The utility of aminoterminal pro-B-type natriuretic peptide for the detection of preclinical systolic and diastolic dysfunction in the community

Background: There is scant data regarding methods to identify subjects in the community with preclinical left ventricular (LV) systolic and diastolic dysfunction. Methods: A population-based sample of 1229 older adults underwent examination with transthoracic echocardiography and measurement of circulating aminoterminal pro-Btype natriuretic peptide (N-BNP) levels. Heart failure status was ascertained according to past history and clinical examination. The ability of N-BNP to detect preclinical LV ejection fraction (EF)

Impaired sustained attention and executive dysfunction:bipolar disorder versus depression-specific markers of affective disorders

Objective - To identify neurocognitive measures that could be used as objective markers of bipolar disorder. Methods - We examined executive function, sustained attention and short-term memory as neurocognitive domains in 18 participants with bipolar disorder in euthymic state (Beuth), 14 in depressed state (Bdep), 20 with unipolar depression (Udep) and 28 healthy control participants (HC). We conducted four-group comparisons followed by relevant post hoc analyses. Results - Udep and Bdep, but not Beuth showed impaired executive function (p = 0.045 and p = 0.046, respectively). Both Bdep and Beuth, but not Udep, showed impaired sustained attention (p = 0.001 and p = 0.045, respectively). The four groups did not differ significantly on short-term memory. Impaired sustained attention and executive dysfunction were not associated with depression severity, duration of illness and age of illness onset. Only a small number of abnormal neurocognitive measures were associated with medication in Bdep and Beuth. Conclusion - Impaired sustained attention appears specific to bipolar disorder and present in both Beuth and Bdep; it may represent an objective marker of bipolar disorder. Executive dysfunction by contrast, appears to be present in Udep and Bdep and likely represents a marker of depression.

Role of endothelial Nox2 NADPH oxidase in angiotensin II-induced hypertension and vasomotor dysfunction

NADPH oxidase (Nox)-derived reactive oxygen species (ROS) are known to be involved in angiotensin II-induced hypertension and endothelial dysfunction. Several Nox isoforms are expressed in the vessel wall, among which Nox2 is especially abundant in the endothelium. Endothelial Nox2 levels rise during hypertension but little is known about the cell-specific role of endothelial Nox2 in vivo. To address this question, we generated transgenic mice with endothelial-specific overexpression of Nox2 (Tg) and studied the effects on endothelial function and blood pressure. Tg had an about twofold increase in endothelial Nox2 levels which was accompanied by an increase in p22phox levels but no change in levels of other Nox isoforms or endothelial nitric oxide synthase (eNOS). Basal NADPH oxidase activity, endothelial function and blood pressure were unaltered in Tg compared to wild-type littermates. Angiotensin II caused a greater increase in ROS production in Tg compared to wild-type aorta and attenuated acetylcholine-induced vasorelaxation. Both low and high dose chronic angiotensin II infusion increased telemetric ambulatory blood pressure more in Tg compared to wild-type, but with different patterns of BP change and aortic remodeling depending upon the dose of angiotensin II dose. These results indicate that an increase in endothelial Nox2 levels contributes to angiotensin II-induced endothelial dysfunction, vascular remodeling and hypertension. © 2011 The Author(s).

Does post-caesarean dyspareunia reflect sexual malfunction, pelvic floor and perineal dysfunction?

The aim was to define post-caesarean dyspareunia as a sexual and pelvic-perineal symptom. Post-caesarean (80 elective, 104 emergency) and 100 vaginally delivered primiparae had domiciliary interviews at 10 months postpartum. A total of 50 (28% and 27%) post-caesarean and 46 (46%) vaginally delivered, reported dyspareunia. Severely impaired general sexual health occurred in 82 (24% elective, 25% emergency, 35% vaginally delivered) as category 3 (dyspareunia with sexual symptoms) and 27 (10% elective, 7% emergency, 12% vaginally delivered) as category 4 (reduced frequency <6). The risk of dyspareunia (RR 1.14, CI 0.73, 1.77) or impaired general sexual health (RR 0.93, CI 0.32, 2.74) was similar among those with or without perineal trauma. Both caesarean and perineal scars were associated with sexual malfunction. Primiparae with new incontinence had a lower risk of dyspareunia than impaired general sexual health. Awareness of the associations of post-caesarean dyspareunia and impaired general sexual health with incontinence would facilitate appropriate obstetric decision-making. Further research is indicated. © 2011 Informa UK, Ltd.

