Clinicopathological and immunohistochemical featuresof the severe pulmonary form of leptospirosis

Four cases of severe pulmonary form of leptospirosis (SPFL) are described. In all four of these blood culture proven cases, there was severe pulmonary injury characterized by alveolar hemorrhage and acute respiratory failure. Three patients died in less than 48 hours after onset of the first respiratory signs. Leptospiral antigen detection in lung tissues was positive by immunoperoxidase in all three of these cases, suggesting that the microorganism exerts a local direct destructive action. Patients with SPFL should be carefully monitored, as the abrupt onset of severe alveolar hemorrhage can lead to respiratory insufficiency and death. The authors emphasize the importance of radiological findings and blood gas analysis for prompt clinical diagnosis, and suggest that corticosteroids, associated with antibiotics, early respiratory support, and platelet transfusions are useful as an attempt to prevent further development of SPFL.

Clinical and laboratory findings related to a favorable evolution of hantavirus pulmonary syndrome

The medical records of 27 patients with hantavirus pulmonary syndrome were analyzed according to the need for invasive mechanical ventilation in relation to the following data up on hospital admission: age, gender, fever, cough, dyspnea, systolic arterial blood pressure, heart rate, levels of hemoglobin, hematocrit, leukocytes, lymphocytes, platelets, creatinine and arterial blood gases. The volume infused during the first 24 hours after admission, the use of inotropic agents, the use of corticosteroids and the patient outcomes were also evaluated. A favorable outcome was related to systolic blood pressure³ 100mmHg, heart rate lower than 100 beats per minute, creatinine below 1.6mg/dl, arterial blood pH³ 7.35, bicarbonate higher than 15mEq/dl, oxygen saturation higher than 84.1%, lower rehydration volume in the first 24 hours of hospitalization and no use of inotropic agents. Absence of clinical and laboratory signs of circulatory shock up on admission was associated with a favorable outcome of the patients.

Hepatitis C virus and human T-lymphotropic virus coinfection: epidemiological, clinical, laboratory and histopathological features

Twenty-four hepatitis C virus patients coinfected with human T-lymphotropic virus type 1 were compared with six coinfected with HTLV-2 and 55 with HCV alone, regarding clinical, epidemiological, laboratory and histopathological data. Fischer's discriminant analysis was applied to define functions capable of differentiating between the study groups (HCV, HCV/HTLV-1 and HCV/HTLV-2). The discriminant accuracy was evaluated by cross-validation. Alcohol consumption, use of intravenous drugs or inhaled cocaine and sexual partnership with intravenous drug users were more frequent in the HCV/HTLV-2 group, whereas patients in the HCV group more often reported abdominal pain or a sexual partner with hepatitis. Coinfected patients presented higher platelet counts, but aminotransferase and gamma-glutamyl transpeptidase levels were higher among HCV-infected subjects. No significant difference between the groups was seen regarding liver histopathological findings. Through discriminant analysis, classification functions were defined, including sex, age group, intravenous drug use and sexual partner with hepatitis. Cross-validation revealed high discriminant accuracy for the HCV group.

Intervenção educativa junto de um grupo de enfermeiros de um serviço de medicina : impacto na prática da terapêutica inalatória

