Evaluation of the concomitant use of oral preventive treatments and onabotulinumtoxinA in chronic migraine: the PREVENBOX study.

BACKGROUND AND PURPOSE: OnabotulinumtoxinA is an effective preventive treatment for chronic migraine (CM). In CM, in addition to a reduction in headache frequency, a decreased reliance on oral prophylactics is also indicative of treatment effectiveness. This study aimed to quantify the change in the use of oral prophylactics after treatment with onabotulinumtoxinA in patients with CM. METHODS: This was a retrospective, multicentric, cross-sectional study. Patients with CM (International Classification of Headache Disorders-3beta) that had been treated with onabotulinumtoxinA were enrolled consecutively. We collected parameters related to each patient's pre-treatment situation, as well as their current situation, focusing on frequency and intensity of migraine, number of oral prophylactics and the respective cycle of onabotulinumtoxinA. Univariate and logistic regression analyses were performed. RESULTS: We included 542 patients, 90.0% of whom were taking oral preventive treatments. During treatment with onabotulinumtoxinA, 47.8% withdrew at least one prophylactic and 41.6% stopped using oral prophylactics altogether. Factors associated with a reduction or cessation of oral prophylactics were >50% improvement in frequency and intensity, remission to episodic migraine, use of topiramate as an initial treatment, increased number of infiltrations and shorter chronification period (P < 0.05). The multivariate analysis showed that a chronification period <20 months, more than five cycles of onabotulinumtoxinA, >50% improvement in pain intensity and topiramate as an initial treatment were predictors of a reduction in oral prophylactics (area under the curve, 70.3%; P < 0.001). CONCLUSIONS: Our study demonstrated the efficacy and safety of onabotulinumtoxinA. This treatment reduced the use of oral prophylactics. Withdrawal of oral prophylactics was most likely to occur after five cycles of treatment.

Calcitonin gene-related peptide in migraine: from pathophysiology to treatment.

INTRODUCTION: It has been observed in recent years that levels of such molecules as calcitonin gene-related peptide (CGRP) and, to a lesser extent, the pituitary adenylate cyclase-activating peptide are elevated during migraine attacks and in chronic migraine, both in the cerebrospinal fluid and in the serum. Pharmacological reduction of these proteins is clinically significant, with an improvement in patients' migraines. It therefore seems logical that one of the main lines of migraine research should be based on the role of CGRP in the pathophysiology of this entity. DEVELOPMENT: The Spanish Society of Neurology's Headache Study Group decided to draft this document in order to address the evidence on such important issues as the role of CGRP in the pathophysiology of migraine and the mechanism of action of monoclonal antibodies and gepants; and to critically analyse the results of different studies and the profile of patients eligible for treatment with monoclonal antibodies, and the impact in terms of pharmacoeconomics. CONCLUSIONS: The clinical development of gepants, which are CGRP antagonists, for the acute treatment of migraine attacks, and CGRP ligand and receptor monoclonal antibodies offer promising results for these patients.

Short-course radiotherapy in stage IV rectal cancer with resectable disease.

INTRODUCTION: Stage IV rectal cancer with resectable disease presents challenging issues, as the radical treatment of the whole disease is difficult. Surgery and chemotherapy (CT) play an unquestionable role, but the contribution of pelvic radiotherapy (RT) is not very clear. METHODS: In 2009, we established a prospective treatment protocol that included CT, short-course preoperative radiotherapy (SCRT) with surgery of the primary tumour and all metastatic locations. RESULTS: Forty patients were included. Eight (20%) patients did not receive CT due to significant comorbidities. Radical surgery treatment was possible in 22 (55%) patients. The mean follow-up was 42.81 months (3.63-105.97). Overall survival at 24 and 36 months was 71.4% and 58.2%, respectively. There was good local control of the disease, as 97.2% of pelvic surgeries were R0 and there were no local recurrences. CONCLUSION: In stage IV with resectable metastatic disease, the proposed therapeutic regimen seems very appropriate in well selected patients able to tolerate the treatment. We bet on the role of pelvic RT, due to the good local control of the disease in our series.

Evidence and experience with onabotulinumtoxinA in chronic migraine: Recommendations for daily clinical practice. / Evidencia y experiencia de bótox en migraña crónica: Recomendaciones para la práctica clínica diaria.

