Oral Anticoagulants and Atrial Fibrillation: An Update for the Clinical Nurse.

Anticoagulation is an important strategy for the prevention of stroke associated with atrial fibrillation. Development of new oral agents has created a need to educate nurses to administer these medications and provide patient education.

A transgenic Alzheimer rat with plaques, tau pathology, behavioral impairment, oligomeric aß, and frank neuronal loss.

Alzheimer's disease (AD) is hallmarked by amyloid plaques, neurofibrillary tangles, and widespread cortical neuronal loss (Selkoe, 2001). The "amyloid cascade hypothesis" posits that cerebral amyloid sets neurotoxic events into motion that precipitate Alzheimer dementia (Hardy and Allsop, 1991). Yet, faithful recapitulation of all AD features in widely used transgenic (Tg) mice engineered to overproduce Aß peptides has been elusive. We have developed a Tg rat model (line TgF344-AD) expressing mutant human amyloid precursor protein (APPsw) and presenilin 1 (PS1ΔE9) genes, each independent causes of early-onset familial AD. TgF344-AD rats manifest age-dependent cerebral amyloidosis that precedes tauopathy, gliosis, apoptotic loss of neurons in the cerebral cortex and hippocampus, and cognitive disturbance. These results demonstrate progressive neurodegeneration of the Alzheimer type in these animals. The TgF344-AD rat fills a critical need for a next-generation animal model to enable basic and translational AD research.

Acamprosate attenuates cue-induced reinstatement of nicotine-seeking behavior in rats.

Acamprosate is used in the treatment of alcoholism; however, there is little information on its effects on nicotine addiction. The objective of this study was to determine whether acamprosate inhibits cue-induced relapse to nicotine self-administration in the rat. Rats were trained to press a lever to obtain intravenous infusions of nicotine (0.03 mg/kg/infusion) that were associated with the illumination of a cue light. After 29 days of nicotine self-administration sessions, extinction sessions were run during which responses on the active lever did not result in the infusion of nicotine or the illumination of the cue light. After 14 days of extinction sessions the rats received twice-daily injections of saline or acamprosate (50, 100, or 200 mg/kg/intraperitoneally). Seven days later the response to the previously conditioned cue was tested, but only saline infusions were delivered. Pretreatment with all doses of acamprosate reduced responding to a cue previously associated with nicotine. The lowest dose of acamprosate (50 mg/kg) reduced responding for the cue previously associated with nicotine infusions, but had no effect on food-rewarded behavior. These results show that acamprosate reduced cue-induced nicotine-seeking behavior and suggest that acamprosate might be efficacious in treating nicotine addiction in humans.

Impact of clinical variables on predicting disease-free survival of patients with surgically resected renal cell carcinoma.

OBJECTIVE: To determine the value of particular clinical variables for the preoperative prognostic Cindolo formula (PPCF) to predict disease-free survival (DFS) of patients with surgically treated renal cell carcinoma (RCC). PATIENTS AND METHODS: In all, 771 consecutive patients (T1-4NxM0) who had radical or partial nephrectomy were reviewed retrospectively. For each patient with RCC, PPCF was constructed according to clinical size and clinical presentation. On the basis of PPCF, patients were divided into Cindolo good prognosis (CGP) and Cindolo poor prognosis (CPP) groups. We also analysed further clinical variables (Eastern Cooperative Oncology Group score, American Society of Anesthesiologists score, body mass index, hepatic dysfunction, night sweat, fever, value of blood platelets, leukocytes, haemoglobin level, gender, age and location). DFS was estimated using the Kaplan-Meier method. Univariable and multivariable Cox proportional hazard regression models were fitted to determine associations between the PPCF, measured clinical features, and DFS. RESULTS: Four of the variables emerged as statistically significant for DFS from the univariable analysis (P < 0.001), i.e. clinical presentation, clinical tumour size, haemoglobin level and blood platelet count. In the multivariable analysis, only clinical tumour size and blood platelet count remained significant for DFS. By contrast, clinical presentation, used in the PPCF, had no significant influence. According to the PPCF we developed the preoperative Amissah Prognosis Score (PAPS) calculated as (0.19 x clinical size) + (0.492 x platelet count (400/nL = 1) with a threshold between the two resulting prognosis groups at 1.76. The multivariable hazard ratio (95% confidence interval, CI) for the PAPS was 2.98 (2.15-4.12) (P < 0.001) compared to a hazard ratio for the PPCF of 1.36 (0.99-1.87) (P = 0.061). Furthermore, the predictive ability was greater when using the PAPS (area under the curve 0.721; 95% CI, 0.680-0.763; P

Worry, desire, and sexual satisfaction and their association with severity of ED and age.

