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Biomedical subjects

D L Harrison

Publications and source records attributed to D L Harrison.

17 recordsLinked to original sources

Low stomatal and internal conductance to CO2 versus Rubisco deactivation as determinants of the photosynthetic decline of ageing evergreen leaves.

A novel A-Ci curve (net CO2 assimilation rate of a leaf -An- as a function of its intercellular CO2 concentration -Ci) analysis method (Plant, Cell & Environment 27, 137-153, 2004) was used to estimate the CO2 transfer conductance (gi) and the maximal carboxylation (Vcmax) and electron transport (Jmax) potentials of ageing, non-senescing Pseudotsuga menziesii leaves in relation to their nitrogen (N) content and protein and pigment composition. Both gi and the stomatal conductance (gsc) of leaves were closely coupled to Vcmax, Jmax and An with all variables decreasing with increasing leaf age. Consequently, both Ci and Cc (chloroplastic CO2 concentration) remained largely conserved through successive growing seasons. The N content of leaves, as well as the amount of ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) and other sodium dodecyl sulfate-soluble proteins, increased during the first three growing seasons, then stabilized or decreased only slightly afterwards. Thus, the age-related photosynthetic nitrogen use efficiency (PNUE) decline of leaves was not a consequence of decreased allocation of N towards Rubisco and other proteins involved in bioenergetics and light harvesting. Rather, loss of photosynthetic capacity was the result of the decreased activation state of Rubisco and proportional down-regulation of electron transport towards the photosynthetic carbon reduction (PCR) and photorespiratory (PCO) cycles in response to a reduction of CO2 supply to the chloroplasts' stroma. This study emphasizes the regulatory potential and homeostaticity of Cc- rather than photosynthetic metabolites or Ci- in relation to the commonly observed correlation between photosynthesis and gsc.

Carbon Dioxide↗

K15 expression implies lateral differentiation within stratified epithelial basal cells.

Keratins are intermediate filament proteins whose expression in epithelial tissues is closely linked to their differentiated state. The greatest complexity of this expression is seen in the epidermis and associated structures. The critical basal (proliferative) cell layer expresses the major keratin pair, K5 and K14, but it also expresses an additional type I keratin, K15, about which far less is known. We have compared the expression of K15 with K14 in normal, pathological, and tissue culture contexts; distinct differences in their expression patterns have been observed that imply different regulation and function for these two genes. K15 appears to be preferentially expressed in stable or slowly turning over basal cells. In steady-state epidermis, K15 is present in higher amounts in basal cells of thin skin but in lower amounts in the rapidly turning over thick plantar skin. Although remaining high in basal cell carcinomas (noninvasive) it is suppressed in squamous cell carcinomas (which frequently metastasize). Wounding-stimulated epidermis loses K15 expression, whereas K14 is unchanged. In cultured keratinocytes, K15 levels are suppressed until the culture stratifies, whereas K14 is constitutively expressed throughout. Therefore, unlike K14, which appears to be a fundamental component of all keratinocytes, K15 expression appears to be more tightly coupled to a mature basal keratinocyte phenotype.

Amino Acid Sequence↗

The health care cost of drug-related morbidity and mortality in nursing facilities.

BACKGROUND: Preventable drug-related morbidity and mortality within nursing facilities represent a serious problem urgently requiring expert medical attention. The health care costs of drug-related problems can be both immense and avoidable. However, the research to date has been narrow in scope, focusing on the drug costs avoided and failing to consider the wider range of possible negative outcomes and potential drug-related problems. OBJECTIVES: To develop a model of therapeutic outcomes resulting from drug therapy within nursing facilities, to estimate the magnitude of the cost of drug-related morbidity and mortality within nursing facilities in the United States, and to assess the impact of pharmacist-conducted, federally mandated, monthly, retrospective review of nursing facility residents' drug regimens in reducing the cost of drug-related morbidity and mortality. METHODS: Using decision analysis techniques, a probability pathway model was developed to estimate the cost of drug-related problems within nursing facilities. An expert panel consisting of consultant pharmacists and physicians with practice experience in nursing facilities and geriatric care was surveyed to determine conditional probabilities of therapeutic outcomes attributable to drug therapy. Health care utilization and associated costs derived from negative therapeutic outcomes were estimated. RESULTS: Baseline estimates indicate that the cost of drug-related morbidity and mortality with the services of consultant pharmacists was $4 billion compared with $7.6 billion without the services of consultant pharmacists. CONCLUSIONS: Drug-related morbidity and mortality in nursing facilities represent a serious economic problem. For every dollar spent on drugs in nursing facilities, $1.33 in health care resources are consumed in the treatment of drug-related problems. With the current federally mandated drug regimen review, it is estimated that consultant pharmacists help to reduce health care resources attributed to drug-related problems in nursing facilities by $3.6 million.

Cost of Illness↗

Pharmacoeconomics and therapeutic drug monitoring.

