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Factors influencing serum concentrations of levetiracetam in dogs with epilepsy 影响癫痫犬血清中左乙拉西坦浓度的因素。
IF 2.1 2区 农林科学 Q1 VETERINARY SCIENCES Pub Date : 2024-06-18 DOI: 10.1111/jvim.17128
Marine Saint-Maxent, Tristan Juette, Joane Parent, Aude Castel, Thomas Parmentier

Background

Factors affecting serum concentrations of levetiracetam in dogs are unknown and could affect the efficacy of levetiracetam in controlling seizures in dogs with epilepsy.

Hypothesis/Objectives

Higher PO doses of levetiracetam will be needed in dogs to achieve serum concentrations shown to be effective in humans. Determine factors that could influence serum levetiracetam concentrations and justify dose adjustment in some epileptic dogs.

Animals

Sixty-nine client-owned dogs with epilepsy treated with levetiracetam alone or in combination, based on 127 trough serum concentration measurements of levetiracetam.

Methods

Retrospective cohort study. Linear mixed models were used to assess the effect of patient signalment and concurrent drug administration on serum concentrations of levetiracetam and the effect of serum concentration of levetiracetam on seizure frequency reduction.

Results

The PO dose of levetiracetam significantly explained changes in serum levetiracetam concentration, and this causal link was stronger with monotherapy (R2 = 0.59, P < .001). Phenobarbital significantly decreased serum levetiracetam concentration in a dose dependent manner (R2 = 0.30, P = .003). Based on our model, a levetiracetam dosage of 99–216 mg/kg/day is necessary to obtain a serum levetiracetam concentration of 20 μg/mL when used alone or concurrently with 7 mg/kg/day of phenobarbital. No other factors were found to influence serum levetiracetam concentrations. No therapeutic range could be identified.

Conclusion and Clinical Importance

Our data suggest that a dosage of 99–216 mg/kg/day of levetiracetam is needed to achieve a serum concentration known to be therapeutically effective in humans, especially when administered concomitantly with phenobarbital.

背景:影响狗体内左乙拉西坦血清浓度的因素尚不清楚,这些因素可能会影响左乙拉西坦控制癫痫狗发作的疗效:狗体内需要更高的左乙拉西坦剂量才能达到人类有效的血清浓度。确定可能影响血清中左乙拉西坦浓度的因素,并证明对某些癫痫犬进行剂量调整是合理的:根据127次左乙拉西坦血清浓度谷值测量结果,对69只客户饲养的癫痫犬进行左乙拉西坦单独或联合治疗:方法:回顾性队列研究。采用线性混合模型评估患者信号和同时给药对左乙拉西坦血清浓度的影响,以及左乙拉西坦血清浓度对减少癫痫发作频率的影响:结果:左乙拉西坦的给药剂量能显著解释血清中左乙拉西坦浓度的变化,这种因果关系在单药治疗中更为明显(R2 = 0.59,P 2 = 0.30,P = .003)。根据我们的模型,单独使用或与 7 毫克/千克/天的苯巴比妥同时使用时,需要 99-216 毫克/千克/天的左乙拉西坦剂量才能使血清左乙拉西坦浓度达到 20 微克/毫升。没有发现影响血清左乙拉西坦浓度的其他因素。无法确定治疗范围:我们的数据表明,要达到已知对人体有效的血清浓度,需要99-216毫克/千克/天的左乙拉西坦剂量,尤其是与苯巴比妥同时服用时。
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引用次数: 0
Retrospective evaluation of the effect of acid suppressant drugs on leukocyte ratios in dogs with mast cell tumors 回顾性评估抑酸药物对肥大细胞瘤患犬白细胞比率的影响。
IF 2.1 2区 农林科学 Q1 VETERINARY SCIENCES Pub Date : 2024-06-18 DOI: 10.1111/jvim.17133
Sydney Oberholtzer, Xiaojuan Zhu, Andrea Dedeaux, Olya Martin, Emily N. Gould

Background

Acid suppressant drugs (ASDs) are commonly used to decrease gastric acid production, but some evidence exists that ASDs exert immunomodulatory effects. Such an effect has not been investigated in dogs for which ASDs are routinely prescribed.

Hypothesis

Compared to naïve subjects, dogs treated with ASDs will exhibit differences in leukocyte ratios after treatment.

Animals

Fifty-one dogs with mast cell tumors (MCTs).

Materials and Methods

Dogs with MCT that were either AS naïve or treated with ASDs (i.e., histamine-2-receptor antagonists [H2RA] or proton pump inhibitors [PPI]) were included in this retrospective study. Subjects were categorized into 3 treatment groups (AS naïve, H2RA treated, and PPI treated), and leukocyte ratios (neutrophil:eosinophil, lymphocyte:monocyte, and neutrophil:lymphocyte [NLR]) were calculated before and after treatment. A mixed effects analysis of variance on ranks was used to assess differences in ratios between treatments, between pre- and post-treatment time points, and between pre- and post-time points for each treatment. Concurrent administration of antihistamines, corticosteroids, and chemotherapeutic drugs was assessed as a confounding factor.

Results

Famotidine (n = 14/14) and omeprazole (n = 12/12) were the only H2RA and PPI used, respectively. Dogs receiving famotidine had a significant increase in median NLR from pre- to post-treatment (3.429; range, 1.417–15 to 5.631; range, 2.654–92; P < 0.01) compared to PPI treated or AS naïve dogs. No differences existed in chemotherapeutic drug or corticosteroid use between groups.

