Smoking cessation among patients at a university hospital in Curitiba, Brazil.

OBJECTIVE: To determine the prevalence of smoking and the frequency of smoking cessation counseling among patients at a university hospital, as well as to compare smokers and former smokers in terms of smoking history. METHODS: A cross-sectional study involving 629 patients at the Federal University of Paraná Hospital de Clínicas, located in the city of Curitiba, Brazil. RESULTS: Of the 629 patients, 206 (32.7%) were male, 76 (12.1%) were smokers, 179 (28.5%) were former smokers, and 374 (59.5%) were nonsmokers. The mean age of the patients was 49.9 ± 15.0 years (range, 18-84 years). Of the 76 smokers and 179 former smokers, 72 (94.7%) and 166 (92.7%), respectively, were questioned about tobacco use. Smoking history and degree of nicotine dependence were higher among the former smokers (p = 0.0292 and p = 0.0125, respectively). Gender, age at smoking initiation, physician inquiry about tobacco use, and smoking cessation counseling were comparable between the two groups. The smoking cessation rate was 0.70. The prevalence of heavy smoking varied by gender and by age bracket, being higher in males and in the 41-70 year age bracket. CONCLUSIONS: The smoking prevalence in this group of patients was lower than that reported for patients at another university hospital, for adults in Curitiba, and for adults in Brazil. The smoking cessation rate was higher in these patients than in the general population of Curitiba. Smokers and former smokers differed regarding age, smoking history, and degree of nicotine dependence. Heavy smoking and a moderate or high degree of nicotine dependence were not obstacles to smoking cessation.

Cessação de tabagismo em pacientes de um hospital universitário em Curitiba / Smoking cessation among patients at a university hospital in Curitiba, Brazil

OBJETIVO: Determinar a prevalência de tabagismo e do aconselhamento para a cessação do tabagismo em um grupo de pacientes de um hospital universitário, assim como comparar a carga tabágica entre fumantes e ex-fumantes. MÉTODOS: Estudo transversal com 629 pacientes do Hospital de Clínicas da Universidade Federal do Paraná, localizado em Curitiba. RESULTADOS: Dos 629 pacientes, 206 (32,7 por cento) eram do sexo masculino, 76 (12,1 por cento) eram fumantes, 179 (28,5 por cento) eram ex-fumantes, e 374 (59,5 por cento) eram não fumantes. A média de idade dos pacientes foi de 49,9 ± 15,0 anos (variação: 18-84 anos). Dos 76 fumantes e 179 ex-fumantes, 72 (94,7 por cento) e 166 (92,7 por cento), respectivamente, foram indagados sobre o hábito de fumar. A carga tabágica e o grau de dependência de nicotina foram maiores entre os ex-fumantes (p = 0,0292 e p = 0,0125, respectivamente). Gênero, idade ao início do tabagismo, questionamento médico sobre hábito de fumar e orientação para cessação do fumo foram semelhantes entre os dois grupos. O índice de cessação de tabagismo foi de 0,70. A prevalência de fumo pesado variou entre os gêneros e as faixas etárias - maior entre os homens e na faixa etária de 41-70 anos. CONCLUSÕES: A prevalência de tabagismo neste grupo de pacientes foi menor do que a observada em pacientes de outro hospital universitário e na população adulta de Curitiba e do Brasil. O índice de cessação do tabagismo foi maior do que o da população de Curitiba. Fumantes e ex-fumantes diferiram em relação à idade, à carga tabágica e ao grau de dependência. Fumo pesado e dependência média ou elevada não impediram cessação do tabagismo.

OBJECTIVE: To determine the prevalence of smoking and the frequency of smoking cessation counseling among patients at a university hospital, as well as to compare smokers and former smokers in terms of smoking history. METHODS: A cross-sectional study involving 629 patients at the Federal University of Paraná Hospital de Clínicas, located in the city of Curitiba, Brazil. RESULTS: Of the 629 patients, 206 (32.7 percent) were male, 76 (12.1 percent) were smokers, 179 (28.5 percent) were former smokers, and 374 (59.5 percent) were nonsmokers. The mean age of the patients was 49.9 ± 15.0 years (range, 18-84 years). Of the 76 smokers and 179 former smokers, 72 (94.7 percent) and 166 (92.7 percent), respectively, were questioned about tobacco use. Smoking history and degree of nicotine dependence were higher among the former smokers (p = 0.0292 and p = 0.0125, respectively). Gender, age at smoking initiation, physician inquiry about tobacco use, and smoking cessation counseling were comparable between the two groups. The smoking cessation rate was 0.70. The prevalence of heavy smoking varied by gender and by age bracket, being higher in males and in the 41-70 year age bracket. CONCLUSIONS: The smoking prevalence in this group of patients was lower than that reported for patients at another university hospital, for adults in Curitiba, and for adults in Brazil. The smoking cessation rate was higher in these patients than in the general population of Curitiba. Smokers and former smokers differed regarding age, smoking history, and degree of nicotine dependence. Heavy smoking and a moderate or high degree of nicotine dependence were not obstacles to smoking cessation.

