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Biomedical subjects

D R Graber

Publications and source records attributed to D R Graber.

28 records · Page 2Linked to original sources

Studies on (H(+)-K+)-ATPase inhibitors of gastric acid secretion. Prodrugs of 2-[(2-pyridinylmethyl)sulfinyl]benzimidazole proton-pump inhibitors.

The synthesis of N-substituted benzimidazole (H(+)-K+)-ATPase or proton-pump inhibitors is described. These compounds were prepared to function as prodrugs of the parent N-H compound and evaluated for their ability to inhibit gastric (H(+)-K+)-ATPase and gastric acid secretion. The prodrugs reported rely on either in vivo esterase hydrolysis for liberation of the parent compound (type I and type II) or require an acid environment for release of the active drug (type III and type IV). The N-(acyloxy)alkyl-substituted benzimidazoles 9, 11, and 24 showed improved chemical stability in the solid state and in aqueous solutions when compared to their parent N-H compounds. When given orally, 24 was found to be twice as potent as omeprazole in both the Shay rat and inactivation of gastric (H(+)-K+)-ATPase in the rat. The N-ethoxy-1-ethyl-substituted benzimidazoles 48-50 were found equally as effective as the N-H compound for inhibition of rat (H(+)-K+)-ATPase activity. In the Shay rat 48 at 10 mg/kg was approximately twice as active as parent timoprazole.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Synthesis of the four isomers of 5-hydroxy-PGI1.

We wish to report here the syntheses of (5S, 6R)-5-hydroxy-, (5R, 6R)-5-hydroxy-, (5R, 6S)-5-hydroxy-, and (5S, 6S)-5-hydroxy-PGI1 and their methyl ester derivatives. Treatment of (5R, 6S)-epoxy- and (5S, 6R)-epoxy-PGF1alpha methyl esters with acid washed silica gel afforded (5R, 6R)-5-hydroxy- and (5S, 6S)-5-hydroxy-PGI1 methyl esters; correspondingly, silica promoted cyclization of (5S, 6S)-epoxy- and (5R, 6R)-epoxy-PGF1alpha methyl esters yielded (5S, 6R)-5-hydroxy- and (5R, 6S)-5-hydroxy-PGI1 methyl esters. Alternatively, the 5-hydroxyl group was introduced into the PGI1 skeleton via reaction of the 5-mercuric halides with sodium borohydride in the presence of oxygen. Stereochemical assignments were based on their mode of synthesis and 1H nmr shift differences.

Prostaglandins↗

Oxidative ozonolysis of 6-oxo-PGF1alpha, 11,15-diacetate, methyl acetal, methyl ester.

Ozonolysis of 6-oxo-PGF1alpha, 11,15-diacetate, methyl acetal, methyl ester followed by oxidative workup and treatment with diazomethane gave 3-acetoxy-5-hydroxy-2-(methoxycarbonyl) cyclopentane acetic acid, gamma-lactone and dimethyl 3-acetoxy-5[[-(methoxycarbonyl)valeryl]oxy]-1,2-cyclopentane dicarboxylate as two of the major products. The mass spectral properties of the latter compound were identical with those previously published by other investigators.

Chemical Phenomena↗

Curriculum trends in nurse practitioner programs: current and ideal.

The purpose of this study was to ascertain the extent to which nurse practitioner (NP) education programs are addressing curriculum topics related to practice competencies needed for the next century as recommended by the Pew Health Professions Commission and other professional organizations, including the American Association of Colleges of Nursing and the National Organization of Nurse Practitioner Faculties. The study was part of a comprehensive survey of 11 health professions education programs. NP program directors indicated greatest dissatisfaction with curriculum coverage of "use of electronic information systems" and "business management of practice." The three most important curriculum topics identified by respondents were "primary care," "health promotion/disease prevention," and "effective patient-provider relationships/communication," identical to the three topics rated most important by all groups combined. The most significant barriers to change identified by the respondents included "an already crowded curriculum" and "limited availability of clinical learning sites." Findings show that NP program directors perceive that they are doing an effective job addressing most of the 33 curriculum topics, but they also recognize a need to continue to improve their curricula in response to the ever-changing health care environment. Barriers to achieving the desired curricular improvements, however, may be significant. Recommendations for overcoming these barriers to change are offered.

Clinical Competence↗

Spirituality and healthcare organizations.

In recent years, the place of spirituality in organizations has become increasingly discussed and advocated. On a personal level, this may involve achieving personal fulfillment or spiritual growth in the workplace. In the broader sense, spirituality is considered by many to be essential in an organization's interactions with employees, customers, and the community. This article describes a possible role for greater spirituality in healthcare organizations, whose cultures in recent decades have largely excluded spirituality or religiousness. This is the consequence of an analytical, scientific perspective on human health; a reductionist paradigm in biomedical research; and the inevitable bureaucratization occurring in large healthcare organizations. However, in recent decades, numerous scientific articles supporting a connection between faith or religiousness and positive health outcomes have been published. Because individuals seek meaning when experiencing severe illnesses, and humans universally respond to compassion and caring, spirituality among healthcare workers and managers appears highly appropriate. The article describes organizational barriers to the greater inclusion of spirituality in healthcare and presents several approaches to developing a more caring organization. These include eliciting extensive input from all staff and clinicians in identifying core or common values, ethics, and a philosophy of caring. Programs should ensure that the views of nonreligious staff and patients are respected and that clear guidelines are established for the extent and nature of affective or spiritual support for patients.

Ethics, Institutional↗