Atypical Histiocytosis in Red Squirrels (Sciurus vulgaris).

Four red squirrels (Sciurus vulgaris) were subjected to necropsy examination over a 3-year period as part of a broader surveillance study. The squirrels presented with cutaneous, subcutaneous and/or internal swellings and nodules that consisted microscopically of sheets of atypical round cells and multinucleated giant cells. There was moderate anisokaryosis with rare mitoses. Nuclei ranged from oval to indented or C-shaped and some were bizarre, twisted or multilobulated. Many giant cells also had a bizarre morphology, with anisokaryosis within individual cells. Giant cell nuclei were often multilobulated, ring-shaped or segmented. Affected internal organs varied depending on the squirrel, but included lymph node, kidney, intestinal tract and lungs. Representative lesions from each of the four squirrels were negative for acid-fast organisms. Formalin-fixed tissues from all four squirrels and ethanol-fixed tissue from one animal were negative for Mycobacterium by polymerase chain reaction. Immunohistochemically, the majority of mononuclear and multinucleated giant cells in all four squirrels strongly expressed vimentin and class II molecules of the major histocompatibility complex. Otherwise, the atypical mononuclear and multinucleated cells were negative for CD3, Pax-5, Mac387, CD18 and E-cadherin. Based on the combination of cellular morphology, arrangement and immunophenotype, a novel form of atypical histiocytosis is considered most likely in these squirrels, although the exact origin and triggering factors remain uncertain.

Histopathological Characterization of Tail Injury and Traumatic Neuroma Development after Tail Docking in Piglets.

Tail docking of neonatal pigs is widely used as a measure to reduce the incidence of tail biting, a complex management problem in the pig industry. Concerns exist over the long-term consequences of tail docking for possible tail stump pain sensitivity due to the development of traumatic neuromas in injured peripheral nerves. Tail stumps were obtained post mortem from four female pigs at each of 1, 4, 8 and 16 weeks following tail amputation (approximately two-thirds removed) by a gas-heated docking iron on post natal day 3. Tissues were processed routinely for histopathological examination. Non-neural inflammatory and reparative epidermal and dermal changes associated with tissue thickening and healing were observed 1 to 4 months after docking. Mild neutrophilic inflammation was present in some cases, although this and other degenerative and non-neural reparative changes are not likely to have caused pain. Traumatic neuroma and neuromatous tissue development was not observed 1 week after tail docking, but was evident 1 month after tail docking. Over time there was marked nerve sheath and axonal proliferation leading to the formation of neuromata, which were either localized and circumscribed or comprised of multiple axons dispersed within granulation tissue. Four months after tail resection, neuroma formation was still incomplete, with possible implications for sensitivity of the tail stump.

Anatomical and histological study of the dorsal and ventral nasal conchal bullae in normal horses.

The morphology of the dorsal conchal bulla (DCB) and ventral conchal bulla (VCB) are poorly described. The recent recognition that these bullae can become infected, causing chronic unilateral nasal discharge, has stimulated interest in these structures. Fourteen cadaveric horse heads were transected sagittally midline and dissected to expose the nasal conchal bullae. The dimensions of each bulla, the number and orientation of drainage apertures, and cellulae septae were recorded. Randomly selected samples were examined histologically. The mean DCB and VCB lengths were 78  and 57 mm, respectively; equivalent to 13.9 per cent and 10.2 per cent of skull length, respectively. The mean DCB and VCB heights were 29  and 28 mm, respectively; equivalent to 5.2 per cent and 5 per cent of skull length, respectively. The DCB was larger than the VCB, containing more septae, cellulae and drainage apertures. No communications were identified between the bullae and the immediately adjacent paranasal sinuses. Histology revealed that the bullae consist of ciliated, pseudostratified, columnar epithelium over glandular submucosa often overlying turbinate bone and, variably, hyaline cartilage. This more detailed description of equine DCB and VCB anatomy will hopefully facilitate successful treatment of their disorders.