Chapter 8: Fungal infections in immunocompromised patients.

Pulmonary complications are the most common cause of morbidity and mortality in immunocompromised patients, who lack of the basic mechanisms of cellular defense. Regardless of the cause of the immunodeficiency, the most common complications are infections (bacterial, viral or fungal). Among the fungal infections, aspergillosis is the most common (incidence, 1-9%; mortality, 55-92%) following organ transplant. Although pulmonary involvement is the most common form of aspergillosis, central nervous system involvement and sinusitis are not uncommon. On CT scans, the halo sign represents an area of low attenuation around the nodule, revealing edema or hemorrhage. The gold standard for the diagnosis is the culture identification of the fungus in sputum, BAL fluid or biopsy samples. Failing this identification, the detection of galactomannan, which is one of the fungal wall components, has shown sensitivity and specificity of 89% and 98%, respectively. Amphotericin B, liposomal amphotericin B, caspofungin and, especially, voriconazole are effective against the fungus. Although Pneumocystis jirovecii pneumonia can be fatal, the incidence of this disease has decreased due to the prophylactic use of trimethoprim-sulfamethoxazole. In immunocompromised patients presenting with dyspnea and hypoxemia, screening for fungi is indicated. A 14- to 21-day course of trimethoprim-sulfamethoxazole in combination with corticosteroids is usually efficacious. Another rare fungal infection is disseminated candidiasis, which is caused by Candida spp.

Capítulo 8 - Infecções fúngicas em imunocomprometidos / Chapter 8 - Fungal infections in immunocompromised patients

As complicações pulmonares se constituem na maior causa de morbidade e mortalidade no hospedeiro imunocomprometido, devido à deficiência nos mecanismos básicos de defesa. Independente da causa da imunodepressão, infecções bacterianas, virais e fúngicas são as mais frequentes. Entre as infecções fúngicas, a aspergilose é a mais comum (incidência de 1-9 por cento e mortalidade de 55-92 por cento) nos diferentes tipos de transplantados. Embora a forma pneumônica seja a mais frequente, lesões do sistema nervoso central e sinusite não são raras. O sinal do halo em TC de tórax representa uma área de baixa atenuação em volta do nódulo, revelando edema ou hemorragia. O padrão ouro para o diagnóstico é a identificação do fungo por cultura de escarro, amostras de LBA ou biópsia. Na falta dessa identificação, a detecção de galactomanana, um dos componentes da parede celular de Aspergillus sp., tem mostrado sensibilidade e especificidade de 89 por cento e 98 por cento, respectivamente. Anfotericina B, anfotericina B lipossomal, caspofungina e voriconazol têm efeito sobre o fungo, com destaque para esse último. A pneumonia por Pneumocystis jirovecii, que pode ser fatal, teve sua incidência reduzida pelo uso preventivo de sulfametoxazol/trimetoprima. Dispneia e hipoxemia em pacientes imunodeprimidos indicam a necessidade da pesquisa de fungos. O uso de sulfametoxazol/trimetoprima por 14-21 dias associado com corticosteroides costuma ser eficaz. A candidíase disseminada é outra rara enfermidade fúngica causada por Candida spp.