Conclusions

A significant difference in NLR was identified in famotidine treated dogs compared with omeprazole treated or AS naïve dogs.

背景:抑酸药(ASD)通常用于减少胃酸分泌,但有证据表明抑酸药具有免疫调节作用。这种作用尚未在狗身上进行过调查,而ASD是狗的常规处方:动物:51 只患有肥大细胞瘤的狗:51只患有肥大细胞瘤(MCT)的狗:这项回顾性研究纳入了患有肥大细胞瘤的犬只,这些犬只要么未经AS治疗,要么接受了ASDs治疗(即组胺-2受体拮抗剂[H2RA]或质子泵抑制剂[PPI])。受试者被分为 3 个治疗组(AS 天真组、H2RA 治疗组和 PPI 治疗组),并计算了治疗前后的白细胞比率(中性粒细胞:嗜酸性粒细胞、淋巴细胞:单核细胞和中性粒细胞:淋巴细胞 [NLR])。采用等级方差混合效应分析来评估不同治疗方法之间、治疗前后时间点之间以及每种治疗方法前后时间点之间的比率差异。同时服用抗组胺药、皮质类固醇和化疗药物作为混杂因素进行了评估:法莫替丁(n = 14/14)和奥美拉唑(n = 12/12)分别是唯一使用的H2RA和PPI。接受法莫替丁治疗的狗的中位 NLR 从治疗前到治疗后显著增加(3.429;范围,1.417-15 到 5.631;范围,2.654-92;P 结论:法莫替丁和奥美拉唑对狗的 NLR 有显著影响:法莫替丁治疗犬与奥美拉唑治疗犬或 AS 天真犬相比,NLR 有明显差异。
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引用次数: 0
Efficacy and safety of once daily oral administration of sodium-glucose cotransporter-2 inhibitor velagliflozin compared with twice daily insulin injection in diabetic cats 糖尿病猫每天口服一次钠-葡萄糖共转运体-2抑制剂velagliflozin与每天注射两次胰岛素的疗效和安全性比较。
IF 2.1 2区 农林科学 Q1 VETERINARY SCIENCES Pub Date : 2024-06-17 DOI: 10.1111/jvim.17124
Stijn J. M. Niessen, Hans S. Kooistra, Yaiza Forcada, Charlotte R. Bjørnvad, Balazs Albrecht, Franziska Roessner, Esther Herberich, Carla Kroh

Background

Options for treatment of diabetes mellitus in cats are limited to insulin injections and monitoring for hypoglycemia.

Hypothesis

Once daily sodium-glucose cotransporter-2 inhibitor velagliflozin PO is noninferior to insulin injections.

Animals

Client-owned diabetic cats (127 safety; 116 efficacy assessment).

Methods

Prospective, randomized (1 mg/kg velagliflozin), positive controlled (titrated Caninsulin), open label, noninferiority field trial, comparing number of cats with treatment success in ≥1 clinical variable and ≥1 glycemic variable (margin Δ: 15%) on Day 45; secondary endpoints included glycemic and clinical assessments during 91 days.

Results

On Day 45, 29/54 (54%) velagliflozin-treated cats and 26/62 (42%) Caninsulin-treated cats showed treatment success, demonstrating noninferiority (difference −11.8%; upper 1-sided 97.5% confidence interval, −∞ to 6.3%). By Day 91, quality of life (QoL), polyuria, and polydipsia had improved in 81%, 54% and 61% (velagliflozin); on blood glucose (BG) curves, mean BG was <252 mg/dL in 42/54 (78%; velagliflozin) and 37/62 (60%; Caninsulin); minimum BG was <162 mg/dL in 41/54 (76%; velagliflozin) and 41/62 (66%; Caninsulin); serum fructosamine was <450 μmol/L in 41/54 (76%; velagliflozin) and 38/62 (61%; Caninsulin). Velagliflozin's most frequent adverse events were loose feces/diarrhea (n = 23/61, 38%), positive urine culture (n = 19/61, 31%), and nonclinical hypoglycemia (BG <63 mg/dL; n = 8/61, 13%); Caninsulin's: clinical and nonclinical hypoglycemia (n = 35/66, 53%), positive urine culture (n = 18/66, 27%), and loose feces/diarrhea (n = 10/66, 15%). Diabetic ketoacidosis occurred in 4/61 (7%; velagliflozin) and 0/66 (Caninsulin).

Conclusions and Clinical Importance

Once daily oral administration of velagliflozin was noninferior to insulin injections, showed good QoL and glycemia without clinical hypoglycemia.

