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.     

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.     

Monotherapy with enoxaparin for the prevention of recurrent venous thromboembolism.

This study aimed to determine whether a weight-adjusted dose of subcutaneous enoxaparin is as effective and safe as oral acenocoumarol for the secondary prophylaxis of pulmonary embolism. Three hundred and eighty consecutive noncancer outpatients hospitalized with an episode of symptomatic pulmonary embolism selected treatment with acenocoumarol or enoxaparin at a dose of 1 mg/kg once daily after being informed of the type of administration and expected frequency of laboratory monitoring for both medicinal products. Endpoints were symptomatic recurrent thromboembolic events evaluated by standard objective testing, and a composite endpoint of recurrent venous thromboembolism, major bleeding, and death from any cause. One hundred and ninety-nine patients (52%) chose acenocoumarol therapy and 181 chose enoxaparin monotherapy. Four patients in the enoxaparin group (2.2%) and six patients in the acenocoumarol group (3%) had an objective thromboembolic recurrence (hazard ratio, 1.35; 95% confidence interval, 0.38-4.79; P = 0.64). Nine patients in the enoxaparin group (5.0%) had a hemorrhagic complication compared with 11 in the acenocoumarol group (5.5%) (P = 0.81). The hospital length of stay was shorter with enoxaparin compared with acenocoumarol (11 versus 16 days, P = 0.0001). Enoxaparin is as effective and safe as acenocoumarol in the secondary prevention of recurrent thromboembolic disease and is associated with shorter hospitalization.     

Diagnostic value of D-dimer in outpatients with suspected deep venous thrombosis receiving oral anticoagulation.

D-dimer has proved a useful diagnostic tool for the exclusion of deep venous thrombosis (DVT). The objective of this paper was to evaluate the diagnostic performance of a diagnostic algorithm combining clinical probability and D-dimer in outpatients receiving oral anticoagulant treatment (OAT) similar to those regularly applied to nonanticoagulated individuals. We enrolled 70 outpatients on OAT who presented with clinically suspected DVT; a standard diagnostic algorithm including clinical evaluation using the modified Wells score and a quantitative immunoturbidimetric D-dimer assay (STA Liatest D-Di; Diagnostica Stago, Asniéres sur Seine, France) was used. A 3-month follow-up period was applied for those patients in whom DVT was initially excluded. The prevalence of DVT was 18.5% (13/70); four of the diagnoses were made during the 3-month follow-up period. The sensitivity, specificity and negative predictive value of D-dimer were 69.2% (95 confidence interval, 42.4-87.3), 47.4% (95% confidence interval, 35.0-60.1) and 87.1% (95% confidence interval, 71.1-94.9), respectively. In conclusion, D-dimer is of limited value in outpatients on OAT presenting with clinically suspected DVT and should be omitted in such individuals; these patients should always undergo compression venous ultrasound, and repeat ultrasonography within 1 week might be warranted in cases with an initial negative examination.     

Composite prostheses for the repair of abdominal wall defects: effect of the structure of the adhesion barrier component

The component of a composite prosthesis, which makes contact with the visceral peritoneum, can be reabsorbable or non-reabsorbable, and laminar or reticular. This study was designed to determine whether the composition of this second, barrier component could improve its behavior at this interface. Abdominal wall defects in rabbits were repaired using a polypropylene prosthesis (PP), or the composites Sepramesh (PP+h) or Vicryl (PP+v). Fourteen days after surgery, the implants were evaluated by light and scanning electron microscopy, and immunohistochemistry. Prosthetic areas occupied by adhesions (PP: 71.08±5.09, PP+h: 18.55±4.96, P+v: 69.69±16.81%), neoperitoneal thickness (PP: 256.17±21.68, PP+h: 83.11±19.63, PP+v:213.72±35.90 μm) and macrophage counts (PP: 8.73±1.16, PP+h: 27.33±4.13, PP+v: 31.24±3.08%) showed significant differences (P<0.05). The tested biomaterials induced an optimal recipient tissue infiltration. Least adhesion formation was observed on the PP+h implants. This suggests that the second component, although reabsorbable, should be smooth in structure.