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Biomedical subjects

H M Scott

Publications and source records attributed to H M Scott.

At least 37 records · Page 2Linked to original sources

Associations of the bovine major histocompatibility complex DRB3 (BoLA-DRB3) alleles with occurrence of disease and milk somatic cell score in Canadian dairy cattle.

Potential associations were investigated between bovine leucocyte antigen (BoLA) alleles and occurrence of disease. Cows (Holstein n = 835; Jersey n = 66) were examined for polymorphisms of the second exon of the BoLA-DRB3 gene, using the polymerase chain reaction (PCR), followed by digestion of the amplified fragments with three restriction endonucleases. Disease occurrences were recorded for each cow throughout one lactation. Milk somatic cell count data were retrieved through the Dairy Herd Improvement records and converted to somatic cell score (SCS). There were no effects of BoLA alleles on SCS in Jersey cows, but BoLA-DRB3.2*16 was significantly associated (P < or = 0.05) with lower SCS in Holsteins. Since the number of Jerseys was relatively small and prevalence of diseases in this population was low, health records of Jerseys were not analyzed further. BoLA associations with occurrence of disease in Holsteins were investigated using a log-linear model. There was a significant (P < or = 0.05) association between BoLA-DRB3.2*23 and occurrence of severe mastitis, from which coliforms were the most commonly isolated bacteria. The BoLA allele *3 was associated with a lower risk of retained placenta (P < or = 0.05) and alleles *16 (P < or = 0.05) and *22 (P < or = 0.05) with a lower risk of cystic ovarian disease. Although more studies are required to confirm the present findings, it can be concluded that BoLA alleles may have potential usefulness as genetic markers of higher or lower risk of disease occurrence in cows.

Alleles↗

Effects of a core antigen vaccine against gram-negative bacteria on physiologic and yield parameters of dairy cows during late lactation and the dry period.

The objective of the study was to assess the effects of a core antigen vaccine against Gram-negative bacteria on feed consumption, milk yield, somatic cell count, hematologic parameters, and milk progesterone concentrations for dairy cows in late lactation and the dry period. Sixty-eight multiparous Holstein cows from two farms were paired by days in milk and were randomly selected to receive either the vaccine or placebo. Cows received a secondary immunization with the same product (vaccine or placebo) 3 wk following the primary immunization. The physiologic and yield outcomes were measured prior to each immunization, at the time of each immunization, and for one or more periods following each immunization. No significant differences between vaccinated and placebo groups were detected for daily milk weight, daily feed intake, somatic cell score, rectal body temperature, or milk progesterone concentration (pregnant cows). Cows in the vaccinated group had significant elevations in total blood leukocyte counts following the secondary immunization, which was due to an increase in the neutrophil fraction 24 h postimmunization.

Animals↗

Clinical mastitis in dairy cattle in Ontario: frequency of occurrence and bacteriological isolates.

The objective of this study was to describe the frequency of occurrence of clinical mastitis in dairy herds in Ontario. The study group consisted of 65 dairy farms involved in a 2-year observational study, which included recording all clinical mastitis cases and milk sampling of quarters with clinical mastitis. Lactational incidence risks of 9.8% for abnormal milk only, 8.2% for abnormal milk with a hard or swollen udder, and 4.4% for abnormal milk plus systemic signs of illness related to mastitis were calculated for 2840 cows and heifers. Overall, 19.8% of cows experienced one or more cases of clinical mastitis during location. Teat injuries occurred in 2.1% of lactations. Standard bacteriology was performed on pretreatment milk samples from 834 cows with clinical mastitis. The bacteria isolated were Staphylococcus aureus (6.7%), Streptococcus agalactiae (0.7%), other Streptococcus spp. (14.1%), coliforms (17.2%), gram-positive bacilli (5.5%), Corynebacterium bovis (1.7%), and other Staphylococcus spp. (28.7%). There was no growth in 17.7% of samples, and 8.3% of samples were contaminated. Clinical mastitis is a common disease in dairy cows in Ontario; approximately 1 in 5 cow lactations have at lease one episode of clinical mastitis. There is, however, considerable variation in the incidence of clinical mastitis among farms. The majority of 1st cases of clinical mastitis occur early in lactation, and the risk of clinical mastitis increases with increasing parity. Environmental, contagious, and minor pathogens were all associated with cases of clinical mastitis.