背景:治疗猫糖尿病的方法仅限于注射胰岛素和监测低血糖:每天一次的钠-葡萄糖共转运体-2抑制剂velagliflozin PO不劣于胰岛素注射:动物:客户饲养的糖尿病猫(127只安全性评估;116只疗效评估):前瞻性、随机(1 mg/kg velagliflozin)、阳性对照(滴定卡尼胰岛素)、开放标签、非劣效性现场试验,比较第 45 天在≥1 个临床变量和≥1 个血糖变量(差值Δ:15%)方面治疗成功的猫的数量;次要终点包括 91 天内的血糖和临床评估:在第 45 天,29/54(54%)只接受过 velagliflozin 治疗的猫和 26/62(42%)只接受过 Caninsulin 治疗的猫都取得了治疗成功,显示出非劣效性(差异为 -11.8%;单侧 97.5% 置信区间上限为 -∞ 至 6.3%)。到第 91 天,81%、54% 和 61%(velagliflozin)的患者生活质量(QoL)、多尿和多饮得到改善;在血糖(BG)曲线上,平均血糖为结论,具有临床重要性:每日口服一次velagliflozin并不比注射胰岛素效果差,显示出良好的QoL和血糖水平,且无临床低血糖。
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引用次数: 0
Longitudinal analysis of echocardiographic and cardiac biomarker variables in dogs with atrial fibrillation: The optimal rate control in dogs with atrial fibrillation II study 对心房颤动犬的超声心动图和心脏生物标志物变量进行纵向分析:心房颤动犬的最佳心率控制 II 研究。
IF 2.1 2区 农林科学 Q1 VETERINARY SCIENCES Pub Date : 2024-06-14 DOI: 10.1111/jvim.17120
Brigite Pedro, Antonia Mavropoulou, Mark A. Oyama, Christopher Linney, João Neves, Joanna Dukes-McEwan, Ana P. Fontes-Sousa, Anna R. Gelzer

Background

Rate control (RC; meanHRHolter ≤ 125 bpm) increases survival in dogs with atrial fibrillation (AF). The mechanisms remain unclear.

Hypothesis/Objectives

Investigate echocardiographic and biomarker differences between RC and non-RC (NRC) dogs. Determine if changes post-anti-arrhythmic drugs (AAD) predict successful RC in subsequent Holter monitoring. Evaluate if early vs late RC affects survival.

Animals

Fifty-two dogs with AF.

Methods

Holter-derived mean heart rate, echocardiographic and biomarker variables from dogs receiving AAD were analyzed prospectively at each re-evaluation and grouped into RC or NRC. The primary endpoint was successful RC. Between group comparisons of absolute values, magnitude of change from admission to re-evaluations and end of study were performed using Mann-Whitney tests or unpaired t-tests. Logistic regression explored variables associated with inability to achieve RC at subsequent visits. Kaplan-Meier survival analysis was used to compare survival time of early vs late RC.

Results

At visit 2, 11/52 dogs were RC; at visit 3, 14/52 were RC; and at visit 4, 4/52 were RC. At the end of study, 25/52 remained NRC. At visit 2, both groups had increased cardiac dimensions, but NRC dogs had larger dimensions; biomarkers did not differ. At the end of study, RC showed decreased cardiac dimensions and end-terminal pro-brain natriuretic peptide (NT-proBNP) compared with NRC. No variables were useful at predicting RC success in subsequent visits. Survival analysis found no differences between early vs late RC.

Conclusions and Clinical Importance

The RC dogs had decreased cardiac dimensions and NT-proBNP, suggesting HR-mediated reverse-remodeling might benefit survival, even with delayed RC achievement. Pursuit of RC is crucial despite initial failures.

背景:心率控制(RC;meanHRHolter ≤ 125 bpm)可提高心房颤动(AF)犬的存活率。其机制仍不清楚:调查 RC 和非 RC(NRC)犬之间的超声心动图和生物标志物差异。确定服用抗心律失常药物 (AAD) 后的变化是否能预测后续 Holter 监测中成功的 RC。评估早期与晚期 RC 是否会影响存活率:方法:在每次重新评估时对接受 AAD 的狗的 Holter 导出平均心率、超声心动图和生物标记变量进行前瞻性分析,并将其分为 RC 或 NRC 组。主要终点是成功 RC。采用 Mann-Whitney 检验或非配对 t 检验对绝对值、从入院到再评估以及研究结束期间的变化幅度进行组间比较。逻辑回归探讨了与后续就诊时无法实现 RC 相关的变量。Kaplan-Meier 生存分析用于比较早期与晚期 RC 的存活时间:第 2 次检查时,11/52 只狗达到 RC;第 3 次检查时,14/52 只狗达到 RC;第 4 次检查时,4/52 只狗达到 RC。在研究结束时,25/52 的狗仍为 NRC。在第 2 次检查时,两组狗的心脏尺寸都有所增加,但 NRC 狗的尺寸更大;生物标记物没有差异。研究结束时,与 NRC 相比,RC 的心脏尺寸和终末前脑钠肽 (NT-proBNP) 均有所下降。没有任何变量有助于预测后续访问中的 RC 成功率。生存分析发现,早期与晚期 RC 之间没有差异:RC犬的心脏尺寸和NT-proBNP均有所下降,这表明即使延迟实现RC,由心率介导的反向重塑也可能有利于存活。尽管最初失败了,但追求 RC 是至关重要的。
{"title":"Longitudinal analysis of echocardiographic and cardiac biomarker variables in dogs with atrial fibrillation: The optimal rate control in dogs with atrial fibrillation II study","authors":"Brigite Pedro,&nbsp;Antonia Mavropoulou,&nbsp;Mark A. Oyama,&nbsp;Christopher Linney,&nbsp;João Neves,&nbsp;Joanna Dukes-McEwan,&nbsp;Ana P. Fontes-Sousa,&nbsp;Anna R. Gelzer","doi":"10.1111/jvim.17120","DOIUrl":"10.1111/jvim.17120","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Rate control (RC; meanHR<sub>Holter</sub> ≤ 125 bpm) increases survival in dogs with atrial fibrillation (AF). The mechanisms remain unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Hypothesis/Objectives</h3>\u0000 \u0000 <p>Investigate echocardiographic and biomarker differences between RC and non-RC (NRC) dogs. Determine if changes post-anti-arrhythmic drugs (AAD) predict successful RC in subsequent Holter monitoring. Evaluate if early vs late RC affects survival.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Animals</h3>\u0000 \u0000 <p>Fifty-two dogs with AF.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Holter-derived mean heart rate, echocardiographic and biomarker variables from dogs receiving AAD were analyzed prospectively at each re-evaluation and grouped into RC or NRC. The primary endpoint was successful RC. Between group comparisons of absolute values, magnitude of change from admission to re-evaluations and end of study were performed using Mann-Whitney tests or unpaired <i>t</i>-tests. Logistic regression explored variables associated with inability to achieve RC at subsequent visits. Kaplan-Meier survival analysis was used to compare survival time of early vs late RC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>At visit 2, 11/52 dogs were RC; at visit 3, 14/52 were RC; and at visit 4, 4/52 were RC. At the end of study, 25/52 remained NRC. At visit 2, both groups had increased cardiac dimensions, but NRC dogs had larger dimensions; biomarkers did not differ. At the end of study, RC showed decreased cardiac dimensions and end-terminal pro-brain natriuretic peptide (NT-proBNP) compared with NRC. No variables were useful at predicting RC success in subsequent visits. Survival analysis found no differences between early vs late RC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions and Clinical Importance</h3>\u0000 \u0000 <p>The RC dogs had decreased cardiac dimensions and NT-proBNP, suggesting HR-mediated reverse-remodeling might benefit survival, even with delayed RC achievement. Pursuit of RC is crucial despite initial failures.</p>\u0000 </section>\u0000 </div>","PeriodicalId":49958,"journal":{"name":"Journal of Veterinary Internal Medicine","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11256134/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141321057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The diagnostic relevance of mesenteric lymph node biopsy in small intestinal lymphoma in cats 肠系膜淋巴结活检对猫小肠淋巴瘤的诊断意义。
IF 2.1 2区 农林科学 Q1 VETERINARY SCIENCES Pub Date : 2024-06-10 DOI: 10.1111/jvim.17095
Laura Marconato, Valeria Martini, Barbara Banco, Silvia Benali, Veronica Crocchianti, Selina Iussich, Michele Marino, Maria Massaro, Teresa Bruna Pagano, Luca Aresu

