Search PubMed⌕ Search

Biomedical subjects

S Crowley

Publications and source records attributed to S Crowley.

At least 37 records · Page 2Linked to original sources

Labor force planning issues for allied health in Australia.

The aim of this paper is to discuss labor force planning issues for allied health professionals in Australia. Health system reform and changes in the demand for health labor, combined with key characteristics of the professions, will have a profound influence on future needs for career development of allied health professionals. Key issues include the increasing need for allied health professionals to undertake business management and public health training, the growing trend of multiskilling versus specialization, and the need for the professions to diversify their skill base to ensure a range of career options in a changing health care system. The challenge for allied health professions is to improve tools of analysis in relation to labor force planning and to systematically investigate various factors influencing labor force supply and demand, on both a short-term and long-term basis.

Allied Health Personnel↗

Nonenzymatic glycation of mesangial matrix and prolonged exposure of mesangial matrix to elevated glucose reduces collagen synthesis and proteoglycan charge.

Expansion of the mesangial matrix in diabetes occurs after prolonged exposure to the diabetic milieu. To mimic the long-term hyperglycemia of diabetes mellitus we developed tissue culture systems that might approximate the chronic state. This was accomplished in two ways: (1) by growing mesangial cells on extracellular matrix glycated and crosslinked in vitro and (2) by continuously growing cells on their own matrix on filters in elevated glucose medium (500 mg/dl) for up to eight weeks without passage. Synthesis of collagen and proteoglycans was evaluated in cells grown under these conditions. In both these situations, 3H-proline incorporation into collagenase sensitive protein and 35S incorporation into sulfated proteins were reduced compared to control cultures. Despite reduction in 35S incorporation into proteoglycans in the high glucose cultures, total glycosaminoglycan content was unchanged. However, proteoglycans generated by mesangial cells grown in elevated glucose media were of a lower negative charge than controls. In mesangial cells continuously grown on filters, the levels of messenger RNA for collagen types I and IV, biglycan and TGF-beta were not different in cells grown at elevated or standard glucose concentrations for two and four weeks. We conclude that crosslinking of mesangial matrix or continuous culture of cells for prolonged periods of time in high glucose medium, which may also crosslink matrix, suppresses collagen synthesis and reduces the negative charges on matrix proteoglycans without altering mRNA levels.

Animals↗

Outpatient follow-up in women with HIV infection in Parkside Health Authority (UK).

OBJECTIVE: To describe patterns of attendance for follow-up among HIV infected women in Parkside, UK and their correlates. DESIGN: Retrospective cohort study. SUBJECTS: 103 HIV infected women. MAIN OUTCOME MEASURES: Whether patients attended for follow-up between three and 18 months. RESULTS: 31% of women were married and 46% had children. Women born in sub-Saharan Africa were significantly less likely to attend for follow-up after three months (56%) than women born in other areas who had acquired HIV either heterosexually (82%) or through injecting drug use (81%). This pattern persisted on multivariate analysis controlling for whether women were symptomatic, had had a previous positive test, were married or had children. CONCLUSIONS: HIV positive sub-Saharan African women are less likely to reattend for follow-up than women with heterosexually acquired HIV from other areas or those who acquired infection through intravenous drug use. Further studies are needed to identify barriers to follow-up for women and to shape the development of more appropriate and accessible services for HIV infected women, especially those of sub-Saharan African origin.

Adult↗

Reproducibility of the cortisol response to stimulation with a low dose of ACTH(1-24): the effect of basal cortisol levels and comparison of low-dose with high-dose secretory dynamics.

We compared the reproducibility and repeatability of the acute adrenal response to low doses (90 and 500 ng/1.73 m2) of Synacthen (ACTH(1-24)) with that of the standard dose (250 micrograms/1.73 m2). We also examined the effect of basal cortisol levels on peak values achieved after stimulation with a low dose. ACTH(1-24) was given to six male volunteers: 90 ng/1.73 m2 twice at 90-min intervals on day 1, and 90 and 500 ng/1.73 m2 once on day 2 and 250 micrograms/1.73 m2 once on day 3. The rise in serum cortisol concentration with repeated low doses of ACTH was not attenuated (161 +/- 49 (S.D.) nmol/l on initial vs 150 +/- 41 nmol/l on repeat stimulation; P = 0.5) and this was reproducible (161 +/- 49 nmol/l on day 1 vs 148 +/- 15 nmol/l on day 2; P = 0.6). A dose of 500 ng ACTH(1-24)/1.73 m2 produced a maximal adrenal response in that the rise in serum cortisol concentration at 20 min was identical with that produced at the same time by the standard dose of 250 micrograms/1.73 m2. There was a strong positive correlation between the basal cortisol level and peak cortisol concentration after low-dose ACTH stimulation (r = 0.93, P < 0.001) but not between the basal cortisol level and the incremental rise (r = -0.1, P = 0.69). These results suggest that the cortisol response to low-dose ACTH stimulation is reproducible and not attenuated by repeat stimulation at 90-min intervals.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex↗

The effect of glucose on proteoglycans produced by cultured mesangial cells.

