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Biomedical subjects

A D Watson

Publications and source records attributed to A D Watson.

At least 37 records · Page 2Linked to original sources
PubMed1999

Plasma cortisol concentrations following cortisone infusion in dogs before and after treatment with cortisone acetate.

OBJECTIVE: To evaluate effects of iatrogenic hyperadrenocorticism on plasma cortisol concentrations produced by an infusion of hydrocortisone in dogs. PROCEDURE: Plasma cortisol concentrations were measured regularly during a 6 h infusion of hydrocortisone sodium succinate at two dose rates. The infusions were performed before and after treatment for 30 d with oral cortisone acetate at 10 mg/kg/24 h, divided thrice daily. Adrenal activity during the experimental period was assessed by weekly ACTH stimulation tests. RESULTS: Both infusion rates produced lower plasma cortisol concentrations after treatment for 30 d with cortisone. CONCLUSION: Prior exposure to high concentrations of glucocorticoids may result in accelerated metabolism of glucocorticoids administered subsequently. This may necessitate increased dosages when using glucocorticoids to support inadequate adrenal function.

Administration, Oral↗
PubMed1999

Role of group II secretory phospholipase A2 in atherosclerosis: 2. Potential involvement of biologically active oxidized phospholipids.

Secretory nonpancreatic phospholipase A2 (group II sPLA2) is induced in inflammation and present in atherosclerotic lesions. In an accompanying publication we demonstrate that transgenic mice expressing group II sPLA2 developed severe atherosclerosis. The current study was undertaken to determine whether 1 mechanism by which group II sPLA2 might contribute to the progression of inflammation and atherosclerosis is by increasing the formation of biologically active oxidized phospholipids. In vivo measurements of bioactive lipids were performed, and in vitro studies tested the hypothesis that sPLA2 can increase the accumulation of bioactive phospholipids. We have shown previously that 3 oxidized phospholipids derived from the oxidation of 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (PAPC) stimulated endothelial cells to bind monocytes, a process that is known to be an important step in atherogenesis. We now show that these 3 biologically active phospholipids are significantly increased in livers of sPLA2 transgenic mice fed a high-fat diet as compared with nontransgenic littermates. We present in vitro evidence for several mechanisms by which these phospholipids may be increased in sPLA2 transgenics. These studies demonstrated that polyunsaturated free fatty acids, which are liberated by sPLA2, increased the formation of bioactive phospholipids in LDL, resulting in increased ability to stimulate monocyte-endothelial interactions. Moreover, sPLA2-treated LDL was oxidized by cocultures of human aortic endothelial cells and smooth muscle cells more efficiently than untreated LDL. Analysis by electrospray ionization-mass spectrometry revealed that the bioactive phospholipids, compared with unoxidized PAPC, were less susceptible to hydrolysis by human recombinant group II sPLA2. In addition, HDL from the transgenic mice and human HDL treated with recombinant sPLA2 in vitro failed, in the coculture system, to protect against the formation of biologically active phospholipids in LDL. This lack of protection may in part relate to the decreased levels of paraoxonase seen in the HDL isolated from the transgenic animals. Taken together, these studies show that levels of biologically active oxidized phospholipids are increased in sPLA2 transgenic mice; they also suggest that this increase may be mediated by effects of sPLA2 on both LDL and HDL.

Animals↗
PubMed1998

Plasma cortisol responses to three corticotrophic preparations in normal dogs.

OBJECTIVE: To compare cortisol responses to three corticotrophic preparations in normal dogs. ANIMALS: Eight clinically normal dogs (four intact males, four intact females) of medium size. PROCEDURES: Each dog received four treatments on four separate occasions in a duplicated Latin square pattern. Treatments were two adrenocorticotrophin (ACTH) preparations given intramuscularly at 2.2 U/kg, one of the ACTH preparations given intramuscularly at 1 U/kg and a synthetic polypeptide with ACTH-like activity (tetracosactrin, cosyntropin) given intravenously at 5 micrograms/kg. Plasma samples were taken for cortisol assay before and at 0.5, 1, 2 and 4 h after treatment. RESULTS: Plasma cortisol concentrations were similar with the two ACTH preparations and at both dose rates. Tetracosactrin produced smaller mean peak cortisol concentrations, which tended to occur earlier than with ACTH, and smaller values for the area under the curve of plasma cortisol concentration from zero time to 4 h. CONCLUSION: The findings suggest that canine adrenal function can be tested adequately by giving ACTH intramuscularly at 1 U/kg and measuring plasma cortisol in samples taken at 0 and 2 h, or by giving tetracosactrin intravenously at 5 micrograms/kg and determining cortisol concentration at 0 and 1 h.

