Haemophilia in the developing world: the Brazilian experience

The success of haemophilia treatment is based on well-established criteria, and the use of clotting factor concentrates is fundamental. These strategies are seen in the developed world when measures of quality of life are studied or when disabilities are evaluated among haemophilic patients. At the same time, countries in the developing world, with almost 80% of the haemophilia population, are making tremendous efforts to change their diagnosis and treatment methods, in order to improve their healthcare and therefore be able to promote better life for haemophiliacs. However, these goals are threatened when there are many social needs and few economic resources. There is wide variation in conditions in these countries, depending on what has already been done, how many patients the country has, how the blood banking services are planned and obviously, what are the interested parties. Even with so many difficulties, there are ways to work towards and reach the most important goal, which is to prepare the haemophiliacs to be citizens that are as productive and capable of working as are the nonhaemophiliacs. Each country has to take its part; the commitment of the community, physicians and government will be needed to design a model that is compatible with all the necessities and possibilities, and is understood by all the persons involved.     

The allergenic significance of legumes

Leguminous are a cheap source of protein that are cultivated practically throughout the world. They are the main source of food in developing countries. In the Mediterranean area and Middle East, the most commonly consumed legumes are lentils and chickpea. In the United States, United Kingdom and south-east Asia, the major legumes involved in food allergy are considered to be peanut and soy bean, respectively. The clinical manifestations of the allergy to legumes are similar for all legumes and range from oral allergy syndrome, urticaria, angioedema, rhinitis and asthmatic crises to anaphylaxis and even death. Legumes have a high degree of immunological cross-reactivity. Severals authors have described cross-reactivity among different legumes and between legumes and various vegetables. The allergenicity of legumes is mainly is mainly related to allergens from the storage proteins of seeds. Vicilins from this group of proteins could be an important common allergen in clinical allergy to legumes. Profilins are considered to be a cause of cross-reactivity among fruits, vegetables and some pollens and are believed to be a panallergen. Other panallergens of increasing importance are lipid transfer proteins. Few studies have assessed the long-term clinical course of allergy to legumes. Novel therapeutic agents are being investigated for the treatment of peanut allergy and these could be applied to other legumes.     

Drug allergy

Allergy to drugs is very common and its manifestations vary in importance from transitory skin eruptions to fatal reactions. Among the symptoms which are considered due to sensitization are not only the usual allergic symptoms of asthma, rhinitis, urticaria and angio-edema but drug fever, leukocytosis, arthralgia, lymphadenopathy and many types of skin eruptions. There is also considerable evidence that hepatitis, agranulocytosis and thrombocytopenia due to drugs are phenomena of sensitization rather than of primary toxicity. In sensitization due to protein drugs, circulating antibodies are usually demonstrable and skin tests are of value in diagnosis. In cases due to the non-protein drugs, antibodies are rarely demonstrated by the usual methods and skin tests, except for patch tests in certain types of dermatitis, are of little diagnostic value. Pathologic studies have demonstrated widespread visceral lesions, chiefly arteritis and focal necrosis, in patients who showed clinical evidences of drug sensitization. The diagnosis of drug allergy depends primarily on a knowledge of its diverse manifestations and of the symptoms most commonly produced by each type of drug. The degree of specificity and the duration of such sensitizations are so variable that generalizations are impossible. Desensitization with protein substances is often successful but the results of similar attempts with non-protein drugs are inconclusive.     

Counterpoint: invasive aspergillosis and the environment--rethinking our approach to prevention.

Preventive measures are important in the control of invasive aspergillosis (IA) because diagnosis is difficult and the outcome of treatment is poor. If effective strategies are to be devised, it will be essential to have a clearer understanding of the sources and routes of transmission of Aspergillus species. Nosocomial outbreaks of IA highlight the fact that Aspergillus spores are common in the hospital environment. However, in general, such outbreaks are uncommon. Most cases of IA are sporadic in nature, and many of them are now being acquired outside of the hospital setting. Housing patients in high-energy particulate air-filtered hospital rooms helps prevent IA, but it is feasible and cost-effective only for the highest-risk groups and for limited periods. Control measures, which are designed to protect patients from exposure to spores outside the hospital, are even more difficult. Nevertheless, now that high-risk patients are spending more time outside of the hospital, the cost benefits of antifungal prophylaxis and other preventive measures require careful evaluation.     

