Systemic iron reduction via an iron deficient diet decreases the severity of knee cartilage lesions in the Dunkin-Hartley guinea pig model of osteoarthritis.

OBJECTIVE: Iron accumulation is emerging as a player in aging-related disorders due to its propensity for generating reactive oxygen species (ROS). Studies investigating the role of iron in the pathogenesis of primary osteoarthritis (OA) are limited. We designed a proof-of-principle study to determine the effect of systemic iron deficiency, via an iron deficient diet, on knee OA in an animal model. METHODS: Twelve-week-old male Hartley guinea pigs received the standard diet (n = 6) or a diet devoid of iron (n = 6) for 19-weeks. Iron levels were determined in the serum, liver, and articular cartilage. Knees were collected to assess structural changes related to OA (microcomputed tomography, histopathology). Immunohistochemistry was performed to evaluate the presence and distribution of a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS4) and ROS-driven 4-hydroxynonenal (4-HNE)-induced protein adducts. Transcript expression was also assessed. RESULTS: Relative to control animals, an iron deficient diet reduced the concentration of this mineral in serum, liver, and articular cartilage. Iron deficient animals had lower histologic OA scores; decreased subchondral bone mineral density was also noted. This reduction in knee joint pathology was accompanied by a decrease in: ADAMTS4 in synovium; and 4-HNE protein adducts from lipid peroxidation in both the menisci and articular cartilage of iron deficient animals. Expression of iron-related genes in these tissues was also altered in treated animals. CONCLUSIONS: Results from this study suggest that systemic iron levels may play a role in knee OA pathogenesis, with a short-term deficit in dietary iron reducing the severity of knee cartilage lesions.

Prevalence of portal vein thrombosis detected by computed tomography angiography in dogs.

OBJECTIVE: To evaluate dogs with computed tomography angiography of the abdomen for overall prevalence of portal vein thrombosis and prevalence of portal vein thrombosis based on different disease categories. To evaluate dogs with and without portal vein thrombosis for differences in outcome. To compare ultrasound to computed tomographic angiography for identification of portal vein thrombosis. METHODS: Abdominal computed tomography angiography of 223 client-owned animals was reviewed for evidence of portal vein thrombosis. Based on medical records, dogs were assigned to disease categories: (1) liver disease; (2) non-hepatic neoplasia; (3) pancreatitis; (4) infectious disease; (5) immune-mediated disease; (6) other; (7) multiple diseases. Different categories were compared for the prevalence of portal vein thrombosis. Outcome was evaluated in dogs with and without portal vein thrombosis. Ultrasound reports were reviewed to determine the detection of thrombosis on ultrasound. RESULTS: Twenty-eight dogs (13%) had portal vein thrombosis. The pancreatitis category contained the highest percentage of portal vein thrombosis among different categories (eight of 19; 42%). There was a similar outcome between dogs with and without portal vein thrombosis. Of 21 dogs with portal vein thrombosis that had ultrasound performed, ultrasound detected thrombosis in four of 21 (19%) cases. CLINICAL RELEVANCE: In this study, portal vein thrombosis prevalence was higher in dogs with pancreatitis compared to dogs with liver disease, non-hepatic neoplasia and other abdominal or systemic disease. The portal system should be carefully evaluated with imaging in dogs with pancreatitis. As compared to ultrasound, CT angiography is the imaging method of choice for detection of portal vein thrombosis in dogs.

Systemic iron overload exacerbates osteoarthritis in the strain 13 guinea pig.

