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Biomedical subjects

C Sarkar

Publications and source records attributed to C Sarkar.

At least 55 records · Page 3Linked to original sources

Evaluation of diagnostic efficiency of computerized image analysis based quantitative nuclear parameters in papillary and follicular thyroid tumors using paraffin-embedded tissue sections.

Computerized image analysis (IA) system has emerged in recent years as a very powerful tool for objective and reproducible quantification of histological features. It has shown considerable potential for diagnostic application in diverse histological situations. The objectives of the present study were to evaluate the discriminatory diagnostic efficiency of computerized image analysis based quantitative subvisual nuclear parameters in papillary and follicular neoplasms of thyroid. A total of 60 cases were studied. Forty-four cases belonged to training set and 16 cases belonged to a test set. A minimum of 100 nuclei was analyzed in each case using uniform 5 m mm thick hematoxylin stained sections. The IA workstation comprised of an Olympus microscope, a 10 bit digital video camera, an image grabber card and a pentium 120 MHz computer. Optimas 5.2 software was utilized for data collection on 8 morphometric and 8 densitometric parameters. Multivariate stepwise discriminant statistical analysis of data was done with the help of BMDP statistical software release 7.0. Results from a training set revealed correct classification rates of 98.0%, 84.5% and 61.2% for the histological groups of hyperplastic papillae versus papillae of papillary carcinoma (group I), follicular variant of papillary carcinoma versus the broad category of follicular neoplasms consisting of both follicular adenoma and follicular carcinoma (group II) and follicular adenoma versus follicular carcinoma (group III), respectively. Results of test set revealed correct classification rates of 100%, 80% and 50% for groups I, II and III respectively. It was concluded that computerized nuclear IA parameters have potential usefulness for discriminating benign versus malignant papillary lesions of thyroid, follicular variant of papillary carcinoma versus follicular adenoma and/or follicular carcinoma but are of no value in discriminating between follicular adenoma and follicular carcinoma.

Adenocarcinoma, Follicular↗

Composite pituitary adenoma and intrasellar tuberculoma: report of a rare case.

Tuberculous involvement of the pituitary gland is rare. We report a unique case of a composite lesion consisting of pituitary adenoma and intrasellar tuberculoma. A 24-year-old lady presented with features of acromegaly and amenorrhea. Serum growth hormone levels were found to be raised. Radiological investigations were consistent with a pituitary adenoma. Decompression of the lesion was done through trans-sphenoidal approach. Histological examination revealed a growth hormone secreting pituitary adenoma in association with a granulomatous lesion suggesting of pituitary tuberculoma. No other evidence of tuberculosis was found in the brain or spinal cord. This type of dual pathology has been reported only once in the earlier literature.

Adult↗

Effects of administration of nicorandil or bimakalim prior to and during ischemia or reperfusion on survival rate, ischemia/reperfusion-induced arrhythmias and infarct size in anesthetized rabbits.

