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Many Fontan patients with and without systolic ventricular dysfunction are being treated with angiotensin-converting enzyme (ACE) inhibitors, despite its effectiveness remaining unclear. In the present study, we evaluated the short-term effect of enalapril on exercise capacity, vascular and ventricular function in pediatric Fontan patients with moderategood systolic ventricular function. Fontan patients between 8 and 18 years with moderategood systolic ventricular function and without previous ACE inhibitor treatment were included and were treated with enalapril for 3 months. During the first 2 weeks, the dosage was titrated according to systolic blood pressure (SBP). Exercise tests, ventricular function assessed by echocardiography, arterial stiffness measurements, and plasma levels of N-terminal pro-B-type natriuretic peptide assessed before and after a 3-month enalapril treatment period was compared. A total of 28 Fontan patients (median age 13.9 years, 6 to 15 years after Fontan operation) completed the study with a mean dosage of 0.3 +/- 0.1 mg/ kg/d. A total of 6 patients (21 %) experienced a significant drop in SBP and 6 others (21%) experienced other adverse events. Enalapril treatment lowered the SBP (from 110 to 104 mmHg, p = 0.003) and levels of N-terminal pro-B-type natriuretic peptide (from 80 to 72 ng/L, p = 0.036). However, enalapril treatment did not improve exercise capacity, ventricular function, or arterial stiffness. In conclusion, short-term ACE inhibition has no beneficial effect in Fontan patients with moderate-good systolic ventricular function. (C) 2021 The Authors. Published by Elsevier Inc.

Background Mammary gland tumours are the most frequently diagnosed tumours in the female dogs but just a few studies have analysed their epidemiology. Therefore, we set out to describe the epidemiology of canine mammary cancer in the Canary Archipelago, Spain. We analysed a pathology tumour registry (PTR) and identified 7362 samples obtained from 5240 female dogs resident on the Canary Archipelago during an 18-year period (2003–2020). Using a case–control study design, we compared mammary tumour affected dogs with the Canarian canine population registry in order to elucidate the breed associations for these tumours. Results The frequency of a diagnosis of mammary tumours relative to all tumour diagnoses in female dogs decreased during the study period from 62.7% to 48.9%. Contemporaneously, the proportion of dogs diagnosed with mammary tumours who were also neutered increased from 13.6% to 26.9%. There was a negative correlation (R = -0.84) between these changes. Additional findings were that: the proportion of female dogs diagnosed with multiple tumours increased by 23.5% and that the proportion of malignant tumours 89.2% diagnosed has remained stable through the period. Benign mammary tumours were diagnosed at younger ages (9.2 years old) than carcinomas (9.7 years old) and sarcomas (10.4 years old). Epithelial mammary tumours were diagnosed at younger ages in entire female dogs. Samoyed, Schnauzer, Poodle, German Pinscher and Cocker Spaniel were the breeds with the highest odds-ratios (OR) in comparison with the reference (crossbreeds) while Miniature Pinscher, American Staffordshire Terrier, English Pointer as well as some local breeds such as the Canary Warren Hound and the Majorero had the lowest ORs. Conclusions This study provides a description of the changing epidemiology of canine mammary cancer in the Canary Archipelago over the last two decades. We found high rates of CMT with a significant predominance of malignant tumours. Exact risk factors are uncertain, but a combination of environmental, regional socioeconomic affecting human and their pets, and animal management factors are likely to play a part. Specifically, neutering was negatively associated with the proportion of epithelial mammary gland tumours and breeds native to the region were at lower risk of mammary tumours. A deeper analysis of all these factors will facilitate a deeper understanding of the epidemiology of mammary gland tumours in both the canine and the human population.

After the arterial switch operation (ASO) for transposition of the great arteries (TGA), many patients have an impaired exercise tolerance. Exercise tolerance is determined with cardiopulmonary exercise testing by peak oxygen uptake (VO2peak). Unlike VO2peak, the oxygen uptake efficiency slope (OUES) does not require a maximal effort for interpretation. The value of OUES has not been assessed in a large group of patients after ASO. The purpose of this study was to determine OUES and VO2peak, evaluate its interrelationship and assess whether exercise tolerance is related to ventricular function after ASO. A cardiopulmonary exercise testing, assessment of physical activity score and transthoracic echocardiography (fractional shortening and left/right ventricular global longitudinal peak strain) were performed to 48 patients after ASO. Median age at follow-up after ASO was 16.0 (IQR 13.0–18.0) years. Shortening fraction was normal (36 ± 6%). Left and right global longitudinal peak strain were reduced: 15.1 ± 2.4% and 19.5 ± 4.5%. This group of patients showed lower values for all cardiopulmonary exercise testing parameters compared to the reference values: mean VO2peak% 75% (95% CI 72–77) and mean OUES% 82(95% CI 77–87); without significant differences between subtypes of TGA. A strong-to-excellent correlation between the VO2peak and OUES was found (absolute values: R = 0.90, p R = 0.79, p 2peak were lower in patients after ASO compared to reference values but are strongly correlated, making OUES a valuable tool to use in this patient group when maximal effort is not achievable.

Objective: Ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS) is a heterogeneous condition caused by neuroendocrine neoplasms (NENs) located in the lungs, thymus, or pancreas. Our purpose was to evaluate the long-term outcome of these patients. Methods: Retrospective study at a referral center. The charts of 164 patients with Cushing syndrome, followed at our center from 1993 to 2019, were analyzed. Results: EAS was found in 16 patients (9.75%, 9 women, mean age 36.01 years) who had been followed for a median of 72 months. The source of EAS was a NEN in 10 patients (8 bronchial and 2 thymic carcinoid tumors) and a mixed corticomedullary tumor, consisting of a pheochromocytoma and an adrenocortical carcinoma in 1 patient. In 2 of the 6 patients initially considered to have occult EAS, the source of the ACTH excess became apparent after adrenalectomy, whereas in the remaining 4 (25%) patients, it has remained occult. Of the 11 patients in whom resection of the NEN was attempted, 10 patients achieved an early remission (91%), but 4 (25%) of these patients had a recurrence during follow-up (biochemically and clinically silent in 2 patients). Three patients died (18.75%): the young woman with the mixed corticomedullary tumor, a man with a thymic NEN that evolved into a neuroendocrine (NE) carcinoma after 11 years of follow-up, and a woman with a bronchial NEN. Conclusion:The course of EAS varies according to tumor type and grade. Some patients have a protracted course, whereas others may evolve into neuroendocrine carcinomas. Abbreviations: ACTH = adrenocorticotropic hormone; CS = Cushing syndrome; CT = computed tomography; CV = coefficient of variation; EAS = ectopic ACTH syndrome; IQR = interquartile range; NEN = neuroendocrine neoplasm; SCCL = small cell carcinoma of the lung; TSS = transsphenoidal surgery; UFC = urinary free cortisol

In patients after Fontan completion exercise capacity is significantly reduced. Although peak oxygen consumption (VO2peak) is a strong prognostic factor in many cardiovascular diseases, it requires the achievement of a maximal effort. Therefore, submaximal exercise parameters such as oxygen uptake efficiency slope (OUES) may be of value. In the present observational study we evaluated the exercise capacity with maximal and submaximal parameters in a group of Fontan patients with an extracardiac conduit and determined their prognostic value. Sixty Fontan patients followed up in the Leiden University Medical Center who have performed an exercise test were included in this retrospective study. Exercise tests were performed at a median age of 11 years. Fontan patients showed on average lower values for all exercise parameters compared to reference values from a healthy dataset as shown by the %predicted values: VO2peak%:mean 66%(95%CI:64 to 74) and OUES%:mean 72%(95%CI:67 to 77). Twenty percent of the patients were not able to achieve an RER>1.0. RER showed a moderate positive correlation with VO2peak but not with OUES. There was a deterioration of VO2peak% and OUES% over time. OUES was significantly lower in patients with cardiac events in the follow up period. Fontan patients have an impaired exercise performance even at young ages and it deteriorates with age. An important percentage of Fontan patients is not able to reach maximal effort so the use of submaximal parameters, like OUES, should be considered as part of the evaluation. Moreover, OUES could have a prognostic value in this group of patients.