RESUMO: O presente estudo, enquadra-se, no domínio do exercício profissional dos enfermeiros e na formação em serviço destes profissionais e teve por objectivo avaliar, num grupo de enfermeiros de um serviço de medicina, o impacto de uma intervenção educativa na melhoria dos procedimentos a executar na prática da terapêutica inalatória. A amostra do estudo (amostra por conveniência) foi constituída por oito enfermeiros do serviço de medicina do Hospital Curry Cabral (idades compreendidas entre os 24 a 43 anos de idade), sem anterior formação específica na área da terapêutica inalatória, mas com experiencia profissional prévia com doentes respiratórios. O estudo decorreu em dois momentos de avaliação: avaliação 0 (antes da intervenção educativa) e avaliação 1 (após a intervenção educativa). Entre estes dois momentos, foi ministrada, a todos os enfermeiros, uma acção de formação sobre terapêutica inalatória, com componente teórico-prática. Antes e depois da intervenção educativa foram aplicados dois instrumentos: para avaliação dos conhecimentos teóricos, construi-se e aplicou-se, um questionário de auto-avaliação de conhecimentos sobre terapêutica inalatória ao grupo dos enfermeiros, e para avaliação dos conhecimentos práticos e execução de procedimentos, uma grelha de observação da demonstração da técnica de inalação com três dispositivos inalatórios: MDI, MDI com câmara expansora ACE e DPI turbohaler®. Os resultados do estudo mostraram que o grupo dos enfermeiros da nossa amostra detinha já alguns conhecimentos de carácter teórico, de âmbito geral, sobre a terapêutica inalatória, mas conhecimentos pouco sólidos, nomeadamente no que concerne aos fármacos utilizados por via inalatória. Verificou-se, ainda, um deficiente domínio de conteúdos de carácter mais específico e prático sobre terapêutica inalatória, por exemplo a importância de determinados procedimentos - agitação do inalador, tempo de pausa entre cada inalação, cuidados de manutenção da câmara expansora, higienização da cavidade bucal após a inalação dos corticosteróides. Quanto à observação da técnica de inalação, o grupo dos enfermeiros revelou algumas lacunas, quer relativamente à técnica de inalação com MDI, quer do MDI com câmara expansora, observando-se a execução de passos incorrectos e mesmo omissão de passos por parte dos enfermeiros, antes da intervenção educativa.Não nos foi possível realizar a observação da técnica de inalação com dispositivo de pó seco turbohaler®, dado que nenhum dos enfermeiros da nossa amostra se sentiu capaz de manusear de forma correcta este dispositivo, antes e após a formação. Em termos globais, achamos que a formação dada sobre terapêutica inalatória, mostrou melhorar os conhecimentos teóricos e práticos dos enfermeiros neste âmbito. Esta melhoria ficou claramente demonstrada no aumento do número de respostas correctas dadas pelos enfermeiros no questionário efectuado, após a formação. Do mesmo modo, após a formação, registou-se uma melhoria considerável dos conhecimentos específicos e práticos, no que concerne à importância de determinados procedimentos na prática da terapêutica inalatória - agitação do inalador, tempo de pausa entre cada inalação, cuidados de manutenção da câmara expansora, higienização da cavidade bucal após a inalação dos corticosteróides - observando-se, um maior número de respostas correctas assinaladas no questionário. Em contrapartida, os conhecimentos sobre fármacos administrados por via inalatória, ficaram um pouco aquém das expectativas, pois o número de respostas correctas dadas pelos enfermeiros após a formação não foi significativo. Poderemos mesmo dizer que, a acção de formação com maior grau de especificidade sobre fármacos não se revelou eficaz e gerou até alguma ―confusão‖ neste grupo de enfermeiros, parecendo que os conhecimentos anteriores sobre fármacos por via inalatória não estariam consolidados antes da formação. De igual modo, após a formação, registou-se no grupo dos enfermeiros do estudo uma melhoria na performance da técnica de inalação com o MDI e MDI com a câmara expansora. Os enfermeiros do estudo, não só corrigiram os passos ou itens de avaliação da técnica inalatória, anteriormente executados incorrectamente, mas também, mostraram um melhor conhecimento dos passos ou itens de avaliação da técnica de inalação, com menor número de passos ou itens de avaliação omissos, após a formação. Em contrapartida, a acção de formação, no que diz respeito ao dispositivo de pó seco turbohaler®, não cumpriu o seu objectivo, dado que nenhum dos enfermeiros da amostra foi capaz de demonstrar a técnica de inalação com este dispositivo, antes e após a formação. Poderemos dizer que, não sendo um dispositivo da sua prática clínica, os enfermeiros não sentiram necessidade de adquirir estes conhecimentos. Em síntese, podemos concluir que na sua globalidade, a formação dada (com informação actualizada sobre as orientações mais adequadas neste domínio) e o treino formal dos enfermeiros neste âmbito, foi bastante proveitoso, uma vez que, mostrou melhorar os conhecimentos teóricos e práticos na prática da terapêutica inalatória do grupo de enfermeiros doserviço de medicina. Realça-se, no entanto, a importância de uma formação adequada, sentida como útil pelos enfermeiros, faseada, ligada à prática dos profissionais e alternando com momentos de exercício profissional. Os conhecimentos e os procedimentos dos enfermeiros deverão ainda ser monitorizados e avaliados ao longo do tempo, para a detecção de eventuais desvios que a rotina pode introduzir e para levantamento de novas necessidades de formação.