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Biomedical subjects

J R Lawrence

Publications and source records attributed to J R Lawrence.

At least 19 recordsLinked to original sources

Effects of erythropoietin therapy on the lipid profile in end-stage renal failure.

To evaluate the effects of erythropoietin (EPO) therapy on the lipid profile in end-stage renal failure, we undertook a prospective study in patients on both hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD). One hundred and twelve patients (81 HD, 31 CAPD) were enrolled into the study. Lipid parameters [that is, total cholesterol and the LDL and HDL subfractions, triglycerides, lipoprotein (a), apoproteins A and B], full blood count, iron studies, B12, folate, blood urea, aluminium and serum parathyroid hormone were measured prior to commencement of EPO therapy. Ninety-five patients were reassessed 5.2 +/- 0.3 (mean +/- SEM) months later and 53 patients underwent a further assessment 13.1 +/- 0.6 months after the commencement of EPO, giving an overall follow-up of 10.0 +/- 0.6 months in 95 patients. As expected, EPO treatment was associated with an increase in hemoglobin (7.7 +/- 0.1 vs. 9.9 +/- 0.2 g/dl; P < 0.001) and a decrease in ferritin (687 +/- 99 vs. 399 +/- 69 micrograms/liter; P < 0.01). A significant fall in total cholesterol occurred (5.8 +/- 0.1 vs. 5.4 +/- 0.2 mmol/liter; P < 0.05) in association with a fall in apoprotein B (1.15 +/- 0.04 vs. 1.04 +/- 0.06; P < 0.05) and serum triglycerides (2.26 +/- 0.14 vs. 1.99 +/- 0.21; P < 0.05) during the course of the study. Other lipid parameters did not change, although there was a trend towards improvement.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

The role of interactions, sessile growth and nutrient amendments on the degradative efficiency of a microbial consortium.

A degradative microbial consortium consisting of at least nine bacterial and one algal species was isolated from soil with diclofop methyl as the sole carbon source. In continuous flow culture, the presence of the algae increased diclofop methyl degradation and removal by 36%. Batch culture experiments with 14C-labeled diclofop methyl confirmed algal involvement in the mineralization of diclofop methyl as there was no significant difference in the amount of 14CO2 evolved by the bacterial consortium with and without the algal activity when the consortium was cultivated in the dark to inhibit algal growth, while 11% more 14CO2 was produced in the light by the algal-bacterial consortium. Pure cultures isolated from the bacterial consortium could not individually mineralize diclofop methyl as the sole carbon source. However, when supplied with an additional carbon source, two strains could mineralize diclofop methyl. Addition of either the complex growth medium, or a cell-free filtrate from the algal-bacterial consortium to batch systems containing 14C-labeled diclofop methyl resulted in a significant increase in the production of 14CO2 by the bacterial consortium, suggesting co-metabolism of diclofop methyl in the presence of a labile carbon source. Removal of diclofop methyl by the bacterial consortium was increased by 36% when a larger surface to volume ratio was provided by glass beads that allowed extensive biofilm formation. The requirement for exogenous carbon sources and the inability of isolated pure cultures to degrade diclofop methyl indicated that interspecies interactions are necessary for degradation. The positive effect of sessile growth suggested that spatial organization of cells may also be important for degradation.

Bacteria

The evolution of the end-stage renal disease program in Australia.

Australia was an early pioneer of national integrated programs for the management of end-stage renal disease (ESRD). From being a leader in numbers of patients per population treated, it is now in the top 15. The Australian program has a high proportion of living patients with functioning transplants and a high proportion of out-of-hospital dialysis. The proportion of elderly patients is increasing but lower than expected. A particular problem is the treatment of Aboriginal people. The ANZ Data surveys give accurate complete data for the national program. Unique features of the Australian patients are the high incidence of analgesic nephropathy and the low incidence of primary hypertension as a cause of renal failure. Surveys show that it is possible to improve transplantation rates 2 to 3 times. Analysis of Australian data raises the question of whether dialysis and transplantation should be offered to all potential patients regardless of comorbidity or quality of life when health resources are inevitably finite.

Adult

Behavioral analysis of Vibrio parahaemolyticus variants in high- and low-viscosity microenvironments by use of digital image processing.

Digital image analysis and light microscopy were used to study and quantify the growth and behavior of two variants and selected flagellar mutants of Vibrio parahaemolyticus in glass flow cells under high- and low-viscosity conditions. The observations showed a series of surface-associated behaviors, including attachment, microcolony formation, migration, chemotactic movements, and aggregation, indicating a substantial degree of adaptive flexibility and multicellular behavior during growth of V. parahaemolyticus at interfaces.

Bacterial Adhesion

Upholsterers' glue associated with myocarditis, hepatitis, acute renal failure and lymphoma.

A 20-year-old man with heavy exposure to upholsterers' glue presented with life-threatening acute myocarditis, and then rapidly developed acute hepatic necrosis and acute renal failure. He made a rapid and complete recovery from this florid acute illness, only to present three months later with supradiaphragmatic non-Hodgkin's lymphoma. These illnesses have all been described in association with solvent exposure. The unique feature of this case is the occurrence of multiple manifestations which might be attributed to solvent exposure, both acute and chronic, in the same individual.

