Glyphosate induces epithelial mesenchymal transition-related changes in human endometrial Ishikawa cells via estrogen receptor pathway.

Glyphosate based herbicides are the most commonly used herbicide in the world. We aimed to determine whether glyphosate (Gly) induces epithelial mesenchymal transition (EMT) - related changes in a human endometrial carcinoma cell line (Ishikawa cells), and whether the estrogen receptor (ER) pathway is involved in these changes. Ishikawa cells were exposed to Gly (0.2 µM and 2 µM) or 17ß-estradiol (E2: 10-9 M). We detected that Gly increased cell migration and invasion ability compared to vehicle, as did E2. Moreover, a down regulation of E-cadherin mRNA expression was determined in response to Gly, similar to E2-effects. These results show that Gly promotes EMT-related changes in Ishikawa cells. When an ER antagonist (Fulvestrant: 10-7 M) was co-administrated with Gly, all changes were reversed, suggesting that Gly might promote EMT-related changes via ER-dependent pathway. Our results are interesting evidences of Gly effects on endometrial cancer progression via the ER-dependent pathway.

Postnatal exposure to endosulfan affects uterine development and fertility.

Endosulfan is an organochlorine pesticide (OCP) used in large-scale agriculture for controlling a variety of insects and mites that attack food and non-food crops. Although endosulfan has been listed in the Stockholm Convention as a persistent organic pollutant to be worldwide banned, it is still in use in some countries. Like other OCPs, endosulfan is bioaccumulative, toxic and persistent in the environment. Human unintentional exposure may occur through air inhalation, dietary, skin contact, as well as, via transplacental route and breast feeding. Due to its lipophilic nature, endosulfan is rapidly absorbed into the gastrointestinal tract and bioaccumulates in the fatty tissues. Similar to other OCPs, endosulfan has been classified as an endocrine disrupting chemical (EDC). Endocrine action of endosulfan on development and reproductive function of males has been extensively discussed; however, endosulfan effects on the female reproductive tract have received less attention. This review provides an overview of: i) the fate and levels of endosulfan in the environment and human population, ii) the potential estrogenic properties of endosulfan in vitro and in vivo, iii) its effects on uterine development, and iv) the long-term effects on female fertility and uterine functional differentiation during early gestation.

Preoperative MRI evaluation of lesion-nipple distance in breast cancer patients: thresholds for predicting occult nipple-areola complex involvement.

AIM: To identify clinically occult nipple-areola complex (NAC) involvement using preoperative magnetic resonance imaging (MRI), to inform selection of patients eligible for nipple-sparing mastectomy (NSM) or skin-sparing mastectomy (SSM). MATERIAL AND METHODS: This was a retrospective study of 195 patients, who had preoperative breast MRI (February 2011 to January 2017) before undergoing surgical treatments (NSM or SSM) for newly diagnosed breast cancer. Tumour features at MRI (mass or non-mass lesion, diameter, lesion-NAC distance [LND]) and pathology (lesion diameter, histopathological type, receptor status) were recorded, as well as the type of surgery (NSM/SSM) and presence (NAC+) or absence (NAC-) of tumour at intraoperative evaluation of retroareolar tissue. Mann-Whitney test, Fisher's exact test, logistic regression, and receiver operating characteristic (ROC) curve analysis were used for analysis of NAC+ versus NAC- to assess variables that predict NAC tumoural involvement. RESULTS: Over the study period, NAC+ was proven histologically in 71/200 (35.5%) surgical treatments, while there were 129/200 NAC- (72 NSM and 128 SSM performed). LND at MRI was statistically (p<0.001) lower in NAC+ patients than in NAC- patients. The area under the ROC curve (0.82, 95% confidence interval [CI]: 0.76-0.88) indicated 10 mm as the best cut-off, with sensitivity of 82%, specificity of 72%, and accuracy of 79%. A 5-mm cut-off enhanced sensitivity, whereas a 15-mm cut-off favoured specificity. CONCLUSIONS: MRI is a useful tool for identifying NAC+ patients; a 10-mm cut-off for LND assists selection of patients for NSM, although intraoperative retroareolar tissue examination remains mandatory.

