Arthrography for rheumatic disease. When, why, and for whom

The primary rheumatologic indication for an aspiration/arthrogram is the diagnosis of a septic joint. A second indication is the evaluation of a patient who has monoarticular complaints and normal plain radiographs. A third indication in patients who have known arthritis is that the contrast study can be used to evaluate the extent of cartilage destruction, identify complications that exacerbate pain, and determine if a soft tissue mass near the joint is related to the arthritis.     

Working-memory capacity, age, and memory for discourse

Two experiments explored the issue of whether age-related differences in memory for discourse can be explained by age-related differences in working memory capacity. Young and older adults were given a series of tasks designed to measure working memory capacity and memory for paragraphs. Although age-related differences were observed on digit, word, and sentence spans as well as on recall (Experiment 1) and recognition (Experiment 2), retention was not predicted well by scores on any of the span measures for either young or older adults in either experiment. The implications of these findings for hypotheses that age-related declines in working memory are responsible for problems in memory for prose are considered.     

New drugs, procedures, and devices for hypertension

Successful treatment of hypertension is difficult despite the availability of several classes of antihypertensive drug, and the value of strategies to combat the effect of adverse lifestyle behaviours on blood pressure. In this paper, we discuss two promising therapeutic alternatives for patients with resistant hypertension: novel drugs, including new pharmacological classes (such as vasopeptidase inhibitors and aldosterone synthase inhibitors) and new molecules from present pharmacological classes with additional properties in blood-pressure or metabolism pathways; and new procedures and devices, including stimulation of arterial baroreceptors and catheter-based renal denervation. Although several pharmacological targets have been discovered with promising preclinical results, the clinical development of novel antihypertensive drugs has been more difficult and less productive than expected. The effectiveness and safety of new devices and procedures should be carefully assessed in patients with resistant hypertension, thus leading to a new era of outcome trials and evidence-based guidelines.     

Folate recommendations for pregnancy, lactation, and infancy

An adequate intake of folate during pregnancy, lactation, and infancy is essential for maternal and child health and normal growth. Higher folate requirements during pregnancy and lactation are difficult to meet by increased intake of folate-rich food products only. Supplementation with folic acid is recommended not only to meet the higher requirements but also to prevent adverse pregnancy outcomes such as neural tube defects (NTDs). In countries that have implemented food fortification with folic acid, the folate intake has raised but does not yet meet the recommended amount for NTD risk reduction. Women's awareness of the need to supplement with folic acid prior to conception shall be raised in all countries. It is under debate whether a high folic acid intake might have metabolic and functional effects in utero and for the infant. Research is needed to investigate potential alternative folate forms for food fortification programs and to test their efficacy in risk reduction of adverse pregnancy outcomes. Breast-fed infants most likely receive sufficient folate. While the folate level of human milk is simulated in infant formula, data are lacking on the bioavailability and effect of folic acid in infants and on whether a tolerable upper intake level should be defined.     

Melatonin, aging, and age-related diseases: perspectives for prevention, intervention, and therapy

The high incidence of age-related diseases in the increasing population of elderly people has stimulated interest in the search for protective agents that have the capability of preventing premature aging and delaying the onset of degenerative disorders. To preserve health in old age becomes a primary goal for biomedicine, because the increasing longevity in our societies is associated with a rise in morbidity. The difficulties in finding new approaches and safe strategies for prevention, intervention, and treatment are related to the lack of theoretical background as well as to insufficient models to test the efficacy of anti-aging agents. Melatonin is a prime candidate for slowing the aging process and targeting its underlying pathology. Melatonin has profound gerontoprotective and antioxidant activities. Because enhanced oxidative stress plays a crucial role in the aging process and chronic diseases associated with senescence, the adminstration of a potent amphiphilic antioxidant agent with high bioavailability such as melatonin may become a promising, safe, and effective intervention strategy to slow aging and the initiation and progression of age-related disorders. Investigations on melatonin and its anti-aging activity may be of great benefit in increasing life quality of the elderly.     

Endomicroscopy,endocytoscopy, and autofluorescence for polyp characterization

This mini review deals with autofluorescence and cellular imaging using endomicroscopy or endocytoscopy during colonoscopy. Autofluorescence can be used to detect and characterize colorectal lesions whereas endomicroscopy and endocytoscopy are techniques to characterize colonic polyps based on cellular and subcellular patterns.     