OnabotulinumtoxinA has been demonstrated to be effective as a preventive treatment in patients with chronic migraine (CM). Five years after the approval of onabotulinumtoxinA in Spain, the Headache Study Group of the Spanish Society of Neurology considered it worthwhile to gather a group of experts in treating patients with CM in order to draw up, based on current evidence and our own experience, a series of guidelines aimed at facilitating the use of the drug in daily clinical practice. For this purpose, we posed 12 questions that we ask ourselves as doctors, and which we are also asked by our patients. Each author responded to one question, and the document was then reviewed by everyone. We hope that this review will constitute a practical tool to help neurologists treating patients with CM.

Calcitonin gene-related peptide in migraine: from pathophysiology to treatment. / CGRP en migraña: de la fisiopatología a la terapéutica.

INTRODUCTION: It has been observed in recent years that levels of such molecules as calcitonin gene-related peptide (CGRP) and, to a lesser extent, the pituitary adenylate cyclase-activating peptide are elevated during migraine attacks and in chronic migraine, both in the cerebrospinal fluid and in the serum. Pharmacological reduction of these proteins is clinically significant, with an improvement in patients' migraines. It therefore seems logical that one of the main lines of migraine research should be based on the role of CGRP in the pathophysiology of this entity. DEVELOPMENT: The Spanish Society of Neurology's Headache Study Group decided to draft this document in order to address the evidence on such important issues as the role of CGRP in the pathophysiology of migraine and the mechanism of action of monoclonal antibodies and gepants; and to critically analyse the results of different studies and the profile of patients eligible for treatment with monoclonal antibodies, and the impact in terms of pharmacoeconomics. CONCLUSIONS: The clinical development of gepants, which are CGRP antagonists, for the acute treatment of migraine attacks, and CGRP ligand and receptor monoclonal antibodies offer promising results for these patients.

Chromosome aberrations and urinary thioethers in smokers.

Chromosome aberrations, classified as chromosome- and chromatid-type aberrations, were evaluated in 94 individuals. The concentration of thioethers in the urine was also determined. The sample consisted of 41 non-smokers (control group) and 53 smokers, 25 smoked 10-20 cigarettes/day (subgroup IIA) and 28 smoked more than 20 cigarettes/day (subgroup IIB). Our aim was to perform internal dosimetry on smokers using a cytogenetic test, and a test for urinary excretion of thioethers, in order to determine the relation between these 2 methods of dosimetry. Our results show a higher frequency of chromosome aberrations (p less than 0.0001) and a higher excretion of urinary thioethers (p less than 0.0001) in smokers as compared to non-smokers. However, linear regression between these parameters was not statistically significant. In view of the variation between different individuals with regard to the amount of urinary thioethers, it seems more accurate to perform the biomonitoring of smoking by analyzing chromosome aberrations.

[Inappropriate antidiuretic hormone secretion syndrome associated with a pleuropulmonary infection]. / Síndrome de secreción de hormona antidiurética asociado a infección pleuropulmonar.

A case of pleuropulmonary infection without a demonstrable causal agent associated to inappropriate secretion of antidiuretic hormone is reported. Although antidiuretic hormone levels were not measured, unequivocal indirect proof of elevated levels was present as evidenced by characteristic serum and urinary electrolyte abnormalities, other possible causes having been carefully ruled out. The hyposmolar clinical picture was refractory to conservative measures, and it was corrected only when a loculated empyema was surgically drained by way of thoracotomy. The literature on inappropriate secretion of antidiuretic hormone related to pleuropulmonary pathology is briefly reviewed. Particular emphasis is made on the pleural encapsulation in the present case as the factor responsible for perpetuation of pulmonary infection and origin of the hormonal disturbance.

Effect of exposure to light on physico-chemical quality attributes of sliced dry-cured Iberian ham under different packaging systems.

Dry-cured Iberian ham slices were stored under vacuum and under two different atmospheres (N(2)=70% N(2)+30% CO(2); Ar=70% Ar+30% CO(2)) and exposed to lightness or darkness. Physico-chemical, sensory and microbial analysis was carried out throughout 60 days storage. Vacuum samples showed the highest a*-value compared to N(2) and Ar after 30 (P<0.05) and 60 days (P<0.05). The influence of illumination during storage was evident after 60 days of storage, L* and a*-values being lower (P<0.01) in hams exposed to light than those kept in darkness, which can be ascribed to the lower nitrosylmioglobin content in samples exposed to light after 60 days (P=0.001). Ham slices stored in darkness showed the lowest TBARS values (P<0.05) and hexanal content (P<0.05) after 60 days. Slices of ham packed in vacuum showed lower TBARS values than N(2) and Ar batches (P=0.001), these samples being perceived as more rancid (P<0.05). The rest of the sensory attributes were not generally affected by gas mixture or illumination (P>0.05).

Investigation of uniformity in pig carcass and meat quality traits.