Postnatal development and histofunctional differentiation of the oviduct in the broad-snouted caiman (Caiman latirostris).

Caiman latirostris is a South American crocodilian species characterized as a sentinel of the presence of endocrine-disrupting compounds (EDCs). Evaluating developmental events in hormone-dependent organs, such as the oviduct, is crucial to understand physiological postnatal development, to identify putative periods of exposure sensitive to EDCs, and/or to identify biomarkers useful to evaluate the effects of EDC exposure. In this study, we describe the histomorphological features of C. latirostris oviducts by establishing the ontogeny of changes at cellular, tissue and molecular levels from the neonatal to the pre-pubertal juvenile stages. Since the histological diagnosis of the adenogenic oviduct lies on a group of features, here we defined a histofunctional score system and a cut-off value to distinguish between preadenogenic and adenogenic oviducts. Our results showed that the maturation of the C. latirostris oviduct is completed postnatally and characterized by changes that mimic the pattern of histological modifications described for the mammalian uterus. Ontogenic changes in the oviductal epithelium parallel changes at subepithelial level, and include collagen remodeling and characteristic spatial-temporal patterns of α-actin and desmin. The expression pattern of estrogen receptor alpha and progesterone receptor evidenced that, even at early postnatal developmental stages, the oviduct of C. latirostris is a target organ of endogenous and environmental hormones. Besides, oviductal adenogenesis seems to be an estrogen-dependent process. Results presented here provide not only insights into the histophysiological aspect of caiman female reproductive ducts but also new tools to better characterize caimans as sentinels of endocrine disruption.

Digital breast tomosynthesis as an adjunct to digital mammography for detecting and characterising invasive lobular cancers: a multi-reader study.

AIM: To examine the interpretive performance of digital breast tomosynthesis (DBT) as an adjunct to digital mammography (DM) compared to DM alone in a series of invasive lobular carcinomas (ILCs) and to assess whether DBT can be used to characterise ILC. MATERIALS AND METHODS: A retrospective, multi-reader study was conducted of 83 mammographic examinations of women with 107 newly diagnosed ILCs ascertained at histology. Consenting women underwent both DM and DBT acquisitions. Twelve radiologists, with varying mammography experience, interpreted DM images alone, reporting lesion location, mammographic features, and malignancy probability using the Breast Imaging-Reporting and Data System (BI-RADS) categories 1-5; they then reviewed DBT images in addition to DM, and reported the same parameters. Statistical analyses compared sensitivity, false-positive rates (FPR), and interpretive performance using the receiver operating characteristics (ROC) curve and the area under the curve (AUC), for reading with DM versus DM plus DBT. RESULTS: Multi-reader pooled ROC analysis for DM plus DBT yielded AUC=0.89 (95% confidence interval [CI]: 0.88-0.91), which was significantly higher (p<0.0001) than DM alone with AUC=0.84 (95% CI: 0.82-0.86). DBT plus DM significantly increased pooled sensitivity (85%) compared to DM alone (70%; p<0.0001). FPR did not vary significantly with the addition of DBT to DM. Interpreting with DBT (compared to DM alone) increased the correct identification of ILCs depicted as architectural distortions (84% versus 65%, respectively) or as masses (89% versus 70%), increasing interpretive performance for both experienced and less-experienced readers; larger gains in AUC were shown for less-experienced radiologists. Multifocal and/or multicentric and bilateral disease was more frequently identified on DM with DBT. CONCLUSION: Adding DBT to DM significantly improved the accuracy of mammographic interpretation for ILCs and contributed to characterising disease extent.

The eggshell features and clutch viability of the broad-snouted caiman (Caiman latirostris) are associated with the egg burden of organochlorine compounds.

