Reproductive performance of hair ewes and rams implanted with melatonin previous to the anestrus season in northwest Mexico.

Ovine reproductive behavior depends on annual photoperiodic cycle and its impact on endogenous melatonin secretion. In this regard, exogenous melatonin administration previous to the physiological anestrus period could modify the reproductive performance of sheep in the northwest of Mexico. Two independent studies were performed to evaluate such hypothesis in hair sheep implanted with melatonin prior to the anestrus season in latitudes 24° and 25° of Mexico. Study 1 involved 15 rams assigned to one of three treatments receiving 0mg (n=5), 18mg (n=5), or 36mg (n=5) of melatonin subcutaneously. Study variables were measured monthly since implantation (d0) and included testosterone concentration, scrotal circumference, mass motility, individual motility, and sperm concentration. Study 2 included 50 ewes assigned to one of two treatments receiving 0mg (n=25) or 18mg (n=25) of melatonin subcutaneously. In ewes, progesterone concentration and the frequency of females in anestrus were measured during the implantation (-30d), as well as at the beginning (0d) and at the end (45d) of the mating period, while pregnancy rate was determined by ultrasonography 45d after. Continuous variables were analyzed using a mixed effects model considering treatment, time, and the treatment by time interaction as fixed effects. Animal nested within treatment was the random effect. Binary variables were analyzed using the chi-square test. In males, melatonin improved testosterone and sperm concentrations (P<0.05), while in females, a 28% higher pregnancy rate was observed in implanted ewes (P<0.05). Therefore, melatonin enhanced reproductive parameters in both sexes and its exogenous administration previous to the anestrus season in northwest Mexico could be more effective in rams.

Boosting bactericidal immunity of a recombinant Mycobacterium smegmatis strain via zinc-dependent ribosomal proteins.

Tuberculosis (TB) continues to be a major global health burden and kills over a million people annually. New immunization strategies are required for the development of an efficacious TB vaccine that can potentially induce sterilizing immunity. In this study, we first confirmed that various strains of the IKEPLUS vaccine confer a higher survival benefit than BCG in a murine model of intravenous Mycobacterium tuberculosis (Mtb) infection. We have shown that there was a significant increase in the expression of the Rv0282 when IKEPLUS was grown in low zinc and iron containing Sauton medium. We confirmed on biofilm assays that zinc plays a vital role in the growth and formation of Mycobacterium smegmatis ( M. smegmatis ) biofilms. IKEPLUS grown in low zinc media led to better protection of mice after intravenous challenge with very high dosage of Mtb. We also showed that various variants of IKEPLUS induced apoptotic cell-death of infected macrophages at a higher rate than wild type M. smegmatis . We next attempted to determine if zinc containing ribosomal proteins such as rpmb2 could contribute to protective efficacy against Mtb infection. Since BCG has an established role in anti-mycobacterial efficacy, we boosted BCG vaccinated mice with rmpb2 but this did not lead to an increment in the protection mediated by BCG.

Increase of prostaglandin E2 in the reversal of fetal ductal constriction after polyphenol restriction.

OBJECTIVE: Anti-inflammatory substances that inhibit the synthesis of prostaglandins, such as non-steroidal anti-inflammatory drugs (NSAIDs) and polyphenol-rich foods, can cause constriction of the fetal ductus arteriosus. This study aimed to test the hypothesis that reversal of fetal ductal constriction after maternal restriction of polyphenol-rich foods, in the third trimester of pregnancy, is accompanied by increased plasma levels of prostaglandin E2 (PGE2). METHODS: This was a controlled clinical trial of women with singleton pregnancy ≥ 28 weeks undergoing fetal echocardiography. The intervention group included pregnancies with diagnosis of fetal ductal constriction and not exposed to NSAIDs. The control group consisted of third-trimester normal pregnancies. Both groups answered a food frequency questionnaire to assess the amount of total polyphenols in their diet, underwent Doppler echocardiographic examination and had blood samples collected for analysis of plasma levels of PGE2. Intervention group participants received dietary guidance to restrict the intake of polyphenol-rich foods. The assessments were repeated after 2 weeks in both groups. RESULTS: Forty normal pregnancies were assessed in the control group and 35 with fetal ductal constriction in the intervention group. Mean maternal age (26.6 years) and mean body mass index (30.12 kg/m2 ) were similar between the two groups. Intragroup analysis showed that dietary guidance reduced the median consumption of polyphenols (from 1234.82 to 21.03 mg/day, P < 0.001), increasing significantly the plasma concentration of PGE2 (from 1091.80 to 1136.98 pg/mL, P < 0.05) in the intervention group after 2 weeks. In addition, Doppler echocardiography showed reversal of fetal ductal constriction in the intervention group. No significant changes were observed in the control group. CONCLUSIONS: Dietary intervention for maternal restriction of polyphenol-rich foods in the third trimester of pregnancy is accompanied by increase in plasma levels of PGE2 and reversal of fetal ductal constriction. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

