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Biomedical subjects

K R Patel

Publications and source records attributed to K R Patel.

At least 91 records · Page 5Linked to original sources

The dose-duration effect of sodium cromoglycate in exercise-induced asthma.

Eight patients with exercise-induced asthma participated in a single blind dose-duration study comparing the protective effect of inhaled sodium cromoglycate (SCG) in increasing concentrations from 2 to 40 g/l. Saline was used as a control. Effects were assessed from the mean maximal fall in forced expiratory volume in 1 sec (FEV1) after running on a treadmill for 8 min at 20, 150 and 270 min after drug administration. There was no significant difference between the mean baseline values of FEV1, before and after inhalation of saline and SCG on 4 days of exercise testing. In addition, the maximal percentage falls in FEV1 in the three control exercise tests carried out at 20, 150 and 270 min after inhalation of saline were also comparable. The mean percentage fall in FEV1 (s.e.m.) after saline, SCG 2 g/l, SCG 20 g/l and SCG 40 g/l were 29.3 (4.4), 11.7 (4.5), 8.3 (3.1) and 9.4 (2.3) respectively in the first test at 20 min and 24.5 (5.1), 14.9 (4.2), 13.1 (2.5) and 13.7 (2.8) respectively in the second test at 150 after treatment. The inhibitory effect of SCG was statistically significant at all the concentrations used and the protection offered by the three concentrations of SCG was comparable. In the third exercise test at 270 min after treatment, the mean maximum percentage change after saline, SCG 2 g/l, SCG 20 g/l and SCG 40 g/l were 26.1 (4.8), 23.0 (6.1), 16.6 (5.0) and 15.8 (4.7) respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Evaluation of the human basophil degranulation test using the commercially available Baso-kit as a test of immediate-type hypersensitivity in hay-fever sufferers.

The basophil degranulation test (BDT) has failed to gain popular acceptance as a test of immediate-type hypersensitivity since its introduction in clinical medicine in 1961. Recent modification of this technique, however, seemed to have increased its reliability. We have studied a group of twenty-five hay-fever sufferers and a similar age- and sex-matched group of healthy controls to compare the sensitivity of a newly available commercial BDT kit (Baso-kit, Laboratoire des Stallergenes) with specific serum IgE levels and skin-prick tests to meadow-grass pollen. A quantitative correlation was found between the positive BDT (greater than 30% degranulation) and the skin tests, whereas only a qualitative relationship was obtained with specific IgE concentrations. The BDT also identified two subpopulations of responders and non-responders among a third group of hay-fever subjects who had previously been hyposensitized to mixed grass pollen. We conclude that the modified BDT provides a worthwhile addition to the in vitro testing of immediate-type hypersensitivity states.

Basophils↗

Sodium cromoglycate in histamine and methacholine reactivity in asthma.

The effect of increasing concentrations of inhaled sodium cromoglycate (SCG) (2, 10, 20 and 40 g/l) on histamine and methacholine bronchial reactivity was studied in nine patients with extrinsic bronchial asthma. The responses to histamine and methacholine were expressed in terms of provocative concentrations producing 20% fall in the FEV1 (PC20). The PC20 for histamine and methacholine was unaffected by all the concentrations of SCG used in the study. These results suggest that the effect of SCG on the bronchial smooth muscle or on the muscarinic receptors is minimal.

Adolescent↗

Papillomavirus research: a growth area.

Recent advances in papillomavirus research have revealed a fascinating picture of diversity among viral types, specificity of tissue infected, and oncogenic potential. Fine mapping of the viral functions may prove invaluable in furthering our understanding of the mechanisms of their interaction with, and transformation of, the host cell.

Animals↗

Suppression of liver uptake of liposomes by dextran sulfate 500.

