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PubMed1992

Ulcerative colitis and Crohn's disease health status scales for research and clinical practice.

We report the development of ulcerative colitis (UC) and Crohn's disease (CD) Health Status Scales that improve on existing inflammatory bowel disease (IBD) activity measures by their added association with health status. We surveyed 991 members of the Crohn's and Colitis Foundation of America (CCFA) and analyzed the half with greater disease activity (114 UC, 330 CD, ostomies excluded). Our analysis strategy involved (a) identification of items that discriminated active from inactive disease, (b) factor analysis to reduce the items to clusters sharing common symptom relationships, and (c) regression analysis to select those variables best associated with a composite measure of health status (health care use, daily function, psychologic distress). The factor analyses yielded two indexes for UC and CD: "Diarrhea," and "Other GI symptoms" (Cronbach's alpha 0.59-0.84). The regression analyses for both diseases showed that poorer well-being, the Diarrhea index, and dependence on medication for pain were associated with poorer health status. For UC, lower educational attainment and lower steroid dose, and for CD, the Other GI symptoms index and eye disease, also correlated with poorer health status. By design, the UC and CD Scales are better predictors of health status than the survey version of the CD Activity Index (CDAI), explaining 17 and 21% more of the variance of the health status measure. The final UC and CD Health Status Scales can be used in research and clinical care. They contain symptom items used to assess disease activity and also correlate with health status. Prospective assessment is needed to confirm their accuracy in assessing prognosis and treatment response.

Adult↗

PubMed2025

The cellular associates of late life changes in white matter microstructure.

The microstructural architecture of white matter supporting information flow across local circuits and large-scale networks changes throughout the lifespan. However, the genetic and cellular factors underlying age-related variations in white matter microstructure have yet to be established. Here, we examined the genetic associates of individual differences in diffusion-based measures of white matter in a population-based cohort (N=29,862) from the UK Biobank. Estimates of heritability from Genome-Wide Association Study (GWAS) data revealed that genetic factors are linked to population variability in 96.1% of 432 tract microstructural measures. The presence of shared genetic influences was observed to be greater within, relative to between, broad tract classes (commissural, association, projection, and complex cerebellar). Age associations with microstructural changes were estimated across diffusivity measures, with association class tracts showing the greatest vulnerability to age-related decline in older adults. Analyses of imputed cellular associates of age-related changes in white matter revealed a preferential relationship with cell gene markers of oligodendrocytes and other glial cell types, with sparse relationships observed for inhibitory and excitatory cells. These data indicate that white matter tract microstructure is shaped by genetic factors and suggest a role for glial cell-related transcripts in late-life changes in the structural wiring properties of the human brain.

Aging↗

PubMed2005

Hospital practice versus evidence-based obstetrics: categorizing practices for normal birth in an Egyptian teaching hospital.

BACKGROUND: Little is known of common normal labor hospital practices in Egypt or of their relationship to evidence-based obstetrics. This study documented facility-based practices for normal labor and delivery in Egypt for the first time by categorizing 44 practices observed in a busy obstetric teaching hospital according to the World Health Organization (WHO) Technical Working Group on Normal Birth classification of normal birth practices. METHODS: A multidisciplinary approach combined directly observing practices that were applied to individual laboring women and their newborns, observing ward activities, interviews, and focus groups. One hundred seventy-five normal births were observed in their entirety, over 28 days and nights, by medically trained observers using an observation checklist that documented 537 variables for each woman. Mothers were interviewed postpartum, and findings were shared with practitioners for their feedback. Observed practices were categorized according the 1999 WHO classification of 59 practices for normal birth, depending on their usefulness, effectiveness, or harmfulness. RESULTS: There was infrequent use of beneficial practices that should be encouraged and an unexpectedly high level of harmful practices that should be eliminated. Some beneficial practices were applied inappropriately, and practices of unproved benefit were also documented, some of which are potentially harmful to childbearing mothers and their babies. CONCLUSIONS: Hospital practices for normal labor were largely not in accordance with the WHO evidence-based classification of practices for normal birth. The findings are worrying, given the increasing proportion of hospital-based births in Egypt and the country's improved but relatively high maternal and neonatal mortality rates. Obstacles to following evidence-based protocols for normal labor require examination.