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

REASONS FOR PERFORMING STUDY: The morphology of the dorsal (DCB) and ventral (VCB) nasal conchal bullae, including their cellulae, drainage and histology, are poorly described. The recent recognition that these bullae can become infected, causing chronic unilateral nasal discharge has stimulated interest in these structures. A more complete understanding of their anatomy would be useful in the diagnosis and treatment of their disorders. OBJECTIVES: To document the structure, drainage and histology of the equine DCB and VCB. STUDY DESIGN: Descriptive. METHODS: Fourteen fresh cadaveric horse heads, were transected sagittally midline and dissected to expose the nasal conchal bullae. The dimensions of each bulla, the number of drainage apertures, the number of cellulae and orientation of the septae were recorded. Representative samples were collected for histopathology. RESULTS: The mean lengths of the DCB and VCB were 77.7 mm (range 48-105 mm) and 57.1 mm (range 34-86 mm) respectively; equivalent to 13.8% and 10.2% of skull length, respectively. The mean widths of the DCB and VCB were 28.5 mm (range 21-35 mm) and 28.2 mm (range 13-41 mm) respectively; equivalent to 5.1% and 5% of skull length respectively. The median number of drainage apertures from the DCB and VCB were 2 and 1 respectively. The median number of cellulae within the DCB and VCB were 3 and 2, respectively. No communications were identified between the DCB and VCB and the adjacent paranasal sinuses. Histology revealed that the bullae consisted of ciliated, pseudostratified, columnar epithelium supported by a glandular submucosa often overlying turbinate bone and, variably, hyaline cartilage. CONCLUSIONS: The morphology of the equine nasal conchal bullae is quite variable. The DCB is generally a more complex structure than the VCB, containing more septae, cellulae and drainage apertures. This more detailed description of DCB and VCB anatomy will hopefully facilitate successful treatment of their disorders. Ethical animal research: Research ethics committee oversight not currently required by this conference: the study was performed on material obtained from an abattoir. SOURCE OF FUNDING: None. Competing interests: None declared.

A case of antibacterial-responsive mucocutaneous disease in a seven-year-old dwarf lop rabbit (Oryctolagus cuniculus) resembling mucocutaneous pyoderma of dogs.

A seven-year-old, ovariohysterectomised female dwarf lop rabbit (Oryctolagus cuniculus) was referred with severe swelling and erythema of the mucocutaneous junctions of the lips, nares and vulva. Bilateral, severe periocular dermatitis was also present. Heavy pure growths of a member of the Staphylococcus intermedius group were cultured from nasal and aural swabs and skin biopsies. Other possible differential diagnoses were eliminated by standard tests. The clinical features and histopathological characteristics of the biopsies were most consistent with mucocutaneous pyoderma, a dermatosis previously reported in dogs but not in rabbits. Treatment of the bacterial infection with oral marbofloxacin and topical ofloxacin eye drops together with supportive therapy resulted in resolution of the lesions. To the authors' knowledge, this is the first report of mucocutaneous bacterial pyoderma, similar to mucocutaneous pyoderma of dogs, in a rabbit.

Clinical, microbiological and histological findings in lambs affected by 'salivary abomasum disease'.

'Salivary abomasum disease' is a common syndrome in Greece affecting lambs and kids from three to 17 days of age. In this case series, we present clinical and laboratory findings from 37 affected lambs presented alive and subsequently euthanased for welfare reasons and necropsied, and also from 24 other lambs submitted dead that were also necropsied. The clinical signs in the 37 lambs presented alive included lethargy (100 per cent), absence of sucking (83.8 per cent), weakness (37.8 per cent), abdominal distension (40.5 per cent) and increased frequency of urination (24.3 per cent). Diarrhoea was not observed in any affected lambs. At necropsy of these 37 lambs, the abomasum was distended with gas (70.3 per cent), saliva (43.2 per cent) along with mixed milk clots and gastric secretions; while multiple small mucosal and serosal haemorrhages with blood clots ('coffee grains') were recorded (91.9 per cent). Eight of 37 lambs that were examined alive, had elevated blood urea nitrogen concentrations (21.6 per cent). The pH of the abomasal contents ranged from 1.0 to 2.8; Escherichia coli was cultured from six of 37 (16.2 per cent) abomasal fluid samples. A mild to moderate inflammatory cell infiltrate was present in the mucosal lamina propria of 13 of 15 abomasal samples (86.6 per cent). Kidneys were paler than normal in 13 of the total 61 lambs necropsied (21.3 per cent); while acute tubular necrosis was evident on histopathological examination of 11 of 12 examined pale kidneys (91.6 per cent). The low abomasal pH and reported successful treatment with oral sodium bicarbonate suggest that metabolic acidosis may develop during the disease; however, further studies, including blood gas analysis, and determination of D- and L-lactic acid concentrations, are necessary to confirm this hypothesis.

