Clinical, magnetic resonance imaging, and histopathologic findings in 6 dogs with surgically resected extraparenchymal spinal cord hematomas.

BACKGROUND: Extraparenchymal spinal cord hematoma has been described in veterinary medicine in association with neoplasia, intervertebral disk disease, and snake envenomation. There are rare reports of spontaneous extraparenchymal spinal cord hematoma formation with no known cause in human medicine. Multiple cases of spontaneous extraparenchymal spinal cord hematoma have not been described previously in veterinary medicine. OBJECTIVES: To describe the signalment, clinical findings, magnetic resonance imaging (MRI) features, and surgical outcomes in histopathologically confirmed extraparenchymal spinal cord hematomas in dogs with no identified underlying etiology. ANIMALS: Six dogs had MRI of the spinal cord, decompressive spinal surgery, and histopathologic confirmation of extraparenchymal spinal cord hematoma not associated with an underlying cause. METHODS: Multi-institutional retrospective study. RESULTS: Six patients had spontaneous extraparenchymal spinal cord hematoma formation. MRI showed normal signal within the spinal cord parenchyma in all patients. All hematomas had T2-weighted hyperintensity and the majority (5/6) had no contrast enhancement. All dogs underwent surgical decompression and most patients (5/6) returned to normal or near normal neurologic function postoperatively. Follow-up of the patients (ranging between 921 and 1,446 days) showed no progression of neurologic clinical signs or any conditions associated with increased bleeding tendency. CONCLUSIONS AND CLINICAL IMPORTANCE: Before surgery and histopathology confirming extraparenchymal hematoma, the primary differential in most cases was neoplasia, based on the MRI findings. This retrospective study reminds clinicians of the importance of the combination of advanced imaging combined with histopathologic diagnosis. The prognosis for spontaneous spinal cord extraparenchymal hematoma with surgical decompression appears to be favorable in most cases.

Focal intestinal lipogranulomatous lymphangitis in 6 dogs (2008-2011).

BACKGROUND: Lipogranulomatous lymphangitis is inflammation of the intestinal lymphatic vessels and surrounding tissues caused by chronic leakage of lipid-laden chyle. Grossly, lipogranulomas are typically disseminated small masses on the serosa and surrounding lymphatic vessels and consist of epithelioid macrophages, multinucleated giant cells, and cholesterol. Lipogranulomatous lymphangitis is occasionally seen in patients with lymphangiectasia and protein-losing enteropathy (PLE). OBJECTIVES: To characterize the historical features, clinical signs, treatment, histopathology, and outcome of dogs with focal lipogranulomatous lymphangitis. ANIMALS: Six dogs with ultrasonographic evidence of focal, regional small intestinal masses, often with involvement of the adjacent mesentery, and a diagnosis of focal lipogranulomatous lymphangitis based on histopathology of biopsied masses. RESULTS: The median age of dogs was 6.9 years (range 3-10 years). All dogs had total protein, globulin, and albumin concentrations within the reference range at initial presentation and had intestinal masses identified on abdominal ultrasound examination. Histopathologic evaluation of lesions identified severe mural and mesenteric lipogranulomatous lymphangitis. Lymphangiectasia was noted in 5 cases and only in sections within the mass-like lesion; tissue without lipogranulomas had minimal lymphangiectasia, suggesting a localized phenomenon. Postoperative outcomes ranged from remission of clinical signs with no subsequent treatment for 10-12 months in 2 dogs, postoperative management with medical and nutritional management in 3 dogs, and no outcome for 1 case. CONCLUSIONS AND CLINICAL IMPORTANCE: This case series describes a unique mass-like manifestation of intestinal lipogranulomatous lymphangitis and should be considered as a possible differential diagnosis in dogs with an intestinal mass.

Characterization of post transplantation lymphoma in feline renal transplant recipients.

