Contribution of plasma-derived molecules to mucosal immune defence, disease and repair in the airways

This review discusses recent observations, in health and disease, on the release and distribution of plasma-derived molecules in the airway mucosa. Briefly, the new data on airway mucosal exudation mechanisms suggest that the protein systems of plasma contribute significantly to the mucosal biology, not only in injured airways but also in such mildly inflamed airways that lack oedema and exhibit no sign of epithelial derangement. Plasma as a source of pluripotent growth factor, adhesive, leucocyte-activating, etc., molecules may deserve a prominent position in schemes that claim to illustrate immunological and inflammatory mechanisms of the airway mucosa in vivo.     

Effect of chronic theophylline treatment on the methacholine dose-response curve in allergic asthmatic subjects

Dyspnea can have a debilitating effect on psychosocial and physical functioning in patients with chronic obstructive airways disease. Previous research has suggested that treatment of concomitant mood or anxiety symptoms can improve dyspnea and exercise intolerance among patients with respiratory disease. The authors report here on a case series of 7 patients with obstructive airways disease who reported improvements in dyspnea after sertraline 25-100 mg/day was added to their medication regimens. Four of the seven patients did not appear to meet syndromal criteria for a mood or anxiety disorder. Subjective improvements in dyspnea may have been related to relief of mood or anxiety symptoms or to direct effects on central respiratory systems. Controlled studies are needed to clarify the potential antidyspneic effects of sertraline.     

Double talk: changing and conflicting constructions of indigenous mental health

Airway geometry measurements can provide information regarding pulmonary physiology and pathophysiology. There has been considerable interest in measuring intrathoracic airways in two-dimensional (2-D) slices from volumetric X-ray computed tomography (CT). Such measurements can be used to evaluate and track the progression of diseases affecting the airways. A popular airway measurement method uses the "half-max" criteria, in which the gray level at the airway wall is estimated to be halfway between the minimum and maximum gray levels along a ray crossing the edge. However, because the scanning process introduces blurring, the half-max approach may not be applicable across all airway sizes. We propose a new measurement method based on a model of the scanning process. In our approach, we examine the gray-level profile of a ray crossing the airway wall and use a maximum-likelihood method to estimate the airway inner and outer radius. Using CT scans of a physical phantom, we present results showing that the new approach is more accurate than the half-max method at estimating wall location for thin-walled airways.     

A novel T cell-regulated mechanism modulating allergen-induced airways hyperreactivity in BALB/c mice independently of IL-4 and IL-5

The immunoregulatory functions of IL-4 and IL-5 have identified these cytokines as primary targets for the resolution of airways inflammation and bronchial hyperreactivity in asthma. However, the individual contribution of each of these cytokines and of IL-5-regulated eosinophilia to the induction of airways hyperreactivity in mouse models of asthma remains highly controversial. In this investigation, we have used IL-4- and IL-5-deficient mice of the same genetic background in combination with inhibitory mAbs to these cytokines to identify unequivocally the contribution of these factors to the induction of airways hyperreactivity. Sensitization and aeroallergen challenge of wild-type mice with OVA induced pathological changes to the respiratory epithelium, airways eosinophilia, and hyperreactivity to beta-methacholine. Inhibition of the actions of IL-4 and/or IL-5 did not abolish airways hyperreactivity, and in the case of IL-4-deficient mice pretreated with anti-IL-5 mAb, airways hyperreactivity persisted in the absence of pronounced airways inflammation. Airways hyperreactivity was abolished only by anti-CD4+ mAb treatment. However, aeroallergen challenge of IL-5-/- mice showed that morphologic changes to the airways were critically linked to IL-5 and eosinophilia. This investigation demonstrates the existence in BALB/c mice of a novel CD4+ T cell pathway for modulating airways hyperreactivity. These findings may provide an explanation for the dissociation of airways eosinophilia from the development of airways hyperreactivity observed in some cases of asthma and in animal models of this disease.     

Behavioral therapy: its application to reduce disruptive behaviors of the elderly in nursing homes

Nurses who care for the elderly in nursing homes and auxiliary hospitals have many goals. They provide for the health, recreational, social and emotional needs of their patients. They also strive to increase their patients' levels of self-care and self-respect. Unfortunately, because many patients exhibit disruptive behaviors--striking staff or other patients, throwing temper tantrums, lying on the floor in corridors, refusing to take medication and so on, these desirable goals cannot always be met. What nurses need, in addition to their specialized, medically oriented training, is training in a consistent strategy for handling these problems. Behavioral therapy provides this strategy.     

On the use of scaling and clustering in the study of semantic deficits.

