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Biomedical subjects

B L Carter

Publications and source records attributed to B L Carter.

At least 19 recordsLinked to original sources

Ambulatory care pharmacy services: the incomplete agenda.

OBJECTIVE: To review studies that document the impact of clinical pharmacy services in ambulatory care settings and to propose standards of practice and resource allocation needs in ambulatory care. DATA SOURCES: English-language literature from 1970 through 1991 was reviewed and the representative literature is described. STUDY SELECTION: Studies were selected that examined the impact of clinical pharmacy services on patient outcomes and costs. Studies that evaluated pharmacist consultations by blind peer-review panels were also evaluated. DATA EXTRACTION: Trials were assessed based on their methodologies and ability to assess the value of clinical pharmacy services on patient outcomes. DATA SYNTHESIS: Numerous studies from the past 20 years are described illustrating the impact that ambulatory care pharmacy practitioners have made on patient care. These studies demonstrate that clinical pharmacists in ambulatory care not only serve as consultants on pharmacotherapy issues, but also can improve the quality of care for individual patients. CONCLUSIONS: Based on the studies cited and the needs of ambulatory patients, this article highlights the authors' views on what the standards of practice should be for ambulatory care practitioners and where resources should be allocated as ambulatory programs are expanded.

Ambulatory Care

Evaluation of glipizide and glyburide in a health maintenance organization.

OBJECTIVE: To determine if there was a difference in the long-term glycemic control, average daily dose, and cost of therapy in patients with noninsulin-dependent diabetes mellitus (NIDDM) treated with glyburide and glipizide in a health maintenance organization (HMO). DESIGN: Retrospective evaluation of medical and pharmacy records. SETTING: Multispecialty group practice HMO. PATIENTS: 140 NIDDM patients being treated with either glyburide (n = 70) or glipizide (n = 70) were randomly selected from the populations of patients receiving either drug using computerized pharmacy records. MAIN OUTCOME MEASURE: Mean daily doses and blood glucose measurements (fasting blood glucose, random blood glucose, hemoglobin A1C) were stratified in 3-month periods from the time the drug therapy was started or the patient first presented to the clinic for a total of 18 months. Long-term glycemic control was defined as fasting blood glucose less than 8.33 mmol/L (150 mg/dL). RESULTS: The groups were comparable with regard to age (53.4 y glyburide, 56.7 y glipizide), gender (43 M:27 F glyburide, 47 M:23 F glipizide), race (38 W/16 B/16 H glyburide, 45 W/16 B/9 H glipizide), concurrent medical conditions, adverse effects, and compliance. Long-term glycemic control was similar in both groups. Although the number of subjects who were controlled (by definition) tended to be greater in the glyburide group, no clinical or statistical difference was found. There was no statistical difference in mean daily dose between the ethnic groups, but the small numbers preclude further analysis. The glipizide group had a larger percentage increase in dose within the first year than did the glyburide group; however, the percentage increase from the 3-month dose was similar after 18 months (22.7 percent glyburide, 27.5 percent glipizide.) Average daily cost of therapy, based on mean daily dose, was slightly lower for glyburide-treated patients. CONCLUSIONS: If glycemic control is similar with glyburide and glipizide, as seen in this study, economic considerations regarding choice of therapy and formulary inclusion may be appropriate.

Adult

Decision analysis as a quality-assurance screening tool.

BACKGROUND: The purpose of this pilot study was to examine whether the technique of decision analysis, including sensitivity analysis, could be used in a clinical quality-assurance program. METHODS: This research was performed in a family practice residency clinical practice. A computerized decision analysis model was developed for selection of initial drug therapy for hypertension. The medical records of 52 resident-managed patients with hypertension were then reviewed. The residents' drug prescribing was evaluated by faculty reviewers and also by the decision analysis model, including a sensitivity analysis. RESULTS: Faculty reviewers rated the residents' drug choices as "most appropriate" or "acceptable" in 59.6% of cases. There was good agreement between faculty reviewers and the computerized decision analysis model. For example, in those cases in which the resident chose the computer model's first-choice drug, faculty deemed the management as "most appropriate" or "acceptable" 93.3% of the time. When residents selected the computer model's third or fourth choice, faculty judged the residents' therapy as "inappropriate" or "an alternate drug would have been more desirable" in 61.9% of cases. CONCLUSION: The results suggest that computerized decision analysis techniques may be a useful adjunct to other clinical quality-assurance procedures in residency training programs.