Adrenal Cortex Function Tests↗
PubMed1998

Effects of delmadinone acetate on pituitary-adrenal function, glucose tolerance and growth hormone in male dogs.

OBJECTIVE: To characterise the effects of delmadinone acetate on the pituitary-adrenal axis, glucose tolerance and growth hormone concentration in normal male dogs and dogs with benign prostatic hyperplasia. DESIGN: A prospective study involving nine normal male dogs and seven with prostatic hyperplasia. PROCEDURE: Delmadinone acetate was administered to six normal male dogs and seven dogs with benign prostatic hyperplasia at recommended dose rates (1.5 mg/kg subcutaneously at 0, 1 and 4 weeks). Three normal controls received saline at the same intervals. Blood concentrations of ACTH, cortisol, glucose, insulin and growth hormone were measured over 50 days. Intravenous glucose tolerance and ACTH response tests were performed before and after treatment in the nine normal animals. RESULTS: A substantial suppression of basal and 2 h post-ACTH plasma cortisol secretion was demonstrated after one dose in all dogs given delmadinone acetate. Individual responses after the second and third administration varied between recovery in adrenal responsiveness to continued suppression. Plasma ACTH concentration was also diminished after one treatment. No effects were evident on glucose tolerance or serum growth hormone concentrations. CONCLUSION: Delmadinone acetate causes adrenal suppression from inhibition of release of ACTH from the pituitary gland. Treated dogs may be at risk of developing signs of glucocorticoid insufficiency if subjected to stressful events during or after therapy. Neither glucose intolerance nor hypersomatotropism seems likely in male dogs given delmadinone acetate at the recommended dose rate, but the potential for excessive growth hormone secretion in treated bitches remains undetermined.

Adrenal Cortex↗
PubMed1998

Cost-effectiveness comparison of three methods of internal fixation for arthrodesis of the first metatarsophalangeal joint.

We used decision-analysis modeling to determine the most cost-effective fixation device among Herbert screws, AO screws, and the Luhr plate for first metatarsophalangeal joint arthrodesis. The model considered patient-reported outcomes at minimum 2-year follow-up, patient charges for the entire course of care, and event and outcome incidences within each fixation group. AO screws had the lowest average cost of utility and, therefore, are the most cost-effective fixation device for first metatarsophalangeal joint arthrodesis even though utility is highest with the Luhr plate. Operating room costs and union rate most strongly influenced cost-effectiveness.

Arthrodesis↗
PubMed1997

Structural identification by mass spectrometry of oxidized phospholipids in minimally oxidized low density lipoprotein that induce monocyte/endothelial interactions and evidence for their presence in vivo.

Entry of monocytes into the vessel wall is an important event in atherogenesis. Previous studies from our laboratory suggest that oxidized arachidonic acid-containing phospholipids present in mildly oxidized low density lipoproteins (MM-LDL) can activate endothelial cells to bind monocytes. In this study, biologically active oxidized arachidonic acid-containing phospholipids were produced by autoxidation of 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (Ox-PAPC) and analyzed by liquid chromatography and electrospray ionization mass spectrometry in conjuction with biochemical derivatization techniques. We have now determined the molecular structure of two of three molecules present in MM-LDL and Ox-PAPC that induce monocyte-endothelial interactions. These lipids were identified as 1-palmitoyl-2-(5-oxovaleryl)-sn-glycero-3-phosphocholine (m/z 594.3) and 1-palmitoyl-2-glutaryl-sn-glycero-3-phosphocholine (m/z 610.2). These two molecules were produced by unambiguous total synthesis and found to be identical by analytical techniques and bioactivity assays to those present in MM-LDL and Ox-PAPC. Evidence for the importance of all three oxidized phospholipids in vivo was suggested by their presence in fatty streak lesions from cholesterol-fed rabbits and by their immunoreactivity with natural antibodies present in ApoE null mice. Overall, these studies suggest that specific oxidized derivatives of arachidonic acid-containing phospholipids may be important initiators of atherogenesis.

