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[Evidence based medicine: An example in the pediatric setting]

OBJECTIVE: This paper reviews the main steps to incorporate into clinical practice the concepts of evidence-based medicine, which is a strategy to help clinicians take more suitable decisions when confronted with clinical problems. METHOD: Search in Medline database of articles related with evidence-based medicine, review of a number of clinical epidemiology textbooks and selected articles. RESULTS: Evidence-based medicine recognizes two main sources of information for clinical decision making: 1) the individual patient; and 2) clinical epidemiological research. Trough evidencebased medicine the experience accumulated by a trained clinician should be integrated with the best external evidence obtained from systematic research. The appraisal of external evidence requires new knowledge and skills for the practicing clinician. These skills aim at enabling the clinician to make independent critical judgement of the quality of information that will translate into medical actions for his/her patients. Evidence-based medicine provides the tools to 1) keep up with an ever growing burden of health information; 2) efficiently select best available information; 3) critically appraise selected information; 4) synthesize selected information; and 5) integrate selected information into clinical experience in the management of diagnosed health problems. CONCLUSIONS: Evidence-based medicine could be seen as a way to bridge knowledge, skills, and attitudes acquired from clinical experience with the ability to evaluate the best available external evidence generated by scientific research.

Journal Article↗

Classification and treatment of rotator cuff injuries in the overhand athlete.

Rotator cuff injury in athletes results from accumulation of microtrauma to both the static and dynamic stabilizers of the shoulder. Our classification of these injuries and treatment protocol is based on knowledge of the pathophysiology of events leading to rotator cuff failure. Rotator cuff disease is attributed to one of five different modes of failure: primary compressive disease, secondary compressive disease, primary tensile overload, secondary tensile overload, and macrotraumatic injuries. Although disease is categorized based on a single failure mode, there is often significant overlap between the mechanisms of injury leading to the disease. Categorization and, consequently, treatment of the injury rely upon proper identification of the primary pathology and an understanding of the causative factors leading to rotator cuff failure. In most cases conservative management is successful, but, in the refractory cases, minimally invasive surgical techniques have also been successful in returning most athletes to a premorbid level of function.

Adult↗

The S6 kinase signaling pathway in the control of development and growth.

The discussion will focus on the role of the ribosomal protein S6 kinase (S6K) signaling pathway in the regulation of cell growth and proliferation. Although 40S ribosomal protein S6 phosphorylation was first described 25 years ago (Gressner and Wool, 1974), it only recently has been implicated in the translational up-regulation of mRNAs coding for the components of protein synthetic apparatus (Fumagalli and Thomas, 2000). These mRNAs contain an oligopyrimidine tract at their 5' transcriptional start site, termed a 5'TOP, which has been shown to be essential for their regulation at the translational level (Meyuhas et al., 1996). In parallel, a great deal of information has accumulated concerning the identification of the signaling pathway and the regulatory phosphorylation sites involved in controlling S6K activation (Dufner and Thomas, 1999). Despite this knowledge we are only beginning to identify the direct upstream elements involved in growth factor-induced kinase activation (Dennis et al., 2001; Pullen et al., 1998). Use of the immunosuppressant rapamycin, a bacterial macrolide, in conjunction with dominant interfering and activated forms of S6K1 has helped to establish the role of this signaling cascade in the regulation of growth and proliferation (Dennis and Thomas, 2002). In addition, current studies employing the mouse as well as Drosophila melanogaster have provided new insights into physiological function of S6K in the animal (Montagne et al., 1999; Pende et al., 2000). Loss of dS6K function in Drosophila melanogaster demonstrated its paramount importance in development and growth control (Montagne et al., 1999), whereas deletion of the S6K1 gene in the mouse led to an animal of reduced size and the identification of the S6K1 homologue, S6K2 (Shima et al., 1998). Such mice are significantly smaller during fetal development (Shima et al., 1998) and hypoinsulinemic in the adult, conditions known to lead to type 2 diabetes (Pende et al., 2000).

