Peripheral beta-receptor responsiveness in patients with essential hypertension.

Peripheral beta-adrenergic receptor sensitivity was characterized in 24 patients with essential hypertension and in 13 age-matched normotensive subjects using an isoproterenol hydrochloride bolus dose-response technique. Decreased beta-receptor responsiveness to this exogenously administered beta-agonist was observed in hypertensive patients; for an equivalent chronotropic effect, higher doses of isoproterenol were required in hypertensive subjects than in normal subjects. Among "normal-renin" hypertensive patients, beta-receptor responsiveness was directly related to furosemide-stimulated plasma renin activity (PRA), suggesting that independently stimulated PRA may provide an indirect estimate of endogenous beta-receptor sensitivity. Hypertensive patients whose mean arterial pressure fell at least 10 mm Hg after four weeks of treatment with hydrochlorothiazide had even further depression in beta-receptor responsiveness, whereas receptor sensitivity was unchanged in patients whose blood pressure was unaffected. Thus, it is unlikely that this decreased receptor responsiveness in patients with untreated essential hypertension is a direct consequence of elevated arterial pressure.

Growth hormone stimulation of the mitogen-activated protein kinase pathway is cell type specific.

The GH receptor is a member of the cytokine receptor superfamily. Studies in the 3T3-F442A mouse preadipocyte have shown that GH activates the Janus kinase (JAK2), the signal transducers and activators of transcription (STAT1, -3, and -5), and mitogen-activated protein (MAP) kinase. Our previous studies in the human IM-9 lymphocyte have shown that GH activates JAK2 and only STAT5 (not STAT1 or -3). In the studies presented here, we have investigated activation of the MAP kinase (MAPK) pathway in the IM-9 lymphocyte. Western blotting with antiphosphotyrosine-, anti-MAPK-, and anti-phospho-MAPK-specific antibodies as well in vitro kinase assays using a synthetic peptide substrate demonstrate that although GH (200 ng/ml) activates MAPK in 3T3-F442A cells (at 5 and 10 min of treatment), it does not activate MAPK in IM-9 lymphocytes at time points ranging from 5-60 min. Nevertheless, the phorbol ester phorbol 12-myristate 13-acetate (50 ng/ml) does activate MAPK in the IM-9 cell, and immunoprecipitation with specific antibodies indicates that this activation occurs through c-Raf-1. Although the 52- and 66-kDa forms of the adapter protein Shc are tyrosine phosphorylated in response to GH treatment in 3T3-F442A cells, we demonstrate that the predominant forms in IM-9 cells are the 52- and 46-kDa forms, and neither is tyrosine phosphorylated in response to GH. These studies further elucidate the differential signaling by GH in two cell types.

A novel method for assigning TAP1 genotype using restriction enzyme plus PASA methodology.

The function of the TAP gene products appears to be the transport of antigenic peptides into the lumen of the endoplasmic reticulum where peptides are loaded onto HLA molecules. The polymorphisms within the TAP genes and potential disease associations are the subject of intense current study. While several methods have been described for TAP1 genotyping, most of these methods are unable to definitively assign TAP1 genotypes to individuals heterozygous at more than one polymorphic position. A combination named TAP1U was observed in approximately 25% of study subjects. We developed a restriction enzyme based method that allows definitive TAP1 genotypes assignment to 100% of subjects. We also further developed and optimized TAP genotyping by PCR amplification of specific alleles (PASA) that resulted in significant time and cost savings. Hence, we report a novel method for assigning TAP genotypes for TAP1U subjects and the modified PASA reactions. These improvements facilitate the rapid and efficient assignment of TAP genotypes useful for large human disease-gene association studies.

Intentional prescription nonadherence (noncompliance) by the elderly.

Prescription drugs are not always taken as directed. When there is a discrepancy between the use of a drug and the prescription directions, the drug-taking behavior is considered "nonadherent." To determine the extent of prescription non adherence by old persons and the reasons for nonadherence, an in-home survey was made of 111 elderly subjects who were taking prescription drugs. Drug-taking behavior was compared with the behavior implied by the prescription instructions, the reasons for the differences were sought. Of the study sample, 43 per cent showed such differences in use of one or more prescription drugs. The chief type of discrepancy was underuse (90 per cent of nonadherence). No difference was observed in most of the psychosocial variables studied between those who took drugs as directed and those who did not. Hypertensive subjects did not differ from those without hypertension. A large proportion of nonadherence (73 per cent) was intentional. Intentional nonadherence was more likely to occur in subjects who used two or more pharmacies and two or more physicians. Traditional efforts aimed at reducing the incidence of forgetting to take medicines would not seem to be helpful in cases of intentional nonadherence.

Comparative efficacy of pirprofen and aspirin in rheumatoid arthritis.

A six-month double-blind, randomized, parallel-design trial comparing pirprofen, a new nonsteroidal antiinflammatory drug, with aspirin in patients with rheumatoid arthritis is described. The dose of pirprofen, a phenylpropionic acid derivative, was 600 mg per day; the dose of aspirin was 3600 mg per day. Pirprofen was found to be as effective as aspirin in improving the modified articular index, swelling joint index, grip strength, walking time, and duration of morning stiffness. Fewer patients receiving pirprofen reported drug-related side effects than those receiving aspirin, however, the difference was not statistically significant (P less than 0.1). There was no significant difference between groups in the incidence of positive stool guaiac tests (three of 17, pirprofen; five of 18, aspirin). Pirprofen was found to be as safe and effective as aspirin in the management of patients with rheumatoid arthritis.

The clinical pharmacist in a family practice residency program.

