Search

Therapies developed for adult patients with heart failure have been shown to be ineffective in pediatric clinical trials, leading to the recognition that new pediatric-specific therapies for heart failure must be developed. Administration of the recombinant growth factor neuregulin-1 (rNRG1) stimulates regeneration of heart muscle cells (cardiomyocytes) in adult mice. Because proliferation-competent cardiomyocytes are more abundant in growing mammals, we hypothesized that administration of rNRG1 during the neonatal period might be more effective than in adulthood. If so, neonatal rNRG1 delivery could be a new therapeutic strategy for treating heart failure in pediatric patients. To evaluate the effectiveness of rNRG1 administration in cardiac regeneration, newborn mice were subjected to cryoinjury, which induced myocardial dysfunction and scar formation and decreased cardiomyocyte cell cycle activity. Early administration of rNRG1 to mice from birth to 34 days of age improved myocardial function and reduced the prevalence of transmural scars. In contrast, administration of rNRG1 from 4 to 34 days of age only transiently improved myocardial function. The mechanisms of early administration involved cardiomyocyte protection (38%) and proliferation (62%). We also assessed the ability of rNRG1 to stimulate cardiomyocyte proliferation in intact cultured myocardium from pediatric patients. rNRG1 induced cardiomyocyte proliferation in myocardium from infants with heart disease who were less than 6 months of age. Our results identify an effective time period within which to execute rNRG1 clinical trials in pediatric patients for the stimulation of cardiomyocyte regeneration., (Copyright © 2015, American Association for the Advancement of Science.)

Close resemblance of murine and human trials is essential to achieve the best predictive value of animal-based translational cancer research. Kras-driven genetically engineered mouse models of non-small-cell lung cancer faithfully predict the response of human lung cancers to systemic chemotherapy. Owing to development of multifocal disease, however, these models have not been usable in studies of outcomes following focal radiotherapy (RT). We report the development of a preclinical platform to deliver state-of-the-art image-guided RT in these models. Presence of a single tumour as usually diagnosed in patients is modelled by confined injection of adenoviral Cre recombinase. Furthermore, three-dimensional conformal planning and state-of-the-art image-guided dose delivery are performed as in humans. We evaluate treatment efficacies of two different radiation regimens and find that Kras-driven tumours can temporarily be stabilized upon RT, whereas additional loss of either Lkb1 or p53 renders these lesions less responsive to RT.

This paper highlights some recent trends and developments in dialogue on radioactive waste management in the UK. In particular, it focuses on the use of dialogue around options for the management of risk, and describes techniques for stakeholder dialogue in the field of radioactive waste management. The paper summarises past and on-going experience in the UK, and provides an overview of some practical examples from decommissioning of the former reprocessing facility at Dounreay in Scotland. In common with developments and trend in other countries, the UK has moved to a position where there is now widespread recognition that radioactive waste management requires not only sound technical assessment of risk, but also public participation, consultation and stakeholder dialogue on proposed solutions and the associated risks. In fact, the shift of position has arguably been quite pronounced, with formal procedures to identify, clarify and integrate stakeholders' issues and concerns within the decision-making processes. Experience suggests that citizens are capable of engaging with complex technical issues such as radioactive waste. Indeed, the earlier in the decision-making process that public and stakeholder engagement (PSE) occurs--for example, on the consideration of options and alternatives--the greater the chance of reaching a successful outcome that properly reflects the values and opinions of stakeholders. In the UK, the assessment of alternative waste management options is increasingly being addressed through Best Practical Environmental Option (BPEO) studies. Responses to stakeholder engagement processes and experience of conducting BPEO studies emphasise that consultation must be open, transparent, deliberative and inclusive. However, while early consideration of generic approaches and option choices is necessary to generate a climate of openness and understanding, it remains essential to fully engage with local stakeholder and community groups to consider issues associated with proposed developments at a site-specific level. An interesting area where further attention may be warranted is the use in final decision-making of the results from participatory processes such as BPEO studies. Demonstrating clearly that participants' views have influenced decisions appears to be essential for retaining legitimacy and trust, confidence and goodwill.

Objective: To determine the clinical manifestations, morbidity, mortality, and treatment methods for rattlesnake venom poisoning in horses., Design: Retrospective analysis of medical records., Animals: 27 horses with acute venom poisoning attributable to prairie rattlesnakes, and 5 with chronic problems subsequent to a rattlesnake bite., Results: Most horses were bitten on or near the muzzle while on pasture, resulting in head swelling, dyspnea, and epistaxis. Additional manifestations of acute poisoning included fever, tachycardia, tachypnea, cardiac arrhythmia, hemolytic anemia, thrombocytopenia, hemorrhage, thrombosis of venipuncture sites, colic, diarrhea, and prehensile and masticatory dysfunction. Chronic problems included cardiac disease, pneumonia, laminitis, pharyngeal paralysis, and wound complications. The most common chronic problem was cardiac disease. The most commonly used treatments were antibiotics, nonsteroidal anti-inflammatory drugs, tetanus prophylaxis, and airway support. Mortality in the 27 acutely affected horses was 18.5%; the overall mortality was 25%., Clinical Implications: Horses bitten by prairie rattle-snakes may develop multiple, often severe, acute or chronic manifestations of poisoning involving various organ systems. Thorough clinical evaluation, effective treatment, supportive care, and close observation are indicated in horses with rattlesnake venom poisoning.

