[Early and later intrahepatic cholestasis of pregnancy (ICP): Study of adverse pregnancy outcomes]. / Cholestases intrahepatiques gravidiques (CIG) précoces et tardives : étude des complications materno-fœtales.

OBJECTIVE: To compare the risk for adverse pregnancy and fetal outcomes in early or late-onset intrahepatic cholestasis of pregnancy (ICP). METHODS: In a retrospective and unicentric analysis, data were collected for all women with ICP (serum bile acid level over 8mol/L) between June 1, 2008 and January 1, 2015. Patients were divided in early-onset ICP (pregnancy duration at diagnosis<33 weeks) and late-onset ICP (pregnancy duration at diagnosis≥33 weeks). The frequency of adverse pregnancy and fetal outcomes was assessed. RESULTS: Among 138 eligible women, 40 were in the early-onset group and 98 in the late-onset group. Adverse pregnancy or fetal outcomes affected significantly more patients in early-onset ICP group (45% versus 17.3%, P<0.05). Threatened preterm birth (30% versus 10.0%, P<0.05) was significantly increased in early-onset ICP group. Prematurity was higher in early-onset group (40.0% versus 28.0%, P=0.23). Early-onset and severe ICP were not significantly linked (P=0.16). CONCLUSION: Early-onset ICP diagnosed before 33 Weeks is associated with adverse pregnancy outcomes, particularly threatened preterm birth.

Thoracic aortic rupture in horses.

The aorta can rupture at the aortic root or aortic arch. In most breeds, the aortic root is the likely site and rupture leads to aortocardiac fistula with communication between the aorta and the right atrium, right ventricle and/or the interventricular septum. There is a high prevalence of aortic rupture in young Friesian horses and rupture occurs at the aortic arch with pseudoaneurysm and potentially aortopulmonary fistulation. Echocardiographic and post-mortem techniques must be adapted to identify aortic arch rupture that is not generally identified with standard approaches. Given the narrow genetic base of the Friesian breed and the significant differences found in extracellular matrix composition and metabolism between Friesians and Warmbloods, genetic factors are likely to contribute to the condition in the Friesian breed.

Differences in extracellular matrix proteins between Friesian horses with aortic rupture, unaffected Friesians and Warmblood horses.

BACKGROUND: Unlike in Warmblood horses, aortic rupture is quite common in Friesian horses, in which a hereditary trait is suspected. The aortic connective tissue in affected Friesians shows histological changes such as medial necrosis, elastic fibre fragmentation, mucoid material accumulation and fibrosis with aberrant collagen morphology. However, ultrastructural examination of the collagen fibres of the mid-thoracic aorta has been inconclusive in further elucidating the pathogenesis of the disease. OBJECTIVES: To assess several extracellular matrix (ECM) components biochemically in order to explore a possible underlying breed-related systemic ECM defect in Friesians with aortic rupture. STUDY DESIGN: Cadaver study. METHODS: Tissues from affected Friesians (n = 18), unaffected Friesians (n = 10) and Warmblood horses (n = 30) were compared. Samples were taken from the thoracic aorta at the level of the rupture site, from two locations caudal to the rupture and from the deep digital flexor tendon. Total collagen content, post-translational modifications of collagen formation including lysine hydroxylation, and hydroxylysylpyridinoline (HP), lysylpyridinoline (LP) and pyrrole cross-links were analysed. Additionally, elastin cross-links, glycosaminoglycan content and matrix metalloproteinase (MMP) activity were assessed. RESULTS: Significantly increased MMP activity and increased LP and HP cross-linking, lysine hydroxylation and elastin cross-linking were found at the site of rupture in affected Friesians. These changes may reflect processes involved in healing and aneurysm formation. Unaffected Friesians had less lysine hydroxylation and pyrrole cross-linking within the tendons compared with Warmblood horses. No differences in the matrix of the aorta were found between normal Warmbloods and Friesian horses. MAIN LIMITATIONS: Small sample size. CONCLUSIONS: The differences in collagen parameters in tendon tissue may reflect differences in connective tissue metabolism between Friesians and Warmblood horses.

