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Biomedical subjects

J F Jenkins

Publications and source records attributed to J F Jenkins.

13 recordsLinked to original sources

Preparing for the future through genetics nursing education.

PURPOSE: To determine recommendations for curriculum change that are indicated by innovations in genetics. METHODS: Both quantitative and qualitative. The sample (n = 356) consisted of nurses identified as experts in genetics (n = 228) and nurses identified as potential users of genetics education (n = 128). Nurses' opinions of core components of a genetics curriculum were elicited via a mailed survey questionnaire. Participants also provided demographic information and completed the Jones Innovativeness Scale (1997). FINDINGS: Recommended content in genetics education for practicing nurses was identified by both groups of nurses. Innovativeness characterized 3% of the respondents. Ninety-eight percent of respondents said that adopting genetics education is important. In total, 398 items were identified as potential consequences of education that incorporates genetic information. CONCLUSIONS: Identified content provides a template for genetics education programs for nurses. Genetics nursing education was perceived to have positive outcomes for both nurses and clients.

Adult↗

An historical perspective on genetic care.

The outcomes of genetic research endeavors have the potential to transform health care with significant implications for both providers and consumers of clinical services. Professional and public integration of genetics knowledge is key to successful utilization of genetics information. This article will provide an overview of genetics including a historical perspective, examples of genetic health care, the nursing perspective, and ethical considerations and challenges. New scientific explanations for health, disease, responsiveness to treatment, and design of options for care may create personal and professional dilemmas. Nurses have a responsibility to become active participants in confronting the demands resulting from this new knowledge for education, practice, and policy. The purpose of this article is to provide a foundation from which the profession of nursing can build to enhance current skills and knowledge about genetics to prepare for this transformation in health care.

Credentialing↗

New drug therapy for patients with HIV. Nursing implications in the administration of 2',3'-dideoxyinosine (ddI).

2',3'-Dideoxyinosine (ddI) is a dideoxynucleoside currently in Phase I, II, and III trials for antiretroviral therapy. It has been shown to cause objective and subjective improvement in people with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex (ARC). This drug, as with any drug, is not without toxicity. Through thorough patient education and clinical evaluation, incidence of these toxicities may be lessened or avoided.

Acquired Immunodeficiency Syndrome↗

Plasma and cerebrospinal fluid pharmacokinetics of 3'-azido-3'-deoxythymidine: a novel pyrimidine analog with potential application for the treatment of patients with AIDS and related diseases.

We investigated the clinical pharmacokinetics of azidothymidine (N3TdR) as part of a phase I/II trial in the treatment of acquired immunodeficiency syndrome and related diseases. During the 6-week course of therapy, drug levels in plasma, cerebrospinal fluid, and urine were determined by HLPC. The plasma half-life of N3TdR was 1.1 hour. The total body clearance was 1.3 L/kg/hr. At intravenous doses of 5 mg/kg or oral doses of 10 mg/kg, plasma levels were continuously maintained above the target level of 1 mumol/L. Oral bioavailability was 63% +/- 13%. Substantial penetration of N3TdR into cerebrospinal fluid was demonstrated. At doses of 5 mg/kg intravenously or 10 mg/kg orally, cerebrospinal fluid drug levels exceeded and were maintained close to 1 mumol/L. Nineteen percent of the administered dose was excreted unchanged into the urine. Renal clearance was 0.23 L/kg/hr. N3TdR possesses pharmacokinetic properties that would facilitate the long-term treatment of patients with acquired immunodeficiency syndrome: it can be given orally and it penetrates the central nervous system.

Acquired Immunodeficiency Syndrome↗

Phase I and pharmacokinetic study of tiazofurin (TCAR, NSC 286193) administered by continuous infusion.

Tiazofurin (2-beta-D-ribofuranosylthiazole-4-carboxamide, TCAR) is a synthetic C-nucleoside that demonstrated significant in vivo activity against a variety of animal tumors as well as in vitro activity against human tumor-derived cell lines. Thirteen patients were treated with TCAR administered as a 5-day continuous infusion in this Phase I trial. Seventeen complete cycles were administered in three dose levels ranging from 550 to 1450 mg/M2. Dose-limiting toxicities were myelosuppression and neurotoxicity including severe lethargy. Other toxicities including superficial skin peeling, myalgias, and tearing were seen at all doses. One patient had chest pain on day 4 resulting in stopping the drug, however, there was no evidence of cardiac or pericardial disease. Uric acid levels rose within one day in the absence of allopurinol treatment. There were no treatment related deaths. HPLC measurement of drug levels demonstrated steady-state plasma levels during the infusion, and a half-life following the infusion of 7.7 +/- 0.6 hours. Minor abnormalities in renal function were associated with dramatic changes in pharmacokinetics and toxicity. No clinical responses were observed in this trial.

Adult↗

Clinical pharmacology of 5-iodo-2'-deoxyuridine and 5-iodouracil and endogenous pyrimidine modulation.