INTRODUCTION Goiter is very common in patients with acromegaly; its development is correlated to the duration of the disease. Thyroid cells express the IGF-1 receptor and the TSH/IGF-1 interaction has been demonstrated to have a synergistic effect in thyroid cell growth. There is a correlation between IGF-1 levels and the thyroid volume of patients with acromegaly. The aim of this study was to evaluate, in a retrospective case-cohort study of patients with acromegaly, the associated risk factors for thyroid nodules disease in this population. METHODS This was a case-cohort study matched by age, gender, and growth hormone at diagnosis. Cases consisted of acromegalic patients that developed thyroid nodules during the follow up, and controls consisted in acromegalic patients without thyroid nodules. A Cox proportional hazard estimation was carried out for measure the associated risk factors for thyroid nodules disease in acromegalic patients. A nodular thyroid disease-free survival analysis was estimated using the Kaplan-Meier analysis. RESULTS We recruited 49 cases and 56 controls. In a multivariate Cox proportional hazard analysis age and IGF-1 ≥ 2.2 x ULN were significantly related with the presence of thyroid nodules [HR of 2.21 (95% CI; 1.15-4.25, p = 0.01)]. Nodularity-free survival rates in patients who had an IGF-1 X ULN ≥ 2.2 was found to be lower in comparison to those who had IGF-1 X ULN

Introduction Streptococcus pneumoniae (Sp) is the main cause of community-acquired pneumonia in the elderly, hence the importance to establish the prevalence of nasopharyngeal colonization by different Sp serotypes in adults. Methods from December 2009 to June 2010, nasopharyngeal cultures were taken from adults living in rural communities in Mexico for the isolation and serotyping of Sp by the Quellung reaction. Penicillin and ceftriaxone susceptibility tests were performed by the microdilution method. Results two hundred and thirty-six adults over 50 years old, were included. The prevalence of colonization by Sp was 21.6%. The most frequent serotypes were 19A (21%), 6A (13%), 6B and 11A (11%). All isolates were susceptible to ceftriaxone, and 52.8% of the isolates showed penicillin minimal inhibitory concentrations ≥0.12 mg/L. Conclusion this is the first study analyzing the nasopharyngeal colonization by Sp in adults in Mexico. Serotypes not included in any of the pneumococcal vaccines were frequently identified.

In‐house assays for the diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) by quantitative reverse‐transcription polymerase chain reaction (qRT‐PCR), are feasible alternatives, particularly in developing countries. Cycle threshold (C t) values obtained by qRT‐PCR were compared with clinical and laboratory data from saliva of inpatients with COVID‐19 and asymptomatic health workers (AHW) were studied. Saliva specimens from 58 inpatients confirmed by qRT‐PCR for SARS‐CoV‐2 using nasopharyngeal specimens, and 105 AHW were studied by qRT‐PCR using three sets of primers for the N (N1, N2, and N3) gene of SARS‐CoV‐2, according to the CDC Diagnostic Panel protocol, showing a positivity of 88% for inpatients and 8% for AHW. Bivariate analysis revealed an association between C t

Pituitary adenomas (PA) are the second most common intracranial tumors. These neoplasms are classified according to the hormone they produce. The majority of PA occur sporadically, and their molecular pathogenesis is incompletely understood. The present transcriptomic and methylomic analysis of PA revealed that they segregate into three molecular clusters according to the transcription factor driving their terminal differentiation. First cluster, driven by NR5A1, consists of clinically non-functioning PA (CNFPA), comprising gonadotrophinomas and null cell; the second cluster consists of clinically evident ACTH adenomas and silent corticotroph adenomas, driven by TBX19; and the third, POU1F1-driven TSH-, PRL- and GH-adenomas, segregated together. Genes such as CACNA2D4, EPHA4 and SLIT1, were upregulated in each of these three clusters, respectively. Pathway enrichment analysis revealed specific alterations of these clusters: calcium signaling pathway in CNFPA; renin-angiotensin system for ACTH-adenomas and fatty acid metabolism for the TSH-, PRL-, GH-cluster. Non-tumoral pituitary scRNAseq data confirmed that this clustering also occurs in normal cytodifferentiation. Deconvolution analysis identify potential mononuclear cell infiltrate in PA consists of dendritic, NK and mast cells. Our results are consistent with a divergent origin of PA, which segregate into three clusters that depend on the specific transcription factors driving late pituitary cytodifferentiation.

Background: Lumbar radiculopathy is a nerve root disorder whose correct diagnosis is essential. The objective of the present study was to analyze the reliability diagnostic validity of eight neurodynamic and/or orthopedic tension tests using magnetic resonance imaging as the Gold Standard. Methods: An epidemiological study of randomized consecutive cases which was observational, descriptive, transversal, double blinded and was conducted following the Standards for Reporting Diagnostic accuracy studies (STARD) declaration. The sample size was 864 participants. Internal and external validity (CI = 95%) and reliability, were calculated for all tests performed independently. The diagnostic validity of the combined and multiple tests in parallel was also calculated. Results: The analysis indicated that only two tests performed independently had external validity, but neither had reliability or precision. The Straight Leg Raise test and the Bragard test performed in a multiple parallel way showed high sensitivity (97.40%), high negative predictive value (PV&minus, 96.64%) and external validity (Likelihood Ratio&minus, 0.05). The combined test of the Slump test and the Dejerine&rsquo, s triad had internal and external validity. Conclusions: The Straight Leg Raise test and the Bragard test performed in a multiple parallel way and the combined test of the Slump Test and the Dejerine&rsquo, s triad have clinical validity to discard lumbar or lumbar-sacral radiculopathy.

Context Acromegaly registries constitute a valuable source of therapeutic outcome information in real-life. Objective The objective of this work is to analyze surgical and pharmacological outcomes in the Mexican Acromegaly Registry (MAR). Design and Methods Data were extracted from the MAR informatic platform. Surgical remission was defined by a postoperative postglucose (GH) of less than 1 ng/mL and an insulin-like growth factor 1 (IGF-1) of less than 1.2 × upper limit of normal (ULN). Pharmacological remission was defined by a basal GH of less than 1 ng/mL and an IGF-1 of less than 1.2 × ULN. Results A total of 650 surgical outcomes were analyzed (94.6% transsphenoidal). Surgical remission was achieved in 40.15%, whereas 44.15% remained biochemically active. Persistently active disease after surgery was significantly associated with harboring an invasive macroadenoma, a basal GH of greater than 10 ng/mL, and/or an IGF-1 of greater than 2 × ULN at diagnosis on bivariate and multivariate analysis. The outcome of monotherapy with first-generation somatostatin analogs (SSAs) was evaluated in 267 patients (adjunctive in 65%), of whom 28.4% achieved remission. Persistently active disease was significantly associated with harboring an invasive macroadenoma as well as with pretreatment basal GH and IGF-1 levels of greater than 10 ng/mL and greater than 2 × ULN, respectively, on bivariate and multivariate analysis. Combined therapy with SSA and cabergoline was analyzed in 100 patients, of whom 19% achieved remission and 44% remained active; in this subset of patients, only a pretreatment IGF-1 of greater than 2 × ULN was significantly associated with persistent disease activity. Conclusion Surgical and pharmacological outcomes in acromegaly are highly dependent on tumor size/invasiveness as well as on the degree of hypersomatotropinemia.

