Multidisciplinary practice guidelines for the diagnosis, genetic counseling and treatment of pheochromocytomas and paragangliomas

'Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors that arise from chromaffin cells of the adrenal medulla and the sympathetic/parasympathetic neural ganglia, respectively. The heterogeneity in its etiology makes PPGL diagnosis and treatment very complex. The aim of this article was to provide practical clinical guidelines for the diagnosis and treatment of PPGLs from a multidisciplinary perspective, with the involvement of the Spanish Societies of Endocrinology and Nutrition (SEEN), Medical Oncology (SEOM), Medical Radiology (SERAM), Nuclear Medicine and Molecular Imaging (SEMNIM), Otorhinolaryngology (SEORL), Pathology (SEAP), Radiation Oncology (SEOR), Surgery (AEC) and the Spanish National Cancer Research Center (CNIO). We will review the following topics: epidemiology; anatomy, pathology and molecular pathways; clinical presentation; hereditary predisposition syndromes and genetic counseling and testing; diagnostic procedures, including biochemical testing and imaging studies; treatment including catecholamine blockade, surgery, radiotherapy and radiometabolic therapy, systemic therapy, local ablative therapy and supportive care. Finally, we will provide follow-up recommendations (AU)

Multidisciplinary practice guidelines for the diagnosis, genetic counseling and treatment of pheochromocytomas and paragangliomas.

Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors that arise from chromaffin cells of the adrenal medulla and the sympathetic/parasympathetic neural ganglia, respectively. The heterogeneity in its etiology makes PPGL diagnosis and treatment very complex. The aim of this article was to provide practical clinical guidelines for the diagnosis and treatment of PPGLs from a multidisciplinary perspective, with the involvement of the Spanish Societies of Endocrinology and Nutrition (SEEN), Medical Oncology (SEOM), Medical Radiology (SERAM), Nuclear Medicine and Molecular Imaging (SEMNIM), Otorhinolaryngology (SEORL), Pathology (SEAP), Radiation Oncology (SEOR), Surgery (AEC) and the Spanish National Cancer Research Center (CNIO). We will review the following topics: epidemiology; anatomy, pathology and molecular pathways; clinical presentation; hereditary predisposition syndromes and genetic counseling and testing; diagnostic procedures, including biochemical testing and imaging studies; treatment including catecholamine blockade, surgery, radiotherapy and radiometabolic therapy, systemic therapy, local ablative therapy and supportive care. Finally, we will provide follow-up recommendations.

Basic Phage Mathematics.

Basic mathematical descriptions are useful in phage ecology, applied phage ecology such as in the course of phage therapy, and also toward keeping track of expected phage-bacterial interactions as seen during laboratory manipulation of phages. The most basic mathematical descriptor of phages is their titer, that is, their concentration within stocks, experimental vessels, or other environments. Various phenomena can serve to modify phage titers, and indeed phage titers can vary as a function of how they are measured. An important aspect of how changes in titers can occur results from phage interactions with bacteria. These changes tend to vary in degree as a function of bacterial densities within environments, and particularly densities of those bacteria that are susceptible to or at least adsorbable by a given phage type. Using simple mathematical models one can describe phage-bacterial interactions that give rise particularly to phage adsorption events. With elaboration one can consider changes in both phage and bacterial densities as a function of both time and these interactions. In addition, phages along with their impact on bacteria can be considered as spatially constrained processes. In this chapter we consider the simpler of these concepts, providing in particular detailed verbal explanations toward facile mathematical insight. The primary goal is to stimulate a more informed use and manipulation of phages and phage populations within the laboratory as well as toward more effective phage application outside of the laboratory, such as during phage therapy. More generally, numerous issues and approaches to the quantification of phages are considered along with the quantification of individual, ecological, and applied properties of phages.