We investigated the effects of administration of non-hypotensive doses of ATP-sensitive K+ channel (KATP) openers (nicorandil and bimakalim), and a specific mitochondrial KATP channel blocker (5-hydroxydecanoate) prior to and during coronary occlusion as well as prior to and during post-ischemic reperfusion on survival rate, ischemia-induced and reperfusion-induced arrhythmias and myocardial infarct size in anesthetized albino rabbits. The thorax was opened in the left fourth intercostal space and after pericardiotomy the heart was exposed. In Part I, occlusion of the left main coronary artery and hence, myocardial ischemia-induced arrhythmias were achieved by tightening a previously placed loose silk ligature for 30 min. In Part II, arrhythmias were induced by reperfusion following a 20-min ligation of the left main coronary artery. In Part I, early intravenous infusion of nicorandil (100 microg/kg bolus + 10 microg/kg per min) or bimakalim (3 microg/kg bolus + 0.1 microg/kg per min) just prior to and during ischemia increased survival rate (75% and 67% vs. 60% in the control group), significantly decreased the incidence and severity of life-threatening arrhythmias and significantly decreased myocardial infarct size. In Part II also, early intervention by intravenous infusion of nicorandil (100 microg/kg bolus + 10 microg/kg per min) or bimakalim (3 microg/kg bolus + 0.1 microg/kg per min) just before and during ischemia increased survival rate (86% and 75% vs. 55% in the control group), significantly decreased the incidence and severity of life-threatening arrhythmias and significantly decreased myocardial infarct size. However, late intravenous administration of nicorandil or bimakalim at the onset and during reperfusion did not increase survival rate nor confer any antiarrhythmic or cardioprotective effects. The antiarrhythmic and cardioprotective effects of both nicorandil and bimakalim were abolished by pretreating the rabbits with 5-hydroxydecanoate (5 mg/kg, i.v. bolus), a selective mitochondrial KATP channel blocker. In conclusion, intervention by intravenous administration of nicorandil and bimakalim (through the activation of mitochondrial KATP channels), increased survival rate and exhibited antiarrhythmic and cardioprotective effects during coronary occlusion and reperfusion in anesthetized rabbits when administered prior to and during coronary occlusion.

Animals↗

Genetic heterogeneity and alterations in chromosome 9 loci in a localized region of a functional pituitary adenoma.

The molecular alterations reported in pituitary adenomas include mutations at the G(s)alpha in somatotrophinomas, and hypermethylation of the p16 tumor suppressor gene. There are, however, no reports of genomic instability or intratumor genetic heterogeneity in pituitary adenomas. We have studied the microsatellite loci on the short arm of chromosome 9 (9p) and the DNA fingerprinting pattern, of adjacent compartments, about 2 mm across, in a functional chromophobe pituitary adenoma secreting growth hormone and prolactin. The microsatellite loci were studied by PCR amplification using locus specific primers, while the DNA fingerprinting pattern was studied by randomly amplified polymorphic DNA (RAPD) analysis. Normal leukocyte DNA was taken as control. Only one compartment (Ta) showed alterations in several of the microsatellite loci and in the RAPD pattern vis a vis corresponding normal DNA and also the other two compartments of the tumor. This provides evidence for the localized nature of genomic instability in this tumor.

Adenoma↗

Effects of nicorandil administration on survival rate and arrhythmias during reperfusion in anesthetized rabbits.

The aim was to study the effects of nicorandil (an ATP-sensitive K+ channel opener) and tolbutamide (an ATP-sensitive K+ channel blocker) on reperfusion-induced arrhythmias in pentobarbitone and ketamine anesthetized rabbits. Arrhythmias were induced by reperfusion for 20 min following a 15-min ligation of the left main coronary artery with a silk ligature. Rabbits were pretreated with nicorandil (0.47, 0.93 or 1.86 mg/kg i.v.) or tolbutamide (180 mg/kg i.p.) or vehicle (dimethylsulfoxide/saline) before the coronary artery occlusion. In the control group (n = 10), only 60% of the animals survived during reperfusion. Intravenous pretreatment with 0.47, 0.93 or 1.86 mg/kg of nicorandil increased the survival rate to 86% (n = 7), 75% (n = 8) and 86% (n = 7), respectively. Nicorandil pretreatment significantly decreased the incidence and duration of reperfusion-induced life-threatening arrhythmias and increased the number of animals that survived without developing any arrhythmia. Tolbutamide pretreatment was associated with a decreased survival rate of 50% (n = 12) and an increase in the incidence and duration of reperfusion-induced arrhythmias. Pretreatment with nicorandil may result in protection against reperfusion-induced arrhythmias and increased survival in anesthetized rabbits.

Anesthesia↗

Pigmented pleomorphic xanthoastrocytoma: report of a rare case with review of the literature.

We describe a rare case of melanotic pleomorphic xanthoastrocytoma in a 32-year-old man who presented with partial complex seizures. Radiologically, the mass was located in the medial temporal lobe and was solid and cystic. Microscopic examination revealed features of a pleomorphic xanthoastrocytoma with some heavily pigmented cells. The pigment was demonstrated to be melanosomal melanin, which was confirmed by special stains, immunohistochemistry, and electron microscopy.

