Influence Disease Course Research Articles

Early detection of chronic obstructive pulmonary disease (COPD): the role of spirometry as a diagnostic tool in primary care.

Chronic obstructive pulmonary disease (COPD) is common and often undiagnosed in its early stages, especially in smokers, who are also most at risk. Patients can develop severe or very severe disease before they consult a physician. It is therefore important to identify patients at-risk of COPD and check their lung function regularly since early stage disease is often asymptomatic or mistaken for asthma. Primary care physicians are often the first health care providers to encounter patients with COPD in the early stages, and their role in early detection and treatment process is pivotal. Spirometry is a cheap, simple and reliable method for the early detection and monitoring of COPD patients, and for establishing a differential diagnosis. Spirometry gives immediate results and communicating the results to smokers has been shown to motivate them to quit. Early diagnosis and appropriate therapy can positively influence disease course, slowing progression, relieving symptoms and reducing the incidence of acute 'flares', or exacerbations.

Identifying disease modifying genes in multiple sclerosis

Evidence is mounting that genetic variation influences not only susceptibility to multiple sclerosis (MS), but also its course and severity. Identification of disease modifying genes, however, poses unique challenges, especially on how to classify the course and outcome of the disease in ways that may be relevant to analysis of biological factors that might be influenced by genes. The power of the statistical approaches to detect small effects of individual genes in complex disorders such as MS is problematic, and approaches to estimate power must be appropriate for the data. Nonetheless, using contemporary schemes of classification, genetic variants that influence disease course have been found; in fact, a small number have been confirmed to influence disease course in two or more independent studies. This review addresses strategies relevant to identification of disease modifying genes in MS, and summarizes and critically evaluates the current state of knowledge in this area.

Natural history of Alzheimer's disease.

Alzheimer's disease (AD) is the principal cause of dementia in the elderly, and affects about 15 million people worldwide. The earliest symptom is usually an insidious impairment of memory. As the disease progresses, there is increasing impairment of language and other cognitive functions. Problems occur with naming and word-finding, and later with verbal and written comprehension and expression. Visuospatial, analytic and abstract reasoning abilities, judgment, and insight become affected. Behavioral changes may include delusions, hallucinations, irritability, agitation, verbal or physical aggression, wandering, and disinhibition. Ultimately, there is loss of self-hygiene, eating, dressing, and ambulatory abilities, and incontinence and motor dysfunction. Before diagnosis of AD, individuals may have memory complaints, which represent a period of mild cognitive impairment (MCI). Before MCI, there is a prodromal, ill-defined presymptomatic period of disease ('pre-MCI"). In this review, we particularly focus on these earliest stages. We also discuss the more advanced stages of AD, and address factors that may influence disease course. Understanding the natural history of AD will allow better targeting of the disease-modifying treatments that are on the horizon.

Polymorphisms of apolipoprotein E; outcome and susceptibility in multiple sclerosis.

Allelic variants of the apolipoprotein E (APOE) gene influence the course of several neurological diseases. In multiple sclerosis the concentration of APOE in cerebrospinal fluid and its intrathecal synthesis is reduced. Specific isoforms of APOE may also be important and it has been suggested that possession of the epsilon4 allele may be associated with a more aggressive disease process. These data prompted us to re-examine, in a large group of patients with multiple sclerosis, the proposal that allelism in the apolipoprotein gene influences disease course. Genotypes were determined in a well-defined group of 370 unrelated Caucasians with clinically definite multiple sclerosis and in 159 healthy controls. Age at onset, sex, disease duration, disease subtype were recorded. Disability was measured using the Kurtzke expanded disability status score in patients with a disease duration of 10 years or greater. There was no significant difference in APOE allele or genotype frequencies between patients and controls, between disease subtypes or between genders. APOE genotype did not significantly influence age of onset, and no significant relationship between genotype, allele frequency and disease severity was found. This study suggests that individual APOE alleles or genotypes do not determine disease susceptibility or the clinical course of multiple sclerosis.

