The evaluation of tactile dysfunction in the hand in type 1 diabetes: a novel method based on haptics.

AIMS: We present an innovative method based on haptics for the evaluation of the sense of touch in the hand, in people affected by type 1 diabetes. METHODS: Forty individuals affected by diabetes and 20 healthy controls took part in the study; the diabetes group was further divided into two subgroups based on vibration sensitivity in the lower limb. By means of a novel haptic device, tactile sensitivity in the fingertip was measured as the ability of the participants to discriminate slip motion speed. RESULTS: Tactile sensitivity was significantly lower in individuals affected by diabetes as compared to controls. Depending on the subgroup, the difference from the controls was equal to 0.11 (95% CI from 0.029 to 0.186) and to 0.267 (95% CI from 0.198 to 0.336). Within the diabetes group, tactile sensitivity correlated with vibration sensitivity in the upper (p = 0.001) and lower limb (p = 0.003). A significant relationship between nerve conduction parameters and tactile sensitivity was found (p = 0.03). Finally, we combined the different predictors (clinical, vibratory and electroneurography data) by using cluster analysis; tactile sensitivity was found to be significantly different between different clusters (p = 0.004). CONCLUSIONS: Early signs of tactile dysfunction in the hand were found in individuals affected by diabetes, even in absence of diabetic neuropathy. The protocol presented in this study is a promising tool for the assessment of tactile dysfunction in the hand in people affected by type 1 diabetes.

Low-lipid diet reduces frequency and severity of acute migraine attacks.

BACKGROUND AND AIM: There is uncertainty regarding the prevention of migraine crises by changing the lifestyle of patients. The aim of this randomized, crossover intervention trial was to evaluate the effects of a low lipid intake on the incidence and severity of migraine crises, in comparison to a diet with moderate lipid intake. METHODS AND RESULTS: After a 2-month run-in when patients received preventive medication but were left on their habitual diet, a low-lipid or a normal-lipid diet was randomly prescribed for 3 months and thereafter diets were crossed over for the following 3 months. Headache was diagnosed based on the International Classification of Headache Disorders (IHCD) III criteria. The number and severity of attacks were assessed using a self-reported calendar. Adherence to the diet was assessed by a food frequency questionnaire. An analysis was performed on the 83 episodic or chronic migraineurs (63 female and 20 male), in the age range of 18-57 years, who completed both intervention periods. Obese subjects had a significantly higher number of attacks than those overweight or with normal body weight (24.7 ± 8, 16.3 ± 12, and 15.6 ± 11, respectively, p < 0.03) with a significant relationship between the body mass index (BMI) and the number of monthly attacks (r = 0.238, p < 0.03). The number (2.9 ± 3.7 vs. 6.8 ± 7.5, p < 0.001) and severity (1.2 + 0.9 vs. 1.7 ± 0.9, p < 0.01) of attacks significantly decreased during both intervention periods, with a significant difference in favour of the low-lipid diet. CONCLUSIONS: In this group of patients, the low-lipid diet significantly affected the number and severity of migraine attacks in comparison to a normal-lipid diet. ClinicalTrials.gov Identifier: NCT 01917474.

Molecular determinants of positive allosteric modulation of the human metabotropic glutamate receptor 2.

BACKGROUND AND PURPOSE: The activation of the metabotropic glutamate receptor 2 (mGlu2 ) reduces glutamatergic transmission in brain regions where excess excitatory signalling is implicated in disorders such as anxiety and schizophrenia. Positive allosteric modulators (PAMs) can provide a fine-tuned potentiation of these receptors' function and are being investigated as a novel therapeutic approach. An extensive set of mutant human mGlu2 receptors were used to investigate the molecular determinants that are important for positive allosteric modulation at this receptor. EXPERIMENTAL APPROACH: Site-directed mutagenesis, binding and functional assays were employed to identify amino acids important for the activity of nine PAMs. The data from the radioligand binding and mutagenesis studies were used with computational docking to predict a binding mode at an mGlu2 receptor model based on the recent structure of the mGlu1 receptor. KEY RESULTS: New amino acids in TM3 (R635, L639, F643), TM5 (L732) and TM6 (W773, F776) were identified for the first time as playing an important role in the activity of mGlu2 PAMs. CONCLUSIONS AND IMPLICATIONS: This extensive study furthers our understanding of positive allosteric modulation of the mGlu2 receptor and can contribute to improved future design of mGlu2 PAMs.