Introduction to biostatistics: Part 4, statistical inference techniques in hypothesis testing

Statistical methods used to test the null hypothesis are termed tests of significance. Selection of an appropriate test of significance is dependent on the type of data to be analyzed and the number of groups to be compared. Parametric tests of significance are based on the parameters, mean, standard deviation, and variance, and thus are used appropriately when interval or ratio data are analyzed. The t-test and analysis of variance (ANOVA) are examples of parametric tests of significance. Assumptions regarding the data to be analyzed when using the t-test or ANOVA include normality of the populations from which the sample data are drawn, homogeneity of the variances of the populations from which the sample data are drawn, and independence of the data points within a sample group. The t-test is the appropriate test of significance to use if there are only two groups to compare. If there are three or more groups to compare, ANOVA is the appropriate test. ANOVA holds the preset alpha level constant. While ANOVA will imply a significant difference between the groups compared, a multiple comparison test will define which of the three or more groups differ significantly.     

Mechanisms of host defense against infection with Streptococcus pneumoniae.

Various aspects of the host's response to infection by Streptococcus pneumoniae are reviewed. First, the structure of the bacterium is described, with a focus on those elements that are related to its immunogenicity and pathogenicity. The epidemiology of the pneumococcal serotypes, which are differentiated by the molecular structure of the capsule, is considered briefly, and several key points are emphasized--for example, that some pneumococcal types are more pathogenic than others; that variations in biological behavior are based on differences in the chemical composition of the capsule, although the particular factors determining virulence are not known; and that cell wall peptidoglycan, a structure common to all pneumococci, plays an important role in the inflammatory reaction in the tissues. Next, current views on the pathogenesis of pneumococcal infections are discussed. Finally, the roles of type-specific antibodies to the capsular polysaccharide and of complement in the opsonization of pneumococci and the clearance of these bacteria from the bloodstream by the spleen and liver are reviewed.     

Obesity and endocrine disease.

Several endocrine abnormalities are reported in obesity. Some of these abnormalities are considered as causative factors for the development of obesity, whereas others are considered to be secondary effects of obesity and usually are restored after weight loss. Thyroid hormones usually are normal in obesity, with the exception of T3 which is elevated. Prolactin is normal but prolactin response to different stimuli is blunted. GH is low and GH response to stimuli is blunted. IGF-I levels are normal or elevated. Cortisol, ACTH, and urine free cortisol levels are usually normal; however, a hyperresponsiveness of the HPA axis with increased cortisol and ACTH response to stimulatory tests is observed in centrally obese individuals. Total testosterone and SHBG levels are low, but free testosterone levels are usually normal in obese men. LH and FSH levels usually are normal and estrogens are elevated. Norepinephrine levels are elevated, whereas epinephrine levels are low or normal. Aldosterone levels are elevated but renin activity is usually normal. Parathyroid hormone levels are elevated with normal serum calcium levels and increased urine calcium levels. Monogenic mutations that result in severe obesity have been described in several individuals. Also, several endocrine diseases have obesity as one their clinical manifestations. Hypothyroidism, Cushing's syndrome, GH and testosterone deficiency, polycystic ovarian syndrome, insulinoma, hypothalamic lesions, and genetic syndromes often present with obesity. In most of these conditions, appropriate treatment of the primary disease results in weight loss. In addition, the fat cell has been found to be an endocrine organ that produces several peptides that are bioactive and participate in the regulation of adipocyte function.     