The ever increasing rate of inflation and the reality that resources for medical care are limited has led to significant changes in the reimbursement for health care services. These influences have convinced health care policy makers to closely evaluate innovative health services in terms of the benefits and costs. New pharmaceutical services must be economically justified in order to exist in the future. This is crucial to the expansion and adoption of pharmaceutical services. Application of economic evaluations is not new to the health care sector. Until recently, there were no incentives to transfer this interest into widespread use. As health care expenditures have escalated over the past two decades, the number of applications of these techniques has increased. Especially significant are cost-benefit and cost-effectiveness evaluations of medical practice, pharmaceuticals, and other health care technologies. Pharmacoeconomic analysis is an important tool to assist in the evaluation of new pharmaceutical services and technologies. Essentially, economic analytical methods are used to weigh the positive and negative consequences of alternative courses of action. The usefulness of pharmacoeconomic analyses is in resource allocation, with the purpose of achieving the highest return on investment or accomplishing a given objective in the least costly manner. Unfortunately, very few pharmacy programs have been evaluated using pharmacoeconomic techniques. The purpose of this article is to present various methods to assess the economic value of therapeutic drug monitoring services in society and for specific patient populations. Additionally, this article will review the previous attempts and various issues surrounding the economic justification of therapeutic drug monitoring.

Drug Monitoring↗

Insulin-induced hypertension in rats depends on an intact renin-angiotensin system.

This study tested the dependence of insulin-induced hypertension in rats on a functional renin-angiotensin system. Rats were instrumented with chronic artery and vein catheters and housed in metabolic cages. After acclimation, 10 rats began receiving the angiotensin-converting enzyme inhibitor (ACEI) benazepril at 1.8 mg.kg-1.d-1 via a continuous intravenous infusion that was maintained throughout the study; 8 control rats received vehicle. Four days after starting ACEI or vehicle, all rats entered a 5-day control period that was followed by a 7-day insulin infusion at 1.5 mU.kg-1.min-1. Glucose was coinfused at 22 mg.kg-1.min-1 to prevent hypoglycemia. Insulin infusion in control rats increased mean arterial pressure (MAP; measured 24 h/d) from an average of 101 +/- 1 to 113 +/- 2 mm Hg on day 1; MAP averaged 110 +/- 1 mm Hg for the 7-day infusion period. Glomerular filtration rate decreased, although not significantly, from 2.7 +/- 0.1 to 2.1 +/- 0.2 mL/min on day 3. Chronic ACEI decreased baseline MAP from an average of 97 +/- 1 to 79 +/- 1 mm Hg and markedly attenuated the increase in MAP during insulin. MAP averaged 81 +/- 1 mm Hg for the 7-day period and increased significantly, to 85 +/- 2 mm Hg, only on day 3. Likewise, the tendency for glomerular filtration rate to decrease was blunted. These results indicate that insulin-induced hypertension in rats depends on angiotensin II and suggest that a reduction in glomerular filtration rate contributes to the shift in pressure natriuresis.

Angiotensin II↗

Strategic planning in the community pharmacy.

The extent and quality of strategic planning by community pharmacy owners and/or managers was assessed. Also examined were factors that may explain respondents use of the strategic planning process. A mail questionnaire on strategic planning yielded a total of 562 usable surveys (37.4% response rate). An unexpectedly small proportion (less than 31%) of respondents reported using strategic planning. Respondents who conducted strategic planning rated significantly higher the time available for their knowledge of, and the importance of strategic planning than those respondents who did not conducts strategic planning.

Community Pharmacy Services↗

Epitope mapping of monoclonal antibodies to keratin 19 using keratin fragments, synthetic peptides and phage peptide libraries.

To generate tools for monitoring processing and folding in keratin intermediate filaments, a group of monoclonal antibodies reacting with the intermediate filament protein keratin 19 were studied using different approaches to define the structure and localization of their epitopes. The binding pattern to bacterially expressed human keratin 19 fragments allowed the definition of minimal amino acid sequences required for antibody binding. The screening of overlapping 15-residue peptides confirmed and further specified the epitope locations for a subset of the tested antibodies. In addition, the epitope of an antibody with apparent species-restricted specificity (LE64) was revealed by isolating and characterizing a full-length keratin 19 clone from a PtK2 cDNA library. Taken together with species cross-reactivity of individual antibodies and sequence information obtained by probing a phage display library, specific amino acid residues could be highlighted as likely to be involved in the antibody binding.

Amino Acid Sequence↗

The production model as a basis for conducting economic evaluations of regional poison control centers.

To identify the significant inputs, activities, and outputs of a regional poison control center, a production model is described and its potential application to the conduct of economic evaluations delineated. The model can help the researcher identify the significant inputs (costs) incurred through the provision of poison control center services. These inputs directly influence the activities that the poison center is capable of undertaking. Activities undertaken by a poison center are intermediate steps between the inputs and outputs, and serve to convert the various inputs into associated outputs. They form the basis for determining the outputs produced by the poison center services. The outputs derived from poison center services provide the conceptual framework for assessing the effectiveness of a poison center in an economic analysis. Also described are potential applications of the production model in conducting poison center cost-effectiveness and cost-benefit analyses.

