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Biomedical subjects

R Kumar

Publications and source records attributed to R Kumar.

At least 163 records · Page 9Linked to original sources

Neoadjuvant hormonal downsizing of localized carcinoma of the prostate: effects on the volume of normal tissue irradiation.

A prospective evaluation of neoadjuvant hormonal downsizing in patients with localized carcinoma of the prostate was undertaken to assess its effect on normal tissue irradiation. Twenty patients with stage T1 or T2 (A, B) carcinoma of the prostate received 3 months of Lupron prior to definitive radiotherapy. The volumes of the prostate, seminal vesicles, bladder, and rectum from both the pre- and posthormone treatment planning CT were entered onto a 3-D treatment-planning system. The treatment planning parameters were standardized to facilitate comparison of the pre- and posthormonal volumes. Following the three monthly injections of Lupron, the average volume of the prostate was reduced by 37%. As a consequence, the volume of the bladder receiving at least 40, 52, and 64 Gy was reduced by an average of 15, 18, and 20%, respectively. In addition, the volume of the rectum receiving at least 40, 52, and 64 Gy was reduced by an average of 13, 20, and 34%, respectively. In conclusion, in patients with localized prostate cancer, downsizing of the prostate resulted in a reduction in the volume of bladder and rectum receiving high radiation doses. This approach may result in an improvement in the therapeutic ratio by reducing the morbidity of treatment.

Adenocarcinoma

Herniation of the spinal cord. Case report.

Herniation of the spinal cord, or displacement of the cord outside the dura, is so rare that only 13 cases have been reported in the literature. The authors report a new case of spontaneous herniation of the spinal cord in a 38-year-old man who presented with lower left limb paresis and Brown-Séquard syndrome, with a T-8 sensory level. Displacement of the spinal cord was noted on computerized tomography following myelography and on magnetic resonance imaging. The herniated cord was confirmed at operation and reduced intradurally. Postoperatively, the patient showed complete neurological recovery. Based on a review of the literature, herniation of the spinal cord may be classified as spontaneous, iatrogenic, or traumatic. At cervical levels, the spinal cord has herniated into an iatrogenic pseudomeningocele located dorsally. At thoracic levels, spinal cord herniations were reported to be in a preexisting extradural arachnoid cyst located ventrally. The authors propose a pathogenesis for spinal cord herniation based on abnormal positioning of the spinal cord in the dural sleeve and the known anteroposterior movements of the cord that occur with cardiac and respiratory pulsations. The presence of a dural defect situated on the concavity of the spinal curvature is a prerequisite for this rare condition. As adhesions develop between the cord and the edges of the dural defect, cerebrospinal fluid pulsations push the cord into a preexisting cyst. The authors suggest modifying the classification by Nabors, et al., of spinal meningeal cysts to include this mechanism of spinal cord herniation. This diagnosis should also be considered in the differential diagnosis of myelopathy in the absence of a mass lesion.

Adult

Recombinant hemoglobins as blood substitutes: a biotechnology perspective.

Human hemoglobin can be produced in microbial and mammalian organisms using many different expression systems. It is anticipated that recombinant hemoglobins (or globin genes) will have many applications including as an infectious agent-free, inexpensive raw material for a red blood cell substitute, as a vehicle for expression or delivery of other biomolecules, and in gene therapy of inherited hemoglobinopathies. Recombinant expression, combined with site-directed mutagenesis, is facilitating the modification of the functional properties of hemoglobin. Although a functional hemoglobin molecule can be derived using many of the known expression systems, the choice of the production system for manufacturing depends on the scale, acceptable cost, and the associated environmental impact of the various processes. While the efficient bacterial production systems yield a modified, "surrogate" hemoglobin, the transgenic animal-derived product is virtually identical to the human erythrocyte-derived hemoglobin. Both the microbial fermentation, and the mammalian transgenic systems can be geared to produce the enormous quantities of hemoglobin expected to be required to meet the anticipated demand for a successful blood substitute in the future.

Animals

Extrapulmonary lymphangioleiomyomatosis and lymphangiomatous cysts in tuberous sclerosis complex.