Pulmonary complications are the most common cause of morbidity and mortality in immunocompromised patients, who lack of the basic mechanisms of cellular defense. Regardless of the cause of the immunodeficiency, the most common complications are infections (bacterial, viral or fungal). Among the fungal infections, aspergillosis is the most common (incidence, 1-9 percent; mortality, 55-92 percent) following organ transplant. Although pulmonary involvement is the most common form of aspergillosis, central nervous system involvement and sinusitis are not uncommon. On CT scans, the halo sign represents an area of low attenuation around the nodule, revealing edema or hemorrhage. The gold standard for the diagnosis is the culture identification of the fungus in sputum, BAL fluid or biopsy samples. Failing this identification, the detection of galactomannan, which is one of the fungal wall components, has shown sensitivity and specificity of 89 percent and 98 percent, respectively. Amphotericin B, liposomal amphotericin B, caspofungin and, especially, voriconazole are effective against the fungus. Although Pneumocystis jirovecii pneumonia can be fatal, the incidence of this disease has decreased due to the prophylactic use of trimethoprim-sulfamethoxazole. In immunocompromised patients presenting with dyspnea and hypoxemia, screening for fungi is indicated. A 14- to 21-day course of trimethoprim-sulfamethoxazole in combination with corticosteroids is usually efficacious. Another rare fungal infection is disseminated candidiasis, which is caused by Candida spp.

Brazilian guidelines for community-acquired pneumonia in immunocompetent adults - 2009.

Community-acquired pneumonia continues to be the acute infectious disease that has the greatest medical and social impact regarding morbidity and treatment costs. Children and the elderly are more susceptible to severe complications, thereby justifying the fact that the prevention measures adopted have focused on these age brackets. Despite the advances in the knowledge of etiology and physiopathology, as well as the improvement in preliminary clinical and therapeutic methods, various questions merit further investigation. This is due to the clinical, social, demographical and structural diversity, which cannot be fully predicted. Consequently, guidelines are published in order to compile the most recent knowledge in a systematic way and to promote the rational use of that knowledge in medical practice. Therefore, guidelines are not a rigid set of rules that must be followed, but first and foremost a tool to be used in a critical way, bearing in mind the variability of biological and human responses within their individual and social contexts. This document represents the conclusion of a detailed discussion among the members of the Scientific Board and Respiratory Infection Committee of the Brazilian Thoracic Association. The objective of the work group was to present relevant topics in order to update the previous guidelines. We attempted to avoid the repetition of consensual concepts. The principal objective of creating this document was to present a compilation of the recent advances published in the literature and, consequently, to contribute to improving the quality of the medical care provided to immunocompetent adult patients with community-acquired pneumonia.

Diretrizes brasileiras para pneumonia adquirida na comunidade em adultos imunocompetentes - 2009 / Brazilian guidelines for community-acquired pneumonia in immunocompetent adults - 2009

A pneumonia adquirida na comunidade mantém-se como a doença infecciosa aguda de maior impacto médico-social quanto à morbidade e a custos relacionados ao tratamento. Os grupos etários mais suscetíveis de complicações graves situam-se entre os extremos de idade, fato que tem justificado a adoção de medidas de prevenção dirigidas a esses estratos populacionais. Apesar do avanço no conhecimento no campo da etiologia e da fisiopatologia, assim como no aperfeiçoamento dos métodos propedêuticos e terapêuticos, inúmeros pontos merecem ainda investigação adicional. Isto se deve à diversidade clínica, social, demográfica e estrutural, que são tópicos que não podem ser previstos em sua totalidade. Dessa forma, a publicação de diretrizes visa agrupar de maneira sistematizada o conhecimento atualizado e propor sua aplicação racional na prática médica. Não se trata, portanto, de uma regra rígida a ser seguida, mas, antes, de uma ferramenta para ser utilizada de forma crítica, tendo em vista a variabilidade da resposta biológica e do ser humano, no seu contexto individual e social. Esta diretriz constitui o resultado de uma discussão ampla entre os membros do Conselho Científico e da Comissão de Infecções Respiratórias da Sociedade Brasileira de Pneumologia e Tisiologia. O grupo de trabalho propôs-se a apresentar tópicos considerados relevantes, visando a uma atualização da diretriz anterior. Evitou-se, tanto quanto possível, uma repetição dos conceitos considerados consensuais. O objetivo principal do documento é a apresentação organizada dos avanços proporcionados pela literatura recente e, desta forma, contribuir para a melhora da assistência ao paciente adulto imunocompetente portador de pneumonia adquirida na comunidade.

