Background: Pharmacokinetic parameters (PHK) of low-dose weekly paclitaxel (PAC) are not well known, particularly when administered with the cytoprotective agent amifostine (AMI). Methods: Patients with non-small cell lung cancer (NSCLC) received PAC alone or PAC + AMI. Blood samples were drawn at the end of the infusion at 0, 0.25, 0.5, 1, 2 and 4 h for the measurement of plasma PAC using HPLC. Area under the concentration-time curve (AUC), the peak plasma concentrations (Cmax) and the residence time of paclitaxel in plasma at concentrations >0.1 µM (TPP ≧0.1) and >0.05 µM (TPP ≧0.05) were calculated using a two-compartmental model. ANOVA was used for statistical analysis. Results: Pharmacokinetic studies were completed for 43 doses among 11 patients receiving PAC alone and for 26 doses among 8 patients receiving the combination AMI + PAC (from the first to the fifth week). Statistically significant differences in all parameters except AUC were observed between the 2 treatment groups. A significantly higher Cmax was observed for patients receiving PAC + AMI versus PAC alone. Both TPP ≧0.1 and TPP ≧0.05 were also more prolonged in AMI + PAC cycles. Conclusion: AMI produces a prolongation in PAC plasma circulation time. Further specifically designed studies are needed to quantify the resultant effects on PAC’s efficacy and toxicity.

Cholecystokinin (CCK) and its receptor CCK-2R have been shown to promote emotional responsivity and behavioral sensitization to psychostimulants in the rat. An animal model has been developed based on locomotor response to a novel inescapable environment. Animals exhibiting consistent differences in locomotor response to novelty have been termed as high and low responder rats (HR and LR, respectively). This paradigm is deemed to model sensation-seeking, a personality trait closely associated with substance abuse. The present study provides genetic and pharmacological evidence that the CCK-ergic system modulates this behavior. Distinctive patterns of CCK-related gene expression in HR and LR animals occurred beyond the mesolimbic pathways. CCK gene expression was higher in hippocampus, amygdala, and prefrontal cortex, but lower in the ventral tegmental area of HR relative to LR rats. Levels of CCK-2R mRNA were more elevated in LR animals in some areas of the forebrain such as the prefrontal cortex, nucleus accumbens, and hippocampus. Additionally, CCK-2R blockade with the antagonist LY225.910 (0.5 mg/kg) removed phenotype differences in sustained exploration of novel stimuli (i.e., a novel-object) in HR and LR rats exposed to an enriched open-field test series. Finally, CCK-2R blockade also altered M2 and 5-HT7 receptor gene expression in the mediodorsal thalamus (a strategic structure for corticothalamic trafficking) in a phenotype-dependent manner. Taken together, the findings reported here suggest that distinct CCK-ergic function may contribute to promoting individual differences in novelty-seeking behavior.

A case of papillary squamous cell carcinoma of the larynx in a 50-year-old man is reported. The lesion was located in the supraglottic region and grossly presented a characteristic finger-like pattern of growth. The tumour pursued an indolent clinical course, and the patient is well and free of disease after 47 months of follow-up. The present paper recapitulates the macro- and microscopic features of this rare neoplasm and stresses its differential diagnosis with other exophytic squamous cell carcinomas of the region.

A case of atypical carcinoid tumour of the larynx in a 72-year-old woman is presented. The neoplasm was located in the supraglottic region and was first manifest by metastases to the scalp. The presence of amyloid-like material and calcitonin-positive cells were features that resembled medullary carcinoma of the thyroid. Clinically, it pursued an aggressive course that led to death 58 months after diagnosis. The literature is reviewed, particularly that regarding the differential diagnosis.

summary We present a case of a 66 years old male patient who presented a 2 months history of dysphonia. Laryngoscopy showed a left vocal cord palsy. Toracic Computed Tomography indicated the existence of an aortic arch aneurysm, an unusual cause of the left recurrent laryngeal nerve palsy. In this article, we review ethiologic factors, symptomathology, diagnostic procedures and treatment of this kind of vocal cords palsies.