Chloroquine is grossly under dosed in young children with malaria : implications for drug resistance

Background: Plasmodium falciparum malaria is treated with 25 mg/kg of chloroquine (CQ) irrespective of age. Theoretically, CQ should be dosed according to body surface area (BSA). The effect of dosing CQ according to BSA has not been determined but doubling the dose per kg doubled the efficacy of CQ in children aged <15 years infected with P. falciparum carrying CQ resistance causing genes typical for Africa. The study aim was to determine the effect of age on CQ concentrations. Methods and Findings: Day 7 whole blood CQ concentrations were determined in 150 and 302 children treated with 25 and 50 mg/kg, respectively, in previously conducted clinical trials. CQ concentrations normalised for the dose taken in mg/kg of CQ decreased with decreasing age (p<0.001). CQ concentrations normalised for dose taken in mg/m(2) were unaffected by age. The median CQ concentration in children aged <2 years taking 50 mg/kg and in children aged 10-14 years taking 25 mg/kg were 825 (95% confidence interval [CI] 662-988) and 758 (95% CI 640-876) nmol/l, respectively (p = 0.67). The median CQ concentration in children aged 10-14 taking 50 mg/kg and children aged 0-2 taking 25 mg/kg were 1521 and 549 nmol/l. Adverse events were not age/concentration dependent. Conclusions: CQ is under-dosed in children and should ideally be dosed according to BSA. Children aged <2 years need approximately double the dose per kg to attain CQ concentrations found in children aged 10-14 years. Clinical trials assessing the efficacy of CQ in Africa are typically performed in children aged <5 years. Thus the efficacy of CQ is typically assessed in children in whom CQ is under dosed. Approximately 3 fold higher drug concentrations can probably be safely given to the youngest children. As CQ resistance is concentration dependent an alternative dosing of CQ may overcome resistance in Africa.

O gerenciamento de pesquisas fármaco-clínicas no Brasil

O autor realiza revisão da literatura internacional e nacional sobre o tema, descreve as várias fases de desenvolvimento de uma nova droga e faz uma análise crítica da si t uaç;ão do gerenciamento das pesquisas fármaco-clínicas. Discute as posições da Farmacologia Clínica e da Medicina da indústria farmacêutica no exterior e no Brasil. Aponta as dificuldades para realizações e controle destas pesquisas e propõe uma nova abordagem gerencial para as pesquisas fármaco-clínicas. Após um periodo de doze anos, de 1975 a 1987, atuando nos diversos setores do departamento médico-Científico, de algumas indústrias farmacêuticas, com mais de 80% deste período dedicado ao planejamento, implantação, monitorização, conclusão e publicação de pesquisas fármaco-clínicas. Responsável pela publicação de nada menos do que quinze (15) ensaios. Tendo participado em, pelo menos, outras 24 estudos publicados, e mais outros 31 ainda não publicados (anexo 3, neste espaço de tempo. O autor após uma análise da situação, vem propor um método de gerenciamento destas pesquisas fármaco-clínicos realizadas no Brasil, de' forma que' todas as etapas necessárias para que estes ensaios se realizem, sejam metodotizadas, planejadas e devidamente avaliadas, podendo ainda permanecer armazenado e à disposição para pronta recuperação a qualquer tempo. Transformando-se desta forma em um excelente banco de dados, para as mais diversas informações, incluindo as de cunho oficial.

Conhecimento dos adolescentes sobre métodos contraceptivos: pesquisa-ação em uma unidade do programa saúde da família de Natal

