Impact of Prior Drug Allergies on the Risk, Clinical Features, and Outcomes of Idiosyncratic Drug-Induced Liver Injury in Adults.

BACKGROUND: Prior drug allergies are common and may increase susceptibility to adverse medication effects. The aim of this study was to compare the frequency, clinical features, and outcomes of DILI among patients with and without a history of prior drug allergy. METHODS: The EMR at a large liver referral center was searched for all DILI encounters using ICD-10 T-codes for drug poisoning/toxicity and K-71 codes for toxic liver injury between 10/1/2015 and 9/30/2019. Clinically significant liver injury was identified using predefined laboratory criteria, and cases were adjudicated using a 5-point expert opinion scale: 1/2/3 = probable DILI and 4/5 = non-DILI. Drug allergy was defined as a history of anaphylaxis, hives, rash, or pruritus after drug exposure. RESULTS: Among 766,930 patient encounters, 127 unique patients met inclusion criteria with 72 (56.7%) cases adjudicated as probable DILI and 55 (43.3%) as non-DILI. In the probable DILI group, the most frequent suspect drug classes were: antimicrobials (41.9%), herbal and dietary supplements (9.5%), and antineoplastics (8.1%). Twenty-three of the 72 DILI patients (31.9%) had a history of drug allergy before the DILI episode compared to 16 (29.1%) of the 55 non-DILI cases (p = 0.89). However, none of the allergy drugs and suspect DILI drugs were the same although many were in the same drug class. DILI patients with a prior drug allergy were more likely to be female (73.9% vs. 44.9%, p = 0.04) and have lower serum bilirubin (4.0 vs. 7.8, p = 0.08) and INR (1.1 vs. 1.6, p = 0.043) levels at presentation. The likelihood of death or liver transplantation among probable DILI cases with prior drug allergy was lower than those without prior drug allergy (0% vs. 8.2%, p = 0.35). The suspect drug was subsequently documented in the "Drug Allergy" section of the EMR in only 23 (31.9%) of the 72 probable DILI patients, and these patients were more likely to present with a rash (7% vs. 2%, p = 0.006) and higher serum bilirubin levels (10.5 vs. 4.7, p = 0.008) compared to those in whom the suspect drug was not listed as "drug allergy." CONCLUSION: A prior drug allergy history was not associated with a greater likelihood of developing DILI compared to other causes of acute liver injury. However, the probable DILI patients with a history of prior drug allergy tended to have less severe liver injury and clinical outcomes. The low rate of suspect drug documentation in the "Drug Allergy" section of EMR after a DILI episode is of concern and could lead to avoidable harm from inadvertent suspect drug re-challenge.

United States and United Nations pesticide policies: Environmental violence against the Yaqui indigenous nation.

Indigenous Peoples suffer environmental violence related to pesticide exposure, including imported pesticides that are banned in the exporting countries (including the U.S.) due to their known detrimental health impacts and used in or near their traditional territories. The Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) is a U.S. statue that allows "pesticides that are not approved - or registered - for use in the U.S." to be manufactured in the U.S. and exported elsewhere. The UN Rotterdam Convention also allows the global exportation of "banned pesticides." The ongoing exportation of banned pesticides leads to disproportionately high rates of morbidity and mortality, most notably in Indigenous women and children. In this paper, we present evidence describing the documented harms of banned pesticides with a focus on the Yaqui Nation in Sonora, Mexico, give background on the problematic laws allowing these harms, and highlight concrete solutions.

ß-carotene and Bacillus thuringiensis insecticidal protein differentially modulate feeding behaviour, mortality and physiology of European corn borer (Ostrinia nubilalis).

Maize with enhanced ß-carotene production was engineered to counteract pervasive vitamin A deficiency in developing countries. Second-generation biofortified crops are being developed with additional traits that confer pest resistance. These include crops that can produce Bacillus thuringiensis Berliner (Bt) insecticidal proteins. Currently, it is unknown whether ß-carotene can confer fitness benefits through to insect pests, specifically through altering Ostrinia nubilalis foraging behaviour or development in the presence of Bt insecticidal toxin. Therefore the effects of dietary ß-carotene plus Bt insecticidal protein on feeding behaviour, mortality, and physiology in early and late instars of O. nubilalis larvae were investigated. The results of two-choice experiments showed that irrespective of ß-carotene presence, at day five 68%-90% of neonates and 69%-77% of fifth-instar larvae avoided diets with Cry1A protein. Over 65% of neonate larvae preferred to feed on diets with ß-carotene alone compared to 39% of fifth-instar larvae. Higher mortality (65%-97%) in neonates fed diets supplemented with ß-carotene alone and in combination with Bt protein was found, whereas <36% mortality was observed when fed diets without supplemented ß-carotene or Bt protein. Diets with both ß-carotene and Bt protein extended 25 days the larval developmental duration from neonate to fifth instar (compared to Bt diets) but did not impair larval or pupal weight. Juvenile hormone and 20-hydroxyecdysone regulate insect development and their levels were at least 3-fold higher in larvae fed diets with ß-carotene for 3 days. Overall, these results suggest that the effects of ß-carotene and Bt protein on O. nubilalis is dependent on larval developmental stage. This study is one of the first that provides insight on how the interaction of novel traits may modulate crop susceptibility to insect pests. This understanding will in turn inform the development of crop protection strategies with greater efficacy.

