Reversal of startle gating deficits in transgenic mice overexpressing corticotropin-releasing factor by antipsychotic drugs.

Chronically elevated levels of corticotropin-releasing factor (CRF) in transgenic mice overexpressing CRF in the brain (CRF-OE) appear to be associated with alterations commonly associated with major depressive disorder, as well as with sensorimotor gating deficits commonly associated with schizophrenia. In the present study, we tested the hypothesis that antipsychotics may be effective in normalizing prepulse inhibition (PPI) of acoustic startle in CRF-OE mice, which display impaired sensorimotor gating compared to wild-type (WT) mice. The typical antipsychotic haloperidol and atypical antipsychotic risperidone improved PPI in the CRF-OE mice, but were ineffective in WT mice. The atypical antipsychotic clozapine did not influence PPI in CRF-OE mice, but reduced gating in WT mice. This effect of clozapine in the CRF-OE mice may thus be regarded as a relative improvement, consistent with the observed effect of haloperidol and risperidone. As expected, the anxiolytic, nonantipsychotic chlordiazepoxide was devoid of any effect. All four compounds dose-dependently reduced the acoustic startle response irrespective of genotype. These results indicate that antipsychotic drugs are effective in improving startle gating deficits in the CRF-OE mice. Hence, the CRF-OE mouse model may represent an animal model for certain aspects of psychotic depression, and could be a valuable tool for research addressing the impact of chronically elevated levels of CRF on information processing.     

Morbidity, mortality, and long-term survival after sleeve lobectomy for non-small cell lung cancer.

OBJECTIVE: Sleeve lobectomy is a widely accepted procedure for central tumors for which the alternative is pneumonectomy. The purpose of this study is to assess operative mortality, morbidity, and long-term results of sleeve lobectomies performed for non-small cell lung carcinoma (NSCLC). METHODS: A retrospective review of 218 patients who underwent sleeve lobectomy for NSCLC between 1981 and 2005 was undertaken. There were 186 (85%) men and 32 women with a mean age of 61.9 years (range, 19-82 years). Eighty patients (36.6%) had a preoperative contraindication to pneumonectomy. Right upper lobectomy was the most common operation (45.4%). Vascular sleeve resection was performed in 28 patients (12.8%) and was commonly associated with left upper lobectomy (n=20; 9.1%; p=0.0001). The histologic type was predominantly squamous cell carcinoma (n=164; 75%), followed by adenocarcinoma (n=46; 21%). Resection was incomplete in nine (4.1%) patients. RESULTS: There were nine operative deaths; the operative mortality and the morbidity rates were 4.1% and 22.9%, respectively. A total of 14 (6.4%) patients presented with bronchial anastomotic complications: two were fatal postoperatively, seven patients required reoperation, three required a stent insertion, and two were managed conservatively. Multivariate analysis showed that compromised patients (p=0.001), current smoking (p=0.01), right sided resections (p=0.003), bilobectomy (p=0.03), squamous cell carcinoma (p=0.03), and presence of N1 or N2 disease (p=0.01) were risk factors for mortality and morbidity. Follow-up was complete in 208 patients (95.4%). Overall 5-year and 10-year survival rates were 53% and 28.6%, respectively. After complete resection, recurrence was local in 10 patients, mediastinal in 20, and distant in 25. By multivariate analysis, two factors significantly and independently influenced survival: nodal status (N0-N1 vs N2; p=0.01) and the stage of the lung cancer (stage I-II vs III, p=0.02). CONCLUSIONS: For patients with NSCLC, sleeve lobectomy achieves local tumor control, even in patients with preoperative contraindication to pneumonectomy and is associated with low mortality and bronchial anastomotic complication rates. Postoperative complications are higher in compromised patients, smokers, N disease, right sided resections, bilobectomies, and squamous cell cancers. The presence of N2 disease and stage III significantly worsen the prognosis.     

