Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “complex diseases”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 415 records · Page 23Linked to original sources
PubMed1999

Direct power comparisons between simple LOD scores and NPL scores for linkage analysis in complex diseases.

Several methods have been proposed for linkage analysis of complex traits with unknown mode of inheritance. These methods include the LOD score maximized over disease models (MMLS) and the "nonparametric" linkage (NPL) statistic. In previous work, we evaluated the increase of type I error when maximizing over two or more genetic models, and we compared the power of MMLS to detect linkage, in a number of complex modes of inheritance, with analysis assuming the true model. In the present study, we compare MMLS and NPL directly. We simulated 100 data sets with 20 families each, using 26 generating models: (1) 4 intermediate models (penetrance of heterozygote between that of the two homozygotes); (2) 6 two-locus additive models; and (3) 16 two-locus heterogeneity models (admixture alpha = 1.0,.7,.5, and.3; alpha = 1.0 replicates simple Mendelian models). For LOD scores, we assumed dominant and recessive inheritance with 50% penetrance. We took the higher of the two maximum LOD scores and subtracted 0.3 to correct for multiple tests (MMLS-C). We compared expected maximum LOD scores and power, using MMLS-C and NPL as well as the true model. Since NPL uses only the affected family members, we also performed an affecteds-only analysis using MMLS-C. The MMLS-C was both uniformly more powerful than NPL for most cases we examined, except when linkage information was low, and close to the results for the true model under locus heterogeneity. We still found better power for the MMLS-C compared with NPL in affecteds-only analysis. The results show that use of two simple modes of inheritance at a fixed penetrance can have more power than NPL when the trait mode of inheritance is complex and when there is heterogeneity in the data set.

Gene Frequency↗
PubMed1983

Complement-mediated inhibition of immune precipitation in patients with immune complex diseases.

The ability of human sera to prevent the precipitation of antigen-antibody complexes has been investigated. The early complement components including C3 are required for optimal prevention of immune precipitation, whereas the later components are not required. The sera of 36 of 75 patients with seropositive rheumatoid arthritis (RA), 14 of 32 with SLE and four of 17 with glomerulonephritis exhibited reduced capacities to prevent immune precipitation. In contrast sera from patients with seronegative RA, ankylosing spondylitis, psoriatic arthritis or degenerative joint disease were normal in this respect. In SLE and GN sera hypocomplementaemia was frequently associated but not always with failure to prevent immune precipitation, whereas only a small proportion of the patients with seropositive RA and reduced capacity to retain complexes in a soluble form were hypocomplementaemic. Thus the failure of sera to prevent the precipitation of antigen-antibody complexes is not always associated with hypocomplementaemia.

Antigen-Antibody Complex↗
PubMed1976

Gold nephropathy: serologic data suggesting an immune complex disease.

Servlogical tests preformed on a patient with gold-induced nephropathy revealed a multitude of immunological phenomena preceding the onset of proteinuria. These included formtaion of tissue antibodies, rheumatoid factors and circulating immune complexes. An antigen sharing immunological determinants with DOC-extractable tissue antigens was released into circulation before and during proteinuria. Precipitating antibodies against this circulating antigen were found in one serum sample obtained 6 weeks before the complication was diagnosed. In this serum specimen, antibodies were also found which combined with saline extracts, DOC extracts containing the ubiquitous tissue antigen (UTA), and preparations obtained from various human organs by extraction at 100 degrees C followed by precipitation at 71% ethanol concentration (BE preparations). Most of the activities disappeared before the onset of proteinuria. The possible significance of these phenomena in the pathogenesis of nephropathy is discussed.

Adult↗
PubMed2003

A prospective, randomized trial examining the efficacy and safety of clarithromycin in combination with ethambutol, rifabutin, or both for the treatment of disseminated Mycobacterium avium complex disease in persons with acquired immunodeficiency syndrome.

This multicenter, randomized, open-label phase 3 clinical trial compared the safety and efficacy of 3 clarithromycin-containing combination regimens for the treatment of disseminated Mycobacterium avium complex (MAC) disease in persons with acquired immunodeficiency syndrome. A total of 160 eligible patients with bacteremic MAC disease were randomized to receive clarithromycin with either ethambutol (C+E), rifabutin (C+R), or both (C+E+R) for 48 weeks. After 12 weeks of treatment, the proportion of subjects with a complete microbiologic response was not statistically significantly different among treatment arms: the proportion was 40% in the C+E group, 42% in the C+R group, and 51% in the C+E+R group (P=.454). The proportion of patients with complete or partial responses who experienced a relapse while receiving C+R (24%) was significantly higher than that of patients receiving C+E+R (6%; P=.027) and marginally higher than that of patients receiving C+E (7%; P=.057). Subjects in the C+E+R group had improved survival, compared with the C+E group (hazard ratio [HR], 0.44; 95% confidence interval [CI], 0.23-0.83) and the C+R group (HR, 0.49; 95% CI, 0.26-0.92).