OBJECTIVE: Iron is emerging as a key player in aging-associated diseases due to its propensity for driving free radical formation. Studies examining the role of iron in the pathogenesis of primary osteoarthritis (OA) are limited. Our objective was to establish a direct relationship between excess iron and OA by administering iron dextran to a guinea pig strain with decreased propensity for developing this disease. DESIGN: Twenty, 12-week-old Strain 13 guinea pigs received either iron dextran or dextran control intraperitoneally once weekly for 4 weeks; termination occurred at 16 weeks of age. Iron levels were determined systemically (serum and liver) and within diarthrodial joints [femoral head articular cartilage and infrapatellar fat pads (IFPs) of knee joints]. One knee was collected to score structural changes associated with OA via microcomputed tomography (microCT) and histology using published grading schemes. Articular cartilage and IFPs were harvested from contralateral knees for gene expression analyses. RESULTS: Iron overload was confirmed systemically via increased serum iron and liver iron concentration. Articular cartilage and IFPs in the iron dextran group also had higher levels of iron. Excess iron worsened knee OA using both microCT and histologic scoring systems. Gene analyses revealed that exogenous iron altered the expression of iron trafficking proteins, select cytokines, and structural components of cartilage. CONCLUSION: These results demonstrate that systemic iron overload caused cellular iron accumulation in the knee joint. This excess iron is associated with increased expression of local inflammatory mediators and early onset and progression of knee joint OA in Strain 13 animals.

Experimental Transmission of Bighorn Sheep Sinus Tumors to Bighorn Sheep (Ovis canadensis canadensis) and Domestic Sheep.

Bighorn sheep sinus tumors are a recently described disease affecting the paranasal sinuses of Rocky Mountain bighorn sheep (Ovis canadensis canadensis). Several features of this disease suggest an infectious cause, although a specific etiologic agent has not been identified. To test the hypothesis that bighorn sheep sinus tumors are caused by an infectious agent, we inoculated 4 bighorn sheep lambs and 4 domestic sheep lambs intranasally with a cell-free filtrate derived from a naturally occurring bighorn sheep sinus tumor; we held 1 individual of each species as a control. Within 18 months after inoculation, all 4 inoculated domestic sheep (100%) and 1 of the 4 inoculated bighorn sheep (25%) developed tumors within the ethmoid sinuses or nasal conchae, with features similar to naturally occurring bighorn sheep sinus tumors. Neither of the uninoculated sheep developed tumors. Histologically, the experimentally transmitted tumors were composed of stellate to spindle cells embedded within a myxoid matrix, with marked bone production. Tumor cells stained positively with vimentin, S100, alpha smooth muscle actin, and osteocalcin, suggesting origin from a multipotent mesenchymal cell. A periosteal origin for these tumors is suspected. Immunohistochemical staining for the envelope protein of JSRV (with cross-reactivity to ENTV) was equivocal, and PCR assays specific for these agents were negative.

Comparison of endoscopy and sonography findings in dogs and cats with histologically confirmed gastric neoplasia.

OBJECTIVE: To compare sonographic and endoscopic findings in a group of dogs and cats with histologically confirmed gastric neoplasia. METHODS: Retrospective analysis of cases with concurrent abdominal ultrasound and endoscopy to evaluate the presence of gastric wall abnormalities, location and tumour appearance between the two examinations. Sonographic findings of the small intestines, liver, spleen and lymph nodes were recorded. Comparison of the findings from each test and assessment of predictive characteristics for neoplasia was evaluated. RESULTS: In total 17 dogs and 5 cats were included, Sonography identified 50% and endoscopy identified 95% of all gastric neoplasms. Lymphoma was the most commonly missed tumour by sonography. There was sonographic and endoscopic tumour location agreement in 36% of cases (Cohen's kappa = 0 · 25). Animals with sonographically normal small intestines had a statistically greater probability of gastric neoplasia (P = 0 · 035). All cats had lymphoma (P < 0 · 001). CLINICAL SIGNIFICANCE: Sonography and endoscopy are useful for the diagnosis of gastric neoplasia. Endoscopy is more accurate in identifying gastric neoplasia; however, sonography can raise the clinical suspicion for gastric neoplasia and may provide a less invasive means of gathering information before endoscopy. Intraluminal gastric gas or fluid may limit diagnostic capabilities of sonographic evaluation.

Computed tomographic angiography under sedation in the diagnosis of suspected canine pancreatitis: a pilot study.

