Vertical fusion amplitude in normal adults.
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Biomedical subjects
Publications and source records attributed to K Sharma.
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We investigated the effects of glucose concentration in serum-free media on the proliferative growth response of a cultured murine mesangial cell line. Raising the ambient D-glucose concentration from 100 mg/dl to 450 mg/dl stimulated cell proliferation after 24 to 48 hours but had a growth inhibitory effect after 72 to 96 hours of incubation. This biphasic proliferative response to high glucose concentration was not mediated by the elevated osmolarity of the medium and did not occur when L-glucose was used. The early phase of glucose-induced proliferation was associated with increased expression of the immediate early genes c-myc and egr-1 as well as with induction of the S-phase related proliferating nuclear cell antigen (PCNA). Several lines of evidence indicated that the late phase of glucose-induced growth inhibition was mediated by the bioactivation of endogenous transforming growth factor beta (TGF-beta). Neutralizing antibody against TGF-beta prevented the late inhibitory effects of glucose on proliferation. On the other hand, exogenous TGF-beta (1 ng/ml) significantly inhibited basal proliferation in mesangial cells. Furthermore, Northern blot analysis revealed that TGF-beta 1 mRNA was induced by 450 mg/dl glucose in the medium after 48 to 72 hours, but not after 24 hours. Cell cycle analysis demonstrated that mesangial cells incubated in high glucose for 24 hours have a higher percentage of cells in the S-G2 phase of the cell cycle compared with cells grown in normal glucose concentration. After 48 hours of culture in elevated glucose concentration, the percentage of cells in S-G2 phase was decreased, and became comparable to that of cells in normal glucose concentration. However, the addition of neutralizing anti-TGF-beta antibody stimulated the progression of cells towards S-G2 in high glucose medium after 48 hours. The findings of this study demonstrate a biphasic growth response of mesangial cells when they were cultured in high glucose concentration; initially there was a transient stimulation of replication for 24 to 48 hours followed by a sustained inhibition after longer incubation periods. This inhibition may be mediated by the glucose-induced synthesis and/or bioactivation of TGF-beta which can inhibit proliferation of mesangial cells in an autocrine fashion.
Twenty four patients with advanced cancer of cervix were submitted to sequential chemotherapy 5FU and MTX. The response rate was 85% in stage III and 50% in stage IV. Overall response rate was 75%. Patients who had not received radiotherapy earlier responded better than those who had received it earlier. This easy and economical modality has importance in view of late reporting and advanced stage of disease encountered in our set up.
When discussing the rheological properties of normal and leukemic blood it must be considered that blood is a suspension of cells in aqueous solution which is also known as plasma. Whole blood viscosity and plasma viscosity were determined by Rheometer LS30 which allows measuring whole blood and plasma viscosity in the middle and low shear rate ranges. The measurements of the viscosity showed that whole blood and plasma behave as non-Newtonian power law fluid. The values of n (non-Newtonian index) and k (consistency index) of power law fluid were calculated for both leukemic blood and plasma samples. The importance of this phenomenon for the micro-circulation is discussed.
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We investigated the hemorheological, hematological and biochemical parameters in 30 cases of acute lymphocytic leukemia (ALL), 21 cases of acute myelogenous leukemia (AML) and 30 cases of chronic myelogenous leukemia (CML). The parameters studied include whole blood viscosity, plasma viscosity, erythrocyte sedimentation rate (ESR), red cell filterability, hematocrit, platelet count and aggregation, fibrinogen, hemoglobin, leucocyte count, bleeding time and lactate dehydrogenase activity (LDH). In the cases of ALL we observed significant decrease in whole blood viscosity, hemoglobin, hematocrit and platelet count but an increase in plasma viscosity, fibrinogen, bleeding time and LDH activity. In the cases of AML, we observed increase in whole blood viscosity, plasma viscosity, ESR, fibrinogen, leucocyte count, bleeding time and LDH activity but decrease in the hemoglobin, hematocrit and platelet count. In the cases of CML, we observed an increase of whole blood viscosity, plasma viscosity, ESR, fibrinogen elevation but decreases in bleeding time. In all cases, red cell filterability was unaffected.