Fractional excretion of phosphorus and vascular calcification in stage 3 chronic kidney disease.

The role of renal excretion of Pi in relation to vascular calcification (VC) in patients in the early stages of chronic kidney disease (CKD) is controversial. Thus, we determine the relation between fractional excretion of phosphorus (FEP) and VC, measured using two methods in a cross-sectional study of patients with stage 3 CKD. We recorded demographic data, anthropometry, comorbidities and active treatment. We measured 24-hour urine FEP and, in serum, measured fibroblast growth factor 23 (FGF23), α-Klotho, intact parathyroid hormone (iPTH), calcium and phosphorus. VC was measured by lateral abdominal radiography (Kauppila index (KI)) and CT of the abdominal aorta (measured in Agatston units). In 57% of subjects, abnormal VC was present when measured using CT, and in only 17% using lateral abdominal radiography. Factors associated with VC using CT were age, cardiovascular risk factors, vascular comorbidity, microalbuminuria and levels of FGF23, phosphorus and calcium x phosphorus product (CaxP); although only age (OR 1.25, 95% CI 1.11 to 1.41), smoking (OR 21.2, CI 4.4 to 100) and CaxP (OR 1.21, CI 1.06 to 1.37) maintained the association in a multivariate analysis. By contrast, only age (OR 1.35, 95% CI 1.07 to 1.74), CaxP (OR 1.14, CI 1.13 to 1.92) and FEP (OR 1.07,95% CI 1004 to 1.14) were associated with abnormal VC in the lateral abdominal radiography. In conclusion, in patients with stage 3 CKD, the detection of VC by abdominal CT is more sensitive than conventional X-rays. Moreover, CaxP is associated with cardiovascular risk factors and vascular comorbidity; quantification of FEPi in these patients provides additional clinical information in advanced VC detected by KI.

Carotenoids moderate the effectiveness of a Bt gene against the European corn borer, Ostrinia nubilalis.

We assessed the effectiveness of a biofortified maize line (4BtxHC) which accumulates high levels of antioxidant carotenoids that also expressed the insecticidal Cry1Ac Bacillus thuringiensis (Bt) gene against the European corn borer Ostrinia nubilalis. This line had been previously engineered to accumulate carotenoids specifically in the seed endosperm, whereas the Bt gene was expressed constitutively. The concentrations of Bt toxin (Cry 1Ac) in the leaves of the 4Bt and 4BtxHC lines were not significantly different at 47±6 µg/g of fresh weight (FW); neither were they in the kernels of both lines (35±3 µg/g FW). The kernels and leaves were toxic to the larvae of O. nubilalis. However, the insecticidal activity was substantially lower (ca. 20%) than that of lines that expressed only Bt in spite that the two lines showed a quantity of toxin not significantly different in kernels or in leaves. Although the reduced effectiveness of Cry1Ac in kernels may not be entirely surprising, the observation of the same phenomenon in vegetative tissues was unexpected. When semi-artificial diets containing kernels from 4Bt supplemented with different levels of ß-carotene were used in insect bioassays, the ß-carotene moderated the effectiveness of the Bt similarly to the plant material with carotenoid enrichment. To elucidate the biochemical basis of the reduced effectiveness of Bt toxin in the carotenoid-enriched plants, we measured the activity of three enzymes known to be implicated in the detoxification defence, namely, catalase, superoxide dismutase and glutathione S-transferase. Whereas Cry1Ac expression significantly increased SOD and CAT enzymatic activity in the absence of carotenoids, carotenoids, either in 4BtxHC or in artificial diets enriched with ß-carotene, significantly lowered CAT activity. Carotenoids can therefore moderate the susceptibility of the maize borer O. nubilalis to Cry1Ac, and we hypothesize that their role as antioxidants could explain this phenomenon via their scavenging of reactive oxygen species produced during Cry1Ac detoxification in the larvae. The involvement of this mechanism in the decreased mortality caused by Cry1Ac when carotenoids are present in the diet is discussed.

