Mast Cell Activation Profile and TFH13 Detection Discriminate Food Anaphylaxis Versus Sensitization.

BACKGROUND AND OBJECTIVE: The prevalence of food allergy (FA) has increased significantly, and the risk of developing anaphylaxis is unpredictable. Thus, discriminating between sensitized patients and those at risk of having a severe reaction is of utmost interest. To explore mast cell activation pattern and T follicular helper (TFH) 13 presence in sensitized and food anaphylaxis patients. METHODS: Patients sensitized to Lipid transfer protein (LTP) were classified as anaphylaxis or sensitized depending on the symptoms elicited by LTP-containing food. CD34+-derived MCs from patients and controls were obtained, sensitized with pooled sera, and challenged with Pru p 3 (peach LTP). Degranulation, PGD2, and cytokine/chemokine release were measured. The TFH13 population was examined by flow cytometry in the peripheral blood of all groups. In parallel, LAD2 cells were activated similarly to patients' MCs. RESULTS: A distinguishable pattern of mast cell activation was found in anaphylaxis compared to sensitized patients. Robust degranulation, PGD2, and IL-8 and GM-CSF secretion were higher in anaphylaxis, whereas TFG- and CCL2 secretion increased in sensitized patients. Concomitantly, anaphylaxis patients had a larger TFH13 population. MC activation profile was dependent on the sera rather than the MC source. In agreement with that, LAD2 cells reproduce the same pattern as MCs from anaphylactic and sensitized patients. CONCLUSION: The distinct profile of mast cell activation allows to discriminate between anaphylaxis and sensitized patients. Pooled sera may determine mast cell activation independently of mast cell origin. Besides, the presence of TFH13 cells in anaphylaxis patients points to an essential role of IgE affinity.

Retinitis pigmentosa as a clinical presentation of LCHAD deficiency: A clinical case and review of the literature.

Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency is a rare metabolic disease caused by a specific mutation in the HADHA gene, which leads to an alteration in the metabolic pathway of fatty acids. Its most frequent form of presentation at the ophthalmological level is retinitis pigmentosa, and in some cases the ophthalmologist could be the first one to alert the other paediatric specialties to carry out a multidisciplinary approach to the case. The case is presented of a patient with long-chain 3-hydroxyacyl-CoA dehydrogenase deficit detected in neonatal screening, and which clinically debuted as pigmentary retinosis with no alteration in visual acuity as observed in the fundus images and optical coherence tomography of the retina provided. Finally, a review of the literature of this potentially lethal pathology is presented, and the main pathological and clinical features are highlighted.

EWS-FLI1-mediated suppression of the RAS-antagonist Sprouty 1 (SPRY1) confers aggressiveness to Ewing sarcoma.

Ewing sarcoma is characterized by chromosomal translocations fusing the EWS gene with various members of the ETS family of transcription factors, most commonly FLI1. EWS-FLI1 is an aberrant transcription factor driving Ewing sarcoma tumorigenesis by either transcriptionally inducing or repressing specific target genes. Herein, we showed that Sprouty 1 (SPRY1), which is a physiological negative feedback inhibitor downstream of fibroblast growth factor (FGF) receptors (FGFRs) and other RAS-activating receptors, is an EWS-FLI1 repressed gene. EWS-FLI1 knockdown specifically increased the expression of SPRY1, while other Sprouty family members remained unaffected. Analysis of SPRY1 expression in a panel of Ewing sarcoma cells showed that SPRY1 was not expressed in Ewing sarcoma cell lines, suggesting that it could act as a tumor suppressor gene in these cells. In agreement, induction of SPRY1 in three different Ewing sarcoma cell lines functionally impaired proliferation, clonogenic growth and migration. In addition, SPRY1 expression inhibited extracellular signal-related kinase/mitogen-activated protein kinase (MAPK) signaling induced by serum and basic FGF (bFGF). Moreover, treatment of Ewing sarcoma cells with the potent FGFR inhibitor PD-173074 reduced bFGF-induced proliferation, colony formation and in vivo tumor growth in a dose-dependent manner, thus mimicking SPRY1 activity in Ewing sarcoma cells. Although the expression of SPRY1 was low when compared with other tumors, SPRY1 was variably expressed in primary Ewing sarcoma tumors and higher expression levels were significantly associated with improved outcome in a large patient cohort. Taken together, our data indicate that EWS-FLI1-mediated repression of SPRY1 leads to unrestrained bFGF-induced cell proliferation, suggesting that targeting the FGFR/MAPK pathway can constitute a promising therapeutic approach for this devastating disease.

