Application of optical coherence tomography enhances reproducibility of arthroscopic evaluation of equine joints

Peer reviewe

Comparative studies on prognostic markers and signaling pathways for canine and human osteosarcoma

Osteosarcoma is an aggressive bone tumor that occurs naturally mainly in large and medium breed dogs where almost 90% of dogs will develop metastasis predominantly in the lungs. The standard treatments (extirpation of the primary tumor including limb amputation/sparing, post-operative chemotherapy and palliative radiotherapy) have increased survival rates as compared to denying options for therapy upon diagnosis. Despite the advances in various therapies, prognosis remains poor, wit

Towards a staged evidence-based approach for the treatment of tendon injuries in the horse

Healing of tendon lesions, a common disorder in the equine species, is slow and often inadequate because the resulting scar tissue cannot meet the functional demands posed by the everyday athletic activity of many horses, making re-injury the most common and often fatal complication after initial trauma. Many therapies have been tried over time, but none of them thus far has succeeded in significantly improving the functional recovery rate in horses after suffering from a tendon injury. The healing trajectory of tendon injuries can be divided in three partially overlapping phases: the inflammation phase, the proliferative phase and the maturation phase. These phases are charactersied by biological porcesses specific to the phase of healing. Up to now very little attempts have been made to distinguish between these phases when applying a therapy to an injured tendon. In this thesis a specific therapy for each of the stages was studied, although it is acknowledged that therapies might exhibit effects in more than one phase of the healing trajectory. During the inflammatory phase there is an initial enlargement of original the lesion due to proteolytic and biomechanical influences. In an in vitro mechanical study it was shown that this lesion propagation after tendon injury may be mitigated by immobilisation during the early phase of repair, although in vitro work remains necesarry to confirm these findings. The proliferative phase is characterised by cell proliferation and synthesis of extracellular matrix components, such as collagen and glycosaminoglycans. These processes can possibly be enhanced by treatment with platelet rich plasma (PRP), an autologous concentrate of growth factor containing platelets. PRP treatment was evaluated in a blinded placebo-controlled experimental study, in which artificially induced tendon lesions were treated with PRP or placebo and tissue was harvested after 24 weeks. PRP improevd biochemical, biomechanical and histological properies of the treated tendons. Doppler ultrasonography revealed large differences in vascularisation between treated and untreated tendons. Computerised Ultrasonography was used to monitor the healing process and appeared capable of predicting outcome at a relatively early stage of the healing process and revealed clues about some of the mechanisms of action. Extracorporeal Shock Wave Therapy (ESWT), a technique based on physical intervention, was used in vivo on healthy equine tendons. It could be shown that, after an initial boost of metabolic activity in the tendon tissue, there was a long-term (6 weeks after treatment) negative effect on cell-matabolism. Further, a rather severe disorganisation of the normal tendon architecture. Both findings warrant caution in the clinical use of this technique, but might also explain the positive effects ESWT appears to have on more chronic tendon lesions. The thesis concludes that a staged approach for the treatment of tendon injuries is likely to improve the final prognosis of horses that are recoverring from a tendon injury, although functional healing of tendon injuries will remain a problem in equestrian sports and additional research is necessary. Improvement of prognosis can be expected by a proactive approach including early immobilisation and application of novel intratendinous treatments

Man and horse: brothers in arms

It is a long‐standing academic tradition to accept the appointment to a chair by giving an inaugural lecture. The name of the chair to which I was appointed nearly a year ago is Equine Musculoskeletal Biology. In the next 30 minutes I would like to say a few words on all 3 components of this name: equine, musculoskeletal and biology, in the hope of clarifying both what is meant by these terms, and the relationships between them. We shall start, as we ought to, at the beginning

Novel functions for atypical E2Fs, E2F7 and E2F8, in polyploidization and liver cancer

Atypical E2F transcription factors, E2F7 and E2F8, function as transcriptional repressors of E2F target genes and are crucial for controlling the cell proliferation. In this thesis, we reveal that these two factors are crucial for liver cell polyploidization, embryonic development and prevention of liver cancer in mice. In chapter 2, we show that atypical E2Fs, especially E2F8, play an important role in promoting polyploidization in the liver. Loss of E2F7/8 resulted in dramatic reduction in binucleation and polyploidization of hepatocytes. In contrast, single loss of E2F1 enhanced polyploidization in hepatocytes. Interestingly, loss of E2f1 in E2f7/8-deficient liver led to partial rescue of polyploidization defect observed upon loss of E2f7/8. Moreover, we identified a transcriptional network program regulated by repressor E2F8 and activator E2F1 that controls polyploidization in liver. Together, these data suggest opposing functions for classical activator E2Fs and atypical repressor E2Fs in regulating polyploidization in liver. Surprisingly, contrary to long-term theory, we discovered that loss of polyploidization has no impact on liver differentiation and regeneration. We demonstrate in chapter 4 that E2F7 and E2F8 are required for murine embryonic development. While mice mutant for either E2F7 or E2F8 developed normally with no obvious developmental defects, global deletion of both E2F7 and 8 resulted in embryonic lethality owing to vascular and cell survival defects such as dilated blood vessels associated with multifocal hemorrhages and massive apoptosis. Interestingly, loss of either E2F1 or p53 suppressed the massive apoptosis observed in E2f7/8 double knockout embryos, however, the triple knockout embryos still carried the vascular defects and died around same embryonic age, suggesting complex mechanisms underlying the embryonic lethality. As described in chapter 5, we have revealed that E2f7/8 function as tumor suppressor genes and that they can cooperate with the known tumor suppressor gene Rb in preventing liver cancer. Using liver-specific knockout mice, we found that deletion of E2f7/8 results in spontaneous development of hepatocellular carcinoma in mice. Furthermore, additional deletion of Rb along with E2f7/8 resulted in development of tumors earlier than in E2f7/8 deficient livers, indicating that loss of Rb accelerates tumorigenesis

