A high-resolution 15,000(Rad) radiation hybrid panel for the domestic cat.

The current genetic and recombination maps of the cat have fewer than 3,000 markers and a resolution limit greater than 1 Mb. To complement the first-generation domestic cat maps, support higher resolution mapping studies, and aid genome assembly in specific areas as well as in the whole genome, a 15,000(Rad) radiation hybrid (RH) panel for the domestic cat was generated. Fibroblasts from the female Abyssinian cat that was used to generate the cat genomic sequence were fused to a Chinese hamster cell line (A23), producing 150 hybrid lines. The clones were initially characterized using 39 short tandem repeats (STRs) and 1,536 SNP markers. The utility of whole-genome amplification in preserving and extending RH panel DNA was also tested using 10 STR markers; no significant difference in retention was observed. The resolution of the 15,000(Rad) RH panel was established by constructing framework maps across 10 different 1-Mb regions on different feline chromosomes. In these regions, 2-point analysis was used to estimate RH distances, which compared favorably with the estimation of physical distances. The study demonstrates that the 15,000(Rad) RH panel constitutes a powerful tool for constructing high-resolution maps, having an average resolution of 40.1 kb per marker across the ten 1-Mb regions. In addition, the RH panel will complement existing genomic resources for the domestic cat, aid in the accurate re-assemblies of the forthcoming cat genomic sequence, and support cross-species genomic comparisons.

Treatment of a heart base tumor and chylothorax with endovascular stent, stereotactic body radiation therapy, and a tyrosine kinase inhibitor in a dog.

An 8-year-old 28-kg male castrated rough collie was evaluated for persistent chylothorax secondary to right atrial mass. Cardiac ultrasound and computed tomography revealed a right atrial intra- and extraluminal mass with partial obstruction of the cranial vena cava and secondary chylothorax. Vascular stent placement was elected to alleviate cranial vena cava obstruction and secondary chylothorax. An 18 mm × 180 mm self-expanding stent was deployed in the region of the stricture, spanning the cranial vena cava and right atrium. An intrathoracic drainage catheter and subcutaneous port were placed within the right hemithorax, and antiplatelet therapy was initiated. Four weeks later, the dog underwent stereotactic body radiation therapy. Three months following treatment, the dog was diagnosed with supraventricular tachycardia and received antiarrhythmic therapy and antiangiogenic/antiproliferative medication (Palladia™). Subsequent evaluations confirmed the resolution of arrhythmia and pleural effusion. Combined vascular stent placement and stereotactic body radiation therapy for the treatment of a right atrial intraluminal and extraluminal mass leading to cranial vena cava compression and subsequent chylothorax may lead to long-term survival. A good outcome was achieved in this patient due to resolution of pleural effusion, as well as cytoreduction and presumably delayed progression of tumor growth.

Study of enzymatic digestion of cellulose by small angle neutron scattering.

Small angle neutron scattering (SANS) was used to study the structure of Avicel (FD100) microcrystalline cellulose during enzymatic digestion. Digestions were performed in either of two modes: a static, quiescent mode or a dynamic mode using a stirred suspension recycled through a flow cell. The scattering pattern for as-received Avicel in D(2)O buffer is comprised of a low Q power law region resulting from the surface fractal character of the microcrystalline fibers and a high Q roll-off due to scattering from water-filled nanopores with radii approximately 20 A. For digestions in the dynamic mode the high Q roll-off decreased in magnitude within approximately 1 h after addition of enzymes, whereas in the static digestions no change was observed in the high Q roll-off, even after 60 h. These results indicate that only with significant agitation does enzyme digestion affect the structure of the nanopores.

Unilateral and bilateral congenital sensorineural deafness in client-owned pure-breed white cats.