Age-related macular degeneration is associated with increased vascular endothelial growth factor, hemorheology and endothelial dysfunction

OBJECTIVE: To investigate laboratory evidence of abnormal angiogenesis, hemorheologic factors, endothelial damage/dysfunction, and age-related macular degeneration (ARMD). DESIGN: Comparative cross-sectional study. PARTICIPANTS: We studied 78 subjects (26 men and 52 women; mean age 74 years; standard deviation [SD] 9.0) with ARMD attending a specialist referral clinic. Subjects were compared with 25 healthy controls (mean age, 71 years; SD, 11). INTERVENTION AND OUTCOME MEASURES: Levels of vascular endothelial growth factor (VEGF, an index of angiogenesis), hemorheologic factors (plasma viscosity, hematocrit, white cell count, hemoglobin, platelets), fibrinogen (an index of rheology and hemostasis), and von Willebrand factor (a marker of endothelial dysfunction) were measured. RESULTS: Median plasma VEGF (225 vs. 195 pg/ml, P = 0.019) and mean von Willebrand factor (124 vs. 99 IU/dl, P = 0.0004) were greater in ARMD subjects than the controls. Mean plasma fibrinogen and plasma viscosity levels were also higher in the subjects (both P < 0.0001). There were no significant differences in other indices between cases and controls. When "dry" (drusen, atrophy, n = 28) and "exudative" (n = 50) ARMD subjects were compared, there was no significant differences in VEGF, fibrinogen, viscosity, or von Willebrand factor levels. There were no significant correlations between the measured parameters. Stepwise multiple regression analysis did not demonstrate any significant clinical predictors (age, gender, smoking, body mass index, history of vascular disease, or hypertension) for plasma VEGF or fibrinogen levels, although smoking status was a predictor of plasma von Willebrand factor levels (P < 0.05). CONCLUSIONS: This study suggests an association between markers of angiogenesis (VEGF), hemorheologic factors, hemostasis, endothelial dysfunction, and ARMD. The interaction between abnormal angiogenesis and the components of Virchow's triad for thrombogenesis may in part contribute to the pathogenesis of ARMD.

Endothelial NADPH oxidase-2 promotes interstitial cardiac fibrosis and diastolic dysfunction through proinflammatory effects and endothelial-mesenchymal transition

OBJECTIVES: This study sought to investigate the effect of endothelial dysfunction on the development of cardiac hypertrophy and fibrosis. BACKGROUND: Endothelial dysfunction accompanies cardiac hypertrophy and fibrosis, but its contribution to these conditions is unclear. Increased nicotinamide adenine dinucleotide phosphate oxidase-2 (NOX2) activation causes endothelial dysfunction. METHODS: Transgenic mice with endothelial-specific NOX2 overexpression (TG mice) and wild-type littermates received long-term angiotensin II (AngII) infusion (1.1 mg/kg/day, 2 weeks) to induce hypertrophy and fibrosis. RESULTS: TG mice had systolic hypertension and hypertrophy similar to those seen in wild-type mice but developed greater cardiac fibrosis and evidence of isolated left ventricular diastolic dysfunction (p < 0.05). TG myocardium had more inflammatory cells and VCAM-1-positive vessels than did wild-type myocardium after AngII treatment (both p < 0.05). TG microvascular endothelial cells (ECs) treated with AngII recruited 2-fold more leukocytes than did wild-type ECs in an in vitro adhesion assay (p < 0.05). However, inflammatory cell NOX2 per se was not essential for the profibrotic effects of AngII. TG showed a higher level of endothelial-mesenchymal transition (EMT) than did wild-type mice after AngII infusion. In cultured ECs treated with AngII, NOX2 enhanced EMT as assessed by the relative expression of fibroblast versus endothelial-specific markers. CONCLUSIONS: AngII-induced endothelial NOX2 activation has profound profibrotic effects in the heart in vivo that lead to a diastolic dysfunction phenotype. Endothelial NOX2 enhances EMT and has proinflammatory effects. This may be an important mechanism underlying cardiac fibrosis and diastolic dysfunction during increased renin-angiotensin activation.