Adult↗

Spectrum of floppy children in Indian scenario.

OBJECTIVE: To study the clinical profile of paralytic floppy infants undertaking available investigations and detect the frequency of exon7 of survival motor neuron (SMNT) gene deletion among the spinal muscular atrophy (SMA) cases. DESIGN: Descriptive study. SETTING: Tertiary care teaching hospital. SUBJECTS: 70 paralytic floppy infants (40 males/30 females) with age less than 13 years were included in the study. Exclusion criteria included central hypotonia of any cause. Detailed clinical evaluation was done followed by serum creatine phosphokinase levels, electrophysiological studies, muscle biopsy including immunohistochemistry and electron microscopy. Exon7 of SMNT gene deletion studies was done by PCR. RESULTS: Final diagnosis of SMA was assigned to 37 patients followed by congenital myopathy (n = 7), cogenital muscular dystrophy (n = 5), mitochondrial myopathy (n = 4), neuropathies (n = 5) and diaphragmatic SMA (n = 1). Only 15.7% of cases remained unclassified. When EMG was correlated with final diagnosis, it was 80.6% and 75% sensitive and 68.8% and 87.5% specific for neurogenic and muscle disease, respectively. Muscle biopsy revealed neurogenic atrophy in 47.8% cases followed by normal in 37.3% and myopathic pattern in 14.97% cases. Exon7 of SMNT gene was deleted in only 50% of SMA cases. CONCLUSIONS: Spinal muscular atrophy was the commonest cause of floppy children. The low rate of SMNT gene deletion detected needs confirmation with further studies.

Child↗

Ependymoma with extensive lipidization mimicking adipose tissue: a report of five cases.

Lipomatous ependymoma is a recently described entity and only 3 cases of this variant have been reported in the literature. We report 5 cases of this rare variant of ependymoma. Patients age ranged from 4 years to 45 years and, interestingly, all of them were males. Two tumors were supratentorial in location, 2 in the fourth ventricle and 1 was intramedullary. Microscopically all of them showed the classical histology of ependymoma along with lipomatous differentiation. The lipomatous component was composed of cells with a large clear vacuole pushing the nucleus to the periphery and giving a signet ring cell appearance. This component demonstrated positivity for GFAP and S-100 protein thereby confirming its glial lineage. Three of the 5 tumors were high grade (WHO-grade III), had a high MIB-1 labelling index (MIB-1 LI) and showed recurrence on follow-up. However, 2 were low grade (WHO grade II) and patients are free of disease till the last follow up.

Adipose Tissue↗

A comparative survival evaluation and assessment of interclassification concordance in adult supratentorial astrocytic tumors.

Classification and grading of astrocytic tumors has been the subject of several controversies and no universally accepted classification system is yet available. Nevertheless, acceptance of a common system is important for assessing prognosis as well as easy comparative evaluation and interpretation of the results of multi-center therapeutic trials. We report the results of a single center study on comparative survival evaluation along with assessment of inter-classification concordance in 102 cases of supratentorial astrocytic tumors in adults ((3) (3)16 years of age). Hematoxylin and eosin (H&E) stained slides of these 102 cases were reviewed independently by two pathologists and each case classified or graded according to four different classification systems viz. Kernohan, Daumas-Duport (SAM-A), TESTAST-268 and WHO. The histological grading was then correlated with the survival curves as estimated by the Kaplan-Meier method. The most important observation was that similar survival curves were obtained for any one grade of tumor by all the four classification systems. Fifty three of the 102 cases (51.9%) showed absolute grading concordance using all 4 classifications with maximum concordant cases belonging to grades 2 and 4. Intra-classification grade-wise survival analysis revealed a statistically significant difference between grade 2 and grades 3 or 4, but no difference between grades 3 and 4 in any of the classification systems. It is apparent from the results of this study that if specified criteria related to any of the classification systems is rigorously adhered to, it will produce comparable results. Hence, preferential adoption of any one classification system in practice will be guided by the relative ease of histologic feature value evaluation with maximum possible objectivity and reproducibility. We recommend the Daumas-Duport (SAM-A) system since it appears to be the simplest, most objectivized for practical application and highly reproducible with relative ease.