Animals↗

Survey of physician leadership and management education.

Health-care organizations have recognized the need to prepare physicians for various leadership and management positions within their own institutions. In the past, those who desired further education had to search beyond the boundaries of their practice to fulfill this need. The demands of a dynamic and changing health-care environment have created increased pressure on organizations to develop a larger cadre of physician leaders and managers among their staff and to accomplish this outcome in a cost-effective, efficient manner. This article examines the results from a survey of leading medical institutions on the existence of in-house leadership and management educational programming. It also documents the approaches used by the responding organizations and the content of their course work. Numerous institutions are accepting the challenge for increased physician expertise in leadership and management by developing their own in-house programs. Future directions for Mayo initiatives in succession planning will be obtained from this benchmark survey.

Curriculum↗

Hepatic glucose-6-phosphatase development in preterm and full-term guinea-pigs: comparison with rat and human development.

In term infants, hepatic glucose-6-phosphatase activity rises several-fold in the first few days after birth. In contrast, in many preterm infants, the postnatal rise in activity does not occur and the abnormally low levels can persist. In an attempt to determine if prematurity causes long-term changes in levels of glucose-6-phosphatase in liver of all mammals, we have studied the ontogeny of glucose-6-phosphatase in term guinea-pigs, and also in guinea-pigs delivered prematurely by Caesarean section. The activity of hepatic glucose-6-phosphatase in preterm guinea-pigs is about 5-fold lower than in term guinea-pigs at birth but the activity rises rapidly to very similar values to those found in term guinea-pigs. This indicates that prematurity alone does not result in abnormal development of hepatic glucose-6-phosphatase activity in guinea pigs. The changes in liver glucose-6-phosphatase activity in the postnatal period in term guinea-pigs were much smaller than those occurring in term postnatal rats or term infants.

Age Factors↗

Insulin stimulates cell surface aminopeptidase activity toward vasopressin in adipocytes.

We previously discovered that insulin stimulates the marked translocation of a novel membrane aminopeptidase, designated vp165 for vesicle protein of 165 kDa, to the cell surface in adipocytes. To examine the hypothesis that this enzyme acts on peptide hormones, we assessed the relative affinity of the enzyme for 22 peptide hormones by measuring the inhibitory effect of each on the hydrolysis of a fluorogenic substrate, and we directly assayed the cleavage of four of these. Angiotensin III, angiotensin IV, and Lys-bradykinin bound to the enzyme with half-saturation constants between 20 and 600 nM and were cleaved by vp165. Vasopressin bound with lower affinity but at saturation was cleaved more rapidly. Subsequently, the effect of insulin on the rates of cleavage of 125I-labeled vasopressin by intact 3T3-L1 and rat adipocytes was determined. With both cell types, vasopressin cleavage was stimulated approximately threefold. These findings indicate that a physiological role for vp165 may be the processing of peptide hormones and that insulin could enhance the cleavage of extracellular substrates by eliciting the translocation of vp165 to the cell surface.

3T3 Cells↗

Application of the findings of the European Stroke Prevention Study 2 (ESPS-2) to a New Zealand ischaemic stroke cost analysis.

