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Biomedical subjects

F J Muller

Publications and source records attributed to F J Muller.

15 recordsLinked to original sources

Tuberculosis at Edendale Hospital in Pietermaritzburg, Kwazulu Natal, South Africa.

SETTING: Edendale Hospital, Pietermaritzburg, KwaZulu Natal, South Africa, a 1275-bed hospital that serves a mainly ethnic African population of 1.6 million. OBJECTIVE: To describe the demographic and clinical characteristics of hospitalised active tuberculosis (TB) cases, and correlates of their in-hospital survival. METHODS: A retrospective cohort study of adult TB cases admitted to the medical wards, 16 November to 13 December 2001. RESULTS: Of 760 (28%) admissions, 215 had active TB, of whom 26.5% died in hospital. Patients were mostly young, first diagnosed on admission, and had pulmonary TB. Human immunodeficiency virus (HIV) co-infection was common and predicted by lower absolute lymphocyte count (OR 1.2, 95% CI 1.05-1.38). Extra-pulmonary TB, including pleural and pericardial, was significantly associated with not having HIV infection. In-hospital death was predicted by TB diagnosed prior to admission (OR 3.18, 95% CI 1.67-6.07), acquired immune-deficiency syndrome (AIDS) associated disease, and higher total leukocyte count--by higher leukocytes only in patients without AIDS (OR 8.52, 95% CI 2.67-27.13). CONCLUSION: Active TB was common in in-patients at an acute care hospital. TB patients presented late in disease and had high in-hospital mortality. Early detection and effective treatment of active TB in the community is likely to reduce hospitalisation and improve survival.

Adult↗

Cartilage metalloproteases in disuse atrophy.

A canine knee model of disuse atrophy produced by nonrigid fixation (sling) was characterized in respect to variables of proteoglycan size distribution, as well as biomechanical properties versus controls. Using this model, we found, in addition to the accepted dogma attributing changes to reduced protein synthesis by chondrocytes, that there is elevation of proteases and depression of tissue inhibitor of metalloproteases (TIMP) in atrophic knee cartilage. The findings are suggestive of cartilage remodelling reminiscent of bone remodelling in disuse atrophy reported by others. Whether the abnormal changes of protease-TIMP balance in knee cartilage can be retarded prophylactically by concurrent treatment with pentosan polysulfate and insulin like growth factor 1 remains uncertain.

Animals↗

Structural differences between two populations of articular cartilage proteoglycan aggregates.

To determine if articular cartilage contains structurally distinct populations of proteoglycan aggregates, we extracted and purified proteoglycans from canine knee cartilage under associative conditions. Equilibrium density gradient centrifugation separated three proteoglycan populations, on the basis of differences in sedimentation velocity, into groups of 21, 106, and 270 S. Electron microscopic examination showed that the 21 S samples contained free aggrecan molecules and clusters of aggrecan molecules, with a mean of five aggrecan molecules per cluster. The 106 and 270 S samples contained proteoglycan aggregates consisting of central hyaluronan filaments with multiple attached aggrecan molecules. The two populations of aggregates did not differ in mean aggrecan length or in the spacing of aggrecan molecules along the hyaluronan filaments, but the slower sedimenting aggregates (106 S) had significantly shorter hyaluronan filaments as measured by electron microscopy (mean hyaluronan length, 400 compared with 1,162 nm) and one-third as many aggrecan molecules per aggregate (mean number of aggrecan molecules per aggregate, 15 compared with 44). This study shows that articular cartilage contains aggrecan clusters and two structurally distinct populations of proteoglycan aggregates. The differences between the two types of aggregate, in particular the number of aggrecan molecules per aggregate, may reflect differences in their assembly, stability, or turnover and give them different mechanical and biological properties.

Aggrecans↗

Altered structure-function relationships for articular cartilage in human osteoarthritis and an experimental canine model.

A review of the structure-function relationships for normal articular cartilage is provided. This provides the foundation for understanding the roles played by collagen, proteoglycan and water in determining the material properties of the tissue. A summary of biomechanical and compositional changes in human osteoarthritic cartilage is also presented. Finally, the results from our recent interdisciplinary study on an experimental osteoarthritis model is described, and new hypotheses are proposed on the initiating factors responsible for the increase of tissue hydration. At present, it appears that microstructural alterations, rather than compositional changes, of the collagen-proteoglycan solid matrix are responsible for the early increase of hydration and the deterioration of biomechanical properties of articular cartilage.

