Targeted Electromyographic Biofeedback With Endoanal Electrostimulation for Anal Incontinence.

Purpose. Anal incontinence (AI) is a disabling condition with a variable response to conservative physical therapies. We assess the utility of combining electromyographic biofeedback with endoanal electrostimulation targeted to the weakest areas of the pelvic floor using the MAPLe® probe (Multiple Array Probe Leiden Novuqare). Methods. Patients with AI unresponsive to conservative measures were assessed before and after treatment with anorectal manometry (ARM), electromyography (EMG), Wexner Continence Scoring, Visual Analog Scoring (VAS), FIQL and SF-12 quality of life determination. Results. Of 29 patients in the final analysis, there was an improvement in the mean Wexner continence score from 13.59 to 8.03 and a concomitant improvement in the reported VAS from 3.45 to 6.72. Both Wexner continence and VAS scores were maintained during follow-up. Maximum voluntary manometric contraction significantly improved from 91.76 mmHg to 110.33 mmHg with no changes in resting pressure. The EMG values ​​(µV) that significantly improved included the average and peak resistance, the average general voluntary contraction, and the average and peak voluntary contraction for both the external anal sphincter and the puborectalis. In the FIQL, behavior, depression and shame domains improved after treatment and during follow-up with lifestyle improvements detected at 6 and 12 months. Physical and mental components of the SF-12 improved at 6 and 12 months. Conclusions. Targeted electromyographic biofeedback and endoanal electrostimulation using MAPLe® probe in AI patients sustainably improves objective ARM and EMG parameters along with subjective reporting of continence severity, VAS, and quality of life.

Tablet-based sublingual immunotherapy for respiratory allergy.

Allergic respiratory disease represents a significant and expanding health problem worldwide. The gold standard of therapeutic intervention is still grucocorticosteroids, although they are not effective in all patients and may cause side effects. Allergen Immunotherapy has been administrated as subcutaneous injections for treatment of allergic rhinoconjunctivitis and asthma and has been practiced for the past century. Sublingual immunotherapy (SLIT) tablets are now available for grass- or ragweed-induced rhinoconjunctivitis and will be available in Spain for house dust mite (HDM)-induced rhinoconjunctivitis and asthma in the next months. In this review, new developments in the field of tablet-based SLIT for respiratory allergy are summarized, with special emphasis on HDM-induced allergic rhinitis and asthma. SLIT tablets are the best-documented immunotherapy products on the market and represent a more patient-friendly concept because they can be self-administrated at home.

Clinical and virologic follow-up in perinatally HIV-1-infected children and adolescents in Madrid with triple-class antiretroviral drug-resistant viruses.

Drug resistance mutations compromise the success of antiretroviral treatment in human immunodeficiency virus type 1 (HIV-1)-infected children. We report the virologic and clinical follow-up of the Madrid cohort of perinatally HIV-infected children and adolescents after the selection of triple-class drug-resistant mutations (TC-DRM). We identified patients from the cohort carrying HIV-1 variants with TC-DRM to nucleoside reverse transcriptase inhibitors, nonnucleoside reverse transcriptase inhibitors and protease inhibitors according to IAS-USA-2013. We recovered pol sequences or resistance profiles from 2000 to 2011 and clinical-immunologic-virologic data from the moment of TC-DRM detection until December 2013. Viruses harbouring TC-DRM were observed in 48 (9%) of the 534 children and adolescents from 2000 to 2011, rising to 24.4% among those 197 with resistance data. Among them, 95.8% were diagnosed before 2003, 91.7% were Spaniards, 89.6% carried HIV-1-subtype B and 75% received mono/dual therapy as first regimen. The most common TC-DRM present in ≥50% of them were D67NME, T215FVY, M41L and K103N (retrotranscriptase) and L90M (protease). The susceptibility to darunavir, tipranavir, etravirine and rilpivirine was 67.7%, 43.7%, 33.3% and 33.3%, respectively, and all reported high resistance to didanosine, abacavir and nelfinavir. Despite the presence of HIV-1 resistance mutations to the three main antiretroviral families in our paediatric cohort, some drugs maintained their susceptibility, mainly the new protease inhibitors (tipranavir and darunavir) and nonnucleoside reverse transcriptase inhibitors (etravirine and rilpivirine). These data will help to improve the clinical management of HIV-infected children with triple resistance in Spain.