Adult↗

PubMed2005

United Network for Organ Sharing's expanded criteria donors: is stratification useful?

The United Network for Organ Sharing (UNOS) Expanded Criteria Donor (ECD) system utilizes pre-transplant variables to identify deceased donor kidneys with an increased risk of graft loss. The aim of this study was to compare the ECD system with a quantitative approach, the deceased donor score (DDS), in predicting outcome after kidney transplantation. We retrospectively reviewed 49 111 deceased donor renal transplants from the UNOS database between 1984 and 2002. DDS: 0-39 points; >or=20 points defined as marginal. Recipient outcome variables were analyzed by ANOVA or Kaplan-Meier method. There was a 90% agreement between the DDS and ECD systems as predictors of renal function and graft survival. However, DDS identified ECD- kidneys (10.7%) with a significantly poorer outcome than expected (DDS 20-29 points, n = 5,252). Stratification of ECD+ kidneys identified a group with the poorest outcome (DDS >or=30 points). Predictability of early post-transplant events (i.e. need for hemodialysis, decline of serum creatinine and length of hospital stay) was also improved by DDS. DDS predicted outcome of deceased donor renal transplantation better than the ECD system. Knowledge obtained by stratification of deceased donor kidneys can allow for improved utilization of marginal kidneys which is not achieved by the UNOS ECD definition alone.

Adult↗

PubMed1997

Interlaboratory agreement among results of human papillomavirus type 16 enzyme-linked immunosorbent assays.

Serological assays for measuring antibodies to human papillomavirus type 16 (HPV-16) virus-like particles (VLPs) have become important epidemiologic tools in recent years. However, the interlaboratory replicability of these assays has not been assessed. In this investigation, three laboratories tested a panel of specimens obtained from two different groups: 265 subjects in a vulvar cancer case-control study and 107 healthy volunteer blood donors. Each laboratory used an enzyme-linked immunosorbent assay (ELISA), but no attempt was made to standardize assay procedures among the three laboratories. The data showed good day-to-day intralaboratory replicability in laboratory 1 (correlation coefficient, > or = 0.88) and good intra-assay variability in laboratory 3 (correlation coefficient, > or = 0.93). Interlaboratory correlations, likewise, ranged between 0.61 and 0.80 in both case-control study subjects and healthy blood donors, indicating that ELISA optical density (OD) values between laboratories were linearly related regardless of the population. Kappa coefficients (kappa), based on each laboratory's categorical interpretation of its results (as positive or negative), showed good agreement (kappa, > 0.6) in case-control study subjects and moderate agreement (kappa, > or = 0.4) in blood donors, a population that had few strongly positive sera. When OD values near seropositive cutoffs were treated as indeterminates, there was little discordance between laboratories in either population. The data suggest that each laboratory measured the same humoral immune response and that their HPV-16 VLP ELISAs performed similarly (Pearson correlations). Interlaboratory differences, however, probably due to reagents and procedures, were considerably greater than intralaboratory day-to-day variability. Interlaboratory agreement in determining seropositivity (kappa) could be improved by sharing positive and negative serum controls and by treating marginal results as indeterminate. As part of continuing cooperation to improve interlaboratory agreement, we are preparing bulk serum control specimens to be shared and made available to interested researchers.

Enzyme-Linked Immunosorbent Assay↗

PubMed2000

Reduced susceptibility of human immunodeficiency virus type 1 (HIV-1) from patients with primary HIV infection to nonnucleoside reverse transcriptase inhibitors is associated with variation at novel amino acid sites.

Recently, significant numbers of individuals with primary human immunodeficiency virus (HIV) infection have been found to harbor viral strains with reduced susceptibility to antiretroviral drugs. In one study, HIV from 16% of such antiretroviral-naive individuals was shown to have a susceptibility to nonnucleoside reverse transcriptase (RT) inhibitors (NNRTIs) between 2.5- and 10-fold lower than that of a wild-type control. Mutations in the RT domain that had previously been associated with antiretroviral resistance were not shared by these strains. We have analyzed by logistic regression 46 variable amino acid sites in RT for their effect on susceptibility and have identified two novel sites influencing susceptibility to NNRTIs: amino acids 135 and 283 in RT. Eight different combinations of amino acids at these sites were observed among these patients. These combinations showed a 14-fold range in mean susceptibility to both nevirapine and delavirdine. In vitro mutagenesis of the control strain combined with a phenotypic assay confirmed the significance of amino acid variation at these sites for susceptibility to NNRTIs.

