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1.
Vet Surg ; 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38863141

RESUMO

OBJECTIVE: To describe the signalment, treatment, complications, and outcomes of cats treated surgically for ectopic ureters. STUDY DESIGN: Retrospective, multi-institutional study. ANIMALS: Twelve client-owned cats. METHODS: Medical records of cats diagnosed with unilateral or bilateral ectopic ureters were reviewed and analyzed. Data reported included signalment, clinical signs, diagnostics, open celiotomy, or cystoscopic surgical interventions, and outcomes. RESULTS: Seven of the 12 cats in the study population were female or female spayed and the median age at time of presentation was 4 years, with an interquartile range (IQR) of 6 months-14 years. Presurgical diagnostic imaging diagnosed ectopic ureters by abdominal ultrasound (8/10), contrast enhanced computed tomography (3/3), fluoroscopic urography (3/4), or cystoscopy (6/7). Eight of 12 cats had extramural ectopic ureters and six cats were affected bilaterally. Eight affected cats underwent ureteroneocystostomy, one cat underwent neoureterostomy, two cats underwent cystoscopic laser ablation, and one cat underwent nephroureterostomy. Immediate postoperative complications occurred in three cats; one cat required additional surgical intervention. Short-term complications occurred in three cats, and long-term complications in two cats. All cats that underwent surgical or cystoscopic intervention had improvement of their urinary incontinence scores, with complete resolution in 11 cats. CONCLUSION: Surgical correction of ectopic ureters in cats is associated with good long-term outcomes. Ectopic ureters in cats are commonly extramural and bilateral. Postoperative outcomes were acceptable and there were few postoperative complications, with varying forms of surgical correction. CLINICAL SIGNIFICANCE: Ectopic ureters in cats are rare but urinary incontinence can be corrected or improved successfully with surgery.

2.
Vet Surg ; 51(1): 125-135, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34596252

RESUMO

OBJECTIVE: To evaluate protein C (PC) activity after intrahepatic portosystemic shunt (IHPSS) percutaneous transvenous coil embolization (PTCE) in dogs; to identify if PC is associated with clinical status after intervention, and to compare PC with standard biochemical values. STUDY DESIGN: Retrospective case series. ANIMALS: Forty-seven client-owned dogs with IHPSS undergoing PTCE. METHODS: Records were reviewed for preoperative and postoperative PC, hematocrit (HCT), mean corpuscular volume (MCV), albumin (ALB), and blood urea nitrogen (BUN). Ultimate clinical status was classified as excellent, fair, or poor, based on ongoing medical management and the presence of clinical signs. Intrahepatic portosystemic shunt was considered to be completely or incompletely occluded intraoperatively based on angiography. RESULTS: Postoperative PC activity increased in 37/47 (78.7%) dogs with a mean increase of 38.7% ± 2.1%. Ultimate postoperative clinical status was excellent in 16/43 (37.2%), fair in 19/43 (44.2%), and poor in 8/43 dogs (18.6%). No association was detected between preoperative PC (46.8% ± 1.8%) and ultimate clinical status but mean postoperative PC (75.7% ± 1.4%), HCT, MCV, ALB, and BUN were higher in dogs with excellent clinical status. Postoperative PC activity was higher when shunts were completely occluded (96.3% ± 10.9%), which was a finding associated with excellent status. CONCLUSION: Postoperative, but not preoperative, PC activity was higher in dogs with better ultimate clinical status. Similar trends were noted in standard hematological and biochemical values. Complete occlusion of shunts was associated with a higher postoperative PC and superior ultimate clinical status. CLINICAL SIGNIFICANCE: Postoperative PC may provide valuable information about the success of PTCE for IHPSS as it relates to the ultimate status and the need for additional procedures.


Assuntos
Doenças do Cão , Derivação Portossistêmica Transjugular Intra-Hepática , Animais , Doenças do Cão/cirurgia , Cães , Sistema Porta/cirurgia , Veia Porta/cirurgia , Derivação Portossistêmica Transjugular Intra-Hepática/veterinária , Proteína C , Estudos Retrospectivos
3.
J Am Anim Hosp Assoc ; 58(2): 91-95, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-35195709

RESUMO

A feral, domestic shorthair was evaluated for palliative treatment of a pulmonary mass with secondary pneumonia. Because of the patient's temperament and extent of the mass, tracheobronchoscopy, bronchial stenting, and biopsy were elected, followed by adjuvant radiation therapy. Stent placement across the malignantly obstructed bronchus permitted drainage and recruitment of the infected lung lobe. Uncomplicated radiation therapy, stent extension, and debulking due to tissue ingrowth were subsequently performed. Successful palliation was achieved for 323 days with subsequent progressive pulmonary and liver metastases.