Natural pollen exposure increases the response plateau to adenosine 5'-monophosphate and bronchial but not alveolar nitric oxide in sensitized subjects.

BACKGROUND: The effect of allergen exposure on airway responsiveness and exhaled nitric oxide (NO) has been well documented, but no information is available on allergen-induced changes in the response plateau to adenosine 5'-monophosphate (AMP) and in bronchial NO flux (J'aw(NO)) and alveolar NO (CA(NO)). OBJECTIVES: To determine the effect of natural allergen exposure, a proinflammatory stimulus, on the shape of the concentration-response curve to AMP and NO production in airway and alveolar sites. METHODS: Airway responsiveness to high concentrations of methacholine and AMP, J'aw(NO) and CA(NO) values were obtained in 31 subjects with pollen allergy and in 11 healthy controls. Subjects with pollen allergy were studied before and at the height of the pollen season whereas healthy controls were tested on one occasion only. RESULTS: In the group with pollen allergy, natural pollen exposure increased J'aw(NO) (p = 0.03), but had no effect on CA(NO) (p = 0.12). In the 18 subjects with pollen allergy who showed a response plateau to AMP in at least one period, the response plateau to AMP increased from a mean of 13.4% (95% CI: 8.2-18.5) out of season to 22.5% (95% CI: 15.5-29.4, p = 0.004) during the pollen season. Similar results were obtained with methacholine. Compared with healthy controls, subjects with pollen allergy had a higher response plateau and higher J'aw(NO) values. CONCLUSIONS: These findings suggest that inflammatory changes induced by natural allergen exposure in sensitized subjects are predominantly located in the airways and associated with modifications in the shape of the concentration-response curve to direct and indirect agonists.

Substitution rate and milk yield response to corn silage supplementation of late-lactation dairy cows grazing low-mass pastures at 2 daily allowances in autumn.

Feed costs in dairy production systems may be decreased by extending the grazing season to periods such as autumn when grazing low-mass pastures is highly probable. The aim of this autumn study was to determine the effect of corn silage supplementation [0 vs. 8 kg of dry matter (DM) of a mixture 7:1 of corn silage and soybean meal] on pasture intake (PI), milk production, and grazing behavior of dairy cows grazing low-mass ryegrass pastures at 2 daily pasture allowances (PA; low PA=18 vs. high PA=30 kg of DM/cow above 2.5 cm). Twelve multiparous Holstein cows were used in a 4 × 4 Latin square design with 14-d periods. Pre-grazing pasture mass and pre-grazing plate meter pasture height averaged 1.8 t of DM/ha (above 2.5 cm) and 6.3 cm, respectively. The quality of the offered pasture (above 2.5 cm) was low because of dry conditions before and during the experiment (crude protein=11.5% of DM; net energy for lactation=5.15 MJ/kg of DM; organic matter digestibility=61.9%). The interaction between PA and supplementation level was significant for PI but not for milk production. Supplementation decreased PI from 11.6 to 7.6 kg of DM/d at low PA and from 13.1 to 7.3 kg of DM/d at high PA. The substitution rate was, therefore, lower at low than at high PA (0.51 vs. 0.75). Pasture intake increased with increasing PA in unsupplemented treatments, and was not affected by PA in supplemented treatments. Milk production averaged 13.5 kg/d and was greater at high than at low PA (+1.4 kg/d) and in supplemented than unsupplemented treatments (+5.2 kg/d). Milk fat concentration averaged 4.39% and was similar between treatments. Milk protein concentration increased from 3.37 to 3.51% from unsupplemented to supplemented treatments, and did not vary according to PA. Grazing behavior parameters were only affected by supplementation. On average, daily grazing time decreased (539 vs. 436 min) and daily ruminating time increased (388 vs. 486 min) from 0 to 8 kg of supplement DM. The PI rate was 6g of DM/min lower in supplemented than in unsupplemented treatments (17 vs. 23 g of DM/min). The high milk yield response to supplementation may be related to a cumulative effect of the low-mass pasture (low PI) and the low quality of the pasture, which strongly limited energy supply in unsupplemented cows.