It is a descriptive study with a qualitative approach, and an action-research type, which aimed to analyze the changes of knowledge about contraceptive methods invested to a teenager group attended in Igapó Family Healthcare Unit, in the city of Natal/RN, after consent and institutional assent of Ethics Committee of Rio Grande do Norte Federal University (Protocol No. 131/07). It were researched 16 teenagers of both sexes, with age ranging from 11 to 16 years. We used two structured questionnaires, one in the initial diagnosis and another during the seven meetings of the focus group, in addition to the field notes and the meetings discussions transcriptions. The data-collection was performed in the period of two months by a team composed by a nurse the research coordinator, a dentist, a nursing assistant, a community-based healthcare worker and a nursing academic. The quantitative and qualitative data were organized, tagged and categorized into spreadsheet in Microsoft Excel, being held a thematic analysis of speeches performed by the study participants. The results were presented as tables, graphics, photos, drawings and word clippings. The educational strategy developed in focus group allowed adolescents to discuss, exchange ideas and opinions on several contraceptive methods, providing expansion in knowledge of all contraceptives discussed, especially those natural and surgical, which were less mentioned at the beginning of the study. Among the advantages of the contraceptive methods listed by teenagers, was highlighted avoiding pregnancy and STDs in use of the barrier method of condom. As for the disadvantages more frequently noted by the survey with the misuse of barrier methods, was highlighted get pregnant, acquire STD's and do not prevent STD's in hormonal, natural and surgical methods. Adolescents showed consistency between the advantages and disadvantages and types of contraceptive methods, showing a widening in knowledge among them. It may be said that, in general, those surveyed had a good understanding about the use of the various contraceptive methods. Thus, the study participants had positively evaluated all the criteria used to qualify the meetings in the focus group. The action strategy of the focus group should be encouraged by professionals who work with teenagers, since they prefer to live in groups, one characteristic of adolescence.

Muscle lesion treatment in Brazilian soccer players: Theory vs. Practice

Background: In this study we evaluated the rehabilitation profile of Brazilian soccer players which underwent lower limb muscle lesions.Methods: This is a descriptive investigation. We evaluated 139 professional soccer players (1724 years old). We evaluated the following variables: muscle lesion diagnosis, symptoms, non steroidal anti-inflammatory used, physiotherapy treatment, which physiotherapy recourses was used if treated and train adaptation.Results: In great part of the athletes muscle lesion remained between 2 weeks and 1 month. Around 54% were diagnosed by a physician; the other part was diagnosed by a physical therapist. Non steroidal anti-inflammatory were prescribed by physicians in 42% of the cases; in 7% the physical therapist prescribed the medication while in 49% of the cases the masseur prescribed the drug. More than 1/4 of the athletes received physiotherapy treatement between 48 hours and 5 days. Isometric exercise therapy was applied in 15% of the cases. 63% were not accompanied by the physiotherapist on their return to the field. 48% received massages immediately after injury.Conclusion: We presented discrepancy between the recommended theory described by several researches and the practice. We indicate the necessity of recycling in a general context the rehabilitation of muscle injuries.

Effect of Glycolic Extract of Dillenia indica L. Combined With Microcurrent Stimulation on Experimental Lesions in Wistar Rats

This study evaluated the wound healing activity of a glycolic extract of Dillenia indica (GED) prepared from the mature fruits of the plant applied alone or in combination with microcurrent stimulation to skin wounds surgically induced on the back of Wistar rats. Methods. The animals were randomly divided into six groups: (A) negative control group; (B) group receiving microcurrent application (MC; [10 mu A/2 mins]); (C) group treated with GED; (D) group treated with an emulsion containing GED; (E) group treated with GED and MC, and (F) group treated with the emulsion containing GED and MC. Tissue samples were obtained 2, 6, and 10 days after injury and underwent structural and morphometric analysis, Results. There were observed differences in wound healing among the various treatments when compared to the control group. The combination of microcurrent plus extract or microcurrent plus emulsion containing GED was advantageous in all of the studied parameters (P < 0.05) when compared to the other groups with positive effects seen regarding newly formed tissue, number of fibroblasts, and number of newly formed blood vessels. The morphometric data confirmed the structural findings. Conclusion. Microcurrent application alone or combined with GED exerted significant effects on wound healing in this experimental model. This was probably due to the efficacy of microcurrent application since the extract alone did not significantly accelerate the healing process. D indica fruit extract most likely participates in the wound healing process as a result of its anti-inflammatory properties.