Glucocorticoids in systemic sclerosis: patients' beliefs and treatment adherence.

OBJECTIVES: To investigate how chronic intake of glucocorticoids (GCs) is perceived by patients with systemic sclerosis (SSc) in terms of necessity and concerns, and whether such beliefs influence treatment adherence. METHOD: Ninety-eight consecutive SSc patients who they had been taking oral GCs for > 3 months prior to the study were enrolled. All patients underwent a clinical evaluation and laboratory investigations, and were asked to complete four self-administered questionnaires: the Beliefs about Medicines Questionnaire (Specific-BMQ), the four-item Morisky Medication Adherence Scale (MMAS-4), the 36-item Short Form Health Survey (SF-36), and the Health Assessment Questionnaire Disability Index (HAQ-DI). Moreover, patients answered two additional questions investigating their knowledge about GC-related adverse events (AEs). RESULTS: Seventy-seven patients (83.6%) believed in the necessity of GCs for maintaining health but 72.8% also reported concerns about potential AEs to GCs. A high adherence rate was recorded in 64.1% of patients. Only about 20% of patients reported knowing that a daily GC dose and treatment duration influence the burden of GC-related AEs. Patients who believed that GC-related AEs were influenced by the dose scored lower concerns (p = 0.043) and were more frequently labelled as accepting (perceiving high necessity and low concerns) (p = 0.009). CONCLUSIONS: The majority of patients taking GCs perceived them as necessary, but high concerns about chronic GC use exist. Patients with a poorer knowledge of the factors associated with GC-related AEs and those with a poorer quality of life were the most worried about these compounds. Experimental studies assessing the efficacy of educational programmes aiming to increase the adherence to GC therapy should be planned in these patients.

Methodologies to study the surface hydraulic behaviour of urban catchments during storm events.

A good knowledge of the hydraulic behaviour of an urban catchment and its surface drainage system is an essential requirement to guarantee traffic and pedestrian safety. In many cases, inlets have been situated according to spatial density criteria. Indeed a more rational location of inlets on urban catchments must be defined according to an accurate analysis of the relationship between street flow and inlet hydraulic efficiency. Moreover we lack specific hazard criteria in terms of the maximum acceptable flow depths and velocities on the streets that do not cause problems to pedestrians. In this paper the results of two different experimental campaigns are presented. The first was carried out to evaluate inlet hydraulic efficiency; the second was carried out to address the pedestrian stability in urban flood conditions, whose aim was to propose new hazard criteria. On the basis of the experimental results, a methodology was developed to assess flood hazard in urban areas during storm events. If a refined topographic representation of urban areas is available, a two-dimensional numerical simulation of urban flooding can be performed using complete shallow water equations. According to this approach a numerical application for flood hazard assessment in a street of Barcelona is shown.

Prevención de la deformidad de la cabeza femoral con necrosis isquémica en cerdos inmaduros, utilizando ácido ibandrónico y factores de crecimiento / Prevention of deformity of the femoral head in immature pigs by using ibandromic acid and growing factors to induce ischemic necrosis

La enfermedad de perthes en niños presenta como un desafío de tratamiento aún en la actualdad. A pesar de enumerarse varias causas todavía, evitar el colapso de la cabeza femoral es el paradigma que genera múltiples investigaciones. La base de este trabajo de investigación fue provocar en forma mecánica la necrosis avascular de la cabeza femoral y mediante el uso de ácido ibandrónico y concentrado plaquetario demostrar sus beneficios en esta patología.(AU)

Prevención de la deformidad de la cabeza femoral con necrosis isquémica en cerdos inmaduros, utilizando ácido ibandrónico y factores de crecimiento / Prevention of deformity of the femoral head in immature pigs by using ibandromic acid and growing factors to induce ischemic necrosis

La enfermedad de perthes en niños presenta como un desafío de tratamiento aún en la actualdad. A pesar de enumerarse varias causas todavía, evitar el colapso de la cabeza femoral es el paradigma que genera múltiples investigaciones. La base de este trabajo de investigación fue provocar en forma mecánica la necrosis avascular de la cabeza femoral y mediante el uso de ácido ibandrónico y concentrado plaquetario demostrar sus beneficios en esta patología.

