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Biomedical subjects

S L Carney

Publications and source records attributed to S L Carney.

At least 55 records · Page 3Linked to original sources

Effects of tiaprofenic acid and other NSAIDs on proteoglycan metabolism in articular cartilage explants.

Using in vitro methods, we have determined the effects of four NSAIDs on the biosynthesis and turnover of proteoglycans in articular cartilage explants. Over the concentration ranges examined (5 X 10(-7) to 10(-5) mol/L for tiaprofenic acid, naproxen and indomethacin; 5 X 10(-5) to 10(-3) mol/L for aspirin), all the drugs examined, except tiaprofenic acid, reduced the rate of proteoglycan synthesis compared with control tissue. All of the compounds examined reduced the turnover rate of newly synthesised proteoglycans. The products of turnover of explants treated with the various NSAIDs did not appear to be significantly different from those produced by control tissue, as assessed by gel chromatography and electrophoresis. There were some indications, however, of quantitative differences in distribution on both these analytical systems. These results indicate that with the exception of tiaprofenic acid all the NSAIDs examined produced a general reduction in chondrocyte metabolic activity. Thus it seems unlikely that tiaprofenic acid would have a direct detrimental effect on articular cartilage during long term administration.

Animals↗

Effect of parathyroid and antidiuretic hormone on water and calcium permeability in the rat collecting duct.

Because the rat papilla has parathyroid hormone (PTH)-sensitive adenylate cyclase and because of indirect evidence that PTH may alter collecting duct water and also calcium transport, the effects of PTH on rat papillary collecting duct water and calcium transport have been studied. PTH in concentrations of 50 and 500 ng/ml significantly increased diffusional water permeability by 20 and 38%, respectively, while 5,000 ng/ml had no additional effect. This permeability response was small when compared to a 78% increase in water permeability with a maximal (0.5 ng/ml) concentration of antidiuretic hormone (ADH). The normal increase in water permeability with ADH was depressed in the presence of PTH (500 ng/ml) but was overcome when the ADH concentration was increased from 0.5 to 5 ng/ml. Neither PTH nor ADH altered the permeability of the collecting duct to calcium which was low (0.19 +/- 0.03 micron/s). Increasing either the bath or perfusate calcium concentration from 1 to 5 mM did not alter calcium permeability. These studies suggest that PTH acts as a partial agonist to ADH within the papillary collecting duct and that PTH is unlikely to have a major role in collecting duct calcium transport.

Animals↗

Drug effects on a novel model of connective tissue breakdown.

Production of a granulomatous tissue adjacent to cartilage implants in subcutaneous tissues of mice by prior wrapping of cartilage with cotton, induces matrix depletion and a rise in serum levels of the acute phase protein haptoglobin. The granulomatous reaction to cotton could be inhibited partially, following treatment of mice with indomethacin, dexamethasone and cyclophosphamide but only the latter two reduced cartilage matrix loss. D-penicillamine was inactive. Regarding the acute phase response, dexamethasone and D-penicillamine appeared to lower and indomethacin and cyclophosphamide to elevate, serum levels of haptoglobin, but these effects were not statistically significant.

Animals↗

Effects of captopril on circulating T lymphocyte subsets.

Six patients treated with captopril for severe essential hypertension were studied to determine whether the drug significantly altered circulating peripheral blood T (Thymus derived) lymphocytes and T lymphocyte subsets. OKT3+ (functionally mature T lymphocytes), OKT4+ (class II major histocompatibility complex [MHC] reactive T lymphocytes) and OKT8+ (class I MHC reactive T lymphocytes) T lymphocytes were monitored using monoclonal antibodies and flow cytometry before commencement of treatment and then at intervals during 14 months of captopril administration. Results showed a significant increase in the absolute numbers of OKT4+ cells at 2 h (p less than 0.05) and a decrease at 12 weeks (p less than 0.01) during captopril treatment. These findings indicate that captopril has an effect on cellular immunity in vivo.

Aged↗

Effect of trial therapy on subsequent therapy. A review of patients with hypertension who have completed a pharmacological intervention study.

