Drezotomía en el tratamiento del dolor por desaferentización: revisión de resultados y análisis de factores predictores de éxito

Background and objectivesThe treatment of deafferentation pain by spinal DREZotomy is a proven therapeutic option in the literature. In recent years, use of DREZotomy has been relegated to second place due to the emergence of neuromodulation therapies. The objectives of this study are to demonstrate that DREZotomy continues to be an effective and safe treatment and to analyse predictive factors for success.Patients and methodsA retrospective study was conducted of all patients treated in our department with spinal DREZotomy from 1998 to 2018. Bulbar DREZotomy procedures were excluded. A visual analogue scale (VAS) and the reduction of routine medication were used as outcome variables. Demographic, clinical and operative variables were analysed as predictive factors for success.ResultsA total of 27 patients (51.9% female) with a mean age of 53.7 years underwent DREZotomy. The main cause of pain was brachial plexus injury (BPI) (55.6%) followed by neoplasms (18.5%). The mean time of pain evolution was 8.4 years with a mean intensity of 8.7 according to the VAS, even though 63% of the patients had previously received neurostimulation therapy. Favourable outcome (≥ 50% pain reduction in the VAS) was observed in 77.8% of patients during the postoperative period and remained in 59.3% of patients after 22 months average follow-up (mean reduction of 4.9 points). This allowed for a reduction in routine analgesic treatment in 70.4% of them. DREZotomy in BPI-related pain presented a significantly higher success rate (93%) than the other pathologies (41.7%) (p = .001). No association was observed between outcome and age, gender, DREZ technique, duration of pain or previous neurostimulation therapies. There were six neurological complications, four post-operative transient neurological deficits and two permanent deficits.ConclusionDorsal root entry zone surgery is effective and safe for treating patients with deafferentation pain, especially after brachial plexus injury. It can be considered an alternative treatment after failed neurostimulation techniques for pain control. However, its indication should be considered as the first therapeutic option after medical therapy failure due to its good long-term results.     

Genome-wide association analysis of dementia and its clinical endophenotypes reveal novel loci associated with Alzheimer's disease and three causality networks: The GR@ACE project

IntroductionLarge variability among Alzheimer's disease (AD) cases might impact genetic discoveries and complicate dissection of underlying biological pathways.MethodsGenome Research at Fundacio ACE ([email protected]) is a genome-wide study of dementia and its clinical endophenotypes, defined based on AD's clinical certainty and vascular burden. We assessed the impact of known AD loci across endophenotypes to generate loci categories. We incorporated gene coexpression data and conducted pathway analysis per category. Finally, to evaluate the effect of heterogeneity in genetic studies, [email protected] series were meta-analyzed with additional genome-wide association study data sets.ResultsWe classified known AD loci into three categories, which might reflect the disease clinical heterogeneity. Vascular processes were only detected as a causal mechanism in probable AD. The meta-analysis strategy revealed the ANKRD31-rs4704171 and NDUFAF6-rs10098778 and confirmed SCIMP-rs7225151 and CD33-rs3865444.DiscussionThe regulation of vasculature is a prominent causal component of probable AD. [email protected] meta-analysis revealed novel AD genetic signals, strongly driven by the presence of clinical heterogeneity in the AD series.     

Oxidized citrus oil (R-limonene): a frequent skin sensitizer in Europe

BACKGROUND: Peel oil from citrus fruits consists of R-(+)-limonene, which is one of the most commonly used fragrance materials in technical products and in fine fragrances. This substance forms allergenic oxidation products during handling and storage. OBJECTIVE: We wanted to study the frequency of allergic reactions to oxidized R-(+)-limonene in patients with dermatitis and find a suitable test preparation. METHOD: Patch testing with oxidized R-(+)-limonene was performed on 2273 patients at 4 dermatology clinics in Europe. RESULTS: Of the consecutive patients tested, 3.8% to 3.9% had positive reactions in two of the clinics; 6.5% had positive reactions in the third clinic; and 0.3% had positive reactions in the fourth clinic. A total of 63 patients showed positive reactions. In total, 57% of the patients did not react to fragrance mix or balsam of Peru. We recommend testing with 3% oxidized R-(+)-limonene in patients referred for patch testing. CONCLUSION: The high frequency of oxidized limonene allergy provides clinical evidence for the European classification of R-(+)-limonene that contains oxidation products as skin sensitizers.     

Docetaxel, 5-fluorouracil, and leucovorin as treatment for advanced gastric cancer: results of a phase II study

Background: Previous studies have shown that the taxane, docetaxel, is effective in treating gastric cancer. The aim of this study was to assess the efficacy and safety of docetaxel in combination with 5-fluorouracil (5-FU) and leucovorin (LV). Methods: Thirty patients with histologically proven locally advanced and/or metastatic gastric cancer with WHO performance status 0–2 were enrolled and received either 75 or 100 mg/m² docetaxel as a 1-h intravenous infusion on day 1 every 28 days. All patients also received 5-FU (1800 mg/m²) plus LV (500 mg/m²), by continuous intravenous infusion over 24 h on days 1, 8, and 15 every 28 days. Chemotherapy was given for at least two cycles. Results: Of the 25 evaluable patients, 3 showed a complete response, 4 showed a partial response, and 11 patients had stable disease. The overall response rate was 28.0% (95% confidence interval [CI], 10.4, 45.6). The median time to progression was 5.9 months (95% CI, 5.4, 6.5), and the median overall survival was 7.7 months (95% CI, 7.2, 8.3) for the intent-to-treat population. The most frequent grade III and IV hematological toxicities were neutropenia and anemia. Febrile neutropenia was observed in 10% of patients and 2.4% of cycles. The prophylactic use of granulocyte colony-stimulating factor (G-CSF) in 3 patients reduced the incidence and severity of neutropenia. Other hematological toxicities were rare. Conclusion: Docetaxel in combination with weekly 5-FU and LV is effective in treating patients with advanced/metastatic gastric cancer. This new docetaxel-containing combination shows promise as a third-generation treatment option for gastric cancer. Received: December 25, 2001 / Accepted: April 22, 2002 Offprint requests to: M. Constenla     