Animals↗
PubMed1997

Monocyte binding to endothelial cells induced by oxidized phospholipids present in minimally oxidized low density lipoprotein is inhibited by a platelet activating factor receptor antagonist.

Our group has previously demonstrated that oxidized phospholipids derived from mildly oxidized low density lipoprotein (MM-LDL) or oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (oxPAPC) increase monocyte-endothelial interactions. There are indications that the effects of these phospholipids are receptor mediated. Oxidized phospholipids have previously been shown to activate cells via the platelet activating factor (PAF) receptor, therefore, we pretreated human aortic endothelial cells (HAECs) with a PAF-receptor antagonist (WEB 2086) prior to treatment with oxPAPC. WEB 2086 inhibited monocyte binding to endothelial cells induced by oxPAPC (200 micrograms/ml) at concentrations from 1 nM to 10 microM, but had no effect on the induction of monocyte binding induced by lipopolysaccharide (LPS). We were able to isolate and identify several active oxidized phospholipids by combined normal phase high performance liquid chromatography (HPLC) and electrospray mass spectrometry (LC/MS). The induction of monocyte binding to HAECs by two of these partially purified phospholipids was totally abolished by the pretreatment of HAECs with WEB 2086 (100 nM). PAF itself, however, when tested at concentrations from 10 nM to 10 microM had no effect on monocyte binding. These results suggest that several of the oxidized phospholipids present in MM-LDL and oxPAPC induce monocyte binding through a receptor which is perhaps distinct from the PAF-receptor, but can be blocked by the PAF-receptor antagonist WEB 2086.

Aorta↗
PubMed1997

Safe withdrawal of monotherapy for hypertension is poorly effective and not likely to reduce health-care costs.

OBJECTIVE: To carry out a population-based evaluation of withdrawal of treatment in primary care using repeated ambulatory blood pressure monitoring (ABPM) assessment to avoid subjecting patients to prolonged periods of excess risk. METHOD: Patients from two community practices (total population 11 034 patients) being administered monotherapy for hypertension, were identified and invited to participate. Subjects were withdrawn from treatment if they had no significant co-morbidity and daytime ABPM blood pressure was < or = 150/90 mmHg. Antihypertensive therapy was restarted if daytime ABPM blood pressure was > 150/90 mmHg during weeks 4, 8, 12, 26, 39 and 52. RESULTS: Of 126 eligible patients 53 had a co-morbidity and 37 declined to participate. Of the 36 patients who entered the study 10 were excluded because they had elevated ABPM blood pressures during treatment and one because they had echocardiographic left ventricular hypertrophy. Of the 25 patients from whom monotherapy was withdrawn, we restarted treatment of 19 before week 52. If clinic blood pressure monitoring had been used instead of ABPM, different decisions would have been taken in eight of 25 cases. The costs of the ABPM-determined withdrawal of treatment programme were greater than the expected savings in drug costs, even assuming that all six patients from whom treatment was withdrawn remained without treatment for a further 9 years. This conclusion was not sensitive to reducing the number of ABPM measurements and to inflation in study-drug costs. However, if all patients had been treated with the most expensive drug, then even the full ABPM programme could have saved money within 9 years. CONCLUSIONS: Antihypertensive therapy could be withdrawn from only a small proportion of patients in the community on the basis of ABPM. The costs of the programme are likely to exceed savings unless the cost of drugs administered is substantially higher than that observed in this study.

Aged↗
PubMed1997

Canine histiocytic ulcerative colitis.

