Multiple Diseases (multiple + disease)

Distribution by Scientific Domains


Selected Abstracts


IBD and skeletal health: Children are not small adults!

INFLAMMATORY BOWEL DISEASES, Issue 11 2005
Francisco A Sylvester MD
Abstract Patients with inflammatory bowel disease often have decreased bone mass, and fragility fractures can occur. Multiple disease- and treatment related factors, including malnutrition, inflammation, malabsorption, decreased weight-bearing physical activity, and corticosteroids negatively influence bone metabolic activity. Because low-impact fracture is the pathologic expression of critically reduced bone mass and bone quality, knowing the relative risk of fractures in patients with IBD is of great interest. The absolute risk for incident fractures in these patients is still being debated. Clinical and laboratory research is clarifying mechanisms by which IBD can affect the function of osteoblasts and osteoclasts. In this concise review, we aim to provide an update on this topic, with focus on how pediatric IBD affects bone health. [source]


Design and engineering human forms of monoclonal antibodies

DRUG DEVELOPMENT RESEARCH, Issue 3 2004
Manuel L. Penichet
Abstract The antibody molecule has multiple properties that make it a key component of the immune response. These include its ability to recognize a vast array of different foreign substrates and to interact with and activate the host effector systems. Antibodies with defined specificities may serve as "magic bullets" for the diagnosis and therapy of multiple diseases. With the development of the hybridoma technology, it was possible to produce rodent (mouse or rat) monoclonal antibodies that are the product of a single clone of antibody producing cells and have only one antigen binding specificity. However, the therapeutic use of rodent monoclonals antibodies in humans is limited by their immunogenicity, short circulating half-life, and inability to efficiently trigger human effector mechanisms. However, it proved difficult to produce human monoclonal antibodies using the same methods. To address these problems genetic engineering and expression systems have instead been used to produce chimeric, humanized, and totally human antibodies as well as antibodies with novel structures and functional properties. In addition, the use of yeast and human artificial chromosome vectors for animal transgenesis has allowed the development of animal models that produce antigen specific antibodies that are totally human. As a consequence, recombinant antibody-based therapies are now used to treat a variety of clinical conditions including infectious diseases, inflammatory disorders, and cancer. This article summarizes and compares different strategies for designing and engineering human antibodies and their derivatives. Drug Dev. Res. 61:121,136, 2004. © 2004 Wiley-Liss, Inc. [source]


Personality variable differences between disease clusters

EUROPEAN JOURNAL OF PERSONALITY, Issue 2 2003
G. Matthews
Previous studies of personality and health have focused mainly on the influence of psychological factors on single diseases such as cancer and coronary heart disease (CHD), thereby neglecting the problem of comorbidity (i.e. the combination of different diseases). The main focus of the present study was the discrimination between single- and multiple-disease conditions on the basis of personality traits. An extensive battery of personality scales implicated in health was administered to a sample of n=5133 individuals of both genders between the ages of 40 and 65. Subjects also reported their health or illness status. A factor analysis of the personality scales yielded five dimensions clearly interpretable as "Emotional Lability", "Type A Behaviour", "Behavioural Control", "Locus of Control over Diseases", and "Psychoticism". Hierarchical cluster analyses of the subsample of participants who reported suffering from more than one disease led to eight clusters representing individuals with different combinations of diseases. Generally, there were very few significant differences between healthy and single-disease participants with regard to personality. However, mean factor scores calculated for "Emotional Lability" were higher across the multiple-disease groups than in the healthy and single-disease groups. No other personality factor showed this trend. In general the results reported here show the important role negative affectivity (e.g. Emotional Lability, Neuroticism, Depression) plays in differentiating between single and multiple diseases. Copyright © 2003 John Wiley & Sons, Ltd. [source]


Cholesterol homeostasis markers are localized to mouse hippocampal pyramidal and granule layers

HIPPOCAMPUS, Issue 8 2010
Chris M. Valdez
Abstract Changes in brain cholesterol homeostasis are associated with multiple diseases, such as Alzheimer's and Huntington's; however, controversy persists as to whether adult neurons produce their own cholesterol, or if it is outsourced to astrocytes. To address this issue, we analyzed 25 genes most immediately involved in cholesterol homeostasis from in situ data provided by the Allen Brain Mouse Atlas. We compared the relative mRNA expression in the pyramidal and granule layers, populated with neurons, with the rest of the hippocampus which is populated with neuronal processes and glia. Comparing the expression of the individual genes to markers for neurons and astrocytes, we found that cholesterol homeostasis genes are preferentially targeted to neuronal layers. Therefore, changes in gene expression levels might affect neuronal populations directly. © 2010 Wiley-Liss, Inc. [source]