Clinical effects of early treatment with insulin glargine in patients with cystic fibrosis and impaired glucose tolerance.

Diabetes mellitus is an increasing complication of cystic fibrosis (CF), as a result of the improved life expectancy. There is clear association between diabetes and increased morbidity and mortality. Lung function and clinical status deteriorate up to 2-4 yr before the diagnosis of CF-related diabetes (CFRD). The aim of our study was to evaluate the effects, on glucose homeostasis and clinical status, of the early treatment with insulin glargine in CF patients with impaired glucose tolerance (IGT). We selected six subjects with IGT diagnosed at oral glucose tolerance test (OGTT). Median age was 18.12 yr (range 9.2-27.8). Insulin glargine was administered at the median dosage of 0.3 U/kg/day (range 0.2-0.5). After the initial adjustment of the dosage, no patient manifested hypoglycemia during treatment. Median glycosylated hemoglobin (HbA1c) did not show any significant variation during treatment: it was 5.9% at baseline (range 5.5-6.2) and 6.1% (range 5.0-6.7) at the end of follow-up (p=0.496). Median body mass index (BMI) z-score significantly increased during treatment, from -0.95 (range -3.2-+0.6) at baseline to -0.5. (range -3.0-+0.9) at the end of follow-up (p=0.026). Lung function, measured by median forced expiratory volume in the first second (FEV1%), showed a mild but significant improvement during insulin treatment. It was 72.7% at baseline (range 41.5-98.4) and 76.7% (range 42.0-106.8) at the end of follow-up (p=0.027). No significant variation was found between the number of hospitalizations for clinical exacerbation (no./patient/yr) in the last 2 yr before treatment and during follow-up. Median number at baseline was 1.95/patient/yr (range 1-3) and 2.0/patient/yr (range 1-3) at follow-up (p=0.715). Our data seem to indicate that early insulin therapy can be safe, no patient manifested hypoglycemia or other adverse effects during treatment. Insulin is an anabolic hormone implicated in both lipid and protein metabolism. The appearance of IGT out of infections can indicate an early insulin deficiency, with a potential impact on the nutritional and clinical status of the patient, even before the appearance of overt diabetes. Larger controlled trials are necessary to verify if early insulin therapy is able to reduce the deterioration of nutritional status and lung function associated with the onset of IGT.

[Acute myocardial infarction complicated by ventricular aneurysm during pregnancy. A clinical case and review of the literature]. / Infarto acuto del miocardio complicato da sviluppo di aneurisma ventriculare in gravidanza. Descrizione di un caso e revisione della letteratura.

Acute myocardial infarction is an uncommon complication in pregnant women. The case of a 30-years-old patient who suffered of an acute myocardial infarction during the first trimester of pregnancy, with secondary development of left ventricular aneurysm is presented. She had a sudden death 3 months after delivery, while waiting for coronary arteriography.

[Videolaparoscopic adrenalectomy in an unusual case of adrenal mycetoma]. / La surrenectomia video-laparoscopica in un raro caso di micetoma del surrene.

The authors report a rare case of mycetoma of the adrenal gland. Mycetoma is a chronic, localized, non-contagious infection of cutaneous and subcutaneous tissue characterized by tumefaction, aggregates of aetiological agents (Actinomyces or true fungi). Sometimes an unusual site (other tissues or organs) is described in the literature, but to date no cases of adrenal gland mycetoma have been reported. The treatment of choice is surgical with associated penicillin and/or antifungal drugs. In the case reported surgical treatment is performed with a laparoscopic approach. This technique constitutes the gold standard in cases of benign neoplasms of the adrenal gland and incidentalomas. This therapeutic choice is open to criticism if a malignant neoplasm is suspected.

[Laparoscopic surgical treatment of cholecysto-choledochal calculi. A single step solution]. / Trattamento chirurgico laparoscopico della calcolosi colecisto-coledocica. La soluzione in un unico atto.

