Clinical and pharmacokinetic characteristics of intracavitary administration of pegylated liposomal encapsulated doxorubicin in dogs with splenic hemangiosarcoma

BACKGROUND: Canine splenic hemangiosarcoma (HSA) is a fatal malignancy, and most affected dogs die within a few months of diagnosis. Most dogs present with signs from tumor rupture, resulting in hemoabdomen and intra-abdominal dissemination. The abdomen is also the main site of disease recurrence. HYPOTHESIS: Intraperitoneal (IP) administration of doxorubicin will delay or prevent intra-abdominal tumor recurrence and prolong survival in dogs with HSA. ANIMALS: Fourteen dogs with splenic HSA. METHODS: A prospective, unmasked, uncontrolled clinical trial. After staging of disease status and splenectomy, pegylated liposomal encapsulated doxorubicin was administered intraperitoneally (1 mg/kg body weight) every 3 weeks for 4 cycles. All dogs were monitored for recurrence of HSA. Samples of plasma and abdominal fluid were collected for measurement of doxorubicin concentration and pharmacokinetic analysis. Nonlinear mixed-effect modeling was used to describe the pharmacokinetics of liposomal doxorubicin administered IP. RESULTS: All 14 dogs died, 12 because of HSA and 2 from other causes. Postmortem examination was performed on 12 dogs. All 12 dogs died because of HSA-related causes and had hepatic metastases and hemoabdomen. The IP-treated dogs had fewer serosal, mesenteric, and omental metastases than historical controls treated with systemic doxorubicin. Results of the postmortem examination and pharmacokinetic analysis confirmed that IP delivery of doxorubicin resulted in an effective drug concentration with a clearance comparable with that after i.v. delivery. CONCLUSIONS AND CLINICAL IMPORTANCE: IP pegylated liposomal encapsulated doxorubicin administration did not prevent intraabdominal recurrence of HSA in dogs.     

Superficial digital flexor tendonitis in Thoroughbred race horses: outcome following non-surgical treatment and superior check desmotomy

Objective This study documents the results of non-surgical treatment and treatment by superior check desmotomy in Thoroughbred racehorses with superficial digital flexor (SDF) tendonitis. Design A prospective study was made of 124 thoroughbred racehorses with unilateral or bilateral SDF tendonitis. Procedure The flexor tendons were assessed by physical and ultrasonographic examination before treatment, and the lesions detected in affected tendons were characterised according to lesion type, length and cross-sectional area. Ninety three horses were managed non-surgically and 31 by superior check desmotomy. Recurrent or new injuries were defined as injuries affecting a previously injured superficial digital flexor tendon, the contralateral SDF tendon, or the suspensory ligament (interosseous muscle) in either forelimb. Results No statistically significant difference was found in ultrasonographic lesion severity between treatment groups. Horses managed by superior check desmotomy were 1.3 times more likely to complete five or more races than horses managed non-surgically (95% confidence limits 0.93–1.82). Horses treated surgically were 1.2 times more likely to develop recurrent or new injuries after returning to training than horses managed non-surgically (95% CL 0.95–1.55). Horses under-going superior check desmotomy were 5.5 times more likely to develop suspensory desmitis than horses treated non-surgically (95% CL 1.13–26.4). There was no difference in the time to recurrent or new injury between treatment groups. Conclusion There was no statistically significant difference between treatment groups in the proportions of horses able to complete five or more races after an episode of superficial digital flexor tendonitis. Superior check desmotomy did not appear to offer an advantage over non-surgical treatment in preventing recurrent or new injuries in Thoroughbred racehorses. Horses undergoing superior check desmotomy appeared to be at greater risk of developing suspensery ligament injuries than horses managed non-surgically.     

A Double‐blind,Placebo‐controlled,Multicenter, Prospective,Randomized Study of Beraprost Sodium Treatment for Cats with Chronic Kidney Disease

Background

Chronic kidney disease (CKD) is a common progressive and irreversible disease in cats. The efficacy and safety of beraprost sodium (BPS) in cats with CKD have not been evaluated.

Hypothesis/Objectives

To evaluate the efficacy and safety of BPS in the treatment of cats with CKD, as compared to placebo.

Animals

Seventy‐four client‐owned cats with naturally occurring CKD.

Methods

Double‐blind, placebo‐controlled, multicenter, prospective, randomized trial. The cats received BPS (55 μg/cat) or a placebo PO q12 h for 180 days. The primary endpoint was prospectively defined as a change in the serum creatinine (sCr), serum phosphorus‐to‐calcium ratio or urine specific gravity (USG).