Organochlorine compounds (OCCs) are toxic and have been identified as endocrine-disrupting chemicals (EDCs). The broad-snouted Caiman (Caiman latirostris) is an oviparous species widely distributed in South America with potential to accumulate OCCs. The eggshell is formed during passage of the eggs through the oviduct. Since the oviduct is a target of hormone actions, exposure to OCCs could modify eggshell quality, thus affecting clutch viability. Eight clutches were collected from wetlands of Parana River tributaries, in north-eastern Argentina. Two to four eggs per clutch were used to establish the burden of OCCs, eggshell thickness and eggshell porosity. The remaining eggs were incubated in controlled conditions. Ten days after hatching, hatchling survival was assessed. Organochlorine pesticide residues (OCPs) were found in all clutches, while polychlorinated biphenyls (PCBs) were present in all but one clutch. The principal contributors to the OCP burden were members of the DDT family and oxychlordane. Eggshell thickness was 400.9±6.0 µm and, unexpectedly, no association between eggshell thickness and the OCC burden was found. The number of pores in the outer surface was 25.3±4.3 pores/cm². A significant inverse correlation between porosity and OCC burden was found (Pearson r= -0.81, p= 0.01). Furthermore, a decrease in caiman survival with decreased pore density was observed (Pearson r= 0.73, p= 0.04). Our findings highlight another potential negative impact of current and past use of OCCs on wildlife species.

Breast cancer surveillance in patients treated by radiotherapy for Hodgkin's lymphoma.

PURPOSE: The authors evaluated the relative risk of developing radiation-induced breast cancer (BC) in women treated with radiotherapy for Hodgkin's disease (HD) and analysed the imaging features of these breast neoplasms. MATERIALS AND METHODS: We retrospectively studied 54 women who had all undergone radiotherapy between 1980 and 2010 (median age, 36.6 years). Women aged ≤30 years were screened with clinical breast examination, ultrasound (US) and, if necessary, mammography; women >30 years had clinical breast examination, US and mammography. Three women underwent magnetic resonance (MR) imaging as well. RESULTS: Mammography detected seven invasive breast cancers in 6/54 women (11.1%). Median age at diagnosis was 26.1 years for HD and 42.4 for breast cancer. Breast cancer was diagnosed following a median latent period from radiotherapy of 15.1 years. Mean radiation dose was 37.6 Gy in women who developed breast cancer and 31.3 Gy in the other women. CONCLUSIONS: In our study, women who were exposed to radiation for HD had a 6.2-fold higher risk of developing breast cancer than the general population. In consideration of the young age and high breast density, women aged ≤30 years should be monitored by US and MR imaging; women aged >30 years should be monitored by US, mammography and, when necessary, MR imaging.

Saccharomyces boulardii viability and efficacy in horses with antimicrobial-induced diarrhoea.

Saccharomyces boulardii has been successfully used in the prevention and treatment of antimicrobial-associated diarrhoea in humans. We hypothesised that a viable, dried lyophilised preparation of S boulardii would survive in the gastrointestinal tract of horses with antimicrobial-associated enterocolitis, and significantly decrease the duration of diarrhoea. Twenty-one horses, over one year of age, with antimicrobial-associated diarrhoea of up to 72 hours duration, were consecutively randomised in a controlled prospective study. The treatment group received S boulardii (25 g, orally, every 12 hours) until the cessation of clinical signs. S boulardii was successfully cultured in 58.3 per cent of treatment horses on day 3. No statistically significant differences were found in days to return to normal faecal consistency; resolution of watery diarrhoea; return to normal heart rate, respiratory rate and temperature; resolution of leucopaenia; attitude improvement; appetite improvement; and survival at discharge. This is the first study to demonstrate survival of S boulardii in horses with gastrointestinal illness. Further study of the efficacy and safety of S boulardii in horses with antimicrobial-associated diarrhoea in a larger group is warranted.

Cardiac troponin I concentrations in ponies challenged with equine influenza virus.