Perfil farmacoterapéutico de pacientes hospitalizados en la Unidad de Cuidados Paliativos. Hospital San Juan de Dios de Pamplona / No disponible

Objetivo: identificar los fármacos más empleados en una Unidad de Cuidados Paliativos para implementar en un trabajo posterior, las medidas que sean aconsejables al objeto de procurar su correcta utilización y así obtener los mejores resultados en la terapéutica farmacológica. Método: análisis descriptivo y prospectivo de los pacientes hospitalizados en la Unidad de Cuidados Paliativos del Hospital San Juan de Dios de Pamplona. La recogida de datos tuvo lugar durante seis semanas. Se estudiaron las prescripciones farmacoterapéuticas de cada uno de los pacientes, así como la vía de administración empleada, a lo largo del periodo de estudio. Resultados: los 10 grupos de medicamentos más prescritos en estos pacientes son: analgésicos, psicolépticos, antiulcerosos, laxantes, procinéticos, diuréticos, antiinflamatorios y antirreumáticos, antidepresivos, corticosteroides y antitrombóticos. En cuanto a las vías de administración, la oral fue la más habitual al principio del ingreso y la vía subcutánea la más utilizada en las fases finales de la enfermedad. Conclusiones: en el trabajo se identifican los fármacos más frecuentemente prescritos, con la finalidad de que el farmacéutico integrante del equipo asistencial colabore, por su especial competencia en esta materia, en alcanzar una terapéutica farmacológica más individualizada y específica en beneficio de un uso más racional de medicamentos en cuidados paliativos (AU)

Objective: to identify the most frequently used medications in a Palliative Care Unit in order to implement (following further study) the most appropriate measures to encourage and ensure their correct use, and thus achieve optimum results in pharmacological therapy. Method: a descriptive and prospective analysis of thirty patients hospitalized in the Palliative Care Unit at San Juan de Dios hospital in Pamplona. Data were collected over a six-week period. Both medical prescriptions and administration routes were tracked throughout the study period. Results: the ten classes of medications most often prescribed to patients were: analgesics, psycholeptics, antiulcers, laxatives, prokinetics, diuretics, anti-inflammatory /antirheumatic drugs, antidepressants, corticosteroids and antithrombotic agents. Most medications were administered orally in the initial phase of treatment following admission to hospital, whereas subcutaneous administration was more common in the final stages of illness. The pharmacist must collaborate closely with the medical team to provide pharmacological therapies specific for each patient, thus promoting a more rational use of medications during palliative care. Conclusions: the most frequently prescribed medications are identified in this research project, the purpose of which is to enable pharmacists, as members of the care team, to put their particular skills at work in the provision of more individualized and specialized pharmacological therapy approaches through a more rational use of medications in palliative care (AU)

Determination of thyreostatics in animal feed by micellar electrokinetic chromatography.

The determination of the thyreostatics 2-thiouracil, its derivatives (4-methyl-2-thiouracil, 4-propyl-2-thiouracil and 4-phenyl-2-thiouracil) and methimazole in manufactured dried animal feed by micellar electrokinetic chromatography (MEKC) is described. A 99 +/- 5% extraction yield at the 20 micrograms g-1 level (n = 8) was achieved by shaking the milled fodder with methanol-1 M NaOH (80 + 20). Aliquots of the supernatant were injected in a 75 microns x 33.5 cm uncoated silica capillary using pressure; separation was performed at 23 degrees C with 15 kV (positive polarity) in a background electrolyte (BGE) containing 40 mM sodium dihydrogenphosphate, 50 mM sodium dodecyl sulfate and 15 mM Tween 20 at pH 9. When the surfactants were added to the BGE, all the thyreostatics were well resolved and the fodder extracts showed lower backgrounds. The peaks appeared within the 2.25-5.2 min range with efficiencies in the 2.5 x 10(4)-8 x 10(4) range; methimazole appeared in the vicinity of the electroosmotic migration time. Calibration curves were linear within the studied range (20-200 micrograms ml-1, r2 > 0.998). Limits of detection in the extracts of spiked fodder samples ranged from 0.25 to 0.4 microgram ml-1, which corresponded to 0.6-1.0 microgram of drug per gram of fodder. Peak area repeatabilities were about 4% at the 20 micrograms ml-1 level.