We describe the clinical pharmacology and metabolism of 5-iodo-2'-deoxyuridine (IdUrd) during and after a 12-hour infusion. The kinetics of IdUrd were linear between 250 and 1200 mg/m2. The plasma IdUrd concentration reached steady state in less than 1 hour. Total body clearance of IdUrd was 750 ml/min/m2 and the disappearance t1/2 at the end of the infusion was less than 5 minutes. The primary metabolite, 5-iodouracil (IUra), did not reach steady state during the infusion. At the end of the 1200 mg/m2 infusion, the maximum plasma IUra concentration was 100 mumol/L, or about 10 times the simultaneous IdUrd plasma concentration. During the infusion there was at least a fifty- to 100-fold increase in uracil and thymine plasma concentrations. After the infusion, IUra disappearance from plasma was nonlinear, with an apparent Michaelis constant of 30 mumol/L. Plasma uracil and thymine levels slowly decreased after the IdUrd infusion until IUra fell to less than 30 mumol/L. There was subsequently a parallel and more rapid decrease in the plasma concentrations of uracil and thymine. Uridine, 2'-deoxyuridine, and thymidine plasma levels did not change significantly as a result of IdUrd therapy. These changes in endogenous pyrimidine pools are consistent with competitive inhibition of dihydrouracil dehydrogenase by IUra. An in vitro human bone marrow assay was used to determine the relative toxicity of IdUrd and IUra. Although exposure to IUra was tenfold higher than that to IdUrd, IdUrd was at least 100 times more cytotoxic to marrow cells.

Chromatography, High Pressure Liquid↗

Pharmacokinetics of the hypoxic radiosensitizers misonidazole and demethylmisonidazole after intraperitoneal administration in humans.

The hypoxic radiosensitizers misonidazole or demethylmisonidazole were administered i.p. in a 2-liter volume to 6 patients affected by advanced ovarian carcinoma, and the pharmacokinetic course of the two drugs was studied. The clearance of misonidazole and demethylmisonidazole from the peritoneal fluid was 19.1 and 12.4 ml/min, respectively. At 3 hr after drug administration, both radiosensitizers had peritoneal fluid concentrations more than 8 times larger than in the plasma. The concentration x time exposure in the peritoneal fluid was 3.2 times larger than in plasma for misonidazole and 7.6 times for demethylmisonidazole. The advantage of i.p. delivery compared with systemic delivery decreases with distance from the peritoneal surface, but the advantage may be maintained for up to 1 mm or 100 cell layers. These differences between the two routes of administration provide a rational basis for the expectation that a substantial increase of the therapeutic benefits of misonidazole and demethylmisonidazole in potentiating radiation therapy or chemotherapy can be expected in treating tumors confined to the i.p. space.

Female↗

Plasma pharmacokinetics of adriamycin and adriamycinol: implications for the design of in vitro experiments and treatment protocols.

The plasma pharmacokinetics of Adriamycin and adriamycinol following a 15-min infusion of 75 mg/sq m of Adriamycin were studied in ten patients previously untreated with Adriamycin. The disappearance kinetics of Adriamycin could adequately be described by a biexponential equation with an initial half-life of 8-min and a terminal half-life of 30 hr. The major drug exposure (area under the concentration-time curve) occurs during the terminal phase where drug concentrations are generally less than 10(-7) M (0.05 micrograms/ml). An improvement in the high-performance liquid chromatography sensitivity facilitated the determination of the terminal phase. The plasma kinetics of adriamycinol, the major and only known active metabolite of Adriamycin, show a rapid initial increase in plasma concentration followed by a slow decline which parallels that of Adriamycin during the terminal phase. The relative drug exposure of adriamycinol to Adriamycin was approximately 50%. The relationship between the measured plasma drug levels and free drug available for distribution into tissues was studied by comparing the plasma binding characteristics of Adriamycin and adriamycinol. A constant 20 to 25% of the total plasma concentrations of both Adriamycin and adriamycinol was freely diffusible over the whole range of observed concentrations, 20 nM to 2 microM. Thus, the free drug exposure (area under the concentration-time curve) of tumor and host tissues in vivo can be determined from these plasma measurements, since the free drug exposures in plasma and in extracellular fluid are equivalent. These results can also serve as a guide for the design of clinically relevant in vitro studies of Adriamycin and adriamycinol. The pharmacokinetic parameters determined in this study have been used to simulate plasma concentration-time courses for a variety of Adriamycin treatment schedules. Alternatives are suggested which reduce peak plasma Adriamycin concentration while antitumor area under the concentration-time curve is maintained.

Acetylcysteine↗

Recommendations for educating nurses in genetics.

With the ongoing and increasingly rapid pace of genetic discoveries, nurses must be able to incorporate genetic knowledge into their everyday practices of promoting the genetic health of individuals, families, and communities. Although development of genetic health knowledge is in its infancy, nurses are currently expected to integrate information about genetic risks, testing, and treatments for clients throughout the clients' entire lifespan. All nurses must have an understanding of the relationship between genetics and health to appropriately identify and address genetic concerns in their clients. To fulfill these roles, nurses need to improve their knowledge base in genetics. This article provides recommendations for genetics curriculum in continuing and entry-level nursing education programs. These recommendations are outcomes of a research project involving genetics nurse experts as well as nurses new to the area of genetics, and a consensus workshop of nursing faculty involved in curriculum changes subsequent to an intensive genetics continuing education program. Nursing educators are beginning to recognize the importance of education of all nurses about genetics. If, however, all educators do not accept this responsibility, nurses will be left behind in designing and offering health care for the 21st century.

Attitude of Health Personnel↗