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Biomedical subjects

H Sharma

Publications and source records attributed to H Sharma.

At least 55 records · Page 3Linked to original sources

Initial sensitivity, acute tolerance and alcohol consumption in four inbred strains of rats.

Initial sensitivity and acute tolerance to ethanol were determined in a jumping test in separate groups of spontaneously hypertensive (SH) and normotensive Wistar-Kyoto (WKY) rats, and of Dahl salt-sensitive (SS) and salt-resistant (SR) rats. One week later, voluntary consumption of ethanol was studied in all groups. SH rats were found to be more sensitive than WKY, but there was no difference in acute tolerance development between these two strains. SH rats, however, drank significantly more alcohol than the WKY in both the two-bottle choice paradigm and the limited access model. Similarly, SS rats drank significantly more alcohol than the SR rats, although SS rats were found to be more sensitive to ethanol than SR. There was again no difference in acute tolerance development between these two strains. These observations suggest that difference in alcohol consumption in these strains cannot be accounted for by significant differences in acute tolerance or in initial sensitivity to ethanol.

Alcohol Drinking↗

The tissue distribution in rats of [195mPt]carboplatin following intravenous, intraperitoneal and oral administration.

[195mPt]carboplatin has been administered intravenously, intraperitoneally and orally to Wistar rats and the tissue distribution, metabolism, and pharmacokinetics of the drug investigated. The urinary and faecal excretion and toxicity following oral [195mPt]carboplatin administration has also been studied. Virtually identical results have been observed following i.v. and i.p. administration, indicating a rapid absorption of the unaltered compound from the abdominal cavity into the systemic circulation. Thus i.p. administered drug should produce a similar therapeutic response as i.v. administration, but may produce an additional local effect within the peritoneal cavity. Orally administered compound shows a pattern of distribution which is similar to that following parenteral injection for all tissues (except for the increased relative concentration in the stomach tissue), the concentration being lower by a factor of 4-5. However, the overall fraction of the dose retained within the body at 24 h is similar to that following i.v. administration. The toxicity is considerably lower for the orally administered drug compared with i.v. injection. These results clearly show that oral doses could be adjusted to produce a comparable therapeutic effect as i.v. or i.p. doses, and should also result in a higher efficacy against gastric carcinomas than achievable with parenteral administration.

Administration, Oral↗

Effects of shear stress on endothelial cell monolayers on expanded polytetrafluoroethylene (ePTFE) grafts using preclot and fibronectin matrices.

Animal studies have shown that endothelial seeding of vascular prosthetic grafts reduces thrombogenicity and improves their patency. However, for endothelial seeding to be of clinical benefit in humans, it must withstand shear stress of blood flow. Endothelial cells labelled with Indium-111-oxine were seeded in supra-confluent densities on preclot or fibronectin coated ePTFE graft segments over a period of 90 min. These grafts with rapidly formed endothelial cell monolayers were then exposed to varying shear stresses up to a flow rate of 300 ml/min, using tissue culture medium in an artificial flow circuit. Grafts coated with preclot matrix showed 2 h cell retentions of 82.4 +/- 6.8% at 25 ml/min, 79.9 +/- 8.2% at 100 ml/min, 75.4 +/- 9.5% at 200 ml/min and 58.3 +/- 15.5% at 300 ml/min whilst those for the fibronectin matrix were 57.8 +/- 9.9%, 55.2 +/- 13.3%, 55.4 +/- 12.9% and 56.5 +/- 15.2% respectively. Overall the preclot matrix was found to be better than fibronectin (P less than 0.001). Light and scanning electron microscopy revealed well-formed endothelial cell monolayers retained on preclot matrix up to a flow rate of 200 ml/min whereas uncovered patches were seen at 300 ml/min and at all flow rates on fibronectin matrix.

Blood Coagulation↗

Fibronectin coating of expanded polytetrafluoroethylene (ePTFE) grafts and its role in endothelial seeding.

Although fibronectin's role as a matrix to improve endothelial seeding has been demonstrated by other workers, the optimum concentration for use has never been described. Attachment of fibronectin to expanded polytetrafluoroethylene (ePTFE) was measured, using 125I-radiolabeled protein, at different concentrations and for different time periods. The absolute amount of fibronectin bound to the graft increased with the concentrations used in coating (p less than 0.001) and also with time (p less than 0.01); e.g., at 50 micrograms/ml, 90 min of incubation produced a molecular attachment of 4.0 x 10(11)/cm2 of graft. However, its percentage attachment decreased with a rise in concentration (p less than 0.001). After an initial loss of 22% in 30 min, the fibronectin-graft bond was found to be stable when exposed to a shear stress produced by flow at 200 ml/min. No significant difference in the cell adherence could be found in grafts coated with fibronectin concentrations of 50, 150, and 250 micrograms/ml, although it was significantly less at 10 and 25 micrograms/ml (p less than 0.05).