The development of malignant neoplasia following solid organ transplantation and immunosuppression is well recognized in man. Post-transplantation malignant tumours include non-melanoma skin cancers, non-Hodgkin's lymphoma and Kaposi's sarcoma and many of these cancers have a known or suspected viral cause. A similar increased incidence of cancer is seen in cats that have received a renal transplant and lymphoma is the predominant neoplasm in this population. This study examines a population of cats that received renal transplants at the University of Pennsylvania School of Veterinary Medicine and subsequently developed neoplasia. From 1998 to 2010, 111 cats were transplanted and 25 cats developed cancer (22.5%). Fourteen of the 25 cats were diagnosed with lymphoma (56%), making it the most common tumour in this patient population. The median interval between transplantation and diagnosis of lymphoma was 617 days and the median survival time (MST) following the diagnosis of lymphoma was 2 days. Tissues from seven of these cats were available for histopathological review as either samples collected at necropsy examination (n = 5) or biopsy submissions (n = 2). Five of these cats had multiorgan involvement with sites including the liver, spleen, peripheral and mesenteric lymph nodes, small intestine, urinary bladder, heart, mesenteric fat and body wall. Four of the cats with multiorgan disease had involvement of the renal allograft two of which also had lymphoma of the native kidney. All lymphomas were classified as mid to high grade, diffuse large B-cell lymphoma, which is also the most common lymphoma subtype in human cases of post-transplantation lymphoproliferative disorders.

Two hundred three cases of equine lymphoma classified according to the World Health Organization (WHO) classification criteria.

Lymphoma is the most common malignant neoplasm in the horse. Single case reports and small retrospective studies of equine lymphomas are reported infrequently in the literature. A wide range of clinical presentations, tumor subtypes, and outcomes have been described, and the diversity of the results demonstrates the need to better define lymphomas in horses. As part of an initiative of the Veterinary Cooperative Oncology Group, 203 cases of equine lymphoma have been gathered from 8 institutions. Hematoxylin and eosin slides from each case were reviewed and 187 cases were immunophenotyped and categorized according to the World Health Organization classification system. Data regarding signalment, clinical presentation, and tumor topography were also examined. Ages ranged from 2 months to 31 years (mean, 10.7 years). Twenty-four breeds were represented; Quarterhorses were the most common breed (n = 55), followed by Thoroughbreds (n = 33) and Standardbreds (n = 30). Lymphomas were categorized into 13 anatomic sites. Multicentric lymphomas were common (n = 83), as were skin (n = 38) and gastrointestinal tract (n = 24). A total of 14 lymphoma subtypes were identified. T-cell-rich large B-cell lymphomas were the most common subtype, diagnosed in 87 horses. Peripheral T-cell lymphomas (n = 45) and diffuse large B-cell lymphomas (n = 26) were also frequently diagnosed.

Clinical, histopathological and immunohistochemical characterization of canine indolent lymphoma.

Indolent lymphoma comprises up to 29% of all canine lymphoma; however, limited information exists regarding the subtypes and biological behaviour. This retrospective study describes the clinical characteristics, histopathological and immunohistochemical features, treatment, outcome and prognostic factors for 75 dogs with indolent lymphoma. WHO histopathological classification and immunohistochemistry (IHC) for CD79a, CD3, Ki67 and P-glycoprotein (P-gp) was performed. The most common histopathological subtype was T-zone, 61.7%, (MST 33.5 months), followed by marginal zone, 25%, (MST 21.2 months), P = 0.542. The addition of IHC to preliminary histopathological classification resulted in a revised diagnosis in 20.4% of cases. The use of systemic treatment did not influence survival, P = 0.065. Dogs treated with chlorambucil and prednisone did not reach a MST, compared with a MST of 21.6 months with CHOP-based chemotherapy, P = 0.057. The overall MST of 4.4 years confirms that this is indeed an indolent disease. However, the effect of systemic treatment must be determined through prospective trials.

Evaluation of adjuvant doxorubicin-based chemotherapy for the treatment of feline mammary carcinoma.