-------------------ABSTRACT: This study fits in the domain of in-service training of professional nurses. It was aimed to assess the impact of an educational intervention and the consequent improvement of the practice of inhalation therapy in a group of nurses from a medical service The study sample (convenience sample) was consituted by eight nurses from the medical service, Hospital Curry Cabral (aged 24-43 years) without previous special training in the field of inhalation therapy, but with prior experience with patients with respiratory diseases. The study ran in two moments of evaluation: evaluation 0 (before the educational intervention) and evaluation 1 (post-intervention). Between these two moments, a training program about therapeutic inhalation was administered to all nurses, with a double component of theory and practice. Before and after the educational intervention two evaluation tools were applied: for the assessment of theoretical knowledge, the nurses had to fill a self-assessment questionnaire and in order to evaluate their knowledge related to procedural skills as well as their performance, they were observed (and their behaviour recorded on a check-list) during a demonstration of three inhalation techniques with devices: metered dose inhaler, metered dose inhaler with a spacer device ACE® and device turbohaler® The study results showed that the group of nurses in our sample had already some knowledge of theoretical nature (general scope of the inhalation therapy) but little solid knowledge, particularly in regard to drugs used in inhalation. In fact, a relatively weaker knowledge was registerd in what concerns specific and practical knowledge about inhalation therapy, for example, the importance of certain procedures - shaking the inhaler, pause between each inhalation, maintenance care of spacer device, mouth cavity hygiene after inhalation of corticosteroids. As for the observation of the inhaler technique, it was found that the group of nurses had a poor inhalation technique, in what concerns inhalation technique with MDI or MDI with spacer device, with a performance with several incorrect steps, or even omission of steps by nurses before the educational intervention. Finally, as the observation technique of the dry powder device turbohaler ®, we were unable to analyze the observation concerning this device, since none of the nurses in our sample, wast able to handlle it correctly, before and after training.In general terms, we found that the training given on inhalation therapy had a positive impact either in the theorical or the pratical knowledge on inhalation therapy (higher number of correct answers after training). Similarly, after training, there was the considerable improvement of specific and practical skills, namely the importance of certain procedures in the practice of inhalation therapy - shaking the inhaler, pause time between each inhalation, maintenance care of spacer device, sanitizing the buccal cavity after inhalation of corticosteroids. In contrast, knowledge about drugs administered by inhalation, were slightly below expectations, showing a lower number of correct answers given by the nurses after training. The training seemed to be a factor of "confusion" for this group of nurses, whose prior knowledge in this domais was not probably very solid to begin with. After training, the group of nurses in the study improved the performance of inhalation technique with MDI and MDI with spacer device. They not only correcty performed the steps or itens for the assessment of inhalation technique, previously performed incorrectly, but also showed a better understanding of the steps or itens for assessing the inhalation technique, with fewer steps missing (after training). In contrast, training with regard to the device turbohaler ® dry powder, was also below expectations, given that none of the nurses in the sample was able to demonstrate inhaler technique with this device before and after training. This was probably due to the fact that, the nurses did not feel the need to acquire this knowledge and the related practice. In summary, we can say that, overall, the training (with updated information on the appropriate policies in this field) showed an improvement in knowledge and performance in the practice of inhalation therapy. It is however crucial to underline the importance of in-service adequate training programmes, perceived as useful by the nurses, developped in different phases, linked to the nurses’ practice and combining with professional practices. The nurses’ knowledge and skills should also be further monitorized and evaluated in order to detect deviations introduced by the rotinization of procedures and to identify new training needs.