Animals↗

Formation of magnetosomes in magnetotactic bacteria.

The ability of magnetotactic bacteria to orient and migrate along geomagnetic field lines is based on intracellular magnetic structures, the magnetosomes, which comprise nano-sized, membrane bound crystals of magnetic iron minerals. The formation of magnetosomes is achieved by a biological mechanism that controls the accumulation of iron and the biomineralization of magnetic crystals with a characteristic size and morphology within membrane vesicles. This paper focuses on the current knowledge about magnetotactic bacteria and will outline aspects of the physiology and molecular biology of magnetosome formation. The biotechnological potential of the biomineralization process is discussed.

Biotechnology↗

Connective tissue skeleton in the normal left ventricle and in hypertensive left ventricular hypertrophy and chronic chagasic myocarditis.

Pictures certainly are worth a thousand words in the case of the structure of the connective tissue skeleton of normal and diseased myocardium. This report reviews the connective tissue matrix of the normal human myocardial tissue and the pathological myocardial fibrosis in left ventricular hypertrophy due to chronic arterial hypertension in humans and in human chronic chagasic myocarditis. The myocardial connective tissue matrix was studied employing a cell-maceration method that removes the myocardial tissue non-fibrous elements, and leaves behind a non-collapsed matrix, thus allowing a better three-dimensional view. Such information extends our knowledge of the expression of interstitial myocardial fibrous tissue in normal hearts and in hypertensive left ventricular hypertrophy and chronic chagasic myocarditis. The progressive accumulation of interstitial collagen fibers in both chronic cardiac diseases may be expected to decrease myocardial compliance and disrupt synchronous contractions of the ventricles during systole, contributing to a spectrum of ventricular dysfunction that involve either the diastolic or systolic phase of the cardiac cycle or both. In hypertensive heart disease myocardial fibrosis can be also implicated in the genesis of ventricular dysrhythmias, possible causes of sudden death among chronic hypertensive patients. Regarding chronic chagasic myocarditis, myocardial fibrosis is probably implicated in the genesis of malignant ventricular tachyarrhythmias (ventricular tachycardia and ventricular fibrillation), major causes of sudden death among patients with chronic Chagas' heart disease. The collagen distribution could interfere on the electrical properties of the myocardium. Fibrosis can block the cardiac impulse that may recycle (re-entry) through an alternative route and could slow conduction. In addition, the thick collagenous septa encompassing muscle fiber bundles could interfere with lateral impulse conduction, which would favor re-entry. Moreover, the methodology used is a useful tool to study the spatial organization of the collagen fibrils of the myocardium under normal and pathological conditions.

Chagas Cardiomyopathy↗

[Nephrologists and porphyrias].

