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PubMedDate not supplied

Migraine as a complex disease: heterogeneity, comorbidity and genotype-phenotype interactions.

Migraine is a chronic illness interspersed with acute signs and symptoms which is currently defined, according to IHS criteria, in terms of "attacks". However, this should not lead us to ignore a critical point emerging from the simple observation of patients, i.e. the variability of the combinations in which the disease manifests itself in the same individual and especially in different individuals. This heterogeneity underpins both migraine "as attacks" (e.g. presence/absence of aura, different pain severity) and migraine "as a disease" (e.g. different onset, occurrence, association with other diseases, evolution, outcome). Genetic determinants are certainly at the basis of some migraine forms, and the role of genetics is now increasing due to the better phenotypical characterization rendered possible by the 1988 criteria. In most cases, however, migraine occurs as multifactorial inherited character. The level of complexity is further increased by the effect of "modifying" genes (such as those encoding for dopamine receptors), by comorbidity (the non coincidental association with other neurological diseases), and by the fact that the expression of comorbidity varies over time (phenotypical heterochronia). The clinical-descriptive approach allows only a partial understanding of migraine, the nature of which is more complex and heterogeneous than previously thought.

Adult↗
PubMed1990

The behaviour of common measures of association used to assess a vaccination programme under complex disease transmission patterns--a computer simulation study of malaria vaccines.

Case-control studies have been evoked as important alternatives to randomized clinical trials in the evaluation of infectious disease interventions. Using computer simulations, we compare the behaviour of common measures of association derived from case-control studies in the context of a malaria vaccine programme administered under complex transmission conditions. Several simplifying assumptions of previous workers have been relaxed and the simulated conditions are endemic rather than epidemic. The common estimators of association used in case-control studies remain unbiased only in limited circumstances. The term dependent happenings, first defined by Ross in 1916, is resurrected. Since the number of people becoming infected is dependent on the number of people already infected, control programmes in infectious diseases produce direct as well as indirect effects. Three different study designs with different pairs of comparison populations are defined. The choice of comparison population can be used to differentiate direct from indirect effects. In order to clarify the direct effects of a vaccination programme the comparison groups must be subjected to identical transmission intensities. In contrast, the referent group must remain unaffected by consequences of the intervention to determine indirect effects.

Brazil↗
PubMed1978

The canine contagious respiratory disease complex (kennel cough).

Several infectious agents are involved in the kennel cough complex in dogs. They include canine parainfluenza virus (SV5), canine adenovirus 2, Bordetella bronchiseptica, and possibly several mycoplasma species. The importance of each of these agents in the disease syndrome is discussed as well as possible prevention or treatment.

Adenoviridae Infections↗
PubMed1994

[The peripartum disease complex of the sow in industrial swine breeds. 1. Peripartum course of bacteriuria of sows with vaginal-vulvar discharge in a modern swine breeding facility].

In an industrial pig production unit ten sows were selected at random. All the sows had puerperal disease in their anamnesis and all of them revealed at the time of selection--during their late pregnancy--Urinary Tract Infection (UT)I and vaginal-vulvar discharge (VD). Mid-stream early morning urine samples were collected during four days ante partum and during four days post partum. The samples were semiquantitatively examined for E. coli and gram positive cocci. Three sows showed ante partum non significant bacteriuria which turned into significant bacteriuria post partum. The majority of the reminding sows revealed a significant bacteriuria during the whole period of examination.

Animals↗
PubMedDate not supplied

Juvenile nephronophthisis-medullary cystic disease complex: a family study.

Two sisters, eight and six years old, respectively, were admitted to Mackay Memorial Hospital in 1993 with the chief complaints of growth retardation, polyuria and nocturnal enuresis. Poor urinary concentration, sodium wasting, anemia and renal insufficiency were noted during hospitalization. Ultrasonography revealed increased renal echogenicity, loss of corticomedullary differentiation and multiple tiny corticomedullary cysts in both kidneys. Renal histopathology showed mild increase in glomerular mesangial cellularity and matrix, mild focal tubular atrophy with thickening of the tubular basement membrane. Other family members were screened by ultrasonography and found another six patients in two generations of the paternal side. Renal cysts were found in five cases. Three of them had progressively deteriorating renal failure. Five had stable renal function after three years of supportive treatment. Thus, it was concluded that the age of onset does not differentiate medullary cystic disease (MCD) from juvenile nephonophthisis (JN), and that JN and MCD could be considered a clinical complex. The absence of corticomedullary cysts on ultrasonography does not preclude the diagnosis. It is also suggested that any children with clinical symptoms of polyuria, polydipsia, anemia and growth retardation from their early years should be carefully examined, and the family history should be investigated to permit early detection of the disease.

Adult↗
PubMed2003

The ovarian surface epithelium: simple source of a complex disease.

