Histidine Self-assembly and Stability on Mineral Surfaces as a Model of Prebiotic Chemical Evolution: An Experimental and Computational Approach.

The abiotic synthesis of histidine under experimental prebiotic conditions has proven to be chemically promising and plausible. Within this context, the present results suggest that histidine amino acid may function as a simple prebiotic catalyst able to enhance amino acid polymerization. This work describes an experimental and computational approach to the self-assembly and stabilization of DL-histidine on mineral surfaces using antigorite ((Mg, Fe)3Si2O5(OH)4), pyrite (FeS2), and aragonite (CaCO3) as representative minerals of prebiotic scenarios, such as meteorites, and subaerial and submarine hydrothermal systems. Experimental results were obtained through polarized-light microscopy, IR spectroscopy (ATR-FTIR), and differential scanning calorimetry (DSC). Molecular dynamics was performed through computational simulations with the MM + method in HyperChem software. IR spectra suggest the presence of peptide bonds in the antigorite-histidine and aragonite-histidine assemblages with the presence of amide I and amide II vibration bands. The FTIR second derivative inspection supports this observation. Moreover, DSC data shows histidine stabilization in the presence of antigorite and aragonite by changes in histidine thermodynamic properties, particularly an increase in histidine decomposition temperature (272ºC in antigorite and 275ºC in aragonite). Results from molecular dynamics are consistent with DSC data, suggesting an antigorite-histidine closer interaction with decreased molecular distances (cca. 5.5 Å) between the amino acid and the crystal surface. On the whole, the experimental and computational outcomes support the role of mineral surfaces in prebiotic chemical evolution as enhancers of organic stability.

Hypoxemia following hospital discharge after fast-track hip and knee arthroplasty - A prospective observational study subanalysis.

BACKGROUND: Post-operative hypoxemia is prevalent in hospitalized patients and may adversely affect recovery. However, little data exist on the post-discharge phase or details on duration, severity and potential risk factors. Thus, we investigated the incidence and risk factors for severe desaturation during the first post-operative week after THA/TKA by continuous nocturnal oxygen saturation monitoring. METHODS: The study was a secondary analysis of a prospective cohort study of 112 patients undergoing fast-track THA/TKA. Patients with known sleep apnoea were excluded. Oxygen saturation and heart rate were recorded by a wireless wrist-worn pulse oximeter 2 nights before and 7 nights after surgery. Data on demographics, opioid consumption and cognitive function were collected from medical charts, patient diaries and clinical testing respectively. The primary outcome was occurrence of severe desaturation defined as periods with saturation <85% lasting ≥10 minutes. Secondary outcomes included description of various saturation levels and relevant risk factors. RESULTS: Severe oxygen desaturation occurred in 35% of the patients during the first post-operative week. Duration and severity of hypoxemic episodes increased after the first post-operative day. Pre-operative episodes of hypoxemia significantly increased the risk of post-operative hypoxemic events (OR 2.4-4.4, CI 0.4-46), while pre- and post-operative opioid use, age, gender, ASA classification, type of surgery or anaesthesia were significantly related to the development of post-operative hypoxemia. CONCLUSIONS: One third of the patients suffered from increased and prolonged episodes of severe nocturnal hypoxemia during the first week after THA/TKA discharge. Increased risk for severe hypoxemic episodes was related to pre-operative hypoxemia.

A Bayesian framework for the inference of gene regulatory networks from time and pseudo-time series data.

Motivation: Molecular profiling techniques have evolved to single-cell assays, where dense molecular profiles are screened simultaneously for each cell in a population. High-throughput single-cell experiments from a heterogeneous population of cells can be experimentally and computationally sorted as a sequence of samples pseudo-temporally ordered samples. The analysis of these datasets, comprising a large number of samples, has the potential to uncover the dynamics of the underlying regulatory programmes. Results: We present a novel approach for modelling and inferring gene regulatory networks from high-throughput time series and pseudo-temporally sorted single-cell data. Our method is based on a first-order autoregressive moving-average model and it infers the gene regulatory network within a variational Bayesian framework. We validate our method with synthetic data and we apply it to single cell qPCR and RNA-Seq data for mouse embryonic cells and hematopoietic cells in zebra fish. Availability and implementation: The method presented in this article is available at https://github.com/mscastillo/GRNVBEM. Contact: mscastillo@ugr.es.