Numbers needed for treatment and their respective confidence intervals: useful tools to assess clinical significance and uncertainty associated with medical interventions]

This is a narrative review of a concept--number needed to treat (NNT). The proprieties of NNTs are described. Furthermore NNTs as important tools for medical decision are discussed. In particular, conditions that make calculus and the interpretation of NNTs somewhat more complex are commented. Namely, we consider situations where the results are not primarily binary or are expressed as "time to event" or come from a meta-analysis. The inconsistencies that might occur when NNTs are calculated from meta-analysis are discussed in some detail. Definitions for parameters derived from NNTs, as numbers needed to harm (NNH), unqualified success (NNTUS) and unmitigated failure (NNHUF) are given. Finally the usefulness of NNTs and absolute risk reductions to communicate risk to individual patients are considered. It is concluded that despite NNTs being powerful tools for medical decision, in the case of communicating risks to the individual patient absolute risks might be preferable.     

Herbal medicine: Beneficial effects,side effects,and promising new research in the treatment of arrhythmias

Herbal medications and dietary supplements are unregulated in the United States. The use of these medications has dramatically increased over the past decade. Many of these drugs are biologically active, yet physicians are often unaware their patients are using a traditional remedy. Physicians are frequently unfamiliar with the medications being used and the intended effect, as well as the side-effect profiles that accompany them. Recently, some of the herbal mediations that are commonly used in the general population have been shown to be beneficial for the treatment of arrhythmias. Unfortunately, many more have been shown to be detrimental. In this article, the background behind herbal medication and the degree to which herbal medications are being used is reviewed. Herbal medications known to have beneficial effects in the treatment of arrhythmias, as well as those that have known detrimental effects with regard to cardiac arrhythmias, are highlighted. Finally, research that has been done in this field, focusing on those compounds that have been shown to be biologically active in the treatment of cardiac arrhythmias, are reviewed.     

Alcohol consumption and mortality. I. Characteristics of drinking groups

Aims. This is the first of a set of three papers evaluating drinking status and mortality risk. Analyses of multiple studies describe associations of drinking patterns with characteristics hypothesized to confound the relationships between drinking status and mortality. Characteristics which both significantly differentiate drinking groups and are consistent across studies would suggest that mortality studies not controlling for them may be compromised. Design and participants. Associations are evaluated from the raw data of 10 general population studies which contained mortality data. Long-term abstainers are compared to former drinkers, long-term abstainers and former drinkers are compared to light drinkers (by quantity, frequency and volume in separate analyses) and moderate to heavy drinkers are compared to light drinkers. Tetrachoric correlation coefficients assess statistical significance; meta-analysis determines if associations are homogeneous across studies. Measurements. Measures of alcohol consumption are quantity, frequency and volume; long-term abstainers are differentiated from former drinkers. Multiple measures of health, social position, social integration and mental health characteristics are evaluated. Findings. Across studies, adult male former drinkers are consistently more likely to be heavier smokers, depressed, unemployed, lower SES and to have used marijuana than long-term abstainers. Adult female former drinkers are consistently more likely to be heavier smokers, in poorer health, not religious, and unmarried than long-term abstainers. Both types of abstainers tend to be of lower SES than light drinkers and report poorer health (not consistent). Female abstainers are more likely to be of normal or overweight than light drinkers. Conclusions. Characteristics of two groups of abstainers, other than their non-use of alcohol, may confound the associations found between drinking and mortality risk.     

Fungal infections in older adults.

Invasive fungal infections have become an increasing problem in older adults. Infections with opportunistic fungi have increased because older patients are more likely to be considered for transplantation, receive aggressive regimens of chemotherapy for cancer, and take immunosuppressive drugs for nonmalignant diseases. In addition, healthy older adults are now more likely to travel extensively and to indulge in outdoor activities, which put them at risk for exposure to endemic mycoses. Although many of the clinical manifestations of fungal infections in older and younger adults are similar, there are aspects of histoplasmosis, aspergillosis, and cryptococcosis that are unique to older patients. Treatment of older adults with amphotericin B is difficult because of the intrinsic nephrotoxicity of the drug. Although they are less toxic, azoles must be used carefully for treatment of older adults, who are more likely to experience serious drug-drug interactions than are younger persons.     