Acute Kidney Injury

Proteus mirabilis biofilm protection against struvite crystal dissolution and its implications in struvite urolithiasis.

Proteus mirabilis biofilm formation, struvite (MgNH4PO4.6H2O) crystal formation and dissolution in an artificial urine mixture were monitored using computer-enhanced microscopy (CEM) and a 1 x 3 mm. glass flow cell. Image analysis showed that P. mirabilis biofilm formation did not occur to any extent at macroenvironment flow rates greater than two mL/h (equivalent to a microenvironment flow rate of less than 5 microns./sec). Essentially, cells attached to glass surfaces, grew slowly and divided. Daughter cells were generally released directly into the medium where they could then presumably colonize other regions. Microcolonies formed by the adhesion of aggregates of cells from the medium, and over time grew into biofilms. Struvite crystallization due to urease activity and pH elevation above neutrality, was preceded by the deposition of organic matter on the glass surface, followed by the appearance of a number of tiny (one to two microns.) crystals. Crystals forming within a biofilm at low dilution rates took on a characteristic twinned or "X-shaped" appearance (crystal habit) indicative of a rapid growth rate. Those forming outside the biofilm took on a more tabular appearance reflecting their slower growth. When the macroenvironment flow rate of artificial urine (initial pH 5.8) in the glass flow cell was increased from two mL/h to four mL/h, struvite crystals not associated with biofilms dissolved within five to 10 min. Crystals entrapped within the P. mirabilis biofilm withstood flow rates up to 200 mL/h presumably due to the maintenance of an alkaline Mg-saturated microenvironment within the biofilm. These observations may suggest a mechanism by which struvite calculi can grow in spite of neutral or acidic urine pH and resist mild acidification therapy.

Bacterial Adhesion

Optical sectioning of microbial biofilms.

Scanning confocal laser microscopy (SCLM) was used to visualize fully hydrated microbial biofilms. The improved rejection of out-of-focus haze and the increased resolution of SCLM made it preferable to conventional phase microscopy for the analysis of living biofilms. The extent of image improvement was dependent on the characteristics of individual biofilms and was most apparent when films were dispersed in three dimensions, when they were thick, and when they contained a high number of cells. SCLM optical sections were amenable to quantitative computer-enhanced microscopy analyses, with minimal interference originating from overlying or underlying cell material. By using SCLM in conjunction with viable negative fluorescence staining techniques, horizontal (xy) and sagittal (xz) sections of intact biofilms of Pseudomonas aeruginosa, Pseudomonas fluorescens, and Vibrio parahaemolyticus were obtained. These optical sections were then analyzed by image-processing techniques to assess the distribution of cellular and noncellular areas within the biofilm matrices. The Pseudomonas biofilms were most cell dense at their attachment surfaces and became increasingly diffuse near their outer regions, whereas the Vibrio biofilms exhibited the opposite trend. Biofilms consisting of different species exhibited distinctive arrangements of the major biofilm structural components (cellular and extracellular materials and space). In general, biofilms were found to be highly hydrated, open structures composed of 73 to 98% extracellular materials and space. The use of xz sectioning revealed more detail of biofilm structure, including the presence of large void spaces within the Vibrio biofilms. In addition, three-dimensional reconstructions of biofilms were constructed and were displayed as stereo pairs. Application of the concepts of architectural analysis to mixed- or pure-species biofilms will allow detailed examination of the relationships among biofilm structure, adaptation, and response to stress.

Image Processing, Computer-Assisted

Tubular sodium handling and tubuloglomerular feedback in experimental diabetes mellitus.

Tubular Na handling and tubuloglomerular feedback (TGF) activity were assessed using micropuncture techniques during the hyperfiltration phase of streptozotocin-induced diabetes mellitus in Sprague-Dawley rats. Three animal groups were studied, designated as having severe diabetes [blood sugar level (BSL) 18-25 mmol/l], moderate diabetes (BSL 13-18 mmol/l) and control (BSL less than 10 mmol/l). Single-nephron glomerular filtration rate (SNGFR) measured at both late proximal (LP) and early distal (ED) sites was elevated in severe diabetes compared with both other groups. TGF activity, determined as the difference between LP and ED measurements of SNGFR, was significantly increased in severe diabetes (46.4 +/- 6.6 vs. 30.1 +/- 6.5 vs. 14.8 +/- 1.9 nl/min). Tubular Na transport was higher in severe diabetes compared with control, as demonstrated by a decrease in fractional delivery of Na to the LP (42.9 +/- 3.0 vs. 52.9 +/- 1.9%), as well as to the ED site (4.5 +/- 0.4 vs. 12.3 +/- 0.9%). Administration of phlorizin to severely diabetic animals resulted in a BSL comparable to that observed in moderate diabetes, and whole animal GFR, as well as SNGFR, TGF activity, and tubular Na handling were also similar to those found in moderate diabetes. Studies performed during mannitol infusion demonstrated that osmotic diuresis alone was not associated with the changes in TGF and tubular Na handling observed in the diabetic state. These data suggest that the hyperfiltration occurring in early diabetes is associated with enhanced proximal and loop resorption of Na independent of Na-glucose cotransport and osmotic diuresis. Activation of TGF serves to limit the rise in GFR, which results from factors as yet unrecognized in the diabetic state.