BACKGROUND: Congenital sensorineural deafness has been reported frequently in experimental mixed-breed white cats but there is a paucity of data on occurrence of deafness in client-owned pure-breed white cats. OBJECTIVE: To describe hearing status in client-owned pure-breed white cats. ANIMALS: Eighty-four pure-breed client-owned cats with white coat color of 10 registered breeds presented for routine hearing evaluation before breeding (1995-2008). METHODS: Hearing was assessed by click-evoked brainstem auditory evoked response. RESULTS: Overall deafness prevalence was 20.2%; 9 cats (10.7%) were bilaterally deaf and 8 cats (9.5%) were unilaterally deaf. There was no association between sex and deafness status (P= .85). Deafness status was associated with iris color (P= .04). CONCLUSIONS AND CLINICAL IMPORTANCE: Congenital sensorineural deafness frequently occurs in pure-breed cats with white coat color. Unilateral sensorineural deafness was as common as bilateral deafness.

Sequential low-dose rate half-body irradiation and chemotherapy for the treatment of canine multicentric lymphoma.

BACKGROUND: Sequential half-body irradiation (HBI) combined with chemotherapy is feasible in treating canine lymphoma, but prolonged interradiation intervals may affect efficacy. A 2-week interradiation interval is possible in most dogs receiving low-dose rate irradiation (LDRI) protocols at 6 Gy dose levels. HYPOTHESIS: LDRI incorporated into a cyclophosphamide, doxorubicin, vincritine, and prednisone (CHOP)-based chemotherapy protocol is effective for the treatment of lymphoma in dogs. ANIMALS: Thirty-eight client-owned animals diagnosed with multicentric lymphoma. METHODS: Retrospective study evaluating the efficacy and prognostic factors for the treatment of canine lymphoma with sequential HBI and chemotherapy. RESULTS: The median 1st remission was 410 days (95% confidence interval [CI] 241-803 days). The 1-, 2-, and 3-year 1st remission rates were 54, 42, and 31%. The median overall survival was 684 days (95% CI 334-1,223 days). The 1-, 2-, and 3-year survival rates were 66, 47, and 44%. CONCLUSIONS AND CLINICAL RELEVANCE: Results of this study suggest that treatment intensification by a 2-week interradiation treatment interval coupled with interradiation chemotherapy is an effective treatment for dogs with lymphoma.

Oligomerization of membrane-bound diphtheria toxin (CRM197) facilitates a transition to the open form and deep insertion.

Diphtheria toxin (DT) contains separate domains for receptor-specific binding, translocation, and enzymatic activity. After binding to cells, DT is taken up into endosome-like acidic compartments where the translocation domain inserts into the endosomal membrane and releases the catalytic domain into the cytosol. The process by which the catalytic domain is translocated across the endosomal membrane is known to involve pH-induced conformational changes; however, the molecular mechanisms are not yet understood, in large part due to the challenge of probing the conformation of the membrane-bound protein. In this work neutron reflection provided detailed conformational information for membrane-bound DT (CRM197) in situ. The data revealed that the bound toxin oligomerizes with increasing DT concentration and that the oligomeric form (and only the oligomeric form) undergoes a large extension into solution with decreasing pH that coincides with deep insertion of residues into the membrane. We interpret the large extension as a transition to the open form. These results thus indicate that as a function of bulk DT concentration, adsorbed DT passes from an inactive state with a monomeric dimension normal to the plane of the membrane to an active state with a dimeric dimension normal to the plane of the membrane.

A phase II clinical trial of vinorelbine in dogs with cutaneous mast cell tumors.

BACKGROUND: Few effective drugs are available to treat dogs with locally aggressive or metastatic mast cell disease. HYPOTHESIS: Vinorelbine, a semisynthetic derivative of vinblastine, is an effective drug for the treatment of canine mast cell tumors (MCT). ANIMALS: Twenty-four dogs with cutaneous MCT. METHODS: Dogs with at least 1 measurable, cytologically confirmed, and previously untreated cutaneous MCT received a single treatment with vinorelbine at the previously established dosage of 15 mg/m2 IV. Tumor measurements and CBC were evaluated before and 7 days after treatment. Adverse events were graded according to Veterinary Cooperative Oncology Group (VCOG) guidelines. STATISTICS: Data were accrued in accordance with a Simon's 2-stage design with a noninteresting response rate of .05, a target response of .25, and alpha and beta values of .10. RESULTS: Three of 24 dogs (13%) had a response to treatment, including 1 measurable complete response and 1 measurable partial response. The 3rd dog had microscopic complete response to treatment with stable measurable disease. Twenty other dogs (83%) had stable disease and 1 dog (4%) had progressive disease. Neutropenia occurred in 13 dogs (54%) (grade 1, n = 4; grade 3, n = 6; grade 4, n = 3). Gastrointestinal toxicity occurred in 11 dogs (46%) (anorexia: grade 1, n = 3; grade 2, n = 1; grade 3, n = 1; diarrhea: grade 1, n = 2; grade 3, n = 1; vomiting: grade 1, n = 5; grade 3, n = 1). CONCLUSIONS AND CLINICAL IMPORTANCE: Vinorelbine was associated with an overall response rate of 13% and a high prevalence of neutropenia. Additional studies are indicated to determine if repeated dosing of vinorelbine or combination of vinorelbine with other drugs increases the observed biologic activity against canine MCT.

