for symptomatic carotid artery stenosis is investigated. MATERIALS AND METHODS: Forty-seven patients underwent CAS over 10-year period. Forty-nine vessels were treated. Stenosis quantification was done using North American symptomatic carotid endarterectomy trial method. The mean follow-up period by clinical and Duplex examination ranged is 5.6 years. RESULTS: The technical success rate was 100%. There were four deaths (8.1%) and two (4.1%) minor strokes within thirty days of procedure. There was no major strokes. All patients with minor stroke achieved complete recovery at 1-month follow up. Two deaths occurred probably due to hyperperfusion syndrome (HS) and two due to cardiac arrest. CONCLUSION: CAS is an effective treatment modality of symptomatic carotid artery disease but should be carefully done in high-risk groups having severe medical ailments and those having severe bilateral stenosis of the carotid arteries.

Adult↗
PubMed2006

Percutaneous laser disc decompression: clinical experience at SCTIMST and long term follow up.

BACKGROUND: Low backache (LBA) is now increasing in younger population due to misdirected spinal kinetics secondary to improper posture, heavy load lifting and motorbike driving. Hence minimally invasive procedures are increasingly sought after. Among these, PLDD is currently popular and in use. We present our long term follow-up in the use of Nd:YAG laser for PLDD. AIM: To evaluate the efficacy of PLDD in treatment of contained herniation of lumbar discs & long term follow up results. MATERIALS AND METHODS: Forty patients with contained lumbar disc herniation on MRI and who did not respond to 6 weeks conservative treatment were subjected to PLDD. L4-5 disc was treated in 31, L5-S1 in 12 and L1-2 and L3-4 in one each. Nd:YAG laser at 1064 nm was used for the procedure. Total laser energy of 1500-2000 Joules was delivered at the disc space depending upon the size. RESULTS: There was immediate pain relief in 32/40 (80%). According to MacNab criteria good to fair response was seen in 37/40 (92%) and 3 patients (7.5%) responded poorly to this treatment. On follow up which ranged from 1 to 7 years, 34/40 (85%) had pain relief with no need for further treatment. COMPLICATIONS: Significant pain at local puncture site was experienced by 8 (20%), pain during lasing was experienced by one. One patient developed muscular spasm. CONCLUSION: Percutaneous laser disc decompression is a safe, relatively noninvasive and effective treatment modality for contained, nonsequestered, herniated lumbar disc disease in carefully selected patients.

Adult↗
PubMed2005

Hyperperfusion syndrome after supraaortic vessel interventions and bypass surgery.

Cerebral hyperperfusion and hemorrhage is a recognized complication of endarterectomy, aortocarotid bypass surgery or angioplasty and stenting of the carotid or vertebral artery. We performed 87 balloon angioplasty, stenting and bypass surgery of arteries supplying the brain over the last 15 years. We have found 6 cases of hyperperfusion syndrome in a total of 87 procedures. So the incidence of hyperperfusion was noted as 6.89%. Two cases occurred after two combined procedures in a single sitting. Hyperperfusion syndrome is a well-known complication of craniocervical revascularisation procedures. But with proper care, including strict post procedural control of blood pressure and staged procedure in case of multiples vessel stenosis, these complications can be largely avoided.

Adult↗
PubMed2005

Percutaneous vertebroplasty in the management of vertebral lesions.

BACKGROUND: Debilitating backache due to different types of vertebral lesions is a common cause of morbidity in all age groups. Percutaneous vertebroplasty (PV) gives substantial pain relief and stabilizes the weak vertebrae. Most of the information regarding PV comes from the Western literature. The effect of PV in our population should be studied. AIMS: The primary objective is to assess the therapeutic benefit of PV in alleviating back pain and improving the functional status in patients with painful pathologic vertebrae. The secondary objectives are to study the technical aspects of the procedure and their relation to outcome and complications. SETTINGS AND DESIGN: This is a retrospective hospital-based (tertiary teaching hospital) study. MATERIALS AND METHODS: From January 2001 to December 2004, 46 patients underwent PV procedures. Sixty-five vertebroplasties were done in 13 males and 33 female patients. Twenty-four (36.92%) procedures were done for osteoporotic compression collapse, 26 (40.0%) for hemangioma, and 15 (23.07%) for different vertebral body tumors and metastasis. The Wilcoxon signed rank test was used to evaluate the statistical significance of differences between the preoperative and postoperative levels of pain, mobility and analgesic usage. RESULTS: Most of the patients had pain relief within 48 h. Only minor side effects were encountered. No patient had any deficit related to the procedure. On follow up of 3-48 months, all patients had statistically significant improvement in clinical condition (P < 0.001). CONCLUSION: Percutaneous vertebroplasty is a safe and effective procedure in relieving debilitating backache and can be used to treat vertebral lesions in selected cases.