A project of interdisciplinary family medicine education was conducted in which a clinical pharmacist served as a drug therapy consultant-educator in a family practice residency program. The clinical pharmacist provided drug information, advised about drug therapy, taught in formal conferences, prepared and disseminated a drug information bulletin, made rounds with the physicians, provided drug blood level consultation, and conducted a drug utilization review project. The family physicians' attitudes about clinical pharmacy were assessed by interviews before and after the project and by a questionnaire administered after the project. The physicians and the pharmacist in this model were observed to have a greater understanding of the interdisciplinary team practice concept; and an active role for the clinical pharmacist as a teacher and consultant was reinforced.

Evaluation of minoxidil.

The chemistry, pharmacokinetics, mechanism of action, clinical studies, adverse effects, toxicology, indications, contraindications, drug interactions, and dosing of minoxidil, a recently approved antihypertensive agent, are reviewed. Minoxidil is an orally effective vasodilator that selectively relaxes peripheral arteriolar smooth muscle, Reflex tachycardia, renin stimulation, and sodium retention occur when minoxidil is used and so it requires the concomitant use of a diuretic and a sympathoplegic agent, usually a beta blocker. Hirsutism and pericardial effusions are additional adverse effects. Minoxidil is indicated in the management of severe hypertension in patients who do not respond to standard antihypertensive agents. In controlled and unctrolled studies, minoxidil was effective in patients with hypertension secondary to renal or renovascular disease and in patients with essential hypertension. Minoxidil is a potent antihypertensive agent with adverse effects that limit its use to patients resistant or intolerant to other drugs.

Establishing a pharmacy clinic in a city-county health department.

During a one-year rotation at an urban-county health department, a pharmacy resident implemented a pharmacy clinic to serve three major purposes: (1) to provide health care to patients with selected chronic illnesses, (2) to expand the revenue base of the health department pharmacy, and (3) to make possible the clinical instruction of Doctor of Pharmacy students and pharmacy residents. The resident's activities in the clinic included conducting interviews, performing physical examinations, initiating and adjusting therapy, and counseling patients. During the first four months of operation, 36 patients were seen in the clinic a total of 98 times. Seven chronic illnesses, along with a number of minor acute disorders, were evaluated and treated by the pharmacist. The pharmacist billed $1740.00 for patient care activities. The success of this initial program indicates that similar pharmacy clinics would be of benefit to other colleges of pharmacy as well as other institutional ambulatory health care providers.

Comparison of the taste and acceptance of three potassium chloride preparations.

The palatability and acceptance of three commercially available potassium chloride solutions were evaluated. Adult ambulatory patients routinely self-administering potassium chloride solution rate the palatability and acceptance of each preparation. An open-label, three-treatment crossover study design was used. The taste of Klorvess was rated significantly more palatable than Kaochlor (p less than 0.01) or KayCiel (p less than 0.05). Klorvess was rated significantly more acceptable if taken over a long period of time than Kaochlor (p less than 0.01) or KayCiel (p less than 0.01). The average amount consumed of all three products was 57% of the prescribed amount. The amount of Klorvess returned was significantly less than the amount of either KayCiel (p less than 0.01) or Kaochlor (p less than 0.01). The flavoring agents are described and the importance of ensuring that the patient uses an accurate measuring spoon is discussed.

The use of student evaluations in examining clinical teaching in pharmacy.

A procedure for eliciting student ratings of clerkship teacher performance was implemented. The purpose of the study was to determine the reliability of student evaluations, explore the differences in teaching roles in relation to student evaluations, and identify those teaching behaviors that were closely associated with overall teacher effectiveness. Students rated clerkship teachers on eight teaching behaviors, including organization, stimulation and enthusiasm about discipline, ability to establish rapport, active involvement with students, level of knowledge and use of sound reasoning, ability to teach clinical procedures and skills, provision of direction and feedback on learning, and accessibility. A ninth item for evaluation of overall teaching effectiveness was also included. At the end of each clinical rotation, students anonymously rated each teacher on a five-point scale. Student ratings were used to evaluate performance and to identify teachers whose clinical skills needed improvement. As one component of an overall approach to performance review, the student evaluation procedure provided for input from the consumer of the teaching activity. When necessary, educational specialists provided consultation to instructors to identify, in detail, clinical teaching behaviors that needed improvement and to suggest remedial strategies. This article describes the development and use of an approach to assess clinical teaching in the clerkships of the College of Pharmacy. After reviewing the literature to determine the characteristics of clinical teaching, an approach was established that paralleled the needs of the faculty and the constraints of the clinical settings. Once the system was implemented and the data were gathered on clinical teaching, investigations were required to examine the reliability of the survey, to identify those behaviors more closely related to effective clinical teaching, and to determine the advantages and disadvantages of using this approach. As a result, this study examines the literature on assessing clinical teaching, describes the approach developed for the College of Pharmacy, identifies some important behaviors in clinical teaching, and discusses the benefits and limitations of the assessment mechanisms to improve clinical teaching.

Teaching interviewing skills to pharmacy residents.

An instructional program for first-year pharmacy residents in the use of interviewing techniques when assessing the drug therapy of patients is described. The objectives of this project were to (1) teach the appropriate use of interviewing skills and (2) observe the performance of pharmacy residents in assessing the drug therapy of ambulatory patients. Instructional methods included a written self-instructional packet, videotaped lecture and demonstration skits, group discussion, and role playing. Following these, during a four-week period, the residents interviewed patients in the outpatient pharmacy and reviewed their performance on videotape with the instructor. Two simulated patient case situations using a resident posing as a patient who provided predetermined information were used to measure student performance in interviewing patients. An improvement in the ability of the residents to employ the interview techniques and to assess the therapy of patients was noted.