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Biomedical subjects

P Kumar

Publications and source records attributed to P Kumar.

At least 73 records · Page 4Linked to original sources

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↗

Posttransplantation lymphoproliferative disorder of the head and neck: imaging features in seven adults.

PURPOSE: To determine the cross-sectional imaging findings of posttransplantation lymphoproliferative disorder (PTLD) of the head and neck. MATERIALS AND METHODS: Computed tomographic (CT) scans (n = 6) and magnetic resonance (MR) images (n = 2) in seven patients with histopathologically proved PTLD of the Waldeyer (lymphoid) ring or cervical lymph nodes were retrospectively reviewed for abnormalities. RESULTS: The interval between transplantation and PTLD onset was 3.5-108 months (mean, 30 months). All patients had imaging abnormalities involving the Waldeyer ring, and focal 2.0-4. 5-cm masses were present in six patients (unilateral oropharyngeal tonsil in two, bilateral oropharyngeal tonsils in one, nasopharyngeal adenoids in three, unilateral pharyngeal tonsil and ipsilateral nasopharynx in one). In three patients, the mass was centrally low attenuating at CT or isointense to fluid at MR imaging, with enhancing solid peripheral lymphoid tissue. Three patients also had nodal findings: one with a 7-cm low-attenuating nodal mass in the right neck and two with numerous bilateral lymph nodes (mostly normal sized) in the anterior and posterior cervical lymph chains. One patient also had a small mass in the upper mediastinum. CONCLUSION: In the setting of organ transplantation, findings of masses in the Waldeyer ring or an excessive number of cervical nodes should increase the index of suspicion of PTLD.

Adenoids↗

Serial measurement of vascular endothelial growth factor and transforming growth factor-beta1 in serum of patients with acute ischemic stroke.

BACKGROUND AND PURPOSE: Both vascular endothelial growth factor (VEGF) and transforming growth factor-beta1 (TGF-beta1) are expressed in higher than normal concentrations in the penumbra of patients after ischemic stroke. Because both cytokines are central to the processes of angiogenesis, tissue inflammation, and fibrosis, we performed serial measurements of these cytokines in patients with cerebral infarction and determined their relationship to stroke etiology and volume. METHODS: We serially (at days 0, 1, 3, 7, and 14) measured the serum levels of VEGF and active TGF-beta1 in 29 patients with acute ischemic stroke. Age-matched healthy subjects (n=26) were used as controls. RESULTS: Expression of VEGF was significantly increased in the majority of patients after acute stroke at each of the time points compared with normal controls. Highest expression occurred at day 7 (588+/-121 pg/mL; P=0.005), and it remained significantly elevated at 14 days after stroke. Expression of VEGF correlated with infarct volume, clinical disability (Scandinavian Stroke Scale), and peripheral leukocytosis and was significantly higher in patients with atherothrombotic large-vessel disease and ischemic heart disease (P<0.05 in all cases). In contrast, expression of active TGF-beta1 was not significantly different from control patients at any of the measured time points. When the mean concentration of TGF-beta1 from each patient (pooled time points) was compared with the control mean, a significant increase was found in only 2 patients, whereas levels decreased in 12 patients (P<0.05). There was no correlation between circulating active TGF-beta1 and VEGF expression, leukocytosis, stroke subtype, or patient disability as assessed by Scandinavian Stroke Scale score. CONCLUSIONS: VEGF but not TGF-beta1 showed a dramatic increase in serum of stroke patients. Correlation between stroke severity and VEGF concentration suggests it could be involved in the subsequent repair processes resulting in partial recovery after stroke. Correlation between VEGF expression and peripheral leukocytosis suggests that these changes may also reflect the immunologic status of the patient. VEGF may play an important role in the pathophysiology of acute ischemic stroke and could be of value in future treatment strategies.

Acute Disease↗

Steroidogenic alterations in testes and sera of rats exposed to trichloroethylene (TCE) by inhalation.

