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Biomedical subjects

B Perry

Publications and source records attributed to B Perry.

At least 19 recordsLinked to original sources
PubMed2006

Dopaminergic modulation and rod contribution in the generation of oscillatory potentials in the tiger salamander retina.

The roles of rod and cone input and of dopamine in the generation of oscillatory potentials were studied in tiger salamander retina. Under scotopic conditions, oscillations were elicited with a green, but not a red stimulus. With mesopic background illumination, both stimuli caused oscillations. Addition of quinpirole to a mesopic retina eliminated oscillations while SKF-38393 had no effect. Similarly, addition of sulpiride to a light-adapted retina elicited oscillatory activity, but SCH 22390 had no effect. These results suggest that oscillatory potentials are elicited through activation of the rod pathway and are modulated by dopamine through D2-receptors.

Adaptation, Physiological↗
PubMed2003

Translational regulation of the plant S-adenosylmethionine decarboxylase.

It is becoming apparent that control of protein synthesis by metabolites is more common than previously thought. Much of that control is exerted at the level of initiation of mRNA translation, orchestrated by upstream open reading frames (uORFs) and RNA secondary structure. S-Adenosylmethionine decarboxylase (AdoMetDC) is a key enzyme in polyamine biosynthesis and both mammalian and plant AdoMetDCs are translationally regulated by uORFs in response to polyamine levels by distinct mechanisms.

Adenosylmethionine Decarboxylase↗
PubMed2001

Dog ecology and demography information to support the planning of rabies control in Machakos District, Kenya.

A study of 150 dog-owning households from six randomly selected sublocations was conducted in Machakos District, Kenya. Initially, all households were visited to collect information on dog ecology and demography based on WHO guidelines and to collect serum for rabies antibody detection. A second visit was made 1 year later, to obtain follow-up data on births, deaths, dog movements and other events since the first visit. Dog ownership was common, with a range of 53--81% (mean=63%) of households owning dogs in the six sublocations. Dog density for the five more rural sublocations ranged from 6 to 21 dogs km(-2) and for the peri-urban sublocation was 110 dogs km(-2). The dog population was estimated to be growing at 9% p.a. (95% C.I. 4--14%). This growth was a function of very high fecundity (1.3 females per female per year) more than compensating for high mortality, particularly among females. Life expectancy from birth was 3.5 years for males and 2.4 years for females. Half the dogs at any one time were less than 1 year of age. All dogs, by design of the study, were owned. Of these, 69% were never restricted and roamed freely to forage for food and mix with other dogs. Only a small proportion of dogs (5%) were fed commercial dog food. Most households reported observing dogs scavenging their garbage, including: their own dogs (81%), their neighbours' dogs (75%) and unknown dogs (45%). Only 29% of dogs at least 3 months of age were reported to be vaccinated against rabies. The proportion vaccinated varied widely between sublocations (5--68%); 48% of dogs reportedly vaccinated had detectable antibodies, 31% at or above levels considered to indicate seroconversion. The proportion of dogs with detectable antibodies declined according to the time since last vaccination (55% if vaccinated < or = 1 year, 47% < or = 2 years and 36% > 2 years); 20% of dogs reported not to have been vaccinated had detectable rabies antibody. Compared to other dog populations in rural eastern and southern Africa, Machakos District has a high density of dogs. The Machakos dog population is growing, highly dynamic, poorly supervised and inadequately vaccinated against rabies. The main implication for rabies control is that adequate vaccination coverage is unlikely to be achieved, even under optimal delivery, using the current strategy of annual vaccination of dogs older than 3 months.

Animal Husbandry↗
PubMed2001

Can epidemiology and economics make a meaningful contribution to national animal-disease control?