Prone thoracoscopic esophageal mobilization for minimally invasive esophagectomy.

BACKGROUND: Minimally invasive esophagectomy is a complex surgical procedure. We recently began performing thoracic mobilization of the esophagus with the patient in the prone position, not the left lateral decubitus position, in the hope of minimizing the number of technical challenges. METHODS: Six consecutive minimally invasive esophagectomies were performed using prone thoracoscopic esophageal mobilization with creation of cervical anastamosis. Our esophagectomy database was evaluated for outcomes, including operative time, estimated blood loss, complications, and length of hospital stay. RESULTS: We were successful in our first six attempts, with a mean blood loss of 61 cc. Mean operative time for thoracoscopy was 80 min. Operative times were steady over the first six prone cases at 105, 85, 70, 55, 80, and 85 min. Three of the six patients had no complications. Median postoperative length of hospital stay was 11.5 days, and there were no deaths. CONCLUSIONS: This technical report and case series demonstrates that prone thoracoscopic esophageal mobilization appears to be a reasonable alternative to the same procedure performed with the patient in the decubitus position. We find the technique to simplify portions of an otherwise difficult surgical procedure. Further evaluation with larger number of patients should be performed.

A pilot study of botulinum toxin injection for the treatment of delayed gastric emptying following esophagectomy.

OBJECTIVE: Esophagectomy may lead to impairment in gastric emptying, unless a pyloroplasty or pyloromyotomy is performed. These procedures may be technically challenging during minimally invasive esophagectomy, and they are associated with a small but definable morbidity, such as leakage and dumping syndrome. We sought to determine the results of our early experience with injecting the pylorus with botulinum toxin instead of conventional pyloric drainage. METHODS: Fifteen patients who had undergone esophagectomy and injection of the pylorus with botulinum toxin were identified. Twelve patients had undergone botulinum toxin injection at the time of minimally invasive esophagectomy, and the remaining three had been treated endoscopically after surgery. The latter three patients had undergone esophagectomy with either no pyloric drainage (n = 2) or an inadequate pyloromyotomy (n = 1), and they presented in the postoperative period with delayed gastric emptying. The adequacy of emptying after injection was assessed by the patients' ability to tolerate a regular diet, a barium swallow, and a nuclear gastric emptying study. RESULTS: No patient injected with botulinum toxin during esophagectomy developed delayed gastric emptying or aspiration pneumonia in the perioperative period. Eight of these patients underwent a nuclear emptying scan at a median of 4.2 months after surgery, which showed a mean emptying half-life of 100 min. With a median follow-up of 5.3 months, one patient (8%) required reintervention for symptoms of gastric stasis, presumably after the effect of the toxin subsided. All three patients injected postoperatively demonstrated an improvement in symptoms of gastric outlet obstruction and were able to resume a regular diet. CONCLUSIONS: Injection of the pylorus with botulinum toxin can be performed safely in patients undergoing esophagectomy. Longer-term studies are needed to clarify the efficacy and durability of this technique compared to the accepted procedures of pyloromyotomy or pyloroplasty.

Risk Factors for Death in Dogs Treated for Esophageal Foreign Body Obstruction: A Retrospective Cohort Study of 222 Cases (1998-2017).