The aim of this study was to apply the findings of the European Stroke Prevention Study 2 (ESPS-2) to a paper that quantified and described the annual cost of ischaemic stroke in New Zealand, and to compare the cost of alternative drug regimens in the secondary prevention of ischaemic stroke. Comparisons were made between the costs of low-dosage aspirin (acetylsalicylic acid) monotherapy and a combination of modified-release dipyridamole and low-dosage aspirin. Differences in undiscounted costs were calculated over a 2-year period. The New Zealand cost per stroke event was multiplied by the ESPS-2 incremental reduction in stroke events to derive the cost of strokes avoided. As the focus of the paper was on direct medical costs, the primary perspective adopted was that of a healthcare provider or funder, but a societal perspective was also considered by evaluation of direct nonmedical and indirect costs. Compared with aspirin monotherapy, combination therapy generated incremental net direct costs of 18.22 New Zealand dollars ($NZ) per patient or $NZ18,223 per 1000 patients. However, individually, each treatment regimen resulted in direct cost savings when compared with placebo: combination therapy $NZ905.16 per patient; aspirin monotherapy $NZ923.39 per patient (a difference between the 2 regimens of $NZ18.22 per patient). Total direct and indirect incremental cost savings were $NZ40.96 per patient, and $NZ40,963 per 1000 patients, for the combination therapy. The analysis demonstrates that changing patients from low-dosage aspirin to a combination therapy of modified-release dipyridamole plus low-dosage aspirin would result in a small rise in incremental direct costs (using our conservative assumptions relating to hospital and continuing institutional care costs). If less conservative unit cost assumptions were adopted, a more likely outcome would be a saving in direct incremental costs of up to $NZ400 per patient treated.

Aspirin↗

A comparison of the renal and hepatic microsomal glucose-6-phosphatase enzymes.

The liver glucose-6-phosphatase enzyme has been extensively characterized and relatively little is known about the renal microsomal glucose-6-phosphatase enzyme. The reason for lack of study of the renal glucose-6-phosphatase enzyme is that it has been assumed to be the same as the liver enzyme. Immunoblotting with antibodies raised against the liver enzyme revealed differences in apparent molecular weight and antigenicity between the liver and kidney glucose-6-phosphatase enzyme proteins. Characterization of the activity of the renal glucose-6-phosphatase enzyme also showed that it is regulated differently to the liver enzyme in some metabolic states. This implies that the renal and liver glucose-6-phosphatase enzymes may have different roles.

Animals↗

Characterization of the insulin-regulated membrane aminopeptidase in 3T3-L1 adipocytes.

A novel membrane aminopeptidase has been identified as a major protein in vesicles from rat adipocytes containing the glucose transporter isotype Glut4. In this study we have characterized this aminopeptidase, referred to as vp165, in 3T3-L1 adipocytes. The subcellular distributions of vp165 and Glut4 were determined by immunoisolation of vesicles with antibodies against both proteins, by immunofluorescence, and by subcellular fractionation and immunoblotting. Relative amounts of vp165 at the cell surface in basal and insulin-treated cells were assayed by cell surface biotinylation. These experiments showed that vp165 and Glut4 were entirely colocalized and that vp165 increased markedly at the cell surface in response to insulin, in a way similar to Glut4. When intact cells were assayed with a novel, membrane-impermeant fluorogenic substrate for vp165, we found that insulin stimulated aminopeptidase activity at the cell surface. This observation provides direct evidence for the functional consequence of vp165 translocation.

3T3 Cells↗

Economic evaluation of vaccination against influenza in New Zealand.

The objective of this study was to evaluate the costs and benefits of influenza vaccination for the population aged 65 years and over, from the perspectives of individuals and health insurers, government and society. The annual incremental direct medical costs and benefits of influenza vaccination (compared with the nonvaccination, or 'do nothing', option) were evaluated using New Zealand healthcare resource usage and unit cost data [in 1992 New Zealand dollars ($NZ); $NZ1 = $US0.5458, June 1992] applied to cohort studies reported in the literature. The costs and benefits to society as a result of vaccination of people aged 65 years and older (20% of people in this age group are currently vaccinated) were estimated to be: (i) additional direct medical costs of vaccination of $NZ1.42 million [$NZ17.78 per vaccination]; (ii) direct medical costs avoided of $NZ5.35 million ($NZ67.18 per vaccination); and (iii) net benefits of $NZ3.93 million ($NZ49.40 per vaccination). The direct medical costs avoided per dollar cost of vaccination were $NZ1.04 for individuals, $NZ4.69 for government and $NZ3.78 for society as a whole. If the vaccination uptake for this group is increased in 20% increments, the net benefit to society increases by a further $NZ3.93 million per year at each step. If the economic evaluation is extended to include vaccination of at-risk individuals under 65 years of age, net benefits to society increase by 15%. Influenza vaccination for people aged 65 years and over is cost effective from the perspective of society, government and the individual. If the vaccination rate for at-risk individuals in New Zealand could be increased to 60%, the net benefits reported in this study would increase by 200%. However, the costs of promotion and education to achieve this vaccination rate would need to be deducted from the net benefits. Strategies to increase the vaccination rate include altering the cost of vaccinations to the individual, intensifying education and promotion programmes, and changing the mode of delivery.