Sangre y Cirugía. EStrategia de Ahorro en cirugía cardiaca / Blood and Surgery. Strategic saving in cardiac surgery

El incremento de intervenciones quirúrgicas y su mayor complejidad y agresividad, especialmente en cirugía cardiovascular y trasplantes, junto con el envejecimiento de la población ha supuesto un considerable aumento de la demanda de transfusión sanguínea y derivados hemáticos. Los riesgos médicos inherentes al uso de sangre homóloga, el rechazo por motivaciones personales, éticas o creencias religiosas y una insuficiente disponibilidad de hemoderivados consecuencia de la escasezde donaciones, ha condicionado la necesidad del desarrollo de procesos de ahorro de sangre en cirugía y la búsqueda de técnicas alternativas a la transfusión. Problemática que alcanza su máxima expresión en cirugía cardiaca bajo circulación extracorpórea, como consecuencia del alto consumo de sangre de los enfermos cardiológicos intervenidos. Con la experiencia que aporta un promedio de quinientas cirugías anuales de corazón se realiza una revisión sobre las diferentes medidas y procedimientos asociados al ahorro de sangre en cirugía, especialmente en cirugía cardiovascular (AU)

The increase in the number of operations and their greater complexity and aggressiveness, especially in cardiovascular surgery and transplants, together with the aging of the population, has entailed an increase in the demand for transfusion and haematological derivates. The inherent medical risks of homolog blood usage, rejection for personal motivations, ethical and religious beliefs and insufficient availability of haematological derivates as a consequence of the shortage of donations, have conditioned the necessity for the development of processes for saving blood during surgery and the search for alternative techniques to transfusion. This is a problem which has its highest repercussions in cardiac surgery with cardio-pulmonary by-pass because of the high consumption of blood of patients undergoing cardiac surgery. With the experience of approximately 500 operations per year a review of the different measures and procedures associated with saving blood in surgery has been carried out, especially with regard to cardiovascular surgery (AU)

Carcinoma de células fusiformes tipo “fibromatosis-like”: una variante inusual de carcinoma metaplásico de mama asociado a carcinoma ductal / No disponible

El carcinoma de células fusiformes tipo fibromatosis-like esuna variante del carcinoma metaplásico, que ha sido reconocidorecientemente como una entidad distinta e independiente del restode los tumores metaplásicos, que recuerda a la fibromatosis yse caracteriza por ser un tumor de bajo grado, con mejor pronósticoy tendencia a la recidiva local. Presentamos un caso de unapaciente de 71 años con un carcinoma tipo fibromatosis-likeasociado a un carcinoma ductal de la mama. La histología revelóun tumor de células fusiformes simulando una fibromatosis, dondese puede identificar un componente epitelial en forma de carcinomaductal o intraductal en continuidad con el componente deaspecto fusiforme. Inmunohistoquímicamente presentó positividadfocal para marcadores epiteliales y mioepiteliales como citoqueratinasy expresión de marcadores mesenquimales como vimentina.El diagnóstico exacto puede presentar dificultad tantoradiológica como anatomopatológica y plantea el diagnóstico diferencialcon lesiones benignas como fibromatosis, fascitis nodularo malignas como sarcomas. El comportamiento y pronósticono ha sido del todo aclarado aunque se ha visto que es un tumorque se caracteriza por un alto riesgo de recidiva, bajo potencialpara metastatizar en ganglios linfáticos regionales pero con capacidadpara producir metástasis a distancia y por tanto, debería sertratado en consecuencia(AU)

Fibromatosis-like spindle cell carcinoma of the breast is avariant of metaplastic carcinoma that has recently been recognizedas a different entity because of its resemblance to fibromatosisand similar propensity for local recurrence. We presenta case of 71- year-old lady with a fibromatosis-like carcinomaassociated with ductal carcinoma of the breast. Finalhistology revealed a tumor with predominant spindle cells in acollagenous background, simulating a fibromatosis. Inmunohistochemistryshowed focal positivity of ephithelial and myoephitelialmarkers as citokeratins and expression of mesenchymalmarker as vimentin in the tumor. This tumor can posediagnostic difficulty radiologic as histopathology and the differentialdiagnosis includes both benign and malignant spindlecell breast lesions as a fibromatosis, nodule fascitis or sarcomas.The behaviour and prognosis have not been well clarifiedalthough there seems to have high risk of local recurrence, lowpotential to metastasize to regional lymph nodes and potentialfor distant metastasis and should be treated accordingly(AU)

Concentrations of exhaled nitric oxide in asthmatics and subjects with allergic rhinitis sensitized to the same pollen allergen.