After a clinical trial was completed in which two commonly used antihypertensive agents (prazosin and propranolol) were compared, 20 previously untreated men with moderate, asymptomatic, essential hypertension returned to the care of their general practitioners. Twelve months later 17 patients who were still attending the same doctor demonstrated improved blood pressure control with a decrease in their lying diastolic blood pressure from 96 +/- 2 mmHg to 91 +/- 2 mmHg (P less than 0.01). Only two of the 17 patients had not by then achieved satisfactory control. Eleven patients (65%) were still taking at least one of the trial medications; clinicians seemed to prefer prazosin (10 patients). Only one of seven patients was still taking propranolol although five patients had begun treatment with other beta-blocking agents. One patient had ceased drug treatment. This survey indicates that many general practitioners are able to maintain or even improve blood pressure control in patients whose blood pressure has been stabilized initially. However, the reasons for the medication preference were unclear and studies of the clinical behaviour that influences a general practitioner's choice of medication are required.

Adult↗

Electrophoresis of 35S-labeled proteoglycans on polyacrylamide-agarose composite gels and their visualization by fluorography.

We have developed techniques for the electrophoresis of 35S-labeled proteoglycans on polyacrylamide-agarose gel slabs and subsequent fixation, impregnation, and fluorography of such electrophoretograms. The procedure permits the examination of newly synthesized proteoglycan subspecies using a rapid technique, previously unavailable for these labeled molecules.

Adolescent↗

Satisfaction of patients with medical student's clinical skills.

A patient satisfaction-dissatisfaction rating scale was developed to measure patients' perceptions of the attitudes and communication skills of medical students. An 11-item questionnaire was completed by trained patients following an end-of-year clinical assessment of the first- and third-year students of a five-year training program. The patients rated 80 percent of the first-year students and 90 percent of the third-year students as acceptable as future doctors. The patients showed a statistically significant preference for the third-year students (p less than 0.05). To assess the reliability over time of patient reactions, two consecutive third-year student groups were compared, and no significant differences in patient satisfaction-dissatisfaction were apparent. The patients tended to perceive female students as more satisfactory than male students. A weak positive correlation between faculty assessments of students and those of the patients was observed. These results suggest that patients are capable of detecting small general improvements in students' attitudes and general manner across years of training and that the patients' ratings are reliable over time.

Australia↗

Diuretic-induced hypokalemia and altered renal function.

The effect of a maximal dose of a commonly used diuretic, chlorthalidone, on renal function was assessed in 6 patients with untreated essential hypertension. 100 mg daily of chlorthalidone for a 4-week period produced a significant fall in the plasma potassium concentration and total body potassium content by 16 and 4.2%, respectively. Associated with this change in body potassium status was a 10% decrease in the maximum urine concentrating capacity (p less than 0.01). Renal plasma flow, but not glomerular filtration rate, was also depressed (9.2%) by diuretic therapy. These results suggest that small diuretic induced deficits in the plasma potassium concentration as well as the total body potassium status interfere with renal tubular function.

Aged↗

Structure of newly synthesised (35S)-proteoglycans and (35S)-proteoglycan turnover products of cartilage explant cultures from dogs with experimental osteoarthritis.

The structure of newly synthesised proteoglycans from explant cultures of cartilage from joints subjected to transection of the anterior cruciate ligament (osteoarthritic) and from normal (non- or sham-operated) joints was examined. The structure of the products of proteoglycan turnover was also examined using explants of normal and osteoarthritic cartilage maintained in culture for a 48 h chase period. The findings were as follows: Newly synthesised (35S)-proteoglycans extracted from cartilage explants from osteoarthritic joints whether examined 3 weeks, 3 months, or 6 months after surgery were larger than those from corresponding normal cartilage. This can be explained by the synthesis in osteoarthritic cartilage of abnormally long chondroitin sulphate chains on newly synthesised proteoglycans. The extracts also contained a newly formed small proteoglycan species that was unable to interact with hyaluronic acid. The proportion of this species was higher in osteoarthritic cartilage compared with normal, examined 3 weeks after surgery, but was generally absent from cartilage obtained 3 and 6 months after surgery. Compared with controls, a smaller proportion of the (35S)-proteoglycans released into the maintenance medium of explant cultures of osteoarthritic cartilage during a 48 h chase period was able to interact with hyaluronic acid. However, although furnished with longer (35S)-glycosaminoglycan chains, these proteoglycans were smaller than those from control explants.

