Acute and long-term administration of citalopram desensitizes alpha2-adrenoceptors in the rat vas deferens

The aim of this study was to investigate the effect of citalopram, a selective serotonin reuptake inhibitor, on the sensitivity of rat vas deferens alpha2-adrenoceptors and to compare it with the effects of serotonin and the dual noradrenaline-serotonin uptake inhibitor duloxetine. To this end, we studied the inhibitory effect of the alpha2-adrenoceptor agonist bromoxidine on the electrically induced contraction of the vas deferens. Citalopram (1, 3 x 10(3) and 3 x 10(4) nM) applied in-vitro significantly attenuated the concentration-response inhibition induced by activation of alpha2-adrenoceptors on the electrically evoked contraction of the vas deferens (concentration of the agonist required to promote 50% of the maximal effect, EC50, for bromoxidine increased by 232%, 421% and 818%, respectively). Similarly, serotonin also attenuated the concentration-response inhibition mediated by presynaptic alpha2-adrenoceptors (96% increase in EC50). Acute and long-term systemic administration of citalopram and duloxetine also produced a loss in the sensitivity of alpha2-adrenoceptors to bromoxidine (EC50 for bromoxidine increased by 97% and 144%, respectively, after citalopram, and by 214% and 167% after duloxetine). In addition, we observed that an increased fraction of receptors was required to be occupied to yield 50% of the inhibitory effect of bromoxidine after long-term administration of citalopram and duloxetine (KE increased by 142% and 83%). These results are indicative of early-onset and persistent down-regulation of peripheral alpha2-adrenoceptors by citalopram, which may account for some of its side effects.     

Irinotecan,oxaliplatin, and 5-fluorouracil/leucovorin combination chemotherapy in advanced colorectal carcinoma: a phase II study

The purpose of this study was to evaluate the efficacy and tolerance of a combination of irinotecan, oxaliplatin, and 5-fluorouracil (5-FU)/leucovorin in advanced colorectal cancer (ACC). Twenty-six consecutive patients with ACC and an Eastern Cooperative Oncology Group performance status of 0-2 were treated with a combination of oxaliplatin (120 mg/m2 intravenously [i.v.] for 2 hours) on day 1, irinotecan (250 mg/m2 i.v. for 90 minutes) on day 1, and 5-FU (2600 mg/m2 plus leucovorin 500 mg/m2 i.v. in a 24-hour infusion) on day 1 and 15, every 4 weeks. Five of the patients (19.2%) had shown previous chemoresistance. One hundred sixty-two cycles were administered (median, 6; range, 3-13 cycles). All patients were evaluated for toxicity; 23 were evaluable for response. According to intention-to-treat, the overall response rate was 69.2% (18 patients; 95% CI: 48.2%-85.7%), including 3 complete remissions (11.5%). Four additional patients (15.3%) had stable disease, and only 1 (3.8%) progressed. Major toxicities were neutropenia and diarrhea. Grade 3 neutropenia occurred in 9 patients (34.6%), and grade 4 occurred in 1 patient (3.8%). Grade 3 diarrhea occurred in 8 patients (30.7%) and grade 4 in 1 patient (3.8%). Other toxicities were mild. After a median follow-up of 15.5 months, the median progression-free survival was 14 months. Seventeen patients (65.4%) are still alive, and the median overall survival has not been reached yet. This combination of irinotecan, oxaliplatin, and 5-FU/leucovorin is fairly well tolerated and shows promising activity in ACC. This treatment merits further comparison with other combination regimens.     

Does Tumor Depth Affect Nodal Upstaging in Squamous Cell Carcinoma of the Head and Neck?

PURPOSE: The aim of this study was to determine whether tumor depth affects upstaging of the clinically node-negative neck, as determined by sentinel lymph node biopsy with full pathologic evaluation of harvested nodes including step-serial sectioning (SSS) and immunohistochemistry (IHC). PATIENTS AND METHODS: One hundred seventy-two patients with cT1/2 N0 squamous cell carcinoma (SCC) of the oral cavity/oropharynx undergoing primary resection and either sentinel node biopsy (SNB) or SNB-assisted neck dissection as a staging tool for the cN0 neck. Harvested nodes were examined with hematoxylin-eosin staining, SSS, and IHC. Patients upstaged by SSS/IHC were denoted pN1mi. RESULTS: One hundred one of 172 patients were staged pN0, with 71 (41%) patients upstaged. Increasing tumor depth was associated with higher likelihood of upstaging (P < .001). Tumor depth showed a positive correlation with nodal stage according to TNM classification (P < .001). Tumor depth greater than 4 mm appears to be the most appropriate cutoff for risk stratification, although tumors in the oropharynx may require a lower value. CONCLUSION: Tumor depth is an important prognostic factor for patients with SCC of the oral cavity or oropharynx. Tumors greater than 4 mm are associated with greater risk of upstaging; however, this optimum cutoff value may vary between primary tumor sites.     

Analysis of our recent results in the surgical treatment of the hyperparathyroidism (1990-2005)

ObjectiveTo report our recent experience (1990- 2005)in theal treatment of hyperparathyroidismMaterial and methodsUp to now we have operated 153 patients (41 male and 112 female) with ages between 14 and 79 years old studying the clinical symptoms referred by them, preoperative imaging tests, type of hyperparathyroidism, its respective surgery, result or final anatomopathological diagnosis and postoperative complicationsResultsParathyroid adenomas represented a 69.73% while the hyperplasias were about 26.31%. In 6 cases the glands removed were informed as normal. It stands out that the most rare adenomas were located in lower parathyroids with a relation > 5,5:1 respect to the upper ones. Among the complications we obtained 35 postoperative hypocalcemias (31 transient and 4 persistent), one case of recurrent nerve palsy after exposure of 233 nerves, 5 haemorrhages that required reintervention and 4 persistences of hypercalcemia. Globally we were able to reduce the calcium and PTH serum levels with clinical improvement in more than 96% of the operated patientsDiscussion-conclusionThe surgery for hyperparathyroidism provides very good results in general as we stated in other published series