BACKGROUND: Limited data exist describing risk factors for death, and long-term outcomes in dogs with esophageal foreign body (EFB) obstruction. HYPOTHESIS/OBJECTIVES: To evaluate short- and long-term outcomes, and analyze risk factors for death in dogs with EFB obstruction. We hypothesized duration of entrapment and treatment type would affect outcome. ANIMALS: A total of 222 dogs were treated for EFB obstruction at an emergency and referral hospital between March 1998 and March 2017. METHODS: Medical records for dogs with EFB were retrospectively evaluated. RESULTS: Foreign material most frequently was osseous (180/222 [81%]), with distal esophagus the most common location (110/222 [49.5%]). Duration of clinical signs was not associated with risk of death (OR = 1.08, 95% CI 0.99-1.17; P = 0.2). Entrapment was treated by endoscopy (204/222 [91.8%]), surgery after endoscopic attempt (13/222 [5.9%]), and repeat endoscopy after surgery was recommended but declined (5/222 [2.3%]). In-hospital case fatality rate was 11/222 (5%). Risk of death was significantly higher with surgery (OR = 20.1, 95% CI 3.59-112.44; P = 0.001), and 5/5 (100%) of dogs died if undergoing endoscopy after surgery was recommended but declined. Increasing numbers of postprocedural complications (OR = 3.44, CI 2.01-5.91; P < 0.001), esophageal perforation (OR = 65.47, CI 4.27-1004.15; P = 0.003), and postprocedure esophageal hemorrhage (OR = 11.81, CI 1.19-116.77; P = 0.04) increased in-hospital risk of death. Esophageal strictures were reported in 4/189 (2.1%) of survivors available for follow-up. CONCLUSIONS AND CLINICAL IMPORTANCE: Death is uncommon in canine EFB; however, treatment type affects outcome, and these data should be used to guide decision-making in dogs with EFB.

Factors Affecting Platelet Concentration in Platelet Concentrates from Canine Blood Donors.

BACKGROUND: Physiologic factors in dogs that might contribute to enhanced platelet yield in platelet concentrates (PCs) are largely unknown. OBJECTIVE: To determine whether individual differences in weight, age, preprocessing blood chemistry, and CBC variables predict the final platelet concentrations in PCs. Our hypotheses were (1) increased lipemic indices would be positively associated with increased platelet concentrations in PCs and (2) increased preprocessing platelet concentrations would be associated with higher platelet concentrations in the PCs. ANIMALS: All blood donation records of dogs from February 2, 2009 through April 1, 2015 at the University of California-Davis Veterinary Blood Bank were examined with 104 cases included in this study. METHODS: In this retrospective study, data were collected from medical records of canine blood donors. Records were reviewed for internal consistency and accuracy and subjects were included in the study if donor screening and donation occurred on the same day and a viable PC was obtained. Univariate and multivariable regressions were used to test the impact that each variable had on the final platelet concentration in PCs. RESULTS: Final platelet concentration in PCs was positively associated with the predonation CBC platelet values (P < .001), lipemic index (P = .01), and phosphorous levels (P = .001). Collectively these 3 variables explained 29% of the variance in platelet concentrations in PCs. CONCLUSIONS AND CLINICAL IMPORTANCE: Future prospective studies are required to determine if canine blood donations from dogs with lipemia yield PCs with higher platelet concentrations without negatively affecting other blood components.

Evaluation of optimal water fluoridation on the incidence and skeletal distribution of naturally arising osteosarcoma in pet dogs.

Experimental toxicological studies in laboratory animals and epidemiological human studies have reported a possible association between water fluoridation and osteosarcoma (OSA). To further explore this possibility, a case-control study of individual dogs evaluated by the UC Davis Veterinary Medical Teaching Hospital was conducted using ecologic data on water fluoridation based on the owner's residence. The case group included 161 dogs with OSA diagnosed between 2008-2012. Two cancer control groups included dogs diagnosed with lymphoma (LSA) or hemangiosarcoma (HSA) during the same period (n = 134 and n = 145, respectively). Dogs with OSA were not significantly more likely to live in an area with optimized fluoride in the water than dogs with LSA or HSA. Additional analyses within OSA patients also revealed no significant differences in age, or skeletal distribution of OSA cases relative to fluoride status. Taken together, these analyses do not support the hypothesis that optimal fluoridation of drinking water contributes to naturally occurring OSA in dogs.