O pai presente: o desvelar da paternidade em uma família contemporânea

O objeto deste estudo é a figura concreta de um pai, presente em sua corporalidade e afetividade, que se depara com a demanda subjetiva, advinda da exigência de revisão de seu papel no mundo contemporâneo. Buscamos encontrar a paternidade que acolhe e convive com o processo de transformações em marcha: o pai que transita entre valores novos e arcaicos. O acesso a este conhecimento se deu através do método clínico de pesquisa, com apoio da psicanálise. Sem submeter os participantes ao tratamento psicanalítico, aplica seus conceitos na interpretação de fenômeno que tem dimensão subjetiva e também, social. Adotamos a entrevista como principal instrumento e a análise qualitativa enquanto estratégia, por permitir relevância à fala do entrevistado e dela extrair o dado significativo para nossas indagações.

Interações físicas e psicossociais em mulheres com fibromialgia

Fibromyalgia (FM) is a non-inflammatory rheumatic syndrome of unknown etiology, with symptoms of diffuse musculoskeletal pain and presence of specific anatomic sites called tender points. The symptoms are often associated with fatigue, sleep disturbances, morning stiffness, alterations in pain perception, anxiety and depression. Fibromyalgia exhibits a correlation between physical and behavioral symptoms, which have a negative influence on the quality of life of patients. Emotional skills are important factors since they are related to subjective well-being, personal productivity, social interaction and interpersonal relationships. We aim to describe the physical and psychosocial interactions in women with FM, showing the association between perceived social support and affect with symptoms of pain, functionality and mood. We will also describe a body representation of pain in women with FM. Data were collected over 3 years and the sample size ranged between studies. This is an exploratory cross-sectional study conducted with a convenience sample of 63 women with FM and 42 healthy women as a control group (CT), aged 20-76 years, recruited through spontaneous demand at Onofre Lopes University Hospital (HUOL) and the Clinical School of Physiotherapy of Universidade Potiguar (UNP). The Fibromyalgia Impact Questionnaire (FIQ), Beck Depression Inventory (BDI), Social Support Scale (MOS), Hamilton Anxiety Scale and Scale of Positive and Negative Affect Schedule (PANAS), in addition to pressure algometry were used. For data analysis, we used parametric and non-parametric tests and a general linear model with adjustment variables and analysis of variance. A significant difference was found between pain threshold and tolerance, functionality, depression, anxiety, social support, and positive and negative affect between the groups. Affective states and social support were associated with anxiety, depression and functionality. A body was drawn representing pain with higher incidences in trapeze, supraspinatus and second ribs. The reason for studying sensory aspects, affective behavior and social support in FM patients opens perspectives for scientific and clinical research of this syndrome. Women with chronic pain such as FM appear to have altered mood states, less social support and affective dysfunctions, influencing the other symptoms of the syndrome

Angústia e inibição: considerações a partir de um caso clínico

Este trabalho tem como objetivo discutir, a partir de um caso clínico, a articulação entre a Angústia e a Inibição, à luz da psicanálise. Partindo do trauma como fator fundante do psiquismo e desencadeador do estado de desamparo, destacamos a castração, como marca de um perigo a ser recalcado, até chegar à angústia primitiva, afeto que prepara o caminho para a emergência do sujeito. No primeiro momento, abordamos a evolução do conceito de angústia em Freud, ressaltando o modo como ele a articulou à inibição e ao sintoma, marcando, ainda, a diferença entre a angústia, como consequência direta do momento traumático, e como sinal de uma reprodução do trauma originário. Em seguida, investigamos o conceito de angústia em Lacan, enfatizando os avanços conceituais promovidos para o mesmo, notadamente no Seminário X; destacando-se a introdução do conceito de objeto a e os desdobramentos dessa invenção teórica. No segundo momento, focamos no conceito de inibição em Freud, seguido pela leitura lacaniana a esse respeito. Finalmente, refletimos acerca da delimitação que o conceito de objeto a dá às possíveis relações entre sujeito e objeto, buscando extrair algumas consequências clínicas das respostas que o sujeito constrói frente ao enigma do desejo do Outro, entre as quais a inibição e a angústia, articulando, desse modo, o caso clínico às discussões levantadas

Avaliação de parâmetros métricos oculares pela fotografia digital da face: uso do diâmetro da íris como unidade de referência