OBJECTIVE: To describe the clinical manifestations, imaging findings, and histologic features of extrapulmonary lymphangioleiomyomatosis (LAM) in the tuberous sclerosis complex (TSC). DESIGN: We retrospectively reviewed institutional medical records since 1940 to identify patients with TSC and extrapulmonary LAM. MATERIAL AND METHODS: Of 403 patients with TSC, 3 had pulmonary and extrapulmonary LAM and retroperitoneal lymphangiomatous cysts. The clinical, imaging, and histologic features of these three patients were summarized, including analysis of biopsy specimens by conventional histology, immunohistology, radiolabeled ligand-binding assays, and tissue culture. RESULTS: The three young women had characteristic dermatologic findings of TSC and pulmonary LAM. Two patients were of normal intelligence, and one had a recent history of contraceptive use. All three patients had intra-abdominal lymphangiomatous cysts, uterine LAM, and renal angiomyolipomas. Renal and uterine biopsy specimens demonstrated positive immunostaining for melanoma-related antigens and expression of estrogen and progesterone receptors by ligand-binding assay and immunohistology. Cells cultured from LAM tissue of one of the patients exhibited a mitogenic response to estradiol. CONCLUSION: Clinically significant extrapulmonary LAM is a rare manifestation of TSC and may occur in women with this disease who also have pulmonary LAM. The clinical features of these patients confirm the importance of sex steroids in the development of these lesions. Immunohistochemical findings suggest that LAM and angiomyolipomas have a neuroectodermal origin. The development of lymphangiomatous cysts in these patients is probably due to smooth muscle proliferation in lymph vessels, which can result in lymphatic obstruction.

Abdominal Neoplasms

Cisplatin stimulates protein tyrosine phosphorylation in macrophages.

Cisplatin [cis-dichlorodiamine platinum (II)], a potent anti-tumor compound, stimulates immune responses by activating monocyte-macrophages and other cells of the immune system. The mechanism by which cisplatin activates these cells is poorly characterized. Since protein tyrosine phosphorylation appears to be a major intracellular signalling event that mediates cellular responses, we examined whether cisplatin alters tyrosine phosphorylation in macrophages. We found that cisplatin increased tyrosine phosphorylation of several proteins in peritoneal macrophages and in P388D1 and IC-21 macrophage cell lines. Treatment of macrophages with tyrosine kinase inhibitors, genestein and lavendustin A, inhibited cisplatin-stimulated protein tyrosine phosphorylation in macrophages. Macrophages treated with cisplatin also exhibit increased fluorescence with anti-phosphotyrosine-FITC antibody. These data indicate that protein tyrosine phosphorylation plays a role in cisplatin-induced activation of macrophages.

Animals

Induction of protein tyrosine phosphorylation in macrophages incubated with tumor cells.

The cellular and molecular interaction between monocyte/macrophage and tumor cells leading to macrophage activation is not clearly understood. Since protein tyrosine phosphorylation appears to be a major intracellular signalling event, we checked whether the tumor cells alter tyrosine phosphorylation of proteins in macrophages. We found that both L929 and Yac-1 tumor cells induced increased tyrosine phosphorylation of several polypeptides in peritoneal as well as P388D-1 and IC-21 macrophages. Macrophages co-cultured with tumor cells also showed increased fluorescence with anti-phosphotyrosine-FITC antibody. These observations suggest that increased tyrosine phosphorylation plays a role in tumor cell-induced activation of macrophages.

Animals

Pharmacokinetics and bioavailability of 5-ethyl-2'-deoxyuridine and its novel (5R,6R)-5-bromo-6-ethoxy-5,6-dihydro prodrugs in mice.

The pharmacokinetics and oral (po) bioavailability of 5-ethyl-2'-deoxyuridine (EDU) and its novel 5,6-dihydro prodrugs (+)-trans-(5R,6R)-5-bromo-5-ethyl-6-ethoxy-5,6-dihydro-2'-deoxyuridine (BEEDU) and (+)-trans-(5R,6R)-5-bromo-5-ethyl-6-ethoxy-5,6-dihydro-5'-O-valeryl-2'- deoxyuridine (VBEEDU) were determined in male Balb/C mice following intravenous and no administration of a 0.4 mmol/kg dose. EDU was eliminated from blood with a half-life of 35.2 +/- 4.2 min. The mean residence time (MRT) and the area under the blood vs. time curve (AUC) for EDU after iv injection were 45.1 +/- 11.7 min and 1.7 +/- 0.2 mumol.g-1.min, respectively. EDU showed a 49% bioavailability in male.Balb/C mice. The pharmacokinetic parameters and bioavailability of EDU were improved significantly upon administration of the 5,6-dihydro prodrugs BEEDU or VBEEDU. The AUC of EDU after a 0.4 mmol/kg iv dose of BEEDU was 2.1 +/- 0.3 mumol.g-1.min, which is substantially higher than that after iv injection of EDU. The half-life and MRT of EDU were increased to 251.9 +/- 30.2 min and 352.0 +/- 91.5 min, respectively, after injection of BEEDU. The po bioavailability of EDU, after administration of BEEDU, was increased almost 2-fold (81%), compared with that of EDU (49%). The AUC of EDU after iv injection of VBEEDU was 1.8 +/- 0.2 mumol.g-1.min. The half-life and MRT of EDU, the active metabolite of VBEEDU, were 106.0 +/- 23.2 min and 157.0 +/- 40.8 min, which are substantially higher than those for EDU after administration of EDU.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral

Esophageal candidiasis following omeprazole therapy: a report of two cases.