Background

Regional lymph nodes are frequently sampled in cats with suspected intestinal lymphoma; however, their diagnostic value has not been explored.

Objectives

To investigate whether histologic and immunohistochemical analysis of mesenteric lymph nodes correlates with the diagnosis of intestinal lymphoma in cats.

Animals

One hundred 2 client-owned cats diagnosed with intestinal lymphoma.

Methods

Retrospective study. The inclusion criteria required a full-thickness biopsy of the small intestine and concurrent excision of mesenteric lymph nodes. Histologic and immunophenotypic analyses were performed on intestinal biopsies and corresponding lymph nodes. Selected nodal samples diagnosed with reactive lymph nodes underwent clonality testing.

Results

Transmural T-cell lymphomas, encompassing small and large cell types, were predominant (64 cases, 62.7%), with large B-cell lymphomas being more frequently transmural (68.8%) than mucosal (31.2%). Among all lymph nodes examined, 44 (43.1%; 95% CI: 33.9%-52.8%) exhibited neoplastic infiltration. Among cases of small cell lymphoma, 51 out of 72 (70.8%; 95% CI: 59.4%-80.1%) showed no nodal involvement. Clonality results correctly identified 19/30 (63.3%; 95% CI: 45.5%-78.2%) reactive lymph nodes. Concerns were raised regarding clonal identification in the remaining cases and potential misdiagnoses based on phenotypic characteristics.

Conclusion and Clinical Importance

The study underscores the potential drawbacks of relying solely on mesenteric lymph nodes for diagnosing intestinal lymphomas in cats, particularly small cell subtypes. It emphasizes the importance of full-thickness biopsies for assessing transmural infiltration and recommends caution when utilizing mesenteric lymph nodes for histologic, immunohistochemical and clonality evaluations in mucosal lymphomas. Despite limitations, this research highlights the need for comprehensive diagnostic strategies in cats with intestinal lymphoma.

背景:在怀疑患有肠淋巴瘤的猫中,区域淋巴结经常被取样;然而,它们的诊断价值尚未得到探讨:研究肠系膜淋巴结的组织学和免疫组化分析是否与猫肠淋巴瘤的诊断相关:方法:回顾性研究:回顾性研究。纳入标准要求对小肠进行全厚活检,并同时切除肠系膜淋巴结。对肠活检组织和相应淋巴结进行组织学和免疫分型分析。对诊断为反应性淋巴结的部分结节样本进行了克隆性检测:结果:包括小细胞和大细胞类型在内的跨膜T细胞淋巴瘤占主导地位(64例,62.7%),大B细胞淋巴瘤的跨膜发生率(68.8%)高于粘膜发生率(31.2%)。在所有受检淋巴结中,有 44 个(43.1%;95% CI:33.9%-52.8%)出现肿瘤浸润。在小细胞淋巴瘤病例中,72 例中有 51 例(70.8%;95% CI:59.4%-80.1%)无结节受累。克隆结果正确识别了 19/30 个(63.3%;95% CI:45.5%-78.2%)反应性淋巴结。结论和临床重要性:本研究强调了仅依靠肠系膜淋巴结诊断猫肠道淋巴瘤(尤其是小细胞亚型)的潜在缺点。它强调了全厚活检对评估跨壁浸润的重要性,并建议在使用肠系膜淋巴结对粘膜淋巴瘤进行组织学、免疫组化和克隆性评估时要谨慎。尽管存在局限性,但这项研究强调了对患有肠道淋巴瘤的猫采取综合诊断策略的必要性。
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引用次数: 0
Blood-brain barrier dysfunction and decreased transcription of tight junction proteins in epileptic dogs 癫痫犬的血脑屏障功能障碍和紧密连接蛋白转录减少。
IF 2.1 2区 农林科学 Q1 VETERINARY SCIENCES Pub Date : 2024-06-06 DOI: 10.1111/jvim.17099
Erez Hanael, Shelly Baruch, Rotem Kalev Altman, Orit Chai, Kira Rapoport, Dana Peery, Alon Friedman, Merav H. Shamir