The general role of veterinary epidemiology and economics to national animal-disease control throughout the world is considered for the four main groupings of animal diseases: zoonotic, food-borne, endemic and epidemic diseases. This is done by considering how veterinary epidemiology and economics has contributed to priority setting (which diseases come first?), decision-making (for a given disease, which strategy is best?), and disease control implementation (how can optimal delivery and adoption of selected interventions best be achieved?). Within each of these categories, progress made and future opportunities are discussed. In addition, a review is made of how veterinary epidemiology and economics has been institutionalised. We conclude that veterinary epidemiology and economics holds a unique role in the development of national policies and strategies for improved animal health world-wide. However, we consider that we must capitalise more on the unique comparative advantage of the partnership between veterinarians and agricultural economists. We believe that much remains to be done to improve the "institutionalisation" of veterinary epidemiology and economics, and the adoption and impact of the products of our unique partnership, particularly in countries of the developing world.

Agriculture↗
PubMed2000

Physical access to primary health care in Andean Bolivia.

Limited physical access to primary health care is a major factor contributing to the poor health of populations in developing countries, particularly in mountain areas with rugged topography, harsh climates and extensive socioeconomic barriers. Assessing physical access to primary health care is an important exercise for health care planners and policy makers. The development of geographic information system (GIS) technology has greatly improved this assessment process in industrialized countries where digital cartographic data are widely available. In developing countries particularly in mountain areas, however, detailed cartographic data, even in hardcopy form, are nonexistent, inaccurate or severely lacking. This paper uses GIS technology to assess physical access to primary health care in a remote and impoverished region of Andean Bolivia. In addition, it proposes an alternative model of health personnel distribution to maximize physical accessibility. Methods involved extensive fieldwork in the region, utilizing GPS (global positioning system) technology in the development of the GIS and gathering other pertinent health data for the study. Satellite imagery also contributed to the development of the GIS and in the modeling process. The results indicate significant variation in physical access to primary health care across the three study sites. More importantly, this paper highlights the use of GIS technology as a powerful tool in improving physical accessibility in mountain areas of developing countries.

Bolivia↗
PubMed2000

Regional oral absorption, hepatic first-pass effect, and non-linear disposition of salmon calcitonin in beagle dogs.

The dose-dependent disposition, first pass hepatic elimination, and absorption pharmacokinetics (PK) of salmon calcitonin (sCT) were investigated in a canine Intestinal Vascular Access Port (IVAP) model. The PK of sCT were determined after intravenous (IV), subcutaneous (SC), portal venous (PV), and oral (PO) administration of sCT. Regional oral absorption of unformulated sCT was also evaluated by direct administration into the duodenum (ID), ileum (IL), and colon (IC) by means of surgically implanted, chronic catheters. Plasma samples were collected and analyzed by radioimmunoassay (RIA). Salmon calcitonin PK were evaluated using 2-compartmental and model independent methods. Intravenous sCT PK were non-linear over the dose range studied. High dose groups (100-1000 microg) demonstrated higher total plasma clearance (CL) and V(dss) than the low dose groups (1-25 microg). However, the MRT did not change for doses ranging from 10 to 1000 microg. After SC administration, the absorption of sCT was rapid with bioavailability (BA) varying from 21.4 to 52.9%. However, the BA of sCT was low after ID, IL, and IC administration (0.039, 0.064, and 0.021%, respectively). The role of hepatic first-pass elimination was negligible. The results of these studies demonstrate that the elimination of sCT is rapid but does not occur in the liver. Enhanced sCT clearance at higher doses was indicated by increasing V(dss) values, and it is hypothesized that increased renal blood flow and/or saturated plasma protein binding may contribute to the non-linear behavior. The IVAP canine model was found to have utility for probing the absorption and disposition PK of sCT. The combination of high oral bioavailability variability and non-linear disposition of sCT may produce highly variable therapeutic effects. The practical impact of the non-linear disposition of sCT remains to be determined. Based on the current results it appears that the rate-limiting step to the successful oral administration of sCT is its delivery into the portal vein since hepatic metabolism was negligible.

Administration, Oral↗
PubMed2000

An educational intervention for front-line health professionals in the assessment and management of suicidal patients (The STORM Project).