Early patient-reported outcomes versus objective function after total hip and knee arthroplasty: a prospective cohort study.

AIMS: The purpose of this study was to assess early physical function after total hip or knee arthroplasty (THA/TKA), and the correlation between patient-reported outcome measures, physical performance and actual physical activity (measured by actigraphy). PATIENTS AND METHODS: A total of 80 patients aged 55 to 80 years undergoing THA or TKA for osteoarthritis were included in this prospective cohort study. The main outcome measure was change in patient reported hip or knee injury and osteoarthritis outcome score (HOOS/KOOS) from pre-operatively until post-operative day 13 (THA) or 20 (TKA). Secondary measures were correlations to objectively assessed change in physical performance (paced-walk, chair-stand, stair-climb tests) at day 14 (THA) or 21 (TKA) and actual physical activity (actigraphy) measured at day 12 and 13 (THA) or 19 and 20 (TKA). RESULTS: Patients reported improved physical function (HOOS or KOOS) pre-operatively until day 13 (THA) or 20 (TKA) with a mean difference of 7 (95% confidence interval (CI) 1 to 13, p = 0.033) and 6 (95% CI 1 to 12, p = 0.033) percentage points, respectively. By contrast, objectively assessed physical function and activity declined, with no correlations between subjective and objective assessments for either THA or TKA patients (r2 ≤ 0.16, p ≥ 0.314). CONCLUSIONS: Early improvement in patient-reported physical function after THA/TKA does not correlate with objectively assessed function, and patient reported outcomes should not be used as the only measure of recovery. Cite this article: Bone Joint J 2017;99-B:1167-75.

Clinical, nociceptive and psychological profiling to predict acute pain after total knee arthroplasty.

BACKGROUND: Pre-operative identification of high-pain responders for acute pain after total knee arthroplasty (TKA) could lead to targeted analgesic trials and individualized analgesic strategies to improve recovery and potentially reduce the risk of persistent post-surgical pain. The aim of this study was to use simple clinical tests and questionnaires to identify predictive nociceptive and psychological factors for acute post-TKA pain. METHODS: Sixty consecutive TKA patients were included in a prospective descriptive study of pain during a 5-m walk-test 24 h post-operatively as the primary outcome. Predictive variables collected prior to surgery included demographics, nociceptive testing (pressure pain threshold (PPT), cold pressor tolerance, electrical pain threshold and tolerance) and psychological profile (pain catastrophizing scale (PCS) and hospital anxiety and depression scale). The prediction of acute post-TKA pain was assessed by univariate analysis, logistic regressions and ROC curves. RESULTS: Reduced PPT on the arm and increased PCS were predictive variables for moderate/severe post-TKA pain 24 h after surgery (P = 0.007 and P = 0.026, respectively, R-squared 0.21) in the logistic regression model. Odds ratios were 0.67 for a 50 kPa increased PPT and 1.36 for a 5 point increase in PCS. A predictive model with cut-off values of PPT ≤ 245 kPa and PCS≥ 8 point had a sensitivity of 71.4 and a specificity of 62.5. CONCLUSION: Pre-operative widespread pressure pain hypersensitivity and pain catastrophizing are predictive of moderate severe post-TKA pain. If validated in a larger population, the clinically applicable tests should be considered in future interventions aiming to minimize post-operative pain in high-risk patients.

Challenges in postdischarge function and recovery: the case of fast-track hip and knee arthroplasty.

This narrative review updates the recent advances in our understanding of the multifactorial pathogenesis for reduced postdischarge physical and cognitive function after fast-track surgery, using total hip and knee arthroplasty as surgical models. Relevant factors discussed include the surgical stress responses and potential methods for controlling postsurgical inflammation, pain, and cognitive dysfunction. The continuation of moderate to severe pain in up to 30% of patients for 2-4 weeks calls for better understanding of the underlying mechanisms and development of effective multimodal opioid-sparing analgesic regimens. The need for the development of effective physiotherapy programmes on a patient-specific basis is discussed, along with the need for optimal assessment of postoperative function to guide rehabilitation. Other relevant factors discussed include the role of orthostatic intolerance, sleep disturbances, and blood management, and specific patient populations at risk for adverse outcomes, including psychiatric disorders, to identify and guide future interventions for optimizing functional postdischarge outcomes after fast-track surgery.

