Effects of acute intravenous administration of Met-enkephalin in the rabbit: A computer analysis

Intravenous administration of doses of Met-enkephalin ranging from 33.3 to 5000 μg/kg was followed by modifications in the EEG pattern in the rabbit. The changes were a prevalence of strongly synchronized EEG patterns, lasting about 90 min, in the absence of any behavioural sign of drowsiness. A transient fall in arterial blood pressure, lasting 15 sec, was observed immediately following the injection.Quantification of the EEG effects showed a remarkable increase of EEG total power. Such an increase is statistically significant. It was less marked in the posterior leads and appeared to be dose-related as regards its intensity, duration, and latency from injection.Qualitatively such a spectral profile matches the one typical of physiological drowsiness.As regards EEG effects, no tolerance to the peptide developed if the administration was repeated after 90 min.The specific antagonist of opiates both prevented and reversed the hypersynchronization of the tracing.These findings demonstrate that Met-enkephalin crosses the blood-brain barrier in an amount adequate to producing changes in the functional organization of the brain, resulting in EEG patterns corresponding to functional depression.     

Laryngeal tuberculosis

Tuberculosis involvement of the larynx is uncommon. However, it is a highly infectious disease and a hazard to both community and hospital staff. It should be considered in the differential diagnosis of patients presenting with chronic hoarseness. Two patients with laryngeal tuberculosis are the objective of the present report. The diagnosis was established by biopsy followed by isolation and identification of Mycobacterium tuberculosis from sputum.     

Motoneurons innervating facial muscles after hypoglossal and hemihypoglossal-facial nerve anastomosis in rats

Hypoglossal-facial nerve anastomosis (HFA) is the most popular surgical procedure to reinnervate facial muscles after injury of the facial nerve. Section of the hypoglossus causes paralysis and atrophy of the hemi-tongue. In the attempt to overcome this consequence, the hemihypoglossal-facial nerve anastomosis (HHFA) has been proposed and only a half of the main trunk of the hypoglossus is connected to the distal stump of the facial nerve. In the rat, we have studied experimentally the anatomical nuclear changes after HFA and HHFA with the aim of establishing the quantitative motoneuron innervation of facial muscles obtained with each one of the two operative options. Horseradish peroxidase (HRP) injected in both types of anastomosis labeled not only hypoglossal motoneurons, but also facial motoneurons. HFA appeared to offer a significant quantitative motoneuron innervation higher than HHFA and then a higher probable better functional recovery. Both HFA and HHFA performed immediately after section of the facial nerve in rats did not result in a phenomenon of motor hyperinnervation. In our experimental model, the proximal facial nerve stump was coagulated at the stylomastoid foramen to avoid regeneration. Then, the labeled motoneurons into the facial nucleus could really be the expression of axonal projections from facial motoneurons to the hypoglossus nerve and facial muscles. No labeled motoneurons were seen contralaterally as we observed previously after section and repair of several nerves.     

Biomedical signal processing and modeling in cardiovascular systems

This article revisits the subject of short-term heart-rate and arterial-pressure variability from the perspective of model structures that can be useful in defining signal processing algorithms. We draw a general scheme of the oscillation sources and interactions that contribute to cardiovascular control mechanisms and highlight the elements that were considered in different modeling works.The origin, superposition, and interaction of respiratory high-frequency (HF) and vasomotor low-frequency (LF) rhythms is presented as the integration of supraspinal and spinal circuits, vasomotor activity, and pressure control loops. We analyze in detail the necessity of considering all relevant interactions for the algorithms designed to estimate the baroreflex sensitivity. We also pinpoint the components of cardiorespiratory coupling in relation to the analysis of data from the acoustic quantification of the left ventricular volume. Finally, we analyze the tendency to produce complex behaviors even in extremely simplified systems involving interactions between oscillatory mechanisms.     

Targeted therapy with bevacizumab and erlotinib tailored to the molecular profile of patients with recurrent glioblastoma. Preliminary experience

Background

Advances in comprehension of molecular biology of glioblastoma (GBM) have led to the development of targeted therapies. The aim of the present study was to evaluate the efficacy and safety of a targeted therapeutic approach in which administration of bevacizumab and erlotinib was tailored on the molecular profile of recurrent GBM.

Methods

We prospectively enrolled ten adult patients suffering from recurrent GBM who had undergone surgical resection and standard chemo-radiotherapy. Tumor tissue was assessed for the expression of EGFRvIII and MGMT promoter methylation by RT-PCR, and for PTEN and VEGF expression by immunohistochemistry. Normal PTEN status was required for inclusion. Patients with VEGF overexpressing tumors (10/10) were treated with bevacizumab (10 mg/kg iv every 2 weeks in 6-week?cycles); patients whose tumor expressed EGFRvIII (4/10) added erlotinib (150 mg/day orally; 300 mg/day if on enzyme-inducing antiepileptic drugs). Therapy was continued until disease progression or unacceptable toxicity. Primary endpoints of the study were response rate (RR), 6-month progression-free survival (PFS-6), and safety profile.

Results

The RR and PFS-6 were 100 % (4/4) and 50 % (3/6) in patients treated with bevacizumab+erlotinib (n?=?4) and bevacizumab (n?=?6), respectively. In the whole cohort (n?=?10), RR and PFS-6 were both 70 % (7/10); median PFS and overall survival (OS) were 8.0 (3.0–31.0) and 9.5 (5.0–31.0) months, respectively. No grade 3/4 adverse events were observed; three patients treated with bevacizumab+erlotinib displayed grade 1/2 rash not requiring dose reduction; one patient treated with bevacizumab developed intratumoral hemorrhage requiring treatment discontinuation.

Conclusion

To our knowledge, this is the first study on recurrent GBM in which administration of bevacizumab and erlotinib was tailored on the molecular profile of the patient’s tumor. Although we treated a limited number of patients, we obtained significantly higher RR and PFS-6 than those reported in a previous trial lacking molecular tumor analysis.     

Family physician beliefs about cancer screening. Development of a survey instrument

To improve rates at which physicians provide cancer control procedures, it is first necessary to identify physician and environmental characteristics that explain variations in those rates. This study used an attitude-behavior model as a guiding framework to identify beliefs, sources of influence, facilitating conditions, and critical events that may be important determinants of physicians' rates for providing eight cancer control activities. Open-ended, semistructured interviews were conducted with 26 family physicians to discuss the factors that may have affected their policies for providing each of the eight cancer control activities. Content analysis of those interviews produced unique lists of beliefs, sources of influence, facilitating conditions, and critical events for each activity. These lists of factors are more comprehensive than those identified in previous studies. A questionnaire has been developed based on these findings, and a validation study is being conducted to identify the factors that best explain variation in rates at which cancer control activities are performed.