BACKGROUND: Suicide prevention is a health priority in many countries. Improved management of suicide risk may improve suicide prevention. This study aimed to assess the feasibility of health district-wide training in the assessment and management of people at risk of suicide; and to assess the impact of training on assessment and management skills. METHODS: Staff in three health care settings, namely primary care, accident and emergency departments and mental health services (N = 359), were offered suicide risk management training in a district-wide programme, using a flexible 'facilitator' approach. The main outcomes were the rate of attendance at training, and changes in suicide risk assessment and management skills following training. RESULTS: It was possible to deliver training to 167 health professionals (47 % of those eligible) during a 6 month training period. This included 95 primary care staff (39%), 21 accident and emergency staff(42%) and 51 mental health staff (78%). Of these, 103 (69%) attended all training. A volunteer sample of 28 staff who underwent training showed improvements in skills in the assessment and management of suicide risk. Satisfaction with training was high. The expected costs of district-wide training, if it were able to produce a 2.5% reduction in the suicide rate, would be 99,747 pound sterling per suicide prevented and 3,391 pound sterling per life year gained. CONCLUSIONS: Training in the assessment and management of suicide risk can be delivered to approximately half the targeted staff in primary care, accident and emergency departments and mental health services. The current training package can improve skills and is well accepted. If it were to produce a modest fall in the suicide rate, such training would be cost-effective. However, a future training programme should develop a broader training package to reach those who will not attend.

Adult↗
PubMed2000

Quality improvement in a managed care organization from a medical director's perspective: an interview with Bruce Perry. Interview by Douglas Roblin.

BACKGROUND: In late 1994 the Quality Forum commissioned the Interdisciplinary Prevention Committee [IPC]. One of the IPC's charges was to identify priorities for QI in preventive health services. The IPC established priorities through a review of scientific literature, identification of national and state health initiative priorities, and consideration of what services to establish as priorities and of the practicality of implementing low-cost interventions to achieve specific QI goals. Breast cancer screening was selected as a top-ten priority for guideline development and for focused intervention because of the disease's prevalence, morbidity, and mortality and because of the fact that it is most treatable and curable when it is found early through routine screening. The national HEDIS (Health Plan Employer Data and Information Set; National Committee on Quality Assurance (NCQA), Washington, DC] result of 71%, reported in May 1995, provided our baseline performance measurement. This result fell short of our goal of being in the 90th percentile of performance on each HEDIS effectiveness of care measure. In August 1995 the Quality Forum accepted the IPC's recommendations, which had been endorsed by the department of medicine. These recommendations emphasized the importance of annual clinical breast exam and mammography for women of targeted age groups. In November 1997, a new "Excellence in Quality: HEDIS Improvement Team" began work. Its charge was to undertake analyses of underlying causes of reduced performance and to develop additional steps to improve performance by changes in care delivery processes in 1998. In March 1998 the Quality Forum's executive committee designated breast cancer screening one of the six organizationwide quality priorities for 1998 and designated two "owners" who would be accountable for this performance--the chief and director of radiology. RESULTS: The screening rate increased from 73.8% in 1996 to 84.0% in 1999. National benchmarks [90th percentile] in 1998 were 81% for commercially insured members and 84% for Medicare members. The 84% screening rate made the Georgia region the Kaiser Permanente national leader and put the region in the top 10% of all health plans in the United States. CONCLUSIONS: The program has achieved these results with a broad array of activities: Saturday hours, mobile mammography, medical record reminders (fuschia-colored inserts), patient and physician reminders, call-center outreach, provider feedback on performance, and provider financial incentives. Several of these innovations demonstrate the ability to integrate improved care management into evolving service delivery in Kaiser Permanente--such as use of call-center technologies and redesign of primary care delivery. While we cannot point to any one of these innovations as a key driver of improvement, it is clear that substantial improvements in care delivery can be achieved. All these activities are relatively low cost and easily implemented in other managed care organizations and in other areas of medical care.

