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Biomedical subjects

R K Gupta

Publications and source records attributed to R K Gupta.

At least 163 records · Page 9Linked to original sources

Diagnostic assessment of brain tumours and non-neoplastic brain disorders in vivo using proton nuclear magnetic resonance spectroscopy and artificial neural networks.

PURPOSE: Experiments were carried out to assess the potential of artificial neural network (ANN) analysis in the differential diagnosis of brain tumours (low- and high-grade gliomas) from non-neoplastic focal brain lesions (tuberculomas and abscesses), using proton magnetic resonance spectroscopy (1H MRS) as input data. METHODS: Single-voxel stimulated echo acquisition mode (STEAM) (echo time of 20 ms) spectra were acquired from 138 subjects including 15 with low-grade gliomas, 47 with high-grade gliomas, 18 with tuberculomas, 18 with abscesses and 40 healthy controls. Two neural networks were constructed using the spectral points from 0.6 to 3.4 parts per million. In the first network construction, the ANN had to differentiate between tumours from infections, while the second network had to differentiate between all five histological classes. RESULTS: ANN analysis gave a histologically correct diagnosis for low- and high-grade gliomas with an accuracy of 73% and 98% respectively. None of the 62 tumours was diagnosed as an infectious lesion. Among the non-neoplastic lesions, ANN classification was correct in 89% of tuberculomas and in 83% of brain abscesses. The specificity of ANN diagnosis was 98%, 92%, 99%, and 100% for low-grade gliomas, high-grade gliomas, tuberculomas and abscesses respectively. CONCLUSION: The present data show the clinical utility of non-invasive 1H MRS by automated ANN analysis in the diagnosis of tumour and non-tumour cerebral disorders.

Adolescent↗

Variation of post-treatment H-MRSI choline intensity in pediatric gliomas.

Pediatric brain gliomas are not always amenable for complete surgical excision, therefore adjuvant treatment for a large tumor mass is often required. As tumor volume shrinkage may not be a reliable method for assessing response to treatment, information about the tumor growth potential is desirable for an adequate follow-up of the patients. Choline (Cho) signal intensity, determined by proton magnetic resonance spectroscopy imaging (H-MRSI), has proved to be a reliable indicator of the metabolic activity and of tumor progression in various intracranial tumors. In this study we have sought to determine if H-MRSI can be of use in monitoring the response of pediatric gliomas to different forms of therapy. We performed pretreatment and post-treatment H-MRSI in 10 children with biopsed or partially excised brain gliomas. The follow-up period ranged between 6 and 40 months. A total of 38 H-MRSI were performed. All the patients had chemotherapy or radiotherapy. As an indicator of tumor activity we utilized the ratio between tumor/brain Cho signal intensity. Treatment response was evaluated as a function of tumor volume and clinical outcome. In 6 patients whose tumor volume decreased or remained stable we observed that the Cho ratio decreased (p < 0.01) after treatment and remained low during longitudinal follow-up. In the 4 patients whose tumors progressed the Cho ratio increased after treatment. These observations suggest that serial H-MRSI can provide valuable information regarding the response to therapy in pediatric gliomas and therefore be of use in the follow-up of these neoplasms of childhood.

Astrocytoma↗

Variability of polymerase chain reaction detection of the bcl-2-IgH translocation in an international multicentre study.