[Meniscal transplant: clinical and functional experience at one year follow-up]. / Trasplante de menisco: experiencia con seguimiento clínico y funcional a un año.

INTRODUCTION: In Mexico, the first meniscus transplant was performed in 2002. The objective was to describe the clinical evolution of patients with pain associated with postmenisectomy syndrome, who underwent meniscal allograft transplantation (MAT), with bony blocks via arthroscopy, with follow-up to one year. MATERIAL AND METHODS: A retrospective cohort study with a one-year follow-up was conducted. We included patients with joint interlining pain secondary to partial or total menisectomy, between 15 and 55 years of age, of both sexes, who underwent MAT. The clinical evolution was evaluated with visual analogue scale (VAS), SF-36 and Lysholm scale; the results are described in frequencies, percentages and p value was significant at 0.05. RESULTS: We included nine patients; eight men and one woman with an age of 31.3 years (16-52), the follow-up was 16.6 months (12-23). The preoperative VAS was 8.5 (6-10) and, at one year of follow-up, the average of this scale was 1.25 (0-5) (p 0.001). In the follow-up one year after the MAT, the Lysholm scale was on average 91 (68-100) and the SF-36 was on average 79.17 (65-92.92); three patients returned to their sports practice prior to the injury. CONCLUSION: This is the first report in Mexico that describes the one year follow-up of the MAT; significant clinical improvement was demonstrated (p 0.001) with remission of pain in the knee with previous menisectomy and in some cases the return to sports practice.

INTRODUCCIÓN: En México se realizó el primer trasplante de menisco en 2002. El objetivo fue describir la evolución clínica de pacientes con dolor asociado al síndrome postmeniscectomía que fueron sometidos a trasplante de menisco alogénico (MAT), con bloques óseos vía artroscópica con seguimiento a un año. MATERIAL Y MÉTODOS: Se realizó un estudio de cohorte retrospectiva con seguimiento a un año; se incluyeron pacientes con dolor en interlínea articular secundario a meniscectomía parcial o total, entre 15 y 55 años de edad, de ambos sexos, que fueron sometidos a MAT. La evolución clínica se evaluó con EVA, SF-36 y escala de Lysholm; los resultados se describen en frecuencias, porcentajes y valor de p significativa 0.05. RESULTADOS: Se incluyeron nueve pacientes; ocho hombres y una mujer con edad de 31.3 años (16-52), el seguimiento fue de 16.6 meses (12-23). La EVA prequirúrgica fue de 8.5 (6-10) y al año de seguimiento el promedio de esta escala fue de 1.25 (0-5) (p 0.001). En el seguimiento a un año posterior al MAT, la escala de Lysholm fue en promedio de 91 (68-100) y la SF-36 fue en promedio de 79.17 (65-92.92); tres pacientes regresaron a su práctica deportiva previa a la lesión. CONCLUSIÓN: Éste es el primer reporte en México del seguimiento a un año del MAT; se demostró mejoría clínica significativa (p 0.001) con remisión del dolor en la rodilla con meniscectomía previa y en algunos casos el retorno a la práctica deportiva.

Environmental cues that induce the physiology of solid medium: a study on lovastatin production by Aspergillus terreus.

AIMS: The aim of this work was to identify the main environmental factors that induce the special physiology displayed by fungi growing in solid culture-that is, higher secondary metabolite (SM) production-compared with those in submerged culture. METHODS AND RESULTS: Lovastatin-specific production (SP) was used as an indicator of the physiological status, and different model culture systems were used to evaluate the impact of potential solid-state fermentation (SSF) environmental stimuli. Direct contact with air was identified as an important stimulus. Cultures with two or more hours of exposure to air showed typical SSF lovastatin SP (1462% higher than cultures exposed for 0·08 h). Intermediate times of exposure generated intermediate physiological states. Support-related stimuli also induced higher lovastatin SP, even in a liquid environment (679% increase). CONCLUSIONS: Direct contact with air, as well as support-related stimuli, are major environmental cues that induce the physiology of solid medium. SIGNIFICANCE AND IMPACT OF THE STUDY: This knowledge is the starting point to investigate how these environmental cues are sensed and transduced, impacting SM and enzyme production. These results have important applied potential in new strategies to generate overproducing strains, as well as application in the design of novel production systems.