Loss of an apurinic/apyrimidinic site endonuclease increases the mutagenicity of N-methyl-N''-nitro-N-nitrosoguanidine to Escherichia coli.

xthA- Escherichia coli, which are missing a major cellular apurinic/apyrimidinic (AP) endonuclease, are 5- to 10-fold more sensitive than xthA+ bacteria to mutagenesis by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) under conditions that induce the "adaptive response." The xthA(-)-dependent mutations are also dependent on SOS mutagenic processing and consist of both transversion and transition base substitutions. When MNNG-adapted xthA- bacteria are challenged with a high dose of MNNG, more xthA(-)-dependent SOS-dependent mutations are induced, and transversions are enhanced relative to transitions. The mutations induced by challenge are eliminated in xthA- alkA- bacteria, which are also deficient for 3-methyladenine glycosylase II activity. These data are consistent with the hypothesis that AP sites, at least some of which are produced by glycosylase activity, are mutagenic intermediates following cellular DNA alkylation.     

Nouveautés en allergologie : eczéma de contact

With respect to contact allergy, the latest observations relate to the allergens and the test methods. Every year there are a few reports of cases of contact allergy to new products and to others that are little known. The most interesting are the allergens that cause the minor epidemics that are reported by cosmetic vigilance committees, for example, cases caused by depilatory waxes, hairdressing products and perfume components. With respect to the test methods, the standard series continues to evolve. Francophone physicians are in the process of bringing up to date a battery that includes allergens that they are likely to encounter and that they believe should be included sooner or later in the european standard series. Finally, it would be interesting to test irritant products to define more precisely patients’ reactivity threshold so that we could identify those who are hyperreactive and candidates for false positive reactions.     

Radiography in the assessment of musculoskeletal conditions

Plain film radiography is the most widely used imaging technique for diagnosing and monitoring the progression of chronic inflammatory and degenerative joint diseases. Advanced imaging techniques that are better suited for detecting soft-tissue inflammation are available, but they are more costly and some of them may expose the patient to higher doses of radiation. Plain film radiographs are inexpensive, easy to generate, can be compared with baseline and prospective films, and provide a permanent, reproducible record. Radiographs can easily detect the features that are specific to various rheumatological disorders, and serial radiography can be used to assess response to therapy by measuring erosions, joint space narrowing, and other disease-specific features. This chapter discusses the use of radiography for diagnosing and differentiating various rheumatic joint diseases, specifically rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis and osteoarthritis. The most frequently used scoring systems that are used to assess and monitor the severity and progression of these disorders are briefly described.     

RecA-like proteins are components of early meiotic nodules in lily

Early meiotic nodules (also called recombination nodules) are proteinaceous structures about 100 nm in diameter that are associated with forming synaptonemal complexes (SCs) during early prophase I of meiosis. Although their function is unknown, early nodules may be involved in searching for DNA homology before synaptic initiation. Two potential components of early nodules are Rad51 and Dmc1 proteins. These proteins are important for meiotic recombination in eukaryotes and are homologous to RecA, the major protein that catalyzes homologous pairing and DNA strand exchange in prokaryotes. In addition, Rad51 has been localized by immunofluorescence in abundant foci that may correspond to early nodules in yeast, lily, and mouse. In yeast and lily, Dmc1 and Lim15, the lily homolog of Dmc1, colocalize with Rad51. Here, using electron microscopic immunogold localization to spreads of zygotene and early pachytene SCs from lily, we confirm that RecA-like proteins are components of early nodules. The antibody used was generated to full-length tomato Rad51 protein and binds to both Rad51 and Lim15 in immunoblots of lily primary microsporocyte proteins. The labeled early nodules are heterogeneous in size and are associated with both axial elements and SCs. There are two classes of early nodules, those that are densely labeled with gold and those that are not labeled at all. This result may be due to technical limitations associated with using spread preparations or to differences in the nodules themselves. The presence of Rad51 and/or Lim15 proteins in early nodules supports the hypothesis that early nodules are involved in recombination-related events during meiosis.     