Assuntos
Obstrução das Vias Respiratórias , Carcinoma , Doenças do Gato , Cuidados Paliativos , Stents , Obstrução das Vias Respiratórias/cirurgia , Obstrução das Vias Respiratórias/veterinária , Animais , Brônquios/cirurgia , Carcinoma/veterinária , Doenças do Gato/cirurgia , Gatos , Stents/veterinária , Resultado do Tratamento
4.
Vet Radiol Ultrasound ; 61(4): 394-398, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32329210

RESUMO

This retrospective case series describes the radiographic features of suspected suture-associated cystic calculi in six dogs with a history of at least one or multiple prior cystotomies. One of the dogs presented twice. Suspected suture-associated cystic calculi were multifocal, short, predominantly linear mineral opacities localized in the center of the urinary bladder on abdominal radiographs. One patient (n = 1) presented with multifocal round, pin point, and linear radiopaque calculi. The calculi were all calcium oxalate in composition. On gross examination, the calculi had a hollow center. Six cystotomies used monofilament absorbable suture material (polydioxanone [n = 4] or poliglecaprone 25 [n = 1]) in prior cystotomies. Suture material in two of the cases was unknown. Suspected suture-associated cystic calculi are a rare occurrence in veterinary medicine but should be considered in dogs that have a history of prior cystotomy, hollow core on gross analysis, and radiographic evidence of mineral opaque, predominantly linear, cystic calculi.


Assuntos
Cistotomia/veterinária , Doenças do Cão/etiologia , Suturas/veterinária , Cálculos da Bexiga Urinária/veterinária , Animais , Cistotomia/efeitos adversos , Doenças do Cão/diagnóstico por imagem , Doenças do Cão/cirurgia , Cães , Estudos Retrospectivos , Suturas/efeitos adversos , Cálculos da Bexiga Urinária/etiologia
5.
J Zoo Wildl Med ; 46(2): 345-9, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26056891

RESUMO

Urolithiasis is a significant disease concern in Asian small-clawed otters (Aonyx cinerea), with over 60% of captive animals affected. Bilateral ureteral stent placement, using endoscopic and fluoroscopic guidance, and extracorporeal shock wave lithotripsy (ESWL) were performed as salvage procedures in a 13-yr-old intact female Asian small-clawed otter following a 7-yr history of nephrolithiasis and progressive renal insufficiency. Following the procedure, radiographs revealed a slight shifting of urolith position, although a decrease in urolith mass was not observed. As a result of declining quality of life related to severe osteoarthritis, the otter was euthanized 5 wk after the procedure. While this treatment approach was unsuccessful in this case, the technique was clinically feasible, so ESWL and ureteral stent placement may remain a consideration for other individuals of this species presented earlier in the course of this disease.


Assuntos
Endoscopia/veterinária , Litotripsia/veterinária , Nefrolitíase/veterinária , Lontras , Stents/veterinária , Ureter/cirurgia , Animais , Endoscopia/métodos , Feminino , Litotripsia/métodos , Nefrolitíase/terapia
6.
Vet Surg ; 43(2): 199-208, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24350569

RESUMO

OBJECTIVE: To (1) describe minimally invasive transurethral antegrade and retrograde techniques for the placement of self-expanding metallic stents (SEMS) to reestablish urethral patency in cats with non-urolith urethral obstructions and (2) to report the procedural complications, incontinence rates, and long-term effectiveness in maintaining a patent urethra. STUDY DESIGN: Case series. ANIMALS: Cats (n = 8). METHODS: Signalment, history, clinical signs, physical examination, severity of stranguria and incontinence, clinicopathologic data, diagnostic procedures performed, diagnosis, interventional technique, type and dimensions of stent placed, complications and final outcome of 8 cats treated with SEMS for the management of urethral strictures or masses are presented. Each cat was followed for ≥12 months. Follow-up information was obtained from the medical record or by telephone interview of the owner and/or referring veterinarian. RESULTS: Four cats were continent after stent placement, 2 were moderately incontinent, and 2 were severely incontinent. Long-term follow-up (median, 462 days) was available. At follow-up, 5 cats were alive and 3 had been euthanatized at 88, 233, and 305 days. Long-term outcome, as assessed by the authors, was good (1) to excellent (3) in 4 cats, and fair (2) to poor (2) in 4 cats. Owner reported outcomes were excellent in 3/8, good to excellent in 1/8, good in 2/8, and poor in 2/8. CONCLUSION: Palliative stenting of urethral obstructions is a minimally invasive method to re-establish urethral patency in cats.