1. Trichloroethylene (TCE) is an organic unsaturated solvent used in dry cleaning, metal degreasing, thinner for paints/varnishes, anaesthetic agents etc. Human beings are considerably exposed to TCE vapours by inhalation route. 2. TCE has been reported to induce spontaneous abortions and congenital cardiac malformation in occupationally exposed women. However, scanty on-line information is available regarding toxic effects of TCE on male reproductive efficiency in experimental animals. 3. Our earlier observations with TCE inhalation in male rats (376 p.p.m., 4 h/day, 5 days a week) for 12 and 24 weeks using whole body dynamic inhalation chamber consistently showed significant decrease (P<0.05) in total epididymal sperm count and sperm motility. The mating experiments of above TCE inhaled rats with virgin unexposed females showed significantly decreased fertility. 4. These observations prompted us to investigate whether or not primary testicular steroidal precursors (cholesterol and ascorbic acid) and testosterone have any role in TCE induced significantly decreased epididymal sperm count, sperm motility and overall male reproductive inefficiency resulting therefrom. 5. The results indicate significant decrease (P<0.05) in total epididymal sperm count, sperm motility, specific activities of enzymes Glucose 6-p dehydrogenase (G6PDH) and 17 beta hydroxy steroid dehydrogenase (17betaHSD) with concomitant decrease in serum testosterone concentrations in TCE inhaled rats showing reduced male reproductive efficiency. There was net accumulation in total cholesterol contents in testes of TCE exposed rats. 6. The findings in the present study indicate possible impairment of testosterone biosynthesis in TCE inhaled rats after 12 and 24 weeks. These findings also serve in parts to elucidate the mechanism of reproductive inefficiency in TCE exposed rats. The role of testosterone in this phenomenon is being reported for the first time.

17-Hydroxysteroid Dehydrogenases↗

Development of artificial articular cartilage.

Attempts have been made to develop an artificial articular cartilage on the basis of a new viewpoint of joint biomechanics in which the lubrication and load-bearing mechanisms of natural and artificial joints are compared. Polyvinyl alcohol hydrogel (PVA-H), 'a rubber-like gel', was investigated as an artificial articular cartilage and the mechanical properties of this gel were improved through a new synthetic process. In this article the biocompatibility and various mechanical properties of the new improved PVA-H is reported from the perspective of its usefulness as an artificial articular cartilage. As regards lubrication, the changes in thickness and fluid pressure of the gap formed between a glass plate and the specimen under loading were measured and it was found that PVA-H had a thicker fluid film under higher pressures than polyethylene (PE) did. The momentary stress transmitted through the specimen revealed that PVA-H had a lower peak stress and a longer duration of sustained stress than PE, suggesting a better damping effect. The wear factor of PVA-H was approximately five times that of PE. Histological studies of the articular cartilage and synovial membranes around PVA-H implanted for 8-52 weeks showed neither inflammation nor degenerative changes. The artificial articular cartilage made from PVA-H could be attached to the underlying bone using a composite osteochondral device made from titanium fibre mesh. In the second phase of this work, the damage to the tibial articular surface after replacement of the femoral surface in dogs was studied. Pairs of implants made of alumina, titanium or PVA-H on titanium fibre mesh were inserted into the femoral condyles. The two hard materials caused marked pathological changes in the articular cartilage and menisci, but the hydrogel composite replacement caused minimal damage. The composite osteochondral device became rapidly attached to host bone by ingrowth into the supporting mesh. The clinical implications of the possible use of this material in articular resurfacing and joint replacement are discussed.

Aluminum Oxide↗

Impact of anemia in patients with head and neck cancer.

Head and neck squamous cell carcinoma, which is comprised of a heterogeneous group of tumors arising from the epithelial lining of the oral cavity, pharynx, and larynx, is a locoregional disease. Tumor hypoxia and anemia are known to adversely effect the efficacy of radiation therapy, a local treatment modality. Therefore, head and neck cancers represent an ideal model for assessing the impact of anemia following treatment with radiation therapy. Various treatment strategies aimed at increasing tumor oxygenation in head and neck cancer patients (including hyperbaric oxygen and hypoxic cell radiosensitizers) have been studied. These studies have been fueled by evidence that hypoxia adversely effects the radiosensitivity of cells. Although the exact mechanism of action of the oxygen effect is not known, in vitro studies with conventional photon radiation therapy under normoxic conditions have shown an effectiveness of 2.5-3.0 times greater than that achieved under anoxic conditions. Recent studies, including large retrospective analyses, have demonstrated the dramatic adverse impact of anemia upon locoregional tumor control and survival. These studies, which have revealed hemoglobin levels as a powerful prognostic factor, provide compelling evidence for the value of reversing anemia and hence tumor hypoxia in head and neck cancer patients.