Flow-injection spectrophotometric determination of phenolic drugs and carbamate pesticides by coupling with diazotized 2,4,6-trimethylaniline.

A flow-injection (FI) spectrophotometric system is proposed for the determination of phenols and carbamates. In the FI manifolds, the solutions of phenols or carbamates (the latter after hydrolysis with NaOH) were injected into a diazonium ion carrier stream at pH 9.5 (buffered with tetrahydroborate), which was formed by mixing 2,4,6-trimethylaniline (TMA) with nitrate in a sodium dodecyl sulfate aqueous micellar medium. Absorbance was measured at 550 nm. The system combines the advantages derived from the use of TMA for the coupling of phenols in basic micellar media, because of the inhibition of the self-coupling reaction of the reagent, with the precision and speed of the FI procedures. Other diazotized reagents produced excessive blank signals. The procedures were successfully applied to the determination of phenolic drugs (epinephrine, acetaminophen, and gualacol) in pharmaceuticals and carbamates (bendiocarb, benfuracarb, carbaryl, carbofuran, methiocarb, promecarb, and propoxur) in pesticide products and water samples.

Micellar modified spectrophotometric determination of nitrobenzenes based upon reduction with tin(II), diazotisation and coupling with the Bratton-Marshall reagent.

Nitrobenzenes, such as the antibiotic chloramphenicol, the vasodilator nicardipine, and the herbicides dinitramin, dinobuton, fenitrothion, methylparathion, oxyfluorfen, parathion, pendimethalin, quintozene, and trifluralin, were determined by using a spectrophotometric method in the visible region (540 nm). The method was based on the reduction of the nitrobenzenes to arylamines with tin(II) chloride, diazotisation of the arylamines and coupling of the diazonium ions with the Bratton-Marshall reagent. The two latter reactions were performed in a micellar medium of sodium dodecyl sulphate. The linear calibration range was 2x10(-6) to 7x10(-5) M (r>0.999), with limits of detection in the 10(-7) M level, which is 2-6 fold lower with respect to the corresponding spectrophotometric procedure in non-micellar medium. The procedure was applied to the analysis of the compounds in commercial preparations (pharmaceuticals and herbicide formulations) and in water samples, with good recoveries.

[Arterial blood pressure in various groups in the urban population of Morelia City]. / Valores de la presión arterial en diversos grupos de población urbana de la ciudad de Morelia.

Four groups from a urban population of Morelia were inquired, to determine frequency of high blood pressure and provide basic information of arterial hypertension in relation with other variables; 2638 persons were checked. Age ranged from 10 to 90 years, (771 men, 1867 women). Age, sex, weight and height were also measured. Evaluations were performed in the morning with mercury sphygmomanometer registering first and fifth korotkoff's sounds in orthostatic position with a second selective evaluation in sitting position. Availability of medical services and knowledge about presence of arterial hypertension were also evaluated. Blood pressure and prevalence of hypertension had similar behavior with regard to age: pressure recordings were higher in men before 40 years. After this age were higher in women. In general, 14% had high blood pressure, in the second evaluation this value dropped to 7%. For 11% of the studied population, high blood pressure had been previously recorded 7 out of 10 cases of hypertension did not have any control. Three of them had not information about this illness. We found a positive correlation between weight and blood pressure (p less than 0.001) specially among women.

Pharmacokinetics of oral nifedipine: relevance of the distribution phase.