Friesian horses as a possible model for human acquired aortopulmonary fistulation.

BACKGROUND: Acquired aortopulmonary fistulation is a rare condition in humans. It usually results as a late complication of a true or pseudoaneurysm of the thoracic aorta. It is most commonly associated with trauma or surgery, less commonly with atherosclerosis, inflammation, hypertension or Marfan's syndrome. Aortopulmonary fistulation is also seen as a rare complication of acute aortic dissection. On rare occasions, acquired aortopulmonary fistulation is reported in aged patients without any of the above mentioned triggering factors. Thus, these cases should be considered as idiopathic aortopulmonary fistulation. Clearly, the pathogenesis of this condition is not yet completely understood. Friesian horses are highly inbred and are affected by several genetic conditions. Rupture of the thoracic aorta has a relatively high prevalence in Friesian horses and is often characterized by the formation of a pseudoaneurysm with subsequent fistulation into the pulmonary artery. Affected animals may survive for several weeks to months. FINDINGS: Here we performed vascular casting in three affected Friesian horses. In all three cases, an aortic rupture at the caudoventral side of the aorta was connected with a rupture of the main pulmonary artery just proximal to its bifurcation. CONCLUSIONS: Affected Friesians show a consistent location and configuration of the aortic rupture site, very similar to the human condition and therefore could act as a spontaneous model to study this disease.

[Traumatic optic neuropathy: Report of 8 cases and review of the literature]. / Neuropathies optiques post-traumatiques : à propos de 8 cas et revue de la littérature.

Although underestimated, visual involvement is among the most frequent neurological complications of head trauma. There is no consensus in the management of these patients and visual recovery is uncertain. The goal of our study is to describe the clinical presentation and the clinical course of traumatic optic neuropathy in patients with head or maxillo-facial trauma. The clinical records of 8 patients, treated from November 2007 to March 2012, were reviewed in the department of ophthalmology (visual testing) of the university regional medical center in Lille. The most frequent cause of injury was traffic accidents. Unilateral optic neuropathy was observed in 6 cases, and bilateral in two cases, for a total of 10 eyes. Eight presented a significant visual loss<6/12. Improvement of visual acuity was achieved in 5 cases to 9/10 distance acuity without any medical or surgical treatment. One patient required surgical decompression, without improvement of visual acuity, and with persistent oculomotor disturbance and unreactive mydriasis. Traumatic optic neuropathy can cause profound visual acuity loss, especially if it is already significantly decreased on presentation.

Morphometric Properties of the Thoracic Aorta of Warmblood and Friesian Horses with and without Aortic Rupture.

Rupture of the aorta is much more common in Friesians compared with other breeds of horse. Rupture always occurs adjacent to the scar of the ligamentum arteriosum. Previous histological examination of ruptured aortic walls suggested the presence of an underlying connective tissue disorder. Therefore, the aim of the present study was to compare the structural characteristics of the tunica media of the mid-thoracic aorta, distant to the lesion, in warmblood and Friesian horses with and without thoracic aortic rupture. In unaffected Friesian horses, the thickness of the tunica media, as well as the percentage area comprised of collagen type I, were significantly higher compared with the warmblood horses, supporting the hypothesis of a primary collagen disorder in the Friesian horse breed. However, in the tunica media of the affected Friesian horses there was no significant wall thickening. Moreover, the percentage area comprised of elastin was significantly lower, while the percentage area comprised of smooth muscle was higher, compared with unaffected Friesian and warmblood horses. These lesions are suggestive of an additional mild elastin deficiency with compensatory smooth muscle cell hypertrophy in affected Friesians.

Clinical Research Abstracts of the British Equine Veterinary Association Congress 2015.