Reference Equations for Impulse Oscillometric and Respiratory System Model Parameters in Anglo and Hispanic Children / Ecuaciones de referencia para parámetros de oscilometría de impulsos y de modelo del sistema respiratorio en niños anglos e hispanos

Abstract The Impulse Oscillometry System (IOS) has been recognized as a useful diagnostic tool. Previous research by our group has shown that R5 (Resistance at 5 Hz), R5-R20 (frequency dependence of resistance), AX (the "Goldman Triangle") and the extended Resistor-Inductor-Capacitor (eRIC) model-derived parameter Cp (peripheral Compliance) are reliable measures that track respiratory system function. Here we determined the predictive equations from 112 asthmatic and non-asthmatic Anglo and Hispanic children data, that were previously classified into four groups: Normal, PSAI (Probable Small Airway Impairment), SAI (Small Airway Impairment), and Asthma by using regression analysis of IOS and eRIC model parameters as dependent variables regressed against age, height, and weight. Height showed the greatest correlation with IOS and eRIC model parameters and provided the most significant reference values for these measures in Anglo and Hispanic children. These values could serve as a useful framework for diagnosis, early interventions, and treatment of respiratory diseases in this population.

Resumen El Sistema de Oscilometría Impulsos (por sus siglas en Inglés: IOS) ha sido reconocido como una herramienta de diagnóstico útil. Investigaciones previas realizadas por nuestro grupo han demostrado que R5 (Resistencia a 5 Hz), R5-R20 (dependencia a la frecuencia de la resistencia), AX (el "Triángulo de Goldman") y el párametro Cp (Capacitancia periférica) derivado del modelo extendido Resistencia-inductor-condensador (eRIC) son medidas fiables que monitorean la función del sistema respiratorio. El presente estudio determina las ecuaciones de predicción de 112 niños Anglo e Hispanos asmáticos y no asmáticos, que previamente clasificados en cuatro grupos: Normal, PSAI (por su nombre en inglés: Probable daño en las vías aéreas menores), SAI (por su nombre en inglés: Daño en las vías aéreas menores), y Asma. Las ecuaciones de predicción se determinaron mediante análisis de regresión de parámetros del IOS y del modelo eRIC (variables dependientes) contra edad, estatura y peso. La estatura mostró la mejor correlación con los parámetros del IOS y del modelo eRIC, proporcionando los valores de referencia más significativos para estas medidas en niños Anglos e Hispanos. Estos valores podrían servir como un marco de referencia útil para el diagnóstico, intervenciones tempranas, y tratamiento de las enfermedades respiratorias en esta población.

Predicting factors for recurrence in low-grade Ta primary bladder tumours.

OBJECTIVES: Ta bladder tumors constitute 53% of primary bladder neoplasms, 70% of them being low-grade (G1). These tumors present a 15- 38% chance of recurrence during the first year. The aim of this paper is to identify the predicting factors of the first recurrence in a series of TaG1 primary bladder tumors. METHODS: We have retrospectively analyzed patients who were diagnosed with TaG1 primary bladder tumor by transurethral resection between 2004 and 2012. We established their tumor grade and pathological stage according to the WHO's classification guides for 1973 and 2004 as well as 2009's TNM. Those patients who were diagnosed before 2009 did not receive any adjuvant treatment. Those who were diagnosed later on received 40 mg of endovesical Mitomycin C during their immediate post operative period as their only treatment. We define recurrence as the presence of tumor after the first cystoscopy and relapse-free survival (RFS) as the period of time (in months) until the first recurrence appeared. Follow up constitutes the period of time (in months) until the last check-up or first recurrence. We also analyzed different variables: age, gender, smoking habits, muscular representation in the sample, size of the tumor (> or < 1 cm), multiple or single tumors and adjuvant treatment. The survival analysis was performed by the Kaplan-Meier method, using the long-rank test to evaluate the differences between groups. RESULTS: 68 patients were included in the study (73.5% men, 75% smokers). The average age was 61.9 years (the median being 58.5). Average follow up was 33.2 months (median 28.4). 35.3% of patients experienced recurrence. Average RFS was 19.2 ± 12.7 months (median 13.5). The majority of tumors were of a single nature (77.9%), with a size of less than 1 cm (55.9%) and with muscle representation (52.9%). 57.4% of patients did not receive adjuvant treatment. Only the absence of adjuvant treatment was associated with recurrence in uni and multivariate analysis (p<0,001), with a relative risk of 17,5 IC95% (7,6-30,2). CONCLUSION: The absence of adjuvant therapy with Mitomycin C is the only factor that, in a statistically significant way, increases the risk of recurrence, regardless of demographic factors and the characteristics of the tumor.