The laparoscopic era has created a new basis for the management of choledocholithiasis. Many surgeons now regard laparoscopic cholecystectomy and exploration of the common bile duct as the "gold standard". The main advantages of single-stage treatment consist in a significantly shorter hospital stay, very low complication rates and a reduction of average hospital costs. Among 601 cases of cholelithiasis treated over the period from 1994 to 1999, we report 73 cases of common-bile-duct stones. Surgical sphincterotomy was performed in 20 cases and endoscopic sphincterotomy in 24; only in 7 cases was choledochotomy and/or hepaticojejunostomy (3 cases) performed for critical situations. Twenty-two cases of cholelithiasis were treated by laparoscopic cholecystectomy and exploration of the common bile duct. Stone extraction was obtained with a balloon catheter or Dormia basket via a choledochotomy. Surgery was completed by suturing, cholangiography and the placement of sub-hepatic drainages. No mortality or long-term complications were recorded with the laparoscopic procedure; only two immediate complications were reported, both of which were biliary leakages (9%) that resolved spontaneously. With the other procedures, high rates of mortality, morbidity, hospital admissions and technical failure were registered. We regard laparoscopic exploration of the common bile duct as the treatment of choice for bile-duct stones when combined with cholecystectomy. We reserve ERCP plus endoscopic sphincterotomy only for common-bile-duct stones alone, without a gallbladder or gallstones. Open surgery is performed in particular situations such as Mirizzi's syndrome or when other procedures have failed to yield satisfactory results.

[The laparoscopic treatment of esophageal achalasia. Our experience]. / Trattamento laparoscopico dell'acalasia esofagea. Nostra esperienza.

BACKGROUND: Laparoscopic Heller myotomy combined with a Dor fundoplication is considered the procedure of choice to treat esophageal achalasia. The aim of this study is to report a personal experience and to analyse the controversial aspect of this procedure. METHODS: From January 1997 to March 1998 six patients with esophageal achalasia were treated by Heller laparoscopic myotomy with anterior fundoplication. RESULTS: There was one intraoperative perforation of esophageal mucosa, sutured laparoscopically with non postoperative sequelae. There were no surgical mortality and no postoperative morbidity. Complete relief of dysphagia in five of six patients, the good clinical and instrumental results and the satisfaction of these patients, lead to a prudent optimism. CONCLUSIONS: Personal initial experience, although the little number of patients and the short follow-up, confirms that laparoscopic cardiomyotomy is a safe and effective procedure for the treatment of esophageal achalasia.

[The epiphrenic esophageal diverticulum. Its transhiatal laparoscopic treatment]. / Diverticolo esofageo epifrenico. Trattamento laparoscopico trans-iatale.

A new laparoscopic surgical approach to treat an esophageal epiphrenic diverticulum is described. This is a rare disease. Today only 4 cases of laparoscopic transhiatal treatment with good results are reported in the literature. The present case report is an 80 years-old male with medium size epiphrenic diverticulum (10 cm) and very symptomatic dysphagia. Preoperative investigations include barium swallow, upper gastrointestinal endoscopy and esophageal manometry. The laparoscopic transhiatal treatment was carried out without difficulty. Diverticulectomy esophageal myotomy and partial gastric fundoplication (Dor) were performed. No postoperative complication was recorded and optimal result was achieved. In conclusion, the efficacy of laparoscopic approach is underlined and the short and medium-term results are satisfactory.

A spatio-temporal comparison of semantic and episodic cued recall and recognition using event-related brain potentials.

The event-related brain potential (ERP) was used to spatially and temporally map the brain areas active as a function of type of recall (semantic vs. episodic) and episodic retrieval mode (recall vs. recognition) while difficulty of episodic recall was manipulated. ERPs were recorded from 32 scalp sites in 12 subjects, along with behavioral accuracy and recall speed. The results revealed that different but overlapping patterns of ERP activity were elicited during semantic and episodic recall. Recall of both types of information was characterized by ERP activity over left inferior frontal, central, bilateral temporal and posterior inferior brain areas. Compared to semantic recall, episodic recall elicited more activity over the frontal poles and right frontal scalp. Different but overlapping patterns of ERP activity were also found as a function of episodic retrieval mode. While episodic recall and recognition showed similar activity over the frontal poles and central scalp, there was no left inferior frontal activity elicited during recognition and no large, topographically widespread, late positive component (LPC) elicited when the same words were recalled. Manipulation of episodic recall difficulty and analysis of trials when recall failed indicated that these task (i.e., episodic vs. semantic) and retrieval mode (recall vs. recognition) differences in ERP activity were not likely to be due to differences in task difficulty. The results are discussed in terms of processes that the ERP activity may reflect and their similarity to results of PET studies of semantic and episodic retrieval.