The effect of dextran sulfate (DS, 500,000 Mr) and multilamellar vesicles (MLV) as liver blockade agents has been investigated in mice. Intravenous injection of unlabeled MLV prior to radioactive MLV caused moderate reduction in the liver uptake and increased tibia, lung, and spleen uptake. More drastic differences were observed with intraperitoneal injection of DS. When tested in the range of 0-50 mg of DS per kg of body weight, maximal liver blockade occurred at a dose of 50 mg. By using 50 mg of DS per kg, maximal liver blockade occurred at 12 hr after DS injection. The liver blockade was temporary, ending within 48 hr. The intraperitoneal route of injection for DS was more effective for liver blockade than the intravenous route.

Animals↗

The effect of inhaled verapamil on allergen-induced bronchoconstriction.

In eight patients with extrinsic bronchial asthma the effect of inhaled verapamil (3 and 6 mg) was compared with saline on bronchial challenge with extracts of Dermatophagoides pteronyssinus. There was no significant difference in the baseline FEV1 before and after inhalation of saline or verapamil 2.5 mg/ml. However, verapamil at a higher concentration (5 mg/ml) caused bronchoconstriction in four patients who had to be excluded from the part of the study. Verapamil at both these concentrations failed to have an effect on the allergen-induced bronchoconstriction. These findings suggest that verapamil given by inhalation does not prevent mediator release from the lung mast cells following specific allergen challenge.

Adolescent↗

Continuous ambulatory peritoneal dialysis and pulmonary function.

Pulmonary function tests were performed in ten patients established on continuous ambulatory peritoneal dialysis. A decrease in all lung volumes was observed after instillation of dialysate and a further decrease on change from the erect to the supine posture. This change was small and unlikely to have a functionally significant effect in patients with a healthy respiratory system. However, in patients with pre-existing lung disease, respiratory function might be further compromised.

Adult↗

Differential uptake of liposomes varying in size and lipid composition by parenchymal and kupffer cells of mouse liver.

Using liposomes differing in size and lipid composition, we have studied the uptake characteristics of the liver parenchymal and Kupffer cells. Desferal labeled with iron-59 was chosen as a radiomarker for the liposomal content, because Desferal in its free form does not cross cellular membranes. At various time intervals after an intravenous injection of liposomes into mice, the liver was perfused with collagenase, and the cells were separated in a Percoll gradient. It was found that large multilamellar liposomes (diameter of about 0.5 micron) were mainly taken up by the Kupffer cells. For these large liposomes, the rate of uptake by Kupffer cells was rapid, with maximum uptake at around 2 hours after liposome injection. Unexpectedly, small unilamellar liposomes (diameter of about 0.08 micron) were less effectively taken up by Kupffer cells, and the rate of uptake was slow, with a maximum uptake at about 10 hours after liposome injection. In contrast, parenchymal cells were more effective in taking up small liposomes and the uptake of large liposomes was negligible. In addition, liposomes made with a galactolipid as part of the lipid constituents appeared to have higher affinity to parenchymal cells than liposomes made without the galactolipid. These findings should be of importance in designing suitable liposomes for drug targeting.

Animals↗

In vitro uptake and therapeutic application of liposome-encapsulated methotrexate in mouse hepatoma 129.

The biological activities of liposome-encapsulated and non-encapsulated methotrexate (MTX) were compared in vitro and in vivo using mouse Hepatoma 129 ascites tumor cells. Under in vitro conditions, cells accumulated up to 29% of [3H]-MTX when the drug was incorporated in the lipid bilayers of positively charged, unilamellar liposomes. There was no significant uptake of non-encapsulated MTX under the same conditions. A single intraperitoneal injection of liposome-encapsulated MTX (3 mg MTX/kg) increased the mean survival time of tumor-bearing mice to 42.5 +/- 11.2 days, compared to 23.5 +/- 2.2 days for untreated controls. Non-encapsulated MTX had no significant effect on survival time. Thus the in vivo treatment studies appear to agree with the in vitro uptake measurements. Addition of galactolipids to the lipid bilayers of liposomes did not increase in vitro uptake of encapsulated MTX and gave no additional improvement in therapeutic effectiveness. Encapsulation of MTX in liposomes might thus be used to increase uptake of the drug in cells which may be deficient in MTX transport.