Small intestinal ganglioneuromatosis in a dog.

A 9-year-old female neutered collie-cross dog was presented with a 2-month history of persistent diarrhoea, weight loss and intermittent vomiting. Abdominal ultrasonography revealed one loop of jejunum with a markedly thickened and multifocally hyperechoic wall, without loss of wall layering. Laparotomies were performed for biopsy and resection of affected intestine. Histopathological examination revealed small intestinal ganglioneuromatosis (GN). The dog recovered well from surgery and the diarrhoea resolved. Eleven months later the dog has gained weight and remains asymptomatic. This is the first report of small intestinal GN affecting a mature dog, in which pathology was localized to the mucosal lamina propria and surgical treatment resulted in a successful outcome.

Red blood cell transfusion during septic shock in the ICU.

BACKGROUND: Transfusion of red blood cells (RBCs) remains controversial in patients with septic shock, but current practice is unknown. Our aim was to evaluate RBC transfusion practice in septic shock in the intensive care unit (ICU), and patient characteristics and outcome associated with RBC transfusion. METHODS: Prospective cohort study of all adult patients with septic shock (n = 164) in six general ICUs during a 3-month period. Characteristics, other treatments, monitoring and outcome were compared in RBC-transfused and -non-transfused patients. RESULTS: Ninety-nine patients (95% confidence interval 87-111) received a median 900 ml (interquartile range 490-1405) of RBC during septic shock in ICU. Among transfused patients, there were more females [49/99 (49%) vs. 22/65 (34%), P = 0.048] and surgical patients [39/99 (39%) vs. 14/65 (22%), P = 0.02] than among patients not transfused. Also, admission simplified acute physiology score II was higher and minimal haemoglobin levels (days 1-3) were lower in transfused patients compared with those not transfused. In contrast, age, markers of shock and severity organ failure assessment score on day 1 and 90-day mortality did not differ between RBC-transfused and -non-transfused patients. CONCLUSIONS: Most patients with septic shock received RBCs during shock, and these patients had higher disease severity and lower haemoglobin levels than those not transfused. In spite of this, mortality did not differ between groups neither in the unadjusted or adjusted analyses. However, neither the design nor the sample size allows us to make inferences about treatment effects, which underlines the need for large randomised, clinical trials on transfusion in septic shock.

Pulmonary angiocentric lymphoma (lymphomatoid granulomatosis) in a donkey.

A 36-year-old donkey developed dyspnoea, pyrexia, hypoalbuminaemia and oedema. Following continued clinical deterioration the donkey was humanely destroyed. Grossly, there were numerous nodules (5-10mm) scattered throughout the lung. Microscopically, the lung was infiltrated by an angiocentric and bronchocentric to diffuse mixed population of small mature and atypical lymphocytes, histiocytes, plasma cells and fewer eosinophils. The infiltrate was composed of numerous small mature and fewer atypical CD3(+) T lymphocytes. Low numbers of CD20(+) and CD79a(+) B cells, some atypical, accompanied the T cells. These infiltrates were consistent with an angiocentric lymphoma and resembled lymphomatoid granulomatosis, an Epstein-Barr virus (EBV)-associated human tumour. Immunohistochemistry for EBV latent membrane protein and polymerase chain reaction analysis for equine gamma herpesvirus DNA were negative. To the authors' knowledge this is the first case of angiocentric lymphoma reported in a donkey and the first case of lymphomatoid granulomatosis-type disease in an animal in which possible concurrent infection with a gamma herpesvirus has been investigated.

Analysis of airway epithelial regeneration and repair following endobronchial brush biopsy in sheep.