A spatio-temporal analysis of recognition-related event-related brain potentials.

Words correctly recognized as previously studied (i.e. old) elicit greater amounts of positive event-related brain potential (ERP) activity over posterior scalp between 400 and 800 ms than do previously unstudied (i.e. new) words. While investigators have reported that this old/new effect consists of more than one subcomponent, the spatio-temporal parameters of these possible subcomponents, as well as any other patterns of brain activity associated with recognition, remain incompletely specified. Thus, ERPs were recorded from 32 scalp sites while 13 subjects performed four repetitions of a study-test recognition paradigm. The subjects' task was to decide whether each word was old or new and press the appropriate button as quickly as possible. The timing and topography of the ERPs elicited by old and new words was assessed with topographic profile comparisons on the areas with a variety of temporal windows, and visualized with potential and CSD maps. The results revealed that seven patterns of ERP activity, dissociable on the basis of their topography, timing and response to experimental variables, were elicited between 300 and 2000 ms. Three of these appeared as subcomponents of the old/new effect (maximal over left medial frontal, left parietal-occipital and right central-frontal scalp), another was related to decision confidence and/or memory trace strength (maximal over left central scalp) and three others appeared to be related to more general aspects of recognition (maximal over the frontal poles, midline frontal scalp and right frontal scalp). Taken together, the seven distinct patterns of neural generator activity described here support the hypothesis that retrieval of information from episodic memory depends on a collection of different processes that occur in a temporally and spatially distributed neural circuit.

[Laparoscopic incidental diagnosis: treatment during laparoscopic surgery]. / Patologie incidentali in chirurgia laparoscopica. Quale atteggiamento?

BACKGROUND: The authors consider the importance of laparoscopic exploration of the abdominal cavity for the diagnosis of mistaken preoperative pathologies, during laparoscopic surgery. RESULTS: In our series the incidental diagnosis is 5.3%. CONCLUSIONS: The additional treatment diagnosis is realized when there is no great surgical engagement or when there are risks for the patient's life (i.e.: hemorrhagic ovarian cyst). In case of incidental neoplasia diagnosis it would been more appropriate to do a biopsy only, for typing. The realization of demanding or non-programmed surgical operations must be consequent on written consent.

Categorización en el paciente politraumatizado pediátrico / Scoring of pediatric trauma patients

El politraumatismo es la principal causa de mortalidad en niños mayores de 1 año. Los scores de predicción de mortalidad en el politraumatismo constituyen índices de importancia para guiar las acciones terapéuticas y predecir el pronóstico. En el presente trabajo se estudio la capacidad predictiva de mortalidad de dos scores: ITP y MISS en 84 niños politraumatizados internados en la Unidad de Cuidados Intensivos del Hospital Harragan. El ITP con un punto de corte de 3 o menos demuestra una muy elevada especificidad y capacidad predictiva negativa asi como una adecuada sensibilidad. El MISS con punto de corte en 25 demostró alto valor predictivo negativo, pero menor capacidad predictiva positiva. El ITP constituye un recurso diagnóstico predictivo en el lugar del accidente para definir las acciones terapéuticas mientras que el MISS, aunque posee limitaciones puede emplearse en la evaluación de la gravedad en la Unidad de Cuidados Intensivos.

QTc and not QTc dispersion behavior affects the occurrence of ventricular extrasystole during exercise in infarcted patients.