Recommendations of the Task Force on Record-Keeping and Blood Distribution Systems

Abstract. The objectives of an automated donor record system are reviewed and recommendations as to file content and structure of a computer-based system are outlined. Four sections are suggested, data related to donor identification, demography, date of last donation and special services requirements. Alternative means of data entry and donor-donation links are discussed as well as desirable capabilities of unit record and patient record systems. Two types of blood distribution systems are outlined, namely the reactive type where hospital blood bank inventories are replenished on demand and the predictive type where inventory requirements are predicted in advance and inventories are replenished on a fixed, previously agreed on schedule.     

Present-day health education in the field of cardiology

Causes of limited efficiency of efforts to disseminate cardiologic knowledge are analysed. Ways to increase education efficiency are proposed, such as educational dialogue variants, warranting an efficient system for the control of preventive work. Rationale and recommendations are given for the use of television programs and other media. Variants of the adjustment of the educational effort to the level of the audience are proposed. Educational aspects of the work of a rural cardiologic practitioner are pointed out. Formal ways of data presentation are described with reference to current possibilities of the available projection equipment.     

Amputations and ulceration; pitfalls in assessing incidence

In order to direct scientific research, it is pivotal to know the extent of a clinical problem. Therefore, much effort has been undertaken to tally all diabetic foot problems around the world. Incidence and prevalence figures concerning both foot ulcerations and lower extremity amputations have been reported extensively worldwide. The figures presented are being compared with those from other countries, regions or clinics and those with the lowest numbers are deemed best practices.However, for these comparisons to be valid there are many possible pitfalls that are to be considered. A significant number of epidemiological and clinical considerations are to be dealt with and many of these are extremely important to realize when comparing ulceration or amputation rates. The influence of using a certain definition of nominators and denominators are explained. Also, the clinical setting in which the research has been performed is of importance. Many possible pitfalls are discussed in this presentation. Although there are limitations to this type of research, it may be the only way possible to go. In order to compare health strategies in certain areas of the world or to determine the importance of an intervention, incidence and prevalence figures certainly may prove a beneficial effect and therefore justify an intervention. Therefore, given the limitations epidemiological research concerning the prevalence and incidence of foot-related complications still forms the backbone of clinical research in the area of the diabetic foot.     

Management of primary sclerosing cholangitis

Guidelines for clinical practice are intended to indicate preferred approaches to medical problems as established by scientifically valid research. Double blind, placebo-controlled studies are preferable, but reports and expert review articles are also utilized in a thorough review of the literature conducted through the National Library of Medicine's MEDLINE. When only data that will not withstand objective scrutiny are available, a recommendation is identified as a consensus of experts. Guidelines are applicable to all physicians who address the subject, without regard to specialty training or interests, and are intended to indicate the preferable but not necessarily the only acceptable approach to a specific problem. Guidelines are intended to be flexible and must be distinguished from standards of care that are inflexible and rarely violated. Given the wide range of specifics in any health care problem, the physician must always choose the course best suited to the individual patient and the variables in existence at the moment of decision. Guidelines are developed under the auspices of the American College of Gastroenterology and its Practice Parameters Committee and approved by the Board of Trustees. Each has been intensely reviewed and revised by the Committee, other experts in the field, physicians who will use them, and specialists in the science of decision of analysis. The recommendations of each guideline are therefore considered valid at the time of their production based on the data available. New developments in medical research and practice pertinent to each guideline will be reviewed at an established time and indicated at publication to assure continued validity.     

Tobacco cessation and brief advice.

Patients who are enrolled on tuberculosis (TB) treatment are often ill and are seeking ways to get better. They are more likely at that time to adopt risk-reducing health behaviours. Interventions that are neither complicated nor time-consuming are available to health service personnel to help patients undertake smoking cessation. Brief advice to patients repeated at various times throughout their TB care can increase cessation rates. All tobacco use needs to be identified and reasons for quitting enunciated. Patients are thus given a framework for considering smoking cessation. If patients then choose not to stop currently, they can be asked to reconsider at a later visit, and also be cautioned to avoid smoking in the presence of others. Smokers who want to stop can discuss strategies for avoiding craving and withdrawal, and pharmacological agents can be recommended if they are available. Because the brief advice is repeated, patients are reinforced either for having stopped or for their progress towards stopping.