Promoting new approaches for cancer care in the Middle East.

Cancer is now the fastest growing killing disease in the Middle East. Accordingly, there is an urgent need to train local health professionals: oncologists, palliative care experts, oncology nurses, psychologists, along with social workers, physiotherapists and spiritual counselors on strategies for early detection, curative therapies and palliation. Professionals in the region, along with the public, need to convince medical administrators, regulators and policymakers about investing in education and training of YOUNG professionals, as well as those with already proven experience in cancer care. Training is the basis for any future cancer care program, which aims at the integration of palliative care practices into standard oncology care across the trajectory of the illness.

Spirituality in the cancer trajectory.

Spirituality is an essential element of person-centered care and a critical factor in the way patients with cancer cope with their illness from diagnosis through treatment, survival, recurrence and dying. Studies have indicated a significant relationship between spirituality and quality of life. Spirituality, in its broadest sense speaks to the meaning patients find in their lives especially during times of stress, illness and dying. Illness can trigger deep existential issues that could trigger profound suffering and distress. A model is presented that describes the role of each member of the healthcare team in addressing patients' spirituality. Spiritual distress, as a diagnosis, requires attention and treatment just as any other clinical symptom. Spiritual resources of strength need to be identifies and recognized as positive factors in patients' coping. Finally a treatment plan needs to include the spiritual as well as the physical and psychosocial issues of patients. Chaplains and other spiritual care professionals need to be recognized as the experts in spiritual care and should be integral members of the healthcare team. Integrating spirituality as an essential domain of care will result in better health outcomes, particularly quality of life for patients across the trajectory of cancer care.

Patients who want their family and physician to make resuscitation decisions for them: observations from SUPPORT and HELP. Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatment. Hospitalized Elderly Longitudinal Project.

OBJECTIVE: To determine the extent to which older or seriously ill inpatients would prefer to have their family and physician make resuscitation decisions for them rather than having their own stated preferences followed if they were unable to decide themselves. DESIGN: Analysis of existing data from the Hospitalized Elderly Longitudinal Project (HELP) and the Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatment (SUPPORT). SETTING: Five teaching hospitals in the United States. PARTICIPANTS: 2203 seriously ill adult inpatients (SUPPORT) and 1226 older inpatients (HELP) who expressed preferences about resuscitation and about advance decision-making. MEASURES: We used a logistic regression model to determine which factors predicted preferences for family and physician decision-making. RESULTS: Of the 513 HELP patients in this analysis, 363 (70.8%) would prefer to have their family and physician make resuscitation decisions for them whereas 29.2% would prefer to have their own stated preferences followed if they were to lose decision-making capacity. Of the 646 SUPPORT patients, 504 (78.0%) would prefer to have their family and physician decide and 22.0% would prefer to have their advance preferences followed. Independent predictors of preference for family and physician decision-making included not wanting to be resuscitated and having a surrogate decision-maker. CONCLUSIONS: Most inpatients who are older or have serious illnesses would not want their stated resuscitation preferences followed if they were to lose decision-making capacity. Most patients in both groups would prefer that their family and physician make resuscitation decisions for them. These results underscore the need to understand resuscitation preferences within a broader context of patient values.

Physicians and patient spirituality: professional boundaries, competency, and ethics.

Clinical studies are beginning to clarify how spirituality and religion can contribute to the coping strategies of many patients with severe, chronic, and terminal conditions. The ethical aspects of physician attention to the spiritual and religious dimensions of patients' experiences of illness require review and discussion. Should the physician discuss spiritual issues with his or her patients? What are the boundaries between the physician and patient regarding these issues? What are the professional boundaries between the physician and the chaplain? This article examines the physician-patient relationship and medical ethics at a time when researchers are beginning to appreciate the spiritual aspects of coping with illness.

Synthesis and evaluation of potent and selective c-GMP phosphodiesterase inhibitors.

Syntheses and structure-activity relationships (SAR) of cGMP selective phosphodiesterase inhibitors are discussed. Potent and selective inhibitors are produced when the C-2 position of tetracyclic guanine 1 is substituted with alkyl chains containing six carbon atoms.

Developing curricula in spirituality and medicine.

In recent years patients and some members of the medical community have expressed the concern that doctors have forgotten about compassion and too often ignore their patients' spiritual concerns. Patients can and should expect their physicians to respect their beliefs and be able to talk with them about spiritual concerns in a respectful and caring manner. Medical schools must teach their students how to meet these expectations, and health care systems need to provide practice environments that foster compassionate caregiving. Medical educators are recognizing the need to bring the art of compassionate caregiving back into the medical school curriculum. This paper focuses on one approach to achieving this goal, the study of spirituality and medicine. The authors discuss the relationship of spirituality and healing, and describe studies that have shown patients' desire to have spiritual issues addressed by their physicians and the potential health benefits of spiritual beliefs. Finally, they describe common elements of the spirituality courses offered by approximately 50 U.S. medical schools, including 19 schools that have been awarded grants from the National Institute for Healthcare Research for the development of curricula in spirituality and medicine.

Potent tetracyclic guanine inhibitors of PDE1 and PDE5 cyclic guanosine monophosphate phosphodiesterases with oral antihypertensive activity.

Tetracyclic guanines have been shown to be potent and selective inhibitors of the cGMP-hydrolyzing enzymes PDE1 and PDE5. In general, these compounds are inactive or only weakly active as inhibitors of PDE3, which is a major isozyme involved in cAMP hydrolysis. Structure-activity relationships are developed at N-1, C-2, N-3, and N-5 on the core nucleus. Compound 31, with an IC50 of 70 pM, is the most potent inhibitor of PDE1, while 50, with an IC50 of 4 nM, is the most potent inhibitor of PDE5. Compounds 20, 22, 30, and 50 are potent dual inhibitors with IC50 values below 30 nM for both PDE1 and PDE5. Compounds 12, 20, and 28 reduced blood pressure by more than 45 mmHg when administered orally at 10 mg/kg to the spontaneously hypertensive rat (SHR).