Blood Vessel Prosthesis↗

Nasal myiasis: review of 10 years experience.

Nasal myiasis is a manifestation of the nasal cavities by larvae of the fly of genus Chrysomia. It is prevalent in tropical countries. Atrophic rhinitis is the most commonest predisposing factor for this condition. The maggots can cause extensive erosion of the nose, face and intra-cranial structures occasionally causing meningitis and death. Conservative management by packing the nose with a chloroform and turpentine (1:4) mixture followed by manual removal of the dead maggots is an effective method. Recurrence is known but partial closure of both nostrils to improve the condition of nasal mucosa is the important part of management.

Adolescent↗

An autoradiographic study of the intrarenal localisation and retention of cisplatin, iproplatin and paraplatin.

The intrarenal localisation of platinum following the intravenous administration of platinum-195m-labelled cisplatin, iproplatin and paraplatin was studied using autoradiography. Following injection of cisplatin, platinum was distributed throughout the kidney even up to 14 days after treatment. In the case of iproplatin and paraplatin rapid platinum clearance was noted from the glomeruli, blood vessels and renal medulla within 2 h of administration. Relative cortical and medullary platinum radionuclide concentrations for all three agents were determined by Chalkley grid analysis. This showed greater relative concentrations of platinum in the cortex at increasing times following iproplatin and paraplatin compared with cisplatin. It is suggested that the lower renal toxicity of iproplatin and paraplatin than of cisplatin may be due to reduced platinum retention within the pars recta.

Animals↗

A method for the production of iron-52 with a very low iron-55 contamination.

The production and radiochemical separation of 52Fe from 4He irradiation of enriched 50Cr target is described. Methods developed for the recovery of the target material (50Cr) are also described. The yield of 52Fe at 38 MeV incident 4He energy is 1667 +/- 133 MBq/C (163 +/- 13 microCi/microAh) at end of bombardment and the contamination of 55Fe is only 0.008%.

Chromium Isotopes↗

114Inm oxine-labelled lymphocytes--therapeutic applications.

It has shown that, after intravenous administration of autologous lymphocytes labelled with the beta-emitting radionuclide 114Inm, the cells initially migrate normally before succumbing to the toxic effects of the radiation. The radioactive material is then released from the cell and taken up by neighbouring radioresistant macrophages, thereby localizing a field of radiation to the site of lymphocyte death. Using this technique, lymphocytopoenia has been produced in rats. We have measured the whole-body distribution and excretion of radioactivity in patients who received escalating activities of 114Inm-labelled lymphocytes. All patients had active non-Hodgkin's lymphoma involving the spleen and liver which proved resistant to combination chemotherapy and conventional radiotherapy. Following intravenous administration, the labelled cells cleared rapidly from the vasculature with only 15% remaining in the peripheral blood at 30 min. The radioactivity continued to fall over the next 5 days to approximately 3% and was maintained at approximately 2% for up to 90 days. There was an almost immediate uptake of radioactivity by the spleen and liver which reached approximately 85% of the injected dose by 48 h. The localization of radioactivity stabilized by 48 h and thereafter the whole-body content fell by approximately 0.8% per day. Up to 5% of the administered radioactivity accumulated in the bone marrow. The activities administered were too low to produce a therapeutic response and no toxicity was experienced by the patients. A therapeutic study at higher activities is now underway.

Humans↗

A rat model of herpes encephalitis with special reference to its potential for the development of diagnostic brain imaging.

A rat model of herpes encephalitis using intraocular inoculation of herpes simplex virus strain SC16 was investigated. Virus distribution in the brain was examined by virus isolation and immunocytochemical staining using immuno-gold silver and peroxidase-anti-peroxidase. At 5 days post-infection virus was found in the thalamus, hypothalamus, septum, colliculus, geniculate bodies, the pons, trapezoidium and medulla oblongata, but less frequently, in the cerebellum and occipital lobes. Possible routes of spread of virus and the potential of this model in neuro-radiological scanning procedures are discussed.

Animals↗

Production of gallium-66, a short-lived, positron emitting radionuclide.

The excitation functions for the production of 66Ga and some other radionuclides produced by the 4He-particle bombardment of a natural copper target have been measured up to 31 MeV incident energy. The radiochemical separation of 66Ga from the irradiated copper target as well as from the other radionuclides formed is described. The yield of 66Ga at 18 MeV incident energy is 708 microCi/microAh at end of bombardment and the contamination of 67Ga is 0.25%. The intended use of the 66Ga produced is to label monoclonal antibodies for PET scanning.

Gallium Radioisotopes↗

Measurement of radiation dose to the thyroid using positron emission tomography.