Altered proteoglycan metabolism may play a role in the development of diabetic glomerulopathy. This study was conducted to examine the effects of glucose on the production and physical characteristics of proteoglycans generated by rat mesangial cells in culture. Rat mesangial cells were exposed to elevated glucose media (500 mg/dl) or standard glucose media (200 mg/dl) for 8-10 days, and proteoglycan synthesis was determined using 35S-labeling in conjunction with anion exchange and sizing chromatography. Rat mesangial cells generated predominantly chondroitin/dermatan sulfate proteoglycans, with small amounts of heparan sulfate proteoglycans. High glucose did not alter the number of rat mesangial cells after 24 h or after 8-10 days, compared with cells grown under standard glucose conditions. The total amount of glycosaminoglycan generated and the sizes of the major proteoglycans were not different between cultures grown in standard and elevated glucose medium. Levels of mRNA for the proteoglycan, biglycan (as assessed by Northern blot analysis), also were comparable between the standard and elevated glucose conditions. Exposure to media high in glucose did not change the rate of secretion of proteoglycans from the cell layer to the medium, but did result in a greater quantity of radiolabeled proteoglycan deposited in the extracellular matrix. The cell, extracellular matrix and medium proteoglycans isolated from the elevated glucose cultures, consistently eluted from the anion exchange column at a lower [NaCl] compared with those generated under standard glucose conditions, indicating a loss of anionic charges.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Risk of second brain tumour after conservative surgery and radiotherapy for pituitary adenoma.

OBJECTIVE: To assess the risk of second brain tumour in patients with pituitary adenoma treated with conservative surgery and external beam radiotherapy. DESIGN: Long term follow up of a cohort of patients with pituitary adenoma and comparison of tumour occurrence with population incidence rates. SETTING: The Royal Marsden Hospital. SUBJECTS: 334 patients with pituitary adenoma treated with conservative surgery and radiotherapy (median dose 45 Gy) and followed up for 3760 person years. MAIN OUTCOME MEASURES: Second intracranial tumour and systemic malignancy. RESULTS: Five patients developed a second brain tumour: two had astrocytoma, two meningioma, and one meningeal sarcoma. The cumulative risk of developing a second brain tumour over the first 10 years after treatment was 1.3% (95% confidence interval 0.4% to 3.9%) and over 20 years 1.9% (0.7% to 5.0%). The relative risk of a second brain tumour compared with the incidence in the normal population was 9.38 (3.05 to 21.89). There was no excess risk of any other type of second primary malignancy. CONCLUSIONS: There is an increased risk of second intracranial tumour in patients with pituitary adenoma treated with surgery and radiotherapy. Although radiation is likely to be the most important factor contributing to the excess risk, further study is required in a cohort of similar patients not receiving radiation.

Adenoma↗

Interactions of LDL and modified LDL with mesangial cells and matrix.

Hyperlipidemia may play a role in the progression of diabetic and other renal diseases. Low density lipoprotein (LDL) and other proteins including extracellular matrix components undergo nonenzymatic glycation in vivo. We examined the effects of glycation of LDL as occurs in diabetes (4 to 8%) on binding and uptake by mesangial cells and their proliferation. The glycation of LDL (g-LDL) significantly decreased its binding and uptake by mesangial cells by 15 to 20%, indicating that glycated LDL binds to the LDL receptor, but with lower affinity than LDL. Both LDL and g-LDL modestly stimulated [3H] thymidine incorporation into mesangial cells at 5 to 10 micrograms/ml. Native, oxidized (Ox-LDL) and glycated LDL all bound to the extracellular matrix generated by rat mesangial cells in culture. The binding of LDL, Ox-LDL and g-LDL to mesangial matrix was two to four times higher than to mesangial cells. Binding of LDL and g-LDL was significantly higher to glycolaldehyde modified matrix, which serves as an in vitro model for nonenzymatic glycation end-product cross-linking of matrix which occurs in long-standing diabetes. Based on these findings, we propose that glycation of LDL decreases its binding and uptake by the LDL receptor of mesangial cells and may slow its catabolism. Furthermore, LDL bound to extracellular mesangial matrix can undergo oxidation and generate cytotoxic LDL components. This process may be further enhanced by advanced glycation of the mesangial matrix in diabetes, contributing to glomerular pathology.