BACKGROUND: Feline mammary carcinomas (FMC) are locally invasive and highly metastatic tumors. Because of the high metastatic potential, patients often are treated with adjuvant doxorubicin-based chemotherapy, but little data exist to evaluate the effect of this strategy. HYPOTHESIS: Adjuvant doxorubicin-based chemotherapy improves outcome for FMC compared with surgery alone. ANIMALS: Cats with naturally occurring, biopsy-confirmed FMC treated with either surgery alone (Sx) or with surgery plus adjuvant doxorubicin-based chemotherapy (Sx + Chemo). METHODS: Retrospective cohort study. Clinical data were collected and compared to identify differences between groups. Outcome results were determined and compared. Prognostic factors for disease-free survival (DFS) and overall survival were evaluated. RESULTS: Seventy-three cats were evaluated, of which 37 were in the Sx group and 36 in the Sx + Chemo group. No differences in clinical data were found between Sx and Sx + Chemo groups. Median DFS times for the Sx and Sx + Chemo groups were 372 and 676 days, respectively (P= .15) and median survival times (ST) were 1,406 and 848 days, respectively (P= .78). For cats that underwent a unilateral radical mastectomy, ST was significantly longer for the Sx + Chemo compared with the Sx group (1,998 versus 414 days, respectively; P= .03). CONCLUSIONS AND CLINICAL IMPORTANCE: This study did not find a benefit to adjuvant doxorubicin-based chemotherapy in cats with FMC. Additional studies are required to determine whether patient subgroups with negative prognostic factors may benefit from adjuvant chemotherapy.

Pulmonary fibrosis after high cumulative dose nitrosourea chemotherapy in a cat.

Small to intermediate cell alimentary lymphoma was diagnosed in a cat after abdominal exploratory surgery with no prior history of pulmonary disease. Initial response to several chemotherapy regimens was poor, but a long-term remission was achieved with CCNU (lomustine) and corticosteroid therapy. After receiving a total cumulative CCNU dose of 552 mg m(-2) over 12 months, an acute episode of respiratory distress occurred and the cat died. Necropsy identified severe diffuse pulmonary fibrosis and no signs of lymphoma. This is the first report of pulmonary fibrosis following high cumulative dose nitrosourea chemotherapy in a cat.

The semipermeability of simple spherical virus capsids.

Hydrogen-ion titration curves are reported for tomato bushy stunt virus, two strains of cowpea chlorotic mottle virus, and turnip crinkle virus, with particular attention to the hysteresis loops associated with the swelling and contraction of virions. There appears to be an archetypal shape of hysteresis loops, which is shared by viruses in several groups, suggestive of many intermediate states in the swelling of any one particle. In contrast, eggplant mosaic virus behaves as if its protein capsid is impermeable to small ions in mild conditions; its cation-binding sites were revealed by treatment with high concentrations of salt or urea, or at raised temperatures. Putting these observations together with the fact that a spherical virus capsid is a closed, holey, charged surface leads to a theory of titration hysteresis: its key feature is that the protein capsids of simple viruses are inherently semipermeable, with many of the ion-handling properties usually attributed only to complex lipid membranes.

A survey of readily available chelators for buffering calcium ion concentrations in physiological solutions.

Stability constants are reported for the binding of H+, Ca2+ and Mg2+ ions to the chelators commonly abbreviated EGTA, EDTA, HEDTA, DPA, NTA, ADA, and citrate, under uniform conditions of physiological temperature and ionic strength. Other compounds usable as calcium buffers are listed. The theoretical and practical considerations that influence the actual pCa attained in a chelator solution are discussed and a Hepes-buffered saline solution is suggested as a standard of "physiological pH". With these figures it is possible to make a rational choice of chelator to control the pCa and pMg of solutions for investigations in cell physiology, drug action, virus reproduction, and ion binding to proteins.

A survey of the available colorimetric indicators for Ca2+ and Mg2+ ions in biological experiments.

The binding of Ca2+ and Mg2+ ions to commercially available and easily synthesizable metallochromic indicators has been systematically examined at pH 7.35, temperature 37 degrees C, ionic strength 0.16, the conditions of blood plasma. The pCa and pMg midpoints of the colour changes of all the useful indicators are reported. In addition to the well-known indicators arsenzazo III, chlorophosphonazo III, antipyrylazo III, and murexide for Ca2+, and Eriochrome Black T and Eriochrome Blue SE for Mg2+, we draw attention to the values of oxyacetazo I, carboxyazo III, tropolone, methylthymol blue, Mordant Black 32, and the tetracyclines.