Child↗
PubMed1999

Biopharmaceutical approaches for developing and assessing oral peptide delivery strategies and systems: in vitro permeability and in vivo oral absorption of salmon calcitonin (sCT).

PURPOSE: To evaluate a biopharmaceutical approach for selecting formulation additives and establishing the performance specifications of an oral peptide delivery system using sCT as a model peptide. METHODS: The effect of formulation additives on sCT effective permeability and transepithelial electrical resistance (TEER) was evaluated in side-by-side diffusion chambers using rat intestinal segments. Baseline regional oral absorption of sCT was evaluated in an Intestinal and Vascular Access Port (IVAP) dog model by administration directly into the duodenum, ileum, and colon by means of surgically implanted, chronic catheters. The effect of varying the input rate and volume of the administered solution on the extent of sCT absorption was also evaluated. Citric acid (CA) was utilized in all studies to cause a transient reduction in local pH. In vitro samples and plasma samples were analyzed by radioimmunoassay (RIA). Two oral delivery systems were prepared based on the results of the in vitro and IVAP studies, and evaluated in normal dogs. RESULTS: Maximal permeability enhancement of sCT was observed using taurodeoxycholate (TDC) or lauroyl carnitine (LC) in vitro. Ileal absorption of sCT was higher than in other regions of the intestine. Low volume and bolus input of solution formulations was selected as the optimal condition for the IVAP studies since larger volumes or slower input rates resulted in significantly lower sCT bioavailability (BA). Much lower BA of sCT was observed when CA was not used in the formulation. The absolute oral bioavailability (mean+/-SD) in dogs for the control (sCT + CA) and two proprietary sCT delivery systems was 0.30%+/-0.05%, 1.10+/-0.18%, and 1.31+/-0.56%, respectively. CONCLUSIONS: These studies demonstrate the utility of in vitro evaluation and controlled in vivo studies for developing oral peptide delivery strategies. Formulation additives were selected, the optimal intestinal region for delivery identified, and the optimal release kinetics of additives and actives from the delivery system were characterized. These methods were successfully used for devising delivery strategies and fabricating and evaluating oral sCT delivery systems in animals. Based on these studies, sCT delivery systems have been fabricated and tested in humans with favorable results.

Administration, Oral↗
PubMed1999

Determination of the sum of bilirubin sugar conjugates in plasma by bilirubin oxidase.

BACKGROUND: A reliable indicator of cholestasis is the presence of abnormal concentrations of bilirubin mono- and diglucuronide [conjugated bilirubin (CB)] in blood. A routine assay of CB is available only to those who possess a certain type of clinical analyzer. We describe a two-point manual method for CB that could be adapted as a rate assay to automated clinical analyzers. METHODS: The measurement of CB is based on its oxidation to biliverdin by bilirubin oxidase. The resulting decrease in absorbance at 460 nm is proportional to the CB concentration. The assay is calibrated with solutions of ditaurobilirubin in human serum. RESULTS: Under the conditions of the assay (0.1 mol/L glycine buffer, pH 10.0; reaction time, 2 min), only 5% of unconjugated bilirubin is oxidized and delta-bilirubin is not oxidized at all. Results obtained with the bilirubin oxidase method agreed well with those obtained by HPLC. The long-term CVs at CB concentrations of 6 and 63.4 mg/L were 20% and 2.6%, respectively. The reference values, established by analyzing 51 plasma specimens from healthy adults, were 0.0-1.2 mg/L, with a mean value of 0.2 mg/L. CONCLUSIONS: The proposed method for CB has good analytical specificity and obviates the requirement for HPLC or a dry chemistry analyzer. The measurement of CB in blood is superior to the measurement of direct bilirubin because an abnormal concentration of direct bilirubin does not necessarily indicate the presence of cholestasis.

Bilirubin↗
PubMed1998

Overexpression of human glutathione peroxidase protects transgenic mice against focal cerebral ischemia/reperfusion damage.

