Phenotypic correlations in a large single-center cohort of patients with BSCL2 nerve disorders: a clinical, neurophysiological and muscle magnetic resonance imaging study.

BACKGROUND AND PURPOSE: BSCL2 heterozygote mutations are a common cause of distal hereditary motor neuropathies (dHMNs). A series of BSCL2 patients is presented and clinical, neurophysiological and muscle magnetic resonance imaging (MRI) findings are correlated. METHODS: Twenty-six patients from five families carrying the p.N88S mutation were identified. Age of onset, clinical phenotype (dHMN, Charcot-Marie-Tooth, spastic paraplegia), physical examination, disability measured as a modified Rankin Scale score and neurophysiological findings were collected. A whole body muscle MRI had been performed in 18 patients. The pattern of muscle involvement on T1-weighted and short time inversion recovery sequences was analysed. Hierarchical analysis using heatmaps and an MRI Composite Score were generated. Statistical analysis was carried out with STATA SE v.15 (TX, USA). RESULTS: The mean age was 51.54 ± 19.94 years and 14 patients were men. dHMN was the most common phenotype (50%) and five patients (19.23%) showed no findings on examination. Disease onset was commonly in childhood and disability was low (modified Rankin Scale score 1.34 ± 1.13) although median time since onset of disease was 32 years (range 10-47). Charcot-Marie-Tooth-like patients were more disabled and disability correlated with age. On muscle MRI, thenar eminence, soleus and tibialis anterior were most frequently involved, irrespective of clinical phenotype. MRI Composite Score was strongly correlated with disability. CONCLUSION: Patients with the p.N88S BSCL2 gene mutation are phenotypically variable, although dHMN is most frequent and generally slowly progressive. Muscle MRI pattern is consistent regardless of phenotype and correlates with disease severity, probably serving as a reliable outcome measure for future clinical trials.

Utilidad de una plataforma telemática para la prevención de reingresos en pacientes dados de alta por una exacerbación de su EPOC / Usefulness of a telematic platform for the prevention of readmissions in patients discharged due to an exacerbation of their COPD

Introducción. Las exacerbaciones de la enfermedad pulmonar obstructiva crónica (EPOC) tienen un impacto negativo en la salud y la calidad de vida de los pacientes con EPOC. Un porcentaje importante de pacientes dados de alta por una exacerbación de esta enfermedad requieren un reingreso. El objetivo de nuestro estudio fue valorar la utilidad de un programa de asistencia telefónica en la prevención de asistencias a urgencias y reingresos en pacientes dados de alta en nuestro servicio por exacerbación de EPOC. Pacientes y métodos. Los pacientes incluidos fueron aleatorizados en 2 grupos: a) grupo de intervención, en el que se realizó una llamada telefónica a los pacientes cada 15 días tras el alta hasta completar un periodo de seguimiento de 90 días, con la finalidad de llevar a cabo un control clínico; b) grupo de no intervención, en el que se efectuó una única llamada telefónica de control clínico a los 90 días del alta para registrar su situación clínica y las incidencias acaecidas durante dicho periodo. Resultados. En relación con la tasa de exacerbaciones, se objetivó una reducción no estadísticamente significativa en ambos grupos (grupo intervención: 4,33 ± 4,21 al inicio del estudio vs 0,55 ± 0,88 al final del estudio; grupo no intervención: 3,81 ± 2,08 al inicio del estudio vs 1,09 ± 1,22 al final del estudio). También se encontró una disminución no estadísticamente significativa de la tasa de ingresos hospitalarios (grupo intervención: 4,11 ± 3,58 vs 0,44 ± 0,72; grupo no intervención 3,72 ± 2,05 vs 0,63 ± 1,20). En cuanto al número de días de ingreso hospitalario, tampoco se encontraron diferencias estadísticamente significativas en los dos grupos (grupo intervención: 7,6 ± 3,47 al inicio del estudio vs 3,3 ± 3,05 al final del estudio; grupo no intervención: 7,45 ± 4,78 al inicio del estudio vs 9,4±15,63 al final del estudio). La mortalidad fue similar en ambos grupos (1 fallecido en cada grupo). Conclusiones. En nuestra muestra, la implantación de un programa de asistencia telemática a los pacientes con EPOC no ha conseguido reducir de una manera significativa la tasa de exacerbaciones, los ingresos hospitalarios o la mortalidad en el grupo intervención en comparación con el grupo no intervención