Effects of patterned peripheral nerve stimulation on soleus spinal motor neuron excitability.

Spinal plasticity is thought to contribute to sensorimotor recovery of limb function in several neurological disorders and can be experimentally induced in animals and humans using different stimulation protocols. In healthy individuals, electrical continuous Theta Burst Stimulation (TBS) of the median nerve has been shown to change spinal motoneuron excitability in the cervical spinal cord as indexed by a change in mean H-reflex amplitude in the flexor carpi radialis muscle. It is unknown whether continuous TBS of a peripheral nerve can also shift motoneuron excitability in the lower limb. In 26 healthy subjects, we examined the effects of electrical TBS given to the tibial nerve in the popliteal fossa on the excitability of lumbar spinal motoneurons as measured by H-reflex amplitude of the soleus muscle evoked by tibial nerve stimulation. Continuous TBS was given at 110% of H-reflex threshold intensity and compared to non-patterned regular electrical stimulation at 15 Hz. To disclose any pain-induced effects, we also tested the effects of TBS at individual sensory threshold. Moreover, in a subgroup of subjects we evaluated paired-pulse inhibition of H-reflex. Continuous TBS at 110% of H-reflex threshold intensity induced a short-term reduction of H-reflex amplitude. The other stimulation conditions produced no after effects. Paired-pulse H-reflex inhibition was not modulated by continuous TBS or non-patterned repetitive stimulation at 15 Hz. An effect of pain on the results obtained was discarded, since non-patterned 15 Hz stimulation at 110% HT led to pain scores similar to those induced by EcTBS at 110% HT, but was not able to induce any modulation of the H reflex amplitude. Together, the results provide first time evidence that peripheral continuous TBS induces a short-lasting change in the excitability of spinal motoneurons in lower limb circuitries. Future studies need to investigate how the TBS protocol can be optimized to produce a larger and longer effect on spinal cord physiology and whether this might be a useful intervention in patients with excessive excitability of the spinal motorneurons.

Population stratification: a fundamental instrument used for population health management in Spain: good practice brief

Changing health services from a disease-centred to a patient-centred approach was one of objectives of the Spanish Strategy for Approaching Chronicity in the National Health System (2012). A strategic priority for facilitating this transformation was considered to be identification of the health needs of every patient, so that interventions could be tailored. In the framework of the project “Stratification of the population of the National Health System”, a locally developed and tested “population grouper”, Adjusted Morbidity Groups (AMG), was used in the majority of the Spanish regions to stratify patients’ risks according to morbidity and complexity (Ministry of Health, Social Services and Equality, 2018). Risk stratification is widely used in population health management, health service planning and clinical management. Stratification of the health risks of people with chronic diseases has been adopted in many European countries to strengthen population health management and provide better-tailored services. Some countries have purchased or adapted existing software, and others, like Spain, have developed novel, country-specific population tools for grouping and health risk assessment (Dueñas-Espín et al., 2016; Nalin et al., 2016). These practices are aligned with the European framework for action on integrated health services delivery as one of the key strategies for moving towards people-centred health services (WHO Regional Office for Europe, 2016).

Platelet-rich plasma and its effect in bone regeneration in mandibular fractures. Controlled clinical trial / Plasma rico en plaquetas y su efecto en la regeneración ósea en fracturas mandibulares. Ensayo clínico controlado

Background: Currently there is great interest in developing clinical applications of platelet-rich plasma to enhance bone repair. Aim: To assess bone regeneration in mandibular fractures, with the application of this adjuvant. Methods: Twenty patients with mandibular fractures were included in a randomized clinical trial. Patients of the experimental group (n = 10) were submitted to internal fracture reduction and administration of platelet-rich plasma, and patients of the control group (n = 10) were submitted to the same surgical procedure without plasma application. Radiologic assessment was made before and at 1 and 3 months after surgery. X-rays were digitalized for analyze intensity and density as reflection of bone regeneration. Results: The average age was 32 ± 11.3 years and 31.2 ± 8.48 years respectively (p = 0.76). The radiographic intensity and density in the experimental group at the 1st and 3rd month were higher in contrast to the control group (p < 0.005). Bone regeneration time was 3.7 ± 0.48 and 4.5 ± 0.52 weeks respectively (p = 0.002). There was no morbidity related to the application of the platelet-rich plasma. Conclusion: The platelet-rich plasma increased the bone intensity and density in the fracture trace allowing bone regeneration and recovery in shorter time than patients in which it was not used.