Prenatal ethanol exposure alters met-enkephalin expression in brain regions related with reinforcement: possible mechanism for ethanol consumption in offspring.

The endogenous opioid system is involved in ethanol reinforcement. Ethanol-induced changes in opioidergic transmission have been extensively studied in adult organisms. However, the impact of ethanol exposure at low or moderate doses during early ontogeny has been barely explored. We investigated the effect of prenatal ethanol exposure on alcohol intake and Methionine-enkephalin (Met-enk) content in rat offspring. Met-enk content was assessed in the ventral tegmental area [VTA], nucleus accumbens [NAcc], prefrontal cortex [PFC], substantia nigra [SN], caudate-putamen [CP], amygdala, hypothalamus and hippocampus. Pregnant rats were treated with ethanol (2g/kg) or water during GDs 17-20. At PDs 14 and 15, preweanlings were evaluated in an intake test (5% and 10% ethanol, or water). Met-enk content in brain regions of infants prenatally exposed to ethanol was quantitated by radioimmunoassay. Ethanol consumption was facilitated by prenatal experience with the drug, particularly in females. Met-enk content in mesocorticolimbic regions - PFC and NAcc - was increased as a consequence of prenatal exposure to ethanol. Conversely, Met-enk levels in the VTA were reduced by prenatal ethanol manipulation. Prenatal ethanol also increased peptide levels in the medial-posterior zone of the CP, and strongly augmented Met-enk content in the hippocampus and hypothalamus. These findings show that prenatal ethanol exposure stimulates consumption of the drug in infant rats, and induces selective changes in Met-enk levels in regions of the mesocorticolimbic and nigrostriatal systems, the hypothalamus and hippocampus. Our results support the role of mesocorticolimbic enkephalins in ethanol reinforcement in offspring, as has been reported in adults.

Effects of level of feeding on energy utilization by Angora goats.

Twelve mature Angora does were used in a replicated 3 × 3 Latin square to determine effects of feeding level on energy utilization. Fiber growth and change in tissue (nonfiber) mass were determined in the first 4 wk of 6-wk periods, preceded by 14 or 18 d of adaptation. Determination of ME intake and gas exchange measures occurred in wk 4, followed by feeding near maintenance, then fasting in wk 5 and 6 to determine the ME requirement for maintenance (ME(m)). A 60% concentrate diet was fed at levels to approximate 100, 125, and 150% of assumed ME(m) [low, medium (med), and high, respectively]. Digestibilities and diet ME/GE were not affected by treatment with different amounts of feed offered and subsequent intake near ME(m). Heat energy during fasting (261, 241, and 259 kJ/kg of BW(0.75); SEM = 8.7) and efficiency of ME used for maintenance (71.6, 69.6, and 69.2%; SEM = 2.29) were similar among treatments, although ME(m) differed (P < 0.04) between med and high (365, 344, and 377 kJ/kg of BW(0.75) for low, med, and high, respectively; SEM = 10.3). Tissue gain was less (P < 0.01) for low than for the mean of med and high (MH; -0.6, 23.7, and 29.8 g/d), although clean fiber growth only tended (P < 0.09) to differ between low and MH (5.60, 6.57, and 7.36 g/d for low, med, and high, respectively; SEM = 0.621). Intake of ME was greater (P < 0.01) for MH than for low (6.87, 8.22, and 8.41 MJ/d for low, med, and high, respectively). Total heat energy was less (P < 0.02) for low vs. MH and tended (P < 0.07) to be greater for high than for med (6.03, 6.31, and 6.77 MJ/d); mobilized tissue energy was low but greater (P < 0.02) for low vs. MH (0.16, 0.01, and 0.04 MJ/d for low, med, and high, respectively). Efficiency of ME use for fiber growth was similar among treatments (17.2, 16.3, and 17.7% for low, med, and high, respectively; SEM = 1.61). In conclusion, efficiency of ME use for fiber growth was similar to the NRC recommendation regardless of feeding level, although ME(m) was decreased perhaps because of experimental conditions used. Energy appeared partitioned to fiber growth, but preferential usage was not complete possibly because energy metabolism for tissue accretion reached a plateau with the greatest feeding level.