REASONS FOR PERFORMING STUDY: Selective 5-HT4 receptor agonists such as prucalopride are used as human prokinetics, since activation of 5-HT4 receptors on intestinal cholinergic neurons facilitates acetylcholine release. 5-HT4 receptors, linked to adenylyl cyclase, act via generation of cAMP. None of the 4 in vitro studies on 5-HT in horses provided evidence for neuronal 5-HT4 receptors, but none used the protocol as described in human studies [1-4]. OBJECTIVES: To investigate whether functional 5-HT4 receptors are present in the equine small intestine. STUDY DESIGN AND METHODS: In vitro organ bath set up, applying electrical field stimulation (EFS) in longitudinal and circular smooth muscle strips. RESULTS: Results were similar in both muscle layers. In the presence of 0.3 mmol/l NG-Nitro-L-arginine methyl ester and 0.3 µmol/l apamine, excluding effects of the inhibitory transmitters NO and ATP, EFS induced voltage-dependent on-contractions; these were neurogenic as they were abolished by 3 µmol/l tetrodotoxin. At a voltage inducing 50% of the maximal amplitude, the submaximal EFS-induced contractions were cholinergic as atropine (1 µmol/l) abolished them. Prucalopride (0.3 µmol/l) did not increase the amplitude of these submaximal EFS-induced contractions. Even in the presence of the nonselective phosphodiesterase inhibitor IBMX, previously shown to enhance the effect of neuronal 5-HT4 receptors by inhibiting breakdown of their 2nd messenger cAMP [5], prucalopride (3 µmol/l) had no influence. Also 5-HT (10 µmol/l), a full agonist at 5-HT4 receptors, tested in the presence of methysergide and granisetron to exclude interaction with other 5-HT receptor subtypes, did not enhance EFS-induced submaximal contractions. CONCLUSIONS: There is no evidence for presence of 5-HT4 receptors on the cholinergic neurons of the equine small intestine. These results question the application of 5-HT4 prokinetic drugs in horses. Ethical animal research: Research ethics committee oversight not currently required by this conference: the study was performed on material collected at an abattoir. Sources of funding: None. Competing interests: None declared.

Esophageal Dysfunction in Friesian Horses: Morphological Features.

Megaesophagus appears to be more common in Friesian horses than in other breeds. A prevalence of approximately 2% was observed among Friesian horses presented to the Wolvega Equine Clinic and the Utrecht University Equine Clinic. In this study, morphologic changes in the esophagi of Friesian horses with megaesophagus were compared with those of 6 control horses. Of 18 horses with clinically observed megaesophagus, only 12 animals had esophageal dilation at necropsy, usually involving the thoracic portion. Muscular hypertrophy of the distal esophagus was present in only one-third of the affected horses, indicating that this change is not the most relevant cause of megaesophagus in Friesians. Increased deposition of clumped and disorganized collagen was present in these clinically affected horses mainly in the non-dilated portion of the esophagus. At necropsy, a decrease in neural elements and elastin was present principally in horses with megaesophagus. Mild degeneration and necrosis of the tunica muscularis along the entire length of the esophagus were present in clinically affected horses and encountered only rarely in control animals. There were no significant differences among affected and control horses with respect to inflammation, mineralization, or the number of cells of Cajal. The increased occurrence of megaesophagus in the Friesian breed compared with other horse breeds, together with the presence of abnormal collagen in very young foals, supports the hypothesis that megaesophagus is hereditary in Friesians.

[Uterine artery pseudoaneurysm: an unusual cause of postpartum hemorrhage]. / Le pseudo-anévrysme de l'artère utérine: une cause parfois ignorée d'hémorragie secondaire du post-partum.

Uterine artery pseudoaneurysm is a rare complication of cesarean section. It can lead to severe postpartum hemorrhage. We report three cases of pseudoaneurysm diagnosed late after cesarean delivery, one followed by hemorrhagic shock. Ultrasound may point to the diagnosis, but arteriography of uterine arteries is decisive for the diagnosis. Selective artery embolization is recommended for treatment. Main advantages are complete occlusion of the pseudoaneurysm and fertility preservation.