Antecedentes: Actualmente existe interés en el desarrollo de aplicaciones clínicas del plasma rico en plaquetas (PRP) para mejorar la regeneración ósea (RO). Objetivo: Evaluar la RO en fracturas mandibulares con la aplicación de PRP. Métodos: Ensayo clínico controlado. Se incluyeron 20 pacientes con fractura de ángulo mandibular. El grupo de estudio (n = 10) se sometió a reducción de la fractura, fijación interna y aplicación de PRP, y el grupo control (n = 10) al mismo procedimiento sin administración de plasma. Se evaluaron en el preoperatorio y al primer y tercer mes posterior a la reducción mediante digitalización radiográfica para evaluar la regeneración ósea. Resultados: El promedio de edad fue de 32 ± 11.3 y 31.2 ± 8.48 años, respectivamente (p = 0.76). La intensidad y la densidad radiográfica al mes y a los 3 meses fueron superiores en el grupo de estudio que en el grupo control (p< 0.005). El tiempo de regeneración fue de 3.7 ± 0.48 y 4.5 ± 0.52 semanas, respectivamente (p = 0.002). Conclusiones: El PRP aumentó la intensidad y la densidad ósea en el trazo de las fracturas, sugestivas de RO, y recuperación en menor tiempo, en contraste con el grupo control.

Oral glutamine reduces myocardial damage after coronary revascularization under cardiopulmonary bypass. A randomized clinical trial.

BACKGROUND: Glutamine is the most abundant free amino acid in the body. It modulates immune cell function and is an important energy substrate for cells in critically ill patients. Reduction of injury cardiac markers had been observed in patients receiving intravenous glutamine and in a pilot study with oral glutamine. The aim of this study was to analyze the effect of preoperative oral supplementation of glutamine on postoperative serum levels of cardiac injury markers. METHODS: A randomized clinical trial was performed in 28 Mexican patients with ischemic heart disease who underwent cardiopulmonary bypass with extracorporeal circulation. Patients were randomly assigned to receive oral glutamine (0.5 g/kg/day) or maltodextrin 3 days before surgery. Cardiac injury markers as troponin-I, creatine phosphokinase, and creatine phosphokinase-Mb were measured at 1, 12, and 24 hours postoperatively. RESULTS: At 12 and 24 hours serum markers levels were significantly lower in the glutamine group compared with controls (p = 0.01 and p = 0.001, respectively) (p = 0.004 and p < 0.001, respectively). Overall, complications were significantly lower in the glutamine group (p = 0.01, RR = 0.54, 95% CI 0.31-0.93). Mortality was observed with 2 cases of multiple organ failure in control group and 1 case of pulmonary embolism in glutamine group (p = 0.50). CONCLUSION: Preoperative oral glutamine standardized at a dose of 0.5 g/kg/day in our study group showed a significant reduction in postoperative myocardial damage. Lower cardiac injury markers levels, morbidity and mortality were observed in patients receiving glutamine.

Oral glutamine reduces myocardial damage after coronary revascularization under cardiopulmonary bypass. A randomized clinical trial / La glutamina oral reduce el daño miocárdico tras revascularización coronaria bajo derivación cardiopulmonar. Un ensayo clínico aleatorizado

Background: Glutamine is the most abundant free amino acid in the body. It modulates immune cell function and is an important energy substrate for cells in critically ill patients. Reduction of injury cardiac markers had been observed in patients receiving intravenous glutamine and in a pilot study with oral glutamine. The aim of this study was to analyze the effect of preoperative oral supplementation of glutamine on postoperative serum levels of cardiac injury markers. Methods: A randomized clinical trial was performed in 28 Mexican patients with ischemic heart disease who underwent cardiopulmonary bypass with extracorporeal circulation. Patients were randomly assigned to receive oral glutamine (0.5 g/kg/day) or maltodextrin 3 days before surgery. Cardiac injury markers as troponin-I, creatine phosphokinase, and creatine phosphokinase-Mb were measured at 1, 12, and 24 hours postoperatively. Results: At 12 and 24 hours serum markers levels were significantly lower in the glutamine group compared with controls (p = 0.01 and p = 0.001, respectively) (p = 0.004 and p < 0.001, respectively). Overall, complications were significantly lower in the glutamine group (p = 0.01, RR = 0.54, 95% CI 0.31-0.93). Mortality was observed with 2 cases of multiple organ failure in control group and 1 case of pulmonary embolism in glutamine group (p = 0.50). Conclusion: Preoperative oral glutamine standardized at a dose of 0.5 g/kg/day in our study group showed a significant reduction in postoperative myocardial damage. Lower cardiac injury markers levels, morbidity and mortality were observed in patients receiving glutamine (AU)