Ventricular tachycardia develops less frequently than supraventricular dysrhythmias and generally is more indicative of cardiac disease. The horse in this report had clinical signs of lethargy and hypophagia and was determined to have sustained ventricular tachycardia. Echocardiography was a valuable diagnostic tool and revealed an echodense area in the left ventricle that had subnormal ventricular performance. A primary heart problem of an inflammatory nature was suspected. The horse responded favorably to treatment with lidocaine, antimicrobials, and aspirin, as well as stall rest. The horse was used successfully as a sire and hunter-jumper after treatment, but subsequently died 2.2 years later of massive hemoperitoneum. Necropsy revealed an extensive area in the left ventricle that appeared thin and fibrotic.

Routine examination of the digestive system relevant to purchase includes gross examination of the feces, auscultation of the abdomen, and examination of the oral cavity and teeth for verification of age and identification of any gross abnormality. Further examination is indicated only when there is a history of diseases such as colic, especially colic surgery, or esophageal obstruction. Special procedures that might be indicated, depending upon the history and findings on the routine physical examination, include rectal palpation of the abdominal viscera; endoscopic examination of the esophagus; abdominal paracentesis; radiographs of the teeth, esophagus, or abdomen; and transabdominal or transrectal ultrasound.

Clinical signs of chronic epididymitis in a stallion included recurrent signs of inguinal pain--retraction of the right testis into the inguinal area, resentment of palpation of the right testis, and right-sided scrotal swelling. The tail of the right epididymis was firm and seemed to be adhered to the testis. The tail of the left epididymis felt firmer than normal. Ultrasonographically, the diameter of the head of the epididymis was considered larger than normal, was hyperechoic in relation to the right testis, and had an irregular border. Several bright 1- to 5-mm-diameter echogenic areas that alternated with less echogenic areas were seen in the head of the right epididymis. Ultrasonographic findings were interpreted as fibrosis attributable to chronic inflammation. Unilateral castration (right-sided) was performed, but the prognosis was guarded because of presumed involvement of the left epididymis.

Eighteen clinically normal horses were used to study the characteristics of normal thoracic fluid. Thoracic fluid was obtained from each horse and was found to be similar to equine abdominal fluid. Total leukocytes averaged 3994/ul, total protein 1.8 g/dl, and specific gravity 1.015. Analysis of thoracic fluid from 16 horses with clinical signs of thoracic disease showed abnormalities in every case. Thoracic fluid analysis alone determined a specific diagnosis in 50% of the cases.

Patent infections with Strongylus vulgaris were established in 6 of 8 helminth-free ponies given 41 to 101 adult worms via nasogastric tube. The parasites were removed from the cecum and ventral colon and transferred within 1 to 2 hours of the death of the donor horses. Eggs were found in the feces of the recipients in 2 or 3 days; egg counts reached maximum, 28 eggs per gram of feces, at 4 weeks after ponies were inoculated. In 6 ponies euthanatized 3 to 7 weeks after parasitic transfers were done, 28% of the inoculated worms were found alive at necropsy. A 7th pony was maintained as a donor for establishing infections for chemotherapy trials and, although never passing more than 6 eggs per gram of feces, shed infective larvae over a period of 2 years.

Echocardiography is a non-invasive, safe means of assessing intracardiac structures and their motion. In the normal motion of the mitral valve there is anterior motion noted during atrial systole. In 3 horses with atrial fibrillation the mitral valve motion had no anterior motion to correspond with atrial contractions. Quinidine returned the electrocardiogram of one horse to a sinus rhythm after which echocardiography demonstrated the reappearance of the anterior motion of the mitral valve.

Four horses with diarrhea had radiographic evidence of large quantities of sand in the gastrointestinal tract. Initially, none of the horses had sufficient fecal sand quantity to suggest sand enteropathy. Diarrhea resolved in all horses within 2 days of oral administration of psyllium hydrophilic mucilloid. Historically, all 4 horses had lost weight or had difficulty maintaining weight. After treatment was administered, the horses either gained weight or were easier to maintain in good condition.

Shetland ponies (n = 4) were given diethylcarbamazine orally at a dose level of 22 mg/kg/day for 1 week before they were inoculated with 800 third-stage larvae of Strongylus vulgaris. Treatment was continued for 86 (1 pony) or 200 days (3 ponies) after the inoculation. As compared with the changes seen in a similarly inoculated group of ponies (group 2) which were not treated, diethylcarbamazine did not prevent the clinical or pathologic changes due to the migrating larvae. Fewer adult parasites were recovered at necropsy from treated ponies than from nontreated (group 2) ponies, even when treatment was discontinued 86 days after inoculation. Treatment appeared to have a detrimental effect on 4th-stage larvae either in the arteries or their intestinal wall, but not until after arterial lesions resulted.

The cultivation and characterization of a cell line derived from the foreskin of a fetal, rhesus monkey (rhfs2) are described. This cell line has proven satisfactory for isolation and assay of a variety of viral agents of human and simian origin. Virus titrations performed on foreskin cells yielded titers comparable to, or higher than, those obtained in rhesus monkey kidney cells (LLC-MK2). Replicate isolation attempts in our laboratory from simian clinical specimens have proven rhfs2 superior to LLC-MK2 for ease of detection and frequency of isolation.