Surgery as an Adjunctive Treatment for Multidrug-Resistant Tuberculosis: An Individual Patient Data Metaanalysis.

BACKGROUND: Medical treatment for multidrug-resistant (MDR)-tuberculosis is complex, toxic, and associated with poor outcomes. Surgical lung resection may be used as an adjunct to medical therapy, with the intent of reducing bacterial burden and improving cure rates. We conducted an individual patient data metaanalysis to evaluate the effectiveness of surgery as adjunctive therapy for MDR-tuberculosis. METHODS: Individual patient data, was obtained from the authors of 26 cohort studies, identified from 3 systematic reviews of MDR-tuberculosis treatment. Data included the clinical characteristics and medical and surgical therapy of each patient. Primary analyses compared treatment success (cure and completion) to a combined outcome of failure, relapse, or death. The effects of all forms of resection surgery, pneumonectomy, and partial lung resection were evaluated. RESULTS: A total of 4238 patients from 18 surgical studies and 2193 patients from 8 nonsurgical studies were included. Pulmonary resection surgery was performed on 478 patients. Partial lung resection surgery was associated with improved treatment success (adjusted odds ratio [aOR], 3.0; 95% confidence interval [CI], 1.5-5.9; I(2)R, 11.8%), but pneumonectomy was not (aOR, 1.1; 95% CI, .6-2.3; I(2)R, 13.2%). Treatment success was more likely when surgery was performed after culture conversion than before conversion (aOR, 2.6; 95% CI, 0.9-7.1; I(2)R, 0.2%). CONCLUSIONS: Partial lung resection, but not pneumonectomy, was associated with improved treatment success among patients with MDR-tuberculosis. Although improved outcomes may reflect patient selection, partial lung resection surgery after culture conversion may improve treatment outcomes in patients who receive optimal medical therapy.

New celecoxib multiparticulate systems to improve glioblastoma treatment.

Treatment of malignant gliomas consists of resection followed by radiotherapy and chemotherapy. Celecoxib (CXB), a selective COX-2 inhibitor, is able to control inflammation and pain, to improve the efficacy of radiotherapy, and to inhibit at high doses the growth of cancer cells. Two new delivery systems for CXB are developed: microspheres (MPs) for implantation in the brain after partial/complete removal of the tumor, and nanoparticles (NPs) for their potential to cross the blood brain barrier and deliver CXB into the CNS. Cell culture assays performed in PC12, SKN-AS and U373-MG cells demonstrate the antiproliferative affects of CXB, with EC50 values of 99.81 µM and 82.4 µM in U373-MG and SKN-AS cells. Encapsulation efficacy of CXB in formulation MP2 (20% CXB) was 74.6 ± 2.2% with a zero-order release rate of 47.8 µg/day/20mg microspheres for 34 days. Uncoated and polysorbate 80-coated CXB-NPs are prepared by nanoprecipitation. Mean sizes of uncoated and coated CXB-NPs were 173.6 ± 44.9 nm and 100.6 ± 62.1 nm. Cerebral cortex images showed a marked increase of fluorescence when the surfactant-coated NPs were administered to rats. These results suggest that both CXB formulations (MPs and NPs) are adequate systems to enhance the effects of chemotherapy in the treatment of malignant brain tumor.

Randomized clinical trial comparing endoscopic treatment with dextranomer hyaluronic acid copolymer and Cohen's ureteral reimplantation for vesicoureteral reflux: long-term results.