Effects of stage of lactation and dietary concentrate level on energy utilization by Alpine dairy goats.

Twenty-four lactating and 13 nonlactating Alpine goats were used to determine effects of stage of lactation and dietary concentrate level on energy utilization. Diets comprising 60 or 20% concentrate (60%C and 20%C, respectively) were consumed ad libitum by lactating animals and at a level of intake near maintenance by nonlactating animals. Measurement periods were d 25 to 31 (early), 87 to 94 (mid), and 176 to 183 (late) of lactation. Eleven observations were made in early and mid lactation for each diet, and 8 and 7 were made in late lactation for the 60%C and 20%C diets, respectively. Efficiency of metabolizable energy (ME) use for maintenance (66.9, 71.4, and 61.1% for early, mid, and late lactation, respectively) and the maintenance ME requirement (479, 449, and 521 kJ/kg of BW(0.75) for early, mid, and late lactation, respectively) determined with nonlactating animals differed among stages of lactation. The efficiency of ME use for maintenance was similar between diets, but the maintenance requirement tended to be greater for the 60%C than for the 20%C diet (504 vs. 463 kJ/kg of BW(0.75)). The latter difference may have involved greater ME intake for the 60%C diet, resulting in a slightly greater difference between ME intake and total heat energy for the 60%C compared with the 20%C diet (11 vs. -8 kJ/kg of BW(0.75)). Intake of ME by lactating goats was greater for the 60%C than for the 20%C diet (18.6 vs. 16.3 MJ/d). Recovered energy in lactation from mobilized tissue tended to be greater for the 60%C than for the 20%C diet (8.44 vs. 6.55 MJ/d) and differed among stages of lactation (2.60, 1.59, and 1.13 MJ/d in early, mid, and late lactation, respectively). Recovered energy in tissue gain was similar among stages of lactation and between diets and was not different from 0. Efficiency of use of dietary ME for lactation differed among stages of lactation (59.5, 51.9, and 65.4% for early, mid, and late lactation, respectively) and tended to be greater for the 60%C than for the 20%C diet (64.2 vs. 54.9%). The efficiency of use of dietary ME for maintenance and lactation was similar among stages of lactation and was greater for the 60%C compared with the 20%C diet (64.3 vs. 60.9%). Predicted milk yield from National Research Council requirements was reasonably accurate. In conclusion, using data of nonlactating goats to study energy utilization for maintenance in lactation has limitations. Efficiency of energy use by lactating dairy goats consuming diets high in concentrate appears greater than that by goats consuming diets low in concentrate. Despite differences in nutrient requirement expressions, observations of this study support National Research Council recommendations of energy requirements of lactating dairy goats.

Effects of stage of lactation and level of feed intake on energy utilization by Alpine dairy goats.

Thirty-six lactating Alpine does were used to determine effects of stage of lactation and level of feed intake on energy utilization. Twelve does were assigned to measurement periods in early, mid, and late lactation (wk 5, 13, and 27, respectively). For 6 does of each group, after ad libitum consumption of a 60% concentrate diet, feed intake was restricted to near the metabolizable energy (ME) requirement for maintenance (ME(m)) for 8 d followed by fasting for 4 d. For other does, fasting immediately followed ad libitum consumption. Intake of ME was similar among stages of lactation with ad libitum intake (22.1, 22.1, and 19.8 kJ/d in early, mid, and late lactation, respectively). The efficiency of ME use for maintenance determined with does fed near ME(m) averaged 81%. Fasting heat energy was greater for ad libitum consumption than for near ME(m) consumption [368 vs. 326 kJ/kg of body weight (BW)(0.75)] and was numerically lowest among stages in late lactation with near ME(m) intake (334, 350, and 295 kJ/kg of BW(0.75) in early, mid, and late lactation, respectively) and ad libitum consumption (386, 384, and 333 kJ/kg of BW(0.75) in early, mid, and late lactation, respectively). The efficiency of use of dietary ME for lactation was greater for consumption near ME(m) than for consumption ad libitum (67.9 vs. 58.6%) and with ad libitum consumption tended to decrease with advancing stage of lactation (63.9, 57.3, and 54.5% for early, mid, and late lactation, respectively). Estimated ME(m) was greater for ad libitum intake than for near ME(m) intake and was lowest during late lactation (429, 432, and 358 kJ/kg of BW(0.75) for near ME(m) intake and 494, 471, and 399 kJ/kg of BW(0.75) for ad libitum intake in early, mid, and late lactation, respectively). However, because of increasing BW as the experiment progressed, ME(m) (MJ/d) was similar among stages of lactation with both levels of intake. The efficiency of ME use for maintenance and lactation was similar among stages of lactation and greater with near ME(m) intake than ad libitum intake (77.1 vs. 67.7%). In conclusion, the ME(m) requirement (kJ/kg of BW(0.75)) of does in late lactation was less than in early and mid lactation. A marked effect of restricted feed intake subsequent to ad libitum consumption on estimates of efficiency of energy use for maintenance and lactation was observed compared with use of nonlactating animals. Level of feed intake can have substantial effect on estimates of energy utilization by lactating dairy goats.