As usually occurs for rare diseases, the word "PORPHYRIA" often recalls a confused topic with shaded boundaries, presenting "bullous" skin lesions, rare opportunity of diagnosis in clinical practice, unknown pathogenesis, and almost absent therapeutic options. The goal of this review is to draw attention to this topic, as new diagnostic and therapeutic tools might change the natural history of this disease. Porphyrias are disorders resulting from abnormalities of porphyrin metabolism. Porphyrins are molecules made up of four pyrrol rings, which constitute haeme-proteins, including haemoglobin. Following the "trigger" enzyme delta-aminolevulinic acid (ALA) synthase, which is capable of condensing succynil CoA and glycine, seven additional enzymes are involved in the process that eventually leads to haeme biosynthesis. Porphyrias are the result of total or partial deficiencies in these seven enzymes involved in haeme synthesis. Usually, the final haeme product exerts a negative feed-back on its synthesis. The enzyme deficiency that occurs in porphyrias is responsible for reduced haeme production, which, in turn, allows the cascade to be stimulated by increased activity of the trigger enzyme, ALA-synthase (ALA-s). However, due to the subsequent enzyme defects, notwithstanding increased ALA-s activity, haeme synthesis is blunted and intermediate metabolites accumulate. Clinical manifestations depend on which step the enzymatic defect occurs: if enzymatic defects are in the initial steps of the metabolic cascade, early metabolic intermediates will accumulate [i.e. ALA and porphobilinogen (PBG)] responsible for attacks of neurological dysfunction; if the enzymatic defects are in the final steps, sunlight-induced cutaneous lesions (phtotosensitivity) due to porphyrin accumulation in the skin will develop. The seven major human porphyrias may be classified into "hepatic or erythropoietic porphyrias" depending on the organ/tissue where metabolic alterations are more evident, or "acute or chronic porphyrias" depending on the prevalence of clinical symptoms, if neurologic (acute) or cutaneous (chronic). Only a small number of people with inherited enzyme deficiency will develop overt clinical disease, mainly because of the role of acquired aggravating and precipitating factors, such as drugs, hormonal causes, infection, caloric restriction, alcohol. The biochemical diagnosis of porphyrias relies on the detection of the consequences of increased ALA-s activity in the liver: overproduction, accumulation and increased excretion of early (ALA, PBG) or late (porphyrins) intermediate compounds in plasma, faeces and urine. A major difficulty arises from the knowledge that such abnormalities may be completely absent during the remission phases of the disease. Only in very specialised Centres it is now possible to measure specific haeme synthesis enzyme defects, and to perform molecular diagnosis by DNA analysis. The true prevalence of the diseases is unknown, ranging from 1:500 to 1:50,000. Therapeutic strategies include withdrawal of all common precipitants (drug, alcohol, fasting, infection), use of opiates and chlorpromazine, carbohydrates (300-400 g/day) and infusion of human haemine. Genetic therapies are being studied for the future.

Adult↗

[Relationships between biochemical qualities of paddy rice and climate conditions in the Anning River Valley].

Based on the experimental data of paddy rice planted geographically periodically without control in the Anning River Valley of Sichuan Province, this paper quantitatively analyzed the effects of meteorological conditions from 40 days before heading to ripeness on the biochemical qualities of paddy rice, and developed a model about the integrated relationships between biochemical qualities of paddy rice and mean temperature, daily range of temperature and daylight hours, which would be of significance both for the instruction of paddy distribution in the Anning River Valley and for improving rice qualities via adjusting planting time. The results showed that climate conditions had a great effect on the biochemical qualities of paddy rice, which was different in ways and in critical periods. The period when the correlation between some ingredients of rice and climate conditions was most significant was before or after, or from before to after full heading, which widened the existing knowledge about the period which was important for paddy rice qualities forming. Applying this finding in the Anning River Valley during 2002-2003, the accumulated high-grade paddy farming area stood at 73,000 hm2, 30,000 hm2 more than that in 2001, and brought 0.2 billion yuan increment to the peasants, promoting the development of high-grade paddy greatly.

Amino Acids↗

Transmission of mutans streptococci.

It has been shown that early establishment of mutans streptococci in the mouth of infants increases risk of caries. Extensive studies on the timing of infection, and on sources and routes of transmission of the organism have been performed. Results of many studies suggest that the source of mutans streptococci is the mother, especially her saliva. Methods used to attempt to verify this hypothesis have developed considerably in recent years. Recent research and work in progress using methods based on DNA analysis have increased and will extend knowledge about transmission. This review summarizes the results obtained by different methods of transmission of mutans streptococci. The final goal of studies is to accumulate adequate information for prevention strategies of mutans streptococcal infection.

Child, Preschool↗

[Development of the concept of antidotes: the contribution of clinical toxicology].