PURPOSE: To compare efficacy of Cohen's ureteral reimplantation and endoscopic treatment with Dx/HA in patients with primary VUR grades II, III and IV. METHODS: From April 2002 to June 2004, patients over 1 year old with VUR grade I, II, III or IV were included. Patients were randomized into two groups: endoscopic treatment (ET) or ureteral reimplantation (UR). In the ET group, an ultrasonography study was performed 24 h and 1 month after surgery, and two voiding cystourethrographies at 3 and 6 months post treatment. In the UR group, an ultrasonography study was done 7 days and 1 month after surgery and a micturial cystography 6 months post surgery. A postoperative nuclear direct cystogram was performed 5 years later in both groups. RESULTS: A total of 41 patients were included in this study: in ET 22 patients with 35 refluxing ureters and in UR 19 patients with 32 refluxing ureters. The VUR grades in ET were: 16 grade II, 16 grade III and 3 grade IV; and in UR: 15 grade II, 12 grade III and 5 grade IV. VUR was resolved in 91% (32/35) of ET (28% of ureters needed a second injection), and in 100% of UR group. Five years after the procedure, VUR was still resolved in 30/32 of ET and 32/32 of UR. CONCLUSION: Short- and long-term follow up shows that multiple endoscopic treatment of VUR grades II, III and IV with Dx/HA is as effective as ureteral reimplantation.

Neuroprotective Properties of Standardized Extracts of Hypericum perforatum on Rotenone Model of Parkinson's Disease.

Hipericum perforatum is a well-known herbal for its antidepressant property. Recently, it has been shown to have nootropic effects against neurodegenerative disorders. The aim of the present study was to evaluate the protective role of chronic administration of two standardized extract of Hypericum perforatum SHP1 rich in hyperforin (6%) and SHP2 extract poor in hyperforin (0.2%) on the neurodegeneration induced by chronic administration of rotenone in rats. Quercetin in liposomes, one active constituent, was tested in the same experimental conditions. The animals received pretreatments with SHP1 (4 mg/Kg, ip), SHP2 (4 mg/Kg, ip) or quercetin liposomes (25 and 100 mg/kg, ip) 60 min before of rotenone injection (2.5 mg/kg) for 45 days. Pretreatment of the animals with SHP1 and SHP2 efficiently halted deleterious toxic effects of rotenone, revealing normalization of catalepsy in addition to amelioration of neurochemical parameters. Also, SHP1 reduced neuronal damage, diminishing substantia nigra dopaminergic cell death caused by the pesticide, indicating benefit of neuroprotective therapy. In general, the SHP1 was more active than SHP2. In addition, SHP1 inhibited the apoptotic cascade by decreasing Bax levels. The results presented here indicate that mainly hyperforin and quercetin, may be involved in the neuroprotective action of Hypericum standardized extracts. Combination of dietary antioxidants could provide better therapeutic advantage for the management of Parkinson, and possibly other neurodegenerative disorders. Therefore H. perforatum standardized extract enriched in hyperforin, could be a better alternative for depressed elderly patients with degenerative disorders exhibiting elevated oxidative stress status.

Clinical and microbiological features of a cystic fibrosis patient chronically colonized with Pandoraea sputorum identified by combining 16S rRNA sequencing and matrix-assisted laser desorption ionization-time of flight mass spectrometry.

Clonal isolates identified as various nonfermentative Gram-negative bacilli over a 5-year period from sputum cultures of a 30-year-old cystic fibrosis patient were successfully reidentified as Pandoraea sputorum by combining 16S rRNA sequencing and matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). Decreased lung function improved after 1 year of azithromycin and inhaled 7%-hypertonic saline treatment.

Longitudinal studies of ischemic penumbra by using 18F-FDG PET and MRI techniques in permanent and transient focal cerebral ischemia in rats.

