Effects of Anesthetic Agents on Focal Adhesion Kinase (pp125FAK) Tyrosine Phosphorylation in Rat Hippocampal Slices

Background: Tyrosine protein kinase proteins exert a prominent control on signaling pathways and may couple rapid events, such as action potential and neurotransmitter release, to long-lasting changes in synaptic strength and survival. Whether anesthetics modulate tyrosine kinase activity remains unknown. The aim of the current study was therefore to examine the effects of intravenous and volatile anesthetics on the phosphorylation of focal adhesion kinase (pp125FAK), a functionally important nonreceptor tyrosine kinase, in the rat hippocampus.

Methods: Phosphorylation of pp125FAK was examined in hippocampal slices by immunoblotting with both antiphosphotyrosine and specific anti-pp125FAK antibodies. Experiments were performed in the absence (control) or presence of various concentrations of pharmacologic or anesthetic agents or both.

Results: Clinically relevant concentrations of thiopental, propofol, etomidate, isoflurane, sevoflurane, and desflurane induced a concentration-related increase in tyrosine phosphorylation. In contrast, ketamine (up to 100 [mu]m) and the nonimmobilizer F6 (1,2-dichlorohexafluorocyclobutane, 25 [mu]m) did not significantly affect pp125FAK phosphorylation. The anesthetic-induced increase in pp125FAK phosphorylation was blocked by GF 109203X, RO 318220, and chelerythrin (100 [mu]m), three structurally distinct inhibitors of protein kinase C and U 73122 (50 [mu]m), an inhibitor of phospholipase C. The propofol- and isoflurane-induced increase in pp125FAK phosphorylation was reversible and showed nonadditivity of effects with phorbol 12-myristate 13-acetate (an activator of protein kinase C, 0.1 [mu]m). In contrast, ketamine (up to 100 [mu]m), MK801 (10 [mu]m, an N-methyl-d-aspartate receptor antagonist), bicuculline (10 [mu]m, a [gamma]-aminobutyric acid type A receptor antagonist), and dantrolene (30 [mu]m, an inhibitor of the ryanodine receptor) were ineffective in blocking anesthetic-induced activation of tyrosine phosphorylation.     

Single-Blind, Randomized Study Comparing Chromated Glycerin, Polidocanol Solution, and Polidocanol Foam for Treatment of Telangiectatic Leg Veins

BACKGROUND: A single-blind, randomized, comparative study was performed to evaluate the efficacy of pure chromated glycerin (CG), polidocanol (POL) 0.25% solution, and POL 0.25% foam (Monfreux technique) for treatment of telangiectasias and reticular leg veins. OBJECTIVE: To determine the relative efficacy and safety of two sclerosing agents and foam. METHOD: Of 150 randomized patients presenting comparable areas (lateral face of thigh) of telangiectasias and reticular leg veins, 147 could be evaluated by photographic assessment, patients' satisfaction score, and pain at injection sites. Internal and external agreement for the photographic assessment was good for two independent blinded experts. RESULTS: CG cleared vessels significantly better than POL solution or foam (p<0.002). The patients' satisfaction score was also higher in the CG group, although the difference did not reach statistical significance. CG was significantly more painful at injection sites. Other side effects were very few, precluding any statistical comparison. Foam was associated with more side effects (microthrombi, matting) than CG or POL solution. Three patients treated with POL foam experienced a transient visual disturbance. CONCLUSION: This study shows that CG is superior to POL solution and foam for sclerotherapy of leg telangiectasias.     

Neuropathy associated with “benign” anti-myelin-associated glycoprotein IgM gammopathy: Clinical,immunological, neurophysiological pathological findings and response to treatment in 33 cases

We studied 33 patients presenting with a peripheral neuropathy associated with non-malignant anti-myelin-associated glycoprotein (MAG) IgM monoclonal gammopathy (MG) in an attempt to delineate their clinical, immunological, electrophysiological and pathological characteristics; we also reviewed our experience concerning long-term follow-up and therapy. Peripheral neuropathy associated with non-malignant anti-MAG IgM MG was observed mostly in males (sex ratio 7.2), and mean age at onset was 67 years (range 46–81). A predominantly sensory pattern was noted in more than 80% of cases, although some patients were affected by a predominantly motor peripheral neuropathy. Although disease progression was slow in most cases, 45% of patients suffered severe disability, and in 2 cases, the patient's death appeared to stem directly from the neuropathy. The electrophysiological findings were indicative of a demyelinating process in 90% of cases, and electron microscopic examination of nerve biopsy specimens demonstrated widening of the myelin lamellae in more than 95% of cases. Most of our patients showed a disappointing response to steroids and chemotherapy or plasma exchanges. Intravenous immune globulin, evaluated in 17 patients, had a transient, mostly subjective effect in 35% and led to a clear-cut improvement in 24% of cases. We did not observe any correlation between the severity of the clinical picture and the anti-sulphoglucuronyl paragloboside antibody titre; in individual cases, clinical improvement occurred without lowering of IgM levels. Although the severity and the rate of progression may greatly vary from patient to patient, the combination of clinical, electrophysiological and pathological features delineates a characteristic pattern in peripheral neuropathy associated with non-malignant anti-MAG IgM MG.     

Is there a place for gastroenterostomy in patients with advanced cancer of the head of the pancreas?

