Selected biomarkers of oxidative stress in healthy Beagle dogs: A preliminary study.

Introduction: While oxidative stress has been studied in pathologic conditions in dogs, data in presumably healthy dogs and standardized protocols are lacking. This work purposed to bridge the gap by presenting provisional physiological ranges for oxidative stress biomarkers in a group of Beagle dogs. Methods: Based on our long-standing clinical expertise in the field of oxidative stress, nine plasma biomarkers of oxidative stress were evaluated for their concentrations (mean ± SD) in 14 healthy adult Beagle dogs. Results: Selected biomarkers were: vitamins C (7.90 ± 1.36 µg/mL) and E (34.1 ± 6.63 µg/mL), zinc (0.80 ± 0.17 mg/L), copper (0.54 ± 0.048 mg/L), selenium (256 ± 25.7 µg/L), total and oxidized glutathione (822 ± 108 µM and 3.56 ± 1.76 µM), myeloperoxidase (67.4 ± 56.2 ng/mL), and isoprostanes (340 ± 95.3 ng/mL). Glutathione peroxidase activity and superoxide anion production in whole blood were also measured. Glutathione peroxidase activity was 473 ± 34.0 IU/g of hemoglobin and superoxide anion production in whole blood was 18,930 ± 12,742 counts per 30 min. Reduced glutathione/oxidized glutathione and copper/zinc ratios were, respectively, 280 ± 139 and 0.70 ± 0.15. Sex-related differences were recorded for zinc (p = 0.0081), copper/zinc ratio (p = 0.0036) and plasma isoprostanes (p = 0.0045). Conclusion: Provisional physiological norms covering 95% of our group were proposed for each biomarker and should be of interest for future studies of canine oxidative stress.

Hodgkin lymphoma and female fertility: a multicenter study in women treated with doxorubicin, bleomycin, vinblastine, and dacarbazine.

Preservation of fertility has become a growing concern in young females with Hodgkin lymphoma (HL). However, the rate of pregnancy after the current most frequently prescribed ABVD (doxorubicin [Adriamycin], bleomycin, vinblastine, and darcarbazine) chemotherapy for HL has rarely been studied. In this study, we aim to determine the impact of ABVD on the fertility of women treated for HL. We conducted a noninterventional, multicenter study of female patients of childbearing age who were treated for HL. Two healthy apparied women nonexposed to chemotherapy (our controls) were assigned for each patient. Fertility was assessed by the number of pregnancies and births after HL treatment. Sixty-seven patients were included. The median age at diagnosis was 24.4 years (range, 16-43). HL was a localized disease for 68.7%. Of all the patients, 53.7% started at least 1 pregnancy after treatment vs 54.5% of the controls (P = .92). Of all the patients who desired children, 81% had at least 1 pregnancy. Patients treated with ABVD did not have a longer median time to pregnancy (4.8 years in the group of patients and 6.8 years for controls). Across patients, there were 58 pregnancies and 48 births (ratio, 1:2) and 136 pregnancies and 104 births (ratio, 1:3) for the control cohort. No increase in obstetric or neonatal complications has been reported in HL in our study. The number of pregnancies, births, and the time to start a pregnancy in young women treated with ABVD for HL is not different from that of controls. Therefore, females with HL treated with ABVD should be reassured regarding fertility.

Imaging Findings in Dogs and Cats With Presumptive Sclerosing Encapsulating Peritonitis.

This retrospective case series describes imaging findings in seven dogs and two cats with a presumptive diagnosis of sclerosing encapsulating peritonitis (SEP) between 2014 and 2021. Peritoneal effusion was present in all animal patients. Sonographically, echogenic fluid with or without echogenic intraperitoneal septations, gathered or corrugated bowel loops, and abdominal lymphadenomegaly were suggesting an inflammatory process and the presence of adhesions. Gathering of the bowel with abdominal distension and/or signs of intestinal obstruction were major findings on radiographs. Abdominal fat stranding was an additional finding in animals undergoing a CT examination. Previous surgery, pregnancy, and the presence of a perforating foreign body were potential predisposing causes in 4/9 animals. Peritonitis was septic in 4/9 animals