Noninvasive monitoring of doxorubicin cardiotoxicity: a pilot study of two dogs

The cardiotoxicity of anthracycline anticancer agents, most notably doxorubicin, limits their use in treating a wide variety of cancers. Currently available methods for assessment of anthracycline‐induced cardiotoxicity (AIC) often lack specificity and sensitivity. The purpose of this pilot investigation was to determine noninvasive diagnostic methods that are predictive for AIC. Two mongrel dogs were anesthetized for injection of doxorubicin (22.5 mg) directly into the left coronary artery. Doxorubicin injection was repeated 2 weeks later. Dogs were followed for 12 weeks or until heart failure was documented. Dogs were monitored before and at serial time points after doxorubicin using echocardiography and signal‐averaged electrocardiography as well as ambulatory ECG monitoring. Blood was also collected for measurement of cardiac troponin I and T concentrations. Doxorubicin was readministered at 6 and 12 weeks after the second injection, as interim data analysis did not reveal adequate evidence of cardiomyopathy. Dog‐1 appeared to be more sensitive than Dog‐2 to AIC based upon gradual changes in variables of cardiac function and earlier time to failure (113 days). In contrast, Dog‐2 had inconsistent changes in cardiac function and a longer time to failure (139 days). Dog‐1 also had greater peak plasma cardiac troponin I levels (17.96 ng/ml) as compared to peak levels in Dog‐2 (4.08 ng/ml). In addition, Dog‐1 had increased ventricular extrasystolic contractions (VE)(0/day at baseline, 443/day one week prior to death), whereas dog‐2 showed very few VE's throughout. Spectral analysis of ECG data also revealed a significant decrease over time in total spectral power in Dog‐1 from 37,148 at baseline to 603 msec²/Hz one week prior to death, indicating decreased parasympathetic tone. Endomyocardial biopsies revealed minor changes despite significant clinical abnormalities. These data indicate differences in susceptibility to AIC between Dog‐1 and Dog‐2, and suggest a role for these noninvasive measures in monitoring the heart during chemotherapy.     

Clinical Evaluation of Tavocept to Decrease Diuresis Time and Volume in Dogs with Bladder Cancer Receiving Cisplatin

Background

Transitional cell carcinoma is the most common bladder cancer of dogs. Cisplatin combined with piroxicam provides superior response rates, but unacceptable rates of nephrotoxicity. Tavocept is a chemoprotectant that has mitigated cisplatin toxicity and decreased the required infusion/diuresis volume in clinical trials in humans.

Hypothesis/Objectives

We hypothesized that Tavocept would decrease diuresis volume and time and facilitate safe administration of a cisplatin/piroxicam protocol to dogs with bladder cancer. Secondary objectives were to compare response rate and survival times to an historical comparator group treated without Tavocept.

Animals

Fourteen client‐owned dogs were prospectively enrolled.

Methods

Tumor volume was measured by computed tomography at days 0, 42, and 84. Dogs received combination Tavocept/cisplatin with a shortened diuresis protocol. A total of 4 doses was planned, with concurrent administration of piroxicam. Serial biochemical analyses were evaluated for azotemia.

Results

A 90‐minute infusion/diuresis time was used for all dogs. Three dogs (21%) had concurrent increases in serum creatinine (>2.0 mg/dL) and BUN (>42 mg/dL) concentrations; 2 of these dogs were isosthenuric. This frequency of nephrotoxicity is significantly less (P = 0.0406) than that of an historical control group treated without Tavocept. Overall response rate was 27%. Median survival time was comparable to historical controls (253 vs. 246 days).

Conclusions and Clinical Importance

Tavocept decreased the required diuresis time with cisplatin from > 6 hours to 90 minutes, while also decreasing occurrence of azotemia. Survival time was comparable, but the response rate was inferior to an historical comparator group. Further evaluation in other tumors susceptible to platinum agents is warranted.     

Effect of hay type on cecal and fecal microbiome and fermentation parameters in horses

The effect of hay type on the microbiome of the equine gastrointestinal tract is relatively unexplored. Our objective was to characterize the cecal and fecal microbiome of mature horses consuming alfalfa or Smooth Bromegrass (brome) hay. Six cecally cannulated horses were used in a split-plot design run as a crossover in two periods. The whole plot treatment was ad libitum access to brome or alfalfa hay fed over two 21-d acclimation periods with subplots of sampling location (cecum and rectum) and sampling hour. Each acclimation period was followed by a 24-h collection period where cecal and fecal samples were collected every 3 h for analysis of pH and volatile fatty acids (VFA). Fecal and cecal samples were pooled and sent to a commercial lab (MR DNA, Shallowater, TX) for the amplification of the V4 region of the 16S rRNA gene and sequenced using Illumina HiSeq. The main effects of hay on VFA, pH, and taxonomic abundances were analyzed using the MIXED procedure of SAS 9.4 with fixed effects of hay, hour, location, period, and all possible interactions and random effect of horse. Alpha and beta diversities were analyzed using the R Dame package. Horses fed alfalfa had greater fecal than cecal pH (P ≤ 0.05), whereas horses fed brome had greater cecal than fecal pH (P ≤ 0.05). Regardless of hay type, total VFA concentrations were greater (P ≤ 0.05) in the cecum than in feces, and alfalfa resulted in greater (P ≤ 0.05) VFA concentrations than brome in both sampling locations. Alpha diversity was greater (P ≤ 0.05) in fecal compared with cecal samples. Microbial community structure within each sampling location and hay type differed from one another (P ≤ 0.05). Bacteroidetes were greater (P ≤ 0.05) in the cecum compared with the rectum, regardless of hay type. Firmicutes and Firmicutes:Bacteroidetes were greater (P ≤ 0.05) in the feces compared with cecal samples of alfalfa-fed horses. In all, fermentation parameters and bacterial abundances were impacted by hay type and sampling location in the hindgut.     