Treatment of MRI-Diagnosed Trigeminal Peripheral Nerve Sheath Tumors by Stereotactic Radiotherapy in Dogs.

BACKGROUND: Stereotactic radiotherapy (SRT) is an emerging technique for treating tumors in animals. OBJECTIVES: To assess the outcome of dogs with suspected intracranial trigeminal nerve peripheral nerve sheath tumors (PNST) treated with SRT. ANIMALS: Eight dogs with presumptive PNST. METHODS: This was a retrospective study of dogs identified by searching UC Davis Veterinary Medical Teaching Hospital medical records for dogs treated with SRT for a presumed PNST. Presumptive diagnosis was based on magnetic resonance imaging. SRT was delivered in 3 dose fractions of 8 Gray (Gy) on consecutive days or every other day to a total dose of 24 Gy. RESULTS: Median disease-specific survival was 745 days (range: 99-1375 days, n = 6). No signs of acute adverse effects of radiation treatment were recorded. Late radiation effects versus tumor progression could not be confirmed histopathologically because of few animals undergoing necropsy. CONCLUSIONS AND CLINICAL IMPORTANCE: This study provides preliminary evidence that dogs with PNST benefit from SRT in terms of long-term survival. The treatment appears to be well tolerated and requires fewer anesthetic events for animals compared to full-course radiation.

Perfusion and Volume Response of Canine Brain Tumors to Stereotactic Radiosurgery and Radiotherapy.

BACKGROUND: Stereotactic radiosurgery (SRS) and stereotactic radiotherapy (SRT) are highly conformal, high-dose radiation treatment techniques used to treat people and dogs with brain tumors. OBJECTIVES: To evaluate the response to SRS- and SRT-treated tumors using volume and perfusion variables and to measure the survival times of affected dogs. ANIMALS: Prospective study of 34 dogs with evidence of brain tumors undergoing stereotactic radiosurgery (SRS) or stereotactic radiotherapy (SRT). METHODS: Computed tomography and MRI imaging were used to calculate tumor volume and perfusion at baseline, and at 3 months and 6 months after treatment. Survival analysis was performed to evaluate treatment efficacy. RESULTS: Mean tumor volume significantly declined from baseline to the first recheck by -0.826 cm(3) (95% CI: -1.165, -0.487) (P < .001); this reduction was maintained at the second recheck. Blood flow and blood volume declined significantly in the tumor after treatment. Median survival was 324 days (95% CI: 292.8, 419.4), and 4 dogs survived longer than 650 days. Neither actual tumor volume (hazard ratio = 1.21, P = .19) nor the change in tumor volume from the baseline (hazard ratio = 1.38, P = .12) significantly affected the hazard of death because of the tumor. CONCLUSIONS AND CLINICAL IMPORTANCE: Stereotactic radiosurgery and SRT are effective treatments for reducing tumor volume, blood flow, and blood volume. Treated dogs surviving for more than 1 year are more likely to die from other causes than of their primary brain tumor. SRS and SRT should be considered for noninvasive treatment of intracranial brain tumors.

Evidence for vertical phase separation in densely grafted, high-molecular-weight poly(-isopropylacrylamide) brushes in water.

The detailed conformational change of poly(N-isopropylacrylamide) (PNIPAM) brushes at high grafting density in D2O was investigated as a function of temperature using neutron reflection. PNIPAM chains were grafted at high surface density from gold and silicon oxide surfaces by atom transfer radical polymerization. Whereas single layer profiles were observed for temperatures below and above the transition region, bilayer profiles were observed for a narrow range of temperatures near the transition. This nonmonotonic change in the concentration profile with temperature is discussed in the context of theoretical models of vertical phase separation within a brush.

Spinal cord swelling preceding syrinx development. Case report.