Adult

Therapy of acute thromboembolism with heparin and warfarin.

The indications, efficacy, dosage, administration, and monitoring of heparin and warfarin therapy for acute thromboembolic events are reviewed, with emphasis on recent changes in treatment recommendations. High-dose heparin therapy is indicated for acute deep-vein thrombosis and pulmonary embolism. Heparin therapy as an adjunct to thrombolytic agents for acute myocardial infarction is becoming increasingly accepted. Heparin therapy for acute thromboembolic events consists of a dosage that elevates the activated partial thromboplastin time to 1.5 to 2.0 times the control value; formerly, 1.5 to 2.5 times control was considered therapeutic. The recommended heparin dosage is a bolus dose of 70-100 units/kg followed by an infusion of 15-25 units/kg/hr. To prevent recurrent thromboembolism, most patients require long-term therapy following acute treatment; this typically consists of warfarin, which should be initiated on day 1 or 2 of heparin therapy whenever possible. For most indications, the intensity of warfarin has been reduced to a dosage that elevates the prothrombin time to 1.3 to 1.5 times control. Alternative therapies (low-molecular-weight heparins) and routes (subcutaneous heparin) should be further investigated. Current recommendations for heparin and warfarin therapy of acute thromboembolism include reduced intensity of both drugs and shortened duration of therapy. Since the therapeutic ranges for both heparin and warfarin therapy have been compressed, closer monitoring may be necessary to achieve and maintain adequate anticoagulation.

Acute Disease

Potential use of aldose reductase inhibitors to prevent diabetic complications.

Reviewed are (1) the biochemical basis and pathophysiology of diabetic complications and (2) the structure-activity relationships, pharmacology, pharmacokinetics, clinical trials, and adverse effects of aldose reductase inhibitors (ARIs). ARIs are a new class of drugs potentially useful in preventing diabetic complications, the most widely studied of which have been cataracts and neuropathy. ARIs inhibit aldose reductase, the first, rate-limiting enzyme in the polyol metabolic pathway. In nonphysiological hyperglycemia the activity of hexokinase becomes saturated while that of aldose reductase is enhanced, resulting in intracellular accumulation of sorbitol. Because sorbitol does not readily penetrate the cell membrane it can persist within cells, which may lead to diabetic complications. ARIs are a class of structurally dissimilar compounds that include carboxylic acid derivatives, flavonoids, and spirohydantoins. The major pharmacologic action of an ARI involves competitive binding to aldose reductase and consequent blocking of sorbitol production. ARIs delay cataract formation in animals, but the role of aldose reductase in cataract formation in human diabetics has not been established. The adverse effects of ARIs include hypersensitivity reactions. Although the polyol pathway may not be solely responsible for diabetic complications, studies suggest that therapy with ARIs could be beneficial. Further research is needed to determine the long-term impact and adverse effects of ARIs in the treatment of diabetic complications.

Aldehyde Reductase

Pharmacotherapy and the primary care physician.

Clinical pharmacy services and pharmacotherapy specialists did not begin in primary care settings. Rather, the initial interdisciplinary teams took root in large hospitals and tertiary medical center inpatient services during the middle 1960s. By the early 1970s, however, numerous papers appeared that described a unique and exciting practice model that incorporated primary care physicians and clinical pharmacists. The sole purpose of the interdisciplinary concept was to allow each member to contribute their own expertise to improve patient care. In my experience, primary care physicians have been eager to consult clinical pharmacists and other health professionals. I believe that the reason for this is a fundamental philosophy that distinguishes these physicians from other medical specialists. Ingrained in their philosophy are concepts such as continuity of care and care of the entire patient. The latter relates, not only to multiple organ systems, but also the spiritual and behavioral characteristics of the person. The primary care physician is also viewed as the coordinator for all health care services required by their patients. Most primary care physicians welcome others' expertise as long as they continue to be the health care coordinator for the patient. The health care structure of the United States continues to shift to ambulatory care. This will provide additional opportunities for the types of group models described in this article. After 20 years, the positive impact that physician and pharmacotherapist teams can have on drug therapy is being recognized on a broader scale. These models should continue to move from the academic laboratory to private group practice.(ABSTRACT TRUNCATED AT 250 WORDS)

Drug Therapy

Therapy for hypercholesterolemia.

