Histamine H3 receptor antagonists ameliorate attention deficit/hyperactivity disorder-like behavioral changes caused by neonatal habenula lesion.

A partial agonist and a full antagonist of the histamine H3 receptor have been suggested to have therapeutic effects on cognitive deficits in psychiatric disorders. We have previously shown that neonatal habenula lesion (NHL) induces behavioral deficits that resemble the symptoms of attention deficit/hyperactivity disorder (ADHD). In this study, we examined the effects of three H3 antagonists on ADHD-like behavioral changes caused by NHL in rats. Behavioral tests and administration of the H3 receptor antagonists were performed in juvenile rats with NHL. H3 antagonist administration to juvenile rats dose dependently improved NHL-induced hyperlocomotion, impulsive behavior, and attention deficit. These results suggest that histamine H3 antagonists may be used as alternative therapeutic drugs for the treatment of ADHD.

Foal Fractures: Osteochondral Fragmentation, Proximal Sesamoid Bone Fractures/Sesamoiditis, and Distal Phalanx Fractures.

Foals are susceptible to many of the same types of fractures as adult horses, often secondary to external sources of trauma. In addition, some types of fractures are specific to foals and occur routinely in horses under 1 year of age. These foal-specific fractures may be due to the unique musculoskeletal properties of the developing animal and may present with distinct clinical signs. Treatment plans and prognoses are tailored specifically to young animals. Common fractures not affecting the long bones in foals are discussed in this article, including osteochondral fragmentation, proximal sesamoid bone fractures/sesamoiditis, and distal phalanx fractures.

Physeal Fractures in Foals.

Physeal fractures are common musculoskeletal injuries in foals and should be included as a differential diagnosis for the lame or nonweightbearing foal. Careful evaluation of the patient, including precise radiographic assessment, is paramount in determining the options for treatment. Prognosis mostly depends on the patient's age, weight, and fracture location and configuration.

Diagnosis and Treatment Considerations for Nonphyseal Long Bone Fractures in the Foal.

Many long bone fractures that are not considered repairable in the adult horse are repairable in the foal. This is largely because of reduced patient size and more rapid healing in the foal. When there is no articular communication, the long-term prognosis for athletic function can be very good. Emergency care and transport of the foal with a long bone fracture is different than the adult.

Trauma as a Cause for Hepatopathy in Newborn Göttingen Minipigs.

Routine husbandry procedures during animal toxicity studies can result in incidental pathological changes. We report on trauma-induced hepatopathy in newborn Göttingen minipigs. Sixty-four neonatal minipigs were allocated to 13- and 26-week treatment arms. There was a 4-week recovery period for both arms. The animals were divided into 2 treatment groups and a vehicle group and were dosed 3 times daily by direct oral administration using a syringe. During the feeding procedure in the first weeks, the animals had to be handled firmly. After 13 weeks, randomly distributed foci of degeneration/necrosis and focal congestion and/or hemorrhage were found in the livers of several animals from all groups. Reduced incidence and severity were evident in the recovery phase, and the lesions were absent after 26 weeks. These changes were considered as related to the manual handling of the animals. Knowledge of these findings is crucial for interpretation of studies utilizing newborn minipigs.

IMAGING DIAGNOSIS - USE OF MULTIPHASE COMPUTED TOMOGRAPHIC UROGRAPHY IN THE DIAGNOSIS OF URETERAL TEAR IN A 6-DAY-OLD FOAL.

A 6-day-old foal was evaluated for depression and inappetence. After initial stabilization, the filly developed a hypochloremic metabolic alkalosis and persistent hypercreatinemia. Abdominal ultrasound revealed fluid accumulation around the left kidney and a well-defined rounded fluid filled structure dorsal to the urinary bladder. Computed tomography revealed a partial tear of the left ureter with distension of the retroperitoneal membrane. Exploratory celiotomy was performed to allow left kidney nephrectomy. At 6 months follow-up, the filly was growing normally without complications. Ultrasound and CT imaging in this case provided an accurate diagnosis and a presurgical aid to select the appropriate therapeutic approach.

Effectiveness of a nonpenetrating captive bolt for euthanasia of 3 kg to 9 kg pigs.

