N-terminal analysis of aggrecan fragments lost from bovine nasal cartilage cultured in the presence of recombinant human interleukin 1alpha revealed a predominant ARGSVIL sequence with an additional ADLEX sequence. Production of the ARGSVIL-containing fragments has been attributed to the action of a putative proteinase, aggrecanase. The minor sequence (ADLEX) corresponds to a new reported cleavage product; comparison of this sequence with the available partial sequence of bovine aggrecan indicates that this is the product of a cleavage occurring towards the C-terminus of the protein. Matrix metalloproteinase (MMP) inhibitors inhibited aggrecan loss from bovine nasal explants incubated in the presence of recombinant human interleukin 1alpha. A strong correlation between inhibition of aggrecan metabolism and inhibition of stromelysin 1 (MMP 3) (r=0.93) suggests a role for stromelysin or a stromelysin-like enzyme in cartilage aggrecan metabolism. However, the compounds were approx. 1/1000 as potent in inhibiting aggrecan loss from the cartilage explants as they were in inhibiting stromelysin. There was little or no correlation between inhibition of aggrecan metabolism and inhibition of gelatinase B (MMP 9) or inhibition of collagenase 1 (MMP 1). Studies with collagenase inhibitors with a range of potencies showed a correlation between inhibition of collagenase activity and inhibition of collagen degradation in the cartilage explant assay. This indicates that in interleukin 1alpha-driven bovine nasal cartilage destruction, stromelysin (or a closely related enzyme) is involved in aggrecan metabolism, whereas collagenase is principally responsible for collagen degradation.

Aggrecans↗

PubMed1997

Seasonal variation of suicide in South Africa.

Seasonal trends in South African suicide incidence were investigated with a view to ascertaining whether they are consistent with those in the northern hemisphere regarding: (1) the existence of the expected pattern; (2) this pattern being more pronounced for less urbanized groups; and (3) the presence of a secondary fall peak for youth and females. Log-linear modelling was performed to investigate the effect of month and relevant demographic variables on the suicide counts. The 16,389 nationally registered suicide deaths during 1980-1989 were analysed. The expected pattern, with a peak in the spring (that is, in September/October) or summer and a trough in winter, was present. This pattern was more pronounced for a sub-group that is less urbanized and for another sub-group with a relatively low standard of living. The secondary peak in autumn was not present for youth or females. In the northern hemisphere, this secondary peak has been ascribed to sociodemographic factors associated with the commencement of the academic year and (for females) bioclimatic factors associated with gender-specific biological circannual rhythms. The fact that the academic year commences in summer in South Africa indicates that the present findings are consistent with the former explanation.

Adolescent↗

PubMed1997

Audit of public sector primary diabetes care in Cape Town, South Africa: high prevalence of complications, uncontrolled hyperglycaemia, and hypertension.

This study was undertaken to investigate the prevalence of diabetes complications and level of glycaemic and blood pressure control in Black African patients at the primary care level in the public sector Cape Town, South Africa. A stratified random sample of 300 patients attending the three largest ambulatory diabetes clinics in community health centres in Black African residential areas of Cape Town (100 patients from each) during the last 6 months of 1992 was selected. Each patient had a clinical examination, interview, and 1 year retrospective record review. Eighty-one per cent of the sampled patients were reviewed, 90% were non-insulin-dependent (NIDDM) and 10% were treated with insulin. The mean duration of diabetes was 8 (range 0-28) years. Acceptable glycaemic control was present in 49.4% (95% Confidence Intervals 45.6-53.5) of patients while 38.5% (CI 24.8-52.2) of hypertensive patients had acceptable blood pressure control. The prevalence of any grade of retinopathy was 55.4% (CI 48.90-62.9), proliferative and preproliferative retinopathy 15.6% (CI 8.5-22.8), cataracts 7.9% (CI 4.4-11.4), peripheral neuropathy 27.6% (CI 15.2-39.4), absent foot pulses 8.2% (CI 5.2-12.6), amputations 1.4% (CI 0.4-2.4), persistent proteinuria 5.3% (CI 2.5-8.1) and an elevated albumin-creatinine ratio 36.7% (CI 29.0-44.4). The complications were not documented in the clinic records of the preceding year with the exception of 1 patient with absent foot pulses and the 12 patients with proteinuria. The high prevalence of suboptimal glycaemic and blood pressure control as well as complications of diabetes, largely unrecorded in the preceding years' clinic notes, demonstrates the deficiency of and need for preventative diabetes care at the primary care level. The design, institution, and evaluation of effective intervention programmes are a priority to improve the quality of care provided and the health of diabetic patients.

