Urinary incontinence and its association with death, nursing home admission, and functional decline

OBJECTIVES: To determine whether urinary incontinence (UI) is an independent predictor of death, nursing home admission, decline in activities of daily living (ADLs), or decline in instrumental activities of daily living (IADLs). DESIGN: A population-based prospective cohort study from 1993 to 1995. SETTING: Community-dwelling within the United States. PARTICIPANTS: Six thousand five hundred six of the 7,447 subjects aged 70 and older in the Asset and Health Dynamics Among the Oldest Old study who had complete information on continence status and did not require a proxy interview at baseline. MEASUREMENTS: The predictor was UI, and the outcomes were death, nursing home admission, ADL decline, and IADL decline. Potential confounders considered were comorbid conditions, baseline function, sensory impairment, cognition, depressive symptoms, body mass index, smoking and alcohol, demographics, and socioeconomic status. RESULTS: The prevalence of UI was 14.8% (18.5% in women; 8.5% in men). At 2-year follow-up, subjects incontinent at baseline were more likely to have died (10.9% vs 8.7%; unadjusted odds ratio (OR)=1.29, 95% confidence interval (CI)=1.02-1.64), be admitted to a nursing home (4.4% vs 2.6%, OR=1.77; 95% CI=1.18-2.63), and to have declined in ADL function (13.6% vs 8.1%; OR=1.78, 95% CI=1.36-2.33) and IADL function (21.2% vs 13.8%; OR 1.69, 95% CI 1.39-2.05). However, after adjusting for confounders, UI was not an independent predictor of death (adjusted OR (AOR)= 0.90, 95% CI=0.67-1.21), nursing home admission (AOR=1.33, 95% CI=0.86-2.04), or ADL decline (AOR=1.24, 95% CI=0.92-1.68). Incontinence remained a predictor of IADL decline (AOR=1.31; 95% CI=1.05-1.63), although adjustment markedly reduced the strength of this association. CONCLUSION: Higher levels of baseline illness severity and functional impairment appear to mediate the relationship between UI and adverse outcomes. The results suggest that, although UI appears to be a marker of frailty in community-dwelling elderly, it is not a strong independent risk factor for death, nursing home admission, or functional decline.     

Alcohol dehydrogenase genetic polymorphisms, low-to-moderate alcohol consumption, and risk of breast cancer

BACKGROUND: In vitro, human isoenzymes encoded by genes homozygous for the ADH1C*1 or ADH1B*2 alleles metabolize ethanol to acetaldehyde at a faster rate than those homozygous for the ADH1C*2 or ADH1B*1 allele. Because alcohol is a known risk factor for breast cancer, we evaluated the joint association of genetic variants in ADH and alcohol consumption in relation to breast cancer. METHODS: A nested case-control study of 321 cases and matched controls was conducted. Five single nucleotide polymorphisms (SNPs) in the ADH1C and ADH1B genes were genotyped. Logistic regression was used to assess odds ratios (ORs) and 95% confidence limits (CIs) for each SNP. Haplotype analysis of all 5 SNPs was also undertaken. RESULTS: Among drinkers, the median intake of total alcohol was 13 g/wk (10th-90th percentiles; 4.5-135.9) in cases and 18 g/wk (10th-90th percentiles; 4.5-104.1) in controls. Women who drank alcohol tended to be at an increased risk of developing breast cancer compared with those who did not drink (OR=1.40%, 95% CI 0.97-2.03), particularly those who were premenopausal at the time of breast cancer diagnosis (OR=2.69%, 95% CI: 1.00-7.26). Of the known functional alleles, breast cancer risk was not significantly increased among carriers of at least 1 ADH1C*1 or ADH1B*2 allele, when compared with those homozygous for the genotype at each locus. However, breast cancer risk tended to be lower among women who inherited the G allele at ADH1B IVS1+896A>G (OR=0.62, 95% CI 0.37-1.04). Overall haplotype frequencies were not significantly different between cases and controls. CONCLUSIONS: In this study low levels of alcohol are associated with a modest increase in breast cancer risk that is not altered by known functional allelic variants of the ADH1B and 1C gene. The protective association conferred by the G allele at ADH1B IVS1+896A>G needs further evaluation.     