Merkel cells (MCs) are neuroendocrine cells involved with tactile sense, growth, differentiation, and homeostasis of the skin as well as in different cutaneous diseases. Specific staining techniques are required for their identification because they are not easily visible in paraffin sections stained with hematoxylin and eosin. The present study assess the histochemical features of the MCs in dogs comparing with those described for other mammals in the literature and with the use of immunohistochemistry. A systematic study of samples from MCs-rich areas from healthy dogs was carried out by use of several histologic stains, including metachromatic staining, silver stains, methylene blue, periodic acid-Schiff stain, and osmium-based staining method. MCs were detected by the Grimelius argyrophilic stain in 86.7% of the specimens. The staining was showed as dark-brown granular cytoplasmic and consistently polarized to the basal cell cytoplasm matching with the cellular distribution of the characteristic neurosecretory granules. Some modifications in the standard staining protocol, including rinsing, silver reimpregnation, and counterstain dye, enhanced the MCs identification in stratified squamous epithelium. When compared with Cytokeratin 20-immunolabeled serial sections several MCs appeared nonstained with the argyrophilic method. These differences in MC numbers between stains were statistically significant. Other histologic stains failed to identify MCs in the specimens. The results of this study indicate that Grimelius argyrophilic stain is a suitable method for demonstration of MCs in the stratified squamous epithelium of skin and mucosa. Discussion on its utility when compared with immunohistochemistry and a review of the scientific literature is also presented. Anat Rec, 302:1458-1464, 2019. © 2018 Wiley Periodicals, Inc.

Context The term micromegaly has been used to describe a subset of patients who have elevated IGF-1 levels but apparently normal basal GH (bGH) concentrations and often a glucose-suppressed GH of Objective To evaluate the prevalence, clinical spectrum, and therapeutic outcome of acromegaly with normal bGH at diagnosis. Design and Methods Retrospective analysis of a cohort of patients with acromegaly diagnosed and treated at a tertiary care center. Results A cohort of 528 patients with acromegaly was stratified according to bGH at diagnosis: group 1, Conclusion Normal bGH acromegaly is uncommon in real life. These patients have some distinctive features that argue against this being simply acromegaly in its early stages.

Context Diabetes and hypertension are frequent comorbidities of acromegaly. Objective To analyze the course of diabetes and hypertension at diagnosis and after multimodal therapy in a large cohort of patients with acromegaly. Design and Setting Retrospective study at a tertiary care center. Patients and Methods A total of 522 patients with acromegaly treated according to a preestablished protocol. Main Outcome Measures Prevalence of diabetes and hypertension and its relationship with biochemical indices of acromegalic control. Results The cohort was stratified according to disease activity upon last visit to clinic: (1) surgical remission (n = 122), (2) pharmacologically controlled (n = 92), (3) active disease (n = 148), (4) insulinlike growth factor (IGF)-1 discordance (n = 64), and (5) growth hormone (GH) discordance (n = 96). The prevalence of diabetes and hypertension at diagnosis was 30% and 37%, respectively, and did not change upon the last visit (30.6% and 38%). Both comorbidities were more prevalent at diagnosis and on the last visit than in the general population. Diabetes was less prevalent on the last visit in patients who achieved surgical remission than in those who persisted with active disease (25% vs 40%, P = 0.01). Upon multivariate analysis, diabetes was associated with an IGF-1 at diagnosis >2× upper limit of normal, with the persistence of active acromegaly, the presence of hypertension upon the last visit, with the presence of a macroadenoma, and with female sex. Conclusion Our findings underscore the importance of an integral approach when managing these patients, focusing not only on the control of GH and IGF-1 levels but also on the timely diagnosis and the specific treatment of each comorbidity.

AIMS Staging is the gold standard for predicting malignant melanoma outcome but changes in its criteria over time indicate ongoing evolution. One notable recent change from the 8th edition of the American Joint Committee on Cancer (AJCC) staging manual was removal of mitotic count. We explore the extent to which this feature is limited by interobserver error in order to find ways to improve its fitness for use should it be revisited in future staging versions. METHODS AND RESULTS In a cohort of 476 patients with melanoma ≤1.0 mm, a mitotic count of 0 versus 1 was significant for metastasis-free survival, but not melanoma-specific or overall survival. In 10 melanomas that were 0.9-1.0 mm thick, the mitotic count intraclass correlation coefficient for histopathologists was 0.58 (moderate agreement). Uniquely, we also assessed agreement for specific putative mitotic figures, identifying precise reasons why specific mitotic figures qualified for scoring or elimination. A kappa score was 0.54 (moderate agreement). We also gathered data on other staging features. Breslow thickness had an intraclass correlation coefficient of 0.41 (moderate agreement) and there was a systematic difference between histopathologists among cases (P = 0.04). Every case had a range that crossed the AJCC8 0.8-mm pT1a/pT1b staging boundary. Ulceration was only identified in two of the 10 cases. For ulceration, kappa agreement score was 0.31 (fair). CONCLUSION This study supports the removal of mitotic count from staging, but shows that its scoring is substantially affected by interobserver variation, suggesting that more prescriptive guidelines might have a beneficial impact on its prognostic value.

Chronic obstructive pulmonary disease (COPD) is a complex and multifactorial disease with a strong genetic component. Our objective is to identify the genetic variants associated with COPD risk and its severity in Mexican Mestizo population. We evaluated 1285 single-nucleotide polymorphisms (SNPs) of candidate genes in 299 smokers with COPD (COPD-S) and 531 smokers without COPD (SWOC) using an Illumina GoldenGate genotyping microarray. In addition, 251 ancestry informative markers were included. Allele A of rs2545771 in CYP2F2P is associated with a lower risk of COPD (p = 4.02E-10, odds ratio [OR] = 0.104, confidence interval [CI] 95% 0.05-0.18). When the COPD group was stratified by severity according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD; levels III + IV vs. I + II), 3 SNPs (rs4329505 and rs4845626 in interleukin 6 receptor [IL6R] and rs1422794 in a disintegrin and metalloproteinase domain 19 [ADAM19]) were associated with a lower risk of suffering the most severe stages of the disease. rs2819096 in the surfactant protein D (SFTPD) gene was associated with a higher risk of COPD GOLD III + IV (p = 7.79E-03, OR = 1.80, CI 95% 1.16-2.79). Finally, the haplotype in IL6R was associated with a lower risk of suffering from more severe COPD, whereas the haplotype in ADAM19 was associated with a higher risk (p = 7.40E-03, OR = 2.83, CI 95% 1.20-6.86) of suffering from the severe stages of the disease. Our data suggest that there are alleles and haplotypes in the IL6R, ADAM19, and SFTPD genes associated with different severity stages of COPD; in CYP2F2P, rs25455771 is associated with a lower risk of COPD.