In the past decade, several studies have used scaling and clustering techniques to document semantic storage deficits in patients with Alzheimer's disease and in schizophrenia. In this article the authors argued that many of the conclusions drawn from these studies are unjustified by the data. They reviewed the methodology used in these studies and presented data from simulation studies to further investigate the validity of their conclusions. The authors elaborate on the criteria needed to exclude alternative accounts of the data and present empirical data from patients with Alzheimer's disease and normal control participants to demonstrate that analyses of the patients' proximity data do not provide unambiguous evidence for a generalized semantic storage deficit. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Preventing therapy dropout in the real world: The clinical utility of videotape preparation and client estimate of treatment duration.

Practicing clinicians realize that patients' dropping out of therapy is detrimental to treatment outcome and can prove costly to psychotherapists in terms of financial and personal consequences. Two procedures to prevent therapy dropout were tested in the "real-world," naturalistic environment of a health maintenance organization (HMO). Whereas video preparation significantly reduced dropout, opportunity to estimate treatment duration did not. Results were obtained from 125 randomly assigned adult outpatients. Findings suggest that psychologists in clinical and administrative positions may experience reduced dropout rates by providing new patients with videotaped instructional material about what they might expect in the psychotherapy process. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Psychology, serendipity, and public health: A reply to Suls and O'Leary.

Responds to comments by J. M. Suls and K. D. O'Leary (see PA, Vol 75:11530, and 11521, respectively) regarding their study on motivation for health behavior with adolescents. They agree with Suls' suggestion that a systems approach may eventually provide the necessary understanding of preventive health behavior and with O'Leary's comments on the effect of rewards, but they uphold their conclusions. It is noted that some societal changes in health behavior have occurred (i.e., less smoking, less sugar consumption) that are serendipitous to the findings of their study. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

What is proper cancer care in the era of managed care?

Managed care and proper cancer care need not be mutually exclusive entities. Managed-care organizations (MCOs) that are committed to patients and society should have the following characteristics: accountability for results, cost containment, measurement of outcomes, health promotion and disease prevention programs, resource consumption management, emphasis on primary care, and continuous quality improvement. Whether these commitments are upheld depends on when and with whom the MCO contracts to provide care and which medical and quality assurance protocols it follows. If proper cancer care is to become a reality in the managed-care era, the oncology community must take a proactive stance. Oncologists must provide the market with an appropriate, efficient disease management plan for cancer. In concert with MCOs, the oncology community must define and, through partnerships, promote the seamless integration of proper cancer care. Patients and advocates should insist that MCOs' quest for efficiency allows for flexibility to address individual patients' circumstances.     

Randomised controlled trial comparing hospital at home care with inpatient hospital care. II: cost minimisation analysis

OBJECTIVES: To examine the cost of providing hospital at home in place of some forms of inpatient hospital care. DESIGN: Cost minimisation study within a randomised controlled trial. SETTING: District general hospital and catchment area of neighbouring community trust. SUBJECTS: Patients recovering from hip replacement (n=86), knee replacement (n=86), and hysterectomy (n=238); elderly medical patients (n=96); and patients with chronic obstructive airways disease (n=32). INTERVENTIONS: Hospital at home or inpatient hospital care. MAIN OUTCOME MEASURES: Cost of hospital at home scheme to health service, to general practitioners, and to patients and their families compared with hospital care. RESULTS: No difference was detected in total healthcare costs between hospital at home and hospital care for patients recovering from a hip or knee replacement, or elderly medical patients. Hospital at home significantly increased healthcare costs for patients recovering from a hysterectomy (ratio of geometrical means 1.15, 95% confidence interval 1.04 to 1.29, P=0.009) and for those with chronic obstructive airways disease (Mann-Whitney U test, P=0.01). Hospital at home significantly increased general practitioners' costs for elderly medical patients (Mann-Whitney U test, P<0.01) and for those with chronic obstructive airways disease (P=0.02). Patient and carer expenditure made up a small proportion of total costs. CONCLUSION: Hospital at home care did not reduce total healthcare costs for the conditions studied in this trial, and costs were significantly increased for patients recovering from a hysterectomy and those with chronic obstructive airways disease. There was some evidence that costs were shifted to primary care for elderly medical patients and those with chronic obstructive airways disease.     

