肺动脉高压的当代治疗

直到20世纪90年代,钙通道阻滞剂和肺移植仍是仅有的动脉型肺动脉高压(PAH)的治疗措施.然而随着对PAH病理生理机制认识的明确,特异性治疗药物也不断开发.目前用于PAH的特异治疗药物分为3类:前列环素类似物、磷酸二酯酶5抑制剂及内皮素受体拮抗剂.     

Fish oil-enriched nutritional supplement attenuates progression of the acute-phase response in weight-losing patients with advanced pancreatic cancer.

The presence of an acute-phase protein response (APPR) has been suggested to shorten survival and contribute to weight loss in patients with pancreatic cancer. Fatty acids derived from fish oil have been shown to alter proinflammatory cytokine production and acute-phase protein synthesis in vitro. The present study was designed to determine the effects of a fish oil-enriched nutritional supplement on the concentrations of a range of individual acute-phase proteins (APP) in patients with advanced pancreatic cancer. In a sequential series, 18 patients with pancreatic cancer received the supplement (providing 2 g eicosapentaenoic acid and 1 g docosahexaenoic acid/d) for 3 wk while another 18 received full supportive care alone. Six healthy subjects served as additional controls. Acute-phase proteins were measured before and after the 3-wk intervention period in cancer patients. At baseline, albumin, transferrin and pre-albumin were significantly reduced and fibrinogen, haptoglobin, alpha-1-acid glycoprotein, alpha-1-antitrypsin, ceruloplasmin and C-reactive protein (CRP) were significantly elevated in the cancer patients compared with healthy controls, reflecting their roles as negative and positive acute phase proteins, respectively. In the supplemented cancer group, the only significant change in APP concentrations over the 4-wk study period was an increase in transferrin. In the control cancer group there were further significant reductions in albumin, transferrin and pre-albumin, and a significant increase in CRP concentration. These results suggest that many positive and negative APP are altered in advanced pancreatic cancer. The APPR tends to progress in untreated patients but may be stabilized by the administration of a fish oil-enriched nutritional supplement. This may have implications for reducing wasting in such patients.     

Breast cancer incidence following low-dose rate environmental exposure: Techa River Cohort, 1956�C2004

In the 1950s, the Mayak nuclear weapons facility in Russia discharged liquid radioactive wastes into the Techa River causing exposure of riverside residents to protracted low-to-moderate doses of radiation. Almost 10 000 women received estimated doses to the stomach of up to 0.47 Gray (Gy) (mean dose=0.04 Gy) from external γ-exposure and ¹³⁷Cs incorporation. We have been following this population for cancer incidence and mortality and as in the general Russian population, we found a significant temporal trend of breast cancer incidence. A significant linear radiation dose–response relationship was observed (P=0.01) with an estimated excess relative risk per Gray (ERR/Gy) of 5.00 (95% confidence interval (CI), 0.80, 12.76). We estimated that approximately 12% of the 109 observed cases could be attributed to radiation.     

Measuring patients' attitudes to care across the primary/secondary interface: the development of the patient career diary.

BACKGROUND: A growing number of new ways of organising services across the primary/secondary interface are being introduced and evaluated. The principal motive for such reorganisation is to improve the efficiency of health care. However, unless the impact of the new services on patients is investigated and taken into account, it is possible that patients' reactions could be negative, a factor that could lead to unexpected consequences in the use and costs of services. OBJECTIVE: To develop a measure of patients' attitudes towards care across the interface between primary and secondary care. DESIGN: Generation of questions to be included in the measure from a qualitative study of patients' experiences of care across the interface; administration of pilot versions of the measure to samples of patients referred to secondary care; refinement of questions guided by analysis of response patterns, principal components analysis and internal consistency; administration of the final version of the patient career diary in complete form retrospectively to patients referred to secondary care, and one section alone to patients attending outpatient departments for follow up appointments. Face validity was assessed by analysis of open comments in a sample of 50 diaries, and review of the diary by 34 health professionals. Construct validity was assessed by investigation of levels of correlation between components of each section of the diary and the components of the healthcare section overall. SETTING: In the final field test, patients were attending various hospital services, including cardiology, dermatology, neurology, gynaecology, general surgery, general medicine, ophthalmology, trauma and orthopaedics, and gastroenterology. RESULTS: The final version of the diary included 109 questions in seven sections: general practitioner (GP) visits and referral, other GP visits, first outpatient visit, other outpatient visits, inpatient stay and discharge, care after discharge, and care overall. Response rates were poor for retrospective completion of the entire diary, but excellent when a section was given separately. Principal components analysis confirmed that components relating to issues identified as important to patients in the qualitative study had been included in the diary. Levels of internal consistency were good, and comments of patients and health professionals supported validity. CONCLUSION: The patient career diary is a valid and reliable measure of patients' attitudes to care across the interface. It should be given in sections to ensure adequate response rates, and is suitable for use in the evaluation or quality of patterns of care across the interface. In future, the impact on patients of new ways of organising services across the interface should be investigated by use of measures such as the patient career diary.     

Advances in Pharmacologic Modulation of Nitric Oxide in Hypertension

A number of structural and functional mechanisms have been identified in the pathogenesis of hypertensive vascular disease, each of which requires effective therapy to reduce global cardiovascular risk. Hypertension, together with other cardiovascular risk factors, promotes endothelial dysfunction as evidenced by decreased nitric oxide (NO) release and reduced vascular responsiveness to normal vasodilatory stimuli. In addition, the mechanical forces inherent in hypertension activate neurohormonal mechanisms, including the renin-angiotensin system, which modulate vessel wall structure and function. Antihypertensive drugs may have class-specific hemodynamic and physiologic effects that attenuate these vascular disease processes. Pharmacologic approaches that enhance endothelial NO bioavailability have been shown to restore vasodilation while reducing clinical events. These agents improve NO bioavailability by increasing endogenous production through enzymatic mechanisms or by promoting the direct release of NO by its redox congeners in a spontaneous fashion. In this article, we review the basic mechanisms of endothelial dysfunction along with the use and comparative therapeutic benefits of various pharmacologic interventions, with particular emphasis on antihypertensive agents.