Purpose: To evaluate reproducibility and precision of ocular measurements by digital photograph analysis, in addition to the transformation of the measures according to the individual iris diameter as an oculometric reference. Methods: Twenty-four eyes have been digitally photographed in a standardized way at two distances. Two researchers have analyzed these printed images using a caliper and these digital forms by ImageJ 1.37 (TM). Several external ocular parameters were estimated (mm and as iris diameter) and methods of measurement compared regarding their precision, agreement and correlation. Results: Caliper and digital analysis of oculometric measures provided significant agreement and correlation, nevertheless the precision of digital measures was higher. The estimates of numeric transformation from oculometric measures according to individual iris diameter resulted in great correlation to caliper measures and high agreement when compared to different distances of taking the photographs. Conclusions: Facial digital photographs allowed oculometric precise and reproducible estimates, endorsing clinical research usefulness. Using iris diameter as individual oculometric reference disclosed high reproducibility when facial photographs were taken at different distances.

Use of corticosteroid therapy on the modulation of uterine inflammatory response in mares after artificial insemination with frozen semen

In order to modulate uterine inflammatory response and evaluate the effect of corticosteroid therapy on fertility, 90 cycles of 45 mares were used for artificial insemination with frozen semen, using three different protocols: G1 - inseminated with frozen semen (800 x 10(6) viable spermatozoa pre-freezing) + 20 mL of seminal plasma; G2 - inseminated with frozen semen (800 x 10(6) viable spermatozoa pre-freezing) + corticosteroid therapy; G3 - inseminated with frozen semen (800 x 10(6) viable spermatozoa pre-freezing) + 20 mL of seminal plasma + corticosteroid therapy. Corticosteroid therapy consisted on one administration of prednisolone acetate (0.1 mg/Kg - Predef (R)) when mares presented 35mm follicles and uterine edema, concomitantly with the unique dose of hCG (human chorionic gonadotropin), then repeated each 12 hours until ovulation. on first fertility trial, with normal mares, there was no difference between control and treated groups (p>0.05), using seminal plasma associated with corticosteroid therapy (40 vs. 38%, respectively) or corticosteroid therapy alone (40 vs. 45% respectively). The second fertility trial, performed with mares with previous history of post-insemination endometritis, demonstrated a significant increase of pregnancy rate when mares were submitted to corticosteroid therapy (0.0 vs. 64.5%, respectively; p<0.05). Corticosteroid therapy was shown to be safe, with no physical or reproductive alterations on treated mares, demonstrating to be an adequate option to those animals with history of post-breeding or post-insemination endometritis. Further clinical research is necessary to confirm these results and contribute to the establishment of preventive therapy for cases of post-insemination endometritis.

Propolis: Is there a potential for the development of new drugs?

Introduction: Propolis has plenty of biological and pharmacological properties and its mechanisms of action have been widely investigated in the last years, using different experimental models in vitro and in vivo. Researchers have been interested in the investigation of isolated compounds responsible for propolis action; however, there is lack of clinical research on the effects of propolis.Strategy and objectives: Since propolis-containing products have been marketed and humans have used propolis for different purposes, the goal of this review is to discuss the potential of propolis for the development of new drugs, by comparing data from the literature that suggest candidate areas for the establishment of drugs against tumors, infections, allergy, diabetes, ulcers and with immunomodulatory action.Conclusions: The efficacy of propolis in different protocols in vitro and in vivo suggests its therapeutic properties, but before establishing a strategy using this bee product, it is necessary to study: (a) the chemical nature of the propolis sample. (b) Propolis efficacy should be compared to well-established parameters, e.g. positive or negative controls in the experiments. Moreover, possible interactions between propolis and other medicines should be investigated in humans as well. (c) Clinical investigation is needed to evaluate propolis potential in patients or healthy individuals, to understand under which conditions propolis may promote health. Data point out the importance of this research field not only for the readers and researchers in the scientific community waiting for further clarification on the potential of propolis but also for the pharmaceutical industry that looks for new drugs. (C) 2010 Elsevier B.V. All rights reserved.