As stroke is a major cause of disability and death in the western world, there is great interest in the basic mechanisms by which ischemia/reperfusion (I/R) causes damage. To this end, extensive research has been carried out which identifies reactive oxygen species (ROS) as key participants in brain damage resultant from I/R. Brain tissue is protected from ROS damage by antioxidant enzymes, such as superoxide dismutase (SOD) and glutathione peroxidase (GP). Overexpression of SOD in transgenic mice has already been demonstrated to confer protection against I/R damage in murine stroke models. We are using transgenic mice overexpressing the intracellular form of glutathione peroxidase (GP1) to determine the protective capacity of overexpression of this enzyme on stroke damage. 1 h of focal cerebral ischemia followed by 24 h of reperfusion was induced using the intraliminal suture method. Volume of infarction was reduced by 48% in GP1 mice compared to nontransgenic littermates. Brain edema was reduced by 33%. Behavioral deficits agreed with histologic data. Overexpression of glutathione peroxidase confers significant protection against I/R damage in our stroke model possibly through direct scavenging of ROS or through the influencing of signalling mechanisms which lead to tissue damage.

Animals↗
PubMed1998

Beliefs of eight exemplary oncology nurses related to Watson's nursing theory.

In this paper selected findings of a qualitative study of eight exemplary oncology nurses are presented. The focus is on the views of these nurses about key elements of nursing practice, namely, the nature of health, human beings, nurse-patient relationships, nursing care, and the nursing environment. In the first part of the paper, the research methodology used in the study is outlined. Subsequently, the oncology nurses' beliefs about the five central components of nursing practice are described and related to Jean Watson's theory of nursing.

Attitude of Health Personnel↗
PubMed1997

Combination of dobutamine and myocardial contrast echocardiography to differentiate postischemic from infarcted myocardium.

OBJECTIVES: This study tested whether the combination of dobutamine echocardiography (DE) and myocardial contrast echocardiography (MCE) was superior to either technique alone in identifying postischemic myocardium and in differentiating it from necrotic myocardium. BACKGROUND: Wall motion abnormalities at rest occur in postischemic myocardium in the presence of infarction, stunning or hibernation, alone or in combination. Various investigators have suggested that either DE or MCE can be used to identify the presence of myocardial viability. METHODS: We studied a total of 53 mongrel dogs in an open chest model of coronary occlusion of various durations followed by reperfusion and dobutamine administration (10 microg/kg body weight per min). MCE with aortic root injections of Albunex (area under the curve) and DE (percent thickening fraction) were performed at the different stages. Postmortem triphenyltetrazolium chloride (TTC) staining was used to identify myocardial necrosis. RESULTS: Thirteen dogs underwent brief (15 min) occlusions and developed no necrosis (Group I). Of 40 dogs that underwent prolonged (30 to 360 min) occlusions, 14 had no infarction (Group II), whereas 26 did (Group III: 12 papillary muscle, 7 subendocardial, 7 transmural). MCE (expressed as percent change from baseline) demonstrated changes that paralleled the blood flow changes observed by radiolabeled microspheres at all interventions (r = 0.67, p < 0.0001). Regional ventricular function improved with dobutamine administration in the ischemic region in all three groups. The sensitivity (88%) for detecting myocardial viability was superior when the two techniques were combined; however, a poor specificity (61%) was observed. CONCLUSIONS: Contractile reserve and perfusion data are complementary when assessing regional wall motion abnormalities in postischemic myocardium. DE alone cannot differentiate postischemic from infarcted myocardium; simultaneous data on myocardial perfusion are required. The combination of DE and MCE is superior to either technique alone for identifying the absence of myocardial necrosis.

Animals↗
PubMed1997

Mutant presenilins of Alzheimer's disease increase production of 42-residue amyloid beta-protein in both transfected cells and transgenic mice.

