Alpha-adrenoceptor-mediated modulation of 5-HT2 receptor agonist induced impulsive responding in a 5-choice serial reaction time task

The activation of 5-HT2A receptors has been shown to enhance the probability of premature responding, regarded as a form of motor impulsive behaviour. At the behavioural level, the interaction of alpha-adrenoceptors and 5-HT2 receptors has been linked to head twitch behaviour, regarded as an experimental model of compulsive behaviour. The aim was to determine whether the probability of premature responding induced by an excess activation of 5-HT2A receptors can be modulated by the blockade of alpha1- or alpha2- adrenoceptors. In the experiments, the 5-choice serial reaction time task was used to measure attention and response control of the rats. The experiments assessed the effects of (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI) 0.1-0.2 mg/kg subcutaneously, a 5-HT2A/2C agonist, and prazosin, an alpha1-adrenoceptor antagonist, alone or in combination, on the performance of rats. In an additional experiment to examine the possible role of the alpha2-adrenoceptors, a potent, selective and specific alpha2-adrenoceptor antagonist, atipamezole, was given alone or in combination with DOI. Results showed that DOI increased the probability of premature responses, but it did not affect the choice accuracy. Prazosin (0.1 or 0.3 mg/kg, subcutaneously), given on its own had no effects on probability of responding prematurely, but prazosin (0.3 mg/kg.) was able to attenuate the DOI-induced responding. Atipamezole (0.1 mg/kg, s.c.) did not attenuate the effect of DOI on probability of premature responding. When given at lower doses, DOI (0.03 mg/kg) and atipamezole (0.03 mg/kg) synergistically increased the probability of premature responding, whereas a higher dose of atipamezole (0.3 mg/kg) on its own increased the probability of responding prematurely, but this effect was not additive to that of 0.1 mg/kg DOI. These data indicate that 5-HT2 receptor activation enhances impulsive responding and this effect can be diminished by the blockade of alpha1-adrenoceptors. Atipamezole, an alpha2-antagonist, enhances the probability of premature responding and shares the mechanism of action with the 5-HT2 agonist in this respect. These results provide evidence for an interaction between the serotonergic 5-HT2 receptors and alpha-adrenoceptors in the modulation of response control to the motor impulsivity type of behaviour (premature responding) in addition to that of compulsory behaviour (head shakes) found previously.     

Galanin and neuropeptide Y reduce cholinergic transmission in the heart of the anaesthetised mouse

(1) This study investigated the effects of galanin (GAL) on inhibition of cholinergic (vagal) activity in the mouse heart using control galanin knockout (GAL-KO) and GAL-1R receptor knockout (GAL-1R-KO) mice. (2) In pentobarbitone anaesthetised mice, supramaximal stimulation every 30 s of the vagus nerve innervating the heart, increased pulse interval (PI) by approximately 50 ms or decreased heart rate by approximately 100 beats min-1. This response was attenuated by intravenous administration of GAL (dose ranged from 0.8 to 13 nmol kg-1) in a dose-dependent manner. (3) In GAL-KO mice, the magnitude of inhibition of the increase in PI (DeltaPI) following a bolus dose of GAL was not different from the DeltaPI in control mice, and neuropeptide Y (NPY), previously shown to attenuate vagal inhibitory activity in mice, evoked a comparative inhibition of DeltaPI in GAL-KO mice. (4) In GAL-1R-KO mice, an intravenous, bolus injection of GAL had no inhibitory effect on vagal activity. (5) In control mice, stimulation of the sympathetic nerve at 25 V, 10 Hz for 2 min in the presence of propranolol evoked a long-lasting attenuation of DeltaPI. The inhibitory effect on DeltaPI was reduced in the presence of the NPY Y2 antagonist, BIIE0246. (6) In GAL-1R-KO mice, stimulation of the sympathetic nerve in the presence of propranolol evoked an attenuation of DeltaPI not significantly different from the response in control mice in the presence of BIIE0246. Following administration of BIIE0246 in GAL-1R-KO mice, the inhibition of DeltaPI that followed stimulation of the sympathetic nerve was abolished. (7) These findings support the view that the nerve terminals of parasympathetic neurons in the mouse heart possess both GAL-1R and NPY Y2 receptors which, when activated, reduce acetylcholine release.     