Clinical variables associated with leprosy reactions and persistence of physical impairment

Introduction Leprosy is a chronic disease that affects skin and peripheral nerves. Disease complications include reactional episodes and physical impairment. One World Health Organization (WHO) goal of leprosy programs is to decrease the number of grade 2 impairment diagnoses by 2015. This study aims to evaluate clinical factors associated with the occurrence of leprosy reactions and physical impairment in leprosy patients. Methods We conducted a retrospective study of data from medical records of patients followed in two important centers for the treatment of leprosy in Aracaju, Sergipe, Brazil, from 2005 to 2011. We used the chi-square test to analyze associations between the following categorical variables: gender, age, operational classification, clinical forms, leprosy reactions, corticosteroid treatment, and physical impairment at the diagnosis and after cure. Clinical variables associated with multibacillary leprosy and/or reactional episodes and the presence of any grade of physical impairment after cure were evaluated using the logistic regression model. Results We found that men were more affected by multibacillary forms, reactional episodes, and grade 2 physical impairment at diagnosis. Leprosy reactions were detected in a total of 40% of patients and all were treated with corticosteroids. However, physical impairment was observed in 29.8% of the patients analyzed at the end of the treatment and our multivariate analysis associated a low dose and short period of corticosteroid treatment with persistence of physical impairments. Conclusions Physical impairment should receive an increased attention before and after treatment, and adequate treatment should be emphasized.

Immune reconstitution inflammatory syndrome in HIV and sporotrichosis coinfection: report of two cases and review of the literature

We report 2 cases of patients with immune reconstitution inflammatory syndrome (IRIS) associated with cutaneous disseminated sporotrichosis and human immunodeficiency virus (HIV) coinfection. The patients received specific treatment for sporotrichosis. However, after 4 and 5 weeks from the beginning of antiretroviral therapy, both patients experienced clinical exacerbation of skin lesions despite increased T CD4+ cells (T cells cluster of differentiation 4 positive) count and decreased viral load. Despite this exacerbation, subsequent mycological examination after systemic corticosteroid administration did not reveal fungal growth. Accordingly, they were diagnosed with IRIS. However, the sudden withdrawal of the corticosteroids resulted in the recurrence of IRIS symptoms. No serious adverse effects could be attributed to prednisone. We recommend corticosteroid treatment for mild-to-moderate cases of IRIS in sporotrichosis and HIV coinfection with close follow-up.

Surgical treatment of type I neuritis in a teenage boy with borderline tuberculoid leprosy

Exacerbation of the immune response against Mycobacterium leprae can lead to neuritis, which is commonly treated via immunosuppression with corticosteroids. Early neurolysis may be performed concurrently, especially in young patients with a risk of functional sequelae. We report the case of a young patient experienced intense pain in the left elbow one year after the treatment of tuberculoid-tuberculoid leprosy. The pain was associated with paresthesias in the ulnar edge and left ulnar claw. After evaluation, the diagnosis was changed to borderline tuberculoid leprosy accompanied with neuritis of the left ulnar nerve. Early neurolysis resulted in rapid reduction of the pain and recovery of motor function.

Laparoscopic treatment of retroperitoneal fibrosis: report of two cases and review of the literature

OBJECTIVES: We present the results of treatment by laparoscopy of two patients with retroperitoneal fibrosis and review the literature since 1992, when the first case of this disease that was treated using laparoscopy was published. We also discuss the contemporary alternatives of clinical treatment with corticosteroids and tamoxifen. CASE REPORT: Two female patients, one with idiopathic retroperitoneal fibrosis, and other with retroperitoneal fibrosis associated with Riedel's thyroiditis, were treated using laparoscopic surgery. Both cases had bilateral pelvic ureteral obstruction and were treated using the same technique: transperitoneal laparoscopy, medial mobilization of both colons, liberation of both ureters from the fibrosis, and intraperitonealisation of the ureters. Double-J catheters were inserted before the operations and removed 3 weeks after the procedures. The first patient underwent intraperitonealisation of both ureters in a single procedure. The other had 2 different surgical procedures because of technical difficulties during the first operation. Both patients were followed for more than 1 year and recovered completely from the renal insufficiency. One of them still has occasional vague lumbar pain. There were no abnormalities in the intravenous pyelography in either case. CONCLUSIONS: Surgical correction of retroperitoneal fibrosis, when indicated, should be attempted using laparoscopy. If possible, bilateral ureterolysis and intraperitonealisation of both ureters should be performed in the same operation.