Background

Epilepsy in dogs and humans is associated with blood-brain barrier (BBB) dysfunction (BBBD), which may involve dysfunction of tight junction (TJ) proteins, matrix metalloproteases, and astrocytes. Imaging techniques to assess BBB integrity, to identify potential treatment strategies, have not yet been evaluated in veterinary medicine.

Hypothesis

Some dogs with idiopathic epilepsy (IE) will exhibit BBBD. Identifying BBBD may improve antiepileptic treatment in the future.

Animals

Twenty-seven dogs with IE and 10 healthy controls.

Methods

Retrospective, prospective cohort study. Blood-brain barrier permeability (BBBP) scores were calculated for the whole brain and piriform lobe of all dogs by using dynamic contrast enhancement (DCE) magnetic resonance imaging (MRI) and subtraction enhancement analysis (SEA). Matrix metalloproteinase-9 (MMP9) activity in serum and cerebrospinal fluid (CSF) was measured and its expression in the piriform lobe was examined using immunofluorescent staining. Gene expression of TJ proteins and astrocytic transporters was analyzed in the piriform lobe.

Results

The DCE-MRI analysis of the piriform lobe identified higher BBBP score in the IE group when compared with controls (34.5% vs 26.5%; P = .02). Activity and expression of MMP9 were increased in the serum, CSF, and piriform lobe of IE dogs as compared with controls. Gene expression of Kir4.1 and claudin-5 in the piriform lobe of IE dogs was significantly lower than in control dogs.

Conclusions and Clinical Importance

Our findings demonstrate BBBD in dogs with IE and were supported by increased MMP9 activity and downregulation of astrocytic potassium channels and some TJ proteins. Blood brain barrier dysfunction may be a novel antiepileptic therapy target.

背景:狗和人类的癫痫与血脑屏障(BBB)功能障碍(BBBD)有关,可能涉及紧密连接(TJ)蛋白、基质金属蛋白酶和星形胶质细胞的功能障碍。评估 BBB 完整性以确定潜在治疗策略的成像技术尚未在兽医学中进行评估:假设:一些患有特发性癫痫(IE)的狗会表现出 BBBD。发现 BBBD 可能会改善未来的抗癫痫治疗:方法:回顾性、前瞻性队列研究:方法:回顾性、前瞻性队列研究。使用动态对比增强(DCE)磁共振成像(MRI)和减影增强分析(SEA)计算所有犬的全脑和梨状叶的血脑屏障通透性(BBBP)评分。测量了血清和脑脊液(CSF)中基质金属蛋白酶-9(MMP9)的活性,并使用免疫荧光染色法检测了其在梨状叶中的表达。分析了TJ蛋白和星形胶质细胞转运体在梨状叶中的基因表达:结果:对梨状叶的 DCE-MRI 分析发现,与对照组相比,IE 组的 BBBP 得分更高(34.5% vs 26.5%;P = .02)。与对照组相比,IE犬血清、脑脊液和梨状叶中MMP9的活性和表达均有所增加。IE 犬梨状叶中 Kir4.1 和 claudin-5 的基因表达明显低于对照组:我们的研究结果表明,IE 患犬的血脑屏障功能障碍得到了 MMP9 活性增加、星形胶质细胞钾通道和一些 TJ 蛋白下调的支持。血脑屏障功能障碍可能是一种新型抗癫痫治疗靶点。
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引用次数: 0
A dose titration protocol for once-daily insulin glargine 300 U/mL for the treatment of diabetes mellitus in dogs 用于治疗犬糖尿病的每日一次格列美脲胰岛素 300 U/mL 的剂量滴定方案。
IF 2.1 2区 农林科学 Q1 VETERINARY SCIENCES Pub Date : 2024-06-03 DOI: 10.1111/jvim.17106
Antonio Maria Tardo, Linda Mary Fleeman, Federico Fracassi, Alisa Saule Berg, Aria L. Guarino, Chen Gilor

Background

In purpose-bred dogs, insulin glargine 300 U/mL (IGla300) has long duration of action, peakless time-action profile, and low potency, making it suitable for use as a basal insulin.

Hypothesis

To evaluate IGla300 in client-owned diabetic dogs monitored using a flash glucose monitoring system (FGMS).

Animals

Ninety-five client-owned diabetic dogs, newly diagnosed or previously treated with other insulin formulations, with or without concurrent diseases.

Methods

Prospective multi-institutional study. Clinical signs and standardized assessment of FGMS data, using treatment and monitoring guidelines established a priori, guided dose adjustments and categorization into levels of glycemic control.