Assuntos
Doenças do Gato/cirurgia , Stents/veterinária , Obstrução Uretral/veterinária , Animais , Gatos , Feminino , Masculino
7.
J Patient Rep Outcomes ; 8(1): 50, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38743304

RESUMO

AIMS: Caregivers rate improved communication ability as one of the most desired outcomes for successful interventions for individuals with Angelman syndrome (AS). When measuring communication ability in clinical trials, the reliability of such measures is critical for detecting significant changes over time. This study examined the reliability of the Observed-Reported Communication Ability (ORCA) measure completed by caregivers of individuals with AS. METHODS: The ORCA measure was completed by 249 caregivers with 170 caregivers completing the ORCA measure again after 5-12 days. Generalizability theory was used to examine the following sources of measurement error in ORCA scores: concepts, subdomains, assessment points, and the interactions among those facets and the object of measurement: communication ability. Three generalizability studies were conducted to understand the reliability of the ORCA measure for different measurement designs. Decision studies were carried out to demonstrate the optimization of measurement procedures of the ORCA measure. RESULTS: G and Phi coefficients of the original measurement design exceeded the 0.80 threshold considered sufficiently reliable to make relative and absolute decisions about the communication ability of individuals with AS based on their caregivers' observed scores. The optimization procedures indicated that increasing the number of communication concepts and/or assessment points leads to more reliable estimates of communication. CONCLUSION: The ORCA measure was able to reliably distinguish different levels of communication ability among individuals with AS. Multiple assessment points and or more concepts would provide more precise estimates of an individual's communication ability but at the cost of survey fatigue.


Assuntos
Síndrome de Angelman , Cuidadores , Comunicação , Humanos , Síndrome de Angelman/diagnóstico , Cuidadores/psicologia , Reprodutibilidade dos Testes , Masculino , Feminino , Criança , Adulto , Adolescente , Pré-Escolar , Psicometria/métodos , Inquéritos e Questionários , Adulto Jovem
8.
J Vet Intern Med ; 38(2): 878-903, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38217372

RESUMO

Urinary incontinence (UI) is a disorder of micturition that can occur in dogs of any age, sex, and breed depending on the underlying cause and time of onset. Diagnosis and treatment for various causes of UI in dogs have been described by multiple comprehensive single author review articles, but large prospective clinical trials comparing treatment outcomes in veterinary medicine are lacking. The objectives of this consensus statement therefore are to provide guidelines on both recommended diagnostic testing and treatment for various causes of UI in dogs. Specifically, pathophysiology directly related to the canine urinary system will be reviewed and diagnostic and therapeutic challenges will be addressed. A panel of 12 experts in the field (8 small animal internists [L. Adams, J. Bartges, A. Berent, J. Byron, J. Foster, A. Kendall, S. Vaden, J. Westropp], 2 neurologists [J. Coates, N. Olby], 1 radiologist [G. Oetelaar], and 1 surgeon [C. Adin]) was formed to assess and summarize evidence in the peer-reviewed literature and to complement it with consensus recommendations using the Delphi method. Some statements were not voted on by all panelists. This consensus statement aims to provide guidance for management of both male and female dogs with underlying storage or voiding disorders resulting in UI.


Assuntos
Doenças do Cão , Incontinência Urinária , Masculino , Cães , Animais , Feminino , Estudos Prospectivos , Incontinência Urinária/diagnóstico , Incontinência Urinária/terapia , Incontinência Urinária/veterinária , Consenso , Doenças do Cão/terapia , Doenças do Cão/tratamento farmacológico
9.
J Am Vet Med Assoc ; : 1-8, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38579782

RESUMO

OBJECTIVE: To determine the accuracy of 4 preoperative parameters (signalment, urinalysis, urine microbiological culture, and digital radiography) in predicting urocystolith composition, compare accuracy between evaluators of varying clinical experience and a mobile application, and propose a novel algorithm to improve accuracy. ANIMALS: 175 client-owned dogs with quantitative analyses of urocystoliths between January 1, 2012, and July 31, 2020. METHODS: Prospective experimental study. Canine urocystolith cases were randomly presented to 6 blinded "stone evaluators" (rotating interns, radiologists, internists) in 3 rounds, each separated by 2 weeks: case data alone, case data with a urolith teaching lecture, and case data with a novel algorithm. Case data were also entered into the Minnesota Urolith Center mobile application. Prediction accuracy was determined by comparison to quantitative laboratory stone analysis results. RESULTS: Prediction accuracy of evaluators varied with experience when shown case data alone (accuracy, 57% to 82%) but improved with a teaching lecture (accuracy, 76% to 89%) and further improved with a novel algorithm (accuracy, 93% to 96%). Mixed stone compositions were the most incorrectly predicted type. Mobile application accuracy was 74%. CLINICAL RELEVANCE: Use of the 4 preoperative parameters resulted in variable accuracy of urocystolith composition predictions among evaluators. The proposed novel algorithm improves accuracy for all clinicians, surpassing accuracy of the mobile application, and may help guide patient management.