OBJECTIVE: To assess prevalence, breed predilection, response to therapy and prognosis of canine histiocytic ulcerative colitis (CHUC). DESIGN: A retrospective study of cases of CHUC seen at Sydney University Veterinary Teaching Hospital (SUVTH) over a 20-year period (1975-1994). PROCEDURE: Case records of all dogs in which colitis was suspected were reviewed. Dogs were diagnosed with CHUC based on colonorectal biopsy and histopathological examination. RESULTS: CHUC was diagnosed in 8 of 57 dogs presented for colitis. All affected dogs were Boxers and six were female. Dogs with milder clinical signs showed moderately good response to therapy. Four dogs were still alive 1 to 7 years after diagnosis. Three dogs were euthanased, one for reasons other than CHUC, and one was lost to follow-up. CONCLUSIONS: Young boxer dogs with relatively mild signs of CHUC may respond moderately well to medical and dietary therapy with fair prognosis. Euthanasia early in the course of the disease may be unwarranted. Prevalence may be increasing within the SUVTH referral population.

Animals↗
PubMed1997

Retrospective study of 60 cases of feline lymphosarcoma.

OBJECTIVE: To characterise epidemiological and clinical findings, and diagnostic procedures undertaken, in cats with lymphosarcoma at a veterinary teaching hospital. DESIGN: Retrospective case study. PROCEDURE: Hospital records were reviewed for 7159 cats, sick or healthy, examined during a 10-year period (1984 to 1994). Sixty cats with lymphosarcoma were identified and classified by anatomical location of the tumor. Data on breed, age, sex, clinical signs and diagnostic procedures were collated. RESULTS: The prevalence of feline lymphosarcoma in the hospital population was 0.84%. Siamese cats appeared predisposed to lymphosarcoma but other purebreds were not. Males were somewhat overrepresented amongst affected cats. Similar numbers of cases (12 to 18) were seen in each of the four anatomic categories (multicentric, mediastinal, alimentary and extranodal). Cats with mediastinal lymphosarcoma were mostly young and Siamese. Clinical signs in affected cats were varied, usually multiple and often nonspecific. Two of 22 cases tested positive for feline leukaemia virus antigen in blood and 6 of 13 were positive for feline immunodeficiency virus antibody. CONCLUSIONS: Extranodal lymphosarcoma seemed more prevalent in this study than reported elsewhere. Siamese cats in the study population may have had a genetic predisposition to lymphosarcoma. Limited evidence suggested feline leukaemia virus may be less important, and feline immunodeficiency virus more important, in the local population than indicated in overseas reports. Additional studies are needed to investigate breed predisposition and feline leukaemia virus and feline immunodeficiency virus status in Australian cats with lymphosarcoma.

Age Distribution↗
PubMed1997

Lipid oxidation products have opposite effects on calcifying vascular cell and bone cell differentiation. A possible explanation for the paradox of arterial calcification in osteoporotic patients.

Atherosclerotic calcification and osteoporosis often coexist in patients, yielding formation of bone mineral in vascular walls and its simultaneous loss from bone. To assess the potential role of lipoproteins in both processes, we examined the effects of minimally oxidized low-density lipoprotein (MM-LDL) and several other lipid oxidation products on calcifying vascular cells (CVCs) and bone-derived preosteoblasts MC3T3-E1. In CVCs, MM-LDL but not native LDL inhibited proliferation, caused a dose-dependent increase in alkaline phosphatase activity, which is a marker of osteoblastic differentiation, and induced the formation of extensive areas of calcification. Similar to MM-LDL, oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (ox-PAPC) and the isoprostane 8-iso prostaglandin E2 but not PAPC or isoprostane 8-iso prostaglandin F2 alpha induced alkaline phosphatase activity and differentiation of CVCs. In contrast, MM-LDL and the above oxidized lipids inhibited differentiation of the MC3T3-E1 bone cells, as evidenced by their stimulatory effect on proliferation and their inhibitory effect on the induction of alkaline phosphatase and calcium uptake. These results suggest that specific oxidized lipids may be the common factors underlying the pathogenesis of both atherosclerotic calcification and osteoporosis.

Alkaline Phosphatase↗