Adult↗

PubMed1997

Ro 32-3555, an orally active collagenase inhibitor, prevents cartilage breakdown in vitro and in vivo.

1. Ro 32-3555 (3(R)-(cyclopentylmethyl)-2(R)-[(3,4,4-trimethyl-2,5-dioxo-1- imidazolidinyl)methyl]-4-oxo-4-piperidinobutyrohydroxamic acid) is a potent, competitive inhibitor of human collagenases 1, 2 and 3 (Ki values of 3.0, 4.4 and 3.4 nM, respectively). The compound is a selective inhibitor of collagenases over the related human matrix metalloproteinases stromelysin 1, and gelatinases A and B (Ki values of 527, 154 and 59 nM, respectively). 2. Ro 32-3555 inhibited interleukin-1 alpha (IL-1 alpha)-induced cartilage collagen degradation in vitro in bovine nasal cartilage explants (IC50 = 60 nM). 3. Ro 32-3555 was well absorbed in rats when administered orally. Systemic exposure was dose related, with an oral bioavailability of 26% at a dose of 25 mg kg-1. 4. Ro 32-3555 prevented granuloma-induced degradation of bovine nasal cartilage cylinders implanted subcutaneously into rats (ED50 = 10 mg kg-1, twice daily, p.o.). 5. Ro 32-3555 dosed once daily for 14 days at 50 mg kg-1, p.o., inhibited degradation of articular cartilage in a rat monoarthritis model induced by an intra-articular injection of Propionibacterium acnes. 6. Ro 32-3555 is a potential therapy for the treatment of the chronic destruction of articulating cartilage in both rheumatoid and osteoarthritis.

Administration, Oral↗

PubMed1997

Levels of health care at academic and regional hospitals in KwaZulu-Natal.

OBJECTIVE: To assess the levels of health care based on hospital bed utilisation at seven academic and regional hospitals in KwaZulu-Natal. DESIGN: A prospective study. The registrar in charge of patients documented the level of care needed for each patient over 7 consecutive days. Independent assessment by consultants was used to validate the results. SETTING: All wards in public sector regional and tertiary hospitals with acute general beds in Durban and Pietermaritzburg, except intensive care, coronary care and respiratory units. PARTICIPANTS: All inpatients present in the wards. The response rate of wards participating in the study varied between hospitals from 32% to 75%. Data on 14,858 patient days were analysed. OUTCOME MEASURES: Inpatients were classified according to levels of care based on patient days. RESULTS: The proportion of patients in the tertiary (King Edward) and regional hospitals requiring levels of care below that for which the hospital was designated ranged from 54% to 72% of the patient days. Wentworth Hospital, which is a tertiary referral centre, had 30% of its patient days judged to be below the designated level. Patient days below the designated level of care for that hospital were significantly higher in tertiary than in regional hospitals (P < 0.001). CONCLUSIONS: All seven hospitals admitted patients at levels of care below that for which the hospital was designated. These findings have important implications for the efficient utilisation and planning of health and hospital services, and for their evaluation and management.

Bed Occupancy↗

PubMed1996

Trends in cervical cancer mortality in South Africa.

BACKGROUND: Cervical cancer is an important cause of death throughout the world, especially in less developed countries. Reports of trends in cervical cancer mortality from less developed countries have been limited by poor data quality and inaccurate population estimates. This paper examines trends in cervical cancer mortality in South Africa from 1949 to 1990 and discusses the impact of cytology screening on these trends. METHODS: Analysis of national mortality statistics and reconstructed population data. RESULTS: The age-standardized mortality rates for Whites declined after the mid 1960s, while that for Coloureds rose, particularly before the 1970s. These trends were affected predominantly by trends among women in the 35-64 age range. CONCLUSIONS: The pattern of mortality in successive birth cohorts for Whites is consistent with a reduction in age-specific mortality following the advent of cytological screening. The same pattern is not evident in trends for Coloureds, among whom screening has apparently had a minor impact if any at all. The apparent lack of impact of screening in those groups of women most at risk of cervical cancer lends weight to demands for the implementation of equitable and rational screening programmes for cervical cancer in South Africa and internationally.

Adult↗

PubMed1996

Activin inhibition of prostate cancer cell growth: selective actions on androgen-responsive LNCaP cells.