Introduction. COPD exacerbations have a negative impact on health and quality of life of COPD patients. A significant percentage of patients discharged due to an exacerbation of this disease require re-entry. The aim of our study was to assess the usefulness of a telephone assistance program in the prevention of emergency care and readmissions in patients discharged from our service due to exacerbation of COPD. Patients and methods. We included patients, randomized into 2 groups: a) intervention group, in which a telephone call was made every 15 days after discharge until completing a follow-up period of 90 days, in order to carry out a clinical control. b) non-intervention group, in which a single clinical control telephone call was made 90 days after discharge to record their clinical situation and the incidents that occurred during that period. Results. In the exacerbation rate, a non-statistically significant reduction was observed in both groups (intervention group: 4.33 ± 4.21 at the beginning of the study vs 0.55 ± 0.8 at the end of the study, non-intervention group: 3.81 ± 2.08 at the beginning of the study vs 1.09 ± 1.22 at the end of the study). We also found a non-statistically significant decrease in the hospital admissions rate (intervention group: 4.11 ± 3.58 vs 0.44 ± 0.72, non-intervention group 3.72 ± 2.05 vs 0.63 ± 1.20). In relation to the number of hospital admission days, no statistically significant differences were found in the two groups either (intervention group: intervention group: 7.6 ± 3.47 at the beginning of the study vs. 3.3 ± 3.05 at the end of the study; no intervention group: 7.45 ± 4.78 at the beginning of the study vs 9.4 ± 15.63 at the end of the study). Mortality was similar in both groups (1 death in each group). Discussion. In our sample, the implementation of a telematic assistance program for patients with COPD has not significantly reduced the rate of exacerbations, hospital admissions or mortality in the intervention group compared to the non-intervention group

Características de los pacientes con hipertensión pulmonar tromboembólica crónica atendidos en una consulta específica de hipertensión pulmonar / No disponible

La hipertensión pulmonar tromboembólica crónica (HPTEC) es una complicación a largo plazo de la embolia pulmonar sintomática, con una incidencia acumulada del 1-5% en los 2 años siguientes al episodio. Además, alrededor del 40% de los casos tiene su origen en un tromboembolismo venoso asintomático. En estos casos se recomienda la administración de anticoagulación oral a largo plazo. No obstante, hay que tener en cuenta que el único tratamiento curativo es la tromboendarterectomía. Para los pacientes no candidatos a cirugía, con malos resultados tras la misma, o como puente antes de la intervención, está indicado el tratamiento médico. El fármaco más estudiado en esta enfermedad es el bosentán, que ha demostrado que mejora significativamente la resistencia vascular pulmonar y el índice cardíaco. En este artículo se analizan los diferentes tipos de tratamiento disponibles en la actualidad, mediante el análisis de seis casos de HPTEC atendidos en una consulta específica durante un periodo de 2 años (AU)

Chronic thromboembolic pulmonary hypertension (CTEPH) is a long-term complication of symptomatic pulmonary embolism, with an incidence of 1-5% in the two years following the episode. In addition, about 40% of cases stems from asymptomatic venous thromboembolism. In these cases we recommend the administration of long-term oral anticoagulation. However, we must bear in mind that the only curative treatment is thromboendarterectomy. For patients who are not candidates for surgery, with poor results after the same, or as a bridge before surgery, medical treatment is indicated. The most studied drug in this disease is the bosentan, which has shown to significantly improve pulmonary vascular resistance and cardiac index. This article discusses the different types of treatment available today, through the analysis of six cases of CTEPH treated in a separate consultation for a period of two years (AU)