Amino Acid Substitution↗

PubMed2005

KCNH2-K897T is a genetic modifier of latent congenital long-QT syndrome.

BACKGROUND: Clinical heterogeneity among patients with long-QT syndrome (LQTS) sharing the same disease-causing mutation is usually attributed to variable penetrance. One potential explanation for this phenomenon is the coexistence of modifier gene alleles, possibly common single nucleotide polymorphisms, altering arrhythmia susceptibility. We demonstrate this concept in a family segregating a novel, low-penetrant KCNH2 mutation along with a common single nucleotide polymorphism in the same gene. METHODS AND RESULTS: The proband is a 44-year-old white woman with palpitations associated with presyncope since age 20, who presented with ventricular fibrillation and cardiac arrest. Intermittent QT prolongation was subsequently observed (max QTc, 530 ms), and LQT2 was diagnosed after the identification of a missense KCNH2 mutation (A1116V) altering a conserved residue in the distal carboxyl-terminus of the encoded HERG protein. The proband also carried the common KCNH2 polymorphism K897T on the nonmutant allele. Relatives who carried A1116V without K897T were asymptomatic, but some exhibited transient mild QTc prolongation, suggesting latent disease. Heterologous expression studies performed in cultured mammalian cells and using bicistronic vectors linked to different fluorescent proteins demonstrated that coexpression of A1116V with K897T together resulted in significantly reduced current amplitude as compared with coexpression of either allele with WT-HERG. Thus, the presence of KCNH2-K897T is predicted to exaggerate the IKr reduction caused by the A1116V mutation. These data explain why symptomatic LQTS occurred only in the proband carrying both alleles. CONCLUSIONS: We have provided evidence that a common KCNH2 polymorphism may modify the clinical expression of a latent LQT2 mutation. A similar mechanism may contribute to the risk for sudden death in more prevalent cardiac diseases.

Adult↗

PubMed2000

Problem and probable pathological gambling: considerations from a community survey.

OBJECTIVE: To investigate the nature and extent of gambling problems in a region of Canada in which legalized gambling activities were expanded during the 1990s. METHOD: A standardized telephone interview was conducted with a random sample of 738 community-dwelling adults (response rate 74%) in Winnipeg, Manitoba. RESULTS: According to traditional classification criteria, the lifetime prevalence of "probable pathological gambling" was 2.6%. A further 3.0% of the sample met criteria for traditionally defined "problem gambling," and evidence suggests that both types of gamblers share several characteristics. Social or recreational gamblers significantly differed on several variables from individuals who reported gambling problems. CONCLUSIONS: The 2.6% prevalence figure is the highest yet reported in a Canadian epidemiological survey and was obtained in a region that developed a more liberal attitude toward gambling in the 1990s. Further, a continuum of severity was demonstrated by scores on the South Oaks Gambling Screen (SOGS), and a clear and consistent distinction between problem and probable pathological gambling was not apparent. Frequenting casinos and using video poker and slot machines, rather than buying lottery tickets, distinguishes problem or pathological gamblers from recreational gamblers.

Adult↗

PubMed1999

Insight into the molecular evolution of two tropinone reductases.

In tropane alkaloid biosynthesis, two tropinone reductases produce different stereoisomers from a common substrate, tropinone. The two enzymes share 64% of identical amino acids, and highly homologous proteins with variable substrate-binding residues have also been found in tropane alkaloid non-producing species. This exemplifies a simple evolutionary process that plants have taken to acquire a new secondary metabolic pathway.

Alcohol Oxidoreductases↗

PubMed2006

Hereditary Haemorrhagic Telangiectasia (HHT): genetic and molecular aspects.