Urinary incontinence in a Finnish population aged 70 and over. Prevalence of types, associated factors and self-reported treatments

OBJECTIVE: To describe the prevalence, associated factors and self-reported treatments of different types of incontinence in a random older population. DESIGN: A population-based cross-sectional survey. SETTING: Third wave for the Tampere Longitudinal Study on Ageing (TamELSA) in 1999. SUBJECTS: 171 men and 227 women aged 70 and over. MAIN OUTCOME MEASURES: Urge and mixed incontinence combined and associated health and social indicators. RESULTS: The prevalence of stress, urge and mixed incontinence was 2%, 17% and 6%, respectively, in men and 23%, 6% and 30%, respectively, in women. In the logistic regression analyses adjusted for age, urge and mixed incontinence in women were associated with living in an institution (OR [odds ratiol 13.55), comorbidity (OR 1.94), ADL (activities of daily living) disability (OR 3.55), depressive mood (OR 2.49) and fecal incontinence (OR 7.84), while in men an association was found between urge and mixed incontinence and ADL disability (OR 2.59) and depressive mood (OR 2.69). All the men living in an institution were incontinent of urine. Of the incontinent women, 46% used diapers, but collecting devices were rare in men. CONCLUSION: The results emphasise the significance and multifactorial nature of the urge component in geriatric incontinence, which should be considered in both geriatric and general practice.     

Serum lycopene concentrations and carotid atherosclerosis: the Kuopio Ischaemic Heart Disease Risk Factor Study

BACKGROUND: Interest in lycopene is growing rapidly following the recent publication of epidemiologic studies in which high circulating lycopene concentrations were associated with reductions in cardiovascular disease. Lycopene is one of the major carotenoids in the Western diet and is probably one of the protective factors in a vegetable-rich diet. OBJECTIVE: We studied the hypothesis that the intima-media thickness of the common carotid artery (CCA-IMT) would be greater in men with low serum lycopene concentrations. DESIGN: We investigated the relation between serum lycopene concentration and CCA-IMT in 1028 middle-aged men (aged 46-64 y) in eastern Finland who were participants in the Kuopio Ischaemic Heart Disease Risk Factor study and who were examined in 1991-1993. The subjects were classified into quarters according to serum lycopene concentration. RESULTS: In a covariance analysis with adjustment for covariates, the men in the lowest quarter of serum lycopene concentration had a significantly higher mean CCA-IMT and maximal CCA-IMT (P = 0.005 and P = 0.001 for the difference, respectively) than did the other men. The mean and maximal CCA-IMT increased linearly across the quarters of serum lycopene concentration. CONCLUSIONS: A low serum lycopene concentration is associated with a higher CCA-IMT in middle-aged men from eastern Finland. This finding suggests that the serum lycopene concentration may play a role in the early stages of atherosclerosis. Increased thickness of the intima-media has been shown to predict coronary events; thus, lycopene intakes and serum concentrations may have clinical and public health relevance.     

Immunization of Early Adolescent Females with Human Papillomavirus Type 16 and 18 L1 Virus-Like Particle Vaccine Containing AS04 Adjuvant

PurposeIn female individuals 15–25-years of age, the AS04-containing human papillomavirus (HPV)–16/18 vaccine is highly immunogenic and provides up to 100% protection against HPV-16/18 persistent infection and associated cervical lesions up to 4.5 years. Optimal cervical cancer prevention will require prophylactic vaccination against oncogenic HPV 16 and 18 before the onset of sexual activity in early adolescent girls. To establish the feasibility of vaccination in girls 10–14 years of age, we compared the immunogenicity and safety in early adolescent female individuals to those 15–25 years in whom vaccine efficacy has been demonstrated.MethodsWe enrolled 773 female participants aged 10–14 years and 15–25 years to receive the HPV-16/18 L1 VLP AS04 vaccine, which was administered at months 0, 1, and 6. Serum samples were collected at months 0 and 7; antibodies to HPV 16 and 18 VLPs were measured by enzyme-linked immunosorbent assay. Vaccine safety was assessed at 7 or 30 days after each dose; serious adverse events were recorded during the entire study period.ResultsBoth age groups achieved 100% seroconversion for HPV 16 and 18. Participants in the group aged 10–14 years were not only noninferior to those 15–25 years in terms of HPV 16 and 18 seroconversion rates but also had approximately twice as high geometric mean titers. The vaccine was generally safe and well tolerated.ConclusionsThese findings suggest that HPV vaccination during early adolescence is generally safe, well tolerated, and highly immunogenic. The observed higher antibody titers in the group 10–14 years of age are likely to result in longer antibody persistence. Overall, these data support the implementation of prophylactic HPV vaccination in this age group.     

