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Sickle cell disease and nitric oxide: a paradigm shift?

Traditionally the pathophysiology of sickle cell disease is thought to result from the polymerization of hemoglobin S in red cells, under hypoxic conditions, resulting in the occlusion of blood vessels. Adhesion of cells to the venular endothelium also appears to play a role. Recent studies have also suggested that in addition to the polymerization of hemoglobin S in the red blood cell, a deficiency of the endogenous vasodilator, nitric oxide may be involved. Hemoglobin released as a result of hemolysis rapidly consumes nitric oxide resulting in a whole program of events that inhibit blood flow. Therapies directed at decreasing the destruction of nitric oxide, increasing the production of nitric oxide, or amplifying the nitric oxide response may prove beneficial.

Anemia, Sickle Cell↗

Shifting paradigms in prostate cancer; docetaxel plus low-dose prednisone - finally an effective chemotherapy.

Until now, the use of systemic chemotherapy for advanced androgen-independent prostate cancer has had very little to offer to patients. However, in 2004, two large randomised trials investigating docetaxel vs. mitoxantrone have both demonstrated survival improvements, and, in one of the trails, improvements in important secondary clinical outcome measures such as pain relief and quality of life measurements. In this current perspective, these two trials are summarised and discussed. It is concluded that, docetaxel every 3 weeks plus low-dose prednisone can be considered standard treatment for patients with androgen-independent disease.

Antineoplastic Combined Chemotherapy Protocols↗

A shifted paradigm for the further understanding, evaluation, and treatment of lower urinary tract symptoms in men: focus on the bladder.

Lower urinary tract symptoms (LUTS) are highly prevalent among older men and have a negative impact on health-related quality of life. Frequent comorbidity with potential prostatic disease adds complexity to the management of male LUTS. In this review, we discuss the pathophysiological conditions that underlie male LUTS, and examine the relationship between symptoms and urodynamic findings. The contribution of bladder dysfunction to male LUTS, with a particular emphasis on overactive bladder (OAB) symptoms, is explored. We also consider pharmacotherapeutic options for male LUTS. Pharmacotherapies that target the prostate (alpha1-receptor antagonists and 5alpha-reductase inhibitors) often fail to alleviate OAB symptoms, and may not be the most appropriate therapy for men with storage LUTS. Multiple studies have suggested that antimuscarinic therapy alone or in combination with alpha1-receptor antagonists improve OAB symptoms in men with and without bladder outlet obstruction. Although these agents may represent appropriate first-line therapies for men with OAB symptoms, the therapeutic potential of antimuscarinics alone or in combination with alpha1-receptor antagonists in this population should be evaluated in large-scale, well-designed clinical trials.

Adrenergic alpha-Antagonists↗

1990-2001 US general surgery chief resident gastric surgery operative experience: analysis of paradigm shift.

The almost complete disappearance of benign gastric ulcer disease has led to the perception that there may be an insufficient gastric surgery experience for surgery residents. This study analyzed resident-reported gastric procedure experience by chief residents from U.S. programs. The Resident Statistic Summaries (Report C) for 1990-2001 were compiled and analyzed. Results are expressed as the average number of operations performed per resident, standard deviation (SD), and the percentage (%) of total gastric operative cases. For all gastric-related surgery, the average reported cases per chief resident ranged from 9.8-12.4 with a peak in 1990 and a nadir in 1999; in 2001 the reported case average was 11.3 (SD ranged from 6-8). Over the same interval, vagotomy decreased from 24% in 1990 to 7% in 2001, whereas gastric-reduction operations increased from 5%-34%. Total gastrectomy remained a constant less than 1.0 per chief resident (range 0.6-0.8), whereas partial gastric resection (PGR) was unchanged. The percentage of all types of gastric resections slightly diminished from 34% in 1990 to 29% in 2001. U.S. surgical chief residents report a widely variable experience in gastric surgery over the period analyzed. However, their overall experience has not significantly diminished since 1990 although specific procedural volume has varied.

Digestive System Surgical Procedures↗

Paradigm shifts in cardiovascular medicine.

Cardiovascular medicine is changing rapidly with the development, testing, and introduction of new diagnostic and therapeutic methods. New interventional techniques such as the use of drug-eluting stents have important implications for the care of individual patients and the delivery and economics of health care in general. Drug-eluting stents have been shown to improve outcomes among patients undergoing percutaneous coronary intervention by significantly reducing restenosis rates. Two randomized trials have documented that per 100 patients treated with the sirolimus drug-eluting stent, 12.5 to 13.6 patients avoided the need for subsequent target lesion revascularization, when compared with patients treated with conventional stents. The economic effect of the introduction of these stents, which are projected to be two to three times as expensive as conventional stents, is complex and depends on which segment of health care is considered. These stents will be favorably received by patients, physicians, employers, and society as well as payers. However, hospitals may be adversely affected by having increased procedural costs for the stents, along with fewer procedures for evaluation and treatment of restenosis and probably decreased surgical volumes. Drug-eluting stents are only the first of many new technologic advances that will affect cardiovascular care. These procedures have many features in common, including: 1). replacement of major surgical procedures with less invasive approaches; and 2). redistribution of costs, with a decrease in hospital profits but potentially lower costs of health care delivery for society as a whole.

Coronary Disease↗

The residency pathway to dental licensure: the paradigm shift from inception to policy.

Following decades of minimal advancement, the dental licensure reform movement has rallied around the recent introduction of a bold new concept. The New York State Dental Association has introduced and passed legislation that allows the substitution of a successfully completed dental residency program for the traditional clinical licensing examination. The residency must be one approved by the Commission on Dental Accreditation of the American Dental Association. New York's main objective was to elevate the standards required for licensure beyond those of minimal competency. The residency experience provides extensive didactic and clinical experience in a supervised setting relevant to contemporary dental practice.

American Dental Association↗

Paradigm shift.

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Adolescent↗