Idiopathic hematuria of unilateral renal origin in a dog

Idiopathic hematuria of unilateral renal origin was diagnosed in a 3-month-old male Weimaraner. The hematuria had been visible grossly for 6 weeks. Extensive clinicopathologic, radiographic, and histologic evaluations localized the source of the hematuria to the right kidney, but could not identify a cause. Nephrectomy of the right kidney resolved the problem. This case report supports a previous article comparing canine idiopathic hematuria of renal origin with benign essential hematuria of human beings.     

The physics of neutron stars

Neutron stars are some of the densest manifestations of massive objects in the universe. They are ideal astrophysical laboratories for testing theories of dense matter physics and provide connections among nuclear physics, particle physics, and astrophysics. Neutron stars may exhibit conditions and phenomena not observed elsewhere, such as hyperon-dominated matter, deconfined quark matter, superfluidity and superconductivity with critical temperatures near 10(10) kelvin, opaqueness to neutrinos, and magnetic fields in excess of 10(13) Gauss. Here, we describe the formation, structure, internal composition, and evolution of neutron stars. Observations that include studies of pulsars in binary systems, thermal emission from isolated neutron stars, glitches from pulsars, and quasi-periodic oscillations from accreting neutron stars provide information about neutron star masses, radii, temperatures, ages, and internal compositions.     

THE USE OF INTRAPERITONEAL FLUID AS A SIMPLE TECHNIQUE FOR ENHANCING SONOGRAPHIC VISUALIZATION OF THE CANINE PANCREAS

Sonographic evaluation of the pancreas was performed in ten healthy research dogs following intraperitoneal fluid administration. Physiological saline solution was aseptically introduced into the peritoneal cavity of each dog to create an acoustic window that would facilitate sonographic delineation of normal pancreatic tissues. Abdominal ultrasound examinations were performed in all dogs before and after the production of the diagnostic hydroperitoneum. Sonograms of the pancreas and other abdominal organs were scored on the basis of image clarity by experienced and novice ultrasonographers. Statistical analysis was then used to compare the effectiveness of each preparation method. A significant difference (P < 0.05) was established between the scores from the diagnostic hydroperitoneum sonograms and the baseline scans performed without intraperitoneal fluid placement. Sonographic visualization scores for the pancreas and other abdominal organs were increased following production of the diagnostic hydroperitoneum. These results indicate that the technique of diagnostic hydroperitoneum will significantly improve ultrasonographic visualization of the pancreas, and may prove useful in the diagnosis of canine pancreatic disease.     

Retrospective study of cecocolic intussusception (cecal inversion) in nine horses (1982–1998)

We retrospectively evaluated the medical records and obtained follow-up information for nine horses which had been treated for cecocolic intussusception (CCI) between January 1982 and April 1998. During the 16-year study period, CCI was diagnosed in nine of 748 horses in which exploratory celiotomy was undertaken for abdominal pain, representing an incidence of 1.2%. Most affected horses (78%) were less than four years of age (median age was 12 months, age range was five months to 15 years). Cecocolic intussusception affected male horses (78%) more commonly than female horses. The most common clinical presentation was abdominal pain of a severe, acute nature or milder but recurrent signs of abdominal pain persisting in spite of conservative treatment for several days. Correction of CCI by either simple reduction or reduction followed by partial typhlectomy was successful if compromise of the intestine by devitalization and adhesion formation was not found at surgery. Definitive diagnosis of CCI necessitates exploratory celiotomy, although an ultrasonographic examination of the abdomen may confirm the diagnosis in some cases. When recognized early during the course of disease, surgical correction of CCI is associated with a favorable outcome; of the eight horses which underwent surgery in our series, five horses (63%) survived surgical correction of CCI. Handling of compromised gut during reduction of CCI necessitates extreme caution because the risk of intestinal tearing is quite high.     

Treatment of a malignant pheochromocytoma in a dog using 131I metaiodobenzylguanidine

A 12 yr old castrated male Yorkshire terrier was presented with a history of an inoperable pheochromocytoma. Physical examination revealed a large, midabdominal mass. Neurologic examination was normal at presentation. An abdominal computed tomography scan revealed a 215 cm(3) mass in the region of the right kidney. Forty-eight hours after IV injection of 370 megabecquerels (MBq, equivalent to10 millicuries [mCi]) of metaiodobenzylguanidine labeled with radioactive iodine ([(131)I]MIBG), standard planar scintigraphy was performed. A diffuse area of moderate uptake was noted in the midabdominal region. The dog experienced stable disease for 1.5 mo after injection based on a follow-up computed tomography (CT) scan; however, 5 mo after injection, repeat CT imaging revealed progression of the tumor, and a second IV injection of 370 MBq (10 mCi) of [(131)I]MIBG was administered. The dog died 3 wk after the second injection as a result of gastrointestinal blood loss that was believed to be caused by compression-induced bowel ischemia by the mass. A full necropsy was not performed, but the mass was removed for histologic evaluation, which confirmed the diagnosis of pheochromocytoma. This report is the first to document the treatment of canine pheochromocytoma using [(131)I]MIBG.     

Multiple cardiac anomalies in a cat.

A 7-week-old domestic shorthair cat was examined because of congestive heart failure. Echocardiography and angiography were used to identify multiple cardiac anomalies. Because of the uncorrectable nature of the defects, the cat was euthanatized. Necropsy revealed persistent left vena cava, patent foramen ovale, and a right atrial/left ventricular canal. The right atrioventricular valve was replaced by a small ostium, and no chordae tendinae or papillary muscles were observed around the ostium. The pulmonary trunk originated from the right atrium. The right ventricular free wall was approximately 1 mm thick.