Pyrrolidine Dithiocarbamate Prevents Neuroinflammation and Cognitive Dysfunction after Endotoxemia in Rats.

Systemic inflammation, for example as a result of infection, often contributes to long-term complications. Neuroinflammation and cognitive decline are key hallmarks of several neurological conditions, including advance age. The contribution of systemic inflammation to the central nervous system (CNS) remains not fully understood. Using a model of peripheral endotoxemia with lipopolysaccharide (LPS) we investigated the role of nuclear factor-κB (NF-κB) activity in mediating long-term neuroinflammation and cognitive dysfunction in aged rats. Herein we describe the anti-inflammatory effects of pyrrolidine dithiocarbamate (PDTC), a selective NF-κB inhibitor, in modulating systemic cytokines including tumor necrosis factor (TNF)-α and interleukin-1β (IL-1β) and CNS markers after LPS exposure in aged rats. In the hippocampus, PDTC not only reduced neuroinflammation by modulating canonical NF-κB activity but also affected IL-1β expression in astrocytes. Parallel effects were observed on behavior and postsynaptic density-95 (PSD95), a marker of synaptic function. Taken together these changes improved acute and long-term cognitive function in aged rats after LPS exposure.

Health problems in elderly patients during the first post-stroke year

BACKGROUND: A wide range of health problems has been reported in elderly post-stroke patients. AIM: The aim of this study was to analyse the prevalence and timing of health problems identified by patient interviews and scrutiny of primary health care and municipality elderly health care records during the first post-stroke year. METHODS: A total of 390 consecutive patients, ≥65 years, discharged alive from hospital after a stroke event, were followed for 1 year post-admission. Information on the health care situation during the first post-stroke year was obtained from primary health care and municipal elderly health care records and through interviews with the stroke survivors, at 1 week after discharge, and 3 and 12 months after hospital admission. RESULTS: More than 90% had some health problem at some time during the year, while based on patient record data only 4-8% had problems during a given week. The prevalence of interview-based health problems was generally higher than record-based prevalence, and the ranking order was moderately different. The most frequently interview-reported problems were associated with perception, activity, and tiredness, while the most common record-based findings indicated pain, bladder and bowel function, and breathing and circulation problems. There was co-occurrence between some problems, such as those relating to cognition, activity, and tiredness. CONCLUSIONS: Almost all patients had a health problem during the year, but few occurred in a given week. Cognitive and communication problems were more common in interview data than record data. Co-occurrence may be used to identify subtle health problems.

Treinamento esfncteriano anal: Estudo transversal em crianças de 3 a 6 anos de idade

Objective: To assess the practice of children's toilet training through interviews with parents and caretakers. Methods: A cross-sectional study of healthy children using a questionnaire applied to parents or caretakers of 100 consecutive children aged 3 to 6 years old. Results: 97% of the children were home-trained by their mothers and 92% of them used their intuition, previous experience with an older child and grandmothers' experience. Bowel and bladder toilet training started simultaneously in 84% of the cases, whereas 41% of the children mastered stool control earlier. Mothers with lower educational level and of social classes C, D and E initiated the training earlier and one of the related reasons was the cost of disposable diapers. Age in initiation or duration of toilet training was similar for boys and girls. Children presented most of the readiness symptoms for toilet training and only a small number of them used a seat reducer or a foot support. There was no increase in constipation prevalence after toilet training and there was no encopresis. Conclusions: Mothers were responsible for bowel toilet training and initiated it with no specialized help. In C-D-E social classes, the cost of diapers was determinant to initiate bowel toilet training.

Avaliação das repercussões do tratamento para câncer invasor do colo uterino no assoalho pélvico