The study was carried out to provide information on uniformity of commercial pigs on some of the most important traits determining pork quality: carcass, loin, ham and shoulder weights, fatness, drip loss, pH and colour. Three batches of pigs raised at the same farm and slaughtered at four different dates in the same commercial abattoir were considered. Batches included halothane-free females and castrated males, Duroc and Pietrain sire lines and two slaughter weights, but a common maternal line. The first batch was obtained using commercial Duroc sire boars, and included a total of 112 animals (56 castrated males and 56 females). The second batch used Duroc and Pietrain sire boars with the target to achieve two different final weights (105 and 115 kg live weight); 128 animals were controlled (64 castrated males and 64 females), 16 for each combination of sire boar, sex and final weight. The last batch used only Pietrain sire boars with 96 controlled pigs (48 castrated males and 48 females). The uniformity was measured by the coefficient of variation (CV) and the coefficient of dispersion (CD) for all data available, and for groups of common sex, sire breed and slaughter weight. Differences in uniformity were tested among traits and groups by using confidence intervals (CIs) at 95% confidence level (CI95%) for the CV and CD. Results showed a significantly lower uniformity for drip loss (CV = 40.4%, CI95% 36.9% to 44.7%; CD = 32.1%, CI95% 28.7% to 35.4%) and backfat (CV = 22.8%, CI95% 21.1% to 24.8%; CD = 18.3%, CI95% 17.1% to 20.2%) the pH being the most uniform trait (CV = 3.2%, CI95% 3.0% to 3.5%; CD = 2.6%, CI95% 2.4% to 2.9%). When comparing different 'sire breed-sex-slaughter weight' groups, no consistent sex and slaughter weight differences in uniformity were found, but animals from Pietrain sire breed showed a tendency to be less uniform for carcass traits than animals from Duroc sire breed. Nevertheless, variability within those groups was very high and often similar to that observed when considering all the animals from all the groups. Small differences were found comparing uniformity when using the CV or the CD. CIs of these coefficients have proved to be a simple and useful tool for testing differences in uniformity.

Modified atmosphere packaging and vacuum packaging for long period chilled storage of dry-cured Iberian ham.

Dry-cured Iberian ham slices were stored under vacuum and under four different modified atmospheres (60/40=60%N(2)+40%CO(2); 70/30=70%N(2)+30%CO(2); 80/20=80%N(2)+20%CO(2); argon=70%argon+30%CO(2)) at 4+/-1 degrees C during 120 days. Gas composition, moisture content, pH, colour, pigment content, and lipid stability were measured, as well as sensory and microbial analysis were carried out throughout storage. A loss of intensity of red colour (a(*)-values) was observed during storage in ham slices (P<0.05). Consistently, MbFe(II)NO content also decreased throughout storage (P>0.05). Slices of ham packed in 40%CO(2) (60/40) and 30%CO(2) (70/30) showed lower a(*)-values than the rest of the batches after 60 days (P<0.05), though differences were not evident after 120 days (P>0.05). TBARs values showed an upward trend during the storage of packaged slices (P<0.05). Vacuum-packed slices showed the lowest TBARs values and those packed with 40%CO(2), the highest. Sensory attributes did not vary significantly (P>0.05) throughout storage under refrigeration and packed either in vacuum or in modified atmospheres. No safety problems were detected in relation to the microbial quality in any case.

Upper airway obstruction in patients with endothoracic goiter enlargement: no relationship between flow-volume loops and radiological tests.

BACKGROUND: In about 16-85% of subjects with goiter, upper airway obstruction (UAO) is observed. This percentage is higher in patients affected by goiter with endothoracic enlargement. UAO is an indication for surgery. Visual analysis of flow-volume loops (FVL) are the best indicators for UAO, although various studies using clinical and radiological parameters have observed no correlation. OBJECTIVE: To evaluate the presence of UAO in patients with endothoracic goiter enlargement and the relationship between the FVL with the observed symptoms and the measurements obtained by computed tomography (CT). SUBJECTS: Subjects with endothoracic goiter enlargement participated in the study. DESIGN: i) Symptom questionnaire (dysphagia, dyspnea, cough, oppression, dysphonia, and worsened symptoms when prone); ii) analysis: TSH and free thyroxine; iii) cervical ultrasound; iv) cervical-thoracic CT (measurements of area and diameter in the area of maximum stenosis and at 2 cm from the carina); v) chest radiography and vi) forced spirometry: visual analysis of FVL morphology and the maximum forced expiratory volume in 1 s (FEV(1)), forced expiratory flow at 50% vital capacity/forced inspiratory flow at 50% vital capacity and FEV(1)/peak expiratory flow parameters. RESULTS: Fifty subjects participated in the study: 11 men/39 women, median age 73.8 years (43.76-88.43). UAO was diagnosed in 13 cases (26%, confidence interval: 14.6-40.3%) and 27 subjects (54%) presented symptoms suggesting goiter compression. No clinical or radiological variables showed the presence of UAO. CONCLUSIONS: The frequency of UAO in subjects affected by goiter with endothoracic enlargement was lower than that described for goiter patients, and there were no clinical or radiological indicators to establish its presence.