BACKGROUND: Myocarditis is thought to occur secondary to equine influenza virus (EIV) infections in horses, but there is a lack of published evidence. HYPOTHESIS/OBJECTIVES: We proposed that EIV challenge infection in ponies would cause myocardial damage, detectable by increases in plasma cardiac troponin I (cTnI) concentrations. ANIMALS: Twenty-nine influenza-naïve yearling ponies: 23 were part of an influenza vaccine study (11 unvaccinated and 12 vaccinated), and were challenged with 108 EID50 EIV A/eq/Kentucky/91 6 months after vaccination. Six age-matched healthy and unvaccinated ponies concurrently housed in a separate facility not exposed to influenza served as controls. METHODS: Heparinized blood was collected before and over 28 days after infection and cTnI determined. Repeated measures analysis of variance, chi-square, or clustered regression analyses were used to identify relationships between each group and cTnI. RESULTS: All EIV-infected ponies developed clinical signs and viral shedding, with the unvaccinated group displaying severe signs. One vaccinated pony and 2 unvaccinated ponies had cTnI greater than the reference range at 1 time point. At all other times, cTnI was < 0.05 ng/mL. All control ponies had normal cTnI. There were no significant associations between cTnI and either clinical signs or experimental groups. When separated into abnormal versus normal cTnI, there were no significant differences among groups. CONCLUSIONS AND CLINICAL IMPORTANCE: This study demonstrated no evidence of severe myocardial necrosis secondary to EIV challenge with 108 EID50 EIV A/eq/Kentucky/91 in these sedentary ponies, but transient increases in cTnI suggest that mild myocardial damage may occur.

Efficacy and cost-effectiveness of stereotactic vacuum-assisted core biopsy of nonpalpable breast lesions: analysis of 602 biopsies performed over 5 years.

PURPOSE: The authors sought to evaluate the diagnostic accuracy and cost-effectiveness of vacuum-assisted core biopsy (VACB) in comparison with diagnostic surgical excision for characterisation of nonpalpable breast lesions classified as Breast Imaging Reporting and Data System (BI-RADS) categories R3 and R4. MATERIALS AND METHODS: From January 2004 to December 2008, we conducted 602 stereotactic, 11-gauge, VACB procedures on 243 nonpalpable breast lesions categorised as BI-RADS R3, 346 categorised as BI-RADS R4 and 13 categorised as BI-RADS R5. We calculated the diagnostic accuracy and cost savings of VACB by subtracting the cost of the stereotactic biopsy from that of the diagnostic surgical procedure. RESULTS: A total of 56% of the lesions were benign and required no further assessment. Lesions of uncertain malignant potential (B3) (23.6%) were debated at multidisciplinary meetings, and diagnostic surgical biopsy was recommended for 83.1% of them. All malignant lesions (B4 and B5) underwent surgical excision. VACB had a sensitivity of 94.9%, specificity of 98.3% and diagnostic accuracy of 97.7%. The cost savings per VACB procedure were 464.00 euro; by obviating 335 surgical biopsies, the overall cost savings was 155,440.00 euro over 5 years. CONCLUSIONS: VACB proved to have high diagnostic accuracy for characterising abnormalities at low to intermediate risk of malignancy and obviated surgical excision in about half of the cases, allowing for considerable cost savings.

Role of sonoelastography in characterising breast nodules. Preliminary experience with 120 lesions.

PURPOSE: This study was performed to evaluate the diagnostic accuracy of sonoelastography in differentiating and characterising nodular breast lesions. MATERIALS AND METHODS: A total of 120 nodular lesions diagnosed on mammography and/or ultrasonography in 110 women (mean age 51.27 years) were evaluated with sonoelastography and classified according to elasticity score (S1-S5). Needle biopsy was performed in 104/120 cases, whereas 16/120 were sent for follow-up. Sensitivity and specificity of sonoelastography were determined by taking biopsy findings as the gold standard. RESULTS: Biopsy yielded the following results: 66 benign, three equivocal and 35 malignant lesions. Sensitivity and specificity of sonoelastography were, respectively, 88.5% and 92.7%. All nodules with an elasticity score of 5 were malignant, and those with a score

Role of axillary ultrasound in the preoperative diagnosis of lymph node metastases in patients affected by breast carcinoma.