Pseudotumor cerebri associated with lithium therapy in two patients.

The authors report two cases of pseudotumor cerebri in patients taking lithium for treatment of bipolar disorder. Pseudotumor cerebri is a poorly understood syndrome characterized by chronic headaches, bilateral papilledema, and increased intracranial pressure without localized neurologic signs or symptoms, intracranial mass, or hydrocephalus. Ventriculography, computed tomography, and nuclear magnetic resonance imaging reveal normal or small ventricles. Multiple etiologies may include Vitamin A toxicity, obesity, head trauma, hypothyroidism or hyperthyroidism, prolonged steroid therapy or its withdrawal, Addison's disease, Cushing's disease, pituitary insufficiency, and lithium therapy. Patients treated with lithium whose antidiuretic hormone-cyclic adenosine monophosphate mechanism is disturbed are most likely to develop pseudotumor cerebri via disregulation of sodium balance, thyroid-stimulating hormone production, and glucose metabolism. The authors recommend careful medical monitoring to avoid iatrogenic effects of lithium, including pseudotumor cerebri.

Antiulcer agents. 4. Conformational considerations and the antiulcer activity of substituted imidazo[1,2-a]pyridines and related analogues.

Definition of the interrelationship between the conformational characteristics of a series of substituted imidazo[1,2-a]pyridines and their antiulcer activity was investigated by examining the conformational properties of 3-cyano-2-methyl-8-(phenylmethoxy)imidazo[1,2-a]pyridine (1), using a variety of experimental and theoretical methods. The results of these studies was the identification of two distinctly different candidates, designated the "folded" and the "extended" conformation, respectively, to represent the two possible minimum-energy conformations of 1. In order to select the biologically relevant conformer, a group of 3-substituted 2-methylimidazo[1,2-a]pyridines, having either a cis or a trans 2-phenylethenyl substituent at the 8-position were designed as conceptually simple and synthetically accessible semirigid analogues of the respective candidate conformers. Gastric antisecretory activity was found to reside only in the trans isomers (compounds 11, 15, and 17), which mimic the "extended" conformation. This observation led to the construction of 8,9-dihydro-2-methyl-9-phenyl-7H-imidazo[1,2-a]pyrano[2,3-c]pyridi ne-3- acetonitrile (40), a rigid tricyclic analogue that is effectively locked in the "extended" conformation and that exhibited an antiulcer profile comparable to that of prototype 1. These results unequivocally demonstrate that, in accord with expectation for a drug operating at a specific receptor, the conformational characteristics of the molecule have a substantial effect in determining its antiulcer activity. More precisely, it has been demonstrated that it is the "extended" conformation of 1 that represents the "bioactive" form of the drug. These results constitute the basis for a molecular probe that should aid in the investigation of the as yet uncharacterized gastric proton pump enzyme (H+/K+-ATPase), by means of which 1 and its analogues presumably exert their pharmacologic actions.

[Expert evaluation of temporary disability of workers performed by physicians in health care and prevention]. / Expertise de l'incapacité temporaire de travail effectuée par les médecins de l'assistance de cure et prophylaxie.

By means of the inquiry method, informations were obtained regarding the appraisement of temporary working incapacity, performed by 76 doctors, of whom 45 general practitioners and 31 factory doctors. In addition to the data related to the inquiry, the questionnaire contained also the description of five clinical cases. The conclusions of the appraisement and the causes for refusal to deliver a medical certificate are discussed.

3-(aminoalkyl)-1,2,3,4-tetrahydro-5H-[1]benzopyrano[3,4-c] pyridin-5-ones as potential anticholinergic bronchodilators.

A series of 3-(aminoalkyl)benzopyrano[3,4-c]pyridin-5-ones was prepared and tested as potential orally active anticholinergic bronchodilators. Inhibition of methacholine-induced collapse in guinea pigs and inhibition of pilocarpine-induced bronchoconstriction in dogs served as in vivo models. Simultaneous measurement of salivary inhibition in the dog model allowed determination of a pulmonary selectivity ratio. The benzopyrano[3,4-c]pyridin-5-one parent ring system was prepared by Pechman condensation of phenols with a piperidine beta-keto ester. Alkylation with aminoalkyl halides, or with 1-chloro-2-propanone followed by reductive amination, yielded the 3-substituted target compounds. Bronchodilator potency was related to the extent of steric crowding surrounding the side-chain terminal amine function. Addition of a methyl substituent on the carbon alpha to the terminal amine often increased potency or pulmonary selectivity. After secondary pharmacological evaluation, compound 7a, designated CI-923, was selected for clinical trial as a bronchodilator.

Antiulcer agents. 1. Gastric antisecretory and cytoprotective properties of substituted imidazo[1,2-a]pyridines.

A novel class of antiulcer agents, the substituted imidazo[1,2-a]pyridines, is described. The present compounds are not histamine (H2) receptor antagonists nor are they prostaglandin analogues, yet they exhibit both gastric antisecretory and cytoprotective properties. The mechanism of gastric antisecretory activity may involve inhibition of the H+/K+-ATPase enzyme. Structure-activity studies led to the identification of 3-(cyanomethyl)-2-methyl-8-(phenylmethoxy)imidazo[1,2-a]pyridine, SCH 28080 (27), which was selected for further development and clinical evaluation.