Effect of bilateral ovariectomy and ovarian steroid hormones on the antioxidant systems and plasma malondialdehyde levels in Wistar rats.

We studied in the Wistar rat the effect of bilateral ovariectomy and of the administration of estradiol (E2) alone or together with medroxyprogesterone (MPA) on the lipid peroxidation (MDA) and the enzymatic (SOD and catalase) and non-enzymatic (vitamins A and E) antioxidant systems. At 15 days after castration, we observed no variations in the lipid peroxidation levels (MDA), with there being a slight increase in vitamins A and E (p<0.05), catalase (p<0.01), and SOD (n.s.) activity. The addition of estradiol led to a decline (n.s.) in the MDA values and in the catalase and SOD activity, with no modification of the vit. A and E concentrations. The combined (E2+MPA) therapy did not modify the results obtained with E2 alone, although the catalase decline did now reach significance (p<0.05).

Fibrous histiocytoma of the lung.

A case of asymptomatic fibrous histiocytoma of the lung is described in a 14-year-old girl. A left thoracotomy was performed followed by partial resection of the lingula. Postoperative progress was uneventful.

[Mycobacterium fortuitum in patients with chronic renal insufficiency: apropos of 2 cases]. / Mycobacterium fortuitum en pacientes con insuficiencia renal crónica: a propósito de 2 casos.

Mycobacterium fortuitum is a rapidly growing mycobacteria recovered from human infections such as skin, soft tissue, skeletal and pulmonary infectious diseases. We report 2 cases of M. fortuitum isolation from clinical samples from two patients placed on dialysis program. Our clinical findings were: The first, the presence of an abscess in the area of insertion of a CAPD catheter and the second, the detection of a lobar pneumonia in a patient placed on long-term hemodialysis program. We consider this report to be important because of the few reported cases of non tuberculous mycobacterial infections in patients with chronic renal failure.

[HIV related Foix-Chavany-Marie syndrome]. / Síndrome de Foix-Chavany-Marie asociado a VIH.

Automatic-voluntary motor dissociation of the face and lower cranial nerves of brainstem is the hallmark of Foix-Chavany-Marie syndrome (biopercular syndrome). It is commonly caused by ischemic strokes. We present a biopercular syndrome associated with HIV. A 41 year old female who presents a progressive automatic- voluntary motor dissociation of face and lower cranial nerves with later involvement of limbs. She was immunodepressed as a result of HIV. MRI showed bilateral lesions in opercular areas and ventrolateral thalamic nucleus, likely as a result of retrograde neuronal degeneration. Automatic-voluntary dissociation occur after biopercular lesions with sparing of motor pathway proceeding from the cingulate cortex.

Carcinoma arising in the pleural cavity following pneumonectomy for hydatid disease.

We report a case of carcinoma following 42 years of chronic empyema in a patient who underwent surgery for a hydatid cyst at the age of 3. At the time of diagnosis, an esophageal fistula was observed and treated with cyanoacrylate. We hypothesize that chronic inflammation of the pleura, caused by decades of empyema, associated with the presence of heterotopic squamous epithelium due to a long-standing esophago-pleural fistula, led to neoplastic transformation.

17-ketosteroid reductase deficiency in an adult patient without gynaecomastia but with female psychosexual orientation.

A 24 years old male with pseudohermaphroditism due to a deficiency in 17-ketosteroid reductase activity is described. Plasma delta 4 is 21 times higher than normal for an adult male, delta 4/T is greater than 6, both E1 and F2 are elevated and E1/E2 = 3. There is very slight modification of delta 4 on administration of ACTH, dexamethasone, hCG and fluoxymesterone. Steroid concentrations in the spermatic veins and arteries confirm the testicular origin of the increased secretion of delta 4 and E1 and show a lower secretion by the cryptorchidic testis. In vitro testicular tissue incubation and fibroblast studies confirm the 17-ketosteroid reductase deficiency and rule out any other anomaly as the cause of the ambiguous genitalia. Psychologically the patient seemed to be identified with a female social and sexual role in spite of her advanced degree of virilization.