Large complex ventral hernias act as tissue expanders for skin and subcutaneous fat. The purpose of this study is to evaluate outcomes of total abdominal wall reconstruction with component separation, posterior reinforcement, and vertical abdominoplasty in patients with large complex ventral hernias. Between 2010 and 2014, 58 patients underwent total abdominal wall reconstruction with component separation, intra-abdominal reinforcement, and vertical abdominoplasty. Between 2010 and 2012, patients underwent the conventional technique of component separation, while a perforator-preserving technique was performed during 2013 and 2014. Reinforcement material used was either synthetic mesh in clean cases or biologic mesh if contamination was present. All of the excessive skin and subcutaneous fat was removed in a vertical fashion. Data were analyzed with Mann–Whitney’s U test or Fisher’s exact test, as indicated. There were 27 moderately complex and 31 majorly complex hernias. Mean hernia size was 16 × 12 cm. The mean size of the removed skin island was 21 × 12 cm. Patients with contamination during the repair had longer in-hospital stays. Overall the local wound complication rate was 24 %, and was lower with the perforator-preserving technique compared to the conventional technique of component separation (11 vs. 48 %; OR 0.13, CI 0.03–0.5; p = 0.003). The overall postoperative morbidity rate was higher in the presence of contamination, and in patients with lower preoperative serum albumin levels. Mean total follow-up was 14 months with a 1-year recurrence-free survival of 96 %. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Mammary tumours are the most common neoplasms of female dogs. Compared to mammary tumours of humans and cats, myoepithelial (ME) cell involvement is common in canine mammary tumours (CMT) of any subtype. Since ME cell involvement in CMT influences both histogenetic tumour classification and prognosis, correct identification of ME cells is important. This review describes immunohistochemical methods for identification of canine mammary ME cells used in vivo. In addition, phenotypic and genotypic methods to isolate ME cells for in vitro studies to analyse tumour-suppressor protein production and gene expression are discussed. The contribution of ME cells to both histogenetic classifications and the prognosis of CMT is compared with other species and the potential use of ME cells as a method to identify carcinoma in situ is discussed.

Adenoviruses are important pathogens known to infect vertebrate hosts, including a wide range of primates. Despite its importance, data on the diversity of these viruses in non-human primates living in their natural habitat remain scarce. In this study, we conducted a surveillance of adenoviral infection in wild black howler monkeys from two protected natural areas in Mexico. This was achieved by analyzing 67 fecal samples using a nested PCR that targets the adenovirus DNA polymerase gene. Adenoviral DNA was detected in 12 samples from both study sites, with an overall prevalence of 17.9%. The amplified DNA sequences shared 100% nucleotide identity and phylogenetic analyses revealed that the haplotype detected was novel, and clustered with Platyrrhini mastadenovirus A, which was previously described in captive New World monkeys. Our data, along with the previous evidence, confirm that monkeys native to the Americas are the original hosts of these adenoviruses.

Introduction Despite the advanced antibiotic therapies, sepsis continues being a clinical entity with high morbidity and mortality. The ozone/oxygen mixture (O3/O2) has been reported to exhibit positive effects on immunity. The aim of our study was to analyze whether (O3/O2) combined with amoxicillin/clavulanate has any influence on the morbidity and mortality of septic rats. Methods We used 48 Sprague-Dawley rats randomly allocated to 6 groups (n = 8): healthy (C), septic (I), healthy + ozone therapy (O3), septic + amoxicillin/clavulanate (AMC), septic + amoxicillin/clavulanate + ozone therapy (AMC/O3) and septic + ozone therapy (I/O3). O3/O2 was administered rectally at increasing O3 concentrations during 10 days prior to the onset of sepsis model (intraperitoneally injection of fecal material) or saline administration in healthy control rats. Later (post-inoculation), 3 days per week, O3 was also administered. Vital signs were recorded, and microbiological, hematological and histopathological studies were performed. Results The number of surviving animal/total was higher in AMC (8/8) than in AMC/O3 (4/8) p = 0.077. The percentage of surviving animals with pneumonia was higher in AMC/O3 than in AMC (100% vs 37.5%). In dead animals, AMC/O3 rats had a significantly higher percentage of lesions: Cardiac lesions, pulmonary hemorrhages and pleuritis (100%) and serositis/peritonitis (75%). Only Escherichia coli (2 different biotypes) was isolated from blood and/or peritoneal fluid from all infected groups. A significant decrease in the percentage of band neutrophils from the surviviors belonging to AMC/O3 vs AMC was observed (p Conclusion Rectal pre-treatment with O3/O2 aggravates clinic status in septic rats treated with amoxicillin/clavulanate.

Pelvic floor reconstruction with pedicled vertical rectus abdominis myocutaneous flap has been popularized in patients undergoing pelvic exenteration due to locally advanced rectal carcinoma. Abdominal wall fascial dehiscence and incisional hernia may occur as a result of large skin and fascia islands as well as muscle required to close these large defects. The purpose of this paper was to describe a novel technique, consisting of VRAM flap donor-site closure with component separation technique, performed on the contralateral side as the flap harvest, allowing for a lower tension closure between ipsilateral external oblique/internal oblique/transverse abdominis muscles complex and contralateral rectus abdominis muscle. In 10 patients undergoing this technique, no abdominal fascial dehiscence, incisional hernia, or parastomal hernia occurred during a mean follow-up of 15 months. Overall 3-year patient survival rate was 80% with abdominal hernia free-survival rate of 100%. The addition of this technique represents an advance in overall patient care to provide a more successful outcomes in this complex scenario.

The present study evaluated the possible antiallodynic effect induced by [6]-gingerol in rats with L5-L6 spinal nerve ligation (SNL). Moreover, we determined the possible mechanism underlying the antiallodynic effect induced by [6]-gingerol in neuropathic rats. The animals underwent L5-L6 SNL for the purpose of developing tactile allodynia. Tactile allodynia was measured with von Frey filaments. Intrathecal administration of [6]-gingerol reversed SNL-induced tactile allodynia. The [6]-gingerol-induced antiallodynic effect was prevented by the intrathecal administration of methiothepin (30 μg per rat; nonselective 5-hydroxytryptamine [5-HT] antagonist), WAY-100635 (6 μg per rat; selective 5-HT

Summary Naturally occurring mammary tumours are uncommon in prosimians. A 20-year-old female ring-tailed lemur ( Lemur catta ) developed bilateral enlargement of the mammary glands. Surgical removal revealed that both masses were comprised of multiple nodules and cystic areas that entirely replaced the normal glands. Histologically, a benign neoplastic biphasic cellular proliferation, composed of luminal–epithelial and basal–myoepithelial components, was identified. Immunohistochemical analysis for expression of cytokeratin (CK) AE1/AE3, CK7, CK5 + 8, CK14, vimentin, p63 and 14-3-3σ highlighted the biphasic nature of the neoplasm. A low mitotic count, low Ki67 labelling index, expression of oestrogen receptor-α, lack of expression of human epidermal growth factor receptor and a 3-year disease-free period without recurrence supported the benign nature of the tumour. Macroscopically, histologically and immunohistochemically this neoplasm resembled benign adenomyoepithelioma of the breast in women. This is the first complete report of a naturally occurring mammary tumour in a ring-tailed lemur.