Cost-Benefit Analysis↗

Heart failure. A decision analytic analysis of New Zealand data using the published results of the SOLVD Treatment Trial. Studies of Left Ventricular Dysfunction.

This study sought to evaluate the changes in direct medical costs and life-years gained or lost by adding enalapril to conventional treatment (digoxin and diuretics) for heart failure (HF). The published results of the Studies of Left Ventricular Dysfunction (SOLVD) Treatment Trial, and a decision analytical model developed by the University of Pennsylvania, were used in combination with New Zealand data to undertake the evaluation. All costs were measured in 1993 New Zealand dollars ($NZ) [$NZ1 = $US0.5509, September 1993]. Potential net cost savings per patient treated over a 4-year period were $NZ652 together with an additional 2 months of life gained. If these individual potential cost savings are extended to the New Zealand population who have HF (but are at present not receiving an ACE inhibitor) then $NZ6 517 000 in discounted health sector costs could be avoided. The model was sensitive to changes in the price of enalapril, to estimates of the population with HF, the percentage of the population with HF treated with enalapril, and to hospital unit costs for nonfatal cases of HF. The study demonstrated that the addition of enalapril to the conventional treatment of HF was cost effective when compared with conventional medical therapy alone.

Angiotensin-Converting Enzyme Inhibitors↗

Hysterectomy for nonmalignant conditions: cost to New Zealand society.

AIMS: The aim of the study was to estimate the annual hospital costs to New Zealand society of hysterectomy for nonmalignant conditions in women between puberty and menopause, and to compare international rates for all hysterectomies. METHODS: The records of patients aged between 15 and 54 years inclusive, who had a hysterectomy for a nonmalignant menstrual condition, were researched. Hospital costs were estimated using specific hospital unit costs and prices. RESULTS: The 4390 hysterectomies for nonmalignant conditions represent 69% of the total hysterectomies undertaken in New Zealand in 1991. Estimated costs for all hospitals were $17 million or $3868 per hysterectomy. The all ages all conditions hysterectomy rate per 100,000 women of 365 (368 in 1992) in New Zealand is higher than in some other developed countries. CONCLUSIONS: Further reduction in the rate of hysterectomy in New Zealand may save hospital costs but these savings should be offset against the costs of any other treatment options chosen. Although it was found that unit costs of public hospitals were higher than those of private hospitals the case mix for the two types of hospital may differ and public hospital cost reductions may not be possible. Economic evaluation of alternative treatment options would be improved if all relevant costs (direct, indirect and intangible) were known. Further research is needed to determine the reasons why New Zealand women elect to have hysterectomies, why most choose a private hospital, and changes (before and after hysterectomy) in productivity, out of pocket expenses, and quality of life for these patients.

Adolescent↗

Cloning and characterization of a novel insulin-regulated membrane aminopeptidase from Glut4 vesicles.

The insulin-regulated glucose transporter isotype GlutT4 expressed only in muscle and adipose cells is sequestered in a specific secretory vesicle. These vesicles harbor another major protein, referred to as vp165 (for vesicle protein of 165 kDa), that like GluT4 redistributes to the plasma membrane in response to insulin. We describe here the cloning of vp165 and show that it is a novel member of the family of zinc-dependent membrane aminopeptidases, with the typical large extracellular catalytic domain and single transmembrane domain but with a unique extended cytoplasmic domain. The latter contains two dileucine motifs, which may be critical for the specific trafficking of vp165, since this has been shown to be the case for this motif in GluT4. However, the tissue distribution of vp165 is much wider than that of GluT4; consequently, vp165 may also function in processes unrelated to insulin action and may serve as a ubiquitous marker for a specialized regulated secretory vesicle.