INTRODUCTION: This study evaluates worry about sexual and relationship functioning, sexual desire, and sexual satisfaction as indicators of sexual quality of life in men of different age groups suffering from mild to severe erectile dysfunction (ED). AIM: To increase insight in the mechanisms of some key indicators of sexual quality of life in different age groups. METHODS: The study sample consisted of 904 men with mild to severe ED. Mean age was 60.7 years (standard deviation [SD] = 12.4) and mean erectile function (EF) (International Index of Erectile Function [IIEF]) score was 14.5 (SD = 8.9). Multivariate analyses of variance were conducted to test the differences in outcomes among two age groups (65 65) and two levels of ED (16 16). MAIN OUTCOME MEASURES: We analyzed age, severity of ED, and interrelated indicators of sexual quality of life as worry about sexual or relationship functioning, sexual desire, and overall sexual satisfaction. Beyond, we aimed to see on which of these measures their interaction had specific independent effects. RESULTS: Younger men at a higher level of ED reported higher levels of worry about sexual and relationship functioning than older men with high ED. Older men reported slightly less sexual desire than younger men; also, more ED was associated with lower sexual desire. Finally, men with less severe ED reported higher sexual satisfaction than men with more severe ED, whereas at all levels of ED severity, older men reported more sexual satisfaction than younger men. CONCLUSIONS: Indicators of sexual quality of life among men with ED are poorer in those with more severe ED. However, younger men with severe ED worries concerning sexual functioning were more pronounced than among their older counterparts. Independent of the degree of severity of ED, older men indicated lower sexual desire but higher overall sexual satisfaction. Observed age-group differences were very small, however.

Eszopiclone stimulates the hypothalamo-pituitary-adrenal axis in the rat.

Eszopiclone (Lunesta®) is used for the treatment of insomnia. It is the S (+)-enantiomer of racemic zopiclone, a cyclopyrrolone with no structural similarity to the hypnotic drugs zolpidem and zaleplon or to the benzodiazepines and barbiturates. Although eszopiclone interacts with the gamma-aminobutyric acid A-type (GABA(A)) receptor complex, it has a different binding profile than other sedative/hypnotic agents and modulates the receptor complex in a unique manner. Thus, eszopiclone might produce different pharmacological effects compared to other sedative/hypnotic agents. Beside their behavioral properties, sedative/hypnotic drugs affect the hypothalamo-pituitary-adrenal (HPA) axis. In general, low doses of benzodiazepine-type drugs decrease, whereas high doses increase the activity of the HPA axis. Furthermore, benzodiazepines reduce stress-induced increases in HPA axis activity. The goal of the present study was to characterize the effects of eszopiclone on the HPA axis in the rat. Male rats were injected with saline or eszopiclone and trunk blood was collected for the measurement of plasma levels of adrenocorticotropin (ACTH) and corticosterone by radioimmunoassay. The acute administration of eszopiclone produced dose-dependent increases in plasma levels of ACTH and corticosterone, and tolerance developed to these effects after repeated drug administration. Pretreatment with eszopiclone did not affect stress-induced stimulation of the HPA axis. These results show that eszopiclone and the benzodiazepine-type drugs differentially affect the HPA axis.

Erectile dysfunction, discrepancy between high prevalence and low utilization of treatment options: results from the 'Cottbus Survey' with 10 000 men.

OBJECTIVE: To investigate the age-stratified prevalence of erectile dysfunction (ED) and its comorbidities, and to assess the population's knowledge, utilization, and general attitude towards the treatment for ED. SUBJECTS AND METHODS: In all, 10 000 men received a 35-item questionnaire including the International Index of Erectile Function (IIEF) and sociodemographic questions regarding life style, comorbidities, quality of sexual life and knowledge or experience of ED therapy. In all, 3124 responses were included (31.2%), 2499 men lived in well established partnerships and were assessed as the basic study group. RESULTS: In the entire population the prevalence rate of ED was 40.1%. However, although known, medical treatment for ED is used only by a minority of affected men. The prevalence of ED was independently associated with age, peripheral arterial occlusive disease, hypertension, ischaemic heart disease, diabetes mellitus, and liver diseases. Correlations between sexual quality of life (QoL) and ED were statistically significant (P < 0.01) and moderate to strong (absolute values: Spearman's rho 0.35-0.76). Although 96% of the study population knew at least one phosphodiesterase type 5 (PDE5) inhibitor by name, only 53% considered taking the medication and only 9% of the men with ED had had experience with available PDE5 inhibitors. CONCLUSIONS: The sexual QoL was significantly reduced by ED. Despite high levels of awareness and general acceptance of oral medication for ED, experience with PDE5 inhibitors was low. Further investigation is required to evaluate the general impact of ED on sexual QoL and the need or wish for treatment.