Hereditary Haemorrhagic Telangiectasia, or Rendu-Osler-Weber syndrome, is a rare autosomal dominant disorder involving the vascular system and is characterised by a highly variable expressivity and age-dependent penetrance. Diagnosis is based on the presence of at least three of four of the following symptoms: spontaneous epistaxis, cutaneous telangiectases, arteriovenous malformations in internal organs and familiarity. Recurrent complications are severe anaemia, stroke, portal and pulmonary hypertension. The peculiar characteristic of this disease is the diffusion of arteriovenous malformations, that is, localised abnormal arteriovenous connections affecting both microvasculature and large vessels. HHT is actually a heterogenous genetic disorder, divided into two clinically indistinguishable forms: HHT1 caused by mutations in endoglin gene mapping on chromosome 9q, and HHT2 caused by mutations in ALK1 located on chromosome 12q. Haploinsufficiency is the underlying mechanism for endoglin and most ALK1 mutations. Such mutations lead to a deficiency in angiogenesis, i.e. the sprouting of new vessels from pre-existing ones. To date, little is still known about the mechanism(s) responsible for lesion formation, development and slow growth. Current models focus on the role that TGF-beta superfamily members, a vast group of multifunctional cytokines, play in endothelial responses to angiogenic stimuli. As both genes seem to act in TGF-beta signal transduction pathways, SMAD proteins are also thought to be involved. There is no clear explanation accounting for the strong variability shown even among members of the same family despite the sharing of the same disease-causing mutation, and why lesions are spatially discrete.

Activin Receptors, Type II↗

PubMed1989

Cytochromes P-450 of sea birds: cross-reactivity studies with purified rat cytochromes.

1. Polyclonal antibodies against rat cytochrome P-450c (IA1), P-450d (IA2), P-450b (IIB1), P-450h (IIC11) and P-450j (IIE1), were used to probe liver microsomes prepared from six sea bird species collected from the Irish Sea between 1978 and 1988. 2. Significant cross-reactivity in all the sea bird species was seen only with antibodies to P450 IA1. Expression of cross-reactivity proteins was highly variable between individual birds, which show evidence of environmental induction. 3. Shared epitopes to P450 IA1 and IA2 were seen on a single protein expressed in liver microsomes from the cormorant (Phalacrocorax carbo). 4. Antibodies against members of rat P450 gene family II showed a small degree of cross-reactivity with sea bird microsomes. Antibodies against P450 IIB1 and IIC11 showed weak cross-reactivity in all species with little inter-individual variation. Antibodies to P450 IIE1 showed no cross-reactivity in any bird species. 5. P450 gene family I appears to be well represented in sea birds while P450 gene family II is not well developed in this group of lower vertebrates.

Animals↗

PubMed2006

Resection of a left insular cavernoma aided by a simple navigational tool. Technical note.

The management of cavernous malformations of the brain is markedly influenced by the location of the lesions themselves. In the last decade, resection of cavernomas arising in the dominant insular lobe has been deemed safe only with the guidance of neuronavigation. Most navigation equipment, however, shares some minor drawbacks, including costs, longer operating time, and a variable loss of accuracy due to intraoperative brain shift. In this paper the authors present the case of a left dominant insular cavernoma that was successfully removed using a novel form of navigation that they call magnetic resonance imaging-based corticotopography. This technique, which is unaffected by the brain shift phenomenon, provided a simple and inexpensive alternative to standard neuronavigation. Selected cases of subcortical brain lesions could be conveniently approached using the same technique.

Adult↗

PubMed1992

Mean airway pressure: physiologic determinants and clinical importance--Part 1: Physiologic determinants and measurements.