Results

The sCr increased significantly (P = 0.0030) in the placebo group (mean ± SD: 2.8 ± 0.7 to 3.2 ± 1.3 mg/dL) but not in the BPS group (2.4 ± 0.7 to 2.5 ± 0.7 mg/dL). The difference between the groups at day 180 was significant (0.8 mg/dL, 95% CI: 0.2 to 1.3 mg/dL, P = 0.0071). The serum phosphorus‐to‐calcium ratio was significantly (P = 0.0037) increased in the placebo group (0.46 ± 0.10 to 0.52 ± 0.21 mg/dL) but not in the BPS group (0.50 ± 0.08 to 0.51 ± 0.11 mg/dL). There was no significant change in the USG in either group. An adverse event judged as being treatment‐related included vomiting that occurred in 1 case in the placebo group. No clinically relevant change was observed in the CBC and other blood chemistry tests.

Conclusions and Clinical Importance

Beraprost sodium treatment was well tolerated and safe in cats with CKD. BPS inhibited the reduction in renal filtration function as measured by sCr increase.     

Efficacy and Toxicity of Intracavitary Administration of Pegylated Liposomal Encapsulated Doxorubicin (DOXIL) in Dogs with Hemangiosarcoma

Introduction:  Canine hemangiosarcoma (HSA) is a fatal malignancy and most dogs die within 6–8 months of diagnosis. The spleen is a common primary site, representing 50% of all cases. These dogs typically present with clinical signs due to tumor rupture and intra‐abdominal dissemination; the abdomen is also the main site of disease progression when these patients fail. Direct delivery of chemotherapy into the abdominal cavity may therefore be a rational approach in this malignancy.
Methods:  14 dogs with stage 2 or 3 splenic HSA were recruited. Doxil at a dose of 1 mg/kg was diluted in saline and administered via ultrasound‐guidance into the abdominal cavity. The dogs were scheduled to receive 4 treatments every 3 weeks. Samples of plasma and abdominal fluid were collected for pharmacokinetic analysis. All dogs were monitored for recurrence and complete necropsies were requested at death.
Results:  8 dogs with stage 3 and 6 dogs with stage 2 HSA were enrolled. All 14 dogs have died, 12/14 due to tumor and 2 from other causes. There was no difference in median survival days between stages (stage 2: 244, stage 3: 125, p = .22). All 12 dogs that died due to tumor‐related causes failed with intra‐abdominal recurrence. Necropsies showed that the dogs in this study had relatively fewer extra‐abdominal metastasis compared to dogs treated with systemic chemotherapy. Pk analysis showed detectable plasma doxorubicin 1 and 2 weeks after treatment.
Conclusion:  Direct abdominal administration of Doxil did not prevent intra‐abdominal recurrence; however, it appeared to provide effective systemic coverage.     

Focal eosinophilic proctitis with associated rectal prolapse in a pony

Focal intramural nodules were palpated in the rectal wall of a 12-year-old pony mare presented for rectal prolapse. Eosinophilic proctitis was diagnosed by examination of fine needle aspirates and biopsy of the largest rectal nodule. After treatment with a course of corticosteroids, the rectal nodule and accompanying peripheral eosinophilia resolved. There was no recurrence of the condition during the follow-up period of 20 months. Focal eosinophilic proctitis appeared to be an unusual cause of tenesmus and rectal prolapse in this case.     

Polymorphs of Alumina Predicted by First Principles: Putting Pressure on the Ruby Pressure Scale

Fully optimized quantum mechanical calculations indicate that Al2O3 transforms from the corundum structure to the as yet unobserved Rh2O3 (II) structure at about 78 gigapascals, and it further transforms to Pbnm-perovskite structure at 223 gigapascals. The predicted x-ray spectrum of the Rh2O3 (II) structure is similar to that of the corundum structure, suggesting that the Rh2O3 (II) structure could go undetected in high-pressure x-ray measurements. It is therefore possible that the ruby (Cr3+-doped corundum) fluorescence pressure scale is sensitive to the thermal history of the ruby chips in a given experiment.     