Correlation between osteochondral changes depicted by magnetic resonance imaging and disease progression

PURPOSE: To determine the consequences of the chronic use of systemic corticosteroids in children with juvenile rheumatoid arthritis by means of evaluating osteochondral effects depicted by magnetic resonance imaging. PATIENTS AND METHODS: We reviewed clinical and magnetic resonance imaging findings in 69 children (72 knees) with juvenile rheumatoid arthritis. Two groups were studied. Group I: 34 (49.3%) children had previous or current use of systemic corticotherapy (22 girls; 12 boys; mean age: 11.3 years; mean disease duration: 5.9 years; mean corticotherapy duration: 2.9 years; mean cumulative dose of previous corticosteroids: 5000 mg); Group II: 35 (50.7%) children had no previous use of corticosteroids (27 girls; 8 boys; mean age: 11.7 years; mean disease duration: 5.3 years). The groups were compared statistically. RESULTS: In the group that had received corticotherapy (Group I), osteochondral abnormalities were significantly correlated to long-standing disease (>3.5 years; p<0.001). This correlation was not found in the group that had no previous history of corticotherapy (Group II). No correlations were established between median dose of corticosteroids and magnetic resonance imaging findings. CONCLUSION: It is important to further investigate the long-term intra-articular effects of systemic corticotherapy to ensure that the side effects of the aggressive therapy will not be more harmful for the joints than the symptoms suffered over the natural course of the disease.

Complications of tracheobronchial foreign body aspiration in children: report of 5 cases and review of the literature

Foreign body aspiration (FBA) is one of leading causes of death in children, especially among those younger than 3 years of age. The inhalation of a foreign body may cause a wide variety of symptoms, and early diagnosis is highly associated with the successful removal of the inhaled foreign material. Despite the great advances in endoscopic procedures and anesthesia, a large number of difficulties and complications still result from foreign body aspiration. We describe 5 cases of serious acute complications following aspiration of foreign bodies that became lodged in the tracheobronchial tree, including pneumomediastinum, pneumothorax, total atelectasis, foreign body dislodgment, and need for thoracotomy in children admitted into our intensive care unit in 1999 and 2000; these were all situations that could have been prevented with early recognition and prompt therapeutic intervention.