For most patients, hypercholesterolemia can be effectively lowered with drug therapy but only after several issues have been considered. First, drug therapy should never be considered without adequate dietary intervention. Dietary therapy may be effective for many patients with mild to moderate elevations in cholesterol. None of the drugs used to treat lipid disorders are benign agents. There is still debate about the interpretations of recent studies, the ability to generalize from studies to the whole population, and the cost effectiveness of drug treatment. Within the framework of the AHA and NCEP guidelines, an individualized approach to therapy is prudent. This should be initiated with maximal patient education because drug therapy will be maintained for the long-term or for life. The LDL and HDL levels, age, sex, other CHD risk factors, cost of treatment, patient awareness, and motivation must all be assessed when making treatment decisions. When drug therapy is considered for patients with isolated hypercholesterolemia, bile acid sequestrants are the drugs of choice.

Anticholesteremic Agents

Once-daily propranolol for hypertension: a comparison of regular-release, long-acting, and generic formulations.

This randomized, single-blind, crossover study compared three formulations of propranolol, each given once daily for hypertension. After an initial titration phase, subjects randomly received regular-release, long-acting, or a generic propranolol formulation. Each drug was given for 4 weeks and each active treatment was separated by a washout phase to allow blood pressure to return to baseline. Twelve subjects received all three active treatments. Systolic and diastolic blood pressures and pulses were significantly reduced from baseline by all formulations. There was no significant difference among drugs. Examination of diastolic blood pressures suggested some loss of antihypertensive control at the end of the dosing interval. These results indicate that it may be possible to administer propranolol once daily for hypertension and that there is no advantage for using the long-acting form.

Adult

Initial drug therapy for hypertensive patients with hyperlipidemia.

Hypertension and hyperlipidemia are cardiovascular risk factors that commonly coexist. Studies have indicated that it is important to control both risk factors to achieve significant reductions in morbidity and mortality. Recent debate has focused upon whether traditional step I antihypertensive agents can substantially lower these risks because of their effects on plasma lipids. This debate continues to be unresolved. However, for the patient with elevated lipid levels, diuretics and beta-blockers may make the management of the lipid disorder more difficult. Therefore it may be desirable to select alternative step I antihypertensive agents that will not interfere with the therapy for hyperlipidemia. Alternative step I agents include alpha 1-blockers, ACE inhibitors, and calcium channel blockers. These agents either have no effect on plasma lipids or they improve the lipid profile. Generally, these drugs are well tolerated and provide good alternatives for patients with hyperlipidemias. The initial drug of choice can be chosen depending upon other patient variables such as age, race, or concomitant diseases.

Adrenergic alpha-Antagonists

Evaluation of a Bayesian regression program for predicting warfarin response.

The ability of a Bayesian regression program (Warfcalc) to predict warfarin response was evaluated retrospectively in 48 inpatients and prospectively in 10 inpatients. The prothrombin ratio (PR) on the last day of inpatient therapy was predicted using zero (naive) to five sequential, daily PR feedbacks. Bias and precision were measured using mean error (ME) and mean absolute error (MAE), respectively. Root mean squared error (RMSE) was used as a combined measure of bias and precision. In the retrospective group, the use of five PR feedbacks yielded the lowest ME, MAE, and RMSE (0.22, 0.30, and 0.45, respectively). The use of two and three daily PR feedbacks resulted in larger prediction errors compared with the use of naive parameters. Further evaluation of the retrospective patient data indicated that deletion of PR feedbacks associated with an activated partial thromboplastin time greater than 100 s and exclusion of metabolic inhibitors in the estimation of warfarin clearance resulted in more reliable predictions (ME = 0.07, MAE = 0.20, RMSE = 0.28). Similarly, deletion of such PR feedbacks and metabolic inhibitors from the prospective data and use of PRs for the first 5 days of therapy yielded ME, MAE, and RMSE values of 0.07, 0.21, and 0.27, respectively. The variance for prothrombin complex activity (PCA) as a function of the variance in the prothrombin time (PT) was investigated using Monte Carlo simulation assuming four different random error models for the PT measurements. These error models yielded functions that exhibit a maximum coefficient of variation at PCA values of 40-70%.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

Antihypertensive drug-prescribing patterns of internists and family physicians.