Objective: Treatment alternatives for persistent and recurrent Cushing disease (CD) include pituitary surgical re-intervention, radiation therapy (RT), pharmacotherapy, and bilateral adrenalectomy (BA). The decision of which of these alternatives is better suited for the individual patient rests on clinical judgment and the availability of resources. This retrospective cohort study was performed at a referral center to evaluate the long-term efficacy of different secondary interventions for persistent and recurrent CD. Methods: We evaluated the hospital charts of 84 patients (77 female, median age 34 years, median follow up 6.3 years) with CD diagnosed, treated, and followed at our multidisciplinary clinic according to a pre-established protocol. Results: Of the 81 patients who were initially treated with transsphenoidal surgery (TSS), 61.7% had a long-lasting remission, 16% had persistent disease, and 22% achieved remission but relapsed during follow-up. The most frequently used secondary treatment was pituitary re-intervention, followed by ketoconazole, RT, and BA. Early remissions were observed in 66.6% of the re-operated and in 58.3% of the radiated patients; long-lasting remission was achieved in 33.3% and 41.6% of these patients, respectively. Nelson syndrome developed in 41.6% of the patients who underwent BA. Upon last follow-up, 88% of all the patients are in remission, and 9.5% are biochemically controlled with ketoconazole. Conclusion: The efficacy of treatment alternatives for recurrent or persistent CD varies considerably among patients and multiple interventions are often required to achieve long-lasting remission. Abbreviations: ACTH = adrenocorticotrophic hormone; BA = bilateral adrenalectomy; CBG = cabergoline; CD = Cushing disease; CV = coefficient of variation; DXM = dexamethasone; IQR = interquartile range; RT = radiation therapy; SRS = stereotactic radiosurgery; TSS = transsphenoidal surgery; UFC = urinary free cortisol; ULN = upper limit of normal

Acromegaly is usually due to the excessive secretion of GH by a pituitary adenoma. It is frequently accompanied by comorbidities that compromise quality of life and results in elevated mortality rates.To evaluate mortality and morbidity in patients with acromegaly receiving multimodal care.Tertiary care center.Retrospective evaluation of 442 patients (65.4% women; mean age, 43.5 ± 13.1 y) followed for a median of 6 years (interquartile range [IQR], 3-10).Twenty-two patients died during the study period (4.9%), representing a total standardized mortality ratio (SMR) of 0.72 (95% confidence interval [CI], 0.41-1.03). Standardized mortality ratios were 1.5 and 0.44 for patients whose last GH was above and below 2.5 ng/mL, respectively; 1.17 and 0.16 for those whose last GH was above and below 1 ng/mL, respectively; and 0.94 and 0.46 for those whose last IGF-1 was above and below 1.2 times the upper limit of normal (ULN), respectively. The prevalence of diabetes mellitus, hypertension, heart disease, and cancer was 30%, 35%, 8%, and 4.7%, respectively. The most common cause of death was cancer. On multivariate analysis, diabetes, heart disease, and cancer were related to a baseline GH10 ng/mL; the presence of cancer and the last IGF-1 were significant predictors of mortality. Survival decreased as the latest GH levels increased from1 ng/mL to5 ng/mL and as IGF-1 increased from1.2 to2 times the ULN.Mortality in acromegaly can be successfully reduced, provided patients are treated using a multimodal approach with careful management of comorbidities.

Merkel cells (MCs) are specialized skin receptors characterized by their particular location and close association with nerve terminals. They also are cells with a presumptive neuroendocrine function and are considered as part of the diffuse neuroendocrine system. By using commercially available monoclonal and polyclonal antibodies in samples of dog skin, MCs were properly distinguished from other clear cell types in the epidermis. They expressed cytokeratins 7, 8, 20, EpCAM, NSE, CGA, SYN, S100 protein, and NF, presented diverse cytological features and arrangements depending on the location considered, and showed pronounced heterogeneity with markedly different expression and distribution patterns for antibodies used. Anti-CK20 presented as the most reliable and specific antibody for their identification. The present study increases our knowledge of MCs and establishes a basis for future studies of the role(s) of the MCs in diseased tissues of the dog skin, including the cutaneous neuroendocrine (Merkel cell) tumour.

We measured the abundance of sarcoplasmic masses within skeletal muscle myocytes of an adult female stranded pigmy sperm whale (Kogia breviceps). The presence of these masses in other species has been reported in association with myopathies, including myotonic dystrophy, the most frequently related pathology. Other histopathologic muscle changes included a high number of internal nuclei, variations in fiber size and shape, and the predominance of type I fibers.

Objective Successful surgery does not always resolve all the clinical consequences of hypercortisolism in patients with Cushing’s disease (CD). Our purpose was to integrally evaluate a group of CD patients cured by pituitary surgery and look for the persistence of CD symptoms, signs, and comorbidities. Methods We performed clinical and biochemical evaluations of 29 CD patients (2 males) cured by pituitary surgery. All patients underwent early (median 12 months) and late (median 58 months) postoperative evaluations. We sought information regarding hypercortisolism-related symptoms and signs, as well as metabolic, cardiovascular, reproductive, and psychologic comorbidities. Results The prevalence of obesity dropped from 72.4% at diagnosis to 31% at early evaluation but increased again to 44.8% at the late evaluation. Diabetes was present in 14 patients (48.3%) at diagnosis and persisted in 9 at the late evaluation. Hypertriglyceridemia was present in 58.6% and 55.1% of patients at diagnosis and at the late follow-up, respectively. The prevalence of hypercholesterolemia was 79.3% at diagnosis, decreased to 55.1% at the early evaluation, and increased to 65.5% at the late evaluation. Menstrual abnormalities were originally present in 15 of 20 women, and 8 of the 15 had recovered normal periods when seen at the last evaluation. Among the 24 patients with depression at diagnosis, 11 and 6 still exhibited mood abnormalities at the early and late evaluations, respectively. Conclusion In a variable proportion of patients, the cardiovascular, metabolic, and emotional comorbidities of CD persist after long-term remission, irrespective of the initial degree of hypercortisolism. (Endocr Pract. 2013; 19:252-258)

Three new species of the earthworm genus Zapatadrilus are described from Tamaulipas, Mexico: Zapatadrilus aurelius sp. nov., Zapatadrilus huastecus sp. nov., and Zapatadrilus montezumensis sp. nov. Delimitation of the new species was supported by morphological and molecular (genetic distances) evidence. Diagnostic characters of the three new species include: tubulo-racemose prostates in segments 18 and 20, penial setae absent, typhlosole present and intestine beginning in 17/18. Z. montezumensis sp. nov. is separated by its metandric condition, Z. aurelius sp. nov. by the last hearts in 13 and Z. huastecus sp. nov. by the shape of the spermathecae and patterns of genital markings.

The neurobiology of neuropathic pain is caused by injury in the central or peripheral nervous system. Recent evidence points out that mangiferin shows anti-nociceptive effect in inflammatory pain. However, its role in inflammatory and neuropathic pain and the possible mechanisms of action are not yet established. The purpose of this study was to determine the possible anti-allodynic effect of mangiferin in rats with spinal nerve ligation (SNL). Furthermore, we sought to investigate the possible mechanisms of action that contribute to these effects. Mechanical allodynia to stimulation with the von Frey filaments was measured by the up and down method. Intrathecal administration of mangiferin prevented, in a dose-dependent fashion, SNL-induced mechanical allodynia. Mangiferin-induced anti-allodynia was prevented by the intrathecal administration of L-NAME (100μg/rat, non-selective nitric oxide synthase inhibitor), ODQ (10μg/rat, inhibitor of guanylate-cyclase) and glibenclamide (50μg/rat, channel blocker of ATP-sensitive K

Merkel cells (MCs) are specialized cutaneous receptor cells involved with tactile sense. Although the distribution of MCs has been extensively studied in humans and rodents, their precise distribution and density throughout skin in the dog has not previously been determined. Knowledge of their distribution could facilitate understanding of their functions. By using of immunohistochemistry, density, and anatomical mapping of the MCs population in the dog skin was determined. Assessment of the MCs innervation was also achieved. Different patterns were noted in epidermis, hair follicles, or mucosa, including variable-sized clusters, linear or horse-shaped arrangements, and scattered and individualized cells. MCs revealed great variations in density and distribution over the body surface, with the highest numbers in oral mucosa and facial skin. There was no correlation of MCs density with age, sex, type of breed, coat type or pigmentation. Between 41 and 65% of MCs in hairy and glabrous skin and 8-18% of MCs in oral mucosa were in intimate contact with intraepithelial axon terminals. These findings indicate that canine MCs are numerous in sensory receptive areas and may be associated with the tactile sense in the dog. The present article enhances the knowledge of the skin structure in this species. Anat Rec, 299:1157-1164, 2016. © 2016 Wiley Periodicals, Inc.