Introducción: la glutamina es el aminoácido libre más abundante en el cuerpo. Modula funciones celulares inmunológicas y es un sustrato importante de energía. Se observó reducción de los marcadores de daño cardiaco en pacientes que recibieron tanto glutamina intravenosa como oral en un estudio piloto. Nuestro objetivo fue analizar el efecto preoperatorio con suplementación de glutamina oral sobre los niveles postoperatorios de los marcadores de lesión cardiaca. Métodos: ensayo clínico aleatorizado con 28 pacientes mexicanos con cardiopatía isquémica y sometidos a bypass cardiopulmonar con circulación extracorpórea. Los pacientes fueron asignados al azar para recibir glutamina oral (0,5 g/kg/día) o maltodextrina 3 días antes de ser operados. La troponina-I, creatinina fosfoquinasa y creatinina fosfoquinasa-Mb fueron medidas a la hora, 12 y 24 horas postoperatorias. Resultados: a las 12 y 24 horas los niveles séricos de marcadores fueron menores en el grupo de glutamina comparado con los controles (p = 0,01 y p = 0,001, respectivamente) (p = 0,004 y p < 0,001, respectivamente). Las complicaciones fueron menores en el grupo de glutamina (p = 0,01, RR = 0,54, 95% IC 0,31-0,93). La mortalidad ocurrió en 2 casos con dos falla orgánica múltiple en el grupo control y 1 caso de tromboembolia pulmonar en el grupo de glutamina (p = 0,50). Conclusión: la administración estandarizada de glutamina oral de manera preoperatoria (0,5 g/kg/día) en nuestro estudio demostró una reducción significativa del daño miocárdico postoperatorio. Los niveles séricos de marcadores cardiacos, la morbilidad y mortalidad fueron menores en los pacientes que recibieron glutamina (AU)

One month of omega-3 fatty acid supplementation improves lipid profiles, glucose levels and blood pressure in overweight schoolchildren with metabolic syndrome.

BACKGROUND: This study sought to investigate the effects of omega (ω)-3 polyunsaturated fatty acid (PUFA) supplementation on the lipid profiles and glucose (GLU) levels of overweight (OW) schoolchildren with metabolic syndrome (MS). METHODS: Thirty-nine OW schoolchildren with MS, including 19 girls and 20 boys, received 1-month of dietary supplementation with gel capsules containing ω-3 fatty acids. Fasting lipid profiles and GLU levels were measured before and after supplementation. RESULTS: Both sexes of OW schoolchildren with MS who received daily supplementation with 2.4 g of ω-3 fatty acids for 1 month displayed improved lipid profiles, reduced fasting GLU levels and reduced blood pressure (BP). CONCLUSIONS: These findings support the addition of omega-3 fatty acid supplementation to programs aiming to improve the metabolic status of OW children with MS, although additional research on the longer-term safety and efficacy of this treatment in this population is required.

Impact of maternity care policy in Catalonia: a retrospective cross-sectional study of service delivery in public and private hospitals.

BACKGROUND: As a result of the growing number of interventions that are now performed in the context of maternity care, health authorities have begun to examine the possible repercussions for service provision and for maternal and neonatal health. In Spain the Strategy Paper on Normal Childbirth was published in 2008, and since then the authorities in Catalonia have sought to implement its recommendations. This paper reviews the current provision of maternity care in Catalonia. METHODS: This was a descriptive study. Hospitals were grouped according to their source of funding (public or private) and were stratified (across four strata) on the basis of the annual number of births recorded within their respective maternity service. Data regarding the distribution of obstetric professionals were taken from an official government survey of hospitals published in 2010. The data on obstetric interventions (caesarean, use of forceps, vacuum or non-specified instruments) performed in 2007, 2010 and 2012 were obtained by consulting discharge records of 44 public and 20 private hospitals, which together provide care in 98% of all births in Catalonia. Proportions and confidence intervals were calculated for each intervention performed in all full-term (37-42 weeks) singleton births. RESULTS: Analysis of staff profiles according to the stratification of hospitals showed that almost all the hospitals had more obstetricians than midwives among their maternity care staff. Public hospitals performed fewer caesareans [range between 19.20% (CI 18.84-19.55) and 28.14% (CI 27.73-28.54)] than did private hospitals [range between 32.21% (CI 31.78-32.63) and 39.43% (CI 38.98-39.87)]. The use of forceps has decreased in public hospitals. The use of a vacuum extractor has increased and is more common in private hospitals. CONCLUSIONS: Caesarean section is the most common obstetric intervention performed during full-term singleton births in Catalonia. The observed trend is stable in the group of public hospitals, but shows signs of a rise among private institutions. The number of caesareans performed in accredited public hospitals covers a limited range with a stable trend. Among public hospitals the highest rate of caesareans is found in non-accredited hospitals with a lower annual number of births.