The objective of this study was to determine the effectiveness of a nonpenetrating captive bolt, Zephyr-E, for euthanasia of suckling and weaned pigs from 3 to 9 kg (5-49 d of age) using signs of insensibility and death as well as postmortem assessment of traumatic brain injury (TBI). The Zephyr-E was used by 15 stock people to euthanize 150 compromised pigs from 4 farrowing and nursery units from commercial farms and 2 research stations. Brainstem reflexes, convulsions, and heartbeat were used to assess insensibility, time of brain death, and cardiac arrest following Zephyr-E application. Skull fracture displacement (FD) was quantified from computed tomography (CT) scans (n = 24), macroscopic scoring was used to assess brain hemorrhage and skull fracture severity (n = 150), and microscopic scoring was used to assess subdural hemorrhage (SDH) and parenchymal hemorrhage within specific brain regions that are responsible for consciousness and vital function (n = 32). The Zephyr-E caused immediate, sustained insensibility until death in 98.6% of pigs. On average, clonic convulsions (CC) ceased in 82.2 s (± 3.4 SE), brain death was achieved in 144.9 s (± 5.4 SE), and cardiac arrest occurred in 226.5 s (± 8.7 SE). Time of brain death and cardiac arrest differed significantly among stock people (P = 0.0225 and P = 0.0369). Age was positively related to the duration of CC (P = 0.0092), time of brain death (P = 0.0025), and cardiac arrest (P = 0.0068) with shorter durations seen in younger pigs. Average FD was 8.3 mm (± 1.0 SE). Macroscopic scores were significantly different among weight classes for subcutaneous (P = 0.0402) and subdural-ventral (P = 0.0037) hemorrhage with the lowest severity hemorrhage found in the 9-kg weight category. Microscopic scores differed among brain sections (P = 0.0070) for SDH with lower scores found in the brainstem compared to the cerebral cortex and midbrain. Parenchymal hemorrhage differed among brain sections (P = 0.0052) and weight categories (P = 0.0128) with the lowest scores in the midbrain and brainstem and the 7- and 9-kg weight categories. The Zephyr-E was highly effective for the euthanasia of pigs up to 9 kg (49 d) based on immediate insensibility sustained until death. Postmortem results confirmed that severe skull fracture and widespread brain hemorrhage were caused by the Zephyr-E nonpenetrating captive bolt.

Neonatal amygdala lesions alter mother-infant interactions in rhesus monkeys living in a species-typical social environment.

The current study examined the effects of neonatal amygdala lesions on mother-infant interactions in rhesus monkeys reared in large species-typical social groups. Focal observations of mother-infant interactions were collected in their social group for the first 12 months postpartum on infants that had received amygdala lesions (Neo-A) at 24-25 days of age and control infants. Early amygdala lesions resulted in subtle behavioral alterations. Neo-A females exhibited earlier emergence of independence from the mother than did control females, spending more time away from their mother, whereas Neo-A males did not. Also, a set of behaviors, including coo vocalizations, time in contact, and time away from the mother, accurately discriminated Neo-A females from control females, but not Neo-A and control males. Data suggest that neonatal amygdalectomy either reduced fear, therefore increasing exploration in females, or reduced the positive reward value of maternal contact. Unlike females, neonatal amygdala lesions had little measurable effects on male mother-infant interactions. The source of this sex difference is unknown.

Neonatal injury rapidly alters markers of pain and stress in rat pups.

Less than 60% of infants undergoing invasive procedures in the neonatal intensive care unit receive analgesic therapy. These infants show long-term decreases in pain sensitivity and cortisol reactivity. In rats, we have previously shown that inflammatory pain experienced on the day of birth significantly decreases adult somatosensory thresholds and responses to anxiety- and stress-provoking stimuli. These long-term changes in pain and stress responsiveness are accompanied by two-fold increases in central met-enkephalin and ß-endorphin expression. However, the time course over which these changes in central opioid peptide expression occur, relative to the time of injury, are not known. The present studies were conducted to determine whether the observed changes in adult opioid peptide expression were present within the first postnatal week following injury. The impact of neonatal inflammation on plasma corticosterone, a marker for stress reactivity, was also determined. Brain, spinal cord, and trunk blood were harvested at 24 h, 48 h, and 7 d following intraplantar administration of the inflammatory agent carrageenan on the day of birth. Radioimmunoassay was used to determine plasma corticosterone and met-enkephalin and ß-endorphin levels within the forebrain, cortex, midbrain, and spinal cord. Within 24 h of injury, met-enkephalin levels were significantly increased in the midbrain, but decreased in the spinal cord and cortex; forebrain ß-endorphin levels were significantly increased as a result of early life pain. Corticosterone levels were also significantly increased. At 7 d post-injury, opioid peptides remained elevated relative to controls, suggesting a time point by which injury-induced changes become programmed and permanent.

Tandem insults of prenatal ischemia plus postnatal raised intrathoracic pressure in a novel rat model of encephalopathy of prematurity.