Adolescent↗

Intrasellar tuberculoma--an enigmatic pituitary infection: a series of 18 cases.

OBJECTIVE: Intrasellar tuberculomas are rare and only few case reports have been described in the literature. We report a series of 18 cases of histologically proven intrasellar tuberculomas, which, to the best of our knowledge, is the largest series in the English literature. METHODS: A total of 1143 pituitary lesions, between 1984 and June 1999, were operated for various reasons in our institute. Of these, 18 cases were histopathologically proven intrasellar tuberculomas. The clinical profile was reviewed in detail. Radiological data and histopathological slides were also reviewed. RESULTS: The age ranged from 8 to 43 years (average 23.6 years) with a female preponderance. The duration of symptoms varied from 15 days to 2 years (average 4 months), the most common symptoms being headache followed by decrease or loss of vision. Five patients had features of pan-hypopituitarism whereas three had raised prolactin (PRL) levels. In six patients, both sella as well as sphenoid sinus were involved. In one patient the lesion was extending from the sella over the clivus. Clinically as well as radiologically, these lesions were mistaken for pituitary adenomas except for one case where tuberculoma was suspected on imaging. In three patients, there was past history of pulmonary tuberculosis, in one patient of tuberculous meningitis, and in one patient, of spondilytis of the spine. In one patient there was cervical lymphadenopathy along with features of acromegaly (also proved by high levels of serum growth hormone) and radiology revealed a pituitary pathology. Microscopic examination of the excised lesion revealed a composite lesion consisting of a pituitary adenoma and tuberculoma, which has not been documented in literature to date. One patient died during the hospital stay. All the other patients were put on antitubercular chemotherapy following surgery and had good outcomes. CONCLUSION: Intrasellar tuberculomas are rare. These may be suspected in female patients especially if radiological imaging shows involvement of paranasal sinuses and pituitary fossa along with thickening of pituitary stalk. Simultaneous involvement of clivus may also be an additional feature. The incidence of pituitary tuberculosis is likely to increase with a rise in the incidence of AIDS.

Adolescent↗

Extensive intra-tumor heterogeneity in primary human glial tumors as a result of locus non-specific genomic alterations.

Genomic changes are a hallmark of the neoplastic process. These range from alterations at specific loci and defined karyotypic changes which influence tumor behavior to generalized alterations exemplified by microsatellite instability. Generalized genomic changes within a tumor would be evidence in favor of the mutator hypothesis which postulates a role for such extensive changes during tumorigenesis. In this report, we have used the DNA fingerprinting technique of randomly amplified polymorphic DNA (RAPD) analysis to study genomic alterations within primary human astrocytic tumors (gliomas) in a locus non-specific manner. The RAPD fingerprinting profile of consecutive segments of tumors 2 mm across was studied; 17 astrocytic (high- and low-grade) tumors were sectioned end to end. Tissue from 50 consecutive sections, 40 microm thick (total 2 mm across), was pooled and taken to be a tumor compartment. DNA was subjected to RAPD amplification by 15 random 10-mer primers. A tumor segment was taken to have a DNA fingerprinting pattern different from others in the same specimen when its RAPD profile differed from others by at least one band of one RAPD reaction. All but one of the tumors showed compartments with a unique genetic profile, indicating genomic instability leading to widespread intra-tumor genetic heterogeneity. Eight tumors were also studied for loss of heterozygosity (LOH) of the p53 and D17S379 loci in the different segments as examples of alteration of specific tumor influencing loci. Three showed LOH of p53, which was limited to only one compartment of each tumor. The extensive intra-tumor genetic instability detected in this study is suggestive of the overall high rate of change in the genomes of tumors including those of a lower grade. It is hypothesized that some of these altered clones, which manifest as zones of heterogeneity in a solid tumor, may accumulate changes at loci known to influence tumor behavior, and thus clinical outcome.