BACKGROUND: Computed tomography (CT) is highly accurate for diagnosing pancreatitis in humans. The diagnosis of pancreatitis in dogs is based on clinical signs, laboratory findings, and ultrasonographic (US) changes. There are, however, inherent limitations in relying on laboratory and ultrasound findings for the clinical diagnosis of pancreatitis in dogs. HYPOTHESIS/OBJECTIVES: We hypothesized that CT angiography would be a rapid and reliable method to confirm pancreatitis in dogs compared to ultrasonography. The aim was to describe the CT characteristics and compare them to ultrasound findings and correlate the CT appearance to the severity of the patients' clinical course. ANIMALS: A prospective pilot case series; 10 dogs with pancreatitis were enrolled if the history, clinical signs, laboratory, and ultrasonographic findings were indicative of pancreatitis. METHODS: A 3-phase angiographic CT was performed under sedation. Afterward, each dog had US-guided aspirates of the pancreas collected and blood drawn for cPLi assay. Images were evaluated for portion of visible pancreas, pancreatic size and margin, pancreatic parenchyma, presence of peripancreatic changes and contrast enhancement pattern. The results were compared with outcome. RESULTS: An enlarged, homogeneously to heterogeneously attenuating and contrast-enhancing pancreas with ill-defined borders was identified in all dogs. CT identified more features characterizing pancreatic abnormalities compared to US. Thrombi were found in 3/10 dogs. Three dogs with heterogeneous contrast enhancement had an overall poorer outcome than those with homogenous enhancement. CONCLUSIONS AND CLINICAL IMPORTANCE: CT angiography under sedation was used in dogs to confirm clinically suspected pancreatitis and identified clinically relevant and potentially prognostic features of pancreatitis in dogs.

Effects of FSH and LH on ovarian and follicular blood flow, follicular growth and oocyte developmental competence in young and old mares.

Objectives of the experiment were to determine the effects of mare age and gonadotropin treatments on dominant follicle vascularity, ovarian blood flow and dominant follicle growth and to associate follicular vascularity with oocyte developmental capacity. Growing follicles >30 mm from young (4-9 years) and old (>20 years) mares were assessed for blood flow using color Doppler ultrasonography before maturation induction with recombinant equine LH (eLH) and immediately prior to oocyte collection at 20-24 h after eLH. Pulsed Doppler was used to obtain resistance indices of ovarian arteries ipsilateral to preovulatory follicles. For eFSH-treated estrous cycles, eFSH administration was started after detection of a cohort of follicles ≥20 to <25 mm and continued until a follicle >30 mm. Oocytes were harvested using transvaginal, ultrasonic-guided aspirations and cultured and injected with sperm at 40 ± 1 h after eLH. Presumptive zygotes were incubated, and rates of cleavage (≥2 cells) and blastocyst formation were obtained. Embryos were transferred nonsurgically into recipients' uteri, and pregnancy rates were assessed. Vascularity (number of color pixels per total pixels) was higher (P=0.003) in the follicles of old compared to young mares, with no significant interaction of eFSH or eLH. Effects of eFSH and time from eLH on follicle vascularity were not significant. The vascularity of follicles associated with oocytes that did compared to those that did not form blastocysts was greater (P=0.048), although follicular vascularity was less (P=0.02) for follicles associated with oocytes that did compared to those that did not develop into pregnancies. Resistance indices were not different for age, eFSH treatment, time after eLH administration and oocyte developmental potential. Growth of the dominant follicle was not associated with vascularity, although advanced age tended (P=0.09) to have a negative effect on follicle growth.

Amniotic fluid embolism: a case with non-cardiogenic pulmonary edema.

We report an uncommon case of amniotic fluid embolism (AFE) in a 24-year-old woman with a 26th-week, second pregnancy. Clinical manifestations were dominated by acute respiratory distress and pulmonary edema. Recovery was complete. Early invasive hemodynamic studies showed normal function of the left ventricle with a low pulmonary artery occluded pressure. These findings are controversial to the concept of cardiogenic pulmonary edema in AFE.