Although aryl hydrocarbon receptor-interacting protein (AIP) mutations are rare in sporadic acromegaly, their prevalence among young patients is nonnegligible. The objectives of this study were to evaluate the frequency of AIP mutations in a cohort of Mexican patients with acromegaly with disease onset before the age of 30 and to search for molecular abnormalities in the AIP gene in teeth obtained from the "Tampico Giant". Peripheral blood DNA from 71 patients with acromegaly (51 females) with disease onset30 years was analysed (median age of disease onset of 23 years) and correlated with clinical, biochemical and imaging characteristics. Sequencing was also carried out in DNA extracted from teeth of the Tampico Giant. Five patients (7 %) harboured heterozygous, germline mutations of the AIP gene. In two of them (a 9-year-old girl with gigantism and a young man with symptoms of GH excess since age 14) the c.910CT (p.Arg304Ter), well-known truncating mutation was identified; in one of these two cases and her identical twin sister, the mutation proved to be a de novo event, since neither of their parents were found to be carriers. In the remaining three patients, new mutations were identified: a frameshift mutation (c.976_977insC, p.Gly326AfsTer), an in-frame deletion (c.872_877del, p.Val291_Leu292del) and a nonsense mutation (c.868A T, p.Lys290Ter), which are predicted to be pathogenic based on in silico analysis. Patients with AIP mutations tended to have an earlier onset of acromegaly and harboured larger and more invasive tumours. A previously described genetic variant of unknown significance (c.869C T, p.Ala299Val) was identified in DNA from the Tampico Giant. The prevalence of AIP mutations in young Mexican patients with acromegaly is similar to that of European cohorts. Our results support the need for genetic evaluation of patients with early onset acromegaly.

Background: Chronic obstructive pulmonary disease (COPD) patients often present considerable individual medical burden in their symptoms, limitations, and well-being that complicate medical treatment. To improve their overall health status, while reducing the number of exacerbations, a multidisciplinary approach including different elements of care is needed. The aim of this study was to evaluate the effects of a remote support program on COPD patients at high risk of experiencing worsening of their disease and other health-related outcomes. Methods: An observational, multicenter, prospective study aimed at evaluating the impact of a 7-month remote support program on COPD patients in exacerbations control and changes in health status measured with the COPD assessment test (CAT). Factors associated with a clinically relevant decrease in CAT were assessed using a logistic regression analysis. Results: A total of 114 subjects started the program. The majority of the study population were males (81.6 %), retired (70.2 %), without academic qualifications or with a low level of education (68.4 %), and ex-smokers (79.8 %). The mean +/- SD age was 69.6 +/- 9.1 years and the BMI was 27.8 +/- 5.5 Kg/m(2). Overall, 41.9 % (95 % CI 31.9-52.0) patients, significantly improved health status (CAT decrease >= 2 points). Univariate analysis showed that significant improvement in CAT was associated with baseline CAT scores [high CAT score 19.2 (+/- 7.5) vs. low CAT score 12.4 (+/- 6.4); OR = 1.15, 95 % CI: 1.07-1.24; p < 0.001] and with being non-compliant [62.5 % (15/24) of non-compliant vs 34.7 % (24/69) of compliant patients significantly improved CAT scores; OR = 3.13, 95 % CI: 1.19-8.19; p = 0.021). After controlling for the effect of all variables in a multivariable logistic regression model, the only factor that remained significant was baseline CAT score. The proportion of smokers in the total population remained constant during the study. There was a significant reduction in the number of exacerbations after entering this remote support program with median -1 (IQR: -2, 0), (p < 0.001). The Morisky-Green questionnaire showed an increase of treatment compliance, namely at baseline, 25.8 % (24/93) of patients were noncompliant while in the end 66.7 % (16/24) of them became compliant) (p = 0.053). Conclusions: A remote support program for high-risk COPD patients results in an improvement of the patients' health status, particularly in those with initially poor health status, and it helps to reduce COPD exacerbations., The ESOPO study was funded by Takeda Pharmaceutical Spain SA.

BACKGROUND The safe and appropriate use of long-acting beta-agonists (LABAs) for the treatment of asthma has been widely debated. In two large clinical trials, investigators found a potential risk of serious asthma-related events associated with LABAs. This study was designed to evaluate the risk of administering the LABA salmeterol in combination with an inhaled glucocorticoid, fluticasone propionate. METHODS In this multicenter, randomized, double-blind trial, adolescent and adult patients (age, ≥12 years) with persistent asthma were assigned to receive either fluticasone with salmeterol or fluticasone alone for 26 weeks. All the patients had a history of a severe asthma exacerbation in the year before randomization but not during the previous month. Patients were excluded from the trial if they had a history of lifethreatening or unstable asthma. The primary safety end point was the first serious asthma-related event (death, endotracheal intubation, or hospitalization). Noninferiority of fluticasone–salmeterol to fluticasone alone was defined as an upper boundary of the 95% confidence interval for the risk of the primary safety end point of less than 2.0. The efficacy end point was the first severe asthma exacerbation. RESULTS Of 11,679 patients who were enrolled, 67 had 74 serious asthma-related events, with 36 events in 34 patients in the fluticasone–salmeterol group and 38 events in 33 patients in the fluticasone-only group. The hazard ratio for a serious asthmarelated event in the fluticasone–salmeterol group was 1.03 (95% confidence interval [CI], 0.64 to 1.66), and noninferiority was achieved (P = 0.003). There were no asthma-related deaths; 2 patients in the fluticasone-only group underwent asthmarelated intubation. The risk of a severe asthma exacerbation was 21% lower in the fluticasone–salmeterol group than in the fluticasone-only group (hazard ratio, 0.79; 95% CI, 0.70 to 0.89), with at least one severe asthma exacerbation occurring in 480 of 5834 patients (8%) in the fluticasone–salmeterol group, as compared with 597 of 5845 patients (10%) in the fluticasone-only group (P

Mexican-American women are disproportionately vulnerable to cardio-metabolic dysfunction and related health conditions such as cardiovascular disease and diabetes. Research shows that low socioeconomic status contributes to this populations excess vulnerability to cardio-metabolic dysfunction, but little is known about the contribution of cultural factors to these associations.The current study explored the association between fatalism and cardio-metabolic dysfunction in a randomly selected community cohort of middle-aged Mexican-American women and examined whether fatalism could be conceptualized as a pathway linking socioeconomic status to cardio-metabolic dysfunction in this population.Participants included 300 women (ages 40-65), recruited from San Diego communities located near the Mexican border, who completed a self-administered survey battery and underwent a fasting clinical exam between the years 2006 and 2009.Linear regression analyses and mediation analyses utilizing bootstrapping procedures were performed to test study hypotheses. After controlling for age, menopausal status, and acculturation level, fatalism was associated with cardio-metabolic dysfunction. Although slightly attenuated, this relationship persisted after accounting for socioeconomic status. In addition, individuals of low socioeconomic status displayed more fatalistic beliefs and higher cardio-metabolic dysfunction after accounting for relevant covariates. Finally, the indirect effect of socioeconomic status on cardio-metabolic dysfunction via fatalism reached statistical significance.Fatalism may be an important independent risk factor for cardio-metabolic dysfunction in Mexican-American women as well as a mechanism linking socioeconomic status to cardio-metabolic health.