Clinical cytology of companion animals: Part II . Cytology of subcutaneous swellings, skin tumours and skin lesions

Clinical Cytology of Companion Animals: Part 2. Clinical Cytology of Companion Animals: Part 2. Cytology of subcutaneous swellings, skin tumours and skin lesions Subcutaneous swellings, skin tumours, and skin lesions are extremely well suited for cytological examination via FNAB (Fine needle aspiration biopsy). Aspiration can be performed without difficulty, and causes little or no pain except with processes on the feet or the nose, and even in these cases, anaesthesia is seldom required. An impression smear or scraping can easily be made of open lesions, but it is advisable to perform FNAB from the edges of the wound as well. Cytological examination can in many cases lead quickly to the correct diagnosis and be of decisive importance to the choice of therapy and to the prognosis. The cytological examination of FNAB of skin tumours and subcutaneous swellings often makes histological examination unnecessary. Histological examination costs more time, is more invasive, and more expensive. However, it should be emphasized that follow-up histological examination almost always offers a solution in the event that cytological examination is insufficient, and some processes can only be determined by histological examination. Cytological examination of skin tumours and to a lesser extent also skin lesions and subcutaneous swellings forms a good start for veterinarians who wish to become familiar with cytology. Many diagnoses are rather easy to make and to verify subsequently via a second opinion by an experienced cytologist or by histological examination. This paper is organized in a way to help the inexperienced cytologist quickly on the way to the fi rst diagnosis but also to help recognize as such the preparations that are diffi cult to interpret. The evaluation of the latter can be left to an experienced cytologist. The reader is further advised to consult one of the many cytology books that are available, as in this article only condensed information can be given due to publication limits. The following advice is offered to the inexperienced cytologist in order to avoid erroneous diagnoses: 1. Examine only cell-rich, well streaked-out preparations. 2. Interpret the cytology as far as possible in relation to the clinical information such as age of the patient, past history, and the macroscopic appearance, rate of growth, and location of the tumour. 3. For the time being have all diagnoses, including those made without diffi culty, verifi ed by an experienced cytologist or by histological examination. It can be difficult to differentiate skin tumours and subcutaneous swellings. Skin tumours can spread subcutaneously and subcutaneous processes can infiltrate the dermis, and both can cause skin lesions. Usually it is possible by inspection and palpation to correctly localize a process. This is important in obtaining a FNAB because the origin can give specific indications of the nature of the process (Table 1)

Intraperitoneal antineoplastic drug delivery: experience with a cyclophosphamide, vincristine and prednisolone protocol in cats with malignant lymphoma

In this retrospective study, the efficacy and safety were examined for an intraperitoneal chemotherapy protocol-cyclophosphamide, vincristine and prednisolone (IP-COP) in 26 cats with malignant lymphoma. Certainly in cats fiercely resisting IV administration the IP route is a more practical method, safer for the administrator and less stressful for the cat. Complete remission (CR) rate was 76.9% (n=20). Median duration of first remission was 421 days. Estimated 1- and 2-year disease free period were 67.1 and 48.0%, respectively. Median duration of survival was 388 days and estimated overall 1- and 2-year survival periods were 54.7 and 46.9% respectively. Young cats had a more favourable prognosis. Reaching CR was essential for long-term survival. No specific IP-related adverse events (AE) were seen. AE were generally scored as mild and were not excessively abundant. These results indicate that the IP route is a safe and effective alternative for the administration of COP protocol chemotherapeutics

The early development of medial coronoid disease in growing Labrador retrivers: Radographic, computed tomographic, necropsy and micro-computed tomographic findings

Abstract Medial coronoid disease (MCD) encompasses lesions of the entire medial coronoid process (MCP), both of the articular cartilage and the subchondral bone. To detect the earliest signs of MCD, radiography and computed tomography were used to monitor the development of MCD in 14 Labrador retrievers, from 6 to 7 weeks of age until euthanasia. The definitive diagnosis of MCD was based on necropsy and micro-computed tomography findings. The frequency of MCD in the dogs studied was 50%. Radiographic findings did not provide evidence of MCD, ulnar subtrochlear sclerosis or blunting of the cranial edge of the MCP. Computed tomography was more sensitive (30.8%) than radiography (0%) in detecting early MCD, with the earliest signs detectable at 14 weeks of age. A combination of the necropsy and micro-computed tomography findings of the MCP showed that MCD was manifested as a lesion of only the subchondral bone in dog