Patricia M. McManus

Linking Hematopoiesis to Endochondral Skeletogenesis through Analysis of Mice Transgenic for Collagen X

Each skeletal element where marrow develops is first defined by a hypertrophic cartilage blueprint. Through programmed tissue substitution, the cartilaginous skeletal model is replaced by trabecular bone and marrow, with accompanying longitudinal tissue growth. During this process of endochondral ossification, hypertrophic cartilage expresses a unique matrix molecule, collagen X. Previously we reported that transgenic mice with dominant interference collagen X mutations develop variable skeleto-hematopoietic abnormalities, manifested as growth plate compressions, diminished trabecular bone, and reduced lymphatic organs (Nature 1993, 365:56). Here, histology and flow cytometry reveal marrow hypoplasia and impaired hematopoiesis in all collagen X transgenic mice. A subset of mice with perinatal lethality manifested the most severe skeletal defects and a reduction of marrow hematopoiesis, highlighted by a lymphocyte decrease. Thymic reduction is accompanied by a paucity of cortical immature T cells, consistent with the marrows inability to replenish maturing cortical lymphocytes. Diminished spleens exhibit indistinct lymphatic nodules and red pulp depletion; the latter correlates with erythrocyte-filled vascular sinusoids in marrows. All mice display reduced B cells in marrows and spleens, and elevated splenic T cells. These hematopoietic defects underscore an unforeseen link between hypertrophic cartilage, endochondral ossification, and establishment of the marrow microenvironment required for blood cell differentiation.

Multiple myeloma in 16 cats: a retrospective study

Background: There is limited published information regarding feline multiple myeloma. Diagnostic criteria are derived from canine studies and to our knowledge, have not been critically reviewed for cats. Objective: To evaluate the clinical and laboratory findings in cats with multiple myeloma and appraise diagnostic criteria. Methods: Retrospective evaluation of medical records was performed. Inclusion required an antemortem diagnosis of multiple myeloma using 2 of 4 criteria: 1) ≥20% plasma cells in the bone marrow, or ≥10% if atypical plasma cells; 2) paraproteinemia; 3) radiographically‐evident osteolysis; 4) light chain proteinuria. Alternatively, a postmortem diagnosis was based on the findings of multiple plasma cell neoplasms, with marrow involvement. Results: Sixteen cats were diagnosed with multiple myeloma between 1996 and 2004, with a median age of 14.0 years; 9 of 16 (56%) were castrated males, and 7 of 16 (44%) were spayed females. Laboratory abnormalities included hyperglobulinemia (14/16, 87.5%), with 11/14 (78.5%) monoclonal and 3/14 (21.4%) biclonal gammopathies; hypoalbuminemia (4/16, 25%); light chain proteinuria, (4/9, 44.4%); hypocholesterolemia (11/16, 68.7%); hypercalcemia, (3/15, 20%); nonregenerative anemia, (11/16, 68.7%); regenerative anemia, (1/16, 6.2%); neutropenia (5/15, 33.3%); thrombocytopenia (8/16, 50%); and marrow plasmacytosis (14/15, 93.3%). Plasma cells were markedly immature, atypical, or both in 10 of 12 (83.3%) cats. Focal or multifocal osteolysis was noted in 6 of 12 (50%) cats for which radiographs were available for review; generalized osteopenia was found in 1 (8.3%) cat. Noncutaneous, extramedullary tumors were found in all cats assessed, 7/7 (100%), including spleen (6), liver (3), and lymph nodes (4). The disease in 1 of 2 cats with cutaneous tumors progressed to plasmacytic leukemia. Conclusions: Common findings in feline multiple myeloma include atypical plasma cell morphology, hypocholesterolemia, anemia, bone lesions, and multi‐organ involvement. Based on the results of this study, we advocate modifying diagnostic criteria in cats to include consideration of plasma cell morphology and visceral organ infiltration.

Rescue therapy with doxorubicin-based chemotherapy for relapsing or refractory feline lymphoma: A retrospective study of 23 cases⋆

This study examined the efficacy of doxorubicin-based chemotherapy used for rescue therapy in refractory feline lymphoma. Records of 23 cats with lymphoma treated with chemotherapy who received doxorubicin for the first time in a rescue setting were reviewed. Seventeen (74%) of the 23 cats had only one treatment of doxorubicin. Five (22%) of the 23 cats had a positive response to doxorubicin and were given additional doses. The response to therapy in 4/5 of these responders could be assessed objectively, of which, two cats (9%) achieved partial remission (PR) and two cats (9%) achieved complete remission (CR). The two cats that achieved CR had differing response durations (6 weeks and greater than 47 months). Three of these five (60%) responders had also received concurrent other chemotherapy in addition to doxorubicin. Cell type and the use of concurrent chemotherapy were significant predictors of response. Cats with small-medium cell lymphomas (P=0.001) and cats that received concurrent chemotherapy with doxorubicin rescue (P=0.007) were more likely to respond favorably. This study suggests that doxorubicin-based chemotherapy is not an effective rescue protocol for feline lymphoma.

Immune‐Mediated Neutropenia in 2 Dogs

Immune‐mediated neutropenia, also termed autoimmune neutropenia (AIN), is an uncommon event, rarely documented within veterinary literature, although the clinical profile and probable pathogenesis have been outlined in detail within medical literature. In this paper, we review 2 different manifestations of this disorder. The 1st case primarily involved peripheral destruction of mature neutrophils, with little impact on marrow precursors, whereas the 2nd case resulted in suppression of neutrophilic granulopoiesis within marrow. In both cases, absolute neutrophil counts dropped below 200/mL.

Dr. William Medway (1927–2006): teacher and colleague from yesterday, remembered today, and influencing tomorrow

From 1958 to 1988, Dr. Bill Medway’s name was synonymous with clinical pathology for veterinary students, house staff, and fellow faculty at the University of Pennsylvania School of Veterinary Medicine, where he was Professor and Chief of Clinical Laboratory Medicine. By co-authoring and co-editing one of the first substantial textbooks on veterinary clinical pathology in 1969, his influence in the field of laboratory medicine extended beyond the Penn community. However, many Penn students did not know that the mammals that inspired his passion for clinical pathology and were the source of his happiest and most satisfying professional experiences swam underwater! Indeed, his finest and most enduring legacy lies in his pioneering research and instruction in the field of aquatic mammal medicine and clinical pathology, which included varied publications that ranged from reports of bacterial and mycotic infections in marine mammals to Dirofilaria immitis infection in a harbor seal to the effects of prolonged halothane anesthesia on cetaceans, as well as chapters on clinical pathology of marine mammals. Dr. Medway imparted his expertise in various forums, including as a teacher in the Aquavet Program, a joint PennCornell instructional program for veterinary students and veterinarians conducted every summer since 1977 at the Marine Biological Laboratory in Woods Hole, Massachusetts. Members of the ASVCP will be most interested in his studies of the clinical pathology of dolphins and manatees, done over 3 decades beginning in the 1960s. Some of these works stood alone as the only information available for these species for over 30 years and continue to be cited. Between 1963 and 1967 many of us were watching a dolphin by the name of Flipper dance, play, and talk in movies and on television. As we were entertained, Dr. Medway and co-author Dr. Joseph Geraci were drawing blood from 6 bottlenose dolphins during a tagging event that resulted in publication of a paper describing their hematology in 1964 and their blood chemistries in 1965. The investigation pre-