At present, the goal of stroke research is the identification of a potential recoverable tissue surrounding the ischemic core, suggested as ischemic penumbra, with the aim of applying a treatment that attenuates the growth of this area. Our purpose was to determine whether a combination of imaging techniques, including (18)F-FDG PET and MRI could identify the penumbra area. Longitudinal studies of (18)F-FDG PET and MRI were performed in rats 3 h, 24 h and 48 h after the onset of ischemia. A transient and a permanent model of focal cerebral ischemia were performed. Regions of interest were located, covering the ischemic core, the border that progresses to infarction (recruited tissue), and the border that recovers (recoverable tissue) with early reperfusion. Analyses show that permanent ischemia produces severe damage, whereas the transient ischemia model does not produce clear damage in ADC maps at the earliest time studied. The only significant differences between values for recoverable tissue, (18)F-FDG (84±2%), ADC (108±5%) and PWI (70±8%), and recruited tissue, (18)F-FDG (77±3%), ADC (109±4%) and PWI (77±4%), are shown in (18)F-FDG ratios. We also show that recoverable tissue values are different from those in non-infarcted tissue. The combination of (18)F-FDG PET, ADC and PWI MRI is useful for identification of ischemic penumbra, with (18)F-FDG PET being the most sensitive approach to its study at early times after stroke, when a clear DWI deficit is not observed.

[Treatment of hepatocellular carcinoma using precision transcatheter arterial chemoembolization (TACE): results of two years' experience in a general hospital]. / Quimioembolización de hepatocarcinoma mediante TACE-precisión: resultados al 2.° año en un hospital general.

OBJECTIVES: To present our experience in the use of microspheres preloaded with adriamycin (DC Bead(®)) in the transcatheter arterial chemoembolization (TACE) of hepatocellular carcinoma, in a two-year prospective multidisciplinary study in consecutive patients to evaluate the efficacy, safety, and tolerance of this procedure. MATERIAL AND METHODS: From May 2007 to January 2010, we performed 30 TACE procedures in 17 patients (3 women and 14 men; mean age, 68 years; age range, 56-85 years). We performed a mean of 1.76 procedures per patient using the precision TACE protocol. Outcomes were evaluated using the RECIST-EASL criteria by clinical, laboratory, CT, and MRI follow-up at 1, 3, 6, and 12 months. RESULTS: The procedure was considered an initial technical success in all cases. The total dose was delivered in seven cases; in the remaining cases, the total dose was not reached (mean dose, 80mg). An objective response was observed in 64.7% of patients: a complete response was observed in 29.41% and a partial response in 35.29%. Disease was stabilized in 23.52% and progressed in 11.76%. We observed two cases of abscess/necrosis and one of ischemic cholecystitis. There were no deaths or cases of liver failure related with the procedure. CONCLUSIONS: TACE using microspheres preloaded with adriamycin (DC Beads®) is safe and effective, given the low rate of complications, good tolerance in patients, and increased tumor response.

[Interventional radiology for bile duct stones]. / Litiasis de las vías biliares en manos del radiólogo intervencionista.

OBJECTIVE: This article describes our experience in the percutaneous technique of expelling bile duct calculi into the duodenum by dilating the papilla with a balloon catheter. MATERIAL AND METHODS: We prospectively studied 365 patients (173 men, 192 women; mean age, 75 years; range 26-98) with bile duct calculi (single=213, multiple=152). In 102 cases, residual stones were percutaneously expelled into the duodenum via an indwelling T-tube; in 263 cases, primary (non-residual) stones were expelled from the hepatic or cystic duct through the common bile duct into the duodenum. The technique consisted of dilating the papilla with an angioplasty catheter and expelling the stone into the duodenum with an occlusion balloon; prior mechanical fragmentation was performed in only 48 cases. Percutaneous biliary drainage to the exterior was maintained for 2 to 8 days. RESULTS: The procedure was successful on the first attempt in 91.5% of cases and in 94.3% after the second attempt. The procedure failed in 16 cases, mainly due to the large size of the calculi. Residual lithiasis was resolved in 99% of cases and primary (non-residual) lithiasis was resolved in 91%. There were 23 major complications including 6 cases with poor clinical outcome and death (mortality at 30 days was 1.6%). CONCLUSIONS: Percutaneous anterograde evacuation of bile duct stones by dilating the papilla with an angioplasty catheter and expelling the stones with an occlusion balloon is effective, nontraumatic, and safe; this procedure maintains the anatomic and functional integrity of the sphincter. When performed by an experienced interventional radiologist, it is a viable alternative to choledochotomy.