Transient neonatal zinc deficiency due to a new autosomal dominant mutation in gene SLC30A2 (ZnT-2).

Transient neonatal zinc deficiency (TNZD) has a clinical presentation similar to that of acrodermatitis enteropathica but is caused by a low zinc concentration in maternal breast milk. TNZD becomes clinically evident during breastfeeding and is resolved by weaning and the introduction of complementary nutrition. We present a 4-month-old girl with TNZD due to a new autosomal dominant mutation (663delC) in the maternal SLC30A2 gene not previously described in the literature.

Quetiapine extended-release (Seroquel-XR) versus amitriptyline monotherapy for treating patients with fibromyalgia: a 16-week, randomized, flexible-dose, open-label trial.

RATIONALE: Previous open-label studies have suggested that quetiapine could be a valuable alternative for treating fibromyalgia. OBJECTIVE: This study aims to compare the efficacy and tolerability of extended-release quetiapine with amitriptyline for treating fibromyalgia. METHODS: This study was a randomized, open-label, flexible-dose, non-inferiority trial. Patients with fibromyalgia were randomized to receive quetiapine extended-release (XR) (N = 45) (50 to 300 mg daily) or amitriptyline (N = 45) (10 to 75 mg daily) for 16 weeks. The primary endpoint was the change from baseline to endpoint in the Fibromyalgia Impact Questionnaire (FIQ) total score; the non-inferiority threshold was established at 8 points. The secondary outcomes included sleep quality, anxiety, depression, and quality of life. RESULTS: Twenty-two (49%) patients in the quetiapine group and 34 (76%) patients in the amitriptyline group completed the study. We found a reduction of 9.8 points in the total FIQ score at the endpoint for the quetiapine-treated patients compared to 13.9 points for the amitriptyline-treated patients, for a difference of 4.14 points (80% confidence interval (CI) -0.70 to 8.98). No significant differences were found between the quetiapine XR and amitriptyline groups for any of the secondary outcomes. The proportion of patients discontinuing treatment due to adverse events was higher in the quetiapine group (n = 14, 31.1%) than the amitriptyline group (n = 3, 6.6%). CONCLUSIONS: Our results appear to indicate that quetiapine XR does not provide similar efficacy to amitriptyline for treating patients with fibromyalgia. Quetiapine XR had a worse tolerability than amitriptyline in this population, possibly due to a relatively high starting dose.

Ozone therapy as add-on treatment in fibromyalgia management by rectal insufflation: an open-label pilot study.

OBJECTIVES: The objectives of this study were to evaluate the effectiveness and tolerability of ozone therapy by rectal insufflation as add-on therapy in fibromyalgia management. DESIGN: Patients with fibromyalgia received 24 sessions of ozone therapy during a 12-week period. At each session, the administered dose of ozone was 8 mg (200 mL of gas, at a concentration of 40 µg/mL). Ozone sessions were given 5 days a week during the first 2 weeks, twice a week from weeks 3-6, and weekly from weeks 7-12. Fibromyalgia Impact Questionnaire (FIQ) was the main outcome measure, and was administered at baseline and at weeks 4, 8, and 12. Secondary outcome measures, administered at baseline and at endpoint, were the Pittsburgh Sleep Quality Index, the Beck Depression Inventory, the State and Trait Anxiety Inventory, and the SF-12, the abbreviated form of the Short Form Health Survey. Emergent adverse reactions to treatment were recorded. RESULTS: FIQ total scores decreased significantly during the study period, with the decrease being observed in the first 4 weeks of the study. Significant improvement was also seen both in depression scores and in the Physical Summary Score of the SF-12. Transient meteorism after ozone therapy sessions was the most frequently reported side-effect. CONCLUSIONS: At the dose and number of sessions used in this study, ozone therapy by rectal insufflation seems to be beneficial for physical symptoms and depression of fibromyalgia.