BACKGROUND: Some studies have reported that the levels of exhaled nitric oxide (ENO) in asthmatics are similar to those in subjects with allergic rhinitis, and it has been postulated that atopic status might be the determinant of enhanced nitric oxide production in asthma. OBJECTIVES: The aim of this study was to determine differences in ENO levels between asthmatics and subjects with allergic rhinitis sensitized to the same allergen, and to correlate these levels with airway responsiveness. METHODS: Nineteen patients with asthma and 18 subjects with allergic rhinitis monosensitized to Parietaria pollen were enrolled in the study. ENO values and airway responsiveness to methacholine and adenosine 5'-monophosphate (AMP) were measured during the pollen season. The response to each bronchoconstrictor agent was measured by the provocative concentration required to produce a 20% fall in FEV1 (PC20). ENO was measured with the single-exhalation method. RESULTS: The geometric mean (95% confidence interval) ENO values were significantly higher in asthmatics than in subjects with allergic rhinitis: 72.4p.p.b. (54.9-93.3p.p.b) vs. 44.7p.p.b. (30.9-64.6p.p.b., P = 0.03). In asthmatics, a significant correlation was found between ENO and PC20 AMP values (p = -0.57, P=0.02), whereas no correlation was detected between ENO and PC20 methacholine (p = -0.35, P = 0.14). CONCLUSIONS: Our results suggest that atopy is not the only determinant of increased ENO levels detected in subjects with asthma, and that responsiveness to AMP may be a more sensitive marker for assessing airway inflammation in asthma compared to methacholine.

Estrogen modulates norepinephrine-induced accumulation of adenosine cyclic monophosphate in a subpopulation of immortalized luteinizing hormone-releasing hormone secreting neurons from the mouse hypothalamus.

A subpopulation of luteinizing hormone-releasing hormone (LHRH)-producing cells that express the intermediate filament protein vimentin and the neuronal marker neurofilament 145, but not neurofilament 200 nor glial fibrillary acidic protein, has been isolated from GT1-7 cultures. These cells express the mRNA encoding estrogen receptor alpha (ERalpha) and respond to physiological concentrations of 17beta-estradiol (E2) by reducing the accumulation of cyclic adenosine monophosphate induced by norepinephrine, but not that induced by direct activation of adenylate cyclase. These results indicate that the activity of LHRH-producing neurons may be directly modulated by estrogen. In addition, they are suggestive of an estrogen-dependent desensitization of the beta-adrenoceptor in these cells.

Effect of inhaled budesonide on seasonal changes in sensitivity and maximal response to methacholine in pollen-sensitive asthmatic subjects.

The aim of this study was to investigate the effect of inhaled budesonide on modifications of the provocative concentration of agonist causing a 20% fall in forced expiratory volume in one second (FEV1) (PC20) and maximal response plateau to inhaled methacholine during the pollen season in pollen-sensitive subjects with mild asthma. The effects of inhaled budesonide (800 micrograms.day-1) on the threshold value (PC20) and maximal response plateau to inhaled methacholine were studied in 28 pollen-sensitive subjects with mild asthma during a pollen season in a randomized, double-blind, placebo-controlled parallel fashion. They were challenged with methacholine (up to 200 mg.ml-1) in February (preseasonal assessment) and during the middle of the pollen season (in May and again in June). Subjects treated with budesonide (n = 13) were protected from the decrease in PC20 seen in the placebo (n = 15) group (geometric mean PC20 placebo group: preseasonal = 8.51, May = 2.19 and June = 1.78 mg.ml-1; budesonide group: preseasonal = 3.71, May = 3.23 and June = 2.40 mg.ml-1; intergroup differences in doubling concentrations, p < 0.05). Among 10 subjects in the placebo group who reached plateau during the preseasonal assessment, seven lost the plateau in May and six in June. In the budesonide group, among seven subjects who reached plateau during the preseasonal assessment, three lost the plateau in May and four in June. Between-group differences were not significant. We conclude that in pollen-sensitive subjects with mild asthma, inhaled budesonide blocks the effects of natural allergen exposure on the methacholine threshold value.(ABSTRACT TRUNCATED AT 250 WORDS)