Using national health weeks to deliver deworming to children: lessons from Mexico.

Mexico established national health weeks (NHWs) in the early 1980s to promote childhood vaccinations. Because of the cumulative worldwide peer-reviewed scientific evidence, the recommendations of the World Health Organization and other international organisations, the political will of the Mexican government and the infrastructure provided by the NHWs, deworming was added to the NHWs in 1993. In addition to the Ministry of Health, several other government organisations participated in administering the deworming component. Tens of millions of school-age and preschool children between the ages of 2 years and 14 years now receive deworming (a single 400 mg dose of albendazole) approximately every 8 months. Between 1993 and 1998 evaluations were carried out in over 90,000 children to determine the effect of NHWs on the prevalence of geohelminth infections. In 1993, the overall prevalence of Ascaris was 20% and that of Trichuris was 15%. Prevalences decreased significantly over time (p <0.001). Treatment efficacy for Ascaris ranged from 91.6% to 85.3%, and for Trichuris, from 97.9% to 42.6%. In 1998, after conducting 12 NHWs with deworming, the respective prevalences were Ascaris 8% and Trichuris 11%. The experience of Mexico in integrating albendazole into its NHWs shows how deworming can be delivered to large numbers of at-risk children using an existing infrastructure. The NHW approach may be generalisable in other countries with successful national vaccination campaigns. The challenge remaining is to sustain the deworming programme until other longer-term behavioural, environmental and socioeconomic changes can be implemented.

[A pilot study of endoscopic experimental transgastric peritoneoscopy and endoscopic gastrorrhaphy in a canine model.]. / Estudio piloto de endoscopia experimental:peritoneoscopia transgástrica y gastrorrafiaendoscópica en modelo canino.

BACKGROUND AND AIMS: Natural Orifice Translumenal Endoscopic Surgery (NOTES) is an experimental technique with potential advantages compared to laparoscopic surgery. Trans gastric peritoneoscopy (TP) is a NOTES technique. The aim of this study was to perform TP, to evaluate feasibility and technical limitations in a survival model. MATERIALS AND METHODS: The following procedures were performed in 4 anesthetized dogs using a single channel video gastroscope: Gastrotomy with needle-knife puncture followed with extension of the incision with a pull-type sphincterotome,pneumoperitoneum with the endoscope,peritoneoscopy and gastrorrhapy using hemoclips and endoloops. RESULTS: All the procedures were accomplished successfully with a mean duration of 80 minutes. Gastrotomy induced minor bleeding.Peritoneal cavity was accessed safely and peritoneoscopy was accomplished without incidents.Retroflexed maneuvers were mandatory to visualize upper abdomen and overinflation oftenly occurred. The closure of the gastric wall incision was successfully obtained. All the animals made an uncomplicated recovery after 7 days. CONCLUSIONS: TP is technically feasible and safe in a canine model. This study highlights several technical limitations and confirms the need for technological development.

Gender differentials of pulmonary tuberculosis transmission and reactivation in an endemic area.

