Peripheral blood dendritic cell subtypes are significantly elevated in subjects with asthma.

BACKGROUND: Dendritic cells (DCs) are crucial for the processing of antigens, T lymphocyte priming and the development of asthma and allergy. Smokers with asthma display altered therapeutic behaviour and a reduction in endobronchial DC CD83 expression compared with non-smokers with asthma. No information is available on the impact of smoking on peripheral blood DC profiles. OBJECTIVE: Determine peripheral blood DC profiles in subjects with and without asthma with differing smoking histories. METHODS: Forty-three asthmatics (17 smokers, nine ex-smokers and 17 never-smokers) and 16 healthy volunteers (nine smokers and seven never-smokers) were recruited. Spirometry, exhaled nitric oxide and venesection was performed. DC elution was by flow cytometry via the expression of DC surface markers [plasmacytoid (pDC) (BDCA-2, CD303), type 1 conventional (cDC) (BDCA-1, CD1c), and type 2 cDC (BDCA-3, CD141)]. RESULTS: Subjects with asthma displayed increases in all DC subtypes compared with normal never-smokers: [type 1 cDCs - asthma [median% (IQR)]: 0.59% (0.41, 0.74), normal never-smokers: 0.35% (0.26, 0.43), P=0.013]; type 2 cDCs - asthma: 0.04% (0.02, 0.06), normal never-smokers: 0.02% (0.01, 0.03), P=0.008 and pDCs - asthma: 0.32% (0.27, 0.46), normal never-smokers: 0.22% (0.17, 0.31), P=0.043, and increased pDC and type 1 cDCs compared with normal smokers. Smoking did not affect DC proportions in asthma. Cigarette smoking reduced pDC proportions in normal subjects [normal never-smokers: 0.22% (0.17, 0.31); normal smokers: 0.09% (0.08, 0.15), P=0.003]. CONCLUSIONS AND CLINICAL RELEVANCE: This study shows for the first time that subjects with asthma display a large increase in peripheral blood DC proportions. Cigarette smoking in asthma did not affect the peripheral blood DC profile but did suppress pDC proportions in non-asthmatic subjects. Asthma is associated with a significant increase in circulating DCs, reflecting increased endobronchial levels and the importance of DCs to the development and maintenance of asthma. (Clinical trials.gov identifier: NCT00411320)

Bronchodilatory effect of the PPAR-gamma agonist rosiglitazone in smokers with asthma.

Smokers with asthma show a reduced response to inhaled corticosteroids. We hypothesized that a peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonist would be superior for the clinical treatment of these asthma patients. Forty-six smokers with asthma were randomized to inhaled beclometasone dipropionate (200 microg per day) or rosiglitazone (8 mg per day) for 4 weeks. Rosiglitazone produced improvements in lung function (forced expiratory volume in 1 s (FEV(1)) = 183 ml, P = 0.051; forced expiratory flow between 25 and 75% of the forced vital capacity (FEF(25-75)) = 0.24 l/s, P = 0.030) as compared with inhaled beclometasone dipropionate. Further trials using PPAR-gamma agonists in steroid-resistant airway disease are indicated.

Effect of low-dose theophylline plus beclometasone on lung function in smokers with asthma: a pilot study.

Smoking is common in asthma and is associated with worse asthma control and a reduced therapeutic response to corticosteroids. The present authors hypothesised that treating smokers with asthma with low-dose theophylline added to inhaled corticosteroids would enhance steroid sensitivity and thereby improve lung function and symptoms. In a double-blind, parallel group exploratory trial, 68 asthmatic smokers were randomised to one of three treatments for 4 weeks: inhaled beclometasone (200 microg day(-1)), theophylline (400 mg day(-1)) or both treatments combined. Outcome measures included change in lung function and Asthma Control Questionnaire (ACQ) scores. At 4 weeks, theophylline added to inhaled beclometasone produced an improvement in peak expiratory flow (39.9 L min(-1), 95% confidence intervals (CI) 10.9-68.8) and ACQ score (-0.47, 95% CI -0.91- -0.04) and a borderline improvement in pre-bronchodilator forced expiratory volume in one second (mean difference 165 mL, 95% CI -13-342) relative to inhaled corticosteroid alone. Theophylline alone improved the ACQ score (-0.55, 95% CI -0.99- -0.11), but not lung function. In the present pilot study, the combination of low-dose theophylline and inhaled beclometasone produced improvements in both lung function and symptoms in a group of smokers with asthma. Larger trials are required to extend and confirm these findings.

Hepatic metastases from an unknown primary neoplasm (UPN): survival, prognostic indicators and value of extensive investigations.