Predictors of success and hospitalization in semi-rigid ureteroscopy for lithiasis as an outpatient procedure.

OBJECTIVES: To analyze the outcomes, predictors of success and predictors of need for hospital admission in our series of patients who underwent ureteroscopy (URS) as a major outpatient surgery (MOS) procedure. METHODS: We carried out a retrospective analysis of 402 patients who had undergone semi-rigid URS for ureteral calculi as a MOS procedure in our center between 2004 and 2012. Patients with previous DJ catheter were excluded. We classified the calculi according to their location (lumbar, pelvic, iliac), size (< or> 1cm) and number (single or multiple). Follow-up was done by plain X-ray of the abdomen and ultrasound one month after surgery. The procedure was considered successful when patients were free from the treated calculi or had ureteral fragments < 3 mm one month after surgery. Univariate and multivariate analyses were carried out to identify the factors involved in success and hospitalization not being required. RESULTS: A total of 269 patients were included. The majority of the stones were single (92.2%), <1 cm in size (76.6%), pelvic (62.1%), and left-sided (57.2%). 89.6% of the procedures were performed as MOS and 82.2% were considered to be successful. In the multivariate analysis, left-sided (p<0.001) and pelvic location of the calculi (p=0,01) were found to be independent predictors for the success of the procedure In terms of hospital admission, the only independent predictor was the presence of intraoperative complications ( p=0.006). CONCLUSIONS: Left-sided and pelvic locations were the independent predictors for the success of the URS. A lack of intraoperative complications was the independent predictor for not requiring hospitalisation.

Identification and expression pattern of a new carotenoid cleavage dioxygenase gene member from Bixa orellana.

Carotenoid cleavage dioxygenases (CCDs) are a class of enzymes involved in the biosynthesis of a broad diversity of secondary metabolites known as apocarotenoids. In plants, CCDs are part of a genetic family with members which cleave specific double bonds of carotenoid molecules. CCDs are involved in the production of diverse and important metabolites such as vitamin A and abscisic acid (ABA). Bixa orellana L. is the main source of the natural pigment annatto or bixin, an apocarotenoid accumulated in large quantities in its seeds. Bixin biosynthesis has been studied and the involvement of a CCD has been confirmed in vitro. However, the CCD genes involved in the biosynthesis of the wide variety of apocarotenoids found in this plant have not been well documented. In this study, a new CCD1 gene member (BoCCD1) was identified and its expression was charaterized in different plant tissues of B. orellana plantlets and adult plants. The BoCCD1 sequence showed high homology with plant CCD1s involved mainly in the cleavage of carotenoids in several sites to generate multiple apocarotenoid products. Here, the expression profiles of the BoCCD1 gene were analysed and discussed in relation to total carotenoids and other important apocarotenoids such as bixin.

HIV-1 vertical transmission in Rio Grande, Southern Brazil.

The aim of this study was to determine the rate and risk factors of HIV-1 mother-to-child transmission (MTCT), the timing of transmission and the transmitted subtype in a population where subtypes B and C co-circulate. One hundred and forty-four babies born to HIV-1-infected mothers were studied. Subtype and timing of transmission were determined by a nested polymerase chain reaction of the gp41 gene. Seven children were infected (4.9%): four were infected intrautero and one intrapartum. The higher frequency of intrautero transmission was statistically significant (P = 0.001). Use of antiretrovirals (ARVs) in the three stages of gestation was a protective risk factor for MTCT (PR = 0.42; CI: 0.21-0.83; P = 0.013). A higher HIV viral load at delivery was the only independent risk factor for MTCT. Early and universal access to ARVs during pregnancy are the most important measures to decrease vertical HIV-1 transmission even in areas where HIV clade distribution differs.