Four-Year Follow-up on Endovascular Radiofrequency Obliteration of Great Saphenous Reflux

BACKGROUND: Endovascular radiofrequency obliteration has been used since 1998 as an alternative to conventional vein stripping surgery for elimination of saphenous vein insufficiency. OBJECTIVE: To demonstrate the long-term efficacy of this treatment modality. METHODS: Data were prospectively collected in a multicenter ongoing registry. Only great saphenous vein above-knee treatments were included in this study. Eight hundred ninety patients (1,078 limbs) were treated prior to November 2003 at 32 centers. Clinical and duplex ultrasound follow-up was performed at 1 week, 6 months, and 1, 2, 3, and 4 years. RESULTS: Among 1,078 limbs treated, 858 were available for follow-up within 1 week, 446 at 6 months, 384 at 1 year, 210 at 2 years, 114 at 3 years, and 98 at 4 years. The vein occlusion rates were 91.0%, 88.8%, 86.2%, 84.2%, and 88.8%, respectively; the reflux-free rates were 91.0%, 89.3%, 86.2%, 86.0%, and 85.7%, respectively; and the varicose vein recurrence rates were 7.2%, 13.5%, 17.1%, 14.0%, and 21.4%, respectively, at each follow-up time point at 6 months, and 1, 2, 3, and 4 years. Patient symptom improvement persisted over 4 years. CONCLUSIONS: Endovascular temperature-controlled radiofrequency obliteration of saphenous vein reflux exhibits an enduring treatment efficacy clinically, anatomically, and hemodynamically up to 4 years following treatment.     

Efficacy of piribedil as early combination to levodopa in patients with stable Parkinson's disease: a 6-month, randomized, placebo-controlled study.

Piribedil is a non-ergot D2/D3 agonist with a significant antagonist action on alpha2A and alpha2C adrenergic receptor subtypes. This double-blind placebo-controlled study was undertaken to confirm the efficacy of 150 mg/day piribedil po in improving motor symptoms of idiopathic Parkinson's disease (PD) in nonfluctuating patients insufficiently controlled by a stable daily dose of levodopa (L-dopa). Efficacy was assessed using the Unified Parkinson's Disease Rating Scale (UPDRS) III score as primary criterion over 4 months. A second comparison was planned at 6 months, after possible adjustment of L-dopa. At 4 months, the rate of response, defined as a 30% decrease from baseline on UPDRS III score, was significantly greater with piribedil compared with placebo (56.4% vs. 37.7%; P = 0.040). At 6 months, the better efficacy of piribedil was maintained (61.8% of responders vs. 39.6% on placebo; P = 0.020). The difference between groups on UPDRS III change from baseline reached statistical significance only at 6 months: -10.0 points in the piribedil group vs. -6.7 points in the placebo group (P = 0.037). Secondary end-points were not significantly different. The most frequently reported adverse events were gastrointestinal symptoms (27 of 61 patients in the piribedil group vs. 13 of 54 patients in the placebo group). In conclusion, a 6-month oral administration of 150 mg/day piribedil in combination with L-dopa is well tolerated, except for minor gastrointestinal symptoms at the beginning of the treatment and significantly improves motor symptoms compared with placebo in PD nonfluctuating patients.     

Assessment of disease activity in rheumatoid arthritis with (18)F-FDG PET.

The aim of this study was to assess synovitis by (18)F-FDG PET in an individual joint analysis and in a global analysis of rheumatoid arthritis (RA) disease activity and to compare (18)F-FDG PET parameters with clinical, biologic, and sonographic (US) rheumatoid parameters. METHODS: Three hundred fifty-six joints were assessed in 21 patients with active RA: the knees in all subjects and either wrists as well as metacarpophalangeal and proximal interphalangeal joints in 13 patients, or ankles and the first metatarsophalangeal joints in the remaining 8 patients. PET analysis consisted of a visual identification of (18)F-FDG uptake in the synovium and measurements of standardized uptake values (SUVs). Independent assessors performed the clinical and US examinations. RESULTS: PET positivity was found in 63% of joints, whereas 75%, 79%, and 56% were positive for swelling, tenderness, and US analysis, respectively. Both the rate of PET-positive joints and the SUV increased with the number of positive parameters present (swelling, tenderness, US positivity) and with the synovial thickness. The mean SUV was significantly higher in joints where a power Doppler signal was found. In a global PET analysis, the number of PET-positive joints and the cumulative SUV were significantly correlated with the swollen and tender joint counts, the patient and physician global assessments, the erythrocyte sedimentation rate and C-reactive protein serum levels, the disease activity score and the simplified disease activity index, the number of US-positive joints, and the cumulative synovial thickness. CONCLUSION: (18)F-FDG PET is a unique imaging technique that can assess the metabolic activity of synovitis and measure the disease activity in RA.