Results

The initial IGla300 dose was 0.5 U/Kg q24h for newly diagnosed dogs and (median dose [range]) 0.8 U/Kg (0.2-2.5) q24h for all dogs. Glycemic control was classified as good or excellent in 87/95 (92%) dogs. The IGla300 was administered q24h (1.9 U/kg [0.2-5.2]) and q12h (1.9 U/kg/day [0.6-5.0]) in 56/95 (59%) and 39/95 (41%) dogs, respectively. Meal-time bolus injections were added in 5 dogs (0.5 U/kg/injection [0.3-1.0]). Clinical hypoglycemia occurred in 6/95 (6%) dogs. Dogs without concurrent diseases were more likely to receive IGla300 q24h than dogs with concurrent diseases (72% vs 50%, respectively; P = .04).

Conclusions and Clinical Importance

Insulin glargine 300 U/mL can be considered a suitable therapeutic option for once-daily administration in diabetic dogs. Clinicians should be aware of the low potency and wide dose range of IGla300. In some dogs, twice-daily administration with or without meal-time bolus injections may be necessary to achieve glycemic control. Monitoring with FGMS is essential for dose titration of IGla300.

背景:在专门饲养的狗中,胰岛素格列卫 300 U/mL(IGla300)具有作用时间长、无峰时间-作用曲线和低效力等特点,因此适合用作基础胰岛素:实验动物:95 只客户饲养的糖尿病犬:动物:95 只客户饲养的糖尿病犬,新诊断的或以前用其他胰岛素制剂治疗过的,有或没有并发症:方法:前瞻性多机构研究。临床症状和 FGMS 数据的标准化评估,采用事先制定的治疗和监测指南,指导剂量调整和血糖控制水平分类:新诊断犬的 IGla300 初始剂量为 0.5 U/Kg q24h,所有犬的初始剂量(中位剂量 [范围])为 0.8 U/Kg (0.2-2.5) q24h。87/95(92%)只狗的血糖控制情况为良好或极佳。56/95(59%)和 39/95(41%)只狗分别在 24 小时(1.9 U/kg[0.2-5.2])和 12 小时(1.9 U/kg/天[0.6-5.0])注射 IGla300。5 只犬增加了餐时栓剂注射(0.5 U/kg/次[0.3-1.0])。临床低血糖发生率为 6/95(6%)。没有并发症的狗比有并发症的狗更有可能接受 IGla300 q24h(分别为 72% vs 50%; P = .04):结论和临床意义:格列美脲胰岛素 300 U/mL可被视为糖尿病犬每日给药一次的合适治疗选择。临床医生应注意 IGla300 的低效力和宽剂量范围。对于某些犬只,可能需要每天给药两次,同时进行或不进行餐时栓剂注射,以达到控制血糖的目的。使用 FGMS 进行监测对于 IGla300 的剂量滴定至关重要。
{"title":"A dose titration protocol for once-daily insulin glargine 300 U/mL for the treatment of diabetes mellitus in dogs","authors":"Antonio Maria Tardo,&nbsp;Linda Mary Fleeman,&nbsp;Federico Fracassi,&nbsp;Alisa Saule Berg,&nbsp;Aria L. Guarino,&nbsp;Chen Gilor","doi":"10.1111/jvim.17106","DOIUrl":"10.1111/jvim.17106","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>In purpose-bred dogs, insulin glargine 300 U/mL (IGla300) has long duration of action, peakless time-action profile, and low potency, making it suitable for use as a basal insulin.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Hypothesis</h3>\u0000 \u0000 <p>To evaluate IGla300 in client-owned diabetic dogs monitored using a flash glucose monitoring system (FGMS).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Animals</h3>\u0000 \u0000 <p>Ninety-five client-owned diabetic dogs, newly diagnosed or previously treated with other insulin formulations, with or without concurrent diseases.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Prospective multi-institutional study. Clinical signs and standardized assessment of FGMS data, using treatment and monitoring guidelines established a priori, guided dose adjustments and categorization into levels of glycemic control.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The initial IGla300 dose was 0.5 U/Kg q24h for newly diagnosed dogs and (median dose [range]) 0.8 U/Kg (0.2-2.5) q24h for all dogs. Glycemic control was classified as good or excellent in 87/95 (92%) dogs. The IGla300 was administered q24h (1.9 U/kg [0.2-5.2]) and q12h (1.9 U/kg/day [0.6-5.0]) in 56/95 (59%) and 39/95 (41%) dogs, respectively. Meal-time bolus injections were added in 5 dogs (0.5 U/kg/injection [0.3-1.0]). Clinical hypoglycemia occurred in 6/95 (6%) dogs. Dogs without concurrent diseases were more likely to receive IGla300 q24h than dogs with concurrent diseases (72% vs 50%, respectively; <i>P</i> = .04).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions and Clinical Importance</h3>\u0000 \u0000 <p>Insulin glargine 300 U/mL can be considered a suitable therapeutic option for once-daily administration in diabetic dogs. Clinicians should be aware of the low potency and wide dose range of IGla300. In some dogs, twice-daily administration with or without meal-time bolus injections may be necessary to achieve glycemic control. Monitoring with FGMS is essential for dose titration of IGla300.</p>\u0000 </section>\u0000 </div>","PeriodicalId":49958,"journal":{"name":"Journal of Veterinary Internal Medicine","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11256126/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141237942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Primary phenotypic features associated with caudal neck pathology in warmblood horses 与温血马尾颈病变有关的主要表型特征。
IF 2.1 2区 农林科学 Q1 VETERINARY SCIENCES Pub Date : 2024-06-03 DOI: 10.1111/jvim.17125
Sue Dyson, Shichen Zheng, Monica Aleman

Background

Detailed descriptions of clinical signs associated with radiological findings of the caudal cervical vertebral column are not available.