[Antiphospholipid syndrome and pregnancy: Obstetrical prognosis according to the type of APS]. / Syndrome des anticorps antiphospholipides et grossesse : pronostic obstétrical selon le type de SAPL.

OBJECTIVE: The objective of our study was to compare treatment-based obstetrical outcomes in women with either thrombotic or obstetrical antiphospholipid syndrome (APS). MATERIALS AND METHODS: This was a historical cohort study conducted between 1998 and 2009 in 23 patients who had a total of 83 pregnancies. The syndrome was diagnosed using the 2006 Sapporo criteria. RESULTS: Thirty-one of these 83 pregnancies were valid before the diagnosis was made. A live infant was born in 22% of them, the infant being small for gestational age in 26% of cases. The fetus died in utero in a further 26% of cases. Pregnancies were subdivided into 2 groups depending on whether the initial event leading to APS diagnosis was obstetrical or thrombotic. Treatment (aspirin and low molecular weight heparin) was based on this classification: the latter was given in a curative dose for thrombotic events, in a preventive dose for obstetrical events. No fetal loss was observed when treatment was administered according to the protocol. Nevertheless, 20% of the pregnancies with obstetrical APS were complicated by smallness for gestational age and only 38% of the infants were live births. More than 87% of the thrombotic forms treated were free of complications and led to birth of a living child. CONCLUSION: Appropriate treatment appears to improve the prognosis for pregnancies in patients with APS. These patients are nevertheless at increased risk of an obstetrical event and require close monitoring, especially in obstetrical manifestations, which appear to have a poorer prognosis. Multidisciplinary follow-up by an experienced team is essential.

Thoracic aortic rupture and aortopulmonary fistulation in the Friesian horse: histomorphologic characterization.

Aortic rupture in horses is a rare condition. Although it is relatively common in the Friesian breed, only limited histopathologic information is available. Twenty Friesian horses (1-10 years old) were diagnosed with aortic rupture by postmortem examination. Ruptured aortic walls were analyzed with histology and immunohistochemistry. Based on the histologic and immunohistochemical findings, these cases were divided into 3 groups: acute (n = 4, 20%), subacute (n = 8, 40%), and chronic (n = 8, 40%). Features common to samples from horses in all groups included accumulation of mucoid material; disorganization and fragmentation of the elastic laminae; aortic medial smooth muscle hypertrophy; and medial necrosis of varying degrees, ranging from mild and patchy in the acute cases to severe midzonal necrosis in the chronic cases. Inflammation, most likely secondary to medial necrosis, varied from predominantly neutrophilic infiltrates in the media and periadventitial tissue in the acute group to the presence of mainly hemosiderophages in the periadventitial tissue in the chronic group. Medial fibrosis with aberrant collagen morphology was seen in the subacute group and, more commonly, in the chronic group. Only minimal changes were seen in the aortic vasa vasorum. Smooth muscle hypertrophy and accumulation of mucoid material were not related to the age of the lesions. The findings of this study suggest that a connective tissue disorder affecting elastin or collagen in the aortic media is potentially the underlying cause of aortic rupture in Friesian horses.

Aortic rupture and aorto-pulmonary fistulation in the Friesian horse: characterisation of the clinical and gross post mortem findings in 24 cases.