Understanding the fundamental processes involved in repairing the airway wall following injury is fundamental to understanding the way in which these processes are perturbed during disease pathology. Indeed complex diseases such as asthma and chronic obstructive pulmonary disease (COPD) have at their core evidence of airway wall remodeling processes that play a crucial functional role in these diseases. The authors sought to understand the dynamic cellular events that occur during bronchial airway epithelial repair in sheep. The injury was induced by endobronchial brush biopsy (BBr), a process that causes epithelial débridement and induces a consequential repair process. In addition, the current experimental protocol allowed for the time-dependent changes in airway wall morphology to be studied both within and between animals. The initial débridement was followed by evidence of dedifferentiation in the intact epithelium at the wound margins, followed by proliferation of cells both within the epithelium and in the deeper wall structures, notably in association with the submucosal glands and smooth muscle bundles. Seven days after injury, although the airway wall was thickened at the site of damage, the epithelial layer was intact, with evidence of redifferentiation. These studies, in demonstrating broad agreement with previous studies in small animals, indicate the wider relevance of this system as a comparative model and should provide a solid basis upon which to further characterize the critical cellular and molecular interactions that underlie both effective restitution and pathological repair.

Lymphoproliferative disease with features of lymphoma in the central nervous system of a horse.

Lymphoma (malignant lymphoma, lymphosarcoma) is uncommon in horses in the United Kingdom. This report describes an unusual form of lymphoproliferative disease with features of lymphoma restricted to the central nervous system (CNS) and with no evidence of a primary lesion elsewhere. Immunohistochemical examination defined an overwhelming predominance of T lymphocytes with admixed B lymphocytes and activated macrophages. This case exemplifies the challenges associated with definitive diagnosis of lymphoproliferative disease of the equine CNS.

Carcinoma ex pleomorphic adenoma with sebaceous differentiation in the mandibular salivary gland of a dog.

A carcinoma ex pleomorphic adenoma was diagnosed in the left mandibular salivary gland of an 8-year-old female spayed dog. The animal presented with a large nonpainful swelling in the left submandibular region. A computed tomography scan detected an irregularly enhancing soft tissue mass that was closely associated with the left external ear canal and extended to the left wing of the atlas. On surgical exploration, the mass was intimately associated with the left mandibular salivary gland. Both the mass and the adjacent gland were removed, and the diagnosis was determined by histopathology. The tumor was comprised of basaloid and low columnar epithelial cells, many glandular units formed by well-differentiated sebocytes, and multifocal regions of necrosis, mineralization, and hemorrhage. Salivary gland tumors with sebaceous differentiation are very rare in animals, with one previously reported case in a cat.

A comparative review of melanocytic neoplasms.

Melanoma is a devastating disease frequently encountered within both veterinary and human medicine. Molecular changes linked with neoplastic transformation of melanocytes include mutations in genes that encode proteins intrinsic to the regulatory pathways of two tumor suppressor proteins (retinoblastoma protein and p53), proto-oncogene mutation to oncogenes, altered expression of epithelial cadherin and CD44 adhesion molecules, and upregulation of angiogenic factors and other growth factors. Histologic evaluation of the primary mass is the most common means of diagnosis, with cytology used more frequently to document metastasis. Melanoma's highly variable histologic and cytologic patterns can make diagnosis by either method problematic. Adherent epithelioid morphology, including signet ring forms, and nonadherent round and spindle forms are recognized, with pigmentation an inconsistent finding. The site of the tumor, the thickness of the primary tumor or depth of invasion, and the number of mitotic figures per high-power field or per millimeter are used histologically to predict biologic behavior, whereas site and degree of pleomorphism are typically used for cytologic preparations. Diagnosis of amelanotic melanoma can be aided by ancillary diagnostic techniques. Tumor cells are usually positive for vimentin, S100, neuron-specific enolase, and Melan-A, and negative for cytokeratin. Melan-A as a positive marker is not as sensitive as the others are but is likely more specific. Monoclonal antibodies to human melanosome-specific antigens 1 and 5 cross-react with canine antigens for a combined sensitivity rate of 83%. Mouse monoclonal antibody IBF9 specifically recognizes canine melanoma antigen and also has good sensitivity. Serologic markers, including cytokines, cell adhesion molecules, and melanoma-inhibitory activity, are being investigated as potential sentinels of melanoma. Currently, there is no single diagnostic technique capable of differentiating benign from malignant melanocytic neoplasms or predicting survival time.

Calcium, cross-bridges, and the Frank-Starling relationship.

The steep relationship between active force and length in cardiac muscle is based on a length dependence of myofilament Ca(2+) sensitivity. However, it is not muscle length but the lateral spacing between actin and myosin filaments that sets the level of Ca(2+) sensitivity, mainly through modulation of myosin-mediated activation of the thin filament.

