Differential effects of within-day continuous vs. transient dopamine D2 receptor occupancy in the development of vacuous chewing movements (VCMs) in rats.

Accumulating evidence suggests that antipsychotics (APs) that lead to sustained blockade of dopamine D(2) receptors are more likely to induce acute extrapyramidal side effects (EPS) compared to APs that only occupy D(2) receptors transiently. It is unclear, however, whether a similar relationship exists for long-term AP-induced motoric side effects like tardive dyskinesia (TD). The objective of this study was to ascertain whether transient (via daily subcutaneous (s.c.) injections) vs continuous (via osmotic minipump) AP-induced D(2) receptor occupancy differentially affects the development of haloperidol-induced vacuous chewing movements (VCMs), an animal model of TD. Six groups of 12 rats received 0.1, 0.25, or 1 mg/kg of haloperidol or vehicle (n=36) via osmotic minipump (to provide within-day sustained) or daily s.c. injection (within-day transient) for 8 weeks. VCMs were measured on a weekly basis and D(2) occupancy levels were measured in vivo using [(3)H]-raclopride at the end of the experiment. Minipump-treated rats developed HAL dose-dependent D(2) occupancies of 0.1 mg/kg/day (57%), 0.25 mg/kg/day (70%), and 1 mg/kg/day (88%). S.C.-treated rats also developed HAL dose-dependent D(2) occupancies of 0.1 mg/kg/day (83% peak, 3% trough), 0.25 mg/kg/day (89% peak, 0% trough), and 1 mg/kg/day (94% peak, 17% trough). A total of 43% of rats given 0.25 and 1 mg/kg/day of HAL via minipump developed high VCMs compared to only 8% of the rats given the same doses via daily s.c. injections. The 0.1 mg/kg dose did not give rise to VCMs beyond vehicle levels regardless of the route of administration. These findings support the contention that D(2) occupancy levels induced by chronic HAL must be high and sustained through the day before significant risk of VCMs, and perhaps also TD, emerges.     

Evaluation of bone height and bone density after tooth extraction: an experimental study in minipigs.

OBJECTIVE: The objective of this study was to radiographically quantify bone density and bone height preservation in tooth extraction alveolus filled with xenograft. STUDY DESIGN: The maxillary and mandibular fourth deciduous molars and fourth premolars of 6 minipigs were removed. Randomly, in 3 animals the right side was used as the test side and in the other 3 animals the left side was the test side. Intraoral radiographs were performed to compare the condition at the initial time and 3 months later. Measurements of bone height and bone density were performed using KS300 (Zeiss) software. RESULTS: After 3 months, there was a statistically significant smaller bone height loss for the test group. The test group presented a statistically greater bone density immediately after tooth extraction. However, after 3 months there was no statistically significant difference between the groups. CONCLUSIONS: The results suggest that treatment of postextraction alveolus with xenograft can preserve bone height initially but differences in bone density compared to when no xenograft is used are not sustained.     

Factors associated with mortality and functional disability after hip fracture: an inception cohort study

Hip fracture results in excess mortality and functional disability. This study sought to identify predictors of mortality and limited functional ability 1 year after hip fracture. We conducted a 1-year follow-up of a prospective population-based inception cohort of 218 hip fracture patients who had been consecutively admitted and discharged from hospital during the previous year. Mortality was observed to be independently associated with poor mental status (relative risk [RR]=6.96; 95% confidence interval [95% CI], 1.73–28.00), prefracture limited functional ability (RR=4.35; 95% CI, 1.32–14.36), institutionalized disposition at discharge (RR=2.92; 95% CI, 1.02–8.38), and male gender (RR=2.44; 95% CI, 1.01–5.93). Independent predictors of limited functional ability were prefracture functional disability (RR=34.14; 95% CI, 3.13–372.33), poor mental status (RR=9.71; 95% CI, 1.57–59.82), age >80 years (RR=4.03; 95% CI, 1.48–11.00), and female gender (RR=3.57; 95% CI, 0.08–0.98). On discharge, special attention and care should thus be given to all patients displaying any of the above predictive factors.     

A principal components analysis self-organizing map.

We propose a new self-organizing neural model that performs principal components analysis. It is also related to the adaptive subspace self-organizing map (ASSOM) network, but its training equations are simpler. Experimental results are reported, which show that the new model has better performance than the ASSOM network.     