La punción-aspiración es una técnica segura y eficazen el tratamiento del neumotórax espontáneo primario / Needle aspiration is safe and effective for treating primary spontaneous pneumothorax

Objetivo: Demostrar la eficacia y seguridad de la técnica de punción-aspiración (PA) en el tratamiento del neumotórax espontáneo primario (NEP).Método: Estudio retrospectivo basado en una base de datos prospectiva de pacientes con neumotórax espontáneo primario que acudieron al servicio de urgencias (10 años).Se compara a los pacientes en los que se ha realizado la punción-aspiración (PA) frente a los que no. Además, se compara en términos de recidivas, reingresos, necesidad de cirugía o complicaciones, el grupo con un manejo ambulatorio frente al grupo de manejo hospitalario, y se analizan las variables asociadas al éxito de la técnica. Resultados: Se observan características similares en cuanto a las variables descriptivas(sexo, lado del neumotórax, hábito tabáquico, volumen aspirado) entre los dos grupos. La PA parece ser un factor protector en cuanto a la necesidad de ingreso con una OR0,7 (IC95: 0,62-0,78). No se observan diferencias significativas en cuanto a recidivas, reingresos o necesidad de intervención quirúrgica. Ninguna variable descriptiva ha mostrado relación con el éxito o fracaso de la técnica. La incidencia de complicaciones condicha técnica ha sido del 2,4%.Conclusiones: La técnica de PA es segura y eficaz como primer escalón en el tratamiento del NEP y reduce los ingresos hospitalarios sin aumentar el riesgo de reingreso o recidiva (AU)

Objective: Our main aim was to demonstrate the efficacy and safety of needle aspiration for treating primary spontaneous pneumothorax. Methods: Retrospective study of data collected prospectively for patients who came to the emergency department with primary spontaneous pneumothorax over a 10-year period. We compared patients who underwent needle aspiration to those who did not. Patients who were hospitalized were compared to those managed as outpatients in terms of recurrences, readmissions, need for surgery, and complications. Variables that might be related to the success of the procedure were explored. Results: Patients who underwent needle aspiration were similar to those who did not with respect to sex, side affected, and pneumothorax size (volume), and smoking status. Needle aspiration seems to be a protective factor against hospitalization (odds ratio, 0.7; 95% CI, 0.62-0.78). No significant between-group differences were detected with respect to recurrence, readmission, or need for surgery. None of the descriptive variables were related to success or failure of needle aspiration. The incidence of complications of needle aspiration was 2.4%Conclusions: Needle aspiration is a safe, effective first-line treatment for primary spontaneous pneumothorax and does not increase risk for readmission or recurrence (AU)

Refugial isolation and divergence in the Narrowheaded Gartersnake species complex (Thamnophis rufipunctatus) as revealed by multilocus DNA sequence data.

Glacial-interglacial cycles of the Pleistocene are hypothesized as one of the foremost contributors to biological diversification. This is especially true for cold-adapted montane species, where range shifts have had a pronounced effect on population-level divergence. Gartersnakes of the Thamnophis rufipunctatus species complex are restricted to cold headwater streams in the highlands of the Sierra Madre Occidental and southwestern USA. We used coalescent and multilocus phylogenetic approaches to test whether genetic diversification of this montane-restricted species complex is consistent with two prevailing models of range fluctuation for species affected by Pleistocene climate changes. Our concatenated nuDNA and multilocus species analyses recovered evidence for the persistence of multiple lineages that are restricted geographically, despite a mtDNA signature consistent with either more recent connectivity (and introgression) or recent expansion (and incomplete lineage sorting). Divergence times estimated using a relaxed molecular clock and fossil calibrations fall within the Late Pleistocene, and zero gene flow scenarios among current geographically isolated lineages could not be rejected. These results suggest that increased climate shifts in the Late Pleistocene have driven diversification and current range retraction patterns and that the differences between markers reflect the stochasticity of gene lineages (i.e. ancestral polymorphism) rather than gene flow and introgression. These results have important implications for the conservation of T. rufipunctatus (sensu novo), which is restricted to two drainage systems in the southwestern US and has undergone a recent and dramatic decline.