OBJECT: Encephalopathy of prematurity (EP) is common in preterm, low birth weight infants who require postnatal mechanical ventilation. The worst types of EP are the hemorrhagic forms, including choroid plexus, germinal matrix, periventricular, and intraventricular hemorrhages. Survivors exhibit life-long cognitive, behavioral, and motor abnormalities. Available preclinical models do not fully recapitulate the salient features of hemorrhagic EP encountered in humans. In this study, the authors evaluated a novel model using rats that featured tandem insults of transient prenatal intrauterine ischemia (IUI) plus transient postnatal raised intrathoracic pressure (RIP). METHODS: Timed-pregnant Wistar rats were anesthetized and underwent laparotomy on embryonic Day 19. Intrauterine ischemia was induced by clamping the uterine and ovarian vasculature for 20 minutes. Natural birth occurred on embryonic Day 22. Six hours after birth, the pups were subjected to an episode of RIP, induced by injecting glycerol (50%, 13 µl/g intraperitoneally). Control groups included naive, sham surgery, and IUI alone. Pathological, histological, and behavioral analyses were performed on pups up to postnatal Day 52. RESULTS: Compared with controls, pups subjected to IUI+RIP exhibited significant increases in postnatal mortality and hemorrhages in the choroid plexus, germinal matrix, and periventricular tissues as well as intraventricularly. On postnatal Days 35-52, they exhibited significant abnormalities involving complex vestibulomotor function and rapid spatial learning. On postnatal Day 52, the brain and body mass were significantly reduced. CONCLUSIONS: Tandem insults of IUI plus postnatal RIP recapitulate many features of the hemorrhagic forms of EP found in humans, suggesting that these insults in combination may play important roles in pathogenesis.

[Treatment of long bone fractures in 125 newborn calves. A retrospective study]. / Behandlung von Frakturen der langen Röhrenknochen bei 125 neugeborenen Kälbern. Eine retrospektive Untersuchung.

OBJECTIVES: Retrospective study of the causes, location, configuration, treatment and outcome of long bone fractures in newborn calves. MATERIAL AND METHODS: The medical records of 125 calves presented during a 16-year period because of fracture of the humerus (3 calves), radius/ulna (14), femur (50) or tibia (58) were evaluated. The majority of calves (61.6%) sustained the fractures during assisted delivery. Of 125 calves, 107 were treated and 18 were euthanized because of concurrent diseases. Conservative treatment was used in 16 calves and surgical treatment in 91. Four of the latter were euthanized because of muscle contraction which prevented fracture reduction, and five others died in surgery. RESULTS: Fracture healing occurred after conservative treatment in 10 of 16 calves and after surgical treatment in 44 of 82 calves. The outcome was better in calves with plate and clamp-rod internal fixation (37/58 healed) than with intramedullary pinning (4/16 healed) or external fixation (3/8 healed). There were significant associations (chi2-test, p<0.01) between concurrent diseases and choice of therapy and fracture healing. Of 67 calves that developed complications, only 26 could be cured. Common complications were implant loosening and instability, which were often followed by osteomyelitis and sepsis. Implants were removed in 39 of 44 surgically treated calves that survived up to 6 months postoperatively. Long-term follow up (> 6 months postoperatively) by clinical and radiographic re-examination (25 calves) or telephone inquiry (29 calves) revealed that 54 animals were sound and had returned to their intended use. CONCLUSIONS AND CLINICAL RELEVANCE: The treatment of long bone fractures in newborn calves remains difficult because of a high incidence of complications. These are most likely attributable to trauma during delivery, which results in insufficient colostrum intake and predisposes to concurrent diseases. In addition, the characteristics of juvenile bones do not provide sufficient physical strength for implants. Therefore, professional and diligent assistance during forced extraction, particularly in presentations with "stifle lock" or "hip lock", is required to minimize the incidence of long bone fractures in newborn calves. Most cases require surgical fixation, which is time consuming, expensive and carries a guarded prognosis.

The use of nylon cable ties to repair rib fractures in neonatal foals.

Commercially available nylon cable ties were used as a method of internal fixation for displaced rib fractures in 8 equine neonates. The procedure was effective, well-tolerated, rapid, and inexpensive. The use of nylon cable ties as internal fixation for displaced rib fractures in foals is an effective surgical procedure.

Pravastatin prevents miscarriages in mice: role of tissue factor in placental and fetal injury.