The impact of kidney donation on the psychological health of 31 living related donors was assessed by administering certain psychological tests before and after the operation (for donating the kidney). The results indicated a significant rise in the somatization subscale of the Middlesex Hospital Questionnaire (MHQ) from a mean of 1.61 to 3.23. There was no significant change in the other variables of these instruments or in the locus of control score. Only about one-fourth of the donors had prior knowledge of renal transplant. In almost all cases, the decision to donate had been voluntary and immediate, motivated by a concern for the recipient; there was virtually no second thoughts or regrets subsequently, which was apparently partly related to the opinions of other relatives who positively valued the act of donation.
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Chronic intermittent treatment of LH-RH superagonist Buserelin alone or in combination with testosterone enanthate were given to adult male langurs for 90 days to evaluate antispermatogenic activity of alone and combination therapy, maintenance of normal androgenicity, possible toxic effects of agonist treatment, related side effects of testosterone supplementation and complete reversibility of the procedure. A gradual decrease in sperm count was recorded in both treatment groups, along with reduced motility and vitality of the spermatozoa. In the combination group, oligospermia was achieved in 4 out of 5 animals, whereas, only 2 animals became oligospermic in the agonist alone group. Significant decrease in serum testosterone levels along with impaired libido and other testosterone withdrawal symptoms were observed in the Buserelin alone group, conversely normal testosterone levels and libido were observed in the combination group. An elevation in haematological variables and serum total protein concomitant with a slight gain in body weight of the animals were recorded in the combination group; these changes were not encountered in the agonist alone group. Reversibility of all the altered parameters to control range was observed in both treatment groups following 75 to 90 days of treatment withdrawal.
Chinese hamster ovary (CHO-WBLT) cells growing in McCoy's 5a with 10% fetal bovine serum (FBS) were adapted to 0.5% FBS in CHO-1 Complete Media System, a serum-free medium from Ventrex. Cells in these two media were exposed to 10(-7) M and 10(-8) M mitomycin C (MMC) for 24 h. Comparison of cell growth over 10 days showed that cells in 0.5% serum proliferate, though at a slower rate than cells in 10% serum. Treatment with MMC revealed that at 10(-7) M, MMC is cytotoxic to cells to both the media; at 10(-8) M, MMC is non-cytotoxic to cells in both media.
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The case presented is of a patient with migratory polyarthritis and serological evidence of a recent streptococcal infection, consistent with the diagnosis of acute rheumatic fever, who in addition had multisystem disease manifestations. This case supports the concept that the sequelae of streptococcal infection can encompass a broader clinical spectrum than is suggested by the Jones criteria for the diagnosis of acute rheumatic fever.
We report uptake of a thymidine analogue 125-Iodine-5-iodo-2'-deoxyuridine (125IUdR) by nude mice bearing human xenografts of choriocarcinoma or colonic cancer. When 125IUdR was given alone, uptake by intestinal tissues was 5-10 times greater than by the tumours as measured by tissue gamma counting. This ratio was reversed when hydroxyurea or cytosine arabinoside were used as inhibitors of ribonucleotide reductase and were given in combination with 5-fluorouracil or methotrexate to inhibit thymidine synthesis shortly before injecting 125IUdR. Counting the radioactivity in tissues removed 24 hours after 125IUdR gave tumour to highest normal tissue ratios of up to 15:1, but the corresponding nuclear grain counts, which is probably a more reliable indicator of selective uptake into DNA, were in excess of 100:1. The addition of unlabelled IUdR to the regimen only reduced the uptake of 125IUdR when given in relatively large amounts. For this approach to be exploited it is concluded that the tumour must be resistant at the cell level to the inhibitor of DNA synthesis either de novo or as a result of prior exposure to it. This inhibitor can then be used to block uptake of the potentially toxic nucleoside analogue by normal renewal tissues while it is taken up by the resistant cancer cells. By inhibiting synthesis of the corresponding normal nucleosides with inhibitors to which the cancer cells are not resistant, incorporation of the toxic analogues into tumour DNA was enhanced. Although 125IUdR is a convenient agent for exploring this approach and is highly cytotoxic when incorporated in DNA, the clinical potential of reverse role chemotherapy probably lies with the development of toxic non-radioactive nucleoside analogues.