Adipose Tissue↗

Fatty acyl-CoA esters inhibit glucose-6-phosphatase in rat liver microsomes.

In native rat liver microsomes glucose 6-phosphatase activity is dependent not only on the activity of the glucose-6-phosphatase enzyme (which is lumenal) but also on the transport of glucose-6-phosphate, phosphate and glucose through the respective translocases T1, T2 and T3. By using enzymic assay techniques, palmitoyl-CoA or CoA was found to inhibit glucose-6-phosphatase activity in intact microsomes. The effect of CoA required ATP and fatty acids to form fatty acyl esters. Increasing concentrations (2-50 microM) of CoA (plus ATP and 20 microM added palmitic acid) or of palmitoyl-CoA progressively decreased glucose-6-phosphatase activity to 50% of the control value. The inhibition lowered the Vmax without significantly changing the Km. A non-hydrolysable analogue of palmitoyl-CoA also inhibited, demonstrating that binding of palmitoyl-CoA rather than hydrolysis produces the inhibition. Light-scattering measurements of osmotically induced changes in the size of rat liver microsomal vesicles pre-equilibrated in a low-osmolality buffer demonstrated that palmitoyl-CoA alone or CoA plus ATP and palmitic acid altered the microsomal permeability to glucose 6-phosphate, but not to glucose or phosphate, indicating that T1 is the site of palmitoyl-CoA binding and inhibition of glucose-6-phosphatase activity in native microsomes. The type of inhibition found suggests that liver microsomes may comprise vesicles heterogeneous with respect to glucose-6-phosphate translocase(s), i.e. sensitive or insensitive to fatty acid ester inhibition.

Acyl Coenzyme A↗

Multiple transport protein defects in a patient with glycogen storage disease type 1: GSD 1b/1c beta.

A male child presented at 5 months of age with vomiting, diarrhoea, hypoglycaemia and hepatomegaly. Histology on a frozen liver biopsy suggested glycogen storage disease (GSD), while biochemical analyses confirmed an elevated glycogen content and normal activities of the GSD enzymes with the proviso that a variant of GSD 1 should be considered. The patient presented at 9 months of age with severe lactic acidosis and hypoglycaemia. A glucagon tolerance test and galactose load test on the patient produced no glycaemic response. A second biopsy was obtained and appropriately handled for the investigation of variants of the glucose-6-phosphatase enzyme (G6Pase) complex. Results showed that the patient had a deficiency of two transport proteins of the G6Pase complex, namely glucose-6-phosphate translocase and pyrophosphate translocase, i.e. GSD 1b/1c beta. These results were confirmed by additional kinetic analyses which provided confirmation of the double translocase deficiency. Evidence for inhibitors to these translocases was not found. The patient's treatment has resulted in the hypoglycaemia now being well controlled; however, at 3 years of age, height and weight are markedly lagging and he is moderately developmentally delayed. Neutropenia has not been found and neutrophil function is normal. Double enzyme deficiencies are very rare and possible explanations which might lead to this phenotype are considered. This, to the authors' knowledge, is the first report of a double translocase deficiency causing GSD type 1.

Antiporters↗

Pharmacoeconomic evaluation of roxithromycin versus amoxycillin/clavulanic acid in a community-acquired lower respiratory tract infection study.

A cost-effectiveness study of roxithromycin versus amoxycillin/clavulanic acid using data from a 242 patient multicentre trial in Australia and New Zealand was undertaken in the general practice treatment of infections of the lower respiratory tract (LRTI). Those patients assigned to roxithromycin required on average 1 day less of treatment, significantly fewer extended courses of treatment, and fewer patients experienced side effects considered to be related to the treatment. The cost benefit (difference between the two treatment costs) per clinical success was A$17.04*. By substituting roxithromycin for amoxycillin/clavulanic acid, Australia would save A$ 1.704 million per 100,000 episodes of LRTI. The results demonstrate that savings in direct costs can be achieved by substituting roxithromycin for amoxycillin/clavulanic acid in the treatment of community-acquired LRTI.

Adolescent↗