10.
Vet Surg ; 42(4): 440-7, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23298302

RESUMO

OBJECTIVE: To evaluate the efficacy and safety of a percutaneously controlled urethral hydraulic occluder (HO) device for the treatment of refractory urinary incontinence (RUI) in female dogs with various urogenital anomalies. STUDY DESIGN: Case series. ANIMALS: Female dogs with RUI (n = 18). METHODS: Retrospective evaluation of dogs after a silicone ring (HO) was surgically placed around the proximal urethra. The ring was connected to a subcutaneous injection port with actuating tubing. Residual incontinence was treated with percutaneous infusion of sterile saline into the device to provide extraluminal urethral compression. Dogs were assessed for continence (owner-assessed 10-point continence scale) and complications at standard time points. RESULTS: All 18 dogs had significantly improved continence scores (P < .001) after HO placement (median and mean score pre-HO = 2.8 and 3.3; post-HO = 10 and 8.9, respectively) with a median follow-up time of 32 months. "Functional" continence (score ≥ 9) was achieved in 67% of dogs after HO placement, though only 13/18 clients were compliant with inflations. Of dogs belonging to compliant owners, 12 (92%) had a functional continence score. Six dogs (33%) did not require inflation to achieve continence. Urethral obstruction occurred as a complication in 3 dogs. CONCLUSIONS: Use of an HO device was an effective long-term treatment for RUI when traditional options failed. The technique was associated with some complications, and these risks should be considered before use.


Assuntos
Uretra/cirurgia , Incontinência Urinária/veterinária , Esfíncter Urinário Artificial/veterinária , Animais , Cães , Feminino , Fenômenos Mecânicos , Desenho de Prótese , Estudos Retrospectivos , Incontinência Urinária/cirurgia
11.
Can J Vet Res ; 87(1): 74-81, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36606034

RESUMO

The objective of this study was to evaluate unidimensional (mm), bidimensional (mm2), or tridimensional (mL) computed tomography (CT) tumor measurements for ability to discriminate changes in lesion size and predict survival in dogs with nonresectable hepatic carcinoma treated with drug-eluting bead transarterial-chemoembolization (DEB-TACE) and to compare CT response via Response Evaluation Criteria in Solid Tumors 1.1 (mm), World Health Organization (mm2), ellipsoid and spherical volume (mL), and percent necrosis, for their ability to differentiate treatment responders. This was a prospective, single-arm clinical trial. DEB-TACE was performed to varying levels of blood flow stasis in 16 client-owned dogs with nonresectable hepatic carcinoma. Computed tomography imaging responses were assessed and compared to median survival time. Results revealed that initial, follow-up, or changes in unidimensional, bidimensional, or tridimensional tumor measurements were not associated with survival. Larger bidimensional and tridimensional tumor measurements/body weight on initial and follow-up CT were significantly associated with a shorter median survival time [bidimensional (P = 0.04, 0.016) and tridimensional (P = 0.025, 0.015), respectively]. A higher percent necrosis on initial CT was significantly associated with a shorter median survival time (P = 0.038). Ellipsoid volumetric criteria detected treatment response most frequently; however, response classification was not associated with median survival time. Computed tomography bidimensional and tridimensional tumor measurements/body weight before and after DEB-TACE may help to predict median survival time for dogs undergoing DEB-TACE for hepatic carcinoma.