Lung Cancer and COPD: a Common Combination

Background and objectiveTo analyse frequency, characteristics and patient survival with lung cancer (LC) and Common Obstructive Pulmonary Disease (COPD), comparing them with patients that do not have COPD.Material and methodsA retrospective study, of patients diagnosed by means of cytohistology. Survival was estimated by the Kaplan-Meier method. Statistical analysis was carried out using SPSS 15.0.ResultsA total of 996 patients were diagnosed, 39.8% with COPD. Mean age70±9.19 years. GOLD stages: I 18.2%, II 53.6%, III 24%, IV 4.2%. The histological types: squamous cell carcinoma 48.2%, adenocarcinoma 22%, and small cell carcinoma 22.5%. Survival was longer in the COPD group.ConclusionsLC and COPD are combined in 39.8%. Squamous cell type is more frequent and survival was longer in the COPD group.     

Program for the Prevention of Smoking in Secondary School Students

Background and ObjectiveSchool smoking prevention programs have never yielded the expected results. The aim of this study was to analyze the efficacy of an intensive smoking prevention program created by the educational community in which it was to be applied.Population and MethodA 3-year smoking prevention program was carried out among the students of Fuentesaúco Secondary School in Zamora, Spain. The Babilafuente Secondary School in Salamanca, Spain was the control group. The program included both prevention and treatment activities. The former were carried out in the school, in out-of-school situations, and in the community. The questionnaire of the European Smoking Prevention Framework Approach was used.ResultsA total of 417 students aged 12 to 17 years participated in the study. Of these, 54.4% belonged to the intervention group and 45.6% to the control group. Smokers represented 36.7% of the population. After the intervention smokers represented 40.1% of the Fuentesaúco students compared with 46.1% of the Babilafuente students, though the difference was not statistically significant. With respect to the cognitive determinants of smoking behavior, after the intervention significant differences in favor of the intervention group were only observed in the subjects’ perception of the behavior of their siblings, peers, and teachers.ConclusionsThe use of smoking prevention programs in schools should be reconsidered, and their evaluation should be based on educational rather than clinical criteria. Proposed changes in the program include decreasing its intensity, starting with students of an earlier age and seeking greater involvement of parents.     

Plasma levels and vascular effects of vasopressin in patients undergoing coronary artery bypass grafting.

OBJECTIVE: Recent studies have suggested that endogenous vasopressin (AVP) acts as a spasmogen during coronary artery bypass grafting (CABG). Given that AVP could induce vasospasm in the grafted vessel, we assessed the release of this peptide during and after CABG, and explored ways of counteracting its contractile effect on the internal mammary artery (IMA). METHODS: Plasma levels of AVP were determined by radioimmunoassay in 16 patients before, during and after CABG. Using isometric force recording techniques, we also investigated the mechanisms involved in the contractile effect of AVP in ring preparations of IMA specimens taken from 95 patients. RESULTS: Plasma AVP levels peaked after the start of cardiopulmonary bypass (CPB) and correlated well with serum osmolality (Pearson's r=0.9490; P<0.0001; n=16). An inverse correlation was observed between plasma AVP levels recorded at this stage and the maximal contraction induced in vitro by AVP in vascular rings from the same patients (Pearson's r=-0.6968; P<0.01; n=16). No change in the AVP response was produced by endothelium removal, exposure to the NO precursor (3 x 10(-4)M L-arginine), inhibition of nitric oxide (NO) synthase (3 x 10(-5) M L-NAME) or soluble guanylate cyclase (3 x 10(-6) M 1H-[1,2,4]oxadiazol [4,3,-alpha]quinoxalin-1-one (ODQ)), removal of the superoxide anion (100 U/ml superoxide dismutase (SOD) plus 1200 U/ml catalase) or hydroxyl radical (10(-4) M deferoxamine), or specific alpha1 - (10(-6) M prazosin) or endothelin (10(-5) M bosentan) receptor antagonism. In contrast, adenylate cyclase activation (3 x 10(-8) M forskolin) reduced the contractile response to AVP, while prostanoid synthesis (3 x 10(-6) M indomethacin) inhibition and blockade of Ca2+ -activated potassium channels (KCa) (10(-3) M tetraethylammonium (TEA)) enhanced AVP contraction. Age, gender and smoking also modified the AVP response. CONCLUSION: Our findings suggest a role for AVP as a modulator of vascular tone in human IMA. The effect of AVP is dependent on prostanoids and Ca2+ -activated K+ channels, so its dysfunction in pathophysiological cardiovascular processes could mean that AVP, among other factors, produces vasospasm in IMA grafts.