Effects of acute ethanol administration on methionine-enkephalin expression and release in regions of the rat brain.

The dopaminergic mesolimbic system plays a key role in mediating the reinforcing properties of ethanol and other drugs of abuse. Ethanol reinforcement and high alcohol drinking behaviour have been suggested to involve the ethanol-induced activation of endogenous opioid systems. Ethanol may alter opioidergic transmission at different levels, including opioid peptide biosynthesis and release, as well as binding to opioid receptors. The aim of this work was to investigate the effects of different ethanol doses on methionine-enkephalin (Met-enk) release from the rat nucleus accumbens (NAcc). Ethanol effects were also studied on Met-enk content in the NAcc, prefrontal cortex (PFC) and caudate-putamen (CP). Met-enk release was studied by microdialysis in Wistar anesthetized rats and peptide concentrations were quantitated by radioimmunoassay. Ethanol was administered by intraperitoneal injection after a 2-h basal release period. Ethanol doses of 0.5, 1 and 2.5 g/kg induced a 2.7-, 4.9- and 3.4-fold increase in Met-enk release from the NAcc. However, ethanol responses followed different kinetics, with earliest effects observed with the highest ethanol dose. In comparison, a 2.5-fold increase in peptide release was produced by 100 mM KCl. Ethanol, at a dose of 2.5 g/kg, induced a significant 66.7% decrease in Met-enk content in the NAcc, as well as a 76.4% reduction in peptide levels in the CP. Lower ethanol doses did not alter Met-enk content in these regions. On the other hand, an ethanol dose of 0.5 g/kg produced a non-significant decrease in Met-enk levels in the PFC. Our results suggest that ethanol-induced changes in enkephalin expression and release in regions of the mesocorticolimbic and nigrostriatal pathways could be involved in ethanol central effects. Released enkephalins by ethanol may modulate the dopaminergic activity of mesolimbic neurons and play a critical role in ethanol reinforcement mechanisms.

Culture-independent analysis of lactic acid bacteria diversity associated with mezcal fermentation.

Mezcal is an alcoholic beverage obtained from the distillation of fermented juices of cooked Agave spp. plant stalks (agave must), and each region in Mexico with denomination of origin uses defined Agave species to prepare mezcal with unique organoleptic characteristics. During fermentation to produce mezcal in the state of Tamaulipas, not only alcohol-producing yeasts are involved, but also a lactic acid bacterial community that has not been characterized yet. In order to address this lack of knowledge on this traditional Mexican beverage, we performed a DGGE-16S rRNA analysis of the lactic acid bacterial diversity and metabolite accumulation during the fermentation of a typical agave must that is rustically produced in San Carlos County (Tamaulipas, Mexico). The analysis of metabolite production indicated a short but important malolactic fermentation stage not previously described for mezcal. The denaturing gradient gel electrophoresis (DGGE) analysis of the 16S rRNA genes showed a distinctive lactic acid bacterial community composed mainly of Pediococcus parvulus, Lactobacillus brevis, Lactobacillus composti, Lactobacillus parabuchneri, and Lactobacillus plantarum. Some atypical genera such as Weissella and Bacillus were also found in the residual must. Our results suggest that the lactic acid bacteria could strongly be implicated in the organoleptic attributes of this traditional Mexican distilled beverage.

Technical Note: The relationship between heart rate and energy expenditure in growing crossbred Boer and Spanish wethers.