Animals

Metolazone in treatment of severe refractory congestive cardiac failure.

17 patients with New York Heart Association (NYHA) class IV congestive cardiac failure, refractory to conventional treatment, were additionally treated with oral metolazone (1.25-10 mg daily). 12 improved sufficiently to be discharged from hospital (NYHA class II or III, mean weight loss 8.3 kg), 1 of whom died at home 4 weeks later. The other 5 patients were treated with intravenous dobutamine for 72 h; 2 responded (average weight loss 4.4 kg), and 2 responded to subsequent reintroduction of metolazone. 4 of these 5 patients died, 2 in hospital of acute myocardial infarction. Overall, 15 patients with very severe refractory cardiac failure improved sufficiently to be discharged from hospital. Treatment was associated with mild transient hypokalaemia in 7 patients, and hyponatraemia and renal impairment in 1, for whom metolazone dosage had to be reduced. Failure to respond to the introduction of metolazone may indicate an especially poor prognosis.

Aged

Micropuncture comparison of nephron function during acute and chronic ADH excess in the rat.

1. The aim of this study was to compare the effect of acute versus chronic ADH administration on the handling of sodium, potassium and water by the nephron. Simultaneous clearance and free-flow micropuncture experiments were performed on rats, infused with hypotonic Ringer solution, following either 1-3 h ('acute') or 10-12 days ('chronic') of continuous treatment with arginine vasopressin, 50 mU/h. A third group of animals receiving no exogenous ADH acted as controls. 2. Chronic ADH treatment led to more profound concentration of the urine and antidiuresis than acute treatment, due to enhanced extraction of water in the renal medulla. 3. Fractional sodium excretion during this protocol was increased after 'acute' but not 'chronic' ADH treatment. The acute natriuretic response was brought about principally along the length of the proximal tubule, probably due to volume expansion and increased arterial blood pressure. 4. Fractional excretion of potassium was also increased by 'acute' ADH, but this response was due to stimulation of potassium secretion in the late distal tubule. 5. It is concluded that acute and chronic exposure to ADH have different effects on nephron function, as a result of both direct and indirect actions.

Animals

Anorexia tardive: a diagnosis of exclusion?

An elderly female patient is described in whom rapid severe weight loss appeared initially to be of psychogenic origin and self-induced. A diagnosis of late-onset anorexia nervosa or anorexia tardive was made when early investigations revealed no abnormality apart from changes that were consistent with malnutrition, and when typical behavioural and psychological factors together with putative psychodynamic issues were revealed. At first, nasogastric feeding was beneficial, but a stormy hospital course ensued. Further investigations revealed the presence of neoplastic disease which at post-mortem examination proved to be small-cell carcinoma of the lung.

Aged

Iatrogenic Buschke's disease (Michelin man syndrome)

Scleredema [corrected] adultorum as originally described by Buschke in 1900, is cutaneous thickening of unknown aetiology. Since then several cases have been reported which have illustrated different aspects of the disease but the exact aetiology, pathogenesis and prognosis remain uncertain. Disease of possible iatrogenic origin appears not to have been described previously.

Blood Protein Electrophoresis

Comparison of performance of final-year students from three Australian medical schools.

Between 1984 and 1986, 888 final-year medical students from The Universities of Sydney, Western Australia and Newcastle took part in trial examinations that comprised multiple-choice questions, modified essay questions and a patient management problem. Differences in student performance among the schools were small. In 1984 and 1985, Newcastle students performed less well than did Sydney students on multiple-choice questions that were prepared by The University of Sydney, but there was no difference between the schools in 1986. Sydney students performed better than did Newcastle students on the multiple-choice question paper that was prepared by The University of New South Wales in 1984, but in the last two years no differences have been detected between the schools in performance on this paper. The performance on modified essay questions in 1984 suggested that Newcastle students were stronger in behavioural sciences and weaker in pathological sciences than were Sydney students. Sydney students performed less well than did Newcastle students in the patient management problem in 1985, particularly in the area of the use of clinical investigations. On the one occasion of testing that involved students from The University of Western Australia (in 1985), these students performed best of the three schools in the patient management problem, and roughly equally with students from Sydney and Newcastle in the multiple-choice question papers. Differences among the schools usually amounted to less than 10% and might have been accounted for by differences in familiarity with test instruments. We conclude that medical students are likely to graduate from The University of Sydney, Western Australia and Newcastle with similar levels of knowledge of internal medicine. Possible differences in problem-solving ability require further study, particularly in the clinical setting.

Australia