Extension model of lactation curves to evaluate the effect of the recombinant bovine somatotropin on milk yield in Holstein cows / Modelo de extensão de curvas de lactação para avaliar o efeito da somatotropina bovina recombinante sobre a produção de leite em vacas Holstein

An extension model of lactation curves was used to determine the effect of recombinant bovine somatotropin (bST-r) on milk yield in Holstein dairy cattle. This model use the fitted values obtained by the Wood model, and was tested on the records of 66 cows. The milk yield predicted with the extension model and the observed yield were compared and no significant differences were observed (P>0.05). Once the extension model was validated, the milk yield tests of 199 cows were used. The cows received bST-r 500mg by subcutaneous injections. The injections were applied after 100 days in milk at 14-day intervals (seven injections). The observed milk yield was compared with the yield expected by the extension model. An increase of 5.3 percent was observed in milk yield in response to the bST-r. This increase is lower than that reported in the literature in response to the growth hormone in dairy cattle. It is concluded that extension model used in the present work is reliable for extending the lactation curve in Holstein cows, and the increase in milk yield in response to the application of bST-r, determined in the same animal using the extension model, was lower than that reported by other authors.

Um modelo de extensão de curvas de lactância foi utilizado para determinar o efeito da somatotropina bovina recombinante (bST-r) sobre a produção de leite em vacas Holstein. Este modelo, que utiliza os valores ajustados obtidos pelo modelo de Wood, foi testato nos registros de 66 vacas. A produção de leite predita com o modelo de extensão e a produção observada foram comparadas e não se observaram diferenças significativas (P>0,05). Uma vez validado o modelo de extensão, utilizaram-se os controles de produção de leite (de cada 15 dias) de 199 vacas. As vacas receberam injeções de 500mg de bST-r via subcutânea. As injeções fora aplicadas a partir dos 100 dias de lactação a intervalos de 14 dias (sete injeções). A produção de leite observada foi comparada com a produção esperada com o modelo de extensão. Observou-se um incremento de 5,3 por cento na produção de leite em resposta à bST-r. Este incremento foi menor que o relatado na literatura em resposta ao hormônio do crescimento em vacas leiteiras. O modelo de extensão usado é confiável para estender a curva de lactação na vaca Holstein, e o aumento do rendimento de leite em resposta à aplicação de bST-r, determinado no mesmo animal usando o modelo de extensão, foi inferior ao observado por outros autores.

Fast, sensitive and highly discriminant gas chromatography-mass spectrometry method for profiling analysis of fatty acids in serum.

A method for the determination of fatty acids in serum based on GC-MS (micro-SIS detection mode) has been developed and the separation and cis/trans isomers have been identified. A prior two-step extraction/derivatization procedure accelerated by ultrasound allows individual determination of esterified (EFAs) and non-esterified fatty acids (NEFAs), and shortening of the derivatization steps to 5 min for EFAs and 15 min for NEFAs. The total analysis time for 39 fatty acids was 61 min. The minimum LOD and LOQ values were 0.002 and 0.006 microg/ml, respectively. The proposed method was validated for EFAs and NEFAs using two different methods and the results show no statistical differences between the proposed method and those used as reference. The proposed derivatization-extraction methodology is suitable for fatty-acid analysis of human serum, and can be applied to nutritional and epidemiological studies.

Fast and selective determination of triterpenic compounds in olive leaves by liquid chromatography-tandem mass spectrometry with multiple reaction monitoring after microwave-assisted extraction.

A method for fast and selective determination of the main triterpenic compounds present in olive leaves - oleanolic, ursolic and maslinic acids as triterpenic acids and, uvaol and erythrodiol as triterpenic dialcohols - is reported here. Quantitative isolation of the analytes has been accomplished in 5min by microwave assistance using ethanol as extractant. Due to the medium polarity of triterpenic acids and dialcohols, different ethanol-water ratios were tested in order to select the optimum extractant composition for their solubilisation. Microwave assistance provided a significant shortening of the leaching time as compared to conventional procedures by maceration, which usually requires at least 5h. After extraction, determination was carried out by liquid chromatography-tandem mass spectrometry (LC-MS-MS) with a triple quadrupole (qQq) mass detector without any clean-up step prior to chromatographic analysis. Highly selective identification of triterpenes was confirmed by multiple reaction monitoring (MRM) using the most representative transitions from the precursor ion to the different product ions, while the most sensitive transitions were used for MS-MS quantitation. Total analysis performed in 25 min enables the characterization of a fraction with particular interest in the pharmacological area.