Calcium ions and the control of proliferation in normal and cancer cells.

Several lines of evidence suggest tha Ca2+ ions control cell proliferation: Ca2+ entry into cytoplasm acts as a general mitogen; serum and serum-replacements induce Ca2+ influx; the Ca2+ concentrations in growth media required to support the proliferation of normal cells are much higher than those required for cancer cells; serum and growth factors reduce the Ca2+ requirements of normal cells; tumour promoters alter Ca2+ fluxes via a mechanism used principally by growth factors. Minor supporting evidence includes the effects of various drugs and viruses, and the behaviour of tumour cell mitochondria and intercellular junctions. It is still not possible to decide exactly where and when inside cells the critical effect of Ca2+ on proliferation occurs, but we discuss at length the practical problems of understanding Ca2+ movements in tissue-culture cells. Carried to its logical conclusion, present evidence suggests that an overridden or bypassed Ca2+ control process may be the key, common determinant of unrestrained proliferation in cancer cells.

The generality of cation-binding sites in rod-shaped viruses.

Hydrogen-ion titration curves have been measured for two filamentous plant viruses (clover yellow mosaic virus and potato virus X) and two filamentous bacterial viruses (fd and Pf1) with and without Ca2+ or Mg2+ ions present, and for the protein of the PM6 mutant of tobacco mosaic virus. The bacterial viruses do not possess the 'strong' cation-binding sites found in all plant viruses, but they have 'weak' sites that can be assigned to juxtaposed carboxylate groups on their external surfaces. The strong sites in plant viruses still cannot be assigned to any particular amino-acid side chains, but they must be located in the region of high electronegativity near the axis.

Titration behaviour of three strains of tobacco mosaic virus.

Hydrogen ion titration curves of the virions and proteins of three strains of tobacco mosaic virus (Y-TAMV, U2, and cowpea) were measured in the absence and the presence of Ca2+, Mg2+, or Mn2+ ions, and compared with the analogous curves for the type strain (vulgare). Extinction coefficients were also measured for all four strains' virions and proteins. Y-TAMV is very like vulgare in its cation affinities: the virion has probably three groups per protein subunit that titrate near neutral pH and significantly bind metal ions; the RNA-free protein has very little affinity for Ca2+, although moderate Ca2+ concentrations favour the existence of larger polymers. U2 and cowpea strain virions bind cations significantly more strongly than do Y-TAMV or vulgare virions: their polymerized proteins, too, have significant affinities for Ca2+ ions, which make their titration and sedimentation behaviours relatively sensitive to added calcium. These cation-binding differences correspond well with the differences between the strains' protein sequences. The features common to all four strains are that the virions are apparently structurally invariant and have at least one site per subunit with Ca2+ affinity in the region of 10(-5)M, while the RNA-free proteins lack the high-affinity sites but have weaker Ca2+ affinities in the region of 10(-3)M. Some of the cation-binding sites probably lie near the central holes of the virions.

The roles of small ions, especially calcium, in virus disassembly, takeover, and transformation.

Three related hypotheses are proposed. (1) Many simple viruses disassemble in the act of crossing a membrane, drawing energy from ionic disequilibria across the membrane. (2) Many of the metabolic changes early in virus infection are due to altered ion fluxes across membranes and the consequently altered ion concentrations in cytoplasm. (3) The crucial determinant of the transformed phenotype is also a change in ion concentrations. Ca2+ ions may play a major role in these effects.

Hydrogen-ion binding by tobacco-mosaic-virus protein polymers.

Hydrogen ion titration curves of tobacco mosaic virus protein have been measured in various conditions of protein concentration, temperature, ionic strength, and rate of pH change. The polymers present at each stage are deduced from turbidity and sedimentation data, plus published information. A simple semi-quantitative analysis of the curves is given, and the pK values of the two abnormal carboxylates in single helix are estimated as 6.4 and about 7.0. Disks, and some faster-forming unknown polymers in the same size range, have been abnormal carboxylate with pK 6.9. These results are most easily interpreted in terms of electrostatic interactions between carboxylates, probably at the axial ends of the protein subunits.