BACKGROUND: The capacity of the polymerase chain reaction (PCR) to detect very low numbers of cells bearing a t(14;18) translocation has led to its application in assessment of the results of treatment for follicular lymphoma, and suggestions that therapy might be guided by molecular studies. To test the reliability of PCR a collaborative study was undertaken to compare results from different laboratories in Europe and North America. METHODS: Twenty laboratories with records of publication in molecular diagnostics were sent blood from normal donors with varying numbers of t(14;18)-bearing cells added from a cell line with a translocation in the major breakpoint region (MBR) of the bcl-2 gene. Samples contained 1000, 100, 10, 1 or 0 cells per ml of whole blood and were sent blinded in duplicate. PCR methodology varied widely, with the total number of amplification cycles between 30 and 70, and 13 different primers used for the MBR region. Twelve laboratories used nested PCR and eight single round amplification. RESULTS: The sensitivity of nested and single round PCR was similar at 100 cells/ml but below this the nested method proved significantly more sensitive. The false positive rate was 28%, with 11 samples from 9 laboratories reported as positive when no t(14;18) cells were added. PCR product size and sequence analysis showed that false positives were due to contamination from cell-line DNA rather than background translocations in the donors. There was no significant difference in false positive rates between nested and single round techniques. CONCLUSION: The polymerase chain reaction to detect bcl-2-IgH rearrangements is presently carried out with widely disparate results. Further effort is required to bring forward a standard PCR protocol which can be re-tested in different laboratories to improve accuracy and reproducibility. The application of quantitative techniques such as real-time PCR may resolve many of the problems presently encountered.

Adult↗

Tumour necrosis factor polymorphisms and susceptibility to follicular lymphoma.

Follicular lymphoma is characterized in 85% of patients by the presence of a t(14;18) chromosomal translocation that results in overproduction of BCL2. In this study the distribution of high and low expressing TNF alleles at the TNF (-308) and LTalpha (+252) polymorphic sites in 121 patients with follicular lymphoma and 88 control individuals has been analysed. A reduction in high expressing haplotypes in patients compared to normal controls was found (P = 0.055), with no significant difference observed in response rate or overall survival between patients with high or low expressing haplotypes. These results suggest that the TNF locus, or an adjacent locus within the MHC region, is an important genetic risk factor in this disease.

Adult↗

Predicting mosquito repellent potency of N,N-diethyl-m-toluamide (DEET) analogs from molecular electronic properties.

Specific molecular electronic properties of 30 N,N-diethyl-m-toluamide (DEET) analogs demonstrate functional dependence with their reported duration of protection against mosquito bites, thus providing predictors of insect repellent efficacy. No single electronic property is sufficient to predict repellent efficacy as measured by protection time, rather a set of specific electronic properties is required. Thus, the values of the van der Waals surface electrostatic potential by the amide nitrogen and oxygen atoms, the atomic charge at the amide nitrogen atom, and the dipole moment must all be in optimal ranges for potent repellency. The electronic properties were calculated using the AM semi-empirical quantum chemical method using commercial software. These easily calculable predictors of repellent efficacy should be useful in predicting the relative efficacy of newly designed compounds, thus guiding the selection of new repellents for testing.

Animals↗

Responses of male and female mosquitoes to repellents in the World Health Organization insecticide irritability test system.

A study was conducted to compare responses of male and female Aedes aegypti (Linn.) and Aedes taeniorhynchus (Wiedemann) to 9 olfactory repellents in the World Health Organization insecticide irritability test system. An irritant insecticide (permethrin) and a control were included for comparison. Aedes aegypti exhibited significantly more takeoffs than Ae. taeniorhynchus, and female mosquitoes exhibited significantly more takeoffs than males. Permethrin induced significantly more takeoffs than the control, but olfactory repellents did not. Certain 2- and 3-factor interactions of test materials, species, and sexes were statistically significant. This study supports a previous conclusion that the World Health Organization test method does not measure contact repellency (irritancy) and olfactory repellency equally.

Aedes↗

Magnetization transfer MR imaging in CNS tuberculosis.