Assessment of Gastrointestinal Motility in Renal Transplant Recipients by Alternate Current Biosusceptometry

Background. Gastrointestinal (GI) complications are common after renal transplantation, mainly owing to immunosuppressive therapy. Assessment of GI transit time can facilitate rational management of these disorders.Objective. We evaluate the GI transit parameters in renal transplant recipients taking tacrolimus, azathioprine, and prednisone with the use of the alternate current biosusceptometry (ACB) technique and compared them with healthy volunteers.Methods. Ten renal transplant recipients and 10 healthy volunteers were enrolled in this study. After an overnight fast, patients and volunteers ingested a standard meal containing magnetic markers. The biomagnetic monitoring was performed at 10-minute intervals for at least 8 hours to obtain gastric emptying as well as the colonic arrival time-intensity curves. Mean gastric emptying time (MGET), mean colon arrival time (MCAT), and mean small intestinal transit time (MSITT) were quantified and compared between control and patient groups with results expressed as mean +/- SD.Results. The MGET measured by the ACB technique was 48 +/- 31 minutes and 197 +/- 50 minutes for patients and healthy subjects, respectively. MSITT and MCAT values calculated for patients versus volunteers were 171 +/- 71 minutes versus 197 +/- 71 minutes and 219 +/- 83 minutes versus 373 +/- 52 minutes, respectively. Renal transplant recipients showed significantly faster; gastric emptying and colon arrival times (P < .001) compared with normal volunteers; however, small intestinal transit time was not significantly different (P = .44).Conclusions. In stable renal transplant recipients, the GI transit parameters were significantly faster than in normal healthy volunteers. ACB sensors are versatile technologies that can be used for clinical research, because they offer an excellent opportunity to evaluate GI transit in a noninvasive manner without the use of ionizing radiation.

Panorama atual da ética em pesquisa em seres humanos

In the last decades, medical care has been increasingly permeated by the concept of evidence-based-medicine, in which clinical research plays a crucial role in establishing diagnostic and treatment. Following the improvements in clinical research, we have a growing concern and understanding that some ethical issues must be respected when the subjects are human beings. Research with human subjects relies on the principles of autonomy, beneficence, no maleficence and justice. Ordinance 196/96 from the National Health Board adds to the Brazilian legislation such renowned bioethical principles.Aim: Discuss the main ethical aspects involved in research with human subjects.Materials and Methods: Critical analysis of Ordinance 196/96 and related literature.Conclusion: Ordinance 196/96 rules research with human subjects; nevertheless, it requires more in-depth discussions regarding the informed consent, use of placebo, research with vulnerable populations and research in developing countries.

Teledermatologia - Passado, presente e futuro

Teledermatology is the area of Telemedicine that studies the application of telecommunication and information technology to dermatology practice without the presence of a specialist. It is a potential manner to deliver health planning, research, education, clinical meetings, second medical opinions and dermatological care to populations who cannot easily travel. The evolution, cost reduction and dissemination of telecommunication and information technology have enabled the implementation of low cost and comprehensive teledermatology systems to support clinical practice all over the world. © 2005 by Anais Brasileiros de Dermatologia.

Efeito do praziquantel incorporado a lipossomas nos diferentes estágios de desenvolvimento dos ovos de Schistosoma mansoni

Mansonian schistosomiasis is caused by an intravascular digenetic trematode Schistosoma mansoni. Praziquantel (PZQ) and oxamniquine (OXA) are the drugs of choice for the treatment of this disease. However, both drugs are subject to some limitations in their action and cases of tolerance and resistance have been reported. Moreover, tolerance and resistance cases have been reported. For this reason, there is an urgent need for research on new alternatives aimed at improving the action of existing drugs, such as the incorporation of these drugs into liposomes. In this study, the efficiency of action of liposome- encapsulated praziquantel (lip.PZQ) on oviposition by S. mansoni, strain BH, was assessed in Mus musculus mices (SPF Swiss mice). Four PZQ and lip.PZQ doses (47; 60; 250 e 300mg/kg) were tested. Some mice were treated 30 days post-infection and others after 45 days. The oogram analyses showed that the most effective lip.PZQ treatment was 300mg/kg dose given on the 45th day post infection, which reduced the number of S. mansoni eggs per gram of tissue.