Brain Neoplasms↗

Role of 17p13.3 chromosomal region in determining p53 protein immunopositivity in human astrocytic tumors.

Immunohistochemistry of p53 protein is being increasingly performed as a clinical service as well as in research for prediction of tumor behavior. Although early reports suggested that p53 immunopositivity was associated with p53 gene alterations, recent evidence indicates that this is not always true. Earlier, we had demonstrated the significant association of loss of heterozygosity (LOH) of the chromosomal region 17p13.3 with higher grades of human astrocytic tumors. This was independent of the heterozygosity status of p53. LOH of p53 was taken as an indicator of p53 gene alteration, which was substantiated by sequencing a subset of the tumors. In the present study, we report that p53 immunopositivity in 40 of the same set of tumors (five could not be evaluated because of paucity of tissue) was significantly associated with LOH of 17p13.3 region (Fisher's exact two-tailed, P = 0.012; odds ratio, 12) but not with LOH of p53 (Fisher's exact two-tailed, P = 0.324; odds ratio, 2.24). This indicates that the gene(s) on the 17p13.3 region of the human chromosome may be influencing the p53 immunopositivity status of glial tumors and possibly other tumors in general. This has great implications in interpreting p53 immunohistochemistry results of biopsies of various tumor types as due to p53 mutations alone. The study thus points to a new molecular correlate for p53 immuno-positivity in tumors.

Brain Neoplasms↗

Choroid plexus papilloma: a clinicopathological study of 23 cases.

BACKGROUND: Choroid plexus papillomas (CPPs) are rare, accounting for less than 1% of all intracranial tumors in adults. However, they are relatively more common in childhood and constitute 1.5 to 4% of intracranial tumors. DESCRIPTION: They are most often located in the lateral ventricle, followed by the fourth and third ventricles and, rarely, in the cerebellopontine angle. The radiological appearance of a CPP as a cyst with a mural nodule is a curiosity. Bone formation is rare in CPPs and only 6 cases have been described in the literature. Neuromelanin production is also extremely rare and only 2 cases have been reported to date. CONCLUSION: In the present communication, 23 cases of CPP are analyzed and rare clinical, pathological, and radiological features are described.

Adolescent↗

Pituitary adenoma with neuronal choristoma: a report of two rare cases.

Two rare cases of pituitary adenoma with neuronal choristoma are described. Both patients were female and presented with features of acromegaly with elevated growth hormone and prolactin levels. Radiologically, both lesions were predominantly intrasellar in location with extension into suprasellar region, but hypothalamus was not involved. Histopathological examination revealed a mixture of chromophobe pituitary adenoma cells and neuronal cells. In both cases, the adenoma component was positive for growth hormone and prolactin. Interestingly, immunopositivity for alpha-subunit, cytokeratin and prolactin was seen in the adenoma and neuronal cells in one case. Our findings support the hypothesis that the neuronal cells possibly arise from adenoma cells as a result of metaplasia.

Acromegaly↗

Simultaneous alterations of retinoblastoma and p53 protein expression in astrocytic tumors.

The genetic alterations frequently involved in glial malignancies are in the tumor suppressor genes, Rb and p53. An altered Rb expression or p53 overexpression is thought to indicate defective tumor suppression and subsequently more aggressive tumors. Therefore, to assess the alterations in the conjoint expression of Rb and p53 proteins in formalin fixed paraffin embedded sections, 64 astrocytic tumors were studied (16 astrocytomas,7 gemistocytic astrocytomas, 19 anaplastic astrocytomas and 22 glioblastomas) using the avidin biotin immunoperoxidase technique. Fifty two cases (81.25%) were found to be positive for p53 protein. Seventeen of these showed aberrant heterogenous staining for pRb, of which 7 were glioblastomas. Only one case of astrocytoma showed aberrant expression of both p53 and Rb. Thus, of the 64 tumors, simultaneous aberrant expression of both p53 and Rb was seen in 21.9% of cases. This was more commonly observed among glioblastoma cases (7/22). No statistical difference was found between the survival rate of heterogenous pRb and p53 positivity in different grades of tumors. In glioblastomas, the survival rate appeared to be less in patients expressing heterogenous pRb, but this was not statistically significant. These results lead us to suspect that p53 and pRb pathways are inactivated, either through mutation or as part of the neoplastic process in astrocytic tumors.