BACKGROUND AND PURPOSE: CNS tuberculosis may simulate other granulomas and meningitis on MR images. The purpose of this study was to improve the characterization of lesions in CNS tuberculosis and to assess the disease load using magnetization transfer (MT) imaging. METHODS: A total of 107 tuberculomas in seven patients with or without meningitis and 15 patients with tuberculosis meningitis alone were studied. Fifteen patients with cysticercus granulomas with T2 hypointensity, five patients each with viral and pyogenic meningitis, and two patients with cryptococcal meningitis were also studied. The MT ratios were calculated from tuberculomas, cysticercus granulomas, and thickened meninges in tuberculous, viral, pyogenic, and cryptococcal meningitis and were compared within each pathologic group and with the MT ratio of different regions of normal brain parenchyma. Detectability of lesions on T1-weighted MT spin-echo (SE) images was compared with that on conventional SE and postcontrast MT-SE images. RESULTS: Thickened meninges appeared hyperintense relative to surrounding brain parenchyma in the basal and supratentorial cisterns on precontrast MT-SE images in all 18 patients with tuberculosis meningitis. These meninges were not seen or were barely visible on conventional SE images, and enhanced on postcontrast MT-SE images. The MT ratio from the thickened meninges of tuberculous meningitis was significantly lower than that from the meninges in cryptococcal and pyogenic disease and significantly higher than the meninges in viral meningoencephalitis. The MT ratio from T2 visible and invisible tuberculomas appeared to be significantly lower than that of normal white matter. The MT ratio of T2 hypointense cysticercus granuloma was significantly higher than that of T2 hypointense tuberculoma. CONCLUSION: Precontrast MT-SE imaging helps to better assess the disease load in CNS tuberculosis by improving the detectability of the lesions. With the use of MT ratios, it may be possible to differentiate tuberculosis from similar-appearing infective lesions on MR images.

Adolescent↗

Laboratory evaluation of AI3-37220, AI3-35765, CIC-4, and deet repellents against three species of mosquitoes.

Four repellents, N,N-diethyl-3-methyl-benzamide (deet), 2-hydroxy-methyl-cyclohexyl acetic acid lactone (CIC-4), and 2 piperidines (1-[3-cyclohexen-1-ylcarbonyl] piperidine [AI3-35765] and 1-[3-cyclohexen-1-ylcarbonyl]-2-methylpiperidine [AI3-37220]) were evaluated alone and in combination against Aedes aegypti, Anopheles stephensi, and Culex quinquefasciatus using a modified in vitro test system. This method was a valuable tool for comparing effective concentrations of the new compounds. Because of the controlled conditions of the test, it was possible to use the results of assays that had been conducted over a 5-year period and to perform the many replications necessary to evaluate combinations of compounds. The new candidate repellents were generally as effective as deet. Although speculative at this time, there was some evidence of synergistic interaction. Repellent combinations of CIC-4/AI3-37220/AI3-35767, deet/AI3-35765, and deet/AI3-37220/AI3-35765 against An. stephensi and CIC-4/AI3-35765, deet/AI3-37220/AI3-35765, AI3-37220/AI3-35765, and CIC-4/AI3-37220 against Ae. aegypti were more effective than the component compounds alone.

Aedes↗

Variation in the protection periods of repellents on individual human subjects: an analytical review.

Mosquito repellent test data from the literature were analyzed to estimate mean protection periods and among-subjects standard deviations. Standard deviations were a linear function of the means. Numbers of subjects needed to determine mean protection periods of 1-8 h with confidence limits of +/- 0.5, 1.0, 1.5, and 2.0 h at the 99 and 95% levels of confidence were computed from regression values of the standard deviation, and a table of sample sizes was constructed for use in planning repellent tests.

Animals↗

Parainfectious conus myelitis.