REASONS FOR PERFORMING STUDY: In horses, aortic sinus of Valsalva aneurysms or tears in the aortic root are well-recognised conditions in breeding stallions, often leading to sudden death. A more uncommon form of aortic rupture, located proximal to the ligamentum arteriosum has been reported in 3 Friesian horses. OBJECTIVES: The purpose of this study was to phenotypically characterise aortic rupture and aorto-pulmonary fistulation in Friesian horses in terms of clinical and post mortem data based on 24 cases. METHODS: Friesian horses that were diagnosed with aortic rupture and aorto-pulmonary fistulation over a period of 13 years (1997-2010) at the Department of Equine Sciences of Utrecht University (n = 15) and Wolvega Equine Hospital (n = 9), were included in this study. Case history, results of clinical examination and gross post mortem findings were screened and analysed. RESULTS: Some cases were found dead without prior symptoms, but in several cases signs such as recurrent colic, peripheral oedema and sustained tachycardia were present for several weeks prior to cardiac failure. Clinical examination during hospitalisation revealed increased rectal temperature, peripheral oedema and increased jugular pulse with a bounding arterial pulse. In the majority of horses an aortic rupture of the aortic arch near the ligamentum arteriosum, concurrent with a circumferential cuff of perivascular haemorrhage and aorto-pulmonary fistulation, was found at post mortem examination. CONCLUSIONS: Aorto-pulmonary fistulation in conjunction with aortic rupture is more common in Friesians than previously estimated. In some cases findings demonstrate a progressive pathology rather than acute cardiac failure and sudden death. An appropriate approach is necessary during post mortem examination of the heart in order not to overlook the diagnosis. POTENTIAL RELEVANCE: Equine practitioners should realise that in Friesian horses presented with a history of recurrent false colic, coughing, sustained tachycardia and/or peripheral oedema, aortic rupture and aorto-pulmonary fistulation should be included in the differential diagnosis.

Morphological changes in the small intestinal smooth muscle layers of horses suffering from small intestinal strangulation. Is there a basis for predisposition for reduced contractility?

REASONS FOR PERFORMING STUDY: Intestinal strangulation often leads to enterectomy after which ileus can develop. This has prompted research to look into possible pathophysiological processes triggering equine ileus. However, morphological changes of the small intestinal smooth muscle in relation to equine colic have not yet been studied. OBJECTIVES: The presence of some smooth muscle proteins was morphologically assessed and quantified in control and colic horses. In addition, the up- or down-regulation of heat shock proteins (HSP20 and HSP27) influencing the contractility of smooth muscles was studied. METHODS: Cranial resection margins of 18 strangulated small intestinal samples were collected. Small intestinal control samples were collected from 11 horses subjected to euthanasia for other than gastrointestinal-related reasons. Formaldehyde-fixed tissue was paraffin-embedded and processed for conventional staining and immunohistochemistry. Snap-frozen full-thickness biopsies were collected for western blot analyses. RESULTS: Evaluating the muscle layer microscopically, colic samples showed significantly more signs of degradation than controls (P = 0.026) of which vacuolar degeneration was most prominent (P = 0.009). In colic samples, myosin protein levels were decreased (P = 0.022) whereas desmin (P = 0.049) and HSP20 protein levels (P = 0.005) were elevated. CONCLUSIONS: In colic samples, microscopic lesions at the level of the muscle layer indicate a stress response. In addition, modified amounts of structural proteins such as myosin and desmin together with increased HSP20 levels could perhaps provide a basis for explaining the malfunctioning of the intestinal muscle layer. POTENTIAL RELEVANCE: Post operative ileus, following small intestinal strangulation and resection, could be related in part to a dysfunctional muscle layer. In addition to microscopic signs of degeneration, myosin and HSP20 were affected. Pharmacological interventions might alter HSP20 expressions and thus serve a protective effect.

The use of slaughterhouse-obtained small intestinal tissue as control material in histological studies should be applied with prudence.