The mechanism by which mutations in the presenilin (PS) genes cause the most aggressive form of early-onset Alzheimer's disease (AD) is unknown, but fibroblasts from mutation carriers secrete increased levels of the amyloidogenic A beta 42 peptide, the main component of AD plaques. We established transfected cell and transgenic mouse models that coexpress human PS and amyloid beta-protein precursor (APP) genes and analyzed quantitatively the effects of PS expression on APP processing. In both models, expression of wild-type PS genes did not alter APP levels, alpha- and beta-secretase activity and A beta production. In the transfected cells, PS1 and PS2 mutations caused a highly significant increase in A beta 42 secretion in all mutant clones. Likewise, mutant but not wildtype PS1 transgenic mice showed significant overproduction of A beta 42 in the brain, and this effect was detectable as early as 2-4 months of age. Different PS mutations had differential effects on A beta generation. The extent of A beta 42 increase did not correlate with presenilin expression levels. Our data demonstrate that the presenilin mutations cause a dominant gain of function and may induce AD by enhancing A beta 42 production, thus promoting cerebral beta-amyloidosis.

Alzheimer Disease↗
PubMed1996

Fluorinated benzazepines: 1. Synthesis, radiosynthesis and biological evaluation of a series of substituted benzazepines as potential radiotracers for positron emission tomographic studies of dopamine D-1 receptors.

We have prepared N-alkyl, aryl, fluoroalkyl, fluoroaryl and iodoaryl derivatives of 7-chloro-8-hydroxy-3-methyl-1-(3'-aminophenyl)-2,3,4,5-tetrahydro-1 H-3-benzazepine (SCH 38548) as high-affinity ligands for the dopamine D1 receptor. Binding affinities of the compounds for dopamine D1, D2, and serotonin 5-HT2 receptor sites in rat brain homogenates were measured. The affinity of SCH 38548 for dopamine D1 receptors was found to be 0.53 +/- 0.46 nM, whereas lower affinities (in the micromolar range) for dopamine D2 and serotonin 5-HT2 receptors were found. Alkylation (ethyl, n-propyl and benzyl) and acylation (benzoyl) of the amino group of SCH 38548 did not decrease affinities for the D1 receptors significantly. The fluoroethyl, fluoropropyl, and fluorobenzyl derivatives showed approximately an 8-fold, 9-fold, and 3-fold decrease in affinity for the D1 sites compared to SCH 38548. The N-4-fluorobenzoyl derivative, however, showed a similar affinity for the D1 sites as for SCH 38548. All four fluorinated derivatives exhibited weak binding at D2 and serotonin 5-HT2 receptors. The N-(4-18F-fluorobenzoyl)SCH 38548 was prepared by reacting SCH 38548 with 4-18F-fluorobenzoyl fluoride in 2-5% radiochemical yield with a specific radioactivity of approximately 600-700 Ci/mmol. The N-(3-18F-fluoropropyl)SCH 38548 was prepared by reacting SCH 38548 with 18F-fluoropropyl iodide in 2-5% radiochemical yield with a specific radioactivity of approximately 600-700 Ci/mmol. N-(4-18F-fluorobenzoyl)SCH 38548 failed to localize in the dopaminergic sites in the rat and rhesus monkey brain. Biodistribution of N-(3-18F-fluoropropyl)SCH 38548 in rats showed specific uptake and retention (0.64% injected dose/g at 30 min) of the radiotracer in the striata, with striata-to-cerebellum ratios reaching 12 at 2 h postinjection (p.i.). Positron emission tomography scans in rheusus monkeys indicate selective uptake of the radiotracer in the striata. After IV injection of N-(3-18F-fluoropropyl)SCH 38548, a rapid brain uptake of the tracer from blood was observed. Initial uptake in the striata and cerebellum was approximately 0.02% of injected dose/cc. Nonspecific uptake from the tissue surrounding the striata cleared slowly. The striata-to-cerebellum ratio increased from 1.20 to 3.5 min postinjection to approximately 2.5 at 120 min p.i. The specific uptake of N-(3-18F-fluoropropyl)SCH 38548 in the striata was displaced by IV administration of SCH 24518 (2 mg/kg).

Animals↗