Mofetil micofenolato como alternativa de tratamiento para pacientes pediátricos con hepatitis autoinmune resistentes e intolerantes a esteroides y azatioprina

Introducción y objetivo: el tratamiento inicial en los pacientes pediátricos sigue siendo prednisona sola o en combinación con azatioprina, disminuyendo la dosis gradualmente entre la semana 4 y 8 una vez obtenida mejoría de las aminotranferasas. Los pacientes se mantienen con dosis bajas de esteroides necesarias para mantener niveles de aminotranferasas normales. El mofetil micofenolato es una alternativa terapéutica en aquellos pacientes que no responden o son intolerantes a azatioprina y esteroides. El objetivo del presente trabajo es evaluar la eficacia del mofetil micofenolato en pacientes pediátricos con diagnóstico de hepatitis autoinmune que eran intolerantes o no respondían a prednisona y azatioprina. Resultados: se incluyeron 6 pacientes con diagnóstico de hepatitis autoinmune en edades comprendidas de 7 a 15 años con un promedio de edad de 11,5+2,5 años, con edad de diagnóstico entre los 5 a 10 años, 4 del sexo masculino y 2 del sexo femenino. Cuatro (4) de los pacientes presentaban elevación de AST entre 62 y 258 con promedio 211,5+ 96,21 y ALT 104 y 334 con promedio 144,17+ 85,29 previa indicación del mofetil micofenolato, recibiendo tratamiento con prednisona y azatioprina y 2 tenían aminotranferasas normales, pero requerían dosis de esteroides altas sin poder reducirlas ya que presentaban elevación de aminotranferasas. Desde el punto de vista histológico, 3 pacientes presentaban arquitectura alterada, extensa fibrosis portal y septal, con tendencia a la formación de nódulos. Espacios porta ensanchados, con infiltrado inflamatorio mixto, 2 pacientes evidenciaban cirrosis con actividad leve y 1 hepatitis a células gigantes. Todos los pacientes recibieron mofetil micofenolato a 600 mgs/m2 superficie corporal/ dosis cada 12 horas. Luego de la administración del mofetil micofenolato, las dosis de prednisona se pudieron reducir a 0,25 y 0,5 mgs/ Kg/ día con normalización de aminotranferasas AST promedio 52 + 29,33 y ALT 40,16+ 9,15 excepto en 1 paciente en quien las aminotranferasas disminuyeron 2 veces su valor pero sin normalización de las mismas. Conclusión: el uso de mofetil micofenolato en pacientes pediátricos con hepatitis autoinmune en combinación con esteroides resulta eficaz para la mejoría de los parámetros bioquímicos que reflejan inflamación hepática y constituye una alternativa en pacientes pediátricos.

Introdución And Objective: The initial treatment in pediatric patients remains as prednisone alone or in combination with azathioprine and the dose is diminished gradually between week 4 and 8 once improvement of aminotranferase is obtained, staying the patients with low doses of steroids necessary to maintain normal levels of aminotranferase. The mycophenolate mofetil is a therapeutic alternative in those patients who do not respond or are intolerants to azathioprine and steroids. The objective of the present essay is to evaluate the effectiveness of mycophenolate mofetil in pediatric patients with diagnosis of autoimmune hepatitis that were intolerant or did not respond to prednisone and azathioprine. Results: 6 patients with diagnosis of autoimmune hepatitis were included with age ranging from 7 to 15 years with an average of 11,5+2,5 years, with age at diagnosis between 5 and 10 years, 4 male and 2 female 4 of the patients presented elevation of AST between 62 y 258 with an average 211,5+ 96,21 and ALT 104 y 334 with average 144,17+ 85,29 previous indication of mycophenolate mofetil, receiving treatment with prednisone and azathioprine and 2 had normal aminotranferase but they required high doses of steroids without being able to reduce them because of its elevation. From the histological point of view 3 patients presented altered architecture, extensive portal and septal fibrosis, with tendency to form nodules, widened portal spaces, with inflammatory compound infiltration, 2 patients presented cirrhosis with slight activity and 1 patient presented giant cell hepatitis. All the patients received mycophenolate mofetil at the dose of 600 mgs/m2 corporal surface every 12 hours. Following the administration of mycophenolate mofetil the doses of prednisone could be reduced to 0.25 and 0.5 mgs/kg day with normalization of aminotranferase AST in average 52 + 29,33 and ALT 40,16+ 9,15, except in 1 patient in which aminotranferase diminished 2 times its value but without its normalization. Conclusion: The use of mycophenolate mofetil in pediatric patients with autoimmune hepatitis in combination with steroids is effective in the improvement of the biochemical parameters that determine liver inflammation and constitutes an alternative in these patients.

Modulation of neurotransmitter systems by dehydroepiandrosterone and dehydroepiandrosterone sulfate: mechanism of action and relevance to psychiatric disorders.