PURPOSE: This study was conducted to evaluate the diagnostic accuracy of axillary ultrasound (US) alone or in combination with fine-needle-aspiration cytology (FNAC) in patients with breast carcinoma, in comparison with the final histological examination (sentinel node biopsy and/or axillary dissection). MATERIALS AND METHODS: Between January 2005 and June 2008, we evaluated 427 breast cancer patients with axillary US. The findings were classified according to the following criteria: hilum and cortex morphology, ratio between longitudinal and transverse diameter and ratio between hilar and longitudinal diameter of the lymph node. Patients with breast lesions

Percutaneous vertebroplasty: the follow-up.

PURPOSE: This article reports on our experience treating vertebral fractures with percutaneous vertebroplasty. A clinical and imaging follow-up designed to identify the early (especially pulmonary embolism of bone cement) and late complications of the technique is proposed. MATERIAL AND METHODS: On the basis of the current guidelines, 101 patients were selected: 64 osteoporotic and 37 neoplastic. A total of 173 vertebrae were treated. Procedures were performed with both computed tomography and fluoroscopic guidance. Residual pain was evaluated with a visual analogue scale score immediately after vertebroplasty and 1, 15, 30, 90, 180 and 270 days later. Spine and chest radiographs were obtained 24 h after vertebroplasty; spine radiography was repeated 30 days later. RESULTS: Therapeutic success was obtained in 88% of osteoporotic patients and in 84% of neoplastic patients. Pulmonary cement emboli were identified in four patients, all of whom were asymptomatic. CONCLUSIONS: Percutaneous vertebroplasty is a safe and effective technique for the treatment of osteoporotic and neoplastic vertebral fractures. Clinical and imaging followup allows effective patient monitoring and early detection of possible complications.

Endurance exercise is associated with increased plasma cardiac troponin I in horses.

REASON FOR PERFORMING STUDY: Information is lacking regarding the influence of long distance exercise on the systemic concentration of cardiac troponin I (cTnI) in horses. OBJECTIVES: To determine if the concentration of cTnI in horses competing in 80 and 160 km endurance races increases with exercise duration and if cTnI concentrations can be correlated with performance data. METHODS: Blood samples for the measurement of cTnI and 3 min electrocardiogram recordings were obtained from horses prior to, during and after completion of 80 and 160 km endurance races at 3 ride sites during the 2004 and 2005 American Endurance Ride Conference competition seasons. RESULTS: Full data sets were obtained from 100 of the 118 horses. Endurance exercise was associated with a significant increase in cTnI over baseline in both distance groups. Failure to finish competition (poor performance) was also associated with an increased cTnI concentration over baseline at the time of elimination when data from both distances were combined. Other than one horse that developed paroxysmal atrial fibrillation, no arrhythmias were noted on the 3 minute ECG recordings that were obtained after endurance exercise in either distance group. CONCLUSIONS: Systemic concentrations of cTnI increase in endurance horses competing in both 80 and 160 km distances. Although final cTnI concentrations were significantly increased over their baseline values in horses that failed to finish competition, the degree of increase was not greater than the increase over baseline seen in the horses that successfully completed competition. The clinical significance of increased cTnI in exercising horses could not be ascertained from the results of this study. POTENTIAL RELEVANCE: These data indicate that cardiac stress may occur in horses associated with endurance exercise. Future studies utilising echocardiograpy to assess cardiac function in horses with increased cTnI are warranted.

Right ventricular pressure dynamics and stress echocardiography in pharmacological and exercise stress testing.

