Diversity of patients

The principles of autonomy, beneficence, nonmaleficence, and justice form a foundation for analysis of ethical quandaries. In addition, a comprehensive ethical analysis will include considerations of cultural and reh-gious diversity of patient-subjects, health care providers and interpersonal relationships an assessment of the profession-based duties and obligations of the health care professionals, including an examination of relevant professional oaths and codes and an analysis of relevantly similar previous bioethical dilemmas. 

It is well known that there is a major problem in the health care system in the United States related to providing new drugs that are effective and relatively safe in a wide diversity of patients with undifferentiated diseases whose individual dose-response relationship varies based on genetic, disease, environmental, and life-style factors. While many may argue over... 

With such commonness in the numbers that matter, then one might expect a similar spectrum of diseases treated and similar diversity of patient responses over several civilizations. Ancient records, therefore, could in principle not only provide evidence as to efficacy of drugs for different patients, but perhaps even give fresh information about responses to drug molecules in use today, or alternatively help discover new drugs. There are two caveats of particular importance. 

Other things being equal, the greater and the more diverse a patient s needs, the broader the range of services likely to be used and the greater the number of outcome dimensions that an evaluation might he expected to need in order to gauge their impact fully. 

The study of the genome supports the fundamental unity of human beings throughout the world. We all share at least 99.9% of the letters of code (nucleotide sequence) in our genome [1, 77]. And yet, it is remarkable that the extraordinary diversity of human beings at the genetic level is encoded by less than 0.1% variation in our DNA. In a sense, this is the variation that is the basis for pharma-cogenomics. In any physician s practice, patients are predisposed to different con-... 

Shock presents with a diversity of signs and symptoms. Patients with hypovolemic shock may present with thirst, anxiousness, weakness, lightheadedness, and dizziness. Patients may also report scanty urine output and dark-yellow-colored urine. 

Interleukin 1 (IL-1) is produced mainly by activated monocytes-macropha-ges, and its principal action is to stimulate thymocytes. A pleiotropic cytokine, IL-1 induces the expression of a large diversity of cytokines such as IL-6, leukaemia inhibitory factor (LIF), and other proinflammatory molecules (Di-marello 1994). IL-1 and TNF-a carry out as part of their function increasing the expression of NF-/cB and JNK (c-Jun N-terminal kinase). The importance of IL-1 in OCS is demonstrated because the IL-1-receptor-deficient mouse is resistant to ovariectomy (OVX)-induced bone loss (Lorenzo et al. 1998). The importance in pathological bone loss is also illustrated by the fact that treatment with IL-1 receptor antagonist slows down bone erosion for patients affected with rheumatoid arthritis (Kwan et al. 2004). IL-1 increases osteoclast differentiation rather than mature osteoclast activity, and infusion of IL-1 into mice induces hypercalcemia and bone resorption. Finally, IL-1 and TNF-a... 

The search for more potent, selective and safe PPARa agonists has been challenging and only a limited number of compounds have progressed into the clinic. A number of phenoxyacetic acid derivatives and other diverse structures have emerged recently. Oral administration of LY-518674 (6) produced a 208% elevation in HDL and a 96% decrease in serum TG in apoA-I transgenic mice [38,39]. Recent clinical studies with compound 6 revealed a decrease in TG and an increase in HDL similar to fenofibrate. However, compound 6 also raised LDL-C in a dose-dependent fashion, and to a much higher level than seen with fenofibrate [28]. Both agents also raised serum creatinine levels above the upper limits of normal in 35-38% of patients [28]. 

Microbiological assays for vitamin Bi2 are diverse most are simple, but require some experience and confidence. In our hands they have proved uniformity reliable for evaluating the vitamin Bi2 status of patients and are extremely useful research tools. Perhaps too much emphasis has been placed upon space, good and meticulously cleaned equipment, and trained personnel (G18). The Bi2 assays to be discussed here have been developed as practical methods. Four organisms have... 

To further illustrate the diversity of hydrolytic opening reactions, we turn our attention to an isothiazole ring as found in the antipsychotic agent ziprasidone (11.129). This drug is subject to various reactions of oxidation and reduction, but also undergoes hydrolytic cleavage of the C=N bond of the isothiazole ring. Evidence for this reaction was afforded by detection of radioactive metabolite 11.130, a sulfonamide, in the urine of patients dosed... 

The mechanism of action of inhalational anesthetics is unknown. The diversity of chemical structures (inert gas xenon hydrocarbons halogenated hydrocarbons) possessing anesthetic activity appears to rule out involvement of specific receptors. According to one hypothesis, uptake into the hydrophobic interior of the plasmalemma of neurons results in inhibition of electrical excitability and impulse propagation in the brain. This concept would explain the correlation between anesthetic potency and lipophilicity of anesthetic drugs (A). However, an interaction with lipophilic domains of membrane proteins is also conceivable. Anesthetic potency can be expressed in terms of the minimal alveolar concentration (MAC) at which 50% of patients remain immobile following a defined painful stimulus (skin incision). Whereas the poorly lipophilic N2O must be inhaled in high concentrations (>70% of inspired air has to be replaced), much smaller concentrations (<5%) are required in the case of the more lipophilic halothane. 

First, they can be used to generate hypotheses. Because of their nature when data are extracted from the literature across diverse study protocols meta-analyses can be extremely useful in generating h)rpotheses particularly concerning subgroups of patients. In this sense their use mirrors one potential objective of a population pharmacokinetic study that may be to determine interesting covaiiates, which influence drug... 

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