AIDS-Related Opportunistic Infections↗
PubMed2006

Systems-based medicine approaches to understand and treat complex diseases. The example of multiple sclerosis.

Systems medicine is an emerging concept that acknowledges the complexity of a multitude of non-linear interactions among molecular and physiological variables. Under this new paradigm, rather than a collection of symptoms, diseases are seen as the product of deviations from a robust steady state compatible with life. This concept requires the incorporation of mathematics and physics to the more classical arsenal of physiology and molecular biology with which physicians are trained today. This review explores the diverse types of information that can be accumulated towards the understanding of multiple sclerosis (MS), a complex autoimmune disease that targets the central nervous system (CNS). The challenge of data integration and modeling of dynamical systems is discussed in the context of disease susceptibility and response to treatment. A theoretical framework that supports the use of combination therapy is also presented.

Animals↗
PubMed1976

Macrophage clearance function and immune complex disease in New Zealand Black/White F1 hybrid mice.

Macrophage clearance function in NZB, NZW, NZB/W, Ajax and B10D2 new mice was assessed by measurement of the rate of clearance (KPVP) of intravenously-injected 125I-labelled polyvinylpyrrolidone (PVP). There were significant strain and age-related variations in KPVP. In particular there was a marked fall in KPVP in NZB/W mice with increasing age. This fall was most apparent in female NZB/W and preceded the age at which renal disease usually develops in these animals. We suggest that ineffective macrophage function and production of low affinity antibody contribute to the early development of immune complex glomerulonephritis in these mice.

Age Factors↗
PubMed2006

[Bacteriological and pathological analysis on the pathogenetic factors for cavitary and nodular bronchiectatic type of pulmonary Mycobacterium avium-intracellulare complex disease].

A total of 101 strains of Mycobacterium avium complex (MAC), consisting of 86 M. avium and 15 M. intracellulare strains, were examined by DNA sequencing. The frequency of radiological types [cavitary (Cav) type and nodular bronchiectatic (NB) type] was similar in each species, thus, both species are equal causes of the two radiological types of MAC disease. We also examined serovars of the isolated strains using extracted glycopeptidelipid antigens and thin layer chromatography. Cav type patients discharged a single serovar MAC, while NB type patients discharged two serovar MACs simultaneously. RFLP pattern obtained by the use of IS1245, revealed no clustering of the strains specific for Cav type and NB type. Histopathological examinations of the bronchial lesions in 40 MAC cases and 49 multi-drug resistant tuberculosis (MDR-TB) cases were performed on the surgically removed lung specimens. Lymphocytic infiltration, epithelioid cell granuloma formation, epithelial desquamation and ulceration, as well as smooth muscle atrophy as a cause of bronchiolectasis, were observed more often and were more severe in the peripheral bronchial walls of the NB type than the Cav type of MAC, and as compared with those of MDR-TB cases.

Diagnosis, Differential↗
PubMed1998

[Diagnostic usefulness of the tuberculin reaction by PPD-B in Mycobacterium avium complex disease].

This study was carried out to clarify the diagnostic usefulness of the skin tests of purified protein derivatives from M. intracellulare (PPD-B) and M. tuberculosis (PPDs). Study subjects consisted of 41 patients with primary infection type of M. avium complex (MAC) disease, 36 patients with pulmonary tuberculosis (TB) and 29 patients with other bacterial respiratory infections including COPD (OB). The patients were sorted out to middle (50-69 y.o.) and old (70-89 y.o.) age groups of each disease. The size of skin redness elicited 48 hours after the PPD-B and PPDs intradermal injections were compared among them. The results were as follows. 1) Both PPD-B and PPDs skin reactions were larger in the middle age group than in the old one for each disease. 2) In PPDs skin tests, the reaction of TB group was the largest among the three diseases. In PPD-B skin tests, that of MAC was the largest. 3) In TB group, PPDs skin reaction was significantly larger than that of PPD-B, while in MAC and OB groups there was no significant difference between the skin reactions of PPDs and PPD-B. 4) Defining significant positive reaction to PPD-B as PPD-B skin reaction exceeding 10 mm and larger than that of PPDs skin reaction, the rate of significant positive reaction to PPD-B was significantly higher in MAC than TB in both age groups. These results showed that the simultaneous skin tests of PPD-B and PPDs were a useful aid in the diagnosis of MAC infection disease when mycobacterial infection diseases were clinically suspected by bacteriological or chest radiographic examinations.

Age Factors↗