Objectives/Hypotheses

Describe the clinical features associated with neck pain or stiffness, neck-related thoracic limb lameness, proprioceptive ataxia consistent with a cervicothoracic spinal cord or nerve lesion, and their frequency of occurrence compared with control horses.

Animals

A total of 223 Warmblood horses.

Methods

Case-control study. Controls and cases were recruited prospectively. All horses underwent predetermined lameness and neurologic examinations. The frequency of occurrence of each clinical feature was compared between cases and controls and relative risk (RR) were calculated.

Results

Ninety-six cases and 127 controls were included. Forty-seven (49%) of the cases were classified as neurologic, 31 (32.3%) had thoracic limb lameness, and 18 (18.7%) had neck stiffness or pain or both. Focal caudal cervical muscle atrophy (46, 47.9%), hypoesthesia (38, 39.6%), patchy sweating (16, 16.7%), hyperesthesia (11, 11.5%), and pain upon firm pressure applied over the caudal cervical articular process joints and transverse processes (58, 60.4%) were only observed in cases (P < .001). Sideways flexion of the neck was restricted in a higher proportion of cases (47/96, 49%) compared with controls (40/127, 31.8%; P = .009, RR 1.5). Hopping-type thoracic limb lameness was only observed in cases, (30, 31.6%). Deterioration in lameness after diagnostic anesthesia occurred in 13/31 (41.9%) cases.

Conclusions and Clinical Importance

Systematic clinical evaluation using the methods described should enable clinical differentiation between horses with caudal cervical lesions and horses with other causes of gait abnormalities.

背景:目前还没有与颈椎尾部放射学检查结果相关的临床症状的详细描述:描述与颈部疼痛或僵硬、颈部相关胸肢跛行、本体感觉共济失调等颈胸脊髓或神经病变相关的临床特征,以及与对照组马匹相比的发生频率:方法:病例对照研究:方法:病例对照研究。对照组和病例均为前瞻性招募。所有马匹都接受了预定的跛足和神经系统检查。比较病例和对照组每种临床特征的发生频率,并计算相对风险(RR):结果:共纳入 96 例病例和 127 例对照。47例(49%)病例被归类为神经系统疾病,31例(32.3%)有胸肢跛行,18例(18.7%)有颈部僵硬或疼痛或两者兼有。仅在病例中观察到局部尾椎颈肌萎缩(46,47.9%)、感觉减退(38,39.6%)、斑片状出汗(16,16.7%)、感觉减退(11,11.5%),以及尾椎颈椎关节和横突上用力按压时疼痛(58,60.4%)(P 结论和临床重要性:使用所述方法进行系统的临床评估应能在临床上区分患有尾椎病变的马匹和因其他原因导致步态异常的马匹。
{"title":"Primary phenotypic features associated with caudal neck pathology in warmblood horses","authors":"Sue Dyson,&nbsp;Shichen Zheng,&nbsp;Monica Aleman","doi":"10.1111/jvim.17125","DOIUrl":"10.1111/jvim.17125","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Detailed descriptions of clinical signs associated with radiological findings of the caudal cervical vertebral column are not available.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives/Hypotheses</h3>\u0000 \u0000 <p>Describe the clinical features associated with neck pain or stiffness, neck-related thoracic limb lameness, proprioceptive ataxia consistent with a cervicothoracic spinal cord or nerve lesion, and their frequency of occurrence compared with control horses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Animals</h3>\u0000 \u0000 <p>A total of 223 Warmblood horses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Case-control study. Controls and cases were recruited prospectively. All horses underwent predetermined lameness and neurologic examinations. The frequency of occurrence of each clinical feature was compared between cases and controls and relative risk (RR) were calculated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Ninety-six cases and 127 controls were included. Forty-seven (49%) of the cases were classified as neurologic, 31 (32.3%) had thoracic limb lameness, and 18 (18.7%) had neck stiffness or pain or both. Focal caudal cervical muscle atrophy (46, 47.9%), hypoesthesia (38, 39.6%), patchy sweating (16, 16.7%), hyperesthesia (11, 11.5%), and pain upon firm pressure applied over the caudal cervical articular process joints and transverse processes (58, 60.4%) were only observed in cases (<i>P</i> &lt; .001). Sideways flexion of the neck was restricted in a higher proportion of cases (47/96, 49%) compared with controls (40/127, 31.8%; <i>P</i> = .009, RR 1.5). Hopping-type thoracic limb lameness was only observed in cases, (30, 31.6%). Deterioration in lameness after diagnostic anesthesia occurred in 13/31 (41.9%) cases.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions and Clinical Importance</h3>\u0000 \u0000 <p>Systematic clinical evaluation using the methods described should enable clinical differentiation between horses with caudal cervical lesions and horses with other causes of gait abnormalities.</p>\u0000 </section>\u0000 </div>","PeriodicalId":49958,"journal":{"name":"Journal of Veterinary Internal Medicine","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11256129/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141199086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Clinical methemoglobinemia secondary to administration of hydroxyurea at therapeutic doses in a dog 一只狗因服用治疗剂量的羟基脲而继发临床高铁血红蛋白症。
IF 2.1 2区 农林科学 Q1 VETERINARY SCIENCES Pub Date : 2024-06-01 DOI: 10.1111/jvim.17127
Manon Rigot, Shane W. Bateman, Xiu Ting Yiew