Esophageal candidiasis was diagnosed at endoscopy in two patients receiving omeprazole therapy. There was no clinical evidence of immunosuppression or any obstructive lesion in the esophagus. There was prompt response of oral ketoconazole. These cases suggest that marked acid reduction may predispose to esophageal candidial infection.

Abdominal Pain

Controlling rheumatic heart disease in developing countries.

The streptococcal infection that leads to rheumatic heart disease, which accounts for one third to half of the cardiac admissions in developing countries, appears to spread especially rapidly in overcrowded living conditions. Rheumatic fever can be prevented by antibiotic treatment for streptococcal sore throat in children (primary prophylaxis), and its progression towards rheumatic heart disease can also be stopped by antibiotic therapy (secondary prophylaxis). At present, the most cost-effective control strategy appears to be secondary prophylaxis.

Child

Technetium-99m-HMPAO SPECT cerebral blood flow study in children with craniosynostosis.

UNLABELLED: Premature closure of cranial sutures (primary craniosynostosis) in children leads to characteristic skull deformities and prevents the constricted brain from growing normally. Although the cause remains unknown, several etiological factors have been cited. Recently, hypovascularity has been reported as a possible cause of craniosynostosis. METHODS: In a prospective study regional cerebral blood flow studies were carried out with 99mTc-HMPAO SPECT in seven children with craniosynostoses. Five preoperative and six postoperative studies were conducted and the results correlated with radiological and surgical findings. RESULTS: Preoperative studies revealed regional hypovascularity in the underlying cerebral hemisphere, corresponding to the fused sutures. Postoperative studies revealed disappearance of these perfusion defects in most cases, indicating normalization of perfusion following surgical decompression. CONCLUSION: This study establishes the presence of cerebral hypovascularity in craniosynostoses and suggests that early surgery and release of craniostenosis is essential to achieve optimum perfusion and brain development.

Brain

The effect of fibrin clots and clot-bound thrombin on the development of platelet procoagulant activity.

We tested different types of clot for their ability to provoke procoagulant activity in platelets: normal clots from platelet poor plasma (des AABB- or fibrin II clots), similar clots in which the adsorbed thrombin has been inhibited by hirudin, and clots obtained by the action of two snake venom enzymes that release only fibrinopeptide A (des AA- or fibrin I clots). Analogous clots from fibrinogen solutions were also tested. In platelet rich plasma (PRP), where platelet coagulant phospholipids (PCP) are rate limiting for thrombin generation, the addition of any type of clot enhances the generation of thrombin thus it induces the appearance of PCP. Clots containing active adsorbed thrombin are the most potent ones in this respect. Lactate dehydrogenase (LDH) levels do not increase in the course of the thrombin generation so the platelets are not damaged in the process. Non-centrifugable PCP could be demonstrated to appear during the process, so the production of procoagulant phospholipid microparticles must be part of the mechanism. Membrane transbilayer phosphatidyl serine movement (flip-flop) can not be demonstrated in PRP as the activated platelets are caught in the emerging clot. In order to demonstrate flip-flop, we tried to investigate the influence of clots on washed platelets. However, contrary to platelets in a plasma milieu, isolated platelets are damaged by fibrin clots, especially in the presence of thrombin, as can be judged from the appearance of LDH. We conclude that, in PRP, clots induce the appearance of PCP from platelets by vesiculation, possibly accompanied by flip-flop and that thrombin accelerates the process but is not an absolute requirement.

Blood Coagulation

Myosin light chains (MLCs) heterogeneity in mammalian smooth and cardiac muscle.