Princípios de terapêutica antibiótica na doença crítica

RESUMO: A infeção é frequente durante a doença crítica, quer como causa da doença crítica quer como complicação da sua evolução. Paradoxalmente, os avanços da medicina moderna aumentaram eles próprios o risco de infeção, ao permitir a sobrevida até idades avançadas, ao criar um novo grupo de doentes imunodeprimidos, nomeadamente doentes tratados com fármacos que interferem com as suas defesas naturais (corticóides, citostáticos), ao aumentar o tempo de vida de hospedeiros com comorbilidades debilitantes. Os antibióticos são um dos elos essenciais no tratamento da infeção. Contudo o seu uso também promove a seleção e crescimento de bactérias resistentes. Para além disso as doses convencionais de antibióticos foram selecionadas numa altura em que a resistência era um fenómeno raro e podem não ser atualmente as mais adequadas. Existe hoje muita evidência acumulada que os doentes críticos sofrem alterações da sua farmacocinética (PK) que podem facilitar a ocorrência de falência terapêutica ou de toxicidade tanto por sub como por sobredosagem de antibióticos. Essas alterações são complexas e difíceis de estudar. Finalmente, também a farmacodinâmica (PD) dos antibióticos pode estar alterada nesta população, podendo haver necessidade de ajustar os alvos terapêuticos de forma individual. O objetivo deste trabalho foi investigar a relação entre a terapêutica antibiótica, as suas características PK e PD, a carga bacteriana e o prognóstico dos doentes críticos. O plano de investigação incluiu: 1. Dados da epidemiologia portuguesa de doentes críticos com infeção; 2. Avaliação da relação entre a carga bacteriana, o tempo até ao início do tratamento antibiótico e o prognóstico dos doentes críticos; 3. Avaliação da evolução da PK durante o tratamento da infeção; 4. Um estudo multicêntrico para avaliação da eficácia da terapêutica com um β- lactâmico doseado de acordo com a relação PK/PD. Na introdução é descrita a importância dos antibióticos, a sua origem e o problema crescente das resistências bacterianas relacionadas com o seu emprego e abuso. É salientada a importância de racionalizar a posologia, de acordo com os conceitos de PK e de PD. No Capítulo 1 são apresentados dados de epidemiologia portuguesa de infeção em doentes críticos, sobretudo retirados de dois estudos prospetivos, observacionais, os quais incluíram mais de 50% da capacidade de internamento em cuidados intensivos existente em Portugal. No Capítulo 2 são descritos os conceitos de PK e as suas alterações nos doentes críticos. De seguida são revistos os conceitos de PD de antibióticos e a sua aplicação a esta população, em particular durante as infeções graves (Capítulo 3). Nos capítulos seguintes são aprofundadas estas alterações da PK nos doentes críticos e as suas causas, de forma a destacar a importância da monitorização da concentração dos antibióticos. São apresentados os dados duma revisão sistemática de PK de antibóticos nesta população (Capítulo 4), pormenorizadas as alterações da PD que comprometem a eficácia da terapêutica antibiótica, facilitam o desenvolvimento de resistências e podem levar a falência terapêutica (Capítulo 5). Consequentemente a compreensão global destas alterações, da sua relevância clínica e a revisão da evidência disponível facilitou o desenvolvimento do próprio plano global de investigação (Capítulos 6 e 7). No Capítulo 6.1 são descritos os antibióticos tempo-dependente e a importância de aumentar o seu tempo de perfusão. Foi desenhado um estudo multicêntrico para comparar a eficácia e segurança da perfusão contínua da piperacilina tazobactam (um antibiótico β-lactâmico associado a um inibidor de β-lactamases) com a mesma dose do antibiótico, administrado em dose convencional, intermitente. A importância de dosear corretamente os antibióticos concentração-dependente foi também avaliada num estudo a primeira dose dos aminoglicosídeos (Capítulo 6.2). Outras estratégias para melhorar os resultados assistenciais dos doentes infetados são abordadas no Capítulo 7, em particular a importância da terapêutica antibiótica precoce, a avaliação da carga bacteriana e a compreensão da variação da PK ao longo do tratamento da infeção. Foi desenvolvido um algoritmo de abordagem terapêutica que incluiu estas alterações da PK e da PD nos doentes críticos. Finalmente no Capítulo 8 são descritos mecanismos de desenvolvimento das resistências bacterianas bem como estratégias para a sua abordagem. O Capítulo final (Capítulo 9) aponta um plano para futuras áreas de trabalho. O elemento chave identificado neste trabalho de investigação é o reconhecimento da variabilidade significativa da PK dos antibióticos durante a doença crítica, a qual condiciona a sua posologia. Estas alterações estão relacionadas com a própria gravidade da doença e tendem a diminuir ao longo do seu tratamento. No entanto nem a gravidade da doença nem as características individuais as permitem prever de forma aceitável pelo que a utilização duma