REASONS FOR PERFORMING STUDY: There is interest in using pharmacological stress testing (PST) as a substitute for exercise stress testing (EST) to evaluate cardiac function in horses. OBJECTIVES: To compare the effect of PST and EST on right ventricular pressure dynamics and stress echocardiography. METHODS: Five horses completed a PST and EST in a randomised crossover design. High fidelity pressure transducers were placed in the right ventricle. Continuous pressure signals were digitally collected and stored, and dP/dtmax, dP/dtmin and tau calculated from these measurements. ECGs were recorded continuously for 20 h. Echocardiography was performed prior to EST and PST, during and after PST, and immediately post EST. Plasma cardiac troponin I concentrations were measured pre- and 3-4 h post stress testing. For PST, 5 microg/kg bwt glycopyrrolate i.v. followed after 10 min by 5 microg/kg bwt/min dobutamine infusion over 10 min was given. EST consisted of a 2 min gallop at 110% speed required to elicit VO2max. RESULTS: Both EST and PST resulted in a significant increase in right-ventricular dP/dtmax and dP/dtmin over baseline (P<0.05) and a significant decrease in tau compared with baseline (P<0.05). EST dP/dtmax and dP/dtmin were significantly greater than PST dP/dtmax and dP/dtmin (P<0.05) and EST tau was significantly less than PST tau (P<0.05). Two minutes post EST and 5 min post PST dP/dtmax were not significantly different, but were significantly less than end-EST and during PST. Tau was also not significantly different between post EST and post PST, but was significantly decreased end-EST compared with during PST. FS were not significantly different between PST and post EST, but during PST and post EST all FS were significantly higher than baseline. Cardiac troponin I concentrations were significantly elevated post PST and were greater than post EST. The clinical relevance of this is unknown. CONCLUSIONS: PST had a similar, although less marked effect on the cardiac parameters related to right-ventricular pressure dynamics and a similar effect on echocardiography as exercise stress testing. POTENTIAL RELEVANCE: PST deserves further evaluation in normal horses and those with cardiac disease, and may be complementary to EST to better identify exercise-induced cardiac dysfunction.

Correlations between exercising arterial blood gas values, tracheal wash findings and upper respiratory tract abnormalities in horses presented for poor performance.

REASONS FOR PERFORMING STUDY: There are limited data on the correlations between arterial blood gas (ABG) values, tracheal wash (TW) cytology and upper respiratory tract (URT) abnormalities. OBJECTIVES: To identify horses with abnormal exercising ABG, and compare the proportions of horses with abnormal ABG and TW cytology, mucus or URT dysfunction with those with normal ABG results and abnormal TW cytology, mucus or URT dysfunction. METHODS: Medical records of 813 horses presenting to the treadmill facility that had a complete treadmill examination, including ABG analysis, TW and URT endoscopy were selected. Diagnoses, ABG results, TW cytology and URT endoscopy were compared. RESULTS: Two hundred and eleven horses met the study criteria of a complete treadmill examination and could have ABG evaluated. There were no significant differences in the age distribution of horses having normal and abnormal ABG or upper respiratory tract (URT) examinations. There was a significantly higher percentage of geldings with abnormal ABG analysis. In the horses with abnormal URT examinations, there were no differences in the proportion of horses having mucus vs. no mucus. However, in the horses with normal URT, there were a higher percentage of horses with visible mucus in the group with abnormal ABG analysis. The majority of horses had abnormal TW cytology and evidence of prior EIPH, with no differences in proportions between the groups. CONCLUSIONS: Because such a large percentage of horses had evidence of inflammation and/or evidence of prior EIPH on TW cytology, it was not possible to determine the effect of these findings on gas exchange. Mucus was present in a larger percentage of cases with abnormal ABG analysis and normal URT examinations, suggesting that the presence of mucus may affect gas exchange. Standardbreds may be more likely to have abnormal gas exchange than Thoroughbreds. A larger number of horses is needed to determine the significance of these findings. POTENTIAL RELEVANCE: Abnormal TW cytology and endoscopic visualised mucus may contribute to impairment of gas exchange, but they do not specifically predict abnormal ABG analysis.

Dynamic pharyngeal collapse in racehorses.