Dehydroepiandrosterone (DHEA) is synthesized in the brain and several studies have shown that this steroid is a modulator of synaptic transmission. The effect of DHEA, and its sulfate ester DHEAS, on glutamate and GABA neurotransmission has been extensively studied but some effects on other neurotransmitter systems, such as dopamine, serotonin and nitric oxide, have also been reported. This review summarizes studies showing the effect of DHEA and DHEAS on neurotransmitter systems at different levels (metabolism, release, reuptake, receptor activation), as well as the activation of voltage-gated ion channels and calcium homeostasis, showing the variety of effects that these steroids exert on those systems, allowing the discussion of its mechanisms of action and its relevance to psychiatric disorders.

Mechanism of enzymatic degradation of the azo dye Orange II determined by ex situ 1H nuclear magnetic resonance and electrospray ionization-ion trap mass spectrometry.

Removal of azo dye effluents generated by textile photography industries is a main issue in wastewater treatment. Enzymatic treatment of dyes appears to be one of the most efficient processes for their degradation. The elucidation of degradation pathways is of special interest considering health and environmental priorities. Ex situ nuclear magnetic resonance (NMR) spectroscopy and electrospray ionization (ESI)-ion trap mass spectrometry performed directly on incubation medium have been used for the first time to follow kinetics of sulfonated azo dye Orange II enzymatic degradation. Nine transformation products were identified using these complementary analyses performed ex situ without any prior treatment. Three types of cleavage are proposed for the degradation pathway: (i) a symmetrical splitting of the azo linkage that leads to the formation of 4-aminobenzenesulfonate (and 1-amino-2-naphthol, not detected); (ii) an asymmetrical cleavage on the naphthalene side that generates 1,2-naphthoquinone and 4-diazoniumbenzenesulfonate as products, with the latter one being transformed into 4-hydroxybenzensulfonate; and (iii) a third degradation pathway that leads to 2-naphthol and 4-hydroxybenzenesulfonate. Moreover, three other intermediates have been identified. This study, which constitutes the first concomitant use of (1)H NMR spectroscopy and ESI-ion trap mass spectrometry in this field, illustrates the indubitable interest of the ex situ approach.

Predatory fauna in cornfields and response to imidacloprid seed treatment.

The composition and abundance of predatory fauna in corn, Zea mays L., were studied by field visual sampling and pitfall traps over a 5-yr period. In visual samplings, the most abundant groups were Araneae, Heteroptera, Carabidae, Coccinellidae, and Staphylinidae, whereas the prevalent predators caught in pitfall traps belonged to Carabidae, Araneae, Dermaptera, and Opilionidae. The most abundant species or genera in the prevalent groups, except in Arachnida, were identified. Application of the insecticide imidacloprid as a seed dressing is common in the study area to prevent wireworm and cutworm damage. By comparing predator composition and abundance in treated and untreated cornfields during the 5 yr, we assessed the impact of imidacloprid seed treatment on predatory fauna. Among the prevalent predator groups found in visual sampling, Araneae, Coccinellidae, and Staphylinidae were not affected by the imidacloprid treatment, whereas Carabidae was only moderately affected in one of the 5 yr studied. On the contrary, Heteroptera was more drastically reduced by the imidacloprid, but the effect varied with the year. Incidence of European corn borer, Ostrinia nubilalis (Hübner), may be increased as result of such heteropteran reduction. In pitfall traps, only Staphylinidae resulted in lower numbers as consequence of the treatment, whereas the rest of the most abundant predator groups, Carabidae, Araneae, Dermaptera, Opilionidae, Trombididae, and Heteroptera, were not caught in significantly different numbers in treated or untreated plots.

Optimización de los recursos en una consulta de ginecología de área / Resource optimization in a gynaecological office

Fundamento: el trabajo en las consultas de ginecología general ha ido cambiando a medida que ha aumentado el porcentaje de pacientes asintomáticas que acuden con la finalidad de beneficiarse del diagnóstico precoz del cáncer. Esto nos ha llevado a modificar la organización de la consulta, planteando el envío de las pruebas complementarias rutinarias por correo, ya que en la mayoría de los casos serán normales y no necesitarán tratamiento ni seguimiento posterior, a corto plazo. Métodos: sobre un total de 387 pacientes, analizamos el porcentaje que pueden beneficiarse del envío de los resultados por correo y descubrimos las situaciones que nos obligan a renunciar a esta posibilidad. Resultados: fue posible el envío de los resultados en 257 casos (66,4 por ciento). En 72 casos (18,6 por ciento) hubo que volver a citar. De estas pacientes, 26 presentaban trastornos menstruales, en 16 existía la sospecha de patología por síntomas o por exploración y en 14 se volvió a citar para confirmar menopausia e iniciar tratamiento. Conclusiones: el acuerdo entre médico y paciente de enviar por correo los resultados no patológicos, permite una más pronta resolución de las revisiones rutinarias y una utilización más adecuada de los recursos del área (AU)