posologia universal, independente da situação clínica concreta, pode ser inadequada. As estratégias para melhorar os resultados assistenciais dos doentes críticos infetados devem ser baseadas na individualização da posologia antibiótica de acordo com os princípios da PK e da PD, preferencialmente apoiadas em doseamentos da sua concentração. ------------------------------------ ABSTRACT: Infection commonly occurred during critical illness, either as a cause or complicating the course of the disease. Advances in medicine had paradoxically increase the risk of infection, both by improving survival to older ages and by introducing a new group of immunosuppressed patients, those who are treated with drugs that interfere with their natural defenses (corticosteroids, cytostatics) and those who survived longer with aggressive diseases. Antibiotics are of paramount importance for treating infection. However the use of these drugs also promote the selection and growth of resistant bacteria. Furthermore conventional antibiotic doses were calculated for less severe patients during a time when resistance was rare. Nowadays there is increasing evidence that critically ill patients experiment altered pharmacokinetics (PK) that may lead to therapeutic failure and/or drug toxicity. Equally, such PK alterations are complex and challenging to investigate. Finally pharmacodynamics (PD) may also be different in this population and antibiotic targets may need to be tailored to the individual patient. The aim of this research was to investigate the relationship between antibiotic therapy, its PK and PD, bacterial burden and critically ill patients outcomes. The research plan comprised of: 1. Epidemiological portuguese data of critically ill infected patients; 2. Relationship between burden of bacteria, time until the start of antibiotics and patient outcomes; 3. Evaluation of PK during treatment of infection; 4. A multicentre study evaluating PK guided β-lactam therapy. The introductory chapter outlines the importance of antibiotics, its origins, the problem of increasing bacteria resistance, related to its use and overuse and the importance of rational drug dosing using PK and PD concepts. In Chapter 1 portuguese epidemiological data of infections in critically ill patients is presented, mostly coming from two prospective observational studies, encompassing more than 50% of critically ill beds available in Portugal. Chapter 2 describes the concepts of PK and the changes occurring in critically ill patients. This is followed by a review of the concepts of PD of antibiotics and its application to this population, especially during severe infections (Chapter 3). In the following chapter these changes in antibiotics PK in critical illness are and its causes are detailed, to outline the importance of therapeutic drug monitoring. Data on a systematic review of antibiotics PK in those patients is provided (Chapter 4). The following chapter (Chapter 5) elucidates important changes in PD, that compromises antibiotic therapy, facilitate the occurrence of resistance and may lead to therapeutic failure. Thus, an understanding of the clinical problem and available evidence facilitated the development of a comprehensive research plan (Chapter 6 and Chapter 7). Chapter 6.1 describes time-dependent antibiotics and the importance of extending its perfusion time. A multicenter study was designed to compare the continuous infusion of piperacillin tazobactam (a β-lactam antibiotic) with the same daily dose, prescribed in a conventional, intermittent dose. The importance of correct dosing of antibiotics was also assessed through a study addressing aminoglycoside (a concentration-dependent antibiotic) therapy (Chapter 6.2), focusing on its first dose. Strategies to improve severe infected patients outcomes were addressed in Chapter 7, namely the importance of early antibiotic therapy, assessing the burden of bacteria and understanding changes in antibiotic concentration during the course of infection. An algorithm to include all the described changes in both PK and PD of critically ill patients was developed. Finally in Chapter 8 mechanisms of the increasing resistance of bacteria are described and strategies to address that problem are proposed. The closing chapter (Chapter 9) lays a roadmap for future work. The key finding of this research is the significant variability of the antibiotics PK during critical illness, which makes dosing a challenging issue. These changes are related to the severity of the infection itself and improve through the course of the disease. However neither disease severity nor individual characteristics are useful to predict PK changes. Therefore, the use of a universal dose approach, regardless of the individual patient, may not be the best approach. Strategies to improve patients’ outcomes should be based on tailoring antibiotics to the individual patient, according to PK and PD principles, preferentially supported by therapeutic drug monitoring.