Animals↗

A comparison of ketotifen with clemastine, ipratropium bromide and sodium cromoglycate in exercise-induced asthma.

Exercise-induced asthma (EIA) was provoked by a standardized treadmill running for 8 min in seven atopic adult asthmatics. The tests were performed using a double-dummy technique after placebo, oral ketotifen, inhaled clemastine, ipratropium bromide and sodium cromoglycate (SCG), in a random single blind-fashion on different days. The mean post-exercise percentage fall in forced expiratory volume in 1 sec (FEV1) was 47 (s.e. 6.95), 39 (s.e. 8.35), 27 (s.e. 7.17), 23 (s.e. 7.69) and 7.0 (s.e. 4.62)% respectively. There was significantly less mean bronchoconstriction with SCG (P less than 0.01), ipratropium bromide and clemastine (P less than 0.05) but not with ketotifen. Six out of seven individual patients had significant protection of EIA with sodium cromoglycate, four with ipratropium bromide, three with clemastine but only one with ketotifen. Ipratropium bromide and clemastine were bronchodilators at rest, whereas SCG and ketotifen were not. Despite its claims to work as a mast cell stabilizing drug, ketotifen in a single dose does not have an effect similar to sodium cromoglycate in EIA, nor does it compare with inhaled clemastine or ipratropium bromide.

Adolescent↗

Dose-response study of sodium cromoglycate in exercise-induced asthma.

Ten patients with exercise-induced asthma participated in a single-blind dose-response study comparing the protective effect of inhaled sodium cromoglycate in increasing concentrations from 2 to 40 mg/ml. Saline was used as a control. Effects were assessed from the mean maximal percentage fall in forced expiratory volume in one second (FEV1) after the patients had run on a treadmill for eight minutes. There was slight bronchodilation evident from the increase in baseline FEV1 after inhalation of sodium cromoglycate, the difference reaching statistical significance with the highest concentration (5.7%, p less than 0.05). After exercise the maximal percentage falls in FEV1 (means and SEM) after saline and after sodium cromoglycate at 2, 10, 20, and 40 mg/ml were 37.3 +/- 4.7, 17.3 +/- 4.1, 10 +/- 3.3, 7.6 +/- 2.4, and 12 +/- 2.9. Sodium cromoglycate inhibited the exercise-induced fall in FEV1 at all the concentrations used in the study (p less than 0.001) and its inhibitory effect increased from 2 to 20 mg/ml. The mean FEV1 returned to baseline values within 15 minutes at higher concentrations of sodium cromoglycate (20 and 40 mg/ml) and a small bronchodilator effect was noted at 30 minutes. The findings suggest that the protective effect of sodium cromoglycate in exercise asthma is dose related. At higher concentration the drug suppresses chemical mediator release from the lung mast cells and may also modify the bronchial reactivity to release mediators.

Adolescent↗

Calcium antagonists in exercise-induced asthma.

Ten patients with exercise-induced asthma participated in a single-blind trial comparing the protective effects of inhaled verapamil (estimated dose 3 mg) and sodium cromoglycate (estimated dose 12 mg). Saline was used as control. Effects were assessed from the mean maximal percentage fall in forced expiratory volume in one second (FEV1) after running on a treadmill for eight minutes. There was no significant change in baseline FEV1 values after each agent. In the exercise periods, however, FEV1 fell by 45.4% (SEM 4.0) after saline inhalation, 18.4% (5.1) after sodium cromoglycate, and 16.7% (4.3) after verapamil. The inhibitory effects of sodium cromoglycate and verapamil were comparable and significantly different from saline (p less than 0.02 and p less than 0.01 respectively). Nevertheless, considerable intrasubject variability was observed. The findings suggest that mediator release, which is calcium dependent, may play an important part in exercise-induced asthma, and calcium antagonists may inhibit post-exercise bronchoconstriction by their blocking effect on calcium channels.

Adolescent↗