Anemia↗

Neonatal autopsies: a 10-year experience.

OBJECTIVES: To identify trends in neonatal autopsy rates at a tertiary care hospital during the last decade, to determine the concordance between antemortem and post-mortem diagnoses, and to describe patient characteristics that influenced diagnostic yield on autopsy. DESIGN: Retrospective review of medical records. SETTING: Tertiary care children's hospital. PATIENTS: All neonatal deaths between January 1, 1984, and December 31, 1993. MAIN OUTCOME MEASURES: For those with autopsies, data included length of stay, diagnostic imaging studies, antemortem diagnoses, and autopsy findings. Autopsy diagnoses were compared with antemortem findings and classified according to concordance. RESULTS: Of 487 neonatal deaths, autopsies were performed in 296 (61%). The autopsy rate declined significantly during 10 years from 71.2% (1984-1988) to 47.7% (1989-1993). New diagnoses were made at autopsy in 44% of cases. Major discordancies were identified in 35 infants (12%); minor discordancies in 95 (32%). Autopsies were more likely to reveal new diagnoses in infants born at 28 to 36 weeks' gestation and in those whose mothers had no prenatal care. Major findings at autopsy were more likely in infants whose mothers had no prenatal care and in infants who died within 6 hours of birth. There was no relationship between new findings at autopsy and age, length of hospital stay, or antemortem imaging studies. CONCLUSIONS: This study reveals a significant decline in neonatal autopsies during a 10-year period. This study also demonstrates that neonatal autopsy continues to provide clinically significant data and remains a valuable tool in perinatal medicine.

Adult↗

Impact of Anemia in Patients With Head and Neck Cancer.

Head and neck squamous cell carcinoma, which is comprised of a heterogeneous group of tumors arising from the epithelial lining of the oral cavity, pharynx, and larynx, is a locoregional disease. Tumor hypoxia and anemia are known to adversely effect the efficacy of radiation therapy, a local treatment modality. Therefore, head and neck cancers represent an ideal model for assessing the impact of anemia following treatment with radiation therapy. Various treatment strategies aimed at increasing tumor oxygenation in head and neck cancer patients (including hyperbaric oxygen and hypoxic cell radiosensitizers) have been studied. These studies have been fueled by evidence that hypoxia adversely effects the radiosensitivity of cells. Although the exact mechanism of action of the oxygen effect is not known, in vitro studies with conventional photon radiation therapy under normoxic conditions have shown an effectiveness of 2.5-3.0 times greater than that achieved under anoxic conditions. Recent studies, including large retrospective analyses, have demonstrated the dramatic adverse impact of anemia upon locoregional tumor control and survival. These studies, which have revealed hemoglobin levels as a powerful prognostic factor, provide compelling evidence for the value of reversing anemia and hence tumor hypoxia in head and neck cancer patients.

Journal Article↗

Acute inhalation toxicity study of 2-fluoroacetamide in rats.

One of the most potent rodenticides is 2-fluoroacetamide (2-FA). Toxicity of this chemical is well documented. However, its inhalation toxicity data is not available in the literature. Hence, acute inhalation toxicity study was carried out by exposing male and female rats to aerosols of 2-FA at different concentrations for 4 h in a dynamically operated whole body inhalation exposure chamber. During and after the inhalation exposure the rats were less active, and showed mild tremors and convulsions. At higher concentrations the rats died after 2-3 days. The estimated 4-h LC50 for male and female rats was 136.6 and 144.5 mg.m-3 respectively. Exposure to 0.7 LC50 for 4 h duration showed an increase in the liver weight of male and female rats 7 days after exposure. Various haematological and biochemical variables determined were within the normal limits. However, histological findings showed injured lung as indicated by desquamation and necrosis of the epithelium of the respiratory tract. Marked hypertrophy of hepatocytes displaying strong acidophilic granulated cytoplasm was observed. Focal dilatation of renal proximal tubules in kidney with cytoplasmic vacuolation, and irregularly placed pyknotic nuclei were seen. The present study shows that 2-FA is a highly toxic chemical through the inhalation route based on the LC50 value. Consequently necessary precautions should be taken during its handling.

Animals↗