Prostate epithelial cell growth is under the control of both steroid and peptide factors. Human prostate cancer cell lines have been used to investigate similar agents in malignancy. Activins are dimeric peptides structurally related to transforming growth factor-beta and produced in the gonads and a wide array of extragonadal tissues. The activins act at the pituitary to regulate the synthesis and secretion of FSH. At other sites, such as bone marrow, liver, and gonads, activin may play an important role in the regulation of cell growth and differentiation. It was the purpose of the current study to determine whether activin had similar actions on prostate cancer cells, specifically the androgen-responsive LNCaP and the androgen-resistant PC-3 cell lines. Using reverse transcription-PCR, messenger RNAs for type I and type II activin receptor subunits as well as the activin-binding protein follistatin were detected in both cell lines. Activin treatment rapidly (<24 h) inhibited LNCaP, but not PC-3, cell growth. The effects of activin were evident at low levels, with a concentration of 5 ng/ml being effective at 24 h, and a concentration of 0.5 ng/ml being effective at 48 h. These results contrasted with the actions of transforming growth factor-beta, which inhibited only PC-3 cells and required a greater treatment duration (96 h) to be effective. To determine whether these prostate cancer cell lines were also producing activin, LNCaP and PC-3 cells were treated with follistatin. Again, only the LNCaP cells responded, with growth acceleration noted by 24 h. As PC-3 cell responses to activin could be independent of cell proliferation, we transfected LNCaP and PC-3 cells with a known activin-responsive promoter/reporter gene construct (p3TP-Lux) and treated cells with activin. Only LNCaP cells produced a measurable response in luciferase activity. Finally, we attempted to determine whether the PC-3 cell resistance to activin was mediated via a transferable factor. PC-3 conditioned medium was added to LNCaP cells in the absence or presence of exogenous activin and had a small, but statistically nonsignificant (P < 0.09), action to blunt the actions of activin. We conclude that activin is a potent growth inhibitor of LNCaP cell growth. Moreover, these cells also produce activin, suggesting that locally derived activin may play a role in regulating cell proliferation. Despite expressing messenger RNAs for activin receptors, PC-3 cells are resistant to activin, perhaps the result of the production of an activin-blocking factor or a defective activin response system. These cell lines will thus serve as useful models in which to further study the cellular basis of activin action.

Activin Receptors↗

PubMed1996

Public sector primary care of diabetics--a record review of quality of care in Cape Town.

AIM: To evaluate the quality of health care received by diabetics. DESIGN: External audit by means of retrospective record review. SITE: Ambulatory outpatient diabetes clinics at community health centres in black areas of Cape Town. METHOD: A stratified random sample (520) of all patients who attended any of five health centres during 1991 was reviewed by a clinician who had been trained to do structured record reviews. RESULTS: The response rate was 73.1%. Of all patients reviewed 91% had non-insulin-dependent diabetes mellitus and the remainder insulin-dependent diabetes mellitus; 65% were female and 35.8% were employed. Only 35% attended optimally. Fingerprick blood glucose values were recorded at 98.4% of visits, blood pressure was recorded at 74.1% of all visits and for 97.4% of patients; urine dipstick test results were recorded at 84.6% of visits and for over 99% of patients in 1991, and weight was recorded at 68.8% of visits. In contrast, fundoscopy was recorded for 6% of patients and examination of the feet was performed in 4.7% of patients. Fewer than half (48.9%) of visits resulted in any change in management. Polypharmacy is frequent, with an average of 2.3 non-hypoglycaemic drugs prescribed per visit. CONCLUSION: Attendance and examination for treatable complications are inadequate. Care is routinised and reactive and there is polypharmacy. RECOMMENDATIONS: Simple but appropriate protocols and matching in-service education are likely to improve the care of and health outcome for diabetics at these sites.

Adult↗

PubMed1994

A national sentinel surveillance network for the measurement of ill-health in South Africa. A prerequisite for epidemiological research and health planning.

Data on births, on deaths by cause and on morbidity are essential in planning appropriate health interventions, but the scarcity of these data in South Africa is striking. Some of the limitations of national mortality and morbidity data collection systems are reviewed. In order to improve the usefulness of vital statistical information, it is proposed that active disease monitoring be introduced in a number of surveillance sites where the population has been properly enumerated. A network of these sites would routinely gather information on births and deaths by cause and on a list of conditions that are: (i) easy to identify clinically; (ii) would bring most people to the attention of health personnel; and (iii) would indicate failure of health service provision, environmental control or resource allocation. The measurement of the geographical variation of a number of conditions, coupled with geographical information on health care indicators and risk and health promotive factors in each site, would facilitate the planning of interventions in a rational manner.

Female↗

PubMed1994

Ro 32-0432, a selective and orally active inhibitor of protein kinase C prevents T-cell activation.