There remains doubt about the need for gastroenterostomy in patients with advanced cancer of the pancreatic head, performed either prophylactically or when passage of food becomes impossible. The records of 142 patients admitted for advanced pancreatic cancer to the Erasmus University Hospital over a period of 11 years were reviewed. We concentrated especially on the pre- and postoperative intake of food in cases involving gastroenterostomy and the morbidity and mortality associated with abdominal surgery in these patients. Of 129 patients without symptoms of gastric outlet obstruction at the time of diagnosis, 31 underwent prophylactic gastroenterostomy. The procedure did not prevent gastric outlet obstruction in 4 patients. Of the remaining 98 patients, 15 developed gastric outlet obstruction. Cox proportional hazards analysis showed no significant difference in the interval to the occurrence of a symptomatic obstruction between these two groups, taking into account other covariables. Postoperative complications and mortality regarding a gastroenterostomy were high, ranging from 9% to 41% and 11% to 33%, respectively. Our results do not indicate that prophylactic gastroenterostomy may significantly prevent future gastric outlet obstruction; therefore, as it also increases morbidity, it should not be performed. A gastroenterostomy to relieve symptoms should be considered carefully, as the success rate is low and is accompanied by a considerable incidence of morbidity and mortality.

---

Resumen Persiste la duda sobre la necesidad de practicar gastroenterostomía en pacientes con cáncer avanzado de la cabeza del páncreas, así sea profiláctica o en presencia de obstrucción al paso de los alimentos. Se revisaron las historias de 142 pacientes con cáncer avanzado de la cabeza del páncreas en el Hospital de la Universidad de Erasmo observados en un periodo de 11 años. El estudio se concentré especialmente sobre la ingesta pre y postoperatoria de alimentos en los pacientos con gastroenterostomía y en la morbilidad y mortalidad asociada con la cirugía abdominal. De 129 pacientes libres de síntomas de obstrucción en el momento del diagnóstico, 31 fueron sometidos a gastroenterostomía profiláctica; el procedimiento no logró prevenir la obstrucción gástrica en 4 casos. De los 98 pacientes restantes, 15 desarrollaron obstrucción gástrico. El análisis proporcional de Cox no demostró diferencia significativa en el intervalo transcurrido hasta la aparición de los sintomas entre los dos grupos, tomando en consideración diversas variables. Las tasas de complicaciones y de mortalidad postoperatoria en relación con la gastroenterostomía fueron elevadas, 9–41% y 11–33%, respectivamente. Nuestros resultados no indican que la gastroenterostomía profiláctica pueda prevenir la obstrucción gástrica y, por cuanto incrementa la morbilidad, no debe ser realizada. La gastroenterostomía por razones de sintomatologia debe ser cuidadosamente considerada, puesto que la tasa de éxito es baja y se acompana de considerable morbilidad y mortalidad.

---

Résumé Réaliser une gastroentérostomie de faÇon prophylactique ou seulement lorsque l'alimentation devient impossible chez un patient ayant un cancer de la tÊte du pancréas reste une question sans réponse. Les dossiers de 142 patients ayant un cancer avancé de la tÊte du pancréas, observés à l'HÔpital Universitaire Erasmus en l'espace de 11 ans, ont été revus. Nous avons noté la possibilité d'alimentation en périodes préet postopératoire ainsi que la morbidité et mortalité en rapport avec la chirurgie chez ces patients. Des 129 patients n'ayant pas de symptÔmes d'obstruction postpylorique au moment du diagnostic, 31 ont eu une gastroentérostomie à titre prophylactique. Cette intervention n'a pu prévenir l'obstruction chez 4 de ces patients. Des 98 autres patients, 15 ont développé une obstruction postpylorique. Une analyse multifactorielle selon le modèle de Cox n'a pu démontrer de différence significative entre les deux groupes pour l'intervalle entre le moment du diagnostic et la survenue de l'obstruction. Le taux de complications et de décès postopératoires après gastroentérostomie était élevée, variant respectivement entre 9% et 41% et 11% et 33%. Nos résultats indiquent que la gastroentérostomie à titre prophylactique ne prévient pas la survenue d'une obstruction postpylorique mais qu'elle accroÎt la morbidité. Dans ces conditions, la gastroentérostomie ne devrait Être réalisée qu'en cas d'obstruction symptomatique, mais en sachant qu'elle n'est pas toujours couronnée de succès et que les taux de mortalité et de morbidité ne sont pas nuls.

     

Quality of life assessment and HIV infection: A review

In the last few years, survival of patients infected with human immunodeficiency virus (HIV) has been improved because of a decreased incidence of some opportunistic complications attributable to prophylactic treatments and antiretroviral drugs. The impact of these agents should also be reflected in the quality of life (QoL) of patients. We have reviewed this topic with an emphasis on different types of measurements such as Q-TWIST, MOS and the Spitzer score which seem to be most appropriate for this patient population. We do not think that a special type of assessment should be designed for HIV-infected persons. It would be less time-consuming to improve already existing validated scores focusing on HIV infection. QoL in intravenous drug users with HIV should be evaluated more often.     

Predictive molecular and genetic toxicology

Conclusion The search for a link between cellular and molecular events involved in delayed-type CHS reactions and the early molecular activation of xenobiotics is a new field of research. It should largely contribute to the debate on the best way forward for predictive toxicology in general.     

Comparison Between Incremental and Single-Dose Allergen Administration in Bronchial Provocation Tests

To study the effect of different schedules of allergen administration on the early (EAR) and late allergic reaction (LAR), 15 asthmatic patients with dual response after allergen challenge were submitted to two consecutive bronchoprovocation tests (BPT). BPT₁ was carried out with semilogarithmic increase of allergen doses until a FEV₁ drop of 20% was recorded. BPT₂ was performed 2 weeks later using the highest allergen dose that had elicited the dual reaction in BPT₁. Both EAR and LAR were very similar for a given patient. As the allergen dose used in BPT₂ is smaller than the cumulative allergen dose administered in BPT₁, this protocol takes into account a possible influence on BPT₂ of bronchial hyperreactivity induced by BPT₁ performed 2 weeks before.