Association Between Patient and Physician Sex and Physician-Estimated Stroke and Bleeding Risks in Atrial Fibrillation

Background

Physicians treating nonvalvular atrial fibrillation (AF) assess stroke and bleeding risks when deciding on anticoagulation. The agreement between empirical and physician-estimated risks is unclear. Furthermore, the association between patient and physician sex and anticoagulation decision-making is uncertain.

Hypoceruloplasminemia and ultrastructural changes resembling Wilson's disease in nonalcoholic liver steatosis. A clinical and pathological study of five cases

We report five cases of asymptomatic patients with persistently abnormal liver function tests in whom copper metabolism abnormalities resulted in a misleading suspicion of Wilson's disease. Ceruloplasmin levels assessed by nephelometric immunoassay, single radial immunodiffusion and the enzymatic method averaged 53.8, 61 and 52.8% of the mean value obtained in age- and sex-matched controls (p less than 0.001). Twenty-four-hour urinary copper excretion was higher than the normal range in three instances. Four patients exhibited hypertriglyceridemia. Liver histology showed fatty change with or without sinusoidal fibrosis. Electron microscopic examination unexpectedly disclosed mitochondrial and lysosomal changes identical to those described in Wilson's disease. The present observations indicate that biochemical and ultrastructural changes suggestive for Wilson's disease may be observed in the absence of increased liver copper content. Whether such cases represent isolated cases of heterozygosity for the Wilson's disease gene remains to be elucidated.     

Disposition and pharmacokinetics of [14C]finasteride after oral administration in humans.

The disposition of [14C]finasteride, a competitive inhibitor of steroid 5 alpha-reductase, was investigated after oral administration of 38.1 mg (18.4 microCi) of drug in six healthy volunteers. Plasma, urine, and feces were collected for 7 days and assayed for total radioactivity. Concentrations of finasteride and its neutral metabolite, omega-hydroxyfinasteride (monohydroxylated on the t-butyl side chain), in plasma and urine were determined by HPLC assay. Mean excretion of radioactivity equivalents in urine and feces equaled 39.1 +/- 4.7% and 56.8 +/- 5.0% of the dose, respectively. The mean peak plasma concentrations reached for total radioactivity (ng equivalents), finasteride, and omega-hydroxyfinasteride were 596.5 +/- 88.3, 313.8 +/- 99.4, and 73.7 +/- 11.8 ng/ml, respectively, at approximately 2 hr; the mean terminal half-life for drug and metabolite was 5.9 +/- 1.3 and 8.4 +/- 1.7 hr, respectively. Of the 24-hr plasma radioactivity, 40.9% was finasteride, 11.8% was the neutral metabolite, and 26.7% was characterized as an acidic fraction of radioactivity. Binding of [14C]finasteride to plasma protein was extensive (91.3 to 89.8%), with a trend suggesting concentration dependency (range 0.02 to 2 micrograms/ml). Little of the dose was excreted in urine as parent (0.04%) or omega-hydroxyfinasteride (0.4%). Urinary excretion of radioactivity was largely in the form of acidic metabolite(s)--18.4 +/- 1.7% of the dose was eliminated as the omega-monocarboxylic acid metabolite. Finasteride was scarcely excreted unchanged in feces. In humans, finasteride is extensively metabolized through oxidative pathways.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cross-antigenicity of horse serum albumin with dog and cat albumins: study of three short peptides with significant inhibitory activity towards specific human IgE and IgG antibodies.

Horse serum albumin is present in the near vicinity of the animal, while dog and cat serum albumins are very common allergens present in house dust. Human patients clinically defined as allergic to horse could react with horse serum albumin by means of IgE or IgG antibodies. Studies regarding the specificities of these antibodies by inhibition enzyme-linked immunosorbent assay (ELISA) and depletion experiments have demonstrated that they are directed against dog serum albumin and cross-react not only with horse serum albumin but with other serum albumins from different origins. To investigate these observations further, we isolated and characterized three tryptic peptides (P1, P2 and P3) from horse serum albumin. The peptide P1 contains loops 1 and 2 of the first domain, P2 is derived from loop 4 of the second domain, and P3 contains the disulphide loop 9 of the third domain. These were able to inhibit the binding of the patients' IgE and IgG antibodies to horse albumin as well as to dog and cat serum albumins. This indicates that these peptides are involved in the observed cross-reactions. They also shared common epitopes, as revealed by human IgE antibodies. After reduction and alkylation, they totally lost their inhibitory capacity, suggesting that the intra-chain disulphide bridges, essential for the preservation of the loop structure, probably maintain their allergenic/antigenic reactivity.     