[Misleading presentation of rhombencephalitis due to Listeria monocytogenes]. / Romboencefalitis por Listeria de presentación equívoca.

INTRODUCTION: Rhombencephalitis due to Listeria monocytogenes may present in a variety of forms. CASE REPORT: We describe the case of a 76 years old male presenting with an acute symmetrical palsy of fifth, seventh, ninth-tenth cranial nerves, ophthalmoparesia and miosis, without evident signs of long tract lesion, mimicking a peripheral nervous system or neuromuscular junction disease. The results of the blood cultures and the magnetic resonance imaging gave the diagnosis of rhombencephalitis due to Listeria. CONCLUSIONS: Rhombencephalitis due to Listeria monocytogenes may present as a symmetric palsy of cranial nerves, therefore it can mimic a cranial nerves multineuritis syndrome.

Romboencefalitis por Listeria de presentación equívoca / Misleading presentation of rhombencephalitis due to Listeria monocytogenes

Introducción. La romboencefalitis por Listeria monocytogenes es una infección del sistema nervioso que se puede presentar de formas muy variadas. Caso clínico. Presentamos a un paciente de 76 años con afectación aguda simétrica de los pares craneales quinto, séptimo, noveno-décimo junto con oftalmoparesia y miosis, sin signos claros de lesión de vías largas de tronco, que orientaron inicialmente a sospechar una enfermedad del sistema nervioso periférico o de placa motora. El resultado de los hemocultivos y de las imágenes de resonancia magnética permitió establecer el diagnóstico de romboencefalitis por Listeria. Conclusiones. La romboencefalitis por Listeria monocytogenes puede manifestarse en forma de parálisis aguda simétrica de pares craneales, pudiendo ser confundida con un cuadro de multineuritis de pares craneales

Introduction. Rhombencephalitis due to Listeria monocytogenes may present in a variety of forms. Case report. We describe the case of a 76 years old male presenting with an acute symmetrical palsy of fifth, seventh, ninth-tenth cranial nerves, ophtalmoparesia and miosis, without evident signs of long tract lesion, mimicking a peripheral nervous system or neuromuscular junction disease. The results of the blood cultures and the magnetic resonance imaging gave the diagnosis of rhombencephalitis due to Listeria. Conclusions. Rhombencephalitis due to Listeria monocytogenes may present as a symmetric palsy of cranial nerves, therefore it can mimic a cranial nerves multineuritis syndrome

Head shape and bite performance in xenosaurid lizards.

Bite performance in lizards influences many aspects of the animal's lifestyle. During feeding, inter- and intrasexual interactions, and defensive behavior, the ability to bite hard might be advantageous. Although biomechanical considerations predict clear relations between head shape and bite performance, this has rarely been tested. Here we investigate the effect of head shape on bite performance in three closely related species of xenosaurid lizards. Our data show that in this family of lizards, bite performance is mainly determined by head height, with high headed animals biting harder than flat headed ones. Species clearly differ in head shape and bite performance and show a marked sexual dimorphism. The dimorphism in head shape also results in an intersexual difference in bite performance. As head height is the major determinant of bite performance in xenosaurid lizards, trade offs between a crevice dwelling life-style and bite performance seem to occur. The evolutionary implications of these results are discussed. J. Exp. Zool. 290:101-107, 2001.

S 15261, a novel agent for the treatment of insulin resistance. Studies on Psammomys obesus. Effect on pancreatic islets of insulin resistant animals.