The clinical study of antidotes has been limited until the recent development of Clinical Toxicology Centers where rare but demonstrative observations were collected and a critical approach for the validation of therapy organized. After the period of setting of respiratory assistance in coma due to acute intoxication by psychotropic drugs, the knowledge of biochemical receptors for toxic molecules and the production of antagonistic molecules allows the setting of drugs with unquestionable efficacity according to the accumulation of data in CTC and to an international collaboration and consensus program. Some pharmacological research considered as necessary have permitted the discovery of new situations as frequent cyanhydric intoxications due to plastic furniture during home fires. The progress in antibodies-antidotes bioformation and pharmaceutical production is necessary to antagonize some acute and often lethal intoxications like these due to colchicine and paraquat.

Antidotes↗

Aerobiology of schools and public institutions--part of a study.

The influence of the indoor climate in relation to the health of persons has mainly been connected with the physico-chemical properties of the environment. Complaints from patients concerning eye, nose and throat problems, hoarseness, headache and fatigue are common, especially in schools and other public institutions with heavy traffic and badly cleaned or water damaged wall-to-wall carpets. The significance of specific allergenic components in dust such as mites, mould, animal dander and pollen is well-known. However, the influence of a dirt-factor or a moisture-factor in the carpets or from ventilation systems leading to accumulation, liberation and inhalation of dust and micro-organisms, on allergic and non-allergic persons has, until recently, been neglected. To obtain knowledge on this influence, a systematical registration of the biological factors based on consecutive investigation has started. Results from registration of airborne micro-organisms show a tendency towards a larger amount of micro-organisms measured 1 m above carpets than above bare floors.

Air Microbiology↗

[Primary biliary cirrhosis (PBC): concept, pathogenesis and classification].

Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease characterized by inflammatory destruction of median size intrahepatic bile ducts. The characteristic histological process is described as chronic nonsuppurative destractive cholangitis (CNSDC). Our knowledge for the pathogenesis of PBC remains incomplete. However, immunological mechanisms seems to play one of the most important role. The immunohistochemical examination represents accumulation of stimmulated T lymphocytes in the portal area. Attachment of CD8 positive T cells to bile duct epithelial cells is observed. The animal model of PBC indicates autoreactive CD4 positive T cells seems to be important at the early stage of PBC and CD8 positive cytotoxic T cells are essential for the progression of the disease. PBC is histologically classified into four overlapping stages by Scheuer. Clinically, PBC is classified into asymptomatic PBC (aPBC), PBC with itching alone (s1PBC) and with jaundice (s2PBC).

Animals↗

[Purine nucleoside phosphorylase (PNP)].

PNP, encoded by 6 exons on human chromosome 14q13, is a homotrimetic enzyme of approximately 96 k dalton. This enzyme reversibly catalyzes the phosphorolysis of purine nucleoside to their respective purine bases and the corresponding pentose-1-phosphate. The ultimate degradative product of purine nucleoside is uric acid, which is a depleted product with the absence of PNP activity. This leads to accumulation of deoxy-guanosine triphosphate, which inhibits the enzyme ribonucleoside reductase resulting in DNA synthesis block and T cell proliferation. Basic and brief knowledge of PNP biochemistry and functional physiology is summarized for the understanding of clinical features of PNP deficiency.

Animals↗

General preventive measures against carcinogenic exposure in the external environment.

Different measures are used to prevent unacceptable carcinogenic exposure from different sources in the external environment, be it accumulated carcinogens from previous pollution, exposure related to life-style, and exposure related to living standards and the organization of the community as a whole. A precondition for goal-directed prevention is knowledge of exposures to carcinogens and measures to minimize or substitute carcinogens in products and in emissions. One of the most significant sources of carcinogens in the outdoor air in many Western countries is the traffic, especially diesel-powered vehicles. Necessary preventive measures include restriction of carcinogenic exhaust from the individual vehicle, plans for the community to diminish transportation needs, as well as to changing the usual behaviour of the individual. Unlike exposure to carcinogens in the surrounding air, exposure to accumulated carcinogens in ground-water and in soil at polluted sites may be diminished by the pattern of use. International aspects are involved in for instance minimizing the risk of getting skin cancer from sunlight. Besides protecting vulnerable individuals there should be a global preservation of the ozone layer. Lowering the risk of long transported air pollution, like radioactivity from accidents at nuclear power stations, demands international efforts to increase safety measures and information about accidents.