L'objectif de cette étude était d'évaluer les mesures tumorales unidimensionnelles (mm), bidimensionnelles (mm2) ou tridimensionnelles (mL) par tomodensitométrie (CT) pour déterminer la capacité de discriminer les changements de taille des lésions et de prédire la survie chez les chiens atteints d'un carcinome hépatique non-résécable traité avec un médicament par chimioembolisation transartérielle par billes à élution (DEB-TACE) et pour comparer la réponse CT via les critères d'évaluation de la réponse dans les tumeurs solides 1,1 (mm), l'Organisation mondiale de la santé (mm2), le volume ellipsoïde et sphérique (mL) et le pourcentage de nécrose, pour leur capacité à différencier les répondeurs au traitement. Il s'agissait d'un essai clinique prospectif à un seul volet. Le DEB-TACE a été réalisé à différents niveaux de stase du flux sanguin chez 16 chiens appartenant à des clients atteints d'un carcinome hépatique non-résécable. Les réponses d'imagerie par tomodensitométrie ont été évaluées et comparées au temps de survie médian. Les résultats ont révélé que les mesures initiales, de suivi ou les modifications des mesures tumorales unidimensionnelles, bidimensionnelles ou tridimensionnelles n'étaient pas associées à la survie. Des mesures tumorales bidimensionnelles et tridimensionnelles plus grandes/poids corporel sur la CT initiale et de suivi étaient significativement associées à un temps de survie médian plus court [bidimensionnel (P = 0,04, 0,016) et tridimensionnel (P = 0,025, 0,015), respectivement]. Un pourcentage plus élevé de nécrose au scanner initial CT était significativement associé à une durée de survie médiane plus courte (P = 0,038). Les critères volumétriques ellipsoïdes ont détecté la réponse au traitement le plus fréquemment; cependant, la classification des réponses n'était pas associée à la durée médiane de survie. La tomodensitométrie bidimensionnelle et tridimensionnelle des mesures tumorales/poids corporel avant et après DEB-TACE peut aider à prédire la durée médiane de survie des chiens subissant DEB-TACE pour un carcinome hépatique.(Traduit par Docteur Serge Messier).


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Doenças do Cão , Neoplasias Hepáticas , Animais , Cães , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/veterinária , Quimioembolização Terapêutica/veterinária , Quimioembolização Terapêutica/métodos , Doenças do Cão/diagnóstico por imagem , Doenças do Cão/terapia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/veterinária , Necrose/terapia , Necrose/veterinária , Estudos Prospectivos , Tomografia Computadorizada por Raios X/veterinária , Resultado do Tratamento
12.
Am J Intellect Dev Disabil ; 128(3): 204-218, 2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-37104860

RESUMO

There is a critical need for high-quality clinical outcome assessments to capture the important aspects of communication ability of individuals with Angelman syndrome (AS). To center the perspective of caregivers, our team developed the novel Observer-Reported Communication Ability (ORCA) measure using best practice guidelines, with the goal of developing a measure that could be administered to caregivers directly without the need for a certified administrator for use in clinical trials. To refine the draft measure, we conducted two rounds of cognitive interviews with 24 caregivers and a quantitative study including 249 caregivers. The results from both studies support the overall content validity, construct validity, and the reliability of the ORCA measure for individuals with AS > 2 years old for use in research contexts. Future work should explore the responsiveness of ORCA measures to changes over time in a diverse sample.


Assuntos
Síndrome de Angelman , Humanos , Pré-Escolar , Reprodutibilidade dos Testes , Cuidadores/psicologia , Comunicação
13.
Am J Intellect Dev Disabil ; 128(3): 185-203, 2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-37104863

RESUMO

Communication deficits have a substantial impact on quality of life for individuals with Angelman syndrome (AS) and their families, but limited qualitative work exists to support the necessary content of measures aiming to assess communication for these individuals. Following best practices for concept elicitation studies, we conducted individual qualitative interviews with caregivers and clinicians to elicit meaningful aspects of communication for individuals with AS. Caregivers were able to discuss their child's specific communication behaviors within a large number of expressive, receptive, and pragmatic functions via numerous symbolic and non-symbolic modalities. These results aligned well with published literature on communication in AS and will be used to inform the design of a novel caregiver-reported measure. Future studies on communication in individuals with AS should focus on gathering quantitative data from large samples of diverse caregivers, which would allow for estimations of the frequency of specific behaviors across the population.


Assuntos
Síndrome de Angelman , Cuidadores , Criança , Humanos , Qualidade de Vida , Comunicação
14.
Children (Basel) ; 10(9)2023 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-37761423

RESUMO

Previous patient-centered concept models of Angelman syndrome (AS) are integral in developing our understanding of the symptoms and impact of this condition with a holistic perspective and have highlighted the importance of motor function. We aimed to develop the motor and movement aspects of the concept models, to support research regarding motor-related digital outcomes aligned with patients' and caregivers' perspectives. We conducted a qualitative analysis of semi-structured interviews of 24 caregivers to explore AS motor-related features, factors influencing them and their impact on patients and caregivers.The most impacted motor features were gait, walking and stair-climbing. Half of caregivers ranked motor symptoms as one of the most burdensome symptoms of AS. Caregivers frequently reported physical therapy, motivation, medical management and age as factors influencing motor function in AS and reported that impaired motor function affected both patients and caregivers. Measures of lower-limb motor function were identified as relevant to monitor drug effectiveness in AS. Caregivers discussed expected benefits of a digital outcome and potential issues with wearable technology in the context of AS. We propose a new motor function patient-centered concept model, providing insights for the development of relevant, motor-related, digital outcomes in AS.