Animals↗

Treatment of osteoarthritis with tiaprofenic acid: biochemical and histological protection against cartilage breakdown in the Pond-Nuki canine model.

Experimental and cage matched control animals were sacrificed 12 weeks after production of ligamentous instability in the right knee, and biochemical studies were performed on eroded OA and normal articular cartilage. Significant protection was afforded by tiaprofenic acid administered orally at 15 mg/kg body weight. Chondroprotection was manifested by reduction of fast sedimenting proteoglycan aggregates, as well as retention of hyaluronate content, and favorable proteoglycan aggregate S value levels. This agent showed significant chondroprotective action under the conditions of these studies.

Administration, Oral↗

Oxytocin-induced water intoxication. A case report.

Oxytocin-induced water intoxication is an uncommon iatrogenic condition with serious potential morbidity and mortality, which is preventable with a rational approach to therapy. Its pathogenesis, management and prevention are discussed.

Abortion, Induced↗

A sectorial centrifuge cell for swinging bucket rotors--application to a velocity gradient centrifugation methodology.

A sectorial cell of 1.55 ml capacity, designed to be used in swinging bucket rotors, is introduced and applied to boundary sedimentation studies. The cell, made of polycarbonate by injection molding, represents an improvement over previously existing models in terms of resistance and attainable speeds. Its use has been extended to polydispersity determination by evaluation of the s value distribution function g(s) = dC/ds. The latter can be corrected to standard conditions (water at 20 degrees C), by using newly derived equations in connection with a cesium sulfate linear density and viscosity gradient which is introduced for boundary stabilization. The cell performance is illustrated with the centrifugal characterization of a polydisperse hyaluronate solution and a paucidisperse proteoglycan A1 preparation. In the latter case a distinctive distribution of aggregates into two polydisperse families of molecules, hitherto not reported in the literature but previously observed with cylindrical cells in this laboratory, has been clearly confirmed. Analysis of plateau dilution during centrifugation indicated absence of artifacts.

Centrifugation, Density Gradient↗

Effects of pulmonary circulation on blood levels of insulin and glucagon in ambulant dogs.

The effect of the lung on insulin and glucagon were studied by comparing aortic and mixed venous levels in ambulant dogs with indwelling catheters. In the resting state ther was no difference for either hormone. After injection of insulin aortic levels exceeded mixed venous for 10 min; mixed venous levels exceeded aortic for the next 36 min. After injection of glucagon mixed venous levels consistently exceeded aortic. Single-pass studied showed an apparent gain in immunoreactive insulin as compared with [14C]inulin and 125I-albumin during passage through the lung; but no effect on glucagon could be demonstrated. A loss of immunoreactive hormone across the lung might be explained by degradation within the capillary lumen be endothelial cell surface peptidases or uptake onto specific receptors. The apparent gain of immunoreactive insulin across the lung might be due to displacement of immunoreactive exogenous hormone competing for receptor sites or modification of exogenous hormone by the lungs with increase in immunoreactivity.

Animals↗

Evidence for a role of proteinpolysaccharides in regulation of mineral phase separation in calcifying cartilage.

Our previous studies have indicated the presence of a macromolecular inhibitor of in vitro mineral growth, as well as a mineral nucleational agent in extracellular matrix fluid aspirated by micropuncture methods from epiphyseal hypertrophic cell cartilage. In this report, new miniaturized methods were used to extract proteinpolysaccharide complexes (PPC) from cartilage, to isolate a light fraction (PPL-C), and further, to separate it into R1, R2, and SR2 subfractions. These methods were applied to PPL-C complexes separated from microdissected epiphyseal cartilages and to cetylpyridinium chloride (CPC) precipitates of extracellular matrix fluid aspirated from similar cartilages. Most of all of the inhibitory action on an in vitro system of mineral growth shown by whole cartilage PPL-C and by cartilage fluid PPC obtained from noncalcifying sites was contained in the R2 fraction which represented (1/4)-[unk] of the total hexuronate. The R2 fraction was diminished or absent from calcified cartilage fluids and from whole calcified epiphyseal septa. The ratio R1 + R2: SR2 ranged from 0.37 to 0.71 in the fluids and whole tissue samples of noncalcified cartilages. The R2 fraction was distinguished from SR2 by a 2- to 3-fold higher protein: hexuronate ratio. These data are interpreted to indicate that the inhibitory R2 fraction was degraded or otherwise inactivated at the zone of provisional calcification and that this inhibitor participates in the physiological mechanism that regulates endochondral calcification.

Animals↗