Eight Boer (75%) x Spanish (BS) and 8 Spanish (S) wethers (155 +/- 8 d of age and 19.2 +/- 2.3 kg of BW initially) were used in a replicated crossover design with a 2 x 2 factorial arrangement of treatments to determine effects of genotype, diet quality, and time of day on energy expenditure (EE), heart rate (HR), and EE:HR with ad libitum, near maintenance, and fasting levels of feed intake. Diets were 65% concentrate or coarsely ground alfalfa hay. Energy expenditure was ranked (P < 0.05) ad libitum > maintenance > fasting (500, 390, and 270 kJ/kg of metabolic BW). Heart rate did not differ between genotypes when fasting and with maintenance intake, but was greater (P < 0.05) for S than for BS when intake was ad libitum (BS: 55, 71, and 92; S: 52, 72, and 100 beats/min for fasting, maintenance, and ad libitum, respectively, SEM = 2.0). There was an interaction in EE:HR (P < 0.05) between level of feed intake and genotype (BS: 5.31, 5.59, and 5.00; S: 5.07, 5.57, and 5.22 kJ/kg of metabolic BW:beat/min for ad libitum, maintenance, and fasting, respectively, SEM = 0.13), without an effect of diet. The effect of time on EE, HR, and EE:HR differed among levels of intake (P < 0.05). General patterns of change in EE and HR as time of day advanced did not differ, but increases near meals followed by decreases were of slightly greater magnitude for maintenance than for ad libitum intake. The ratio of EE:HR was greater for the maintenance level of feed intake than for ad libitum intake at most times. These results indicate similar potential for use of HR to predict EE of different genotypes of growing meat goats and that establishing EE:HR with different diets or levels of intake may not be crucial. Magnitudes of difference among hours suggest that when EE:HR is used to predict EE of confined goats from full-day measurement of HR, EE:HR should be determined over an extended period of time, such as 24 h.

Biocontrol potential and polyphasic characterization of novel native Trichoderma strains against Macrophomina phaseolina isolated from sorghum and common bean.

Native strains of Trichoderma isolated from sorghum and common bean crop soils were investigated to assess their biocontrol potential over the phytopathogenic fungus Macrophomina phaseolina, isolated from diseased plants. The Trichoderma strains were characterized with a polyphasic approach, which combined the analysis of their morphological characteristics, enzymatic activity, macro- and microculture test results, rDNA restriction patterns (AFLP), ITS1-5.8S-ITS2 rDNA sequences, and protein profiles. The integration of these data sets can be used to select new isolates as biological control agents against native fungal phytopathogens. In general, we observed a positive correlation between the secretion of beta-1,3-glucanase and N-acetylhexosaminidase, and the biocontrol capacities of all the Trichoderma isolates. Strains with the best hyperparasitic behavior against M. phaseolina isolated from diseased bean and sorghum were Trichoderma sp. (TCBG-2) and Trichoderma koningiopsis (TCBG-8), respectively.

A prospective and multicenter safety-monitoring study of a short up-dosing schedule of immunotherapy with a mass-units-standardized extract of mites.

A prospective, multicenter pharmacovigilance study was carried out to evaluate the safety of a new 7-dose treatment schedule of subcutaneous immunotherapy as opposed to the conventional 13 doses normally recommended. The study was carried out in 14 centers and included 261 patients (children and adults) with respiratory allergic disease due to sensitization to mites (Dermatophagoides pteronyssinus and/or farinae). A total of 2290 doses were administered under the direct supervision of the participating specialists. One hundred and ten reactions in 63 patients (24.1%) were recorded, representing 4.8% of the total doses administered. Most of the reactions (98) were local. Only 12 were systemic (0.5% of the administered doses) and occurred in 10 patients (3.8% of the sample). Ten reactions reverted quickly with rescue medication. The maintenance dose had to be lowered in one patient and another patient was withdrawn from the study after suffering two asthmatic crises after two consecutive doses. In view of the results obtained, we can conclude that the new schedule shows an acceptable tolerance profile and does not present a greater risk of reactions than the conventional scheme of 13 doses using an identical extract. Moreover, the new schedule represents substantial savings in the number of doses and visits required to reach the maintenance dose.

