肾素抑制剂和高血压

肾素抑制剂已被认为系一类新的抗高血压药物,为降压药物的发展提供了可观的前景。本文就其作用机制及第一个口服肾素抑制剂阿利吉仑(Aliskiren)的临床研究情况作一综述。     

Renin inhibitors: Optimal strategy for renal protection

Diabetic nephropathy and hypertension are the major causes of chronic kidney disease. The renin system plays a key role in the control of blood pressure (BP), as well as in the regulation of renal and adrenal function. Chronic activation of the renin system can lead to organ damage, particularly renal damage; increasing evidence indicates that suppression of the renin system can provide renal protection. Despite the use of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs), the renin system is not completely suppressed. The direct renin inhibitors (DRIs) provide suppression of the entire renin system at the rate-limiting step. Studies in humans with early DRIs indicated potential renoprotective effects, but these agents failed in clinical development due to poor oral bioavailability. Aliskiren is a new orally active DRI with proven BP-lowering effects. Animal studies indicate that aliskiren may provide renal protection, and data from human studies are anticipated.     

Exercise hypertension in the perspective of systemic arterial hypertension. An overview

Systemic arterial hypertension is one of the most wide-spread diseases in the world. It is a chronic disease with a very long asymptomatic phase. At an estimated prevalence in the developed countries of 15 to 20%, it can be assumed that approximately 80% of men and 60% of women with hypertension are either unaware of their condition or are not treated adequately. These figures show that reliable diagnostic measures are needed to provide efficient detection of high blood pressure in a given population. In this regard, exercise testing has proven particularly well-suited. Using standardized ergometry, patients with latent, borderline or manifest hypertension can be identified. Exercise hypertension is defined on the basis of an abnormal blood pressure increase during physical exercise in persons with normal blood pressure at rest. Because of marked interindividual fluctuation in blood pressure, values measured at rest may be of only limited usefulness in the diagnosis of hypertension. In contrast, the blood pressure during dynamic exercise may be particularly informative with respect to probability of future development of manifest hypertension and treatment of high blood pressure. Long-term studies have shown that within five years up to one-third of patients with exercise hypertension develop manifest hypertension at rest. Based on the Canada Fitness Survey data indicating that about 2% of the population demonstrate exercise hypertension, it can be estimated that approximately 200,000 Canadians will develop manifest hypertension within five years. Similar statistics are also applicable for most of the developed countries of the world.(ABSTRACT TRUNCATED AT 250 WORDS)     

Autoimmune pancreatitis in Japan: overview and perspective

Since the rediscovery and definition of autoimmune pancreatitis (AIP) by Yoshida et al. in 1995, the disease has been attracting attention because of its unique clinical features and practical issues. This disease shows very impressive imaging findings, serological changes, and characteristic histopathology. It occurs most commonly in elderly males with painless jaundice or mild abdominal pain; resemblance in imaging findings between AIP and pancreatobiliary cancers poses an important practical issue of differentiation. With increasing recognition of AIP and accumulation of cases, another important feature of this disease has been revealed, i.e., association of extrapancreatic organ involvements. Initially misunderstood because it can be accompanied by other autoimmune disorders, such as Sjögren’s syndrome or primary sclerosing cholangitis (PSC), AIP is now known to be associated with unique types of sialadenitis and cholangitis distinct from Sjögren’s syndrome or PSC. Now the concept of “IgG4-related sclerosing disease” has become widely accepted and the list of organs involved continues to increase. With worldwide recognition, an emerging issue is the clinical definition of other possible types of autoimmune-related pancreatitis called “idiopathic duct-centric chronic pancreatitis (IDCP)” and “AIP with granulocyte epithelial lesion (GEL)” and their relation to AIP with lymphoplasmacytic sclerosing pancreatitis (LPSP). The time has arrived to establish clinical diagnostic criteria of AIP based on international consensus and to discuss regional and racial differences in the clinicopathological features of AIP. Consensus guidelines are also required for the ideal use of steroids in the treatment of AIP to suppress recurrence efficiently with minimal side effects. There are many issues to be settled in AIP; international collaboration of experts in the pancreas field is necessary to clarify the entire picture of this unique and important disease.     

Outdoor air pollution: overview and historical perspective

Outdoor air pollution is a significant public health hazard in population centers throughout the world. Recognition of air pollution as a nuisance dates back many centuries. Decades of research have established a strong link between air pollution and a spectrum of adverse health effects. Health care practitioners rarely consider the health risk of air pollution in the course of patient care and generally do not provide risk modification strategies as part of patient management. The purpose of this article is to provide front line clinicians with: 1) an overview of the evolution in scientific understanding about air pollution and its health effects, 2) an introduction to the hazards contemporary air pollution presents to patients, and 3) an introduction to the contributions of specific pollutants to outdoor air quality.     