Cardiac tamponade in systemic lupus erythematosus. Report of four cases

OBJECTIVE: To report and assess the incidence of cardiac tamponade in systemic lupus erythematosus as a cardiac manifestation of the disease. METHODS: We reviewed the medical records of 325 patients diagnosed with systemic lupus erythematosus according to the American Rheumatism Association and their complementary laboratory tests compatible with cardiac tamponade. RESULTS: In the 325 medical recors reviewed, we found 108 patients with pericardial effusions corresponding to 33.2% of the total and 54% of the patients studied in the active phase of the disease. Clinical assessment and transthoracic echocardiogram allowed the clinical diagnosis of cardiac tamponade in only 4 (1.23%) patients, 3 of whom were females, white, with ages ranging from 25 to 44 years. The pericardial fluid was hemorrhagic or serosanguineous with high levels of FAN and positivity for LE cells. In the treatment, we successfully used pericardicentesis associated with high doses of corticosteroids. In clinical and laboratory follow-up performed for a period of 3 years, neither recrudescence of the pericardial effusion nor evolution to constriction occurred. CONCLUSION: Even though rare (1.23%), cardiac tamponade in patients with systemic lupus erythematosus has a benign evolution when properly treated, according to our experience.

Hypertension in Patients with Cancer

There is a known association between chemotherapy and radiotherapy for treatment of cancer patients and development or worsening of hypertension. The aim of this article is to review this association. A literature search was conducted for articles reporting this association on the databases PubMed, SciELO and LILACS between 1993 and 2013. There was a high coprevalence of hypertension and cancer, since both diseases share the same risk factors, such as sedentary lifestyle, obesity, smoking, unhealthy diet and alcohol abuse. The use of chemotherapy and adjuvant drugs effective in the treatment of cancer increased the survival rate of these patients and, consequently, increased the incidence of hypertension. We described the association between the use of angiogenesis inhibitors (bevacizumab, sorafenib and sunitinib), corticosteroids, erythropoietin and non-steroidal anti-inflammatory drugs with the development of hypertension. We also described the relationship between hypertension and carotid baroreceptor injury secondary to cervical radiotherapy. Morbidity and mortality increased in patients with cancer and hypertension without proper antihypertensive treatment. We concluded that there is need for early diagnosis, effective monitoring and treatment strategies for hypertension in cancer patients in order to reduce cardiovascular morbidity and mortality.

Estimulació beta-adrenèrgica en la síndrome del destret respiratori agut (SDRA)

Estudi elaborat a partir d’una estada al Royal Brompton Hospital, Londres, Regne Unit, durant octubre i novembre del 2006.Els beneficis de la estimulació beta-adrenèrgica en pacients amb lesió pulmonar aguda (LPA) són coneguts, però no es disposa de dades sobre el possible efecte antiinflamatori. El condensat d'aire exhalat (CAE) és una tècnica no-invasiva de recollida de mostres del tracte respiratori inferior, podent ser útil en la monitorització de patologies respiratòries. S’ha usat marcadors biològics en el CAE de pacients ventilats mecànicament amb LPA per estudiar el possible efecte antiinflamatori que el salbutamol hi podria exercir. El CAE va ser recollit abans i després de l'administració de salbutamol inahalat. Inmediatament després es va mesurar la conductivitat i el pH abans i després de la desgasificació amb heli. Es va mesurar la concentració de nitrits i nitrats. Les mostres varen ser liofilitzades i guardades a -80ºC. La concentració de leucotriè B4 es va mesurar després de la reconstitució de la mostra. Els resultats s'expressen com a mitjana (error estàndard de la mostra). No s'han detectat diferències entre els valors de CAE basals dels pacients amb LPA i els de referència de la població sana de Barcelona. Es conclou doncs que el CAE és una tècnica no invasiva que pot ser usada en la monitorització de paceints ventilats mecànicament. El salbutamol inhalat incrementa de manera significativa el pH del CAE dels paceints amb LPA, tot i que un efecte directe de la inhalació de slabutamol no pot ser desestimat.

Influence of seasons and sampling strategy on assessment of bioaerosols in sewage treatment plants in Switzerland

An assessment of sewage workers' exposure to airborne cultivable bacteria, fungi and inhaled endotoxins was performed at 11 sewage treatment plants. We sampled the enclosed and unenclosed treatment areas in each plant and evaluated the influence of seasons (summer and winter) on bioaerosol levels. We also measured personal exposure to endotoxins of workers during special operation where a higher risk of bioaerosol inhalation was assumed. Results show that only fungi are present in significantly higher concentrations in summer than in winter (2331 +/- 858 versus 329 +/- 95 CFU m(-3)). We also found that there are significantly more bacteria in the enclosed area, near the particle grids for incoming water, than in the unenclosed area near the aeration basins (9455 +/- 2661 versus 2435 +/- 985 CFU m(-3) in summer and 11 081 +/- 2299 versus 2002 +/- 839 CFU m(-3) in winter). All bioaerosols were frequently above the recommended values of occupational exposure. Workers carrying out special tasks such as cleaning tanks were exposed to very high levels of endotoxins (up to 500 EU m(-3)) compared to routine work. The species composition and concentration of airborne Gram-negative bacteria were also studied. A broad spectrum of different species within the Pseudomonadaceae and the Enterobacteriaceae families were predominant in nearly all plants investigated. [Authors]