A prospective and multicenter safety-monitoring study of a short up-dosing schedule of immunotherapy with a mass-units-standardized extract of mites

A prospective, multicenter pharmacovigilance study was carried out to evaluate the safety of a new 7-dose treatment schedule of subcutaneous immunotherapy as opposed to the conventional 13 doses normally recommended. The study was carried out in 14 centers and included 261 patients (children and adults) with respiratory allergic disease due to sensitization to mites (Dermatophagoides pteronyssinus and/or farinae). A total of 2290 doses were administered under the direct supervision of the participating specialists. One hundred and ten reactions in 63 patients (24.1 %) were recorded, representing 4.8 % of the total doses administered. Most of the reactions (98) were local. Only 12 were systemic (0.5 % of the administered doses) and occurred in 10 patients (3.8 % of the sample). Ten reactions reverted quickly with rescue medication. The maintenance dose had to be lowered in one patient and another patient was withdrawn from the study after suffering two asthmatic crises after two consecutive doses. In view of the results obtained, we can conclude that the new schedule shows an acceptable tolerance profile and does not present a greater risk of reactions than the conventional scheme of 13 doses using an identical extract. Moreover, the new schedule represents substantial savings in the number of doses and visits required to reach the maintenance dose (AU)

Se ha llevado a cabo un estudio prospectivo y multicéntrico de farmacovigilancia, con el objetivo de valorar la seguridad de una nueva pauta en inmunoterapia subcutánea de 7 dosis, frente a las 13 de la pauta convencional habitualmente recomendada. El estudio se realizó en 14 centros, incluyéndose 261 pacientes (niños y adultos) con enfermedad alérgica respiratoria por sensibilización a ácaros (Dermatophagoides pteronyssinus y/o farinae). Se administraron un total de 2.290 dosis, todas ellas bajo la supervisión directa de los especialistas participantes. Se registraron 110 reacciones en 63 pacientes (24,1 por ciento), lo que supone un porcentaje sobre el total de dosis administradas del 4,8 por ciento. La mayoría de reacciones (98) fueron locales. Tan sólo 12 fueron sistémicas (0,5 por ciento sobre las dosis administradas) las cuales ocurrieron en 10 pacientes (3,8 por ciento de la muestra). En 10 casos revertieron rápidamente con medicación de alivio, en 1 caso fue necesario bajar la dosis de mantenimiento, y en 1 paciente se decidió retirarle del estudio por padecer 2 crisis asmáticas en dos dosis consecutivas. A la vista de los resultados obtenidos, podemos concluir que la nueva pauta ensayada presenta un adecuado perfil de tolerancia, no existiendo mayor riesgo de reacciones al compararlo con el perfil de la pauta convencional de 13 dosis utilizando idéntico extracto. Además, la nueva pauta supone un notable ahorro en el número de dosis y visitas necesarias para alcanzar la dosis de mantenimiento (AU)

Pinus pollen aerobiology and clinical sensitization in northwest Spain.

BACKGROUND: Pinus pollen allergy has been generally considered to be rare and clinically insignificant. In our geographical area, Pinus pollen constitutes one of the most predominant pollen together with Poaceae and Urticaceae pollen. Pinus pinaster and Pinus radiata are the main species. OBJECTIVE: This work aimed to determine the atmospheric fluctuations and the existence of patients monosensitized to Pinus pollen in our region. METHODS: Patients attending our outpatient clinic in the last 4 years with positive cutaneous tests to Pinus pollen and with respiratory symptoms were selected. They were skin tested with commercial extracts of a battery of inhalants including Pinus pollen. Serologic specific IgE to Pinus pollen was performed by CAP system (Pharmacia & Upjohn, Uppsala, Sweden). Airborne Pinus pollen counts in our city were obtained for a 5-year period (1995 to 1999). RESULTS: We present 10 patients with sensitivity to Pinus pollen and with symptomatology coinciding with Pinus pollen season (February to April). Most of these patients were monosensitizated to Pinus pollen and suffered from seasonal rhinoconjunctivitis. Pinus pollen is present in our area in large amounts from February to April with a peak pollen count in March and April. CONCLUSIONS: Pinus pollen may be an important allergen since by itself can be the only cause of allergic disease. Therefore, we think that it must be taken into account in patients living in areas with high Pinus pollen concentrations and with seasonal respiratory disease.