Several lines of circumstantial evidence support the assumption that protein kinase C (PKC) activation together with elevated levels of cytosolic Ca++ are necessary for T-cell activation and proliferation in response to a physiological stimulus, i.e., MHC class II restricted antigen presentation. By using a potent, cell-permeable and selective inhibitor of PKC, Ro 32-0432, we have tested this hypothesis. Ro 32-0432 inhibits interleukin-2 (IL-2) secretion, IL-2 receptor expression in, and proliferation of, peripheral human T-cells stimulated with phorbol ester together with phytohemagglutin or anti-CD3, but does not inhibit IL-2 induced proliferation in cells already stimulated to express IL-2 receptors. Proliferation of the influenza peptide antigen HA 307-319-specific human T-cell clone (HA27) after exposure to antigen-pulsed autologous presenting cells was also inhibited by Ro 32-0432. Oral administration of Ro 32-0432 inhibited subsequent phorbol ester-induced edema in rats demonstrating the systemic efficacy of the compound to inhibit PKC-driven responses. Induction of more physiologically T-cell driven responses such as host vs. graft responses and the secondary paw swelling in adjuvant-induced arthritis were also inhibited by Ro 32-0432. These data demonstrate the crucial role for PKC in T-cell activation and that selective p.o. bioavailable PKC inhibitors are efficacious in preventing T-cell driven chronic inflammatory responses in vivo. Inhibition of PKC represents an important mechanistic approach to prevent T-cell activation and compounds of this class may have important therapeutic applicability to chronic inflammatory and autoimmune diseases.

Administration, Oral↗

PubMed1994

Cervicography.

Explore the source record for details and available documents.

Cervix Uteri↗

PubMed1993

Therapeutic potential of protein kinase C inhibitors.

The serine/threonine protein kinase, protein kinase C (PKC) is a family of closely related isoforms which are physiologically activated by diacylglycerol generated by the binding of a variety of agonists to their cellular receptors. Free fatty acids may also play a role in activating PKC. The enzyme apparently mediates a wide range of signal transduction processes in cells and, therefore, inhibitors directed selectively against PKC may have wide-ranging therapeutic potential. This review highlights the evidence that inappropriate activation of PKC occurs in a number of disease states. Such evidence, however, is often seriously flawed because it relies on the use of phorbol esters, which are potent and direct PKC activators but may not mimic the physiological triggering of the enzyme in cells, or on the use of non-selective protein kinase inhibitors such as H7 and staurosporine. A new generation of bis-indolylmaleimides, derived from the lead provided by staurosporine, shows a high degree of selectivity for PKC over closely related protein kinases and such agents may provide more appropriate tools to investigate the role of PKC in cellular processes.

Alzheimer Disease↗

PubMed1993

Isokinetic trunk strength and lifting strength measures. Differences and similarities between low-back-injured and noninjured workers.

Fifty-eight back pain patients and 21 entry-level Postal Service workers without low-back pain were evaluated using a variety of lumbar function measures. Isolated trunk strength and full lifting strength were gauged with isokinetic and isometric methods. Lumbar range-of-motion was computed using toe-touch and goniometers. Conventional clinical techniques such as toe touch and straight leg raise were effective in distinguishing back-injured from normal subjects. Isometric and isokinetic peak force and torque tests failed to show significant differences between low-back pain and job applicant groups. When compared with published norms, our job applicant group was significantly deconditioned. Our data suggest that asymptomatic, deconditioned subjects could be mistaken for back-impaired patients or symptom magnifiers.

Adult↗

PubMed1993

The prevalence and identification of risk factors for NIDDM in urban Africans in Cape Town, South Africa.

OBJECTIVE: To determine the prevalence of NIDDM and associated risk factors in urban Africans in Cape Town, South Africa. RESEARCH DESIGN AND METHODS: With a three-stage, proportional, stratified, random cluster method, we sampled 1000 Africans, > 30 yr of age, living in African residential areas in Cape Town. We assessed glucose tolerance with a 75-g oral glucose tolerance test, according to World Health Organization criteria, and obtained anthropometric and demographic data. RESULTS: The response rate was 79%. The prevalence of NIDDM was 8.0% (confidence interval 5.8-10.3%), age-adjusted to world population figures and that of impaired glucose tolerance, 7.0% (confidence interval 4.9-9.1%). Multivariate analysis indicated that increased age (odds ratio 4.18), upper-segment fat distribution (odds ratio 2.94), proportion of life spent in an urban area (odds ratio 2.32), and obesity (odds ratio 2.31) were significant independent risk factors for NIDDM. In contrast, sex, family history, alcohol intake, and physical activity were not independent risk factors. Only increased age (odds ratio 4.06) was a significant risk factor for impaired glucose tolerance. CONCLUSIONS: The prevalence of NIDDM in urban Africans in Cape Town, South Africa, is moderately high, and considerably higher than previous reports from Africa. The association of NIDDM with urbanization has important implications in view of the large-scale urbanization occurring in southern Africa.

Adult↗