Abnormal coronary vasomotion during exercise in patients with normal coronary arteries and reduced coronary flow reserve.

A reduced coronary flow reserve has been reported in patients with ischemialike symptoms and normal coronary arteries. In 13 such patients, both coronary vasomotion and flow reserve were studied. The luminal area of the proximal and distal third of the left anterior descending and left circumflex artery were determined by biplane quantitative coronary arteriography using a computer-assisted system. Patients were studied at rest, during submaximal supine bicycle exercise (4.0 minutes, 116 W), and 5 minutes after sublingual administration of 1.6 mg nitroglycerin. Heart rate, mean pulmonary pressure, and mean aortic pressure as well as the percent change of both proximal and distal luminal area were determined. In 10 of the 13 patients, coronary sinus blood flow was measured by coronary sinus thermodilution technique at rest and after dipyridamole infusion (0.5 mg/kg in 15 minutes) 10 +/- 5 days after quantitative coronary arteriography. Coronary flow ratio (dipyridamole/rest) and coronary resistance ratio (rest/dipyridamole) were determined in these patients. Patients were divided into two groups according to the behavior of the coronary vessels during exercise (vasodilation, group 1; vasoconstriction, group 2). Coronary vasodilation of the proximal (luminal area +26%, p less than 0.001) and distal (+45%, p less than 0.001) artery was observed in seven patients (group 1) during exercise and after sublingual nitroglycerin (+46%, p less than 0.001; and +99%, p less than 0.001, respectively). In group 2 (n = 6), however, there was coronary vasoconstriction of the distal vessel segments (-24%, p less than 0.001) during exercise, whereas the proximal coronary artery showed vasodilation (+26%, p less than 0.001) during exercise. After sublingual nitroglycerin, both vessel segments elicited vasodilation (distal coronary, +44%, p less than 0.001; proximal coronary artery, +47%, p less than 0.001). Coronary flow ratio amounted to 2.5 in group 1 and 1.2 in group 2 (p less than 0.05) and coronary resistance ratio to 2.7 in group 1 and to 1.2 in group 2 (p less than 0.05), respectively. Thus, among patients with ischemialike symptoms and normal coronary arteries, there is a group of patients (group 2) with an abnormal dilator response of the distal coronary arteries to the physiologic dilator stimulus of exercise and a reduced dilator capacity of the resistance vessels after dipyridamole (abnormal coronary vasodilator syndrome). The nature of this exercise-induced distal coronary vasoconstriction is not clear but might be due to an abnormal neurohumoral tone that may cause or contribute to the blunted vascular response during exercise.

Comparison of casual, ambulatory and self-determined blood pressure measurement.

In this study, self-determined, ambulatory and casual blood pressure measurements were studied in patients with mild to moderate essential hypertension. 31 patients were studied during a 7-day period: casual blood pressures were taken on the 1st, 4th and 7th day. Pressure monitoring for 24 h using a noninvasive ambulatory blood pressure recorder was performed on the 1st and 7th day. Patients recorded blood pressure daily at home at least 3 times each day. On the 1st day, the mean casual blood pressure was significantly higher than either mean self-determined blood pressure or mean 24-hour ambulatory blood pressure. There was no significant difference between ambulatory daytime means and self-determined means. Casual blood pressures decreased from day 1 to day 7 significantly, while no significant difference in self-determined or ambulatory readings was observed. On the 7th day casual blood pressures were still significantly higher than self-determined measurements. Our results show that values obtained from daytime ambulatory measurements and self-determined measurements were equivalent. A fall in blood pressure with serial observations was found only in casual blood pressure, while no significant change occurred with either self-determined or ambulatory pressure. Since self-determined blood pressure measurements are easier and more economical to perform than ambulatory measurements, self-determined measurement is an excellent alternative to obtain representative blood pressure values for the diagnosis and treatment of hypertension.