Leukemia circulation kinetics revealed through blood exchange method.

Leukemias and their bone marrow microenvironments undergo dynamic changes over the course of disease. However, little is known about the circulation kinetics of leukemia cells, nor the impact of specific factors on the clearance of circulating leukemia cells (CLCs) from the blood. To gain a basic understanding of CLC dynamics over the course of disease progression and therapeutic response, we apply a blood exchange method to mouse models of acute leukemia. We find that CLCs circulate in the blood for 1-2 orders of magnitude longer than solid tumor circulating tumor cells. We further observe that: (i) leukemia presence in the marrow can limit the clearance of CLCs in a model of acute lymphocytic leukemia (ALL), and (ii) CLCs in a model of relapsed acute myeloid leukemia (AML) can clear faster than their untreated counterparts. Our approach can also directly quantify the impact of microenvironmental factors on CLC clearance properties. For example, data from two leukemia models suggest that E-selectin, a vascular adhesion molecule, alters CLC clearance. Our research highlights that clearance rates of CLCs can vary in response to tumor and treatment status and provides a strategy for identifying basic processes and factors that govern the kinetics of circulating cells.

Spontaneous pneumothorax in a dog with a history of successfully treated heartworm disease: A case report.

OBJECTIVE: To describe a dog presented with spontaneous pneumothorax secondary to chronic pulmonary changes associated with a history of resolved canine heartworm disease. CASE OR SERIES SUMMARY: A 7-year-old 25.2kg female spayed German Shepherd mix was presented for management of spontaneous pneumothorax. The dog had a history of heartworm disease that underwent therapy prior to adoption, and the dog was heartworm antigen negative (SNAP 4Dx) during hospitalization for the pneumothorax. An exploratory thoracotomy was performed due to an unresolving pneumothorax requiring multiple thoracocenteses. Perioperatively, the lungs did not expand with positive pressure ventilation and diffuse, multifocal to coalescing areas of darkened tissue that were grossly consistent with necrosis and/or hemorrhage were noted. The dog was euthanized intraoperatively due to an assumed poor prognosis. Histopathologic examination findings were consistent with chronic reactive changes related to previous heartworm infection. No neoplastic or infectious etiologies were identified. NEW OR UNIQUE INFORMATION PROVIDED: Spontaneous pneumothorax is a known complication of active heartworm infection. However, this case represents the first report of spontaneous pneumothorax secondary to chronic pulmonary changes caused by resolved heartworm infection.

Leukemia circulation kinetics revealed through blood exchange method.

Leukemias and their bone marrow microenvironment are known to undergo dynamic changes over the course of disease. However, relatively little is known about the circulation kinetics of leukemia cells, nor the impact of specific factors on the clearance of circulating leukemia cells (CLCs) from the blood. To gain a basic understanding of leukemia cell dynamics over the course of disease progression and therapeutic response, we apply a blood exchange method to mouse models of acute leukemia. We find that CLCs circulate in the blood for 1-2 orders of magnitude longer than solid tumor circulating tumor cells. We further observe that: i) leukemia presence in the marrow can limit the clearance of CLCs in a model of acute lymphocytic leukemia (ALL), and ii) CLCs in a model of relapsed acute myeloid leukemia (AML) can clear faster than their untreated counterparts. Our approach can also directly quantify the impact of microenvironmental factors on CLC clearance properties. For example, data from two leukemia models suggest that E-selectin, a vascular adhesion molecule, alters CLC clearance. Our research highlights that clearance rates of CLCs can vary in response to tumor and treatment status and provides a strategy for identifying basic processes and factors that govern the kinetics of circulating cells.

Diagnosis and Conservative Management of Primary Lymphedema Resulting From Multiple Aplastic Lymphocenters in a Dog.

A 6-week-old 7.4-kg (16.3-lb) sexually intact male Great Dane with a history of severe peripheral edema within the head, neck, limbs, and tail since birth was referred for further evaluation. A whole-body computed tomography examination documented severe subcutaneous edema multifocally associated with numerous hypoplastic and aplastic lymphocenters, particularly the left axillary, iliosacral, inguinal, and popliteal lymphocenters bilaterally. A congenital anomaly of the lymphatic system resulting in lymphedema was strongly suspected. The dog was managed with a combination of low-fat diet, rutin, and furosemide initially. In addition, the owner used a combination of compression socks and therapeutic massage several times daily along with carprofen and gabapentin for pain and inflammation. The patient was hospitalized to receive supportive care several times over a 2-year period for treatment of fever associated with cellulitis resulting in secondary wounds and infections. To the author's knowledge, this report represents the first case of presumed congenital lymphedema diagnosed with computed tomography and successful long-term medical management without surgical intervention.

Measuring kinetics and metastatic propensity of CTCs by blood exchange between mice.

Existing preclinical methods for acquiring dissemination kinetics of rare circulating tumor cells (CTCs) en route to forming metastases have not been capable of providing a direct measure of CTC intravasation rate and subsequent half-life in the circulation. Here, we demonstrate an approach for measuring endogenous CTC kinetics by continuously exchanging CTC-containing blood over several hours between un-anesthetized, tumor-bearing mice and healthy, tumor-free counterparts. By tracking CTC transfer rates, we extrapolated half-life times in the circulation of between 40 and 260 s and intravasation rates between 60 and 107,000 CTCs/hour in mouse models of small-cell lung cancer (SCLC), pancreatic ductal adenocarcinoma (PDAC), and non-small cell lung cancer (NSCLC). Additionally, direct transfer of only 1-2% of daily-shed CTCs using our blood-exchange technique from late-stage, SCLC-bearing mice generated macrometastases in healthy recipient mice. We envision that our technique will help further elucidate the role of CTCs and the rate-limiting steps in metastasis.

Unilateral MRI using a rastered projection.

Unilateral magnetic resonance techniques, where magnet and radio frequency (RF) coil are placed on one side of the sample, can provide valuable information about a sample which otherwise cannot be accommodated in conventional high spectral resolution magnetic resonance systems. A unilateral magnetic resonance imaging approach utilizing the stray field from a disc magnet and a butterfly geometry RF coil is described. The coil excites spins in a volume centered around an arc through the sample. Translating the RF coil relative to the magnet and recording the signal at each translational location creates a projection of the signal in a tomographic slice through the sample. Rotating the RF coil relative to the sample and repeating the translation creates projections through the sample at different angles. Backprojecting this information yields an image. A proof of concept device operating on this principle at 12.4 MHz was constructed and characterized. Projections through three phantoms are presented with a 1.2-4 cm field of view, thickness of 102 microm, and at a distance of 3mm from the RF coil and 14 mm from the magnet. The edge spread function (ESF) was measured resulting in a 4mm full width at half maximum (FWHM) line spread function (LSF) estimation using a Gaussian model. An example of one reconstructed image is presented.