Community-acquired pneumonia continues to be the acute infectious disease that has the greatest medical and social impact regarding morbidity and treatment costs. Children and the elderly are more susceptible to severe complications, thereby justifying the fact that the prevention measures adopted have focused on these age brackets. Despite the advances in the knowledge of etiology and physiopathology, as well as the improvement in preliminary clinical and therapeutic methods, various questions merit further investigation. This is due to the clinical, social, demographical and structural diversity, which cannot be fully predicted. Consequently, guidelines are published in order to compile the most recent knowledge in a systematic way and to promote the rational use of that knowledge in medical practice. Therefore, guidelines are not a rigid set of rules that must be followed, but first and foremost a tool to be used in a critical way, bearing in mind the variability of biological and human responses within their individual and social contexts. This document represents the conclusion of a detailed discussion among the members of the Scientific Board and Respiratory Infection Committee of the Brazilian Thoracic Association. The objective of the work group was to present relevant topics in order to update the previous guidelines. We attempted to avoid the repetition of consensual concepts. The principal objective of creating this document was to present a compilation of the recent advances published in the literature and, consequently, to contribute to improving the quality of the medical care provided to immunocompetent adult patients with community-acquired pneumonia.

Carcinomatous lymphangitis as the initial manifestation of ovarian adenocarcinoma.

Carcinomatous lymphangitis accounts for approximately 8% of all cases of metastatic pulmonary tumors. The most common primary sites are breast, lung, stomach, prostate and pancreas. We describe herein the case of a 42-year-old woman in whom the first manifestation of an ovarian adenocarcinoma was carcinomatous lymphangitis of the lung, an unusual presentation of the disease.

Linfangite carcinomatosa pulmonar como manifestação inicial de adenocarcinoma de ovário / Carcinomatous lymphangitis as the initial manifestation of ovarian adenocarcinoma

A linfangite carcinomatosa corresponde a cerca de 8 por cento das neoplasias pulmonares metastáticas. Os sítios primários mais comuns são mama, pulmão, estômago, próstata e pâncreas. Descrevemos o caso de uma paciente de 42 anos na qual a primeira manifestação de um adenocarcinoma de ovário foi a linfangite carcinomatosa, uma forma incomum de apresentação da doença.

Carcinomatous lymphangitis accounts for approximately 8 percent of all cases of metastatic pulmonary tumors. The most common primary sites are breast, lung, stomach, prostate and pancreas. We describe herein the case of a 42-year-old woman in whom the first manifestation of an ovarian adenocarcinoma was carcinomatous lymphangitis of the lung, an unusual presentation of the disease.

Comparison between azithromycin and amoxicillin in the treatment of infectious exacerbation of chronic obstructive pulmonary disease.

OBJECTIVE: To compare the efficacy, safety, and tolerability of azithromycin and amoxicillin in the treatment of patients with infectious exacerbation of chronic obstructive pulmonary disease. METHODS: This study was conducted at six medical centers across Brazil and included 109 patients from 33 to 82 years of age. Of those, 102 were randomized to receive either azithromycin (500 mg/day for three days, n = 49) or amoxicillin (500 mg every eight hours for ten days, n = 53). The patients were evaluated at the study outset, on day ten, and at one month. Based on the clinical evaluation of the signs and symptoms present on day ten and at one month, the outcomes were classified as cure, improvement, or treatment failure. The microbiological evaluation was made through the culture of sputum samples that were considered appropriate samples only after leukocyte counts and Gram staining. Secondary efficacy evaluations were made in order to analyze symptoms (cough, dyspnea, and expectoration) and pulmonary function. RESULTS: There were no differences between the groups treated with azithromycin or amoxicillin in terms of the percentages of cases in which the outcomes were classified as cure or improvement: 85% vs. 78% (p = 0.368) on day ten; and 83% vs. 78% (p = 0.571) at one month. Similarly, there were no significant differences between the two groups in the secondary efficacy variables or the incidence of adverse effects. CONCLUSION: Azithromycin and amoxicillin present similar efficacy and tolerability in the treatment of acute exacerbation of chronic obstructive pulmonary disease.