The validity of self-reports on chronic disease: characteristics of underreporters and implications for the planning of services

Data on the prevalence of chronic morbidity are valuable for identifying health care needs and for designing services to meet these needs. Morbidity data are frequently collected through surveys based upon self-reports of disease. However, there is evidence in the literature that people tend to underreport the presence of chronic disease. Our study identified factors related to the underreporting of chronic disease. We interviewed a proportional stratified sample of 521 sick-fund members from two typical urban primary care clinics in Israel. The respondents' self-reports were compared to the diagnoses recorded in medical sources of information. Our findings show that more than half of the respondents with chronic diseases failed to report at least one disease. By using multivariate analysis, we were able to untangle the interrelated effects of age and multiple disease. The findings indicate that "number of diseases"--a variable not taken into account in previous studies--had the greatest effect on underreporting. When controlling for number of diseases, age had an independent effect, although a much smaller one. We also found that the rate of underreporting varies by type of disease. We conclude that chronic morbidity estimates based upon self-reports may lead to the deficient planning of health care services. If possible, alternative sources should be used for collecting morbidity data, especially from patients with multiple diseases and from the elderly. Further research is needed in order to improve estimates of chronic morbidity.     

New strategies in the medical management of asthma

Asthma, a common chronic inflammatory disease of the airways, may be classified as mild intermittent or mild, moderate, or severe persistent. Patients with persistent asthma require medications that provide long-term control of their disease and medications that provide quick relief of symptoms. Medications for long-term control of asthma include inhaled corticosteroids, cromolyn, nedocromil, leukotriene modifiers and long-acting bronchodilators. Inhaled corticosteroids remain the most effective anti-inflammatory medications in the treatment of asthma. Quick-relief medications include short-acting beta2 agonists, anticholinergics and systemic corticosteroids. The frequent use of quick-relief medications indicates poor asthma control and the need for larger doses of medications that provide long-term control of asthma. New guidelines from the National Asthma Education and Prevention Program Expert Panel II recommend an aggressive "step-care" approach. In this approach, therapy is instituted at a step higher than the patient's current level of asthma severity, with a gradual "step down" in therapy once control is achieved.     

Cellular heterogeneity of CFTR expression and function in the lung: implications for gene therapy of cystic fibrosis

Cystic fibrosis (CF) has become a paradigm disorder for the clinical testing of gene therapies in the treatment of inherited disease. In recent years, efforts directed at gene therapy of CF have concentrated on improving gene delivery systems to the airway. Surrogate endpoints for complementation of CFTR dysfunction in the lung have been primarily dependent on correction of chloride transport abnormalities. However, it is now clear that the pathophysiology of CF airways disease is far more complex than can be solely attributed to altered chloride permeability. For example, in addition to functioning as a chloride channel, CFTR also has been implicated in the regulation of other apical membrane conductance pathways through interactions with the amiloride sensitive epithelial sodium channel (ENaC) and the outwardly rectifying chloride channel (ORCC). Superimposed on this functional diversity of CFTR is a highly regulated pattern of CFTR expression in the lung. This heterogeneity occurs at both the level of CFTR protein expression within different cell types in the airway and the anatomical location of these cells in the lung. Potential targets for gene therapy of CF include ciliated, non-ciliated, and goblet cells in the surface airway epithelium as well as submucosal glands within the interstitium of the airways. Each of these distinct cellular compartments may have functionally distinct roles in processes which affect the pathogenesis of CF airways disease, such as fluid and electrolyte balance. However, it is presently unclear which of these cellular targets are most pathophysiologic relevant with regard to gene therapy. Elucidation of the underlying mechanisms of CFTR function in the airway will allow for the rational design of gene therapy approaches for CF lung diseases. This review will provide a summary of the field's current knowledge regarding CFTR functional diversity in the airway and the implications of such diversity for gene therapies of CF lung disease.     

Physical assessment of the musculoskeletal system

Recently, some investigators have observed elevated concentrations of chloride in the airway surface fluid (ASF) overlying respiratory epithelia from cystic fibrosis (CF) patients compared with ASF overlying non-CF epithelia. Others have shown that this elevated ASF salt concentration can inactivate human beta-defensin-1, an antimicrobial peptide secreted by respiratory epithelia. This could impair the primary epithelial defense against bacteria in the CF airway, thereby forcing a greater reliance on polymorphonuclear leukocyte (PMN)-mediated defenses. Pseudomonas aeruginosa (Psa) flourishes in the CF airway despite the presence of abundant PMN. We therefore investigated whether elevated ASF chloride concentration in CF might also compromise PMN function. We employed a cell-culture model in which halide concentrations and osmolarity were varied independently. We examined the effects of chloride concentration on three aspects of PMN function: recruitment of PMN to the airway (production of interleukin-8 [IL-8]), PMN antimicrobial activity (killing of Psa), and PMN clearance from the airways (apoptosis and lysis). We found that exposure to elevated chloride concentration increased PMN synthesis of IL-8, decreased PMN killing of Psa, and accelerated PMN apoptosis and lysis. In CF airways, elevated chloride therefore could contribute to the increased number of PMN recruited into the airways, the increased survival of Psa, and the increased quantity of toxic mediators released by PMN into the airways. These effects of elevated chloride on PMN function may provide another causal link between loss of cystic fibrosis transmembrane conductance regulator function and CF lung disease.     

