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Biomedical subjects

P Kumar

Publications and source records attributed to P Kumar.

At least 127 records · Page 7Linked to original sources

Tumor hypoxia and anemia: impact on the efficacy of radiation therapy.

The adverse effects of tumor hypoxia and anemia on the efficacy of radiation therapy have been increasingly recognized. In vitro data indicate that radiation therapy under hypoxic conditions is approximately one third as effective as that under normoxic conditions. There is accumulating clinical evidence of significantly reduced local-regional tumor control and overall survival in anemic patients receiving radiotherapy for head and neck, respiratory tract, pelvic, or genitourinary cancers. In our own study using intraarterial high-dose cisplatin and radiation therapy, we observed that pretreatment hemoglobin level was significantly predictive of complete response (CR) at primary and nodal sites, local-regional failure-free survival, and overall survival by multivariate analyses. With the general lack of success in overcoming the effects of tumor hypoxia through such measures as hyperbaric oxygen and radiosensitizing agents, the focus of clinical research has shifted to directly correcting anemia. A planned randomized trial by the Radiation Therapy Oncology Group will assess the effects of correction of anemia with epoetin alfa on local-regional tumor control and survival in anemic head and neck cancer patients receiving radiation therapy.

Anemia↗

Cytotoxic 2,6-bis(arylidene)cyclohexanones and related compounds.

A number of 2-arylidenecyclohexanones 1, 2, 6-bis(arylidene)cyclohexanones 2 and related Mannich bases 3-5 were prepared. Various torsion angles as well as atomic charges on olefinic carbon atoms were determined by molecular modelling on all compounds. These molecules showed cytotoxicity towards murine P388 and L1210 cells as well as to human Molt 4/C8 and CEM T-lymphocytes. The average cytotoxicity of the dienones 2 was more than three times greater than was found with the monoarylidene analogues 1, and, in general, were slightly more cytotoxic than the Mannich bases 3-5. A number of the compounds displayed potency towards a panel of human tumour cell lines and most of the representative compounds in series 2-5 were selectively toxic to colon cancers and leukaemic cells.

Animals↗

Clinical, biochemical and neurobehavioural studies of workers engaged in the manufacture of quinalphos.

59 workers exposed to different chemicals during the manufacture of quinalphos, an organophosphate pesticide (OP) and 17 control subjects were studied. Despite similar blood acetylcholinestarase (AChE) levels in both the exposed and control subjects, a significant number of exposed subjects had altered plantar and ankle reflexes. Higher nervous functions such as memory, learning and vigilance were also found to be affected in these subjects. These findings were attributed to chronic low dose combined exposure to different chemicals used/formed in the manufacture of quinalphos. The study raises the doubt that monitoring of AChE alone among subjects engaged in the manufacture of OP pesticides may not be an adequate safeguard as regards to their health.

Acetylcholinesterase↗

Preauricular flap for post burn ear lobe reconstruction - a case report.

Burns of the face often affect the ear causing deformation of the pinna or ear lobe due to perichondritis or loss of cartilage and excess scarring. The reconstruction of the ear lobe may be limited due to scarring of the surrounding tissues. We describe a preauricular flap for reconstruction of the anterior and posterior surface of the ear lobe following burn injury. This two stage technique of ear lobe reconstruction by a preauricular flap is not described in the available literature. An inferiorly based preauricular flap was harvested in a young lady who had post burn loss of the right ear lobe. This was folded on itself and sutured to reconstruct both surfaces of the ear lobe. After 6 months, it was released from its attachment at the retromandibular area to define the cheek lobe angle and to shape it. The preauricular flap for ear lobe contouring is a simple and easy technique. An adequate length may be harvested without significant donor site morbidity.

Adolescent↗

Ten years epidemiological study of paediatric burns in Manipal, India.

Three hundred and nine children of burns injuries treated over last 10 years (1989-1998) in Kasturba Hospital, Manipal (India) were studied retrospectively and were analysed for incidence, severity, extent, causes, risk factors and overall mortality. Children of age < 5 years were affected more than children of age > 5 years (76.1 vs. 23.9%). Females were affected more than males (74.1 vs. 25.9%). Most of the children received burn injuries in the range of 0 to 20% BSA (63.1%). Scald (72.5%) followed by flame (22.7%) and electrical burn (3.2%) were most common cause of burn injuries. Overall paediatric burn mortality was 7.4%.

Age Distribution↗

Hypocholesterolemic activity of Marsilea minuta in gerbils.