We describe electroclinical and imaging features of a peculiar type of parainfectious myelitis that selectively involves the conus/epiconus region of the spinal cord. Twelve patients of parainfectious myelitis with MRI evidence of inflammatory lesions in the conus/epiconus region of the spinal cord were studied. All patients underwent full clinical and electrophysiological evaluation along with MRI of the spine. MRI included axial images at the site of lesion. All patients had a unique clinical presentation with urinary symptoms. Careful clinical examination revealed minimal sensorimotor dysfunction in the lower lumbar and sacral segments, which remained unnoticed by most of the patients; three female patients had no sensorimotor deficit. The motor paralysis recorded in four patients was flaccid and areflexic. The sensory level was inconspicuous as it was in the leg area corresponding to the lumbar and sacral spinal segments. Sensory loss was significantly more in the perineal region in those seven patients who had MRI evidence of inflammatory lesion in conus medullaris; two patients had maximum sensory loss in lumbar dermatomal distribution, which corresponded with the focal segmental myelitis involving 'epiconus'. MRI done in the sagittal plane was either normal or only 'suggestive' of myelitis in most of the patients and the inflammatory lesions were much more visible in the axial plane. The lesions predominantly involved central gray matter with spread to adjoining white matter in nine patients; in three patients with pure bladder involvement, lesions were confined to lateral gray matter of the conus medullaris. Our findings indicate that parainfectious myelitis (PIM) selectively involving conus medullaris is an important cause of unexplained acute or sub-acute urinary symptoms in adolescent and adult patients. In suspected cases, MRI must include axial images of the conus-epiconus region, as sagittal images may not always reveal the lesion. Due to initial presentation with urinary symptoms, absent or minimal sensory-motor signs, no transverse level over the trunk and unique MRI features, this condition may be called parainfectious conus myelitis (PICM).

Acute Disease↗

Mg2+ modulates membrane sphingolipid and lipid second messenger levels in vascular smooth muscle cells.

In vitro studies with smooth muscle cells from rat aorta and dog cerebral blood vessels indicate that variation in free Mg2+, within the pathophysiological range of Mg2+ concentrations, found in human serum, causes sustained changes in membrane phospholipids and lipid second messengers. Incorporation of [3H]palmitic acid into phosphatidylcholine (PC) and sphingomyelin (SM) was altered within 15-30 min after modifying the extracellular Mg2+ ion level ([Mg2+]o). Decreased Mg2+ produced a fall in both [3H]SM and [3H]PC over the first 2 h. After an 18-h incubation, the [3H]PC/[3H]SM ratio changed from about 20:1 to about 50:1. Increased [Mg2+]o resulted in a 2- to 3-fold increase in [3H]SM compared to only a small increase in [3H]PC over the same period. There was a reciprocal relationship between [3H]ceramide and [3H]1,2-DAG levels with highest [3H]ceramide and lowest [3H]-1,2-DAG levels seen at lowest [Mg2+]o. The results indicate that a fall in extracellular ionized Mg2+ concentration produces a rapid and sustained decrease in membrane sphingomyelin and a moderate rise in intracellular ceramide. A major effect of lowering [Mg2+]o appears to be a down-regulation of SM synthase. The increased membrane SM content and a concomitant decrease in cell ceramide, in the presence of elevated [Mg2+]o, may be relevant to the apparent protective role of adequate Mg intake on vascular function in humans.

Animals↗

Tumor-associated antigen TA-90 immune complex assay predicts subclinical metastasis and survival for patients with early stage melanoma.