Cost-Benefit Analysis↗

Expression of keratin mRNAs and proteins in normal salivary epithelia and pleomorphic adenomas.

Control of keratin (K) gene expression may be important for cell differentiation in complex epithelia such as salivary gland. To investigate differences in distribution between keratin mRNAs and their respective proteins, a combined in situ hybridization (ISH) and immunohistochemical study was undertaken on nine normal salivary glands and seven pleomorphic adenomas. ISH employed riboprobes to K7, K8, K14, K18, and K19. Immunohistochemistry was performed on adjacent sections using monoclonal antibodies (MAbs) to the same keratins. Normal luminal cells showed abundant hybridization with probes for K7, K8, K18, and K19. Keratin 14 mRNA was present in basal and myoepithelial cells at a low level of expression. Proteins of their keratins were strongly stained. Neoplastic cells showed variable expression of mRNA and protein for K7, K8, K18, and K19. There was a high level of K14 mRNA but variable protein. The findings provide evidence that expression of these keratins in normal salivary epithelia is regulated transcriptionally and that in neoplasia this system is in considerable disarray.

Adenoma, Pleomorphic↗

Serum unconjugated bile acids: qualitative and quantitative profiles in ileal resection and bacterial overgrowth.

Qualitative and quantitative profiles of unconjugated bile acids in the serum obtained over a 24-h period from three patients with ileal resections and one with a bacterial overgrowth are described. Unconjugated serum bile acids were determined using the high sensitivity and resolution of capillary column gas liquid chromatography after their rapid extraction and isolation using reverse phase octadecylsilane bonded silica cartridges and the lipophilic gel Lipidex 1000. Unconjugated serum bile acid concentrations were elevated throughout the day in both ileum resected patients and in conditions involving bacterial overgrowth when compared to healthy subjects. Total conjugated cholic acid concentrations were expectedly low in both intestinal disorders and were without the postprandial increases generally observed in healthy subjects. Qualitative gas chromatographic profiles of serum unconjugated bile acids in bacterial overgrowth distinctly revealed a predominance of deoxycholic acid and other secondary bile acids in all samples, while, in conditions of an impaired enterohepatic circulation, deoxycholic acid was absent or present in only trace amounts. The potential significance of measuring serum unconjugated bile acids in intestinal disorders is discussed.

Adult↗

Evaluating the results of mail survey research.

OBJECTIVE: To present overall guidance enabling the reader to critically evaluate survey research conducted via mail questionnaire. Also considered are the sources of error that may operate during the conduct of survey research and the threats they pose to both the internal rigor of the study and the generalizability of the results. STUDY SELECTION: Not applicable. DATA EXTRACTION: Not applicable. DATA SYNTHESIS: Not applicable. CONCLUSION: Survey research has been used so commonly and for such a wide range of purposes in a large number of fields, that some people may mistakenly conclude that surveys are easy to conduct. Survey research involves much more than generating a set of questions to ask a group of subjects. To draw valid conclusions about the topic of a survey, the pharmacist must be prepared to evaluate the results in light of how well the investigators approached four sources of error--coverage, sampling, measurement, and nonresponse. The evaluation of survey administration procedures primarily concerns determining whether or not a pilot study was conducted, whether proper statistical analyses were conducted, and whether multiple mailing procedures were used. Failure to account for these sources of error, or inappropriate survey administration, could seriously affect both the generalizability and validity of the results.

Data Interpretation, Statistical↗

Cost-effectiveness of regional poison control centers.

BACKGROUND: Poison exposures are a significant public health concern. Despite the impact that regional poison control centers have on reducing morbidity and mortality associated with poison exposures, they are facing a serious financial crisis today resulting in an increased emphasis on their economic justification. METHODS: Using decision-analysis techniques, the cost-effectiveness of the treatment of poison exposures with the services of a regional poison control center compared with treatment without access to any poison control center was evaluated. The relative cost-effectiveness was modeled based on 2 outcomes (morbidity and mortality) for each of 4 typical poison exposures. Additionally, analyses were conducted to test the sensitivity of the cost-effectiveness ratios to outcome probability, average inpatient and emergency department costs, and proportion of poison exposures treated on site by the regional poison control center. A societal perspective was adopted. RESULTS: The regional poison control center was substantially more cost-effective than the treatment of poison exposures without the services of a regional poison control center for both outcomes (morbidity and mortality) in each of the poison exposures considered. The results of the sensitivity analyses demonstrated that the outcomes of the decision analyses do not change regardless of the type of poison exposure, outcome considered, clinical outcome probabilities, average inpatient and emergency department costs, and proportion of poison-exposure cases treated on site by a regional poison control center. CONCLUSIONS: The regional poison control center is consistently more cost-effective in the treatment of poison exposures with an average cost-effectiveness ratio (cost per successful outcome) approximately half of that achieved without the services of a regional poison control center. Finally, significant cost savings to society are realized for each additional successful outcome obtained with a regional poison control center.

Acetaminophen↗