Hygiene: new hopes, new horizons

Although promotion of safe hygiene is the single most cost-effective means of preventing infectious disease, investment in hygiene is low both in the health and in the water and sanitation sectors. Evidence shows the benefit of improved hygiene, especially for improved handwashing and safe stool disposal. A growing understanding of what drives hygiene behaviour and creative partnerships are providing fresh approaches to change behaviour. However, some important gaps in our knowledge exist. For example, almost no trials of the effectiveness of interventions to improve food hygiene in developing countries are available. We also need to figure out how best to make safe hygiene practices matters of daily routine that are sustained by social norms on a mass scale. Full and active involvement of the health sector in getting safe hygiene to all homes, schools, and institutions will bring major gains to public health.     

Epidemiology of sarcoidosis: new frontiers to explore

Epidemiologic studies have been playing frontier roles to explore determinants of sarcoidosis by observing affected persons with the related population. Since 1990, more than 100 epidemiologic papers have been added to the Medline and PubMed databases. Of them, just a few were dated after March 2001. This article is focused on the papers after that time, referring to a number of previous important epidemiologic studies. The review is arranged according to two major epidemiologic categories: (1) host-related findings such as age, sex, race, familial clustering, and lifestyle; and also (2) time- and space-related findings such as exposures, geographical variation, local clustering, climate and seasonal variation, migration, and time-space clustering (transmission).     

Therapy in allergic rhinoconjunctivitis: new horizons.

Allergic Rhinitis (AR) is a common disease that impacts productivity and has significant patient morbidity. We have a variety of agents available for the treatment of AR, but numerous patients still lack good control of symptoms and some are tolerating undesired side effects. Surveys have shown 1/5 of patients with AR are not fully satisfied with their AR medications and almost 1/2 feel they receive insufficient attention from their physicians. Newer agents for the treatment of AR are in development, and an overview of some of these are presented here.     

Hepatocyte transplantation: new horizons and challenges

Hepatocyte transplantation represents an alternative strategy for treating liver disease. Liver repopulation following acute liver failure could, potentially, eliminate the requirement for orthotopic liver transplantation. Similarly, the ability to repopulate the liver with disease-resistant hepatocytes offers new opportunities for correcting genetic disorders and treating patients with chronic liver disease. Recent advances concerning the fate of transplanted cells in the recipient liver, the efficacy of cell therapy in outstanding animal models of human disease, and the isolation of progenitor liver cells capable of differentiating into mature hepatocytes have renewed optimism in regard to treating people with hepatocyte transplantation. Recruitment of an increasing number of investigators to the field and the success of recent pilot studies indicate that hepatocyte transplantation will become routine clinical practice in the near future.     

Medical ethics – new horizons

Abstract. The medical ethics of Hippocrates are no longer sufficient in a society with changing social attitudes and, especially, rapidly developing medical technologies. This Minisymposium is the third in a series of three, dealing with Medical Journals (J Intern Med 1992; 231 : 99–102) and their central role in the distribution of new medical knowledge, bringing them into close contact with Scientific misconduct in medical research (J Intern Med 1994; 235 : 103–35) and Medical ethics (this Minisymposium). The contents of the three Minisymposia are of importance not only to those dealing with medical journals but to all physicians – regardless of whether they are involved in research or in patient care – and to all others involved in health care. The Minisymposium gives a brief history of the development of research ethics, widens the scope of medical ethics and discusses its transcultural aspects. From a more practical standpoint the two last articles deal with the problem of who makes the decisions for whom, and when to stop treatment – both with relevance to one of the most important problems of medicine today: prioritization. The reader should note the difference between ‘medical ethics’, which is the wider concept, and ‘research ethics’, which deal specifically with the relation between the researcher and her/his patient or volunteer.     