A histological study has been conducted on pancreata from insulin resistant sand rats treated with S15261. As previously shown, standard laboratory chow induced dietary hyperinsulinaemia, insulin resistance and hyperlipaemia in sand rats (Psammomys obesus). Degranulation, vacuolization and even necrosis of beta-cells were observed in these animals. These changes were often accompanied by fibrosis and lymphocytic infiltration. Insulin and amylin immuno-reactivity of beta-cells was markedly decreased whilst glucagon secreting cells were localized now in the centre of the islets. Chronic treatment with S15261, a compound able to restore insulin sensitivity in insulin resistant animals, promoted the regranulation of the beta-cells and maintained the usual cytoarchitecture and integrity of the islets.

S15261, a novel agent for the treatment of insulin resistance. Studies on Psammomys obesus.

S15261 is a novel compound that has been proposed for the treatment of insulin resistance syndrome. We have studied the effects of this drug in insulin resistant sand rats (Psammomys obesus). When sand rats are transferred from their natural desert environment and placed on a laboratory chow diet, they become overweight, develop hypertriglyceridaemia, hypercholesterolaemia, become insulin resistant, and ultimately diabetic. In the present study glucose intolerant animals, with very mild if any hyperglycaemia were used. Chronic treatment for a month with S15261 normalised plasma levels of triglycerides and cholesterol. The effects on cholesterol were the result of a decrease in LDL- and VLDL-cholesterol without any modification of HDL-cholesterol. In this study only female sand rats showed elevated plasma glucose levels, which were normalised by S15261. The compound also decreased plasma insulin levels both in male and female sand rats. An oral glucose tolerance test showed a major improvement in glucose tolerance in both male and female animals treated with S15261. These data confirm in another animal model the therapeutic benefits of S15261 in insulin resistant states.

Euglycaemic and biological activities of novel thiazolidine-2,4-dione derivatives.

A new series of thiazolidine-2,4-dione derivatives was obtained by incorporating one or the other of the two carbons of the central chain into different rings. These compounds lower blood glucose levels in the genetically obese and insulin-resistant ob/ob mouse. Moreover, they decreased insulin and triglyceride levels in the Zucker fa/fa rat. Incorporation of the left hand carbon of the chain afforded compounds among which pyrrolidino derivatives 5, 9 and 13 were the most potent. The same carbon atom was used to elaborate different types of rings (benzocyclobutane, benzodioxane), giving rise to compounds 14 and 19 with moderate to good activity. Finally, cyclization using the right hand carbon of the chain gave rise to highly potent benzofurane 24.

Synthesis of 1,2-diacyl-3-nicotinoyl glycerol derivatives and evaluation of their acute effects on plasma lipids in the rat.

Nicotinic acid (CAS 59-67-6) is the only hypolipidemic agent whose activity has been shown both on atherosclerotic lesions and on long term mortality. Unfortunately, its use is hindered by the frequent occurrence ( > 70%) of adverse reactions (i.e. cutaneous rash, pruritus and, most significantly, flush). New prodrugs of nicotinic acid have been prepared by the use of diacylglycerol esters. In the rat, after acute oral administration of these products, a significant decrease of the free fatty acid plasma levels was obtained without the dramatic increase in nicotinic acid plasma levels observed after the oral administration of an equimolecular dose of nicotinic acid. The most interesting ester, S 16961 ((d,l)-1,2-dipalmitoyl-3-nicotinoyl glycerol, CAS 160555-46-4) is undergoing clinical trials.

S15261 antagonises amylin-induced impaired glucose tolerance.

Amylin has been postulated to antagonise or inhibit the action of insulin in peripheral rat tissues and thus contribute to, or be responsible for, the development of insulin resistance. We have recently reported that S15261 is a compound capable of increasing insulin sensitivity in ageing insulin resistant rats. In order to assess whether S15261 had any effects on amylin induced insulin resistance we used a model where amylin causes an impairement in glucose tolerance in an acute manner, by means of an intraportal infusion of the hormone in normal rats. We report here that S15261 can antagonise this amylin-induced impaired glucose tolerance.