The pathophysiology of syrinx development is controversial. The authors report on a patient with progressive cervical myelopathy and a Chiari I malformation in whom spinal cord swelling preceded, by a few months, the development of a syrinx in the same location. The patient underwent a craniocervical decompressive procedure and duraplasty, and complete resolution of cord swelling and syringomyelia was achieved. This report is consistent with the theory that patients with Chiari I malformation have increased transmural flow of cerebrospinal fluid, which causes spinal cord swelling that later coalesces into a syrinx. The pathophysiology of syrinx development from spinal cord edema and the success of surgical decompressive treatments that do not invade the central nervous system support the prompt treatment of patients with spinal cord edema who are at risk for the development of a syrinx.

Clear cell ependymoma in a dog.

A 13-year-old, mixed breed dog presented with a 1-month history of seizures. Magnetic resonance imaging of the brain revealed a 2.2 × 1.0 × 0.9 cm ovoid and elongate cystic mass within the white matter of the left frontal lobe extending caudally from the cribriform plate to the rostral left lateral ventricle. Three fractions of stereotactic radiotherapy were administered and resulted in reduction of the volume of the tumour; however, the clinical signs failed to improve. On post-mortem examination, a single mass 1.5 × 0.3 × 1 cm was found within the left frontal lobe. It consisted of gelatinous, grey, friable tissue bordering a central empty cavity. Microscopical evaluation revealed polygonal neoplastic cells with distinct cytoplasmic borders and one or more intracytoplasmic solid, brightly eosinophilic, sharply defined globules. Immunohistochemically, the neoplastic cells expressed glial fibrillary acidic protein and S100 but were negative for pan cytokeratin, vimentin, olig-2 and synaptophysin. Ultrastructurally, neoplastic cells had dense whorls of intracytoplasmic intermediate filaments and were connected by multiple intermittent long zonula adherens-type junctions. Based on these findings, a diagnosis of clear cell ependymoma was made. This is the first report of this subtype in the dog.

Follow-up study comparing necropsy rates and discrepancies between clinical and pathologic diagnoses at a veterinary teaching hospital: 2009 versus 1989 and 1999.

OBJECTIVES: A follow-up, retrospective study to determine whether the proportion of discrepancies between clinical and pathological diagnoses made during 2009, 1999 and 1989 and the proportion of dogs necropsied have changed. METHODS: Medical records of 148 hospitalised dogs that died or were euthanased in a veterinary medical teaching hospital during 2009 were reviewed. Clinical and pathological diagnoses were recorded, categorised and compared to historical controls using a data set of 623 dogs from a previous study. RESULTS: The proportion of discrepancies was significantly (P<0·001) lower in 2009 (14·9%), compared to both 1999 (37%) and 1989 (39·8%). There was also a significant (P<0·001) decrease in the number of necropsies performed during 2009 (21·4%) compared to both 1999 (48·4%) and 1989 (58·9%). CLINICAL SIGNIFICANCE: There was a marked improvement in the ante-mortem diagnosis of patients in 2009 compared with both 1989 and 1999 as evidenced by the decrease in the proportion of discrepancies between the clinical and pathological diagnoses. Necropsies should still be regarded as a vital tool for teaching, determining the pathological basis of disease, identification of new and emerging diseases, and for an individual animal determining the cause of death.

Clinical outcome in 94 cases of dermal haemangiosarcoma in dogs treated with surgical excision: 1993-2007*.

Canine dermal haemangiosarcoma (HSA) is believed to have a better prognosis compared to HSA in other organs, but outcome has only been reported in a small number of dogs. The purpose of this study was to assess outcome and prognostic factors in a larger cohort of dogs with dermal HSA. Clinical data was collected retrospectively for 94 dogs and histopathology was reviewed in 53 dogs. Median overall survival time was 987 days. Dogs of predisposed breed with ventral location and histologic solar changes had longer survivals. Loco-regional recurrence occurred in 72/94 (77%) dogs. Predisposed breeds with ventral location and multiple masses were more likely to develop recurrence. Non-predisposed breeds with invasive tumours were more likely to develop metastasis. Results suggest that dogs with solar-induced dermal HSA may have high recurrence rates, but prolonged survivals. Dogs with non-solar tumours may be at increased risk for metastasis and shorter survival.