This study aimed to evaluate the reliability of slaughterhouse-obtained small intestinal tissue as control material in equine colic research where molecular stress responses in small intestinal tissue are investigated. For this purpose, small intestinal samples from colic horses were collected during surgery or immediately after euthanasia at the oral border of strangulation resection sites and routinely processed for histopathology (i.c. rinsed with 4°C Krebs' solution, fixated overnight with 4% neutral buffered formaldehyde (FH) at room temperature). Control samples consisted of pieces of mid-jejunum, collected at the slaughterhouse and routinely processed for histopathology under 4 different conditions. The 4 conditions differed with regard to incubation and fixation temperature and whether or not oxygenated Krebs' solution was used. Histological scoring revealed that slaughterhouse samples had a higher mean lesion score (P<0.001) than colic samples. In addition, more slaughterhouse samples had a higher mean inflammation score than colic samples (P=0.001). The inflammatory cells in the small intestine consisted mostly of eosinophils and as such were very suggestive for parasitic infestation. Hypoxia-inducible factor-1α (HIF1α) nuclear immunoreactivity was more pronounced in slaughterhouse tissue, probably as a result of the delay between slaughter and sampling (P=0.034). The histopathological score (P=0.291), the inflammation score (P=0.248) and the HIF1α nuclear immunoreactivity (P=0.538) did not differ between the different collection protocols. It is concluded that slaughterhouse-obtained small intestinal tissue shows distinct alterations and that its use as control tissue when evaluating molecular stress responses should be applied with prudence.

Morphological data indicate a stress response at the oral border of strangulated small intestine in horses.

Strangulation colic often leads to surgery. We aimed to document the molecular response in the non-resected intestine in these horses using quantitative Western blot analysis, and immunohistochemistry. The expression of hypoxia-inducible factor 1-alpha (HIF1α) was investigated together with two molecular pathways initiated after protein destruction: proteasome degradation via ubiquitin chain formation and protein restoration via molecular chaperones such as inducible heat shock protein 70 (HSP70). In addition, the expression of c-fos and c-jun could indicate an early proinflammatory response. Ubiquitin, HSP70, c-jun and c-fos protein levels did not differ between the control and colic samples nor were they related to the clinical outcome in case of strangulation colic. However, the immunohistochemical distribution of several of these proteins (ubiquitin, HSP70 and c-jun) differed significantly between colic and control samples. The elevated presence of ubiquitin in the enterocytes' nucleus, of HSP70 in the smooth muscle cells' nucleus and of c-jun in enteric neurons suggest protective and degenerative pathways are activated in the apparently healthy non-resected tissue in case of strangulation obstruction, perhaps providing a molecular and morphological basis for the development of complications like post-operative ileus.

Risk factors for equine postoperative ileus and effectiveness of prophylactic lidocaine.

BACKGROUND: Postoperative ileus (POI) is a frequent and often fatal complication of colic surgery. Reliably effective treatments are not available. OBJECTIVES: To determine risk factors and protective factors associated with POI, and to assess the effect of lidocaine IV on short-term survival. ANIMALS: One hundred and twenty-six horses that underwent small intestinal colic surgery and that survived for at least 24 hours postoperatively. METHODS: Retrospective cross-sectional study. The association of 31 pre-, intra-, and postoperative variables with POI and the association of lidocaine treatment with short-term survival were investigated. Associations were evaluated with univariable logistic regression models, followed by multivariable analysis. RESULTS: Significant associations of high heart rate (odds ratio [OR] = 1.05, 95% confidence interval [CI] 1.03-1.08), the presence of more than 8 L of reflux at admission (OR = 3.02, 95% CI 1.13-8.02) and the performance of a small intestinal resection (OR = 2.46, 95% CI 1.15-5.27) with an increased probability of POI were demonstrated. Prophylactic lidocaine treatment was significantly associated with a reduced incidence of POI (OR = 0.25, 95% CI 0.11-0.56). Lidocaine treatment was also significantly associated with enhanced short-term survival (OR = 0.30, 95% CI 0.09-0.98). CONCLUSIONS AND CLINICAL IMPORTANCE: The variables associated with an increased risk of POI can be useful in identifying horses at risk of POI and in providing a more accurate prognosis. The results are supportive for lidocaine IV as an effective prokinetic treatment after small intestinal colic surgery.