Methemoglobinemia secondary to administration of hydroxyurea is only reported in veterinary medicine as a result of accidental ingestion of high doses, and once at therapeutic dose in human medicine. A 2.5-year-old female spayed mixed breed dog was presented for acute signs of neurologic disease and diagnosed with severe erythrocytosis without an identified underlying cause, leading to suspicion of polycythemia vera. The dog was managed with phlebotomies, supportive care, and administration of hydroxyurea. Within 2 h of administration of hydroxyurea (37 mg/kg) administration, respiratory distress with cyanosis, and methemoglobinemia developed. Signs resolved within 24 h but recurred after a second administration of lower dosage of hydroxyurea (17 mg/kg) 20 days later. The dog remained asymptomatic except for mild cyanosis but was humanely euthanized for lack of relevant improvement of signs of neurologic disease. This case report documents the repeated occurrence of methemoglobinemia in a dog after administration of hydroxyurea at therapeutic doses.

在兽医领域,只有因意外摄入大剂量羟基脲而继发高铁血红蛋白血症的报道,而在人类医学领域,只有在治疗剂量下继发高铁血红蛋白血症的报道。一只 2.5 岁的雌性去势混血犬因出现急性神经系统疾病症状而就诊,被诊断为严重红细胞增多症,但未找到潜在病因,因此被怀疑患有多血症。该犬接受了抽血、支持性护理和羟基脲治疗。在注射羟基脲(37 毫克/千克)2 小时内,出现了呼吸困难、发绀和高铁血红蛋白血症。这些症状在 24 小时内缓解,但在 20 天后第二次服用较低剂量的羟基脲(17 毫克/千克)后再次出现。除了轻度紫绀外,该犬仍无症状,但由于神经系统疾病症状没有得到明显改善,该犬被人道安乐死。本病例报告记录了一只狗在服用治疗剂量的羟基脲后反复出现高铁血红蛋白血症的情况。
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引用次数: 0
In-hospital mortality in dogs with protein-losing enteropathy and associated risk factors 蛋白流失性肠病犬的院内死亡率及相关风险因素。
IF 2.1 2区 农林科学 Q1 VETERINARY SCIENCES Pub Date : 2024-05-31 DOI: 10.1111/jvim.17123
Connor Hawes, Aarti Kathrani

Background

Risk factors associated with negative outcomes in dogs with protein-losing enteropathy (PLE) are well documented. However, mortality before hospital discharge and associated risk factors are not well described.

Hypothesis/Objectives

Report the percentage of dogs with PLE that do not survive to hospital discharge and identify associated risk factors.

Animals

One-hundred and seven dogs presented to a referral hospital and diagnosed with PLE caused by inflammatory enteritis, intestinal lymphangiectasia or both.

Methods

Retrospective cross-sectional study assessing hospital records. Data on in-hospital mortality and cause were assessed, and presenting signs, treatments prescribed, neutrophil count, lymphocyte count, serum albumin, globulin, and C-reactive protein (CRP) concentrations, and histopathologic findings were compared between survivors and non-survivors.

Results

In-hospital mortality was 21.5% with the most common causes including financial limitations, failure to improve and aspiration pneumonia. Factors associated with mortality during hospitalization included longer duration of hospitalization (P = .04), longer duration of clinical signs (P = .02) and an increase in serum CRP concentration after 1–3 days of in-hospital treatment (P = .02). Higher mortality was identified in Pugs (odds ratio [OR], 4.93; 95% confidence interval [CI], 1.41–17.2; P = .01) and was a result of presumptive aspiration pneumonia in 5/6 of these dogs.

Conclusions and Clinical Importance

Protein-losing enteropathy in dogs has substantial mortality during hospitalization. Monitoring for improvement in CRP concentration after treatment during hospitalization may help predict survival to discharge. Pugs have increased in-hospital mortality because of aspiration pneumonia; measures to prevent, recognize, and promptly treat this complication may improve outcomes in this breed.

背景:与蛋白丢失性肠病(PLE)患犬不良预后相关的风险因素已被充分记录。然而,出院前的死亡率和相关风险因素却没有得到很好的描述:报告患 PLE 的狗在出院前无法存活的比例,并确定相关的风险因素:动物:177只到转诊医院就诊的狗,诊断为由炎症性肠炎、肠淋巴管扩张或两者引起的PLE:方法:对医院记录进行回顾性横断面研究。评估了院内死亡率和病因数据,并比较了存活者和非存活者的症状、治疗方法、中性粒细胞计数、淋巴细胞计数、血清白蛋白、球蛋白和 C 反应蛋白(CRP)浓度以及组织病理学结果:院内死亡率为21.5%,最常见的原因包括经济条件限制、病情未见好转和吸入性肺炎。与住院期间死亡率相关的因素包括住院时间较长(P = .04)、临床症状持续时间较长(P = .02)以及住院治疗 1-3 天后血清 CRP 浓度升高(P = .02)。普格犬的死亡率较高(几率比 [OR],4.93;95% 置信区间 [CI],1.41-17.2;P = .01),其中 5/6 的普格犬死于推测性吸入性肺炎:结论和临床意义:犬蛋白丢失性肠病在住院期间死亡率很高。住院期间监测治疗后 CRP 浓度的改善情况有助于预测出院后的存活率。由于吸入性肺炎,巴哥犬的院内死亡率增加;预防、识别和及时治疗这种并发症的措施可能会改善该犬种的预后。
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引用次数: 0
期刊
Journal of Veterinary Internal Medicine
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