Peptide inhibitors of virus-cell fusion: enfuvirtide as a case study in clinical discovery and development

The peptidic antiretroviral enfuvirtide (Fuzeon) is the first clinically approved antiviral fusion inhibitor and the first antiretroviral that must routinely be administered parenterally. Its extracellular activity results both in activity against current drug-resistant strains of HIV-1 and a low potential for systemic toxicities. As a peptide, enfuvirtide also exhibits few interactions with other antiretrovirals and concomitant medications used in HIV disease. Enfuvirtide shows potent antiretroviral activity and significantly improves medical outcomes in highly treatment-experienced patients with HIV-1 infection, but like other antiretrovirals must be given as part of a carefully selected combination regimen to minimise the risk of emergent drug resistance. Despite its subcutaneous route of administration, clinical data indicate that most patients can accept long-term enfuvirtide treatment with little difficulty or impact on daily activities. The only common adverse event associated with enfuvirtide use is injection-site reactions of generally mild-to-moderate severity, which are seldom treatment-limiting.     

Factor VIII inhibitors: A clinical overview

There is much evidence to indicate that inhibitors to Factor VIII in patients with classical hemophilia are the result of an immunological response to exposure to material (VIII:C or VIII:CAg) that is absent or present in reduced amounts in these patients. The inhibitor is an antibody that is usually restricted in immunochemical composition and in many instances contains predominantly or exclusively γG3 or γG4 heavy chains. Exposure to Factor VIII in many inhibitor patients leads to typical anamnestic responses with marked increases in the level of the inhibitor. The tendency to develop inhibitors and the clinical characteristics of the inhibitor may be affected by genetic factors, basal levels of Factor VIII:C and/or VIII:CAg, and the nature and amount of the “immunizing” material. Currently accepted therapeutic modalities are aimed primarily at the management of acute bleeding episodes.     

Sexuality and aging. An overview

To summarize our ramblings, we want to highlight the following points as you deal with the topic of sexuality and aging: 1. Sexuality, the mix of physical and relational behaviors that gives us both parenting and bonding, is lifelong, extending well beyond the reproductive years, and a normal factor in self-esteem and satisfaction. 2. Aged individuals need sexually and medically what people in general want and need, and the idea of an acceptable decline into a sexless state is insulting. 3. An immense amount of information is available to assist seniors in dealing with physical and emotional problems relating to sexuality, and much can be done by showing sensitivity and by breaking down the habits of concealing problems or attributing them to the demon of age. 4. In sexuality, as well as in all other areas, we need to recognize that older individuals will be present at society's table in increasing numbers and with increasing expectations, and it is up to society to make them welcome--now, because they include our parents, and in the future, because they will include ourselves.     

Echocardiography: An overview

In the past 25 to 30 years echocardiography has become a basic examination in clinical cardiology. Thus, it is becoming increasingly necessary for clinicians to be able to utilize it intelligently. Like all medical procedures echocardiography has advantages and limitations, and physicians need to know both. Some of the limitations are being minimized with advances in examination techniques and instrumentation, but many still exist. One limitation is that the ability to satisfactorily educate and train persons in the various ultrasonic techniques has not kept pace with the worldwide popularity of the examination. As a result, quality control will remain a problem at least in the immediate future. New developments in echocardiography as invasive and noninvasive tools are exciting and indicate that ultrasonic examination of the heart should play an increasingly important role in clinical cardiology.     

Hypoglycaemia: An overview

Hypoglycaemia is a frequent side-effect of treatment with insulin and sulfonylureas for people with diabetes, threatening potentially serious morbidity and preventing optimal glycaemic control. Fear of hypoglycaemia and development of syndromes such as impaired awareness and counterregulatory deficiency provide additional hazards for intensification of treatment. Rapid lowering of HbA1c may be potentially dangerous in type 2 diabetes because of the adverse cardiovascular effects induced by hypoglycaemia. Hypoglycaemia can disrupt many everyday activities such as driving, work performance and recreational pursuits. Measures to reduce the risk of hypoglycaemia are labour-intensive and require substantial resources.     

Hepatic imaging. An overview

For optimal detection and characterization of focal or diffuse liver disease, it is essential to obtain the most appropriate imaging test in the correct clinical setting. Access to clinical information and medical history is, therefore, essential. Moreover, familiarity with currently available modalities for imaging the liver [figure: see text] allows the optimal use of the technical advances in ultrasound imaging, CT scanning, MR imaging, and nuclear scintigraphy technology and contributes to improved diagnostic accuracy.     

Hepatocellular carcinoma. An overview

Hepatocellular carcinoma is a common malignancy affecting approximately one million people around the world every year. The incidence is low in the occidental world and high in locations such as Southeast Asia and sub-Saharan Africa. Hepatocellular carcinoma primarily affects old people, reaching its highest prevalence among those aged 65 to 69 years old. Chronic infection by the hepatitis B virus is the most common cause of this disease. Other important causes are cirrhosis, chronic viral hepatitis (hepatitis C virus, and hepatitis B plus D viruses), alcohol abuse, obesity, hemochromatosis, alfa1-antitripsin deficiency, and toxins similar to aflatoxin. In most cases, hepatocellular carcinoma is asymptomatic and has a low life expectancy. This article presents a review of the most important epidemiological, diagnostic and treatment data about this disease.