Feeding of a Marsilea minuta leaf extract [Fr. I] reduced serum cholesterol and triglycerides by 31 and 63%, respectively, in athero diet fed gerbils. Liver cholesterol and triglycerides were also lowered by 71 and 27%, respectively, in comparison to athero fed controls. Moreover, treatment with Fr. I prevented the accumulation of cholesterol and triglycerides in liver and aorta and was able to dissolve atheromatous plaques of thoracic and abdominal aorta. Fecal excretions of cholesterol and triglycerides were significantly increased in Fr. I fed gerbils.

Animals↗

Antifertility studies of the root extract of the Barleria prionitis Linn in male albino rats with special reference to testicular cell population dynamics.

Oral administration of root extract of Barleria prionitis L. to male rats (100 mg/rat per day) for the period of 60 days did not cause body weight loss. The root extract brought about an interference with spermatogenesis. The round spermatids were decreased by 73.6% (P< or =0.001). No significant change was found in the population of secondary spermatocytes. However, the population of preleptotene spermatocytes were decreased by 41.9%. The extract reduced the fertility of male rats by 100%. Cross sectional surface area of Sertoli cells and mature Leydig cell numbers were significantly reduced (36.9%). The total protein, sialic acid contents of the testes, epididymides, seminal vesicle and prostate were reduced. Testicular glycogen contents were low. Antifertility effects of Barleria seemed to be mediated by disturbances in testicular somatic cells functions (Leydig and Sertoli cells) resulting in the physio-morphological events of spermatogenesis.

Animals↗

Synthesis, radiolabeling, and biodistribution of putative metabolites of iodoazomycin arabinoside.

Scintigraphic evaluation of patients with advanced oncological disease showed uptake of radioactivity in the brain following administration of the hypoxic imaging agent 123I-iodoazomycin arabinoside (123I-IAZA). Three proposed metabolites of IAZA--methyl 5-deoxy-5-iodo-D-arabinofuranoside, methyl 2,3-di-O-acetyl-5-deoxy-5-iodo-alpha-D-arabinofuranoside, and 1-(5-deoxy-5-iodo-alpha-D-arabinofuranosyl)-2-aminoimidazole (IAIA)--were synthesized, radiolabeled with 125I, and investigated in normal and tumor-bearing murine models for their contribution to this unusual phenomenon. The three compounds were readily radiolabeled by melt or solvent exchange procedures. Biodistribution data indicated rapid blood clearance, rapid excretion, and little tissue accumulation in the brain. IAIA showed significant tumor to blood ratios at 4 h (4.3:1) and liver to blood ratios at 24 h (30:1).

Animals↗

Role of staphylococcal superantigens in atopic dermatitis: from colonization to inflammation.

OBJECTIVE: This review article has been prepared in order to enable the readers to understand the role of staphylococcal superantigens (SsAgs) in atopic dermatitis (AD). DATA SOURCES: MEDLINE literature search was performed for obtaining references. Recent reviews, research articles, poster presentations, and letters (to the editor) were meticulously reviewed. RESULTS: (1) SsAgs contribute to the pathogenesis of cutaneous inflammation in AD with five potential mechanisms: Direct stimulation of antigen presenting cells (APCs) and keratinocytes. Stimulation of T cell proliferation [superantigenic binding to T cell receptor (TCR)]. Expansion of skin-homing cutaneous lymphocyte antigen (CLA) (+) T cells. The role of superantigens as allergens. Reduction of apoptosis. (2) Effectiveness of antibiotic therapy in AD patients without signs of bacterial infection is still under discussion. If signs of skin infection are present, antibiotic therapy (topical/oral) may help exacerbations of AD. Prolonged topical/oral antibiotic therapy, however, may cause development of antibiotic-resistant strains of Staphylococcus aureus (SA). CONCLUSIONS: Atopic dermatitis is a genetically determined, chronically relapsing, inflammatory skin disease which has many aspects and a complex immunopathogenesis involving both immediate and cellular immune responses. While the pathogenic role of SsAgs may not be of primary importance, SsAgs appear to be one of the important triggering factors that contribute to the cutaneous inflammation in AD. We suggest that staphylococcal colonization does not always mean SsAg-mediated inflammation, and anti-staphylococcal treatment should be considered in cases with signs of bacterial infection.

Animals↗

Light and scanning electron microscopic studies of the nasal turbinates of the horse.

The nasal turbinates of 5 young horses were studied by light and scanning electron-microscopy. Stratified cuboidal epithelium lined the rostral part of the dorsal and ventral nasal turbinates of the vestibular region. The polyangular microvillus cells of this region were separated by linear depressions. The mid and caudal parts of the dorsal and ventral nasal turbinates and the rostral part of the ethmoturbinates were lined by pseudostratified columnar ciliated respiratory epithelium. Numerous cilia with dilated blebs on the ciliated cells concealed adjacent non-ciliated supporting cells and goblet cells. The olfactory zone consisting of the olfactory vesicle and a dense network of olfactory cilia localized to the caudal part of the ethmoturbinates. The three regions were delineated from each other by transitional zones.