Relationships between maternal risk of insulin resistance and the child''s muscle membrane fatty acid composition

Studies have shown that beta defensins are present in the human airways and may be relevant to the pathogenesis of cystic fibrosis lung disease. Here we report the identification of a novel mouse gene, Defb2, which shows sequence similarity to previously described mouse and human airway beta defensins. Defb2 does not appear to be expressed in the airways of untreated mice but it is upregulated in response to lipopolysaccharide. The induced expression of this gene by an inflammatory stimulus strongly suggests that this defensin contributes to host defence at the mucosal surface of the airways.     

Implicit/explicit memory dissociation in Alzheimer's disease: The consequence of inappropriate processing?

Dual-process theories of recognition posit that perceptual fluency contributes to both familiarity-based explicit recognition and perceptual priming. However, the priming-without-recognition dissociation, as observed through the intact mere exposure effect and impaired recognition in patients with Alzheimer's disease (AD), might indicate that familiarity and perceptual priming are functionally distinct. This study investigated whether the AD patients' processing strategies at testing may explain this priming-without-recognition dissociation. First, we replicated the priming-without-recognition effect in 16 patients who exhibited intact exposure effects despite null recognition. Second, we showed that, under identical conditions, inducing a holistic processing strategy during recognition testing increased AD patients' recognition--performance was similar for AD patients and healthy control participants. Furthermore, prompting analytic processing during both priming and recognition tasks decreased AD patients' performance in both tasks. These findings suggest that the extent to which AD patients use perceptual fluency in priming and recognition tasks is contingent on their processing approach. The choice of processing strategy may depend on how difficult patients perceive the task to be. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Psychosocial effects of level of information and severity of disease on head-and-neck cancer patients

This study examined the psychosocial effects of levels of information available to patients and compared them with those of disease severity. A questionnaire with multiple-choice and open-ended questions assessing quality of life in various domains (e.g., fears and worries, functioning in the family) and scales assessing anxiety, anger, and depression were administered to patients and their partners or closest relatives. The subjects were 55 head-and-neck cancer patients (40 men and 15 women) in disease stages I to IV, grades of tumors G1 to G3-4, with disease durations ranging from three months to 21 years. They were divided into three groups on the basis of the amounts of information they had about their disease and prognosis, and again on the basis of disease severity, based on stages and patients' evaluations. The numbers of psychosocial variables differentiating significantly between the groups deviated significantly from chance in both groupings. The results showed more effects for information than for disease severity. The highly informed were better adjusted in interpersonal relations and had more intimacy with family, but had more fears, anxiety, changes in their lives, worries about health, and concern with physical symptoms. The reports of partners were fewer and lent some support to those of patients. Disease severity affected mostly fears, anxiety, and worries about health.     

Rare disease surveillance

Rare diseases in children account for disproportionate morbidity and mortality and are particularly demanding of both families and health resources. Surveillance may provide data on their epidemiology, aetiology, management and outcome and on the support requirements of affected children. Existing methods for rare disease surveillance include mandatory and voluntary notification schemes, which may be active or passive, hospital discharge databases and death certification data. The recent establishment of the Australian Paediatric Surveillance Unit has facilitated active, prospective, national case ascertainment by voluntary notification of selected rare conditions. Information obtained should enable estimation of incidence rates, evaluation of prevention and management strategies, extend data collected by existing methods and help estimate future health needs.     

The analgesic effect of fentanyl, morphine, meperidine, and lidocaine in the peripheral veins: a comparative study

It has been reported that in patients with inflammatory bowel disease (IBD), the airways are involved, and a number of clinical manifestations have been described. The aim of this study was to investigate the function of the small airways in IBD. Thirty patients with IBD (mean age, 47 yr), 12 with Crohn's disease and 18 with ulcerative colitis, were studied and compared with a control group of 16 normal subjects. Maximal expiratory flow-volume curves were performed breathing room air and a mixture of 80% helium, 20% oxygen. The differences of flows at 50% of FVC (delta Vmax50) and the volume of equal flows (Visov) were calculated as indices of small airways function. In addition, spirometry, lung volumes, and diffusing capacity were measured. Visov was statistically significantly greater in patients with either CD or UC than in control subjects (x +/- SD) (24.99 +/- 1.35 and 25.95 +/- 1.5 versus 20.1 +/- 1.39), (p < 0.01 and p < 0.001, respectively). A reduction in TL(CO) was noticed in the active stage of the disease in both groups of patients (p < 0.05). This may indicate that lung parenchyma is also involved in active IBD. Our results suggest that the function of the small airways and diffusion capacity of the lungs are affected in patients with IBD.