AIM: The objectives of this study were to identify prognostic features for patients with hepatic metastases and unknown primary neoplasms (UPN), determine the common primary tumours, assess the value of diagnostic tests in finding these tumours, and evaluate the impact of therapy and knowledge of the primary tumour on patient survival. MATERIALS AND METHODS: Eighty-eight patients with UPN and liver biopsy proven hepatic metastases over a 10-year period were reviewed (M:F, 58:30; age range 27-91 years, median 64.5 years). Histopathology, diagnostic investigations and success at identifying the primary neoplasm were recorded. In addition, in 70 patients with adenocarcinoma histology (M:F, 48:22; age range 27-91 years, median 65 years), treatment and survival data from the date of biopsy were recorded. RESULTS: The histological spectrum included adenocarcinoma in 70, neuroendocrine in four, squamous cell carcinoma in four, small cell carcinoma in four, carcinoid in two, hepatoma in one and three others. Extensive investigation identified a primary neoplasm in 16/88 patients (18%) including colorectal in six, gastric in two, lung in four, oesophageal in two, prostate in one and carcinoid in one. In the adenocarcinoma group survival data were available for 62/70 patients. Sixteen of 62 patients received active treatment with either surgery, chemotherapy, radiotherapy or a combination protocol. Forty-six of 62 patients received palliative care alone. Median survival for the adenocarcinoma group overall was 49 days. The median survival for treated patients (49 days) versus untreated patients (52 days) was not significantly different (P=0.128). Patients <65 years were more likely to receive active treatment than those >65 years (P=0.006). Age with a hazard ratio (HR) of 1.01 (P=0.178), active treatment (HR=0.65;P=0.194), knowledge of the primary neoplasm (HR=0.60;P=0.213) and male gender (HR=0.88;P=0.642) had no significant effect on survival. CONCLUSION: Although hepatic metastases are associated with poor prognosis, it is essential that a liver biopsy be performed to obtain a histological diagnosis. Adenocarcinoma metastases carry a dismal prognosis, and no prognostic factors, including knowledge of the primary tumour, are significant for patient survival. Extensive investigation is not warranted in patients with adenocarcinoma liver metastases.

Cultural diversity and the case against ethical relativism.

The movement to respect cultural diversity, known as multiculturalism, poses a daunting challenge to healthcare ethics. Can we construct a defensible passage from the fact of cultural differences to any claims regarding morality? Or does multiculturalism lead to ethical relativism? Macklin argues that, in view of a leading distinction between universalism in ethics and moral absolutism, the only reasonable passage avoids both absolutism and relativism. She presents a strong case against ethical relativism and its pernicious consequences for cross-cultural issues in healthcare. She also provides sound criteria for the assessment of a culture's moral progress.

Relationality and consensus in Japan: implications for bioethics policy.

This paper examines the Japanese notion of relationality, that is, the idea that the individual is defined primarily within a web of relationships. Furthermore, it proposes that this relationality provides an ontological basis for morality, particularly the critical need for achieving consensus. This need for consensus is evident in the dispute over brain death. It was also conspicuous in the long-standing debate regarding heart transplantation. By reviewing key features of relationality, the study also demonstrates that the Japanese approach toward consensus reflects certain cultural values such as the importance of nemawashi. This inquiry thereby evokes the brain death and heart transplantation controversy in order to illustrate the critical need for consensus in the decision-making process.

On asking the right questions: personal death vs. brain death in Japan.

This article addresses methodological concerns encountered during the author's recent fellowship tenure at the University of Tokyo's School for International Health. His research addressed matters relating to Japanese views of personal death within the context of the relationship between self and body. He was also interested in learning more about the extent to which these same views influence issues in medical ethics, particularly the ongoing debate over brain death and heart transplantation, which, until June 1997, was legally prohibited. One critical component in methodology involved interviews and discussions with prominent scholars representing various disciplines. The key feature in these meetings centered around specific core questions. The author describes how these questions underwent significant modifications, and discusses how these methodological adjustments in effect reveal notions that are substantive and relevant to the research design pertaining to Japanese views of death, self, and embodiment.

Designing ethicists.

In the United States, disturbing concerns pertaining to both how putative bioethicists are perceived and the potential for the abuse of their power in connection with these perceptions compel close examination. This paper addresses these caveats by examining two fundamental and interrelated components in the image-construction of the ethicist: definitional and contextual. Definitional features reveal that perceptions and images of the ethicist are especially subject to distortion due to a lack of clarity as to the nature and qualifications of the ethicist. Furthermore, the clinical, professional, political, academic, and linguistic contexts in which these ethicists are engaged are contexts of disquieting degrees of power. I argue that the lack of definitional clarity as to what constitutes an ethicist combined with the above volatile contexts together set the stage for the abuse of power on the part of ethicists. Throughout, I question the extent of self-critical analyses among ethicists, and, in view of these components in image-construction and their relationship to power, I challenge the degree of integrity within the field. In conclusion, I propose some areas for further investigation.

Oregon's experiment.

Oregon's systematic design for universal access to health care, known as the Oregon Basic Health Services Act, has provoked heated debate over its rationale, plan and process. It is a novel attempt to address inequities in the distribution of health care for those below the federal poverty level. Its controversial nature compels more informed discussion to guide further analysis. Accordingly, this report is primarily descriptive, aiming to provide a clear synopsis of the Oregon project's history, complex methodology, and strengths and weaknesses.

A chronicle of organ transplant progress in Japan.

This study records the progress of organ transplantation in Japan by reviewing significant developments in five areas: actual transplant legislation; landmark cases notably affecting public impressions of organ transplants; efforts to establish brain death criteria; action on the part of the Japan Medical Association; and current attempts to legislate on brain death. The account demonstrates how the notions of both brain death and heart transplantation have met with strong resistance. The first and only heart transplant occurred in 1968. Through its historical emphasis, this report reveals that, although opposition has not impeded transplant research, the determination of death and the idea of heart transplants remain highly controversial due to specific religious, philosophical, and cultural factors.

Mathematical modelling and simulation of a tennis racket.

By constructing a mathematical model, we consider the dynamics of a tennis racket hit by a ball. Using this model, known experimental results can be simulated on the computer, and it becomes possible to make a parametric study of a racket. Such a simulation is essential in the study of two important problems related to tennis: computation of the resulting forces and moments transferred to the hand should assist understanding of the medical problem 'tennis elbow'; secondly, simulation will enable a study to be made of the relationships between the impact time, tension in the strings, forces transmitted to the rim and return velocity of the ball, all of which can lead to the optimal design of rackets.