BACKGROUND: In most low income countries there are twice as many cases of tuberculosis (TB) reported among men than among women, a difference commonly attributed to biological and epidemiological characteristics as well as socioeconomic and cultural barriers in access to health care. The World Health Organization has encouraged gender specific comparisons in TB rates to determine whether women with TB are less likely than men with TB to be diagnosed, reported, and treated. A study was undertaken to identify gender based differences in patients with pulmonary TB and to use this information to improve TB control efforts. METHODS: Individuals with a cough for more than 2 weeks in southern Mexico were screened from March 1995 to April 2003. Clinical and mycobacteriological information (isolation, identification, drug susceptibility testing and IS6110 based genotyping, and spoligotyping) was collected from those with bacteriologically confirmed pulmonary TB. Patients were treated in accordance with official norms and followed to ascertain treatment outcome, retreatment, and vital status. RESULTS: 623 patients with pulmonary TB were enrolled. The male:female incidence rate ratio for overall, reactivated, and recently transmitted disease was 1.58 (95% CI 1.34 to 1.86), 1.64 (95% CI 1.36 to 1.98), and 1.41 (95% CI 1.01 to 1.96), respectively. Men were more likely than women to default from treatment (adjusted OR 3.30, 95% CI 1.46 to 7.43), to be retreated (hazard ratio (HR) 3.15, 95% CI 1.38 to 7.22), and to die from TB (HR 2.23, 95% CI 1.25 to 3.99). CONCLUSIONS: Higher rates of transmitted and reactivated disease and poorer treatment outcomes among men are indicators of gender differentials in the diagnosis and treatment of pulmonary TB, and suggest specific strategies in endemic settings.

[Teaching of basic heart-lung reanimation to the general public]. / Enseñanza de la reanimación cardiopulmonar básica en población general.

OBJECTIVE: To analyse the efficacy of training in basic paediatric and adult heart-lung reanimation by means of theoretical/practical courses for the general public. DESIGN: Prospective and observational study. SETTING: Chamberi Municipal Health Centre, Madrid. PARTICIPANTS: 360 people aged from 13 to 75. INTERVENTIONS: From 1999 to 2003, 381 people took 26 courses in prevention of accidents and response to them. Theoretical classes in prevention of cardiac/respiratory arrest and in basic heart-lung reanimation (HLR) and practical classes in HLR were given to groups of 5 or 6 students, using dummies of babies, children, and adults. MAIN MEASUREMENTS: At the start and end of the course, 17.2% of the participants were assessed for their theoretical knowledge; and 94.5% had a practical assessment of their HLR skills. At the end of the course all students filled in an anonymous satisfaction questionnaire. RESULTS: In the initial theoretical assessment, the mean score was 3.5+/-1.5 (out of a maximum of 10); in the final assessment, 7.7+/-1.7 (P<.01). 87.2% of participants achieved sufficient practical skills. In the questionnaire, the participants thought the course was very useful for daily life and felt more able to take action. CONCLUSIONS: The basic HLR courses for the general public provide useful theoretical and practical training and manage to improve peoples ability to react correctly and so resolve emergency situations.

[Long-term effect of angiotensin-converting inhibitors in children with proteinuria]. / Efecto a largo plazo de los inhibidores de la enzima conversora de la angiotensina en niños con proteinuria.

BACKGROUND: Prolonged proteinuria is a risk factor for renal damage. Angiotensin-converting enzyme (ACE) inhibitors can reduce proteinuria in adults with different types of nephropathy. PATIENTS AND METHODS: We evaluated treatment with low doses of ACE inhibitors (captopril and enalapril) in nine children with proteinuria due to chronic glomerular nephropathy. The patients' diagnoses were Henoch-Schönlein nephropathy, Berger's disease, Alport's disease, and chronic glomerulonephritis (GN) (membranous GN, focal and segmental GN, and membranoproliferative GN). None of the patients were receiving concomitant treatment. Those who had received corticoids, immunosuppressive or hypotensive drugs during the previous 3 months were excluded. The medication was administered over a prolonged period (mean 26.6 6.36 months). RESULTS: Proteinuria was initially in the nephrotic range (M = 55.34 10.44 mg/m2/h). In all patients concentrations fell significantly after 6 months and at the end of the treatment(p = 0.01 and p = 0.05). No adverse reactions to the medication were observed. The decrease in glomerular filtration rate was not significant. No significant changes in arterial pressure were found during treatment. CONCLUSIONS: ACE inhibitors could be an effective alternative for reducing proteinuria in children with prolonged nephropathy. These inhibitors do not produce the adverse effects associated with other drugs and can therefore be used for long periods.