A comparative study of myosin light chains (MLCs) has been made in the aorta, uterine and cardiac muscles (auricle, ventricle) of mice, pig, sheep and goat. Analysis of myosin light chains by sodium dodecyl polyacrylamide gel electrophoresis (SDS-PAGE) has revealed that (a) aorta myosin from mice, goat and pig has identical myosin light chains profile but pig aorta myosin lacks LC-2f; (b) uterine smooth muscle myosin depicts absence of LC-1f in sheep. Whereas satellite bands of LC-1f and LC-2f fractions are absent in pig uterine myosin, mice shows duplets for both the myosin light chains; (c) the auricular myosin in pig and goat is identical to chicken gizzard myosin used as reference and exhibits ALC-2s and ALC-1s fractions only while sheep auricular myosin lacks in ALC-1f; (d) the mice ventricular myosin depicts two satellite MLCs associated with fast migrating VLC-1s.

Animals

Inhibitors of renal epithelial phosphate transport in tumor-induced osteomalacia and uremia.

Tumors such as sclerosing hemangiomas are sometimes associated with hypophosphatemia and osteomalacia, both of which disappear on removal of the tumor. We identified a heat labile, 8,000-25,000 dalton, inhibitor of renal epithelial phosphate transport in supernatants of cultured sclerosing hemangioma cells obtained from a patient with oncogenic osteomalacia and hypophosphatemia. The inhibitor does not alter glucose or alanine transport in renal epithelial cells, and has a mechanism of cellular action distinct from that of parathyroid hormone (PTH) in that it inhibits phosphate transport in renal epithelia without increasing concentrations of cyclic 3',5' adenosine monophosphate (cAMP); it's activity is not blocked by a PTH receptor antagonist. Sclerosing hemangioma cells also produce a material that cross-reacts with antisera directed against PTH and tumor tissue sections immunostain with PTH antibodies. We have characterized a cDNA that encodes the PTH immunoreactive material. In its longest open reading frame the cDNA encodes a protein of 381 amino acids that does not resemble PTH in its primary structure. Opossum kidney cells transfected with the cDNA do not produce a product that inhibits phosphate transport. Dialysates from patients with end-stage renal disease also contain a substance(s) that inhibits phosphate and glucose transport in opossum kidney cells. The inhibitor(s) of phosphate uptake in dialysates is a heat labile, approximately 30,000 dalton substance that inhibits phosphate transport by a cAMP-independent mechanism. Determination of the structures and physiology of these phosphate transport inhibitors is likely to yield insights into the control of phosphate homeostasis.

Amino Acid Sequence

Hyoid bone and atlas vertebra in established mouth breathers: a cephalometric study.

The position of hyoid bone and atlas vertebra in 29 established mouth breathers (17 boys and 12 girls) in the age group of 10-14 years were cephalometrically evaluated and compared with 23 nose breathers (11 boys and 12 girls). The children of both the groups were selected on the basis of history and clinical examination. The comparisons were made using univariate analysis for male and female groups separately as well as combined. It was observed that mouth breathers do maintain an extended head posture, which was evident from a decrease in distance between the occiput and dorsal arch of atlas vertebra. However the results of the present study did not reveal any distinct characteristics of hyoid bone and atlas vertebra that can be used to predict or associate the craniofacial pattern of mouth breathers.

Adolescent

Ultrasonography of the brain in preterm infants and its correlation with neurodevelopmental outcome.

Two hundred and eighteen preterm neonates had ultrasonography (USG) brain done on third, and/or seventh and fourteenth day of life. Fifty eight (26.3%) had intraventricular/ periventricular hemorrhage, 3 had parenchymal lesions. 46 had Grade I hemorrhage, 9 had Grade II, 2 had Grade III and 1 had Grade IV hemorrhage. Grade III and IV hemorrhages occurred in neonates below 34 weeks gestation. There was an inverse relationship between gestation age and hemorrhage (p = 0.0001). A comparison of incidence of hemorrhage between preterms who were appropriate for gestational age was not significant. Out of the 63 neonates who had serial USGs on the third and seventh day of life, 15 of the 16 bleeds (94%) were detected on the third day itself, indicating it to be a opportune time for doing an USG. USG at term (40 weeks postconceptual age) was done in 99 infants to see if it could correctly predict the neurodevelopmental outcome using the Bayley Scales of Infant Development. Out of these 99 infants, 72 came for the developmental assessment at one year. One neonate who had periventricular leucomalacia with cystic changes on USG at term, was grossly abnormal with cerebral palsy and mental retardation. Six infants showed delayed development with a mean mental development quotient of 79.1 +/- 1.72 at 2 years. The specificity of USG at term for predicting outcome was 89.2% and negative predictive outcome was 90%, indicating that a normal USG at term predicted a good neurodevelopmental outcome.

Cerebral Hemorrhage