Comparação entre a azitromicina e a amoxicilina no tratamento da exacerbação infecciosa da doença pulmonar obstrutiva crônica / Comparison between azithromycin and amoxicillin in the treatment of infectious exacerbation of chronic obstructive pulmonary disease

OBJETIVO: Comparar a eficácia, segurança e tolerabilidade da azitromicina e da amoxicilina no tratamento de pacientes com quadro clínico de exacerbação infecciosa da doença pulmonar obstrutiva crônica. MÉTODOS: Seis centros brasileiros incluíram 109 pacientes com idades entre 33 e 82 anos. Desses pacientes, 102 foram randomizados para receber azitromicina (500 mg por dia por três dias, n = 49) ou amoxicilina (500 mg a cada oito horas por dez dias, n = 53). Os pacientes foram avaliados no início do estudo, após dez dias e depois de um mês. A avaliação clínica, de acordo com os sinais e sintomas presentes após dez dias e após um mês, consistiu na classificação dos casos nas categorias cura, melhora ou falha terapêutica. A avaliação microbiológica foi feita pela cultura de amostras de escarro consideradas adequadas após contagem de leucócitos e coloração de Gram. Avaliações secundárias de eficácia foram feitas com relação aos sintomas (tosse, dispnéia e expectoração) e à função pulmonar. RESULTADOS: Não houve diferenças entre as proporções de casos classificados como cura ou melhora entre os grupos tratados com a azitromicina ou a amoxicilina. Essas proporções foram, respectivamente, de 85 por cento vs. 78 por cento (p = 0,368) após dez dias, e de 83 por cento vs. 78 por cento (p = 0,571) após um mês. Também não foram encontradas diferenças significativas entre os dois grupos quando comparadas as variáveis secundárias de eficácia e a incidência de eventos adversos. CONCLUSÃO: A azitromicina tem eficácia e tolerabilidade semelhantes às da amoxicilina para o tratamento da exacerbação aguda da Doença pulmonar obstrutiva crônica.

OBJECTIVE: To compare the efficacy, safety, and tolerability of azithromycin and amoxicillin in the treatment of patients with infectious exacerbation of chronic obstructive pulmonary disease. METHODS: This study was conducted at six medical centers across Brazil and included 109 patients from 33 to 82 years of age. Of those, 102 were randomized to receive either azithromycin (500 mg/day for three days, n = 49) or amoxicillin (500 mg every eight hours for ten days, n = 53). The patients were evaluated at the study outset, on day ten, and at one month. Based on the clinical evaluation of the signs and symptoms present on day ten and at one month, the outcomes were classified as cure, improvement, or treatment failure. The microbiological evaluation was made through the culture of sputum samples that were considered appropriate samples only after leukocyte counts and Gram staining. Secondary efficacy evaluations were made in order to analyze symptoms (cough, dyspnea, and expectoration) and pulmonary function. RESULTS: There were no differences between the groups treated with azithromycin or amoxicillin in terms of the percentages of cases in which the outcomes were classified as cure or improvement: 85 percent vs. 78 percent (p = 0.368) on day ten; and 83 percent vs. 78 percent (p = 0.571) at one month. Similarly, there were no significant differences between the two groups in the secondary efficacy variables or the incidence of adverse effects. CONCLUSION: Azithromycin and amoxicillin present similar efficacy and tolerability in the treatment of acute exacerbation of chronic obstructive pulmonary disease.

Pulmonary alveolar microlithiasis presenting with crazy-paving pattern on high resolution CT.

Pulmonary alveolar microlithiasis (PAM) is an uncommon chronic disease characterized by calcifications within the alveoli and a paucity of symptoms in contrast to the imaging findings. We present a 59-year-old woman with a 4-year history of shortness of breath on exertion. Lung auscultation revealed random wheezes and fine and coarse crackles. Pulmonary function tests showed a restrictive pattern. The chest radiograph demonstrated a bilateral symmetric micronodular pattern. High resolution CT scan revealed diffuse ground-glass attenuation with superimposed septal thickening ("crazy-paving" pattern). The patient underwent a lung biopsy, which confirmed the diagnosis of PAM. Our case demonstrates that PAM needs to be considerate in the differential diagnosis of lung lesions that present with crazy-paving pattern on the high resolution CT.