Animals↗

[Is the sun our friend?].

Since the beginning of the 19th century the scientific knowledge concerning the effect of the sun rays upon the human organism, mainly on the skin, has been studied and the components of the sun spectrum were specified. During the last years the ozone layer was seriously damaged due to the so called civilization and the very harmful UVC component of the spectrum has entered the earth atmosphere. The accumulation of the unhealthy human habits and the new sun aggression threaten the human skin. The result is the growing number of the skin cancer, incl. melanoma of young people. The whole world dermatologists common opinion is that only the proper knowledge of this sun danger and the daily behaviour change combined with adequate dress and reliable sunscreen are able to prevent the serious damage in not very distant future.

Humans↗

The discovery of the causal agent of Minamata disease.

After the outbreak of an epidemic of a strange disease characterized by severe neurological signs in the small Japanese town of Minamata, a number of scientists in different disciplines were required to identify the causal agent. An account is given of the three-year program, with its disappointments and frustrations as a result of the limitations of knowledge of ecological principles and the absence of adequate techniques for detection and measurement. The lessons that have been learned on how toxic compounds can accumulate and concentrate in food chains are described as are the ecological contributions of environmentally safe waste disposal techniques. This article is based on the recollections of Dr. Shoji Kitamura, who contributed greatly to the discovery of the causative agent of Minamata disease.

Animals↗

The effect of Polbax extract on lipofuscin accumulation in cultured neonatal rat cardiac myocytes.

Polbax, a water-soluble extract of fresh pollen grains and pistils, was tested for its ability to influence the accumulation of lipofuscin (age pigment) in cultured neonatal rat cardiac myocytes. Exposure for 3 weeks to Polbax at concentrations of 0.1, 1.0 or 10 mg/L decreased lipofuscin accumulation morphometrically assayed using laser scanning microscopy images (green excitation light) of formaldehyde-fixed cells, by 24%, 41% or 43%, respectively. Based on the knowledge that oxidative stress and iron-catalysed peroxidation play an important role in lipofuscinogenesis, we suggest that Polbax may slow lipofuscin formation due to antioxidant activities, perhaps involving intralysosomal dismutation of superoxide produced by autophagocytosed mitochondria and/or iron-chelation.

Animals↗

Indium 111 white blood cell imaging of epididymitis.

The clinical diagnosis of epididymitis is frequently substantiated radiographically with pertechnetate 99m (99mTc) testicular scintigraphy and scrotal sonography. Indium 111 (111In) autologous leukocyte imaging in a patient with epididymitis has to our knowledge not been reported previously. The case presented is an elderly man with epididymitis. An 111In-labelled white blood cell scan demonstrated increased tracer accumulation in the region of the right epididymis. This suggests that 111In-labelled leukocyte scanning may be helpful in evaluating an inflammatory process involving the epididymis or testis and potentially may allow for differentiation of epididymitis and orchitis from missed torsion, tumour or cystic lesions.

Bone and Bones↗

Neutrophil-mediated tissue injury and its modulation.

Neutrophils play a key role in the development of the systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS). Since the lungs are the main target in these syndromes, with adult respiratory distress syndrome (ARDS) as the outcome, extensive research has been undertaken to prevent or mitigate ARDS. As evidence of the involvement of neutrophils in ARDS has accumulated, modulation of their function has become a major goal in terms of a therapeutic approach. In this short review, we sought to update our knowledge about neutrophils. Firstly, we summarized the various stimuli which activate neutrophils. Secondly, we described the different mediators, including cytokines, which are released by neutrophils. Lastly, we discussed the possible modulation of their function. Although we cannot assess the clinical usefulness of biochemical substances merely on the basis of their in vitro effects, understanding these mechanisms is fundamental to the success of the new therapeutic approach which is currently under way.

Cytokines↗