Surveys that evaluated antihypertensive drug-prescribing patterns were mailed to 150 family physicians and 150 primary care internists. The initial mailing was followed by a telephone follow-up and a second mailing. Forty-seven percent of family physicians and 41.9% of the internists who were still in practice returned the questionnaire. When asked about their choice of antihypertensive drug therapy for specific patients (based upon age, race, sex, and coexisting disease), the responses of the two specialties were similar. The only statistically significant difference was observed in the responses for a 58-year-old obese white woman with diabetes and renal impairment. In this example, the family physicians were more likely than internists to recommend an angiotensin converting enzyme inhibitor or a beta-blocker (P = .036). This study demonstrates that the majority of physicians individualized initial therapy for hypertension to the specific patient rather than strictly following a stepped-care approach with diuretics or beta-blockers as initial therapy.

Adrenergic beta-Antagonists

Antihypertensive therapy in the elderly.

Control of hypertension in the elderly has been shown to reduce cardiovascular morbidity. Although it is not known if this is also true for isolated systolic hypertension, drug treatment should be considered for systolic pressures over 170 mm Hg that cannot be controlled with nondrug therapy. The diuretics, calcium channel blockers, and the ACE inhibitors are very effective and generally well-tolerated therapy for the elderly. It may be necessary to combine two of these agents for some patients. Beta blockers are particularly useful for patients with ischemic heart disease or prior myocardial infarction. Beta blockers are the only agents which have been shown to be cardioprotective. For all antihypertensive agents, the elderly should be started on low doses. The drugs should then be titrated slowly if necessary. It is common for the elderly to respond to lower dosages than younger patients, and they should be monitored carefully for adverse reactions to medications. Antihypertensives should be administered once or twice daily whenever possible. If these principles are considered, most patients can be effectively controlled with a minimum of side effects.

Aged

Amplification of plasmid copy number by thymidine kinase expression in Saccharomyces cerevisiae.

A 2 micron circle-based chimaeric plasmid containing the yeast LEU2 and the Herpes Simplex Virus type 1 thymidine kinase (HSV-1 TK) genes was constructed. Transformants grown under selective conditions for the LEU2 gene harboured the plasmid at about 15 copies per cell whilst selection for the HSV-1 TK gene led to an increase to about 100 copies per cell. Furthermore, the plasmid copy number could be controlled by the stringency of selection for the TK gene, and the increase in TK gene dosage was reflected in an increase in intracellular thymidine kinase activity. The mitotic stability of the plasmid in "high-copy" and "low-copy" number cells was determined. "High-copy" number cells showed a greater mitotic stability. The relationship of TK expression to plasmid copy number may be useful for the isolation of plasmid copy number mutants in yeast and the control of heterologous gene expression.

Gene Amplification

Imaging modalities for the study of the paranasal sinuses and nasopharynx.

Disease entities affecting the paranasal sinuses and nasopharynx are now evaluated primarily by computed tomography (CT) and magnetic resonance imaging (MRI). Cortical bone is best seen by CT, particularly with thin sections and high-resolution bone mode. Bone marrow and various soft-tissue structures are best evaluated by MRI. This article is a demonstration of the normal anatomy of the area as depicted by both CT and MRI.

Diagnostic Imaging

The secretion and post translational modification of interferons from Saccharomyces cerevisiae.

Studies with three interferon molecules, IFN-alpha 2, IFN-beta 1, and a "hybrid" interferon, IFNX-430 are described which illustrate that both the expression and secretion characteristics of heterologous proteins in yeast cells reflect properties of the proteins themselves. Recombinant DNA techniques have also been used to demonstrate that the efficient processing of mature heterologous proteins from the yeast alpha factor secretion leader can be affected by sequences on the carboxyl side of the initial cleavage site. Secretion studies with heterologous proteins in S. cerevisiae are aimed at maximising yield, the percentage of extracellular product and correct amino terminus sequence. The results presented here show that all three factors are susceptible to currently unpredictable properties of the foreign sequence. This situation, in turn, means that heterologous proteins can be used as tools in the biochemical dissection of the yeast secretion process.

Amino Acid Sequence

Secretion of mammalian polypeptides from yeast.

Yeast cells are capable of expressing and secreting foreign polypeptides into the medium. Mammalian glycoproteins are glycosylated when secreted from yeast although the exact oligosaccharide sequence is not reproduced.

Amino Acid Sequence