15.
Sci Transl Med ; 15(688): eabf4077, 2023 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-36947593

RESUMO

Angelman syndrome is a devastating neurogenetic disorder for which there is currently no effective treatment. It is caused by mutations or epimutations affecting the expression or function of the maternally inherited allele of the ubiquitin-protein ligase E3A (UBE3A) gene. The paternal UBE3A allele is imprinted in neurons of the central nervous system (CNS) by the UBE3A antisense (UBE3A-AS) transcript, which represents the distal end of the small nucleolar host gene 14 (SNHG14) transcription unit. Reactivating the expression of the paternal UBE3A allele in the CNS has long been pursued as a therapeutic option for Angelman syndrome. Here, we described the development of an antisense oligonucleotide (ASO) therapy for Angelman syndrome that targets an evolutionarily conserved region demarcating the start of the UBE3A-AS transcript. We designed and chemically optimized gapmer ASOs targeting specific sequences at the start of the human UBE3A-AS transcript. We showed that ASOs targeting this region precisely and efficiently repress the transcription of UBE3A-AS, reactivating the expression of the paternal UBE3A allele in neurotypical and Angelman syndrome induced pluripotent stem cell-derived neurons. We further showed that human-targeted ASOs administered to the CNS of cynomolgus macaques by lumbar intrathecal injection repress UBE3A-AS and reactivate the expression of the paternal UBE3A allele throughout the CNS. These findings support the advancement of this investigational molecular therapy for Angelman syndrome into clinical development (ClinicalTrials.gov, NCT04259281).


Assuntos
Síndrome de Angelman , Humanos , Síndrome de Angelman/terapia , Síndrome de Angelman/tratamento farmacológico , Alelos , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo
16.
J Vet Intern Med ; 36(2): 441-450, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35129219

RESUMO

BACKGROUND: Aortic and aortoiliac thrombosis in dogs causes disease and death. OBJECTIVE: To describe the procedure and outcomes for stenting the caudal aorta and aortoiliac trifurcation. ANIMALS: Seven client-owned dogs that underwent aortic/aortoiliac stenting for treatment of thrombosis. METHODS: Retrospective multi-center investigation. Medical records were reviewed for dogs that underwent stenting of the aorta or aortoiliac trifurcation between 2008 and 2020. Information collected included history, signalment, clinicopathologic data, diagnostic imaging, procedure reports, and outcomes. RESULTS: Seven dogs with an occlusive thrombus located at or near the aortic trifurcation were included. Four of 7 dogs were non-ambulatory. Hind limbs were paretic in 5 dogs, paralyzed in 1 dog, and claudication alone was noted in 1 dog. Five of the 7 dogs had protein-losing nephropathy (PLN). Of 5 dogs with PLN, 1 had protein-losing enteropathy (PLE) and controlled hypothyroidism and 1 had caudal aortic chondrosarcoma. Two dogs had no identified underlying disease. Angiography was performed before catheter directed thrombolysis and stent placement. No deaths occurred during the procedure. Postoperative complications included pain (4/7), bruising and edema (3/7), bruising only (1/7), and edema only (1/7). Median survival time (MST) of the 7 dogs was 264 days (range, 1-1053 days). Five of 7 dogs were ambulatory within 2 days of stenting and survived to discharge with a MST of 425 days (range, 208-1053 days). CONCLUSIONS AND CLINICAL IMPORTANCE: Stenting of the aorta and aortoiliac trifurcation can provide an apparently safe and effective treatment with rapid return to ambulation for some dogs with aortic thrombosis.