Pregnancy loss and intrauterine growth restriction (IUGR) are serious pregnancy complications, and the triggers and mediators of placental and fetal damage are not completely understood. Using a mouse model of recurrent spontaneous miscarriages (DBA/2-mated CBA/J mice) that shares features with human recurrent miscarriage and fetal growth restriction, we identified tissue factor (TF) as an essential participating factor in placental and fetal injury. We have previously shown that C5a releases antiangiogenic molecule sFlt-1 in monocytes that causes defective placental development and fetal death in DBA/2-mated CBA/J mice. In this study, we found that TF not only activates the coagulation pathway, but it also mediates sFlt-1 release in monocytes causing defective placental development and fetal death. Blockade of TF with a monoclonal antibody inhibited sFlt-1 release, prevented the pathological activation of the coagulation pathway, restored placental blood flow, prevented placental oxidative stress, and rescued pregnancies. We also demonstrated that pravastatin, by down-regulating TF expression on monocytes and trophoblasts, prevented placental damage and protected pregnancies in DBA/2-mated CBA/J mice. These studies indicate that TF is an important mediator in fetal death and growth restriction and that statins may be a good treatment for women with recurrent miscarriages and IUGR.

Management of fractures in field settings.

Limb fractures are common in farm animals, are most commonly found in young stock, and often occur subsequent to trauma during dystocia or handling. Cattle are excellent patients for treatment of orthopedic injuries because they spend a majority of time lying down, have a tremendous potential for bone healing, are more resistant than other animals to contralateral limb breakdown and stress laminitis, and usually do not resist having orthopedic devices on their limbs. This article describes management of fractures, especially for cattle, in field settings; explains how the principles of external skeletal fixation are adapted for cattle; discusses the application of external skeletal fixation to individual bones, and reviews potential complications in the use of external skeletal fixation.

Proximal tibial epiphysiodesis to reduce tibial plateau slope in young dogs with cranial cruciate ligament deficient stifle.

The purpose of this study was to evaluate the ability of proximal tibial epiphysiodesis to reduce the tibial plateau slope in young dogs with cranial cruciate ligament (CCL) deficient stifles. Of the 14 treated dogs, eight had a bilateral injury, for a total of 22 joints. After physical and radiographical examination and measurement of tibial plateau slope, all of the dogs underwent surgery. Insertion of the screw was placed in the most proximal part of the tibial plateau, in its medio-lateral centre, aiming to the tibial shaft and using a K wire predriven as a guide; correct position of the screw was confirmed with intraoperative fluoroscopy or radiography. In all of the dogs the tibial slope was decreased at the time of physis fusion and the degree of change depended on the age and the breed of the dog at the time of surgery. The minimum change was 4 degrees and the maximum was 24 degrees. There was a statistically significant difference between tibial slope measured before surgery compared to tibial slope measured at the last follow-up visit after surgery. This study shows that the partial proximal tibial fusion in dogs with ACL injuries was effective in reducing the tibial slope during the residual growing time to such an extent to stabilize the joint, provided that the surgery had been carried out when there was still residual growing potential. The technique appeared to be mini-invasive and malalignment complications could be avoided by correct and precise insertion of the screw.

Detection of rib trauma in newborn foals in an equine critical care unit: a comparison of ultrasonography, radiography and physical examination.

REASONS FOR PERFORMING STUDY: Previous studies have shown that in man ultrasonography is more accurate than radiography for detecting rib fractures. OBJECTIVES: To describe clinical, radiographic and ultrasonographic findings related with rib fractures in newborn foals in an equine critical care unit; and to compare diagnostic accuracy of ultrasonography to radiography. METHODS: A prospective ultrasonographic study was performed on 29 foals presented to the emergency unit. This study was performed at the Centre Hospitalier Universitaire Vétérinaire (CHUV), University of Montreal. Physical examination as well as radiographic and ultrasonographic examinations were performed. RESULTS: Thoracic radiographs revealed 10 rib fractures in 5 of 26 (19%) foals. Ultrasonography revealed 49 fractures in 19 of 29 (65%) foals of which fillies (n = 13; 68%) were significantly over represented as were fractures to the left thorax (n = 15; 78%). Seventeen of 19 foals (90%) had rib fractures located 3 cm or less from the costochondral junction, the distal part of the rib being displaced laterally in all cases. In 2 foals, where both thoracic radiographs and ultrasonography detected rib fractures, the site of fractures was located on the mid portion of the rib. Rib fractures were detected only by thoracic radiographs in one foal. Sixty-five percent (32/49) of fractured ribs had a moderate displacement (1-4 mm). CONCLUSIONS: Rib fractures are seen frequently in newborn foals in equine critical care units. Ultrasonography is more accurate than radiography and reveals fractures in most patients presented in emergency. The position (costochondral junction) of rib fractures and of the fragments suggest that most thoracic trauma probably occurs during parturition. POTENTIAL RELEVANCE: Ultrasound imaging increases awareness and improves the diagnosis of rib fractures in newborn foals.