Adolescent↗
PubMed2003

Intracranial aneurysmal bone cyst manifesting as a cerebellar mass.

A 17-year-old boy presented with symptoms of raised intracranial pressure for a month. Investigations revealed a large extra-cerebellar mass. The lesion was radically resected. It arose from the petrous bone. Histology revealed that the lesion was an aneurysmal bone cyst [ABC].

Adolescent↗
PubMed2003

Rhabdoid tumor of the thalamus.

Rhabdoid tumors of the central nervous system are uncommon tumors. About 188 cases have been reported in the literature so far. In this report, we describe a case of a rhabdoid tumor of the thalamus in a 35-year-old male patient. Light microscopic and immunohistochemical features are discussed and the relevant literature reviewed.

Adult↗
PubMed2001

Physical evidence for distinct mechanisms of translational control by upstream open reading frames.

The Saccharomyces cerevisiae GCN4 mRNA 5'-leader contains four upstream open reading frames (uORFs) and the CPA1 leader contains a single uORF. To determine how these uORFs control translation, we examined mRNAs containing these leaders in cell-free translation extracts to determine where ribosomes were loaded first and where they were loaded during steady-state translation. Ribosomes predominantly loaded first at GCN4 uORF1. Following its translation, but not the translation of uORF4, they efficiently reinitiated protein synthesis at Gcn4p. Adding purified eIF2 increased reinitiation at uORFs 3 or 4 and reduced reinitiation at Gcn4p. This indicates that eIF2 affects the site of reinitiation following translation of GCN4 uORF1 in vitro. In contrast, for mRNA containing the CPA1 uORF, ribosomes reached the downstream start codon by scanning past the uORF. Addition of arginine caused ribosomes that had synthesized the uORF polypeptide to stall at its termination codon, reducing loading at the downstream start codon, apparently by blocking scanning ribosomes, and not by affecting reinitiation. The GCN4 and CPA1 uORFs thus control translation in fundamentally different ways.

5' Untranslated Regions↗
PubMed2001

Tight binding of the phosphorylated alpha subunit of initiation factor 2 (eIF2alpha) to the regulatory subunits of guanine nucleotide exchange factor eIF2B is required for inhibition of translation initiation.

Translation initiation factor 2 (eIF2) is a heterotrimeric protein that transfers methionyl-initiator tRNA(Met) to the small ribosomal subunit in a ternary complex with GTP. The eIF2 phosphorylated on serine 51 of its alpha subunit [eIF2(alphaP)] acts as competitive inhibitor of its guanine nucleotide exchange factor, eIF2B, impairing formation of the ternary complex and thereby inhibiting translation initiation. eIF2B is comprised of catalytic and regulatory subcomplexes harboring independent eIF2 binding sites; however, it was unknown whether the alpha subunit of eIF2 directly contacts any eIF2B subunits or whether this interaction is modulated by phosphorylation. We found that recombinant eIF2alpha (glutathione S-transferase [GST]-SUI2) bound to the eIF2B regulatory subcomplex in vitro, in a manner stimulated by Ser-51 phosphorylation. Genetic data suggest that this direct interaction also occurred in vivo, allowing overexpressed SUI2 to compete with eIF2(alphaP) holoprotein for binding to the eIF2B regulatory subcomplex. Mutations in SUI2 and in the eIF2B regulatory subunit GCD7 that eliminated inhibition of eIF2B by eIF2(alphaP) also impaired binding of phosphorylated GST-SUI2 to the eIF2B regulatory subunits. These findings provide strong evidence that tight binding of phosphorylated SUI2 to the eIF2B regulatory subcomplex is crucial for the inhibition of eIF2B and attendant downregulation of protein synthesis exerted by eIF2(alphaP). We propose that this regulatory interaction prevents association of the eIF2B catalytic subcomplex with the beta and gamma subunits of eIF2 in the manner required for GDP-GTP exchange.

Binding Sites↗
PubMed1999

Serine 48 in initiation factor 2 alpha (eIF2 alpha) is required for high-affinity interaction between eIF2 alpha(P) and eIF2B.