Full-Length gene enrichment by using an optimized RNA isolation protocol in Bixa orellana recalcitrant tissues.

A reliable protocol is described for isolation of large full-length cDNA from Bixa orellana mature tissues containing large quantities of pigments, phenols, and polysaccharides. This protocol involves the optimization of a commercial RNA extraction protocol in combination with a long distance reverse transcript PCR protocol. The principal advantages of this protocol are its high RNA yield and quality. The resulting RNA is suitable for RNA expression evaluation and production of large, full-length cDNA. This is the first time RNA has been isolated from all mature tissues in the tropical perennial plant B. orellana and has been proved viable for downstream applications, especially important for molecular biology studies on this economically important pigment-producing plant.

Ultrasound-assisted extraction and silylation prior to gas chromatography-mass spectrometry for the characterization of the triterpenic fraction in olive leaves.

One of the most important fractions of bioactive compounds isolated from plants is that formed by triterpenic compounds, which have proved to be anti-bacterial, antifungal, anti-inflammatory, cytotoxic and anti-tumour. A method for leaching and determination of the main triterpenic compounds (oleanolic acid, ursolic acid, uvaol, erythrodiol) in olive leaves is here presented. Quantitative leaching was obtained with ethanol as leachant and ultrasonic assistance for 20 min, a very short time as compared to conventional procedures by maceration, which usually requires at least 5 h. After isolation, an aliquot of the ethanolic leachate was silylated to derivatize the analytes prior to gas chromatography-mass spectrometry analysis. Silylation reaction was also assisted with ultrasound in order to accelerate the derivatization step, which only required 5 min--a dramatic shortening in comparison to conventional silylation of terpenic compounds with derivatization times ranging from 30 min to 3 h. The proposed method has demonstrated to be useful for isolation and characterization of the triterpenic fraction in plants; the capability of ultrasound to assist sample preparation (acceleration of leaching and derivatization) has also been proved.

Long and short-term effect of prednisolone in hospitalized infants with acute bronchiolitis.

OBJECTIVE: To assess long and short-term effect of prednisolone in hospitalized infants with bronchiolitis. METHODOLOGY: A randomized and controlled trial was carried out at the Federal University of Rio Grande, Rio Grande-RS, Brazil. Twenty-eight patients were randomly allocated prednisolone (1 mg/kg/day for 5 days) plus standard care, and 24 patients allocated standard care alone. The primary endpoint was the prevalence of post-bronchiolitis wheezing at 1, 3, 6 and 12 months after hospital discharge. The secondary endpoints were: length of hospital stay, duration of oxygen therapy and time to clinical improvement during the hospitalization. RESULTS: There were no significant differences between the prednisolone and control group in the prevalence of post-bronchioltis wheezing at 1 month (73.1 vs 83.3%, P = 0.5), 3 months (73.1 vs 79.2%, P = 0.7), 6 months (65.4 vs 66.7%, P = 0.9) and 12 months (50.0 vs 58.3%, P = 0.5) after hospital discharge. No reduction was observed in the prednisolone group, compared with the control group, in terms of length of hospital stay (6.0 vs 5.0 days, P = 0.7), duration of oxygen therapy (24.0 vs 24.0 h, P = 0.4) and time to clinical resolution (4.0 vs 4.0 days, P = 0.8). CONCLUSIONS: Prednisolone has no significant effect on reducing the prevalence of post-bronchiolitis wheezing and on improving the acute course of illness in hospitalized infants with bronchiolitis.

Lymphangioleiomyomatosis: CT of diurnal variation of lymphangioleiomyomas.