PURPOSES: To discuss the theoretical relationship of mean alveolar pressure to its most easily measured analog, the mean airway pressure, and to describe the key determinants, measurement considerations, and clinical implications of this index. DATA SOURCES: Relevant articles from the medical and physiologic literature, as well as mathematical arguments developed in this article from first principles. STUDY SELECTION: Theoretical, experimental, and clinical information that elucidates the physiologic importance, measurement, or adverse consequences of mean airway pressure. DATA EXTRACTION: Mathematical models were used in conjunction with data from the published literature to develop a unified description of the physiological and clinical relevance of mean airway pressure. SYNTHESIS: Geometrical and mathematical analyses demonstrate that shared elements comprise mean airway pressure and mean alveolar pressure, two variables that are related by the formula: mean alveolar pressure = mean airway pressure + (VE/60) x (RE-RI), where VE, RE, and RI are minute ventilation and expiratory and inspiratory resistances, respectively. Clear guidelines can be developed for selecting the site of mean airway pressure determination, for specifying technical requirements for mean airway pressure measurement, and for delineating clinical options to adjust the level of mean airway pressure. Problems in viewing mean airway pressure as a reflection of mean alveolar pressure can be interpreted against the theoretical basis of their interrelationship. In certain settings, mean airway pressure closely relates to levels of ventilation, arterial oxygenation, cardiovascular function, and barotrauma. Because mean airway pressure is associated with both beneficial and adverse effects, a thorough understanding of its theoretical and practical basis is integral to formulating an effective pressure-targeted strategy of ventilatory support. CONCLUSIONS: Mean airway pressure closely reflects mean alveolar pressure, except when flow-resistive pressure losses differ greatly for the inspiratory and expiratory phases of the ventilatory cycle. Under conditions of passive inflation, mean airway pressure correlates with alveolar ventilation, arterial oxygenation, hemodynamic performance, and barotrauma. We encourage wider use of this index, appropriately measured and interpreted, as well as its incorporation into rational strategies for the ventilatory management of critical illness.

Airway Resistance↗

PubMed1992

Mean airway pressure: physiologic determinants and clinical importance--Part 2: Clinical implications.

PURPOSES: To discuss the theoretical relationship of mean alveolar pressure to its most easily measured analog, mean airway pressure, and to describe the key determinants, measurement considerations, and clinical implications of this index. DATA SOURCES: Relevant articles from the medical and physiological literature, as well as mathematical arguments developed in this article from first principles. STUDY SELECTION: Theoretical, experimental, and clinical information that elucidates the physiologic importance, measurement, or adverse consequences of mean airway pressure. DATA EXTRACTION: Mathematical models were used in conjunction with data from the published literature to develop a unified description of the physiological and clinical relevance of mean airway pressure. SYNTHESIS: Geometrical and mathematical analyses demonstrate that shared elements comprise mean airway pressure and mean alveolar pressure, two variables that are related by the formula: mean alveolar pressure = mean airway pressure + (VE/60) x (RE - RI), where VE, RE, and RI are minute ventilation and expiratory and inspiratory resistances, respectively. Clear guidelines can be developed for selecting the site of mean airway pressure determination, for specifying technical requirements for mean airway pressure measurement, and for delineating clinical options to adjust the level of mean airway pressure. Problems in viewing mean airway pressure as a reflection of mean alveolar pressure can be interpreted against the theoretical basis of their interrelationship. In certain settings, mean airway pressure closely relates to levels of ventilation, arterial oxygenation, cardiovascular function, and barotrauma. Because mean airway pressure is associated with both beneficial and adverse actions, a thorough understanding of its theoretical and practical basis is integral to formulating an effective pressure-targeted strategy of ventilatory support. CONCLUSIONS: Mean airway pressure closely reflects mean alveolar pressure, except when flow-resistive pressure losses differ greatly for the inspiratory and expiratory phases of the ventilatory cycle. Under conditions of passive inflation, mean airway pressure correlates with alveolar ventilation, arterial oxygenation, hemodynamic performance, and barotrauma. We encourage wider use of this index, appropriately measured and interpreted, as well as its incorporation into rational strategies for the ventilatory management of critical illness.

Adolescent↗

PubMed2004

Autoinflammatory diseases: the hereditary periodic fever syndromes.