Pharmacokinetics of oral Nifedipine was studied in 12 Mexican young healthy volunteers, six men and six women, who received a 10 mg capsule. Plasma levels were determined by a nifedipine specific HPLC assay. Experimental data were fitted and pharmacokinetic parameters were calculated using an open two compartment model. No statistically significant difference was detected between men and women, thus both sexes were considered as a single population. Nifedipine plasma levels rose rapidly (ka = 8.46 +/- 1.96 h-1) reaching a maximum concentration of 145 +/- 23 ng/ml in 0.61 +/- 0.07 h. Plasma levels then decayed with a distribution phase (alpha = 1.98 +/- 0.40 h-1, t1/2 alpha = 0.46 +/- 0.06 h) and a terminal elimination phase (beta = 0.17 +/- 0.03 h-1, t1/2 beta = 4.98 +/- 0.55 h). AUC was 384 +/- 41 ng h/ml. Values of AUC and t1/2 beta were higher than those reported by other authors. Differences in the AUC could be due to ethnic origin, environmental factors or nutritional habits. Ten subjects presented plasma concentration-time curves in which the distribution phase was clearly distinguishable, having a ka/alpha relationship higher than 1.5. For the other two subjects, the distribution phase was not apparent and ka/alpha was lower than 1.5. The results show that an adequate characterization of the distribution phase is required if one pretends to use pharmacokinetic data for dosage regimen design.

[Clinical and pharmacokinetic comparison of 2 oral preparations of nifedipine: 10 mg capsules and 20 mg delayed-release tablets]. / Comparación clinica y farmacocinética de dos formulaciones orales de nifedipina: cápsula de 10 mg. y comprimido de liveración prolongada de 20 mg.

The effects and pharmacokinetic parameters of two oral formulations of nifedipine, 10 mg capsule (Adaltat) and 20 mg slow release tablet (Adalat a.p.). With the 10 mg capsule nifedipine was rapidly absorbed, reaching a maximum concentration of 120 +/- 39 ng/ml in 0.52 +/- 0.07 h, and also rapidly eliminated with an apparent halflife of 5.51 +/- 0.64 h. A fall in blood pressure and a raise in heart rate, that significantly correlated with plasma levels, were observed. 83% of the subjects reported headache, that was probably due to the sudden increase in plasma levels. With the 20 mg slow release tablet nifedipine absorption was slower, reaching a maximum concentration of 39 +/- 7 ng/ml in 1.82 +/- 0.43 h, and the apparent half-life (16.89 +/- 3.14 h) was longer than with the capsule. A fall in blood pressure was observed that significantly correlated with plasma levels; however, there was no significant correlation between these and changes in heart rate. Only 17% of the subjects reported headache. Pharmacokinetic data indicate that, in most subjects, nifedipine therapeutics plasma levels (over 15 ng/ml) can be maintained with the administration of a 20 mg slow release tablet every 12 hours. This, joined to the reduction in side effects, suggest that this formulation is the adequate alternative in chronic treatments with nifedipine, such as arterial hypertension.

Hydralazine tachycardia and sympathetic cardiovascular reactivity in normal subjects.

The correlation between hydralazine-induced tachycardia and overall cardiovascular reactivity to sympathetic stimulation was explored in 50 normal subjects. Blood pressure and heart rate changes after standing, immersion of a hand in cold water, the Valsalva maneuver, and moderate exercise were compared with pressure and rate responses to 20 mg oral hydralazine. The drug did not modify blood pressure but increased heart rate, mainly in the standing position. Because plotting the magnitude of this response suggested a two-population distribution, subjects were divided into hyporeactor and hyperreactor groups. Reactivity did not appear to be related to acetylator phenotype. The magnitude of the cardiac response correlated with heart rate responses to standing and to the Valsalva maneuver; when analyzed separately from hyporeactors, correlation was greater among hyperreactors. Because the orthostatic and Valsalva responses are reflex in nature, these results suggest that hydralazine tachycardia is also reflexly induced, that its magnitude depends on individual baroreceptor sensitivity, which is distributed nonnormally, and that it can be predicted by suitable tests of sympathetic responsiveness.