Animals↗

The ultrastructure of the subcommissural organ ependyma of the goat.

The cells of pseudostratified columnar ciliated ependyma of the subcommissural organ in the goat were classified into two types on the basis of the distribution of chromatin material and nuclear clefts. Amongst the cell organelles the endoplasmic reticulum was highly developed and formed three types of Nebenkerne systems. The type-I Nebenkerne had spiral concentric lamellae and was associated with round lipid droplets. The type-II Nebenkerne, with widely spaced coils, was expanded towards its central and peripheral parts. The type-III Nebenkerne, composed of a meshwork of lamellae, was modified into a vacuolated form. The concentration of mitochondria was greatly increased towards the basal processes of the ependymal cells. The inclusion bodies included small electron-dense bodies, osmiophilic asteroid droplets, large round to spherical bodies and large round osmiophilic bodies with inner structures.

Animals↗

Incidence of incomplete excision in surgically treated basal cell carcinoma: a retrospective clinical audit.

All the patients who had excision of basal cell carcinoma at the regional plastic surgery unit at Manchester over a period of 2 years from January 1995 to December 1996 were included in a retrospective audit. A total of 879 lesions were excised in 754 patients. In 41 lesions (4.7%) the tumour was incompletely excised, 16 of these lesions were further excised; the rest were managed by regular follow-up. The mean age of the incomplete excision group was slightly higher. The site where the incomplete excision rate was highest was the scalps followed by the ear, canthi,eyebrows and nose. There was a higher incidence of squamous differentiation and presence of foci of squamous cell carcinoma in the lesions excised incompletely. There was no statistically significant difference among the different groups of surgeons but in individual grades the rate was lower where more wounds were repaired by direct closure. The concept of a complexity ratio (number of wounds repaired by other methods/number of wounds repaired by direct closure) can be helpful in comparing the incomplete excision rates of different grades of surgeons or departments. The excision of basal cell carcinoma is one of the commonest procedures performed by all grades of surgeons in a plastic surgery department. Incomplete excision leads to further surgery or prolonged follow-up, thus significantly affecting the outcome. As the incidence of incomplete excision can be precisely monitored, it may be a useful tool for clinical governance.

Adolescent↗

Atrial endocardial changes in mitral valve disease: a scanning electron microscopy study.

BACKGROUND: The precise contribution of left atrial appendage (LAA) endocardial damage and dysfunction to the process of thrombus formation in patients with mitral valve (MV) disease, especially in the presence of atrial fibrillation (AF), has not as yet been clearly described. This may be important because the LAA is the usual site for thrombus formation. METHODS: The purpose of this study was to describe endocardial surface changes, through the use of scanning electron microscopy, in the left and right atrial appendages of patients with MV disease and the differences, if any, between patients with mitral stenosis and mitral regurgitation as well as between those with AF and sinus rhythm. Our second objective was to relate endocardial changes to plasma levels of von Willebrand factor (vWf), an established marker for endothelial damage. LAA specimens were obtained immediately after commencement of cardiopulmonary bypass from 35 patients (18 men; mean age 65 years, range 20 to 85) during surgery for MV repair or replacement. Right atrial appendage (RAA) specimens were similarly obtained as controls for individual patients. The specimens were fixed in 2.5% glutaraldehyde solution overnight, stored in Sorensen's phosphate buffer, and examined by means of scanning electron microscopy. Two independent observers documented the most advanced lesion in each specimen as follows: (1) "minimal" changes, with minimal disruption of the endocardium; (2) "intermediate" changes or prethrombotic lesions; and (3) "advanced" changes, with endocardial disruption and thrombotic lesions. Plasma levels of vWf were also measured (enzyme-linked immunosorbent assay) in all patients, and results were compared with those of age- and sex-matched healthy control patients. RESULTS: Advanced changes were more frequently seen in the endocardium of the LAA when compared with the RAA (31% vs 6%), whereas minimal changes were more frequently seen in the RAA compared with the LAA (23% vs 6%) (P =.00167). Similarly, the LAA from patients with mitral stenosis had a higher proportion of "advanced" endocardial changes when compared with patients with mitral regurgitation (67% vs 24%; P =.0066). The LAA in patients with AF had more "advanced" changes (39% vs 27%), but this was not statistically significant. Plasma vWf levels were significantly higher in patients with MV disease compared with healthy control patients (132 +/- 33 IU/dL vs 99 +/- 37 IU/dL; P =.0004) and in patients with advanced LAA changes compared with earlier changes (149 +/- 34 IU/dL vs 121 +/- 31 IU/dL; P =.042). CONCLUSIONS: Endocardial damage occurs in the atrial appendages of patients with MV disease. Potentially thrombogenic changes are more commonly seen in the LAA compared with the RAA and in patients with mitral stenosis compared with mitral regurgitation. These anatomic appearances may contribute to the risk of intra-atrial thrombus formation in patients with mitral valve disease, especially if AF is present.