Human autoinflammatory diseases (HAIDs) are a heterogeneous group of genetically determined affections characterized by seemingly unprovoked inflammation, in the absence of autoimmune or infective causes. The hereditary periodic fever syndromes (HPFSs) are a HAID subset consisting of three main nosologic entities: familial Mediterranean fever (FMF), hyperimmunoglobulinemia D and periodic fever syndrome (HIDS), and tumor necrosis factor receptor superfamily 1A-associated periodic syndrome (TRAPS). FMF and HIDS are autosomal recessive diseases, while TRAPS is dominantly inherited. Although each HPFS presents genetic and phenotypic peculiarities, globally these affections share an intermittent expression, in form of acute attacks of fever variably associated with serosal, synovial and/or cutaneous inflammation, usually self-limiting. Amyloidosis is the most severe, life-threatening complication of FMF and TRAPS, whereas it has not been till now reported in HIDS. The HPFS molecular bases have been recently identified. In this paper, the most recent information on HPFSs is reviewed and summarized.

Acute-Phase Reaction↗

PubMed1986

[Basic methodological considerations in conducting psychological research in Latin America].

This paper suggests that research on human behavior conducted in Latin America must be particularly careful in avoiding the false assumption that methods and constructs developed in one culture are equally valid in another. Three areas are proposed in which researchers must be particularly careful: Proper understanding of the emic/etic difference, that is properly differentiating between what is universal and applicable across cultures (etic) and what reflects the peculiarities of one cultural group. Establishment of appropriate equivalences: Conceptual (where constructs have the same meanings across cultures); linguistic (whereby words share the same connotative and denotative meanings); and, metric. Control of variables related to an individual's subjective culture that may influence response patterns and accuracy (e.g., social desirability, self-presentation needs, etc.).

Behavior↗

PubMed1978

Anthropometric estimation of body density, fat, and lean body weight in women gymnasts.

Measurements from 44 highly skilled women gymnasts were used to evaluate previously derived equations for estimating body composition and to develop new equations by step-wise linear regression. True composition values were computed from body density (DB). Measures were taken of skeletal diameters (D), circumferences (C) and skin-folds (SF). Equations evaluated were those by Sloan et al. (23), F. Katch and Michael (15), Wilmore and Behnke (28), F. Katch and McArdle (18) and Weltman and V. Katch (26). With exception of the Weltman-Katch equation, correlations between true and estimated LBW's were high (.91 to .95) but underestimated true LBW 1.13 to 3.88 kg. Regression analysis suggested adjustment of ordinate values would give these equations acceptable accuracy for use with women gymnasts. New equations were derived from variables that had been selected by using factor analysis to minimize shared variance. Equations derived were DB - 1.024620 + .002024 Neck C--.001435 Supra-iliac SF--.001039 Juxta-um-bilicus SF (R.806, +/- .0061); Fat = .3798--.5809 Neck C + .3253 Abdominal C + .3007 Supra-iliac SF + .2047 Juxta-umbilicus SF, (R .891, +/- 1.29) and LBW = .3973 Height + .8357 Neck C + .4317 Shoulder C--87.203 (R .923, +/- 1.75).

Adult↗

PubMed1994

Human monoclonal rheumatoid factors: incidence of cross-reactions with tissue components and correlation with VH gene usage.

Human monoclonal antibodies with rheumatoid factor (RF) activity, derived from lymphocytes from the synovial tissue of rheumatoid arthritis (RA) patients and the peripheral blood of healthy individuals were examined for cross-reactivity with tissue and cellular antigens. The majority of IgM RF from RA patients (68%) showed reactivity with at least one component, and were frequently multispecific. A very significantly smaller proportion (28%) of the RF derived from healthy individuals demonstrated reactivities against tissue/cellular antigens (P = 0.004). RF from RA patients most commonly reacted with gastric glands (61%), nuclei (50%) and smooth muscle (50%), whereas RF from healthy donors most commonly reacted with gastric glands (20%), smooth muscle (16%), endothelium (16%) and glomeruli (16%). The most striking difference between the two groups was the reactivity with nuclear components, demonstrated by 50% of the RA RF, but by none of the healthy donor RF. As the two groups of antibodies share the same specificity for IgG Fc, but show differences in variable region segment usage, we investigated the relationship between VH gene usage and tissue/cell cross-reactivity using these antibodies and anti-blood group antibodies. Antibodies using VH3 or VH4 gene segments showed a very significantly greater frequency of tissue/cell reactions than those using VH1 (P = 0.0095 and 0.0004 respectively).

Antibodies, Monoclonal↗