Avaliação da eficácia clínica, aceitabilidade e preferência de dois sistemas inalatórios de beclometasona no tratamento da asma: Pulvinal® versus Aeroliser® / Acceptability, preference, tolerance and clinical efficacy of beclomethasone delivered by two inhalation devices in chronic asthma patients: Clenil pulvinal® versus Miflasona Aerolizer®

INTRODUÇÃO: Apenas metade dos pacientes asmáticos fazem o tratamento prescrito, o que torna a baixa adesão ao tratamento um dos principais problemas no manejo desta enfermidade. É possível que dispositivos inalatórios que combinem o melhoramento tecnológico com a simplicidade e o conforto em sua utilização possam minimizar a baixa adesão ao tratamento. OBJETIVO: Comparar a aceitabilidade e preferência de dois dispositivos inalatórios para a administração de beclometasona: Clenil Pulvinal(P) e Miflasona Aeroliser (A). Secundariamente, avaliar a eficácia e tolerabilidade desses dois sistemas inalatórios, no controle da asma crônica. MÉTODO: Foi realizado um estudo multicêntrico, aberto, comparativo, randomizado, cruzado, de grupos paralelos, em pacientes com asma estável. Foram incluídos 83 pacientes com asma clinicamente estável em uso de 500 a 1000 mg/dia de beclometasona. Após 2 semanas de observação, os pacientes iniciaram aleatoriamente, por 4 semanas, com doses equivalentes de P ou A, imediatamente seguido do outro tratamento em estudo por 4 semanas. RESULTADOS: Em ambos os grupos, P e A, a dispnéia de esforço e o VEF1 melhoraram. Não houve diferença quanto à eficácia clínica ou à freqüência de efeitos colaterais. A aceitabilidade foi considerada boa ou excelente nos dois grupos. O P foi preferido por 50,6 por cento dos pacientes e o A por 39 por cento. Caso o paciente necessitasse continuar a medicação, o P seria escolhido por 54,5 por cento e o A por 37,7 por cento. CONCLUSÃO: A eficácia clínica da beclometasona administrada pelos dois dispositivos inalatórios estudados (P e A) foi semelhante, tendo ambos também igual aceitabilidade.

Cytomegalovirus pneumonia after bone marrow transplantation: high resolution CT findings.

Cytomegalovirus (CMV) pneumonia is one of the most common pulmonary complications after bone marrow transplantation (BMT). We describe the high resolution CT (HRCT) findings of 13 patients with CMV pneumonia diagnosed after allogenic BMT. The study included 13 consecutive patients who developed CMV pneumonia after BMT and who had HRCT of the chest performed within 24 h of the onset of symptoms. HRCT scans were reviewed by two radiologists who assessed pattern and distribution of findings. There were nine male and four female patients, ranging from 9 years to 56 years of age (mean age 33 years). BMT was performed for treatment of chronic myelogenous leukaemia (54%), severe aplastic anaemia (23%), acute myelogenous leukaemia (15%) and Fanconi's anaemia (8%). The time elapsed until diagnosis ranged from +18 days to +405 days (median of 54 days, mean +81.6 days). The predominant patterns of abnormality on HRCT scans were ground-glass opacities (69%), small centrilobular nodules (69%) and air-space opacities (54%). The abnormalities were distributed in the central and peripheral zones of the lungs in six cases, only in the periphery in four cases, and only in the central zone in three cases. In all cases the lung lesions were bilateral, and asymmetry was observed in seven cases. The authors conclude that the most common HRCT findings in patients with CMV pneumonia after BMT consist of bilateral asymmetric ground-glass, air-space opacities and small centrilobular nodules.

High-resolution CT findings of respiratory syncytial virus pneumonia after bone marrow transplantation.

OBJECTIVE: The aim of this study was to describe the high-resolution CT findings of respiratory syncytial virus pneumonia in 20 patients who had undergone allogeneic bone marrow transplantation. MATERIALS AND METHODS: The study included 20 consecutive patients who developed respiratory syncytial virus pneumonia after bone marrow transplantation and who had high-resolution CT of the chest performed within 24 hr after the onset of symptoms. The CT scans were reviewed by two chest radiologists who assessed the pattern and distribution of findings. RESULTS: Bone marrow transplantation was performed on 12 male and eight female patients ranging from 3 to 48 years old (mean age, 25 years) for treatment of various forms of leukemia (n = 12), severe aplastic anemia (n = 6), Fanconi's syndrome (n = 1), and paroxysmal nocturnal hemoglobinuria (n = 1). Sixteen patients (80%) had abnormal CT findings. The predominant patterns of abnormality on high-resolution CT scans were small centrilobular nodules (10/20, 50%), air-space consolidation (7/20, 35%), ground-glass opacities (6/20, 30%), and bronchial wall thickening (6/20, 30%). The abnormalities were distributed in the central and peripheral areas of the lungs in nine cases, only in the periphery in five cases, and only in the central regions in two cases. The abnormalities were bilateral and asymmetric in distribution in 13 patients, bilateral and symmetric in two patients, and unilateral in one patient. CONCLUSION: The most common high-resolution CT findings in patients with respiratory syncytial virus pneumonia after bone marrow transplantation consist of small centrilobular nodules and multifocal areas of consolidation and ground-glass opacities in a bilateral asymmetric distribution.