Latent autoimmune diabetes mellitus in adult humans with non-insulin-dependent diabetes: is Psammomys obesus a suitable animal model?

Recent data suggest that in a proportion of NIDDM patients there is a slowly evolving insulitis which results in a latent autoimmune diabetes leading to full insulin-dependence. Many animal models exist of NIDDM but none have reported the spontaneous existence of a similar phenomenon. We have re-examined the histology of pancreata from a few Psammomys obesus who had become insulin-dependent in the late stages of NIDDM. We report here the unexpected finding of the presence of insulitis in these animals and suggest that they could be a model for the clinical observation of latent IDDM in NIDDM patients.

S15261, a new compound for the treatment of the insulin resistance syndrome.

A new oral agent, S15261 (the L-isomer of 3-[2-[2-[4-[2-[alpha-fluorenyl acetyl amino ethyl] benzoyloxy] ethyl amino] 1-methoxy ethyl] trifluoromethyl-benzene), has been developed for the treatment of the so-called "insulin resistance syndrome". In obese, insulin-resistant ageing Sprague-Dawley rats, chronic treatment with S15261 (0.5-2.5 mg.kg-1.day-1 twice per day, for 14 days) resulted in dose-dependent decreases in plasma insulin (43%), and triglyceride levels (36%), and in an increase of the glucose disposal rate during an intravenous glucose tolerance test (IVGTT) (48.5%). An increase in peripheral insulin sensitivity produced by S15261 was revealed by the glucose clamp technique. Thus, the glucose infusion rate was increased by 20% whilst steady-state insulin levels decreased by 15%. At the higher doses S15261 led to a decrease in body weight (3%), plasma glucose (13%) and blood pressure (8 mm Hg) in mildly hypertensive animals. At the doses used to achieve these results, the compound has no hypoglycaemic activity in normoglycaemic animals. Acute administration of S15261 directly into the portal vein provoked a marked increase in glucose disappearance rate during an intravenous glucose tolerance test (60%) and also in the pancreatic response to the glucose challenge. Thus, acute administration of the compound has a direct effect on glucose metabolism. These data suggest that S15261 could be a useful agent for the treatment of the insulin resistance syndrome.

Islet amyloid polypeptide in Psammomys obesus: lack of correlation between insulin resistance and plasma IAPP levels.

Sand rats (Psammomys obesus) develop insulin resistance and diabetes when given a standard laboratory diet. We have examined the presence of islet amyloid polypeptide (IAPP), or amylin, in these animals. IAPP is present in the beta-cells of pancreatic islets, its localization and intensity of immuno-reactivity are, thus, similar to that of insulin. In insulin resistant Psammomys obesus, insulin and IAPP immuno-reactivity in pancreas are markedly decreased, plasma insulin levels are 20-fold higher than in controls but IAPP levels are not different from those of normal animals. Therefore, insulin resistance in Psammomys obesus does not appear to result from an elevated plasma IAPP level nor from development of amyloid deposits.

8-OH-DPAT induces a selective increase in protein intake in ageing overweight animals.

We have examined the effects of a 5-HT1A receptor agonist (8-hydroxy-2-(di-n-propylamino)tetralin, 8-OH-DPAT) on food preference in ageing rats that had been given a 'palatable' meal 15 min before administration of the drug. Ageing rats consumed a greater amount of the 'palatable' pre-meal than the young rats. In young rats lipids were the predominant source of calories, but in old animals lipid and protein consumption was similar. Administration of 8-OH-DPAT resulted in an increase in total caloric intake in both groups. Concomitant with this there was a significant increase in protein intake in both groups, which was most important in ageing rats, where proteins became the predominant source of calories.