The economic consequences of noncompliance in cardiovascular disease and related conditions: a literature review

INTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 2 2008
N. Muszbek
Summary Objectives:, To review studies on the cost consequences of compliance and/or persistence in cardiovascular disease (CVD) and related conditions (hypertension, dyslipidaemia, diabetes and heart failure) published since 1995, and to evaluate the effects of noncompliance on healthcare expenditure and the cost-effectiveness of pharmaceutical interventions. Methods:, English language papers published between January 1995 and February 2007 that examined compliance/persistence with medication for CVD or related conditions, provided an economic evaluation of pharmacological interventions or cost analysis, and quantified the cost consequences of noncompliance, were identified through database searches. The cost consequences of noncompliance were compared across studies descriptively. Results:, Of the 23 studies identified, 10 focused on hypertension, seven on diabetes, one on dyslipidaemia, one on coronary heart disease, one on heart failure and three covered multiple diseases. In studies assessing drug costs only, increased compliance/persistence led to increased drug costs. However, increased compliance/persistence increased the effectiveness of treatment, leading to a decrease in medical events and non-drug costs. This offset the higher drug costs, leading to savings in overall treatment costs. In studies evaluating the effect of compliance/persistence on the cost-effectiveness of pharmacological interventions, increased compliance/persistence appeared to reduce cost-effectiveness ratios, but the extent of this effect was not quantified. Conclusions:, Noncompliance with cardiovascular and antidiabetic medication is a significant problem. Increased compliance/persistence leads to increased drug costs, but these are offset by reduced non-drug costs, leading to overall cost savings. The effect of noncompliance on the cost-effectiveness of pharmacological interventions is inconclusive and further research is needed to resolve the issue. [source]


BDNF and the diseased nervous system: a delicate balance between adaptive and pathological processes of gene regulation

JOURNAL OF NEUROCHEMISTRY, Issue 1 2008
Yinghui Hu
Abstract It is clear that brain-derived neurotrophic factor (BDNF) plays a crucial role in organizing the response of the genome to dynamic changes in the extracellular environment that enable brain plasticity. BDNF has emerged as one of the most important signaling molecules for the developing nervous system as well as the impaired nervous system, and multiple diseases, such as Alzheimer's, Parkinson's, Huntington's, epilepsy, Rett's syndrome, and psychiatric depression, are linked by their association with potential dysregulation of BDNF-driven signal transduction programs. These programs are responsible for controlling the amount of activated transcription factors, such as cAMP response element binding protein, that coordinate the expression of multiple brain proteins, like ion channels and early growth response factors, whose job is to maintain the balance of excitation and inhibition in the nervous system. In this review, we will explore the evidence for BDNF's role in gene regulation side by side with its potential role in the etiology of neurological diseases. It is hoped that by bringing the datasets together in these diverse fields we can help develop the foundation for future studies aimed at understanding basic principles of gene regulation in the nervous system and how they can be harnessed to develop new therapeutic opportunities. [source]


A Robust Genome-Wide Scan Statistic of the Wellcome Trust Case,Control Consortium

BIOMETRICS, Issue 4 2009
Jungnam Joo
Summary In genome-wide association (GWA) studies, test statistics that are efficient and robust across various genetic models are preferable, particularly for studying multiple diseases in the Wellcome Trust Case,Control Consortium (WTCCC, 2007,,Nature,447, 661,678). A new test statistic, the minimum of the p-values of the trend test and Pearson's test, was considered by the WTCCC. It is referred to here as MIN2. Because the minimum of two p-values is no longer a valid p-value itself, the WTCCC only used it to rank single nucleotide polymorphisms (SNPs) but did not report the p-values of the associated SNPs when MIN2 was used for ranking. Given its importance in practice, we derive the asymptotic null distribution of MIN2, study some of its analytical properties related to GWA studies, and compare it with existing methods (the trend test, Pearson's test, MAX3, and the constrained likelihood ratio test [CLRT]) by simulations across a wide range of possible genetic models: the recessive (REC), additive (ADD), multiplicative (MUL), dominant (DOM), and overdominant models. The results show that MAX3 and CLRT have greater efficiency robustness than other tests when the REC, ADD/MUL, and DOM models are possible, whereas Pearson's test and MIN2 have greater efficiency robustness if the possible genetic models also include the overdominant model. We conclude that robust tests (MAX3, MIN2, CLRT, and Pearson's test) are preferable to a single trend test for initial GWA studies. The four robust tests are applied to more than 100 SNPs associated with 11 common diseases identified by the two WTCCC GWA studies. [source]


