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Biomedical subjects

D Tiller

Publications and source records attributed to D Tiller.

At least 19 recordsLinked to original sources

Derivation of nutrient guidelines for streams in Victoria, Australia.

Human induced increases to nutrient concentrations in streams have led to many agencies developing strategies and criteria for nutrient reduction. National or statewide guidelines are generally inappropriate, due to the natural variability in stream ecosystems within political boundaries. This study used an extant aquatic macroinvertebrate-based regionalisation for the state of Victoria, Australia, as the basis for defining regions of relatively homogeneous environmental character. This enabled the selection of ecologically-based regional reference sites and subsequent characterisation of the nutrient status of these sites. Using an extensive biological and nutrient data base for streams across the State, we calculated 50th and 75th percentile concentrations for reference sites within each region. Using these percentiles in conjunction with 'impact and recovery' studies, we defined nutrient guidelines for each region. Although the nutrient data largely supported the biological regionalisation, patterns in the nutrient data did require some minor modifications for the nutrient regions. Relatively unimpacted regions with reference sites in very good-to excellent-condition were assigned guidelines largely based on the 75th percentiles. The more impacted regions, where 'best available' reference sites were of poorer quality, were assigned guidelines based largely on the 50th percentiles. Professional judgement and known extents of impacts across each region provided important contributions to the decision-making process. The derived guideline concentrations are comparable to several cited in the literature and are proposed for use in monitoring, assessment and restoration targets.

Animals↗

Changes of extracellular matrix in a baboon (Papio hamadryas) model of insulin dependent diabetes: studies using electron microscopy and X-ray diffraction techniques.

Extracellular matrix plays an important role in many physiological functions and its abnormalities are thought to play a key role in the pathogenesis of diabetic complications. In this paper we used the techniques of electron microscopy, immunostaining and X-ray diffraction to document some of the early events in the changes of extracellular matrix in a model of insulin dependent diabetes in baboons. Our results show that thickening of basement membrane and enlargement of mesangium are demonstrable in the glomeruli of prepubertal diabetic baboons within 2 years from the onset of diabetes. Concomitant with this was the accumulation of type IV collagen and laminin in the mesangium. By contrast, even the very sensitive technique of X-ray diffraction failed to demonstrate changes in the equatorial direction of collagen molecules of the skin and tendon. We conclude that changes of glomerular extracellular matrix are demonstrable early in insulin dependent diabetes even in prepubertal baboons. These can be used as endpoints in evaluating the efficacy of pharmacological agents such as aminoguanidine in preventing diabetic complications.

Animals↗

Reproductive and neonatal outcomes in captive bred baboons (Papio hamadryas).

Baboons are widely used in biomedical research. Although it is widely held that Papio hamadryas breed well in captivity, each established colony has a different reproductive success often hypothesised to be due to husbandry practices. The National Baboon Colony in Australia is a unique colony that houses Papio hamadryas to mimic that structure seen in the wild. In this article; we have analysed their reproductive parameters and neonatal outcomes. The success of the colony husbandry practices was demonstrated by lack of maternal mortality, low foetal morbidity, and known maternal and paternal linage.

Abortion, Veterinary↗

A baboon (Papio hamadryas) model of insulin-dependent diabetes.

Over a period of four years, streptozocin has been used to induce diabetes in 10 baboons, all of whom are insulin dependent. We describe our experience with their husbandry, induction of diabetes, insulin therapy, metabolic control and growth rate. Streptozocin dosage of 60 mg/kg readily induces hyperglycemia with minimal hepatic or renal toxicity. Using a once daily injection of mixed short and intermediate acting insulins at a dosage of 2-4 U/kg, it is possible to maintain a degree of metabolic control similar to that attained in patients.

Aging↗

T6+ and HLA-DR+ cell numbers in epidermis of immunosuppressed renal transplant recipients.

The increased susceptibility of the skin of chronically immunosuppressed individuals to viral infections and sunlight-induced malignancies suggests specific drug-induced, dysfunction of local immune mechanisms within the sun-exposed skin of these individuals. To help understand the effect of immunosuppressive therapy alone in the absence of ultraviolet light on the immune system of skin, biopsies were collected from non-sun-exposed buttock skin of control, healthy volunteers and kidney transplant recipients immunosuppressed with either azathioprine/prednisone or cyclosporin A/prednisone and examined for incidences of T6+, and HLA-DR+ cells. No significant differences in the incidences of these 2 cell types were found (a) between control individuals and transplants recipients, (b) between transplant recipients receiving either of the immunosuppressive drug regimes, or (c) between transplant recipients who either had or had not developed skin cancer.

Adolescent↗

Verapamil in essential hypertension: a comparison with atenolol plus hydralazine.

The effects of graded doses of verapamil were compared with those of a combination of atenolol and hydralazine in a double-blind, randomised, crossover trial in 16 patients with essential hypertension. During the placebo phase, mean arterial pressure (M.A.P.) was 123 +/- 17 mmHg. Verapamil (dose range 160-480 mg/day) lowered M.A.P. to 109 +/- 7 mmHg (p less than 0.01 vs placebo). The combination of atenolol (50-100 mg/day) and hydralazine (50-200 mg/day) lowered M.A.P. to 100 +/- 11 mmHg (p less than 0.001 vs placebo, p less than 0.05 vs verapamil). Neither regimen produced any deleterious effects on electrocardiographic intervals, echocardiographic indices of left ventricular function or plasma lipids. Verapamil was well tolerated and provided satisfactory alternative therapy in these patients with mild-to-moderate essential hypertension.