Physiological Correlates of Mental Activity: Eye Movements, Alpha, and Heart Rate During Imagining, Suppression, Concentration, Search, and Choice

Rapid eye movements (REMs), EEG alpha, and tonic heart rate (HR) were measured during 6 types of cognitive tasks—imagining a liked person, suppressing thoughts of the person, searching one's mind for alternative solutions, arithmetic involving little concentration, problems involving high concentration, and choosing a preferred activity. The latter 3 required verbalization, the former 3 did not. Only suppression and search did not differ significantly from each other on at least one physiological variable. Imagining, suppression, and search yielded few REMs, high alpha, and low HR. High concentration yielded many REMs, low alpha, and high HR. Choice yielded many REMs, low alpha, and intermediate HR. Low concentration yielded few REMs, low alpha, and high HR. Suppression produced somewhat less alpha than imagining but did not differ significantly in REMs.     

If Mothers Had Their Say: Research-Informed Intervention Design for Empowering Mothers to Establish Smoke-Free Homes

The Empowering Mothers to Establish Smoke-free Homes (EMESH) project developed in response to an interdisciplinary health team seeking effective interventions for reducing/eliminating the environmental tobacco smoke exposure of infants with compromised respiratory status. Two study phases that informed the EMESH intervention design are described. Phase I involved semi-structured interviews with 20 caretakers of infants diagnosed with Bronchopulmonary Dysplasia (BPD). In Phase II, 75 randomly selected medical records of infants with BPD were reviewed to explore the family demographics and staff behavior regarding environmental tobacco smoke (ETS) interventions. Interview results suggest that families are open to partnering with social workers and interdisciplinary team members in addressing infants’ ETS exposure, families’ unique circumstances indicate a need for tailored interventions, and the use of self-efficacy and decisional balance tools are feasible options. Results from the medical records review indicate that many families are economically vulnerable and reside in regions where smoking is common. There is a paucity of staff documentation regarding ETS conversations and interventions, indicating that these conversations may not take place. Together these results suggest a two-pronged approach in the next phases of EMESH: staff training in hosting and documenting ETS conversations and a tailored, parent-driven set of intervention options.     

Dose- and time-dependent gene expression alterations in prostate and colon cancer cells after in vitro exposure to carbon ion and X-irradiation

Hadrontherapy is an advanced form of radiotherapy that uses beams of charged particles (such as protons and carbon ions). Compared with conventional radiotherapy, the main advantages of carbon ion therapy are the precise absorbed dose localization, along with an increased relative biological effectiveness (RBE). This high ballistic accuracy of particle beams deposits the maximal dose to the tumor, while damage to the surrounding healthy tissue is limited. Currently, hadrontherapy is being used for the treatment of specific types of cancer. Previous in vitro studies have shown that, under certain circumstances, exposure to charged particles may inhibit cell motility and migration. In the present study, we investigated the expression of four motility-related genes in prostate (PC3) and colon (Caco-2) cancer cell lines after exposure to different radiation types. Cells were irradiated with various absorbed doses (0, 0.5 and 2 Gy) of accelerated ¹³C-ions at the GANIL facility (Caen, France) or with X-rays. Clonogenic assays were performed to determine the RBE. RT-qPCR analysis showed dose- and time-dependent changes in the expression of CCDC88A, FN1, MYH9 and ROCK1 in both cell lines. However, whereas in PC3 cells the response to carbon ion irradiation was enhanced compared with X-irradiation, the effect was the opposite in Caco-2 cells, indicating cell-type–specific responses to the different radiation types.