PURPOSE: To evaluate the imaging and clinical features of lymphangioleiomyomas and to describe the phenomenon of diurnal variation in the size of lymphangioleiomyomas in patients with lymphangioleiomyomatosis. MATERIALS AND METHODS: One hundred twenty-eight patients with lymphangioleiomyomatosis underwent chest and abdominopelvic computed tomography (CT). Thirteen patients underwent CT in the morning and afternoon of the same day to assess diurnal variation in lymphangioleiomyoma size. RESULTS: Twenty-seven of 128 patients (21%) had 54 lymphangioleiomyomas. The vast majority (96%) of these masses contained material of low attenuation at CT. Associated CT findings included enlarged abdominal lymph nodes, pleural effusions, ascites, and dilatation of the thoracic duct. The prevalence of lymphangioleiomyomas was 15% in patients who had mild pulmonary disease, 19% in patients who had moderate disease, and 26% in patients who had severe disease. Diurnal variation in size of masses was demonstrated in 12 of 13 patients. Seven of the 27 patients who had masses underwent biopsy; all seven were confirmed to have lymphangioleiomyomas. The most common symptoms associated with lymphangioleiomyomas were bloating, abdominal pain, and edema of the lower extremities. The majority of the patients reported worsening of symptoms as the day progressed. CONCLUSION: Lymphangioleiomyomas are common in patients with lymphangioleiomyomatosis. Diurnal variation in size may explain worsening of symptoms during the day.

Prevalence and clinical characteristics of lymphangioleiomyomatosis (LAM) in patients with tuberous sclerosis complex.

The true prevalence of pulmonary lymphangioleiomyomatosis (LAM) in patients with tuberous sclerosis complex (TSC) is unknown. The prevalence of LAM, radiological features, and lung function in patients with TSC was measured. The presence of LAM, as defined by the presence of cysts by high-resolution chest computed tomography (HRCT) scan, was determined in patients with TSC without prior pulmonary disease (Group 1). To determine the significance of early detection, severity of disease in screened patients (Group 1) was compared with that in patients with TSC with a prior diagnosis of LAM (Group 2). Forty-eight patients with TSC and no prior history of LAM were screened. Of the 38 females, 13 (34%) had LAM; LAM was absent in males. Lung function was preserved in patients with TSC who were found to have LAM by screening. In patients previously known to have LAM, FEV(1) and DL(CO) correlated inversely with severity of disease as assessed by CT scan. The prevalence of LAM in women with TSC was 34%, approximately 10-fold that previously reported, consistent with a large hitherto unrecognized subclinical population of patients at risk for pulmonary complications.

Antifungal activity and pharmacokinetics of posaconazole (SCH 56592) in treatment and prevention of experimental invasive pulmonary aspergillosis: correlation with galactomannan antigenemia.

The antifungal efficacy, safety, and pharmacokinetics of posaconazole (SCH 56592) (POC) were investigated in treatment and prophylaxis of primary pulmonary aspergillosis due to Aspergillus fumigatus in persistently neutropenic rabbits. Antifungal therapy consisted of POC at 2, 6, and 20 mg/kg of body weight per os; itraconazole (ITC) at 2, 6, and 20 mg/kg per os; or amphotericin B (AMB) at 1 mg/kg intravenously. Rabbits treated with POC showed a significant improvement in survival and significant reductions in pulmonary infarct scores, total lung weights, numbers of pulmonary CFU per gram, numbers of computerized-tomography-monitored pulmonary lesions, and levels of galactomannan antigenemia. AMB and POC had comparable therapeutic efficacies by all parameters. By comparison, animals treated with ITC had no significant changes in outcome variables in comparison to those of untreated controls (UC). Rabbits receiving prophylactic POC at all dosages showed a significant reduction in infarct scores, total lung weights, and organism clearance from lung tissue in comparison to results for UC (P < 0.01). There was dosage-dependent microbiological clearance of A. fumigatus from lung tissue in response to POC. Serum creatinine levels were greater (P < 0.01) in AMB-treated animals than in UC and POC- or ITC-treated rabbits. There was no elevation of serum hepatic transaminase levels in POC- or ITC-treated rabbits. The pharmacokinetics of POC and ITC in plasma demonstrated dose dependency after multiple dosing. The 2-, 6-, and 20-mg/kg dosages of POC maintained plasma drug levels above the MICs for the entire 24-h dosing interval. In summary, POC at > or =6 mg/kg/day per os generated sustained concentrations in plasma of > or =1 microg/ml that were as effective in the treatment and prevention of invasive pulmonary aspergillosis as AMB at 1 mg/kg/day and more effective than cyclodextrin ITC at > or =6 mg/kg/day per os in persistently neutropenic rabbits.