Community-based multiple screening model,,§¶

CANCER, Issue 8 2004
387 participants Taiwan community-based integrated screening group, Design, analysis of 4, implementation
Abstract BACKGROUND Multiple disease screening may have several advantages over single disease screening because of the economics of scale, with the high yield of detecting asymptomatic diseases, the identification of multiple diseases or risk factors simultaneously, the enhancement of the attendance rate, and the efficiency of follow-up. METHODS An integrated model of community-based multiple screening was designed and conducted between 1999 and 2001 in Keelung, Taiwan. The authors used a Papanicolaou (Pap) smear screening program as a base to integrate other screening regimens encompassing four other neoplastic diseases and three nonneoplastic chronic diseases. Screening methods, the interscreening interval, and the follow-up for each screening regimen were designed based on evidence-based literature and current national screening policy. RESULTS A total of 42,387 subjects participated in the screening activities. A 25% increase in the attendance rate for Pap smear screening was demonstrated after the introduction of multiple disease screening programs. At the first screen, this program yielded a total of 677 asymptomatic neoplasms (16.0 per 1000), including a large proportion of precancerous lesions and small presymptomatic tumors without lymph node involvement. The association between the occurrence of neoplasm and the presence of comorbid nonneoplastic chronic disease was found to be statistically significant (odds ratio, 1.64; 95% confidence interval, 1.38,1.94 [P < 0.05]). The authors also identified 5314 subjects with metabolic syndrome who were at a greater risk for colorectal and oral neoplasias. CONCLUSIONS The results of the current study demonstrate that an outreach and community-based multiple screening program not only enhances attendance rates but also has a high yield of early cases of various diseases simultaneously, and provides a natural opportunity to elucidate the correlation between neoplastic disease and nonneoplastic chronic disease. Cancer 2004. © 2004 American Cancer Society. [source]


Short- and long-term somatostatin analogue treatment in patients with hypoglycaemia related to endogenous hyperinsulinism

CLINICAL ENDOCRINOLOGY, Issue 6 2008
D. Vezzosi
Summary Background, The long-term efficacy of somatostatin analogues on insulinomas has not been studied. Design, A prospective study to evaluate the response of octreotide in 21 patients with hypoglycaemia related to endogenous hyperinsulinism who were not treated by surgery. Results, Reasons for not undergoing surgery were: refusal (n = 3), old age with multiple diseases (n = 5), unlocalized insulinomas (n = 2), malignant unresectable insulinomas (n = 5), multiple insulinomas (n = 3) and diffuse ,-cell disease (n = 3). Hypoglycaemia was responsive to octreotide in 14 of the 21 patients. A short 100-µg octreotide test correctly predicted the efficacy of treatment in six patients with benign insulinomas. Octreoscan scintigraphy was positive in 6 of the 16 patients of whom three were responsive and three unresponsive to octreotide. Octreoscan scintigraphy was negative in 10 of the 16 patients, eight of whom were responsive to octreotide. Subcutaneous octreotide treatment was prolonged for > 6 months (7,144 months, 67 ± 47 months) in 11 responsive patients. No tachyphylaxis was observed. However, the octreotide dose had to be increased in two patients after 3 and 18 months, respectively. Only one patient suffered from symptomatic biliary lithiasis after 3 years of treatment. Conclusion, Long-term octreotide treatment can be used to control hypoglycaemia in patients with endogenous hyperinsulinism who are not eligible for surgery; octreotide efficacy on hypoglycaemia could be predicted by a short 100 µg-octreotide test in patients with benign insulinomas, but was not correctly predicted by Octreoscan scintigraphy. [source]