The ovarian surface epithelium (OSE) is thought to be the origin of most ovarian cancers in humans. OSE is a single cell layer of squamous or cuboidal cells on the surface of ovaries. In contrast to its relatively simple structure, it gives rise to a highly complex group of neoplasms, the epithelial ovarian carcinomas. Thus, in this review, we summarize the development and the main characteristics of normal adult OSE with emphasis on those properties that might contribute to its propensity to undergo neoplastic progression. Secondly, a brief comparison of the biology and endocrinology of normal and neoplastic OSE is being described to understand the mechanisms in the transformation of normal OSE to its neoplastic counterparts. Lastly, recent advances in experimental approaches including in vitro and in vivo models that have contributed to our understanding of the nature of epithelial ovarian cancers are being briefly explored.

Animals↗
PubMed2007

The future of pediatric cancer and complex diseases: aren't they all?

Over the past decade, the investigation of human genetics and disease has pursued both common and uncommon germ-line variation and shown that both can be associated with altered risk for cancer and its outcomes. This line of investigation has not only begun to generate markers for disease but also insights into the biological pathways that are altered in cancer. Already, there is emerging evidence that germ-line genetic variation can alter susceptibility to different types of cancers, including pediatric cancers. It is evident that common genetic variation has emerged as a key component of a comprehensive understanding of pediatric cancer and its outcome. Future studies should unravel the complex interaction between genes and the environment.

Child↗
PubMed1997

Rationale for the prevention of disseminated Mycobacterium avium-intracellulare complex disease.

The survival rate in patients with AIDS who have CD4+ cell counts < 75 cells/microliter is increasing because of improved preventive and treatment strategies for opportunistic infections and also because of the efficacy of antiretroviral drug treatment. These patients are at high risk of developing disseminated Mycobacterium avium-intracellulare (MAC) disease, which decreases both quality of life and life expectancy. Measures aimed at preventing MAC contamination are largely ineffective in decreasing the incidence of disseminated MAC disease in patients with AIDS, because of the large natural reservoir of MAC. Chemoprophylaxis is superior to early bacteriological diagnosis as a preventive strategy, and it is preferable to wait for the appearance of symptoms of disseminated MAC disease before a curative treatment is initiated. Well-conducted studies of clarithromycin or rifabutin monotherapy as chemoprophylaxis have demonstrated a decrease in the incidence of disseminated MAC disease, as well as an increase in quality of life and survival. Clarithromycin, azithromycin and rifabutin have all been shown to be effective as prophylaxis against disseminated MAC disease. Although some combinations of drugs have been shown to be more effective than monotherapy in preventing disseminated MAC disease, these regimens are more costly and have less favourable tolerability profiles than single-agent treatment. In conclusion, chemoprophylaxis is the most effective preventive strategy against disseminated MAC disease and has been shown to improve quality of life and to decrease the risk of death associated with this disease in AIDS patients.

AIDS-Related Opportunistic Infections↗
PubMed1997

On simple repetitive DNA sequences and complex diseases.

Simple repetitive DNA sequences are abundantly interspersed in eukaryote genomes and therefore useful in genome research and genetic fingerprinting in plants, fungi and animals, including man. Recently, simple repeats were also identified in some prokaryotic genomes. Hence the same probes can be applied for multilocus DNA fingerprinting in medically relevant bacteria. Simple repeats including composite dinucleotide microsatellites are differentially represented in different compartments of eukaryote genomes. Expanded triplet blocks in and around certain genes may, for example, cause so-called trinucleotide diseases in man. As a consequence, simple repetitive sequences should also be characterized with respect to their influences on the DNA structure, gene expression, genomic (in)stability and their development on an evolutionary time scale. Here three examples of microsatellites in the human major histocompatibility complex (HLA) are investigated, a (GT)n microsatellite situated 2 kb 5' off the lymphotoxin alpha (LTA) gene, a (GAA)n block in the 5' part of the HLA-F gene and a composite (GT)n(GA)m stretch in the second intron of HLA-DRBl genes. Grossly differing mutation rates are evident in these elements as well as varying linkage disequilibria. The unfolding of these simple repeats in distant human populations is covered including Caucasians, Bushmen and South American Indians. Furthermore, implications of simple repeat neighboring genes are discussed for the multifactorial diseases multiple sclerosis (MS), rheumatoid arthritis (RA) and early onset pauciarticular arthritis (EOPA). Polymorphisms of HLA-DRBl and T cell receptor beta variable (TCRBV) genes confer susceptibility for these autoimmune diseases as demonstrable by intronic simple repeat variability. Microsatellite polymorphisms within the TNF region reveal linkage disequilibria with HLA-DRBl and different promotor alleles of the TNFA gene. Disease associations with TNFA microsatellite alleles are, on the one hand, secondary to associations with HLA-DRBl genes (in MS) or they represent additional risk factors (in RA, EOPA) on the other hand. Evolutionary persistence, various structural conformations and the specific binding of nuclear proteins to several simple repeat sequences refute the preconceptions of biological insignificance for all of these ubiquitously interspersed elements.

Arthritis↗