A preliminary report--heparin counteracts indomethacin effect on ductus arteriosus in very low birthweight infants.

OBJECTIVE: We report a clinical observation showing that continuous exposure to heparin via a central venous catheter is associated with patent ductus arteriosus treatment failure with indomethacin in very low birthweight infants. STUDY SELECTION: A clinical observational case report in infants weighting <1501 g. DATA EXTRACTION: This study compares the rates of patent ductus arteriosus treatment failure during a) the index period from June 2, 2003, to August 22, 2003, when all very low birthweight infants with a peripherally inserted central venous catheter received continuous infusion of heparinized parenteral nutrition; b) the baseline period of 1 yr before the index period; and c) the postindex period of 1 yr after the index period. DATA SYNTHESIS: The rate of patent ductus arteriosus treatment failure with indomethacin increased significantly during the index period compared with the baseline (odds ratio, 7.0; 95% confidence interval, 1.41-34.7; p = .017) and postindex periods (odds ratio, 33.8; 95% confidence interval, 4.72-243; p = .0005). The result was confirmed in logistic multivariable regression analysis. CONCLUSION: This observation, based on a case series and their controls, serves as a basis for a new hypothesis suggesting that continuous exposure to heparin through heparinized central venous infusion significantly increases patent ductus arteriosus treatment failure with indomethacin. This hypothesis needs to be tested in a randomized controlled trial.     

Incremental cost‐effectiveness of double‐reading mammograms

Background. Double reading is a widely used criterion standard in breast cancer screening despite a lack of evidence of the costeffectiveness of the second reading. This study evaluates the incremental costeffectiveness of such a strategy.Design. Costeffectiveness analysis: Nationwide populationbased semiannual screening program for women aged 50–59 in Finland. Participation rate was 91%. All mammograms (95,423) performed during 1990–1995 in three screening centers of the Finnish Cancer Society were read by two radiologists with gradings recorded. The effectiveness of the double reading was the difference in cancers detected in the double compared to that of the single reading. Incremental costs of the double reading for the health care and nonhealth care and the time costs were estimated. The main outcome measure was the incremental cost per additional cancer found as a result of the doublereading strategy.Results. The total number of cancers detected with the double and single reading were 290 and 261, respectively. A significantly higher ratio of carcinoma in situ was the causative pathology in cancers detected only by the second reader. The cost per cancer detected with a single reading was US$ 18,340. The incremental cost of any additional cancer found was US$ 25,523, that is, a 39% higher cost per additional cancer found by double reading.Conclusions. The additional cost per cancer detected by double reading is not drastically higher than with single reading. However, the additional cost per life year saved may be much higher.     

Late hearing results after paraffinplasty or silastic sheeting

Summary The long-term hearing results are presented for 135 ears operated on radically. In 59 of the ears temporary paraffin filling of the tympanic cavity was employed after the removal of the typanic mucosa at operation. The filling material was removed, and the ossiculoplasty was performed about 6 months later. In 76 ears a one-stage operation with tympanoplasty and Silastic sheeting was employed.There were no statistical differences between the groups of ears mentioned according to hearing results early (1 year) or late (5–14 years) postoperatively or in the deterioration of the air-bone gaps after the first postoperative year (P>0.05). The late change in the air-bone gap was significant in both groups (paraffin group: 6.1 dB; Silastic sheeting group: 5.7 dB; P<0.05). The total improvement of hearing late after surgery (as compared to the preoperative hearing) was significantly better in the paraffin group than in ears with Silastic sheeting (P<0.05). Paraffinplasty seems to be a suitable way to avoid tympanic adhesions.     

The preoperative state of infection in chronic otitis media correlated with postoperative hearing results

Summary The postoperative long-term hearing results, with special reference to the state and management of the tympanic mucosa at operation, in 627 ears (574 patients) after an annual clinical follow-up period of 5–14 years are presented. The ears were operated on radically due to chronic otitis media, using the obliterative radical operation technique developed by T. Palva. The air-bone gap improved from the preoperative level significantly more in ears where the tympanic mucosa had been preserved than in ears where it had been removed at operation (p < 0.001). The improvement was also significantly better in dry ears than in ears which were moist or discharging at operation (p < 0.05). The mean late deterioration in the air-bone gap after the first follow-up year was significant in all the groups of ears (p < 0.05), and the mean long-term change in air-bone gap from pre- to late postoperative examination was the improvement of 3.0 dB in ears with, and a deterioration of 2.0 dB in ears without ossicular reconstruction.