Assuntos
Doenças da Aorta , Doenças do Cão , Trombose , Animais , Aorta , Doenças da Aorta/cirurgia , Doenças da Aorta/veterinária , Doenças do Cão/diagnóstico por imagem , Doenças do Cão/cirurgia , Cães , Estudos Retrospectivos , Stents/veterinária , Trombose/cirurgia , Trombose/veterinária , Resultado do Tratamento
17.
J Feline Med Surg ; 24(10): 1017-1025, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-34894831

RESUMO

OBJECTIVES: The aims of this study were to evaluate serum symmetric dimethylarginine (SDMA) and creatinine concentrations in cats with urethral obstruction pre- and post-decompression of the obstruction, and to determine if pre-decompression values were predictive of post-decompression renal function, as measured by SDMA and creatinine. METHODS: This was a prospective observational study. Twenty-five client-owned cats with urethral obstruction were hospitalized for decompression of the obstruction. Serum SDMA and creatinine were prospectively assessed at presentation, 24 h post-decompression and 5-20 days post-decompression. Urinalysis and culture were assessed at presentation and at the final follow-up. Exclusion criteria included positive urine culture, reobstruction or failure to obtain required samples. RESULTS: Mean SDMA concentration dropped by 41.8% from an initial pre-decompression concentration of 17.6 µg/dl to 10.3 µg/dl 24 h post-decompression (P <0.001). The mean creatinine value dropped by 38.4% from an initial pre-decompression concentration of 2.5 mg/dl to 1.5 mg/dl 24 h post-decompression (P <0.001). There was no association between SDMA concentration at initial presentation and SDMA concentration 5-20 days after urethral catheterization (Spearman's ρ = 0.205, P = 0.314). Creatinine concentration upon initial presentation was associated with the 5-20 day values after urethral catheterization (Spearman's ρ = 0.583, P <0.002). Twenty percent of cases were excluded due to bacterial growth on initial urine culture. SDMA and creatinine concentrations were significantly higher in these cases (median 59 µg/dl and 10.9 mg/dl, respectively) compared with those with negative cultures (median 14 µg/dl and 1.6 mg/dl [P <0.002 and P <0.001], respectively). CONCLUSIONS AND RELEVANCE: Both SDMA and creatinine decreased significantly after urethral catheterization, suggesting that renal function post-decompression cannot be predicted by the pre-decompression concentrations of these values.


Assuntos
Doenças do Gato , Insuficiência Renal Crônica , Obstrução Uretral , Animais , Arginina/análogos & derivados , Biomarcadores , Doenças do Gato/diagnóstico , Gatos , Creatinina , Insuficiência Renal Crônica/veterinária , Obstrução Uretral/diagnóstico , Obstrução Uretral/veterinária
18.
J Am Vet Med Assoc ; 260(7): 1-8, 2022 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-35175927

RESUMO

CASE DESCRIPTION: An 8-year-old spayed female Yorkshire Terrier-Poodle dog was evaluated for persistent pollakiuria and stranguria following routine cystotomy for calcium oxalate cystoliths. CLINICAL FINDINGS: The dog presented for a cystotomy with intermittent hematuria. Postoperative radiographs revealed no remaining cystoliths. Urine, cystolith, and bladder mucosal aerobic cultures were negative. Pollakiuria, stranguria, and hematuria developed immediately after surgery and persisted despite antibiotics. Ultrasound revealed suspected fibrous adhesions within the urinary bladder lumen connecting the dorsal and ventral bladder wall creating a septum. This was confirmed cystoscopically 4 weeks after surgery. TREATMENT AND OUTCOME: Cystoscopic-guided laser ablation was performed to incise abnormal tissue connecting the ventral and dorsal bladder wall using a holmium:yttrium-aluminum-garnet laser. Three weeks later, ultrasound revealed adhesion resolution though mild pollakiuria and stranguria persisted. Oxybutynin was prescribed and clinical signs resolved. At 27 months after ablation, hematuria occurred with recurrent cystoliths. These cystoliths were removed by percutaneous cystolithotomy, documenting a cystoscopically normal bladder wall. The patient had normal urination for 55.5 months after ablation, with normal bladder wall thickness on ultrasound repeated at 27 and 36 months after ablation. CLINICAL RELEVANCE: To the authors' knowledge, an adhesion creating a septum between the dorsal and ventral bladder wall has not been previously reported as a complication after cystotomy in any species and should be considered as a cause of persistent lower urinary signs after surgery. Ultrasound identified the lesion in this dog. Because bladder abnormalities can develop quickly after surgery, ultrasound might be considered if urine testing is not supportive of infection. Cystoscopic-guided laser ablation was a successful minimally invasive treatment in this case.