Both a long QTc and a large QTc dispersion (QTcd) can predispose infarcted patients to ventricular arrhythmias. The former simply reflects a general prolongation of ventricular recovery time, whereas QTcd is useful for revealing regional inhomogeneities of ventricular repolarization. The aim of our study was to evaluate QTc and QTcd behavior during exercise in 50 patients (all men) with previous myocardial infarction, and its possible correlation with the occurrence of exercise-induced premature ventricular complexes (EIPVC). Our patients underwent ergometric stress test with a load increase of 25 W, every 2 min, until the maximal age-related heart rate or symptoms were obtained, followed by a 10-min recovery phase. QTc and QTcd measurement was performed at rest (BS) and during exercise at two progressively increasing heart rate steps: 100-115 beats/min (T1) and 116-130 beats/ min (T2). The patients were divided into two groups according to the absence (group A; n = 22) or presence (group B; n = 28) of EIPVC. In terms of QTcd, no significant difference was found between the two groups at BS, T1, and T2. As for the mean QTc (QTcm), it was significantly longer in group B at BS (416 +/- 22 ms versus 395 +/- 19 ms; P = 0.001) and at T1 (431 +/- 24 ms versus 410 +/- 8 ms; P = 0.0001). When group B was further differentiated into two subgroups-Bx and Bz-according to the severity of EIPVC, we noted that patients with the most severe arrhythmic response (group Bz; n = 12) showed a persisting, significantly longer QTcm than group A (BS, 426 +/- 28 ms versus 395 +/- 19 ms; P < 0.05; T1, 445 +/- 24 ms versus 410 +/- 8 ms; P < 0.05; T2, 427 +/- 17 ms versus 412 +/- 14 ms; P < 0.05), and group Bx (n = 16) (BS, 426 +/- 28 ms versus 409 +/- 15 ms; P < 0.05; T1, 445 +/- 24 ms versus 420 +/- 19 ms; P < 0.05; T2, 427 +/- 17 ms versus 410 +/- 17 ms; P < 0.05). Group Bx showed a significantly longer QTcm than group A only at BS (409 +/- 15 ms versus 395 +/- 19 ms; P < 0.05). No significant difference in QTcd was found between the three groups at BS, T1, and T2. We also noted that the relationship between QTcm and QTcd was modified by the exercise, changing from a trend of direct relation at BS, towards an inverse one during effort, which reached significance at T2 (r = -0.319; P = 0.037). Based on our data, EIPVC occurrence seems to be more affected by the total duration rather than by regional inhomogeneities of the ventricular recovery time. In those patients with the most severe arrhythmic response, the autonomic modifications generated by the exercise succeed in attenuating only the regional inhomogeneities, but do not eliminate the differences in total duration of the repolarization period.

Ionic mechanisms of ischemia-related ventricular arrhythmias.

The aim of this review is the utmost simplification of the cellular electrophysiologic background of ischemia-related arrhythmias. In the acute and subacute phase of myocardial infarction, arrhythmias can be caused by an abnormal impulse generation, abnormal automaticity or triggered activity caused by early or delayed afterdepolarizations (EAD and DAD), or by abnormalities of impulse conduction (i.e., reentry). This paper addresses therapeutic intervention aimed at preventing the depolarization of "pathologic" slow fibers, counteracting the inward calcium (Ca) influx that takes place through the L-type channels (Ca antagonists), or hyperpolarizing the diastolic membrane action potential, increasing potassium (K) efflux (K-channel openers) in arrhythmias generated by an abnormal automaticity (ectopic tachycardias or accelerated idioventricular rhythms). If the cause enhanced impulse generation is related to triggered activity, and since both EAD and DAD are dependent on calcium currents that can appear during a delayed repolarization, the therapeutic options are to shorten the repolarization phase through K-channel openers or Ca antagonists, or to suppress the inward currents directly responsible for the afterdepolarization with Ca blockers. Magnesium seems to represent a reasonable choice, as it is able to shorten the action potential duration and to function as a Ca antagonist. Abnormalities of impulse conduction (re-entry) account for the remainder of arrhythmias that occur in the acute and subacute phase of ischemia and for most dysrhythmias that develop during the chronic phase. Reentrant circuits due to ischemia are usually Na channel-dependent. Drug choice will depend on the length of the excitable gap: in case of a short gap (ventricular fibrillation, polymorphic ventricular tachycardia, etc.), the refractory period has been identified as the most vulnerable parameter, and therefore a correct therapeutic approach will be based on drugs able to prolong the effective refractory period (K-channel blockers, such as class III antiarrhythmic drugs); on the other hand, for those arrhythmias characterized by a long excitable gap (most of the monomorphic ventricular tachycardias), the most appropriate therapeutic intervention consists of depressing ventricular excit-ability and conduction by use of sodium-channel blockers such as mexiletine and lidocaine. Compared with other class I antiarrhythmic agents, these drugs minimally affect refractoriness and exhibit a use-dependent effect and a voltage dependent action (i.e., more pronounced on the ischemic tissue because of its partial depolarization).