Effect of dietary vitamin E and selenium supplementation on semen quality in Cairn Terriers with normospermia

Among others, selenium (Se) and vitamin E (VitE) have been provided to dogs to improve semen quality. However, scientific evidence documenting an effect in dogs is lacking. The aim of this study was to investigate the effect of supplementation of these antioxidants on various ejaculate parameters in a randomized, double‐blinded trial using Cairn Terrier males exhibiting normal seminal quality parameters. Three dogs each were fed a standardized diet and supplemented with 0.1 mg Se, 100 mg VitE or 0.1 mg Se + 100 mg VitE/dog for 3 months. Ejaculate analyses (volume, progressive motility, vitality, morphology, concentration) were performed before inclusion (D0) and after 1, 2 and 3 months (+1, +2, +3). At the same time, glutathione peroxidase (GSH‐PX) and VitE in seminal plasma (SP) and GSH‐PX in blood samples were determined. Vitamin E levels in SP were below the detection limit (1.0 mg/L) in all samples. GSH‐PX in blood (164.0–2794.4 IU/L) and SP (18.4–4326.0 IU/L) was highly variable. Supplementation only significantly affected the total percentage of sperm head abnormalities (p = .011). Time significantly affected the percentage of morphologically abnormal sperm (p = .025), sperm head abnormalities (p = .007), proximal droplets (p = .001) and GSH‐PX in SP (p = .015). Additionally, a significant interaction between time and group was identified for the percentage of membrane‐intact sperm (p = .048), head abnormalities (p = .018), acrosomal defects (p = .043) and proximal droplets (p = .002). Although some effects could be identified for selected parameters, we failed to identify a clear trend about how a 3 months VitE and/or Se supplementation affects semen parameters in normospermic Cairn Terriers.     

Testing the usability of truncated angle count sample plots as ground truth in airborne laser scanning-based forest inventories

Airborne laser scanner (ALS)-based forest inventory method usuallyadopt a laser canopy height distribution approach in which forestcharacteristics are predicted using measures such as percentilesof the distribution of laser canopy heights across a fixed area.The method requires a ground-truth sample of accurately measuredfield plots. One possibility for reducing the costs lies inthe use of existing field plots for ground-truth purposes. Themost obvious alternative in Finland would be to use truncatedangle count sample plots of the National Forest Inventory ormore locally data of checking of inventory by compartments.Due to the lack of suitable angle count ground-truth data andcorresponding laser data, we tested this possibility using dataon fixed-area sample plots, in which tree locations were simulated.The trees for a truncated angle count sample plot were thenchosen and the resulting data together with the characteristicsof an ALS-based canopy height distribution were used to constructregression models to predict stem volume, basal area, stem number,basal area median diameter and height. The accuracy of the standattributes was found to be almost as good as in the case ofmodels of fixed-area plots.     

Association of argyrophilic nucleolar organizing regions, Ki-67, and proliferating cell nuclear antigen scores with histologic grade and survival in dogs with soft tissue sarcomas: 60 cases (1996-2002)

OBJECTIVE: To determine whether argyrophilic nucleolar organizing regions (AgNORs), Ki-67, and proliferating cell nuclear antigen (PCNA) scores were associated with histologic grade and survival in dogs with soft tissue sarcomas (STSs). DESIGN: Retrospective study. ANIMALS: 60 dogs with STSs. PROCEDURE: Medical records were examined and histologic specimens were reviewed. Tissue specimens obtained from archival materials were used to prepare sections for histologic staining for AgNOR and immunohistochemical staining for Ki-67 and PCNA labeling. Follow-up monitoring was obtained by reevaluation or telephone conversations with referring veterinarians or owners. RESULTS: 27 (45%) STSs were grade 1, 23 (38%) were grade 2, and 10 (17%) were grade 3. The mean and median AgNOR, Ki-67, and PCNA scores were determined, and significant positive associations among AgNOR and Ki-67 scores with histologic grade and mitotic score were detected. Fifty-four dogs had adequate follow-up examinations and were included in survival analysis and evaluation of prognostic factors. Overall median survival time was > 1,306 days. Twelve of 54 (22%) dogs died of tumor-related causes. Metastatic disease developed in 8 of 54 (15%) dogs. Results of univariate analysis indicated that increased mitotic score, increased AgNOR score, increased Ki-67 score, incomplete surgical margins, noncurative intent surgery, Ki-67 score greater than the median Ki-67 score, and AgNOR score greater than the median AgNOR score were prognostic factors for decreased survival time. Results of multivariate analysis indicated that increased AgNOR score was the only prognostic factor for decreased survival time. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that AgNORs and possibly Ki-67 should be routinely evaluated with histologic grading for STSs in dogs.