Identification and characterization of a novel heme-associated cell surface protein made by Streptococcus pyogenes

Analysis of the genome sequence of a serotype M1 group A Streptococcus (GAS) strain identified a gene encoding a previously undescribed putative cell surface protein. The gene was cloned from a serotype M1 strain, and the recombinant protein was overexpressed in Escherichia coli and purified to homogeneity. The purified protein was associated with heme in a 1:1 stoichiometry. This streptococcal heme-associated protein, designated Shp, was produced in vitro by GAS, located on the bacterial cell surface, and accessible to specific antibody raised against the purified recombinant protein. Mice inoculated subcutaneously with GAS and humans with invasive infections and pharyngitis caused by GAS seroconverted to Shp, indicating that Shp was produced in vivo. The blood of mice actively immunized with Shp had significantly higher bactericidal activity than the blood of unimmunized mice. The shp gene was cotranscribed with eight contiguous genes, including homologues of an ABC transporter involved in iron uptake in gram-negative bacteria. Our results indicate that Shp is a novel cell surface heme-associated protein.     

Parent-child agreement on child psychiatric symptoms assessed via structured interview

Correlations between scores derived from structured interviews with 299 disturbed children aged 6-18 and their parents indicated low-to-moderate levels of agreement regarding the presence and severity of child psychiatric symptoms. Agreement was higher on behavior and conduct problems than on anxiety, fears, obsessions-compulsions, psychotic symptoms and affective disturbances. Parents reported more child behavior and conduct problems than children, whereas children reported more affective and neurotic symptoms than parents. Parent-child agreement also increased sharply with age.     

Reduced incidence of AD with NSAID but not H2 receptor antagonists: the Cache County Study

BACKGROUND: Previous analyses from the Cache County (UT) Study showed inverse associations between the prevalence of AD and the use of nonsteroidal anti-inflammatory drugs (NSAID), aspirin compounds, or histamine H(2) receptor antagonists (H(2)RA). The authors re-examined these associations using data on incident AD. METHODS: In 1995 to 1996, elderly (aged 65+) county residents were assessed for dementia, with current and former use of NSAID, aspirin, and H(2)RA as well as three other "control" medication classes also noted. Three years later, interval medication histories were obtained and 104 participants with incident AD were identified among 3,227 living participants. Discrete time survival analyses estimated the risk of incident AD in relation to medication use. RESULTS: AD incidence was marginally reduced in those reporting NSAID use at any time. Increased duration of use was associated with greater risk reduction, and the estimated hazard ratio was 0.45 with >/=2 years of exposure. Users of NSAID at baseline showed little reduction in AD incidence, regardless of use thereafter. By contrast, former NSAID users showed substantially reduced incidence (estimated hazard ratio = 0.42), with a trend toward greatest risk reduction among those with extended exposure. Similar patterns appeared with aspirin but not with any other medicines examined. CONCLUSIONS: Long-term NSAID use may reduce the risk of AD, provided such use occurs well before the onset of dementia. More recent exposure seems to offer little protection. Recently initiated randomized trials of NSAID for primary prevention of AD are therefore unlikely to show effects with treatment until participants have been followed for several years.     

Currarino triad: Characteristic appearances on magnetic resonance imaging and plain radiography

The Currarino triad is a complex anomaly consisting of an anorectal malformation, a sacral bone defect and a presacral mass. It was first described in 1981 and since then, approximately 250 cases have been reported. Radiology has an important part to play in the diagnosis of this entity, as the imaging features are characteristic. We report a case of Currarino triad in an infant who presented with intractable constipation and discuss relevant MRI and plain radiography findings.     

Glutathione synthesis is essential for mouse development but not for cell growth in culture

Glutathione (GSH) is a major source of reducing equivalents in mammalian cells. To examine the role of GSH synthesis in development and cell growth, we generated mice deficient in GSH by a targeted disruption of the heavy subunit of gamma-glutamylcysteine synthetase (gammaGCS-HS(tm1)), an essential enzyme in GSH synthesis. Embryos homozygous for gammaGCS-HS(tm1) fail to gastrulate, do not form mesoderm, develop distal apoptosis, and die before day 8.5. Lethality results from apoptotic cell death rather than reduced cell proliferation. We also isolated cell lines from homozygous mutant blastocysts in medium containing GSH. These cells also grow indefinitely in GSH-free medium supplemented with N-acetylcysteine and have undetectable levels of GSH; further, they show no changes in mitochondrial morphology as judged by electron microscopy. These data demonstrate that GSH is required for mammalian development but dispensable in cell culture and that the functions of GSH, not GSH itself, are essential for cell growth.     

Pressure-course events in the tabletting of phenylbutazone

The distribution to different compression phases via formation of the 1. derivation of the increased force curve is elucidated by the example of the phenylbutazone (2. AB-DDR) compression by means of an instrumented, slow-motion (1 r. p. m.) excentric press, equipped with piezoelectric force recorders and semiconductor transducers articulated to the upper stamp. In the case of phenylbutazone it is subdivided into at least three sections.