The effect of hydroxyurea on blood viscosity was studied in 10 patients with Philadelphia chromosome positive chronic myelogenous leukemia (CML) and hyperleukocytosis (white blood cell counts over 200 x 10(9)/l). All the patients had visible manifestations of leukostasis such as headache, blurred vision, retinal hemorrhage, pulmonary infiltrates, etc. Contraves LS 30 viscometer was used to measure the blood viscosity at 37 degrees C and at different shear rates on paired leukemic blood samples obtained before and after the hydroxyurea treatment. The blood viscosity was significantly higher in CML patients then normal subjects and decreased after treatment with hydroxyurea. In all the cases plasma viscosity was unaffected by the treatment.
Myasthenia gravis (MG) occurs in up to 44% of patients with thymoma. Thirty-three percent of these neoplasms are invasive but extrathoracic disease is rare. Recently, we saw a patient with MG and recurrent, metastasizing mixed lymphoepithelial thymoma, whose disease was resistant to combination chemotherapy and radiotherapy but who responded dramatically to treatment with daily glucocorticoids. Thus, therapy with daily glucocorticoids should be considered in the treatment of invasive or metastatic thymoma associated with MG, including when conventional surgery, radiotherapy, and chemotherapy have failed.
Highly purified gossypol acetic acid (5 mg/day; oral) alone and in combination with potassium chloride (0.25 mg/day; oral) was tested in adult male langurs for 120 days to evaluate reversibility of its antifertility action and possible hypokalemia. The treatment resulted in severe oligospermia with impairment of sperm motility. Sperm morphological defects were evident. The functional activities of accessory sex glands and libido remained unimpaired. Occurrence of hypokalemia was found more pronounced in the gossypol alone group. Extensive renal potassium loss was evident and conversely the renal excretion of sodium decreased markedly. The activities of serum transaminases increased significantly. Other parameters of blood and of urine did not show any marked alterations. Complete reversal of the above changes was evident following 90 to 105 days of withdrawal of treatment. In conclusion, the oligospermia achieved was reversible and the hypokalemic response of langurs is similar to human and not related to impurity of the drug.
Strokes in young adults are uncommon and often a diagnostic challenge. A retrospective study of strokes due to intracerebral hemorrhage, subarachnoid hemorrhage, or cerebral infarction was undertaken. We reviewed the medical records of 113 young patients aged 15-45 years who were admitted to the Medical Center Hospital of Vermont with a diagnosis of stroke between 1982 and 1987. This group comprised 8.5% of patients of all ages admitted for stroke, 2.3 times the proportion observed in the National Survey of Stroke. Nontraumatic intracerebral hemorrhage was diagnosed in 46 young patients (41%); the main causes included aneurysms, arteriovenous malformations, hypertension, and tumors. Subarachnoid hemorrhage was found in 19 young patients (17%); the majority were due to aneurysms. The remaining 48 young patients (42%) had cerebral infarction, the majority due to cardiogenic emboli and premature atherosclerosis. Mitral valve prolapse, the use of oral contraceptives, alcohol drinking, and migraine were infrequent sole causes of cerebral infarction in the absence of other risk factors. The case-fatality rate for this group of young patients with stroke was 20.4% compared with 23.9% for the National Survey of Stroke. Young adults with stroke deserve an extensive but tailored evaluation, which should include angiography and echocardiography.
We present a kindred with a previously undescribed combination of neuronal Charcot-Marie-Tooth disease, ptosis, parkinsonism, and mild dementia. The propositus, a 72-year-old man, had pes cavus, peripheral neuropathy, ptosis, parkinsonism, hyperreflexia, orthostatic hypotension, central hypoventilation, and mild dementia. Peripheral electrophysiologic studies showed features of an axonal neuropathy. The electroencephalogram showed intermittent 2 to 4 Hz activity symmetrically in the hemispheres. Several family members in 3 generations had pes cavus, neuropathy, ptosis, parkinsonism, and dementia although not all of the features were consistently present. Survival past the 7th decade was common. Autopsy in 2 affected members revealed the neuropathy to be axonal in type and showed mild to moderate loss of anterior horn cells in the spinal cord and pigmentary loss with gliosis in the substantia nigra. This is a unique, benign, autosomal dominant syndrome which shows complete penetrance, variable expression, and both central and peripheral nervous system involvement.