Adult↗

Formative program evaluation and milieu therapy with alcohol abusers.

Evaluated presumably therapeutic components within a therapeutic community in terms of perceived helpfulness by patients and staff of an alcohol treatment unit. Eighteen male patients and 18 staff members participated. A nonparametric statistic was used as an index of treatment philosophy articulation or degree of value-sharing. A core of activities valued congruently by patients and staff was identified.

Adult↗

Effect of age on angiotensin II receptors from rat brain.

1. Angiotensin II receptor binding was studied in specific regions of rat brain at different ages from birth to 14 weeks. 2. The number of specific angiotensin II receptors increased in all regions during the first 2 weeks of life and then decreased to adult levels. Peak numbers of receptors were up to 10 times the adult numbers. 3. The midbrain and thalamus-hypothalamus had maximum numbers of angiotensin II receptors at 2 weeks of age, whereas the rest of the brain regions had maximum number at 1 week. 4. Saralasin-infusion experiments suggested that circulating angiotensin-related peptides could reach brain angiotensin II receptors in 2 week old rats, but not in 6 week old rats. 5. It is postulated that the centrally mediated actions of circulating angiotensin II may be particularly important in the newborn.

Aging↗

Aspirin, protein transacetylation and inhibition of prostaglandin synthetase in the kidney.

1 The effect of aspirin on the kidney has been investigated in mice and rabbits. [Acetyl-(14)C]-aspirin was administered intraperitoneally in doses ranging from subtherapeutic to toxic. The degree of acetylation of protein was determined by the radioactivity remaining on protein precipitates of renal cortex and medulla after sequential washing designed to remove non-covalently bound material. Controls were established, by the use of [carboxyl-(14)C]-aspirin.2 The acetyl-(14)C residue was bound to renal proteins in a linear manner in increasing amounts with increasing dosage up to 100 mg/kg. The [carboxyl-(14)C]-aspirin was not bound and thus the salicylate portion of the molecule was not bound covalently to the renal protein. The time course of the acetylation was rapid, consistent with the rate of aspirin absorption. The disappearance of acetylated protein was slow, with a T(1/2) of 112.5 h in the renal cortex, and 129.5 h in the renal medulla.3 Differential centrifugation, Sephadex chromatography and gel electrophoresis were carried out on tissue homogenates to determine the site of acetylation. The acetylation was greatest in the microsomal fraction, although all protein fractions showed some degree of acetylation.4 The prostaglandin synthetase activity of a particulate preparation from rabbit kidney was determined by a spectrophotometric assay of malondialdehyde formation. Aspirin (10 mg/kg, i.v.) significantly inhibited prostaglandin synthetase in the renal cortex and medulla.5 Aspirin and renal proteins undergo a transacetylation reaction resulting in stable acetylated protein, with acetylation being greatest in the microsomal fraction. Aspirin has been shown to inhibit prostaglandin synthetase and this could lead to functional impairment of the tissue.

Acetylation↗

Effects of timolol and hydrochlorothiazide on blood-pressure and plasma renin activity. Double-blind factorial trial.

The effects of timolol (10 mg thrice daily) and hydrochlorothiazide (50 mg/day) have been compared in a double-blind factorial trial in 20 patients with essential hypertension. There were four randomised test phases of 8 weeks each during which patients received timolol alone, hydrochlorothiazide alone, timolol plus hydrochlorothiazide, and no treatment (placebo). Blood-pressure was measured weekly, alternately at the outpatient clinic and at the patient's home. Supine mean arterial pressure fell from 119 mm Hg in the placebo phase to 110 mm Hg in the hydrochlorothiazide phase, 106 mm Hg in the timolol phase, and 101 mm Hg in the combined timolol plus hydrochlorothiazide phase. Factorial analysis revealed that these effects of the two drugs were additive without any potentiation or antagonism. Mean plasma-renin activity (P.R.A.) was 5-02 ng/ml/3 h in the placebo phase falling to 1-79 in the timolol phase and rising to 9-54 in the diuretic phase, but remaining unchanged in the combined treatment phase (5-40 ng/ml/3 h). The data suggest that the hypotensive action of timolol is not dependent on the concomitant fall in P.R.A. The methods described provide a valuable tool for quantitating the effects of a given drug, and hence a valid basis for objective comparison.

Adrenergic beta-Antagonists↗

Cold agglutinin formation in patients undergoing haemodialysis. A possible relationship to dialyser re-use.

Cold agglutinins with anti-N characteristics were shown to develop in as short a time as four months in patients on home dialysis. It appeared that the development of such antibodies is related to dialyser re-use. Those who were treated without re-using their dialyser did not develop these antibodies. Anti-N may cause early graft failure associated with agglutination in a cold allograft. Moreover, if these antibodies develop in patients on dialysis there may be problems with extracorporeal dialysis and blood transfusion.

Agglutinins↗