Anionic PAMAM Dendrimers Rapidly Cross Adult Rat Intestine In Vitro: A Potential Oral Delivery System?

Purpose. To investigate systematically the effect ofpolyamidoamine (PAMAM) dendrimer size, charge, and concentration on uptakeand transport across the adult rat intestine in vitro using theeverted rat intestinal sac system. Methods. Cationic PAMAM dendrimers (generations 3 and 4)and anionic PAMAM dendrimers (generations 2.5, 3.5, and 5.5) that weremodified to include on average a single pendant amino group wereradioiodinated using the Bolton and Hunter Reagent. ¹²⁵I-Labelleddendrimers were incubated with everted sacs in vitro and thetransfer of radioactivity into the tissue and serosal fluid was followedwith time. Results. The serosal transfer rates seen for all anionicgenerations were extremely high with Endocytic Indices (EI) in the range3.4–4.4 mL/mg protein/h. The concentration-dependence of serosaltransfer was linear over the dendrimer concentration range 10–100mg/mL. For ¹²⁵I-labelled generation 5.5 the rate of tissueuptake was higher (EI = 2.48 ± 0.51 mL/mg protein/h) thanseen for ¹²⁵I-labelled generations 2.5 and 3.5 (0.6–0.7mL/mg protein/h) (p < 0.05). The ¹²⁵I-labelled cationicPAMAM dendrimers (generations 3 and 4) displayed a tissue uptake (EI= 3.3–4.8 mL/mg protein/h) which was higher (p < 0.05)than the rate of serosal transfer (EI = 2.3–2.7 mL/mgprotein/h), probably due to nonspecific adsorption of cationic dendrimer tothe mucosal surface. Conclusions. As the anionic PAMAM dendrimers displayedserosal transfer rates that were faster than observed for other syntheticand natural macromolecules (including tomato lectin) studied in the evertedsac system, these interesting nanoscale structures may have potential forfurther development as oral drug delivery systems.     

Fetal intracranial hemorrhage. Prenatal diagnosis and postnatal outcomes

Objective: To present our experience with 14 cases of fetal intracranial hemorrhage (ICH).

Methods: Cases of fetal ICH detected in our institution between 2005 and 2016 by ultrasonography. Maternal characteristics, ultrasound and MRI findings, and postnatal outcome were noted.

Results: Twelve cases (86.7%) were identified during a third trimester routine scan at a median gestational age of 30.6 weeks. The ICH was classified as Grade 2 in two cases, Grade 3 in three cases, and Grade 4 in nine cases. Nine cases were bilateral and five were unilateral (four left/one right). The 11 MRI available confirmed grade and location and, in six cases (54.5%), added new findings. There were six terminations of pregnancy, one intrauterine fetal death and seven babies born alive. These were followed up for 28 months (range 3–96). Some grade of neurologic impairment was observed in five children (71.4%, one Grade 3/four Grade 4), mainly mild to moderate motor sequelae.

Conclusion: Diagnosis of fetal ICH is amenable to antenatal US. Most of the cases identified are of high grade and usually detected during the third trimester. MRI is a valuable complementary tool in evaluating ICH. Conversely to that previously reported, postnatal survival is high but it entails the risk of adverse neurologic outcome in most neonates.     

Evaluation of organochlorine compounds in peregrine falcon (Falco peregrinus) and their main prey (Columba livia) inhabiting central Spain

The population of peregrine falcon (Falco peregrinus sbs. brookei) inhabiting the Regional Park of southeastern Madrid (RPSM), Spain, has experienced an increase of unsuccessful pairs (from 15% among a total of 20 pairs in 1995 to 55% among a total of 18 pairs in 2001). Traditionally, this area has been known to be contaminated with organochlorine compounds and toxic metals, which are known to be deleterious to the reproductive system of birds. During the breeding seasons of 2000 and 2001, contaminant residues were measured in unhatched eggs of peregrine falcons and liver of their main prey, to determine if they could be affecting the survival of the population. The most abundant contaminants were ortho-polychlorinated biphenyls (ortho-PCBs), ranging from 202.56 to 3,335.16 ng/g (wet wt) in falcon eggs and from 10.25 to 53.51 ng/g (wet wt) in pigeon livers. In all samples, the 2,3,7,8-substituted polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) were detected, although these levels never exceeded 20 pg/g (wet wt). The major contributor to total toxic equivalent quantities (TEQs) were non-ortho-PCBs. Organochlorine levels found in this study may contribute to the entire suite of stressors that are negatively affecting the peregrine population.