Skeletal muscle samples were examined post-mortem in 148 cetaceans over a 12-year period. Histological analysis included haematoxylin and eosin (HE) and periodic acid-Schiff (PAS) staining with and without diastase digestion. In addition, histological muscle sections were immunostained for ubiquitin and fast and slow heavy-chain myosin isoforms. PAS-positive, diastase-resistant inclusions were detected in 26 animals from 11 different species. Older cetaceans were preferentially affected. These intrafibre inclusions varied from large aggregates to multiple coarse granules and were typically associated with type II fibres. All diastase-resistant inclusions were positive for ubiquitin. These features resembled those inclusions described as complex polysaccharide in horses. Based on these histological findings and the ubiquitin staining pattern, a morphological diagnosis of complex polysaccharide storage myopathy is proposed.

Stress is a hypothesized pathway in socioeconomic status (SES)-physical health associations, but the available empirical data are inconsistent. In part, this may reflect discrepancies in the approach to measuring stress across studies, and differences in the nature of SES-stress associations across demographic groups. We examined associations of SES (education, income) with general and domain-specific chronic stressors, stressful life events, perceived stress, and stressful daily experiences in 318 Mexican–American women (40–65 years old). Women with higher SES reported lower perceived stress and fewer low-control experiences in everyday life (ps < .05), but greater chronic stress (education only, p < .05). Domain-specific analyses showed negative associations of income with chronic housing and financial stress (ps < .05), but positive associations of SES with chronic work and care-giving stress (all ps < .05 except for income and caregiving stress, p < .10). Sensitivity analyses showed that most SES-stress associations were consistent across acculturation levels. Future research should adopt a multi-dimensional assessment approach to better understand links among SES, stress, and physical health, and should consider the sociodemographic context in conceptualizing the role of stress in SES-related health inequalities.

Lower socioeconomic status (SES) is associated with poorer health, possibly through activation of the sympathetic nervous system.This study aimed to examine the association between SES and catecholamine levels, and variations by acculturation.Three hundred one Mexican-American women underwent examination with a 12-h urine collection. Analyses tested associations of SES, acculturation (language and nativity), and their interaction with norepinephrine (NOREPI) and epinephrine (EPI).No main effects for SES or the acculturation indicators emerged. Fully adjusted models revealed a significant SES by language interaction for NOREPI (p .01) and EPI (p .05), and a SES by nativity interaction approached significance for NOREPI (p= .05). Simple slope analyses revealed that higher SES related to lower catecholamine levels in Spanish-speaking women, and higher NOREPI in English-speaking women. Although nonsignificant, similar patterns were observed for nativity.Associations between SES and catecholamines may vary by acculturation, and cultural factors should be considered when examining SES health effects in Hispanics.

14-3-3 σ protein is a negative cell cycle regulator, with both reduced and elevated levels associated with cancer in humans. This study assessed the expression of this protein in canine mammary tissues using immunohistochemistry and Western blotting. 14-3-3 σ was detected in 97% of the mammary tissue samples examined and was found in both myoepithelial (MECs) and epithelial (ECs) cells. Expression levels were elevated and reduced in neoplastic ECs and MECs, respectively (P0.001). Intense expression of 14-3-3 σ was detected in neoplastic ECs infiltrating blood vessels and lymph nodes and suggests a possible role for this protein in the malignant transformation of mammary neoplasms. Moreover, double immunostaining for 14-3-3 σ and the MEC-specific marker p63, confirmed that 14-3-3 σ is a highly sensitive marker of MECs since all p63-positive cells were also positive for 14-3-3 σ. However, this protein is not exclusive to MECs as ECs also labelled positively.

Mammary Paget disease, characterized by diffuse infiltration of the nipple and areolar epidermis by carcinoma cells, develops in 1% to 3% of human mammary carcinomas. The purpose of this article is to present 2 cases of intraepidermal adenocarcinoma that resembled human mammary Paget disease, histologically and immunohistochemically, in dogs with underlying mammary carcinoma.

Summary The aim of this study was to determine whether the myoepithelial (ME) cell marker calponin could be used to analyze the integrity of the ME cell layer as a means of identifying canine mammary carcinoma in situ. Tissue from 74 canine mammary lesions was evaluated (two dysplasia, eight benign tumours and 64 carcinomas including one carcinoma in situ). The 63 carcinomas included examples of histological grade 1 (n = 32), grade 2 (n = 23) and grade 3 (n = 8). Expression of calponin was determined by immunohistochemistry. The percentage of proliferating cells surrounded by a single layer of calponin-positive cells formed the basis of classification as type I (≥90%), type II (70–90%) and type III (≤70%). Expression of Ki67 was used to determine the proliferation index (PI). The malignant tumours comprised of an approximately equal mixture of type I, II and III lesions. The two examples of dysplasia, the carcinoma in situ and two thirds of the benign tumours were classified as type I lesions. Some overlap in the level of calponin expression was observed between benign and malignant tumours. Positive correlations between the degree of calponin expression and the type of lesion (i.e. benign versus malignant; R = +0.3, P = 0.08) and the histological grade of malignancy (R = +0.54, P = 0.000001) were found. A negative correlation between the degree of calponin expression and PI (R = +0.027, P = 0.016) was found. The ME cell marker calponin may be used as an aid in the identification of canine carcinoma in situ, but the study of the ME cell layer integrity is not definitive for the diagnosis of malignancy in canine mammary tumours.

Transsphenoidal surgery remains the treatment of choice in acromegaly, yet 40-50% of patients require secondary forms of therapy such as radiation therapy (RT) and somatostatin analogues (SA). We undertook this study to evaluate the efficacy and safety of RT in acromegaly.Forty patients with acromegaly treated with RT (mean dose, 52 Gy) after failed pituitary surgery between 1993 and 2007 were analyzed; all were clinically and biochemically active. Patients were evaluated with yearly hormonal measurements [basal and glucose-suppressed growth hormone (GH), IGF-1, thyroid-stimulating hormone (TSH), free T4, cortisol, luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone or estradiol and prolactin (PRL)] and with magnetic resonance imaging every 2 years.Mean age of patients was 52.9 ± 12.1 years and 85% were female. All subjects had been followed for 1 year, 75% for 3 years, 70% for 5 years and 35% for 10 years. The median basal GH level fell from a baseline of 8.8 ng/mL to 2.27 ng/mL at 5 years (p = 0.001) and to 1.88 ng/mL at 10 years (p = 0.001). A GH1 ng/mL was achieved by 46% and 57% of the patients at 5 and 10 years of follow-up, respectively. The proportion of patients achieving a normal IGF-1 was 36% at 5 years and 43% at 10 years. Before RT, hypothyroidism, hypocortisolism and hypogonadism were present in 44%, 26% and 74% of patients, respectively. After 5 years of follow-up (n = 28), these figures increased to 51%, 41% and 79% and over a third of the group had panhypopituitarism. One patient developed optic neuritis and another patient was diagnosed with a meningioma 10 years after RT. No cerebrovascular events or deaths occurred.RT is an effective, low-cost and reasonably safe means of controlling acromegalic activity, particularly useful in parts of the world where SA are not readily available.