Cerebral vascular hamartomas in five dogs.

Vascular hamartomas are considered developmental lesions rather than true neoplasms. Reports of such anomalies in the canine brain are scarce, and their classification is confusing. This case series of vascular hamartomas from the brains of five dogs was characterized using histochemistry and immunohistochemistry, in addition to gross and microscopic findings. All five hamartomas were located in the telencephalon, three in the pyriform lobe, without any predilection for the left or right side. Each hamartoma consisted of a proliferation of thin-walled vessels which varied in caliber. These vessels were elastin-negative, with varying amounts of collagen and no muscular component. In four of the five hamartomas, lining cells were actin- and factor VIII-positive. All five hamartomas contained glial fibrillary acid protein (GFAP)-positive parenchyma at moderate to high frequency, and four contained neurofilament-positive axons between component vessels. This report shows that vascular hamartomas in the canine brain are structural malformations for which immunohistochemistry is useful for accurate classification.

Growth hormone replacement therapy in children with medulloblastoma: use and effect on tumor control.

PURPOSE: Progress has been made in the treatment of medulloblastoma, the most common childhood malignant brain tumor: However, many long-term survivors will have posttherapy growth hormone insufficiency with resultant linear growth retardation. Growth hormone replacement therapy (GHRT) may significantly improve growth, but there is often reluctance to initiate GHRT because of concerns of an increased likelihood of tumor relapse. PATIENTS AND METHODS: This study retrospectively reviewed the use of GHRT for survivors of medulloblastoma in 11 neuro-oncology centers in North America who received initial treatment for disease between 1980 and 1993 to determine its impact on disease control. A Landmark analysis was used to evaluate the relative risk of relapse in surviving patients. RESULTS: Five hundred forty-five consecutive patients less than 15 years of age at diagnosis were identified. Six-year progression-free survival (mean +/- SD) was 40% +/- 5% in children less than 3 years of age at diagnosis compared with 59% +/- 3% for older patients. Older patients with total or near-total resections (P = .003) and localized disease at diagnosis (P < .0001) had the highest likelihood of survival. One hundred seventy patients (33% +/- 3% of the cohort) received GHRT. GHRT use varied widely among institutions, ranging from 5% to 73%. GHRT was begun a mean of 3.9 years after diagnosis, later in children younger than 3 years at diagnosis (5.4 years). By Landmark analyses, for those surviving 2, 3, and 5 years after diagnosis, there was no evidence that GHRT increased the rate of disease relapse. CONCLUSION: This large retrospective review demonstrates that GHRT is underutilized in survivors of medulloblastoma and is used relatively late in the course of the illness. GHRT is not associated with an increased likelihood of disease relapse.

Hemihyperaesthesia and hyperresponsiveness resembling central pain syndrome in a dog with a forebrain oligodendroglioma.

A 4-year-old male Boxer was presented with neurological signs referable to a right forebrain lesion that was confirmed with computed tomography. Whilst characteristic signs of a unilateral forebrain lesion were observed, the dominant and striking finding was a right-sided hemisensory disturbance characterised by hyperaesthesia and hyperresponsiveness. Necropsy revealed a gelatinous mass confined to the right forebrain that was identified histologically as an oligodendroglioma. The lesion was centred on the internal capsule and involved ventral frontal and temporal lobes and the ventrolateral thalamus, including lateral and medial parts of the ventrocaudal nuclear region (ventrobasilar complex) of the thalamus. On clinical and neuroanatomical grounds, the case exhibited features in common with central pain syndrome in human patients with thalamic lesions. These included a somatosensory disorder of hyperaesthesia affecting an entire side of the head and body, behavioural manifestations consistent with spontaneous pain and a lesion involving the ventrobasilar complex. Of interest, the hemisensory abnormality was ipsilateral to the lesion, contrasting with central pain in humans, in which clinical signs are contralateral to analogous lesions. It is suggested that species-specific differences in spinal cord organisation of pain pathways, particularly the greater bilateral projection of nociceptive afferents to thalamic relay nuclei in carnivores, may account for this disparity. Notably, central pain is rare in human patients with brain tumours, even those affecting the thalamus, and this may also be the case in dogs.