Measurements of the functioning volume of thyroid tissue have been made in 22 patients undergoing radioiodine therapy for thyrotoxicosis, using a prototype multiwire proportional counter positron camera. Tomographic images were produced of the distribution of 124I in the thyroid. Functioning volumes were found to be in the range 21-79 cm3 with volume errors of the order of +/- 4% to +/- 14%. Radioiodine uptake varied from 28% to 98%. Using a value of 6 days for the effective half-life of radioiodine in hyperactive thyroids, radiation doses from a standard therapy administration of 75 MBq of 131I varied from 11 to 48 Gy (compared with a recommended 50-70 Gy). In five cases PET imaging showed a non-uniform distribution of radioiodine in thyroids thought to have uniform uptake from conventional pinhole scintigraphy.

Humans↗

Production of cobalt-55, a short-lived, positron emitting radiolabel for bleomycin.

The production and radiochemical separation of 55Co from deuteron irradiation of enriched 54Fe target is described. Methods used for the recovery and reuse of the target material (54Fe) are also described. The yield of 55Co at 12 MeV incident deuteron energy is 1.7 mCi per mu Ah at end of bombardment and the contamination with 57Co is 0.016%. The 55Co produced is chelated to bleomycin and used for tumour imaging with a positron emission tomographic camera based on multi-wire proportional chamber detectors.

Bleomycin↗

Representation of the path of a non-disintegrating capsule in the gastrointestinal tract using external scintigraphy and computer graphics.

The intestinal transit rate of a single non-disintegrating object has been measured using gamma scintigraphy. Using computer graphics, a three-dimensional visualization of the data has been developed. The display enables viewing from any angle and should be of value in assessing the effect of variables on the transit of pharmaceuticals and other materials.

Capsules↗

In vivo distribution studies of radioactively labelled platinum complexes; cis-dichlorodiammine platinum(II), cis-trans-dichlorodihydroxy-bis-(isopropylamine) platinum(IV), cis-dichloro-bis-cyclopropylamine platinum(II), and cis-diammine 1,1-cyclobutanedicarboxylate platinum(II) in patients with malignant disease, using a gamma camera.

The in vivo distribution in man of the four platinum derivatives cis-dichlorodiammine platinum(II) (DDP), cis-trans-dichlorodihydroxy-bis-(isopropylamine) platinum (IV) (CHIP), cis-dichloro-bis-cyclopropylamine platinum(II) (CP), and cis-diammine 1, 1-cyclobutanedicarboxylate platinum(II) (CBDCA) has been observed. The availability of these compounds labelled with the radioactive isotope of platinum, platinum-191, has made serial in vivo imaging of their distribution possible. Injection of 17-35 MBq (5-28 mg) of the labelled compound IV was followed by imaging, using a gamma camera, with particular reference to the kidneys, liver, and tumour site. Hepatic and renal clearances were observed in all nine patients, but no unequivocal evidence of tumour uptake was found. The left kidney uptake was estimated at times up to 7 days after injection. Mathematical analysis of some of the uptake curves failed to show any significant difference between the clearance times observed. However, the two patients who received CBDCA did show a higher initial renal uptake, falling within the 1st day to levels comparable with those of the other compounds, and the three patients who received DDP showed consistently liver uptake.

Adult↗

Histopathological lesions in the pancreas of the BB Wistar rat as a function of age and duration of diabetes.

Pancreatic histopathology was studied in 121 BBWd, 43 BBWnd, and 33 Wistar rats. Insulitis was the most common inflammatory lesion in both BBW and BBWnd rats. The incidence was inversely associated with age and with duration of diabetes in BBWd rats, but there was no age-related pattern in BBWnd rats. Small end-stage islets were typical of BBWd rats but were not seen in BBWnd rats. Several BBWd rats showed hyperplastic islets months after the onset of diabetes, a pattern that is also seen in a small percentage of human JOD patients. Several non-specific exocrine inflammatory lesions occurred in both BBWd and BBWnd rats: acute and/or chronic pancreatitis, eosinophilic infiltrates, granulomatous lesions and acute and/or chronic interstitial inflammation. Only chronic interstitial inflammation was seen in outbred Wistar rats.

Age Factors↗

Massive upper gastrointestinal hemorrhage from an arteriovenous malformation of the stomach.

Arteriovenous malformations of the stomach are rare; blood loss may be manifested either by chronic anemia or by massive recurrent hemorrhage. We report a patient with massive upper gastrointestinal hemorrhage from a gastric arteriovenous malformation. Emergency operation to control hemorrhage precluded the performance of angiography; diagnosis was made from the appearance of the lesion and dilatation of the veins draining the involved area. Complete operative excision of the lesion was curative.

Angiography↗