To determine the prevalence of diabetes, glucose intolerance and impaired fasting glucose in Mexican patients with acromegaly and establish associations with clinical, anthropometric and biochemical variables. 257 patients with acromegaly were evaluated by a 75 g-oral glucose tolerance test with measurements of both GH and glucose (0, 30, 60, 90 120 min) as well as baseline IGF-1. Normal glucose tolerance (NGT), impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and diabetes (DM) were defined based on the 2003 ADA criteria. NGT, IFG, IGT and DM were found in 27.6, 8.9, 31.6 and 31.9% of the subjects, respectively; 42 of the DM patients were unaware of the diagnosis. Patients with diabetes were older than subjects in the other 3 categories (P = 0.001), and the proportion of women was significantly higher in the DM (74%) and IGT (68%) groups than in the NGT group (52%) (P = 0.004). Odds ratio for the development of DM was 3.29 (95% CI 3.28–3.3). GH and IGF-1 levels were comparable among the different groups. In a multivariable analysis DM was significantly associated with age, presence of a macroadenoma, disease duration and a basal GH > 30 μg/dl. DM and probably IGT are more prevalent in acromegaly than in the general Mexican population. DM was more frequent in females of all ages, in subjects with severely elevated GH concentrations, in patients with macroadenomas, and long-standing disease duration. The odds ratio for DM in our subjects with acromegaly is more than 3 times higher than in the general population.

BACKGROUND AND OBJECTIVE There has not been a formal evaluation of how frequently and to what extent surgical reintervention in patients with persistently active acromegaly may achieve significant, albeit incomplete, reductions in growth hormone (GH) and insulinlike growth factor-I (IGF-I) levels. Of importance, recent studies suggest that the response to radiotherapy and pharmacotherapy is better with lower degrees of hypersomatotropism. The objective of this study was to evaluate the outcome of surgical reintervention in patients with active acromegaly at our institution between 1995 and 2005. METHODS We retrospectively evaluated the outcome in 53 patients with active acromegaly (49 with macroadenomas) who underwent a second operation a mean of 24.1 +/- 25.2 months after the first intervention. Basal and postglucose GH as well as IGF-I levels were analyzed at diagnosis and after the first and second pituitary procedures. RESULTS Basal GH decreased in 38 patients (72%): to

The costs of bird song incurred in a diversity of ways may result in trade-offs in the production and maintenance of elaborate plumage ornaments. In this paper, we examine evolutionary trade-offs between acoustic and visual signalling in trogon birds (Trogonidae). Using multiple regressions with phylogenetically independent contrasts, we found that interspecific variation in male plumage coloration was not significantly predicted by song traits (reduced by PCA) or altitude. Although plumage coloration is expected to decrease with increases in song elaboration, both groups of variables were not related. Given that song and plumage coloration traits are likely targets of sexual selection, we also examined their relationships with sexual plumage dimorphism. We found that male carotenoid-derived coloration was positively related to sexual plumage dimorphism, suggesting that sexual selection on male carotenoid-derived coloration may be stronger than on melanin- or structurally based coloration, or than on acoustic traits. Comparative studies on other bird families accounting for the effects of phylogeny as well as environmental covariates are required to test the generality of our findings in trogons.

Lack of exon 3 of the GH receptor (d3-GHR) has been associated with increased responsiveness to GH therapy. By analogy, we hypothesized that patients with acromegaly bearing the d3-GHR genotype may have a more morbid clinical and biochemical picture.Our objective was to determine whether the GHR genotype, by modifying tissue sensitivity to GH, influences the clinical/biochemical expression of acromegaly and its outcome after treatment.The study was conducted at a specialized clinic at a tertiary care hospital.We conducted a prospective genotype investigation and retrospective analysis and correlation with clinical, biochemical, and outcome data from a group of 148 patients. Samples from 175 healthy blood donors were used as controls. GHR genotyping was performed by real-time PCR.We assessed prevalence of the three GHR genotypes (fl/fl, d3/d3, and d3/fl), associations between the genotypes, and baseline as well as post-therapeutic characteristics.Prevalence of the fl/fl, d3/d3, and d3/fl genotypes was 45, 22, and 32%, respectively, similar to what was found in the controls. Baseline characteristics were similar in carriers of the three genotypes. A positive correlation between IGF-I and log GH concentrations was significant only in homo- or heterozygous d3 carriers. Among d3-GHR carriers, diabetes, but no other comorbidities, was more prevalent (odds ratio = 2.02; 95% confidence interval = 0.96-4.2). d3-GHR carriers had significantly higher IGF-I concentrations after treatment. Multiple regression analysis revealed that the homo- or heterozygous lack of exon 3 was the strongest predictor of persistent biochemical activity (odds ratio = 1.29; 95% confidence interval = 0.65-2.58).The absence of exon 3 of the GHR may be associated with a more morbid acromegalic clinical and biochemical picture and a lower chance of achieving IGF-I normalization after therapy.

Background: Individuals with low socioeconomic position (SEP) and Latino ethnicity are at high risk for the metabolic syndrome. In part, this may reflect that these populations benefit from fewer resilient resources to manage stressful environments, resulting in accentuated psychological and physiological costs (1).Purpose: We examined the direct effects of educational attainment (an indicator of SEP) and psychosocial resources on metabolic syndrome variables, and tested indirect effects of education, via resources.Methods: Participants were 145 middle-aged (M=47.07 years) Latinas recruited from health clinics along the California—Mexico border. Women completed assessments of demographics and resilient resources; metabolic syndrome variables were measured (blood pressure [BP], waist circumference [WC]) or abstracted from medical charts (lipids, glucose).Results: Women with less education reported fewer psychosocial resources (ΔR2=.14, p

This report describes a malignant schwannoma in the diaphragm of a 2-year-old goat. The immunohistochemical and histological features indicated a diagnosis of malignant schwannoma rather than neurofibrosarcoma. The diaphragm represents an unusual location for neoplasia in both domestic animals and human beings. A possible anatomical origin from the phrenic nerve is discussed.

The expression of oestrogen receptor-alpha (ERalpha) and progesterone receptor (PR) was examined in 32 canine genital tract tumours diagnosed as smooth muscle tumours (benign or malignant, pure or mixed). The immunohistochemical expression of calponin was used to assess the smooth muscle differentiation of the tumours. Nineteen human uterine leiomyomas were also examined. Calponin expression was detected in 89.3% of canine and 100% of human genital tract tumours diagnosed as leiomyomas, as well as in the majority of other tumours examined (canine or human, genital or extragenital, benign or malignant) with the exception of canine negative control tumours (cutaneous fibroma and hepatoid gland adenoma). ERalpha was found in 56.3% of canine and 52.6% of human leiomyomas, while PR was found in 84.4% of canine and 94.7% of human tumours. These results indicate that calponin is a good marker for differentiating neoplasia of the canine genital system of uncertain origin, as in human patients. They also show that canine tumours with smooth muscle differentiation of the genital tract of the bitch express steroid hormone receptors, a finding that opens up the possibility of hormone therapy.