Pós-graduação em Ginecologia, Obstetrícia e Mastologia - FMB

Summary of European Association of Urology (EAU) Guidelines on Neuro-Urology

CONTEXT Most patients with neuro-urological disorders require life-long medical care. The European Association of Urology (EAU) regularly updates guidelines for the diagnosis and treatment of these patients. OBJECTIVE To provide a summary of the 2015 updated EAU Guidelines on Neuro-Urology. EVIDENCE ACQUISITION Structured literature searches in several databases were carried out to update the 2014 guidelines. Levels of evidence and grades of recommendation were assigned where possible. EVIDENCE SYNTHESIS Neurological disorders often cause urinary tract, sexual, and bowel dysfunction. Most neuro-urological patients need life-long care for optimal life expectancy and quality of life. Timely diagnosis and treatment are essential to prevent upper and lower urinary tract deterioration. Clinical assessment should be comprehensive and usually includes a urodynamic investigation. The neuro-urological management must be tailored to the needs of the individual patient and may require a multidisciplinary approach. Sexuality and fertility issues should not be ignored. Numerous conservative and noninvasive possibilities of management are available and should be considered before a surgical approach is chosen. Neuro-urological patients require life-long follow-up and particular attention has to be paid to this aspect of management. CONCLUSIONS The current EAU Guidelines on Neuro-Urology provide an up-to-date overview of the available evidence for adequate diagnosis, treatment, and follow-up of neuro-urological patients. PATIENT SUMMARY Patients with a neurological disorder often suffer from urinary tract, sexual, and bowel dysfunction and life-long care is usually necessary. The update of the EAU Guidelines on Neuro-Urology, summarized in this paper, enables caregivers to provide optimal support to neuro-urological patients. Conservative, noninvasive, or minimally invasive approaches are often possible.

Bladder cancer index: cross-cultural adaptation into Spanish and psychometric evaluation.

BACKGROUND The Bladder Cancer Index (BCI) is so far the only instrument applicable across all bladder cancer patients, independent of tumor infiltration or treatment applied. We developed a Spanish version of the BCI, and assessed its acceptability and metric properties. METHODS For the adaptation into Spanish we used the forward and back-translation method, expert panels, and cognitive debriefing patient interviews. For the assessment of metric properties we used data from 197 bladder cancer patients from a multi-center prospective study. The Spanish BCI and the SF-36 Health Survey were self-administered before and 12 months after treatment. Reliability was estimated by Cronbach's alpha. Construct validity was assessed through the multi-trait multi-method matrix. The magnitude of change was quantified by effect sizes to assess responsiveness. RESULTS Reliability coefficients ranged 0.75-0.97. The validity analysis confirmed moderate associations between the BCI function and bother subscales for urinary (r = 0.61) and bowel (r = 0.53) domains; conceptual independence among all BCI domains (r ≤ 0.3); and low correlation coefficients with the SF-36 scores, ranging 0.14-0.48. Among patients reporting global improvement at follow-up, pre-post treatment changes were statistically significant for the urinary domain and urinary bother subscale, with effect sizes of 0.38 and 0.53. CONCLUSIONS The Spanish BCI is well accepted, reliable, valid, responsive, and similar in performance compared to the original instrument. These findings support its use, both in Spanish and international studies, as a valuable and comprehensive tool for assessing quality of life across a wide range of bladder cancer patients.

Bladder augmentation in rabbits with anionic collagen membrane, with or without urotelial preservation. Cistometric and hystologic evaluation

The use of bowel segments to perform bladder augmentation is associated with several metabolic and surgical complications. A great variety of synthetic materials, biodegradable or not, have been tested. Collagen-based biomaterials have shown effectiveness for the regeneration and obtainment of a functional bladder. Assess the functional and histological response of the rabbit bladder to anionic collagen membrane (ACM), either when it is anastomosed to the bladder or it is placed onto bladder after vesicomyectomy. In 15 male rabbit a partial cystectomy was performed. After 4 weeks they were divided in 3 groups. Group 1 (G1) - bladder augmentation with ACM. Group 2 (G2) ACM is placed onto bladder after vesicomyectomy. Group 3 (G3) control group. Maximal bladder capacity (MBC) and weight were assessed with 4 (M1), 8 (M2) and 12 (M3) weeks after partial cystectomy. In M3 was performed the sacrifice and extraction of the bladder and kidneys for anatomopathologic study. There were neither bladder stones, nor implant extrusion in M3. There was a significant increase in MBC in G1 and G2 (p<0.05), but no statistical differences in G3 (p=0.35). There is no significant difference comparing G1 and G2. In M3, both groups have shown a bigger MBC than G3 (p<0.05). The microscopic assessment showed an inflammatory reaction in the bladder augmented, with urothelium preserved. The ACM was effective for the increase of MBC. The bladders with preservation of the urothelium have shown an extensive inflammatory process.