Adult↗

CD105 antagonizes the inhibitory signaling of transforming growth factor beta1 on human vascular endothelial cells.

CD105 (endoglin), a receptor for transforming growth factor beta (TGFbeta), is highly expressed in tissue-cultured, activated endothelial cells in vitro and in tissues undergoing angiogenesis in vivo. The absence of CD105 in knockout mice leads to their death from defective vascular development, but the role of CD105 in the modulation of angiogenesis has not been elucidated. TGFbeta1 is a well-recognized regulator of angiogenesis. Using an antisense approach, we have shown that inhibition of CD105 protein translation in cultured human endothelial cells enhances the ability of TGFbeta1 to suppress growth and migration in these cells. The ability of endothelial cells to form capillary tubes was evaluated by the use of a 3-dimensional collagen matrix system where TGFbeta1 not only reduced the length of capillary-like structures, but also caused massive mortality in CD105-deficient cells compared to control cultures. These results provide direct evidence that CD105 antagonizes the inhibitory effects of TGFbeta1 on human vascular endothelial cells and that normal cellular levels of CD105 are required for the formation of new blood vessels.

Animals↗

Preparation of 99mTc-ethylene dicysteine (99mTc-EC) by transchelation using 99mTc-glucoheptonate (99mTc-GHA) and its evaluation for renal function studies.

The complexation of ethylene dicysteine (EC) with 99mTc needs to be carried out at pH 12 to achieve a high radiochemical yield. However, the preparation of the kit at high pH poses difficulties and requires very stringent preparation conditions, as stannous tin, one of the main ingredients in the kit, is unstable at high pH. Hence, an alternative method, involving the transchelation preparation of 99mTc-EC using 99mTc-glucoheptonate (99mTc-GHA) prepared at pH 6.5, was attempted, prompted by the reported success of the preparation of 99mTc-sestamibi (99mTc-MIBI) by this method. The preparation of 99mTc-EC by this method first involved the formation of 99mTc-GHA by the addition of sodium pertechnetate-99mTc to the Sn-GHA kit vial at pH 6.5. 99mTc-EC was formed by the addition of reconstituted EC solution at pH approximately 12 to the preformed 99mTc-GHA. The reaction was allowed to proceed both at room temperature and on a boiling water bath. The pH of the final product was adjusted to pH approximately 7 with 0.5 M phosphate buffer at pH 4-5, without affecting the quality of the product. The urinary excretion of 99mTc-EC prepared by transchelation, tested in mice, was similar to that of directly prepared 99mTc-EC, indicating that the final product prepared by the two methods was the same. The clinical evaluation of the product formulated by the new procedure showed satisfactory findings, comparable with the reports in the literature.

Adult↗

Ethyleneglycol-bis-(beta-aminoethylether)tetraacetate as a blood anticoagulant: preservation of antigen-presenting cell function and antigen-specific proliferative response of peripheral blood mononuclear cells from stored blood.

We examined the progressive and irreversible loss of antigen-specific lymphoproliferative responses in peripheral blood mononuclear cells (PBMC) obtained from blood exposed for prolonged periods to EDTA as an anticoagulant. The responses of these lymphocytes to interleukin-2 or to concanavalin A were, however, unaffected. The observed loss was not due to depletion of metal ions by EDTA, since the addition of several divalent cations to whole blood during storage in EDTA or to lymphocytes from EDTA-stored blood during antigen stimulation in vitro did not alleviate the defect. Reconstitution of antigen-specific T-cell lines or Percoll-purified T cells with adherent antigen-presenting cells in antigen stimulation assays revealed that the presenting cells and not the effector T-cells were the targets of EDTA-mediated damage. The anticoagulant heparin helped to circumvent this problem. Surprisingly, EGTA, another metal ion chelator, could successfully replace EDTA, with a marginal loss in antigen-specific responses. Lymphoproliferative responses to antigens of Japanese encephalitis virus (JEV) and Mycobacterium tuberculosis were both significantly preserved in EGTA. JEV antigen-specific responses of PBMC obtained from the blood of convalescent JEV patients and stored in EGTA for as long as 24 h (n = 20) were comparable to those of fresh PBMC (n = 10), while PBMC from blood stored in EDTA (n = 17) for 16 h or longer failed to respond. We recommend that EGTA be used as the anticoagulant of choice for applications that require the lymphocyte proliferation assay, especially when on-site testing facilities are not available.

Antigen Presentation↗