Multidisciplinary interventions: mapping new horizons in diabetes care

More than 20 million people in the United States, or 7% of the population, have diabetes, with health care and work-related costs estimated to be $174 billion in 2007. Obesity constitutes one of the major driving factors behind this epidemic. Most drugs currently used to treat diabetes address the primary metabolic defects in type 2 diabetes mellitus, which are insulin resistance and pancreatic islet dysfunction. Incretin augmentation therapies, such as glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase IV inhibitors, restore glucose homeostasis by addressing some of the unmet needs in diabetes therapies related to alpha-cell dysfunction and chronic beta-cell dysfunction. This new group of drugs offers certain advantages because its use is characterized by a low incidence of hypoglycemia and the absence of weight gain. Moreover, the use of fixed-dose combinations of dipeptidyl peptidase IV inhibitors with other oral antidiabetic agents seems very attractive to patients because of their reduced pill intake and minimized financial burden, which may improve adherence. An efficient strategy to slow down the epidemic of diabetes must include these emerging therapies and regimens, coupled with intensive patient education that includes information on treatment benefits and adverse effects, medication costs, and medication regimen complexity.     

Theophylline in chronic obstructive pulmonary disease: new horizons

Although theophylline has side effects when used in bronchodilator doses, increasing evidence shows that it has significant antiinflammatory effects in chronic obstructive pulmonary disease at lower plasma concentrations. These antiinflammatory effects are unlikely to be accounted for by phosphodiesterase inhibition or adenosine receptor antagonism, which require higher concentrations. There is now evidence that theophylline at low therapeutic concentrations is an activator of histone deacetylases and that this activation enhances the antiinflammatory effect of corticosteroids. There appears to be a marked reduction in histone deacetylase-2 in macrophages and peripheral lung of patients with chronic obstructive pulmonary disease, which accounts for amplified inflammation and steroid resistance. Theophylline has been shown to restore steroid sensitivity in vitro. The effect of theophylline on histone deacetylase activity appears to be enhanced by oxidative stress. The mechanism whereby theophylline activates histone deacetylase is not yet known, but it does not involve other known actions of theophylline that account for its side effects. Better understanding of the molecular basis for the action of theophylline might lead to the development of novel drugs.     

Farnesyltransferase inhibitors in hematologic malignancies: new horizons in therapy

Farnesyltransferase inhibitors (FTIs) are small-molecule inhibitors that selectively inhibit farnesylation of a number of intracellular substrate proteins such as Ras. Preclinical work has revealed their ability to effectively inhibit tumor growth across a wide range of malignant phenotypes. Many hematologic malignancies appear to be reasonable disease targets, in that they express relevant biologic targets, such as Ras, mitogen-activated protein kinase (MAPK), AKT, and others that may depend on farnesyl protein transferase (FTase) activity to promote proliferation and survival. A host of phase 1 trials have been recently launched to assess the applicability of FTIs in hematologic malignancies, many of which demonstrate effective enzyme target inhibition, low toxicity, and some clinical responses. As a result, phase 2 trials have been initiated in a variety of hematologic malignancies and disease settings to further validate clinical activity and to identify downstream signal transduction targets that may be modified by these agents. It is anticipated that these studies will serve to define the optimal roles of FTIs in patients with hematologic malignancies and provide insight into effective methods by which to combine FTIs with other agents.     

Predictors of adverse outcomes in acute pancreatitis: new horizons

Acute pancreatitis (AP) continues to be a clinical challenge. The mortality of patients with AP with adverse outcomes like organ failure and infected necrosis can be as high as 43 %. Highly accurate predictors of adverse outcomes are necessary to identify the high-risk patients so that they can be meticulously monitored and managed. However, there are no ideal predictors till date. Over the past several years, a number of single- and multi-parameter predictors have been identified and tested for prediction of adverse outcomes in AP. Out of the different tools tested, blood urea nitrogen and the harmless acute pancreatitis score appears to be useful and feasible in the management of AP under Indian conditions. Other single-parameter predictors like serum creatinine, hematocrit, erythrocyte sedimentation rate, C-reactive protein, and D-dimer need to be put to further tests in high-quality prospective studies with large sample size at the community level. Multi-parameter prediction tools like the bedside index of severity of acute pancreatitis may not be appealing in day-to-day clinical practice.     

Warfarin resistance due to malabsorption

Abstract. A female patient developed warfarin resistance after 2 years of satisfactory therapy. Only a third of orally administered warfarin was absorbed, the clearance of warfarin was normal. The patient was also resistant for dicoumarol, while phenindione had satisfactory effect on the prothrombin time (PT).