Animals↗

Effect of indomethacin on urine concentration and dilution in the rat.

The precise role of prostaglandins in modulating urine concentration and dilution is unclear. Evidence in vitro has recently cast doubt on the accepted theory that renal prostaglandins inhibit the hydro-osmotic effect of vasopressin. Urine clearance studies were performed on indomethacin treated (prostaglandin deficient) and control anaesthetized water diuretic rats both before and during the addition of vasopressin in maximal (10 m-units) and supramaximal (100 m-units) concentrations. Before the addition of vasopressin, indomethacin treatment inhibited the excretion of a water load by 48.7%. The mean papillary sodium concentration was also greater in this group of rats. Vasopressin (10 m-units) increased the urine osmolality in control and indomethacin treated rats; however, the mean urine osmolality was greater in the indomethacin group (1521 +/- 103 compared with 1120 +/- 98 mosmol/kg; P less than 0.01), as was the papillary sodium concentration. A ten-fold increase in vasopressin depressed the papillary sodium concentration to a level similar to that in the control group and produced a marked natriuresis. Consequently, the mean urine osmolalities and urine flows were similar in control and indomethacin treated rats. These experiments suggest that a major function of renal prostaglandins is to increase the ability of the kidney to excrete a water load. Renal prostaglandins do not interfere with the vasopressin induced increase in distal nephron water permeability.

Animals↗

Effect of an optimum dialysis fluid calcium concentration on calcium mass transfer during maintenance hemodialysis.

The effect of an optimum dialysis fluid calcium concentration (1.625 mmol/l) on calcium mass transfer from dialysis fluid to patient was assessed in patients on routine hemodialysis. While there was a mean body gain of only 3.0 mmol of calcium during dialysis, a marked variation occurred with losses and gains of body calcium up to 16.4 and 18 mmol respectively. A significant correlation was noted between the mass transfer of calcium and the dialysis fluid calcium concentration (r = 0.834, p less than 0.01) which was found to vary by at least 5%. This variation was due to a manufacturing variation and not due to inaccurate dilution of the dialysis fluid concentrate. These data suggests that such a manufacturing variation may expose maintenance hemodialysis patients to periods of excessive calcium loss or gain and thereby favor renal osteodystrophy or soft tissue calcification. In keeping with published data, the mean measured dialysis fluid calcium concentration (1.61 +/- 0.02 mmol/l) should be satisfactory for most patients and it is recommended that dialysis fluid concentrates be manufactured with closer tolerance limits.

Adult↗

Demonstration of increased proteoglycan turnover in cartilage explants from dogs with experimental osteoarthritis.

The turnover of proteoglycans (assessed by the release into the medium of newly synthesised [35S]-proteoglycan) in explant cultures of articular cartilage from various anatomical sites of the knee joints (stifle) of mature beagles with experimental osteoarthritis has been studied with the following findings: (a) The proportion of newly synthesised proteoglycans released from cartilage explants maintained in vitro was generally increased for cartilage from operated compared with nonoperated control joints. (b) At 3 weeks after surgery there was a significant increase in the release of [35S]-proteoglycans from explants of the lateral and medial tibial plateaux of operated joints compared with sham-operated joints but not from other sites. On the other hand, when this comparison was made at 3 to 6 months after surgery, significant increases in the release of [35S]-proteoglycans were observed from cartilage of all anatomical areas except the patellar groove. (c) The release of [35S]-proteoglycan from cartilage explant cultures was dependent on live chondrocytes, since freeze-thawing the tissue immediately after labelling markedly reduced the release from both normal and osteoarthritic cartilage.

Animals↗

Evaluating patients' satisfaction with medical students' interviewing skills.

Two studies are reported which examine the use and credibility of patients' reports of medical students' clinical interviewing skills. In the first study patients' high satisfaction via a standard rating form tended to match clinicians' assessment of second-year students' history-taking and physical examination skills. A second study used pre-defined 'ideal' and 'not-ideal' bedside roles by a small group of fourth-year students to examine how perceptive or tolerant hospital inpatients are about clinical interviews, whether this effect is sex-linked, and consequently how useful direct and indirect information obtained from patients is in training medical students' interviewing skills.

Adult↗