Animals↗

Immunofluorescent labeling using covalently linked anti-phycoerythrin antibodies and phycoerythrin polymers.

We have developed methods for covalently attaching anti-phycoerythrin (PE) MAbs to other antibodies, and for using PE or polymers of PE in conjunction with these conjugates to rapidly produce specific, high intensity fluorescent labeling of antigens. The performance of these systems was examined on the surface of microspheres and on the cell surface. The noncovalent means by which PE is incorporated into the label complex in this method makes it possible to use crude algal homogenate successfully as a source of PE in immunofluorescence assays. The intensity of labeling achieved using this method is comparable to, or in some cases better than, that obtained using a direct PE conjugate. With the aim of amplifying the intensity of fluorescence obtained, we produced two types of covalently linked complexes. These were an anti-PE MAb, designated PE6, linked to itself (i.e., PE6-PE6), and PE linked to itself (i.e., PE-PE). When used in a two-stage procedure in place of monomeric PE alone, these complexes increased the intensity of fluorescence obtained on the surface of microspheres by more than fourfold. On the cell surface, the performance of this system varied from one antigen to the next but in most cases was restricted to, at best, a 60% increase in the intensity of fluorescence and in many cases only about a 30% increase.

Antibodies, Monoclonal↗

The use of low doses of ACTH in the investigation of adrenal function in man.

We have investigated the adrenal response, in eight healthy adult men, to low doses of ACTH(1-24) in order to define a dose which will elicit a response similar to that obtained with the short Synacthen test. The studies were performed at 14.00 h and blood samples were withdrawn at 5-min intervals after an i.v. bolus injection of ACTH(1-24). The sampling interval was crucial in determining the timing of the peak response. Using sampling times of 0, 10, 15, 20, 25 and 30 min ensured detection of 47 out of 48 peaks. A dose-dependent rise in plasma cortisol concentration was observed with bolus injections of ACTH(1-24) between 30 and 250 ng/1.73 m2 body surface area. Increasing the dose to 500 ng/1.73m2 (500 times less than that used in the short Synacthen test) elicited an increment of plasma cortisol concentration of 200 nmol/l or greater in all subjects. Pretreatment with dexamethasone (1 mg) did not alter the timing of the peak cortisol concentration but blunted the increase (pretreatment: median, 159 nmol/l; range 83-239; on dexamethasone; median 62 nmol/l; range 21-207; P = 0.04). These data suggest that a dose of ACTH(1-24) of 500 ng/1.73 m2 satisfies the criteria of the short Synacthen test and may provide a useful method of investigating adrenal function.

Adrenal Glands↗

Resolution of nephrotic syndrome and lack of progression of heroin-associated renal amyloidosis.

The case of a patient with nephrotic syndrome and renal insufficiency due to renal amyloidosis secondary to chronic subcutaneous heroin abuse who discontinued her drug habit is reported. During the 6 years following the initial renal biopsy, the patient's nephrotic syndrome remitted: urinary protein decreased from 6.8 g/d to 170 mg/d, serum albumin increased from 2.5 g/dL to 3.9 g/dL, and she was no longer edematous. Serum creatinine remained stable at 1.8 mg/dL and creatinine clearance was also unchanged at 34 mL/min. Repeat renal biopsy showed AA amyloidosis involving the glomeruli, with minimal interstitial inflammation. This appears to be the first case of clinical improvement in heroin-associated renal amyloidosis after cessation of drug injections. As in other cases of AA amyloidosis that have improved, the clinical picture does not correlate with the findings on renal biopsy.

Amyloidosis↗

Controlled clinical trial of ranitidine in bleeding peptic ulcer.

One hundred and two patients were entered into a controlled, randomized clinical trial to assess the value of ranitidine versus placebo, given immediately after entry to hospital to modify the outcome of patients admitted to hospital with acute bleeding from peptic ulceration of the stomach or duodenum. The results indicated that ranitidine could not significantly modify the blood requirements, rebleeding rate or operation rate in this patient population during the initial hospital admission.

Clinical Trials as Topic↗