Assuntos
Doenças do Cão , Cálculos da Bexiga Urinária , Animais , Cistotomia/veterinária , Doenças do Cão/diagnóstico , Doenças do Cão/cirurgia , Cães , Disuria/veterinária , Feminino , Hematúria/veterinária , Bexiga Urinária/cirurgia , Cálculos da Bexiga Urinária/cirurgia , Cálculos da Bexiga Urinária/veterinária
19.
J Feline Med Surg ; 24(4): 328-336, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34124964

RESUMO

OBJECTIVES: The aim of this study was to determine whether preoperative ultrasound imaging characteristic(s) in cats suffering from unilateral benign ureteral obstructions are predictive of outcome after successful renal decompression with a subcutaneous ureteral bypass (SUB) device. METHODS: This was a retrospective study of 37 cats with unilateral, benign ureteral obstruction. Preoperative imaging characteristics (including renal pelvis diameter, parenchymal thickness [transverse plane], renal length and pelvic size:overall renal size) and biochemical data were evaluated for all cats diagnosed with a unilateral ureteral obstruction treated with a SUB device. Any patient with bilateral obstructions or documented bacteriuria/infection in the data collection period was excluded. All patients were followed between 3 and 6 months postoperatively to obtain postoperative biochemical data. Long-term outcome was defined as serum creatinine concentration at 3-6 months postoperatively. RESULTS: No preoperative imaging characteristics or biochemical findings were found to be significantly associated with long-term serum creatinine concentrations. The length of the kidney was found to be associated with change in blood urea nitrogen and creatinine with decompression but not with long-term renal values. CONCLUSIONS AND RELEVANCE: In this study, long-term renal function based on preoperative ultrasound imaging findings could not be predicted in cats with unilateral ureteral obstruction, regardless of the severity of the biochemical parameters, renal pelvic dilation (large or small pelvis), kidney size or thickness of renal parenchyma assessed.


Assuntos
Doenças do Gato , Obstrução Ureteral , Animais , Doenças do Gato/diagnóstico por imagem , Doenças do Gato/cirurgia , Gatos , Creatinina , Feminino , Humanos , Rim/diagnóstico por imagem , Rim/fisiologia , Rim/cirurgia , Pelve Renal , Masculino , Estudos Retrospectivos , Stents/veterinária , Sobreviventes , Obstrução Ureteral/diagnóstico por imagem , Obstrução Ureteral/cirurgia , Obstrução Ureteral/veterinária
20.
J Vet Intern Med ; 36(5): 1792-1799, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35971921

RESUMO

BACKGROUND: Chemoembolization is a viable treatment option for patients with nonresectable hepatic carcinoma (HC) and may allow delivery of chemotherapeutic drugs with decreased systemic toxicity. HYPOTHESIS/OBJECTIVE: Compare the serum concentrations of doxorubicin after chemoembolization or IV administration in the same patient. We hypothesized that locoregional delivery may result in increased tumor chemotherapeutic drug concentrations, reflected by decreased measurable serum drug concentrations. Adverse hematological events were hypothesized to be decreased after locoregional delivery. ANIMALS: Seventeen client-owned dogs with incompletely resectable HC. METHODS: Prospective, single-arm clinical trial. Drug-eluting bead transarterial chemoembolization was performed to varying levels of blood flow stasis (NO STASIS, STASIS). Intravenous doxorubicin (IVC) subsequently was administered in selected patients. Systemic exposure was quantified by area under the serum doxorubicin concentration time curve (AUC), maximum serum doxorubicin concentration (Cmax ), and time doxorubicin was last above the limit of quantitation (Tlast ). Nadir test results after treatments were used to evaluate adverse hematological events. RESULTS: Thirteen NO STASIS treatments, 15 STASIS treatments, and 9 IVC treatments were performed. Maximum serum doxorubicin concentration, AUC, and Tlast were significantly lower when comparing NO STASIS or STASIS to IVC treatments. Of the patients with nadir results available, no adverse hematological events were observed after NO STASIS or STASIS treatments. Two patients developed adverse hematological events after IVC treatment. CONCLUSIONS/CLINICAL RELEVANCE: Drug-eluting bead transarterial chemoembolization offers a viable treatment option for patients with incompletely resectable HC with the potential for increased local tumor doxorubicin concentrations, decreased systemic chemotherapeutic exposure, and fewer adverse hematological events.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Doenças do Cão , Neoplasias Hepáticas , Administração Intravenosa/veterinária , Animais , Antibióticos Antineoplásicos , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/veterinária , Quimioembolização Terapêutica/efeitos adversos , Quimioembolização Terapêutica/métodos , Quimioembolização Terapêutica/veterinária , Doenças do Cão/tratamento farmacológico , Doenças do Cão/etiologia , Cães , Doxorrubicina , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/veterinária , Estudos Prospectivos , Resultado do Tratamento
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