Adolescent↗

A correlative study of gliomas using in vivo bromodeoxyuridine labeling index and computer-aided malignancy grading.

An in vivo bromodeoxyuridine (BrdU) labeling index (LI) was estimated in 43 cases of astrocytic tumors and mixed gliomas by one hour intra-operative intravenous infusion at a dose of 200 mg/m2 and correlated with (a) histological grading using a computer aided malignancy classifier TESTAST-268; and (b) histological typing using WHO classification. The lowest BrdU LI was seen in pilocytic and gemistocytic astrocytomas followed by astrocytomas, anaplastic astrocytomas and glioblastoma multiforme in that order. Mixed oligoastrocytomas followed the pattern of their astrocytic counterparts. Tumors of similar histological type showed different BrdU LI values especially amongst astrocytomas and glioblastomas. A statistically significant difference in the BrdU LI was also noted between the higher TESTAST grades of astrocytomas (T III and IV) versus the lower TESTAST grades (T II). Unlike earlier reports in literature, in the present study the category of BrdU LI of <1 contained no case of anaplastic astrocytoma or glioblastoma multiforme (TESTAST grades III and IV). Likewise, the category of BrdU LI >5 contained only anaplastic astrocytoma and glioblastoma multiforme (TESTAST grades III and IV). Maximum spread of cases was seen in the BrdU LI category of 1-5, not only in terms of histological types but also TESTAST grades. Thus there appeared to be a positive trend of increasing BrdU LI values both with histological types and increasing TESTAST grades. Further, an interesting observation was that by using a combination of TESTAST grades and BrdU LI, the histologically homogenous glioblastoma group could be further subdivided into 4 categories which showed a trend towards prognostic correlation. Thus, this study though preliminary with number of cases being small in some groups, highlights the possible usefulness of combined histological typing, TESTAST grading and in vivo BrdU LI for prognostication of gliomas especially glioblastoma multiforme.

Astrocytoma↗

Intraventricular neurocytoma: a clinicopathological study of 20 cases with review of the literature.

The clinicopathological features of 20 cases of central neurocytomas are described. They accounted for 0.28% of all intracranial tumours diagnosed during a 16 year period (1980-1995). Lower mean age of the patients at diagnosis (23.1 years), male preponderance (M:F=1.8:1) and higher incidence of involvement of the right lateral ventricle (10/20 cases) were noted in this series, in contrast to reports from Western literature. Total removal of the tumour was done in 14 cases while the remaining six underwent partial resection. Morphogically, the tumours had a striking resemblance to oligodendrogliomas (11/20 had been earlier diagnosed as oligodendrogliomas) and an interesting finding was the presence of dilated vascular channels in 12/20 tumours. The diagnosis was confirmed in all cases by immunohistochemistry and/or electron microscopy. While 18 cases were histologically benign, two had features of atypical neurocytoma. Five patients died due to postoperative complications. The remaining patients received postoperative radiation and their follow-up revealed that all of them were doing well at 12 to 72 months after surgery. These neoplasms should be suspected in any young patient with radiological evidence of an intraventricular lesion; for their differentiation from gliomas, immunohistochemistry and electron microscopy should be done. This is important because, unlike gliomas, these tumours have a relatively favourable prognosis and their current treatment of choice is complete surgical removal without adjuvant chemo- or radiotherapy. Copyright 1999 Harcourt Publishers Ltd.

Journal Article↗