Modification of concentration-response curves to inhaled methacholine after the pollen season in subjects with pollen induced rhinitis.

BACKGROUND: The effect of cessation of exposure to pollen on the concentration-response curves to inhaled methacholine was investigated. METHODS: Methacholine inhalation challenges (up to 200 mg/ml) were performed in 13 non-asthmatic patients with grass and/or Parietaria pollen-induced rhinitis during the pollen season, and one and four months after it. Concentration-response curves were characterised by their PC20, position, and plateau. RESULTS: Geometric mean methacholine PC20 increased from 6.4 mg/ml during the pollen season to 28.2 mg/ml and 54.9 mg/ml one and four months after the end of season, respectively. The mean (SE) level of the plateau decreased from 30.5 (4.3%) in the pollen season to 23.3 (3.7)% and 20.1 (3.3)% one and four months after the end of pollen season, respectively. Although the methacholine concentration that produced 50% of the maximal response increased from 2.9 mg/ml to 4.3 mg/ml and 6.0 mg/ml, the differences were not significant. CONCLUSIONS: In non-asthmatic patients with pollen-induced rhinitis cessation of exposure to pollen is associated with significant modifications in the methacholine threshold value and level of plateau, and with a small shift in the concentration-response curves to the right.

Modifications of PC20 and maximal degree of airway narrowing to methacholine after pollen season in pollen sensitive asthmatic patients.

We examined the effect of cessation of exposure to pollen on non-specific airway responsiveness in 10 grass and/or parietaria pollen sensitive asthmatics. Three methacholine inhalation challenges were performed, the first during pollen season (seasonal period), the second 2 months after the end of season (short time after seasonal period), and the third 5 months after the end of season (long time after seasonal period). The dose-response curves to methacholine were characterized by the PC20 (provocative concentration of methacholine required to produce a 20% fall in FEV1) and maximal response plateau, if possible. A maximal response plateau on the dose-response curve was considered to be present if three or more data points for FEV1 fell within a 5% response range. The challenge was stopped when FEV1 dropped more than 50% or the highest concentration of methacholine (200 mg/ml) was reached. The geometric mean (range) methacholine PC20 increased from 1.08 (0.18-37.22) in the seasonal period to 4.67 (0.71-200) mg/ml during the long time after seasonal period (P < 0.01). On the other hand, in six subjects in whom it was possible to obtain a plateau on at least one challenge, the level of the maximal response decreased from (mean +/- s.e.m.) 44.1 +/- 4.9 in the seasonal period to 30 +/- 4.4 during the long time after seasonal period (P < 0.05). These results suggest that in pollen sensitive asthmatic patients, the cessation of exposure to pollen is associated with a reduction of non-specific bronchial responsiveness (PC20 and maximal degree of airway narrowing to methacholine).

Lactate dehydrogenase isoenzymes of the hypothalamus, limbic structures, and the anterior pituitary during the estrous cycle.

Lactate dehydrogenase (LDH) and its isoenzyme (ISO) pattern were measured in the hypothalamus (HYP), amygdala (AMYG), hippocampus (HIP), cerebral cortex and anterior pituitary (PIT) of adult female rats sacrificed at different estrous cycle phases. The HYP, the AMYG and the PIT showed their maximal LDH values at proestrus and the lowest at diestrus. Those of the HIP showed the opposite pattern. The study of the ISO distribution pattern indicated that the cyclic variations of pituitary LDH activity were mainly due to changes of the ISO rich in A subunits, while in the B type they remained constant. By contrast, the cyclic changes of total LDH activity of all the brain structures studied were due to well balanced variations of both A and B subunits.