Stepwise proteolytic removal of the beta subdomain in alpha-lactalbumin. The protein remains folded and can form the molten globule in acid solution.

Bovine alpha-lactalbumin (alpha-LA) is an alpha/beta protein which adopts partly folded states when dissolved at low pH (A-state), by removal of the protein-bound calcium at neutral pH and low salt concentration (apo-state), as well as in aqueous trifluoroethanol. Previous spectroscopic studies have indicated that the A-state of alpha-LA at pH 2.0, considered a prototype molten globule, has a native-like fold in which the helical core is mostly retained, while the beta subdomain is less structured. Here, we investigate the conformational features of three derivatives of alpha-LA characterized by a single peptide bond fission or a deletion of 12 or 19/22 amino-acid residues of the beta subdomain of the native protein (approximately from residue 34 to 57). These alpha-LA derivatives were obtained by limited proteolysis of the protein in its partly folded state(s). A nicked alpha-LA species consisting of fragments 1-,3-40 and 41-123 (nicked-LA) was prepared by thermolytic digestion of the 123-residue chain of alpha-LA in 50% (v/v) aqueous trifluoroethanol. Two truncated or gapped protein species given by fragments 1-40 and 53-123 (desbeta1-LA) or fragments 1-34 and 54-,57-123 (desbeta2-LA) were obtained by digestion of alpha-LA with pepsin in acid or with proteinase K at neutral pH in its apo-state, respectively. The two protein fragments of nicked or gapped alpha-LA are covalently linked by the four disulfide bridges of the native protein. CD measurements revealed that, in aqueous solution at neutral pH and in the presence of calcium, the three protein species maintain the helical secondary structure of intact alpha-LA, while the tertiary structure is strongly affected by the proteolytic cleavages of the chain. Temperature effects of CD signals in the far- and near-UV region reveal a much more labile tertiary structure in the alpha-LA derivatives, while the secondary structure is mostly retained even upon heating. In acid solution at pH 2.0, the three alpha-LA variants adopt a conformational state essentially identical to the molten globule displayed by intact alpha-LA, as demonstrated by CD measurements. Moreover, they bind strongly the fluorescent dye 8-anilinonaphthalene-1-sulfonate, which is considered a diagnostic feature of the molten globule of proteins. Therefore, the beta subdomain can be removed from the alpha-LA molecule without impairing the capability of the rest of the chain to adopt a molten globule state. The results of this protein dissection study provide direct experimental evidence that in the alpha-LA molten globule only the alpha domain is structured.

Trifluoroethanol-assisted protein folding: fragment 53--103 of bovine alpha-lactalbumin.

Fragment 53--103 of bovine alpha-lactalbumin, prepared by limited peptic digestion of the protein at low pH, is a 51-residue polypeptide chain crosslinked by two disulfide bonds encompassing helix C (residues 86--98) of the native protein. Refolding of the fully reduced fragment (four--SH groups) is expected to lead to three fully oxidized isomers, the native (61--77, 73--91) and the two misfolded species named ribbon (61--91, 73--77) and beads (61--73, 77--91) isomers. The fragment with correct disulfide bonds was formed in approx. 30% yield when refolding was conducted in aqueous solution at neutral pH in the presence of the redox system constituted by reduced and oxidized glutathione. On the other hand, when the reaction was conducted in 30% (v/v) trifluoroethanol (TFE), the oxidative refolding to the native isomer was almost quantitative. To provide an explanation of the beneficial effect of TFE in promoting the correct oxidative folding, the conformational features of the various fragment species were analyzed by far-UV circular dichroism measurements. The fully reduced fragment is largely unfolded in water, but it becomes helical in aqueous TFE. Correctly refolded fragment is produced most when the helical contents of the reduced and oxidized fragment in aqueous TFE are roughly equal. It is proposed that 30% TFE promotes a native-like format of the fragment and thus an efficient and correct pairing of disulfides. Higher concentrations of TFE, instead, promote some non-native helical secondary structure in the fragment species, thus hampering correct folding.