Prevention, diagnosis, and treatment of tuberculosis in children and mothers: evidence for action for maternal, neonatal, and child health services

Tuberculosis affected an estimated 8.8 million people and caused 1.4 million deaths globally in 2010, including a half-million women and at least 64 000 children. It also results in nearly 10 million cumulative orphans due to parental deaths. Moreover, it causes 6%-15% of all maternal mortality, which increases to 15%-34% if only indirect causes are considered. Increasingly, more women with tuberculosis are notified than men in settings with a high prevalence of human immunodeficiency virus (HIV), and maternal tuberculosis increases the vertical transmission of HIV. Tuberculosis prevention, diagnosis, and treatment services should be included as key interventions in the integrated management of pregnancy and child health. Tuberculosis screening using a simple clinical algorithm that relies on the absence of current cough, fever, weight loss, and night sweats should be used to identify eligible pregnant women living with HIV for isoniazid preventive therapy or for further investigation for tuberculosis disease as part of services for prevention of vertical HIV transmission. While implementing these simple, low-cost, effective interventions as part of maternal, neonatal, and child health services, the unmet basic and operational tuberculosis research needs of children, pregnant, and breastfeeding women should be addressed. National policy makers, program managers, and international stakeholders (eg, United Nations bodies, donors, and implementers) working on maternal, neonatal, and child health, especially in HIV-prevalent settings, should give due attention and include tuberculosis prevention, diagnosis, and treatment services as part of their core functions and address the public health impacts of tuberculosis in their programs and services.     

Granted, undecided, withdrawn, and refused requests for euthanasia and physician-assisted suicide

BACKGROUND: The aims of this study were to obtain information about the characteristics of requests for euthanasia and physician-assisted suicide (EAS) and to distinguish among different types of situations that can arise between the request and the physician's decision. METHODS: All general practitioners in 18 of the 23 Dutch general practitioner districts received a written questionnaire in which they were asked to describe the most recent request for EAS they received. RESULTS: A total of 3614 general practitioners responded to the questionnaire (response rate, 60%). Of all explicit requests for EAS, 44% resulted in EAS. In the other cases the patient died before the performance (13%) or finalization of the decision making (13%), the patient withdrew the request (13%), or the physician refused the request (12%). Patients' most prominent symptoms were "feeling bad," "tiredness," and "lack of appetite." The most frequently mentioned reasons for requesting EAS were "pointless suffering," "loss of dignity," and "weakness." The patients' situation met the official requirements for accepted practice best in requests that resulted in EAS and least in refused requests. A lesser degree of competence and less unbearable and hopeless suffering had the strongest associations with the refusal of a request. CONCLUSIONS: The complexity of EAS decision making is reflected in the fact that besides granting and refusing a request, 3 other situations could be distinguished. The decisions physicians make, the reasons they have for their decisions, and the way they arrived at their decisions seem to be based on patient evaluations. Physicians report compliance with the official requirements for accepted practice.     

Bortezomib, melphalan, prednisone, and thalidomide for relapsed multiple myeloma

In multiple myeloma (MM), the addition of thalidomide or bortezomib to the standard oral melphalan/prednisone combination significantly increased response rate and event-free survival. In this multicenter phase 1/2 trial, dosing, safety, and efficacy of the 4-drug combination, bortezomib, melphalan, prednisone, and thalidomide (VMPT) was determined. Bortezomib was administered at 3 dose levels (1.0 mg/m2, 1.3 mg/m2, or 1.6 mg/m2) on days 1, 4, 15, and 22; melphalan was given at a dose of 6 mg/m2 on days 1 through 5 and prednisone at 60 mg/m2 on days 1 through 5. Thalidomide was delivered at 50 mg on days 1 through 35. Each course was repeated every 35 days. The maximum tolerated dose of bortezomib was 1.3 mg/m2. Thirty patients with relapsed or refractory MM were enrolled; 20 patients (67%) achieved a partial response (PR) including 13 patients (43%) who achieved at least a very good PR. Among 14 patients who received VMPT as second-line treatment, the PR rate was 79% and the immunofixation-negative complete response rate 36%. The 1-year progression-free survival was 61%, and the 1-year survival from study entry was 84%. Grade 3 nonhematologic adverse events included infections (5 patients), fatigue (1), vasculitis (1), and peripheral neuropathy (2); no grade 4 toxicities were recorded. Initial results showed that VMPT is an effective salvage therapy with a very high proportion of responses. The incidence of neurotoxicities was unexpectedly low.