Phosphorylation of the serine 51 residue in the alpha-subunit of translational initiation factor 2 in eukaryotes (eIF2 alpha) impairs protein synthesis presumably by sequestering eIF2B, a rate-limiting pentameric guanine nucleotide exchange protein which catalyzes the exchange of GTP for GDP in the eIF2-GDP binary complex. To further understand the importance of eIF2 alpha phosphorylation in the interaction between eIF2 alpha(P) and eIF2B proteins and thereby the regulation of eIF2B activity, we expressed the wild type (wt) and a mutant eIF2 alpha in which the serine 48 residue was replaced with alanine (48A mutant) in the baculovirus system. The findings reveal that the expression of both of these recombinant subunits was very efficient (15-20% of the total protein) and both proteins were recognized by an eIF2 alpha monoclonal antibody and were phosphorylated to the same extent by reticulocyte eIF2 alpha kinases. However, partially purified recombinant subunits (wt or 48A mutant) were not phosphorylated as efficiently as the eIF2 alpha subunit present in the purified reticulocyte trimeric eIF2 complex and were also found to inhibit the phosphorylation of eIF2 alpha of the trimeric complex. Furthermore, the extents of inhibition of eIF2B activity and formation of the eIF2 alpha(P)-eIF2B complex that occurs due to eIF2 alpha phosphorylation in poly(IC)-treated rabbit reticulocyte lysates were decreased significantly in the presence of insect cell extracts expressing the 48A mutant eIF2 alpha compared to those for wt. These findings support the hypothesis that the serine 48 residue is required for high-affinity interaction between eIF2 alpha(P) and eIF2B.

Amino Acid Substitution↗
PubMed1999

Conserved bipartite motifs in yeast eIF5 and eIF2Bepsilon, GTPase-activating and GDP-GTP exchange factors in translation initiation, mediate binding to their common substrate eIF2.

In the initiation phase of eukaryotic translation, eIF5 stimulates the hydrolysis of GTP bound to eIF2 in the 40S ribosomal pre-initiation complex, and the resultant GDP on eIF2 is replaced with GTP by the complex nucleotide exchange factor, eIF2B. Bipartite motifs rich in aromatic and acidic residues are conserved at the C-termini of eIF5 and the catalytic (epsilon) subunit of eIF2B. Here we show that these bipartite motifs are important for the binding of these factors, both in vitro and in vivo, to the beta subunit of their common substrate eIF2. We also find that three lysine-rich boxes in the N-terminal segment of eIF2beta mediate the binding of eIF2 to both eIF5 and eIF2B. Thus, eIF5 and eIF2Bepsilon employ the same sequence motif to facilitate interaction with the same segment of their common substrate. In agreement with this, archaea appear to lack eIF5, eIF2B and the lysine-rich binding domain for these factors in their eIF2beta homolog. The eIF5 bipartite motif is also important for its interaction with the eIF3 complex through the NIP1-encoded subunit of eIF3. Thus, the bipartite motif in eIF5 appears to be multifunctional, stimulating its recruitment to the 40S pre-initiation complex through interaction with eIF3 in addition to binding of its substrate eIF2.

Amino Acid Sequence↗
PubMed1998

Reducing agents mitigate protein synthesis inhibition mediated by vanadate and vanadyl compounds in reticulocyte lysates.

Recently, we synthesized and characterized vanadyl saccharides to evaluate the effects of various vanadate and vanadyl complexes, which differ in their oxidation states on various biomacromolecules and cellular activities (1, 2). Here, we report that both vanadate (+V oxidation state) and different vanadyl species (+IV oxidation state) such as vanadyl D-glucose, vanadyl diascorbate, and vanadyl sulfate, impair the formation of polysomes and inhibit the initiation of protein synthesis in hemin-supplemented rabbit reticulocyte lysates. Vanadate inhibits protein synthesis more severely than vanadyl species and is consistent with the idea that vanadate is reduced to vanadyl state intracellularly. The inhibition of protein synthesis caused by low concentrations (10-20 microM) of vanadate and vanadyl species is effectively mitigated by reducing agents such as dithiothreitol, reduced glutathione (GSH), or reduced pyridine dinucleotide. A significant decrease in the protein synthesis inhibition in vanadate-treated lysates by GSH suggests that the mechanism of protein synthesis inhibition by vanadate is different than the action of other oxidants such as heavy metal ions and oxidized glutathione. This suggestion is also consistent with the findings that vanadium compounds do not stimulate phosphorylation of the alpha (alpha) subunit of initiation factor 2 (eIF2) or decrease the guanine nucleotide exchange activity of eIF2B, which is required to exchange GDP for GTP in eIF2.GDP binary complex. The reduction of vanadate to vanadyl state and the subsequent complex formation of vanadyl species with the endogenous reducing compounds or with the -SH groups of certain proteins may be the cause for protein synthesis inhibition in lysates.

Animals↗
PubMedDate not supplied

Anomalous origin of the callosomarginal artery from the A1 segment with an associated saccular aneurysm.

Although anatomic variations are well known in the A1 segment of the anterior cerebral artery (ACA), anomalous origin of a cortical artery from the A1 segment is extremely rare. The only reported cortical branch to arise from the A1 segment is the fronto-orbital artery. We report a case of anomalous origin of the callosomarginal artery (CMA) in association with a saccular aneurysm from the A1 segment of the left ACA in a 35-year-old man who presented with intracerebral hemorrhage. To our knowledge, this is the first report of anomalous origin of the CMA from the A1 segment.

Adult↗