BACKGROUND: TA-90 is a tumor-associated antigen first identified in the urine and sera of patients with metastatic melanoma. In the early stages of disease, TA-90 is present in circulating immune complexes (ICs) that may be detected with an antigen specific enzyme-linked immunosorbent assay (ELISA). In this study, the authors evaluated the efficacy of the TA-90 IC assay in detecting subclinical metastasis of early stage melanoma and predicting the survival of patients with this disease. METHODS: Archival sera were collected preoperatively from 114 patients who underwent wide excision with or without regional lymphadenectomy in the treatment of clinical Stage I melanoma. Sera were analyzed for TA-90 IC in a blinded fashion, and results were correlated with the patient's clinical course as determined by database and chart review. Subclinical metastases were considered present at the time of surgery if the lymphadenectomy specimen was pathologically positive and/or the patient subsequently developed recurrence. RESULTS: The TA-90 IC assay predicted subclinical metastasis in 43 of 56 patients (P < 0.0001), with 14 false-positive and 13 false-negative results. Sensitivity and specificity for the detection of occult metastasis were 77% and 76%, respectively. Positive and negative predictive values were 75% and 77%, respectively. Fifteen of 18 tumor positive regional lymph node basins (83%) and 34 of 46 recurrences (74%) were accurately predicted when considered independently (P < 0.004). Preoperative TA-90 IC status was also highly correlated with survival: 5-year overall and disease free survival rates were 63% and 46%, respectively, for the TA-90 IC positive group, compared with 88% and 82%, respectively, for the TA-90 IC negative group (P=0.0001). A multivariate analysis with standard prognostic variables identified preoperative TA-90 IC status as a strong, independent prognostic factor for both overall and disease free survival. CONCLUSIONS: To the authors' knowledge, TA-90 is the first tumor marker that accurately predicts subclinical metastatic disease and survival for patients with early stage melanoma. For this reason, the TA-90 IC assay has the potential to improve dramatically the prognostic evaluation of patients with this disease. Its role in postoperative risk stratification and early detection of recurrence is being evaluated in a prospective study.

Adult↗

Fine-needle aspiration cytology of malignant retroperitoneal paraganglioma.

The cytologic findings in a fine-needle aspiration sample are described from a large retroperitoneal mass in a 56-yr-old male. The aspiration was performed under CT guidance using a 22-gauge needle, maintaining negative pressure. For cytologic study, on-site smears were prepared and stained by the Papanicolaou method. Additionally, cytospin, filter preparations, cell blocks from the aspirate, histology, and electron microscopy of the tumor tissue were performed. Also, immunodiagnostic staining for neuron-specific enolase (NSE), chromogranin, S-100 protein, vimentin, HMB45, cytokeratin, and Grimelius preparation was performed on cytologic and histologic material. The cytologic material was characterized by cords, suggestive acinar structures, and small follicle-like clusters of cells, while cell blocks from the aspirate showed oval or spindle-shaped nuclei with a somewhat fasciculated appearance. However, sections from the tumor tissue showed an organoid "zellballen" pattern. The nuclei were round, oval, spindly, and epithelioid, with moderate to scanty cytoplasm, smooth nuclear membranes, fine, evenly dispersed chromatin, slight hyperchromasia, and mild pleomorphism. No intranuclear vacuoles were seen. Positive immunohistochemical staining for NSE, chromogranin, and Grimelius preparation was noted in the tumor cells, while staining for vimentin, HMB45, and cytokeratin was negative. Electron microscopy of the tumor tissue revealed the presence of variable numbers of round, membrane-bound, electron-dense neurosecretory granules. The cytohistologic and ultrastructural findings are presented, as well as the results of immunodiagnostic staining which helped in the diagnosis of retroperitoneal paraganglioma, an infrequently reported tumor.

Biopsy, Needle↗

Fine-needle aspiration cytology of renal angiomyolipoma: report of a case with immunocytochemical and electron microscopic findings.

A case is presented in which the diagnosis of renal angiomyolipoma was made by computed tomography (CT)-guided, fine-needle aspiration cytology and the examination of a cell block. The tumor was characterized by epithelioid smooth muscle cells, blood vessels and fat in the cytologic material. The cytodiagnosis was further substantiated by positive staining of the epithelioid muscle cells for markers of muscle-specific actin, HMB45, and trace positivity for vimentin but not with S100 protein, desmin, or cytokeratin. Further studies for the recently described crystalloids were also performed by using the periodic-acid Schiff stain with and without diastase treatment and electron microscopy on the cytologic material. However, no such crystalloids were found. A preoperative cytologic diagnosis of renal angiomyolipoma was considered to be of value due to the difference in management between angiomyolipoma and a renal carcinoma, both of which can present as a renal mass on imaging.

Aged↗