Ingreso en el hospital por asma. Análisis descriptivo y factores pronósticos tras el alta

Few authors have looked at admissions in Spain of patients with acute asthma attacks. The aim of this study was to determine the clinical profile of such patients and analyze factors influencing disease course after release. Asthmatics admitted to our hospital were enrolled prospectively over 12 consecutive months. The patients were telephoned one and four months after release. Demographic and clinical data were collected in addition to data on exacerbations, readmissions, treatment and medical follow-up. Sixty-five patients (44 women and 21 men, mean age 45, SD 19). Most (54%) were admitted in autumn and the most common cause of exacerbation was respiratory tract infection (68%). Before admission, 54% had severe asthma, 32% had moderate asthma and 14% had mild asthma. At least one exacerbation occurred for 54% of patients, while 38% required emergency assistance and 19% were readmitted. Two patients (3%) died of asthma. Multiple factor logistic regression analysis showed a relation between the appearance of exacerbation after release and greater severity of asthma and the absence of long-lasting (beta-adrenergic drugs. Readmission was related to shorter duration of treatment with oral glucocorticoids after release and a higher number of prior hospital admissions. 1) Admission due to asthma occurs mainly in autumn and is probably related to respiratory infections, rather than exclusively to severe asthma. 2) After release, short-term morbidity and mortality due to the disease are high. 3) Disease severity itself and inadequate treatment are both related to poor clinical course after release.

Cancer and Depression

Half of all cancer patients have a psychiatric disorder, usually an adjustment disorder with depression. Anxiety about illness, such as cancer, often leads to delay in diagnosis, which has been estimated to reduce prospects of long-term cancer survival by 10% to 20%. Although earlier studies showed that depressed individuals were at higher risk for cancer incidence, later studies have not confirmed this predictive relationship. Nonetheless, effective psychotherapeutic treatment for depression has been found to affect the course of cancer. Psychotherapy for medically ill patients results in reduced anxiety and depression, and often pain reduction. In three randomised studies, psychotherapy resulted in longer survival time for patients with breast cancer (18 months), lymphoma, and malignant melanoma. The physiological mechanisms for these findings have not yet been determined, but four fundamental possibilities for psychotherapeutic effects on physiological change include health maintenance behaviour, health-care utilisation, endocrine environment, and immune function. Thus, effective treatment of depression in cancer patients results in better patient adjustment, reduced symptoms, reduced cost of care, and may influence disease course. The treatment of depression in these patients may be considered a part of medical as well as psychiatric treatment.

Abnormal class I assembly and peptide presentation in the nonobese diabetic mouse.

Presentation of self-antigens by major histocompatibility complex (MHC) class I molecules requires the function of the MHC class II-linked genes Tap-1 and Tap-2. Evidence suggests that interruption of self-peptide presentation results in reduced cell surface expression of MHC class I molecules and the interruption correlates with progression to diabetic autoimmunity in nonobese diabetic (NOD) mice and humans. NOD mice possess a rare Tap-1 allele (Tap-1b); this is associated with reduced Tap-1 mRNA abundance in lymphocytes from diabetes-prone females and decreased conformationally correct class I molecules on the cell surface. In this study, we demonstrate that, similar to lymphoma cell lines with mutations in Tap-1 or Tap-2, the reduced expression of class I molecules on the surface of lymphocytes from diabetes-prone female NOD mice was normalized by incubation at low temperatures or by exposure to class I allele-specific peptides. As would be expected for cells that express surface class I molecules not associated with peptide, female NOD lymphocytes were resistant to lysis by class I-restricted, peptide-specific cytotoxic T lymphocytes. Furthermore, the rate of class I exit from the endoplasmic reticulum of lymphocytes from female NOD mice was delayed as demonstrated by delayed glycosylation. Male NOD mice, which are not prone to diabetes, lacked these functional defects in class I assembly and had near-normal levels of Tap-1 mRNA and exhibited normal density of class I epitopes that were peptide filled. These results are consistent with the possibility that the rare Tap-1b allele is associated with a quantitative defect in Tap-1 expression that influences disease course.

Psychological interventions in the treatment of cancer

The status of psychological interventions with cancer patients is reviewed. Psychological treatment modalities are being developed and utilized with increasing frequency, although the nature of any relationship between psychological factors and malignant disease remains unclear. Eight variables are identified as being implicated in cases where improvement in disease status has been associated with psychological interventions. Research reports bearing on each of these areas are surveyed, and it is suggested that the variables provide a basis for formulating testable propositions. Clinical research programs could measure changes in medical status following interventions which: 1) alter stress conditions and their management, 2) work through unresolved grief, 3) stimulate will to live, 4) promote realistic positive expectations, 5) mobilize mental capacities for psychophysiological control, 6) constructively handle denial, 7) increase appropriate emotional expression, and 8) strengthen specified personal traits. Considerations related to conducting such research are discussed. The paper concludes by noting that while psychological approaches that influence disease course with cancer patients have yet to receive adequate investigation, palliative psychological interventions which might also have a beneficial effect on medical status are currently available.