REASON FOR PERFORMING STUDY: Dynamic pharyngeal collapse (PC) is a condition seen in racehorses that can be career-ending. OBJECTIVES: To characterise and grade PC and describe the effects of PC on athletic performance. METHODS: Medical records were reviewed for 828 horses, of which 49 (6%) records were identified as horses with a primary diagnosis of PC. Tapes of video-endoscopy of the pharynx during exercise were reviewed. Each video recording was assigned a grade (0-4) reflecting the degree of PC and a classification for severity of upper airway obstruction. Earnings per race prior to diagnosis of PC were compared to earnings per race after diagnosis of PC for all horses, as well as performance index (PI). Available exercising arterial blood gases were reviewed for horses with PC. RESULTS: There were 35 (80%) Thoroughbreds (TB), and 9 (20%) Standardbreds (STD). 32 (73%) had a history of making an upper respiratory noise. 4 (9%) grade 1 PC, 8 (18%) grade 2 PC, 26 (59%) grade 3 PC, and 6 (14%) grade 4 PC. Seven (16%) horses were classified as mild PC, 18 (41%) as low-moderate PC, 14 (32%) as high-moderate PC, and 5 (11%) as severe PC. Of 30 horses 11 had abnormally decreased PaO2 and 8 horses had abnormally elevated PaCO2. A significant decrease was found in earnings per race prediagnosis when compared to post diagnosis earnings per race in horses > or =4 years of age (P = 0.003). A significant decrease was also observed for earnings per race prediagnosis when compared to post diagnosis earnings per race in horses with grade 3 PC (P = 0.03) No significant differences were observed in PI before or after diagnosis of PC. CONCLUSIONS: There was a trend for PC to be observed in more TB than STD, and more males than females compared to the general hospital population. Horses with PC significant had decreases in arterial oxygenation. Racing records after a diagnosis of PC in all horses > or = 4 years of age suggesting that older horses have a guarded prognosis for continued success. POTENTIAL RELEVANCE: This study provides a classification system for dynamic pharyngeal collapse and suggests that older racehorses (> or = 4 years of age) diagnosed with PC and all horses with grade 3 PC have a poor prognosis for return to previous level of performance.

Idiopathic granulomatous pneumonia in seven horses.

The history, clinical signs and pathological findings in seven adult horses with histologically confirmed idiopathic granulomatous disease, primarily of the lungs, are reviewed. They ranged in age from eight to 21 years, five were geldings and two were females, they belonged to five breeds and there were no seasonal or geographical associations. The primary clinical signs were chronic weight loss, exercise intolerance and respiratory distress which did not respond to conventional treatment. The most consistent physical findings were depression, anorexia, tachycardia, tachypnoea and adventitious lung sounds. Thoracic radiographs revealed a diffuse, structured, nodular, interstitial pulmonary pattern in each horse. Haematological measurements suggested a chronic inflammatory process and the cytology of transtracheal washes was consistent with a mild suppurative inflammation. Idiopathic granulomatous pneumonia was confirmed histologically in each of the horses, either postmortem or by a lung biopsy. The horses responded poorly to medical treatment and only one of three treated horses is still alive.

Collagen remodelling in the guinea-pig uterine cervix at term is associated with a decrease in progesterone receptor expression.

In human and guinea-pig parturition, progesterone withdrawal and estrogen action are not mediated by changes in their circulating levels. Instead, these events might be promoted by changes in the responsiveness of the uterus and cervix to progesterone and estrogen via changes in their receptors. In this study, the guinea-pig model was used to investigate whether high levels of progesterone and estrogen at term are associated with regional changes in PR and ERalpha levels in uterus and cervix. PR and ERalpha profiles were established in both subepithelium and the muscular layer of the cervix and the lower uterine horns during pregnancy, parturition and postpartum; while collagen remodelling was measured in the subepithelium. Our data showed that collagen remodelling involved in cervical ripening is temporally and spatially associated with a decrease in PR, whereas high expression of ERalpha is observed. This association was found in the subepithelium of the cervical tissue but not in the same region of the uterus. The muscular region of the cervix and uterus also present a transiently decreased expression of PR while ERalpha levels remain high. Thus, the present results indicate that, before parturition, diminished responsiveness of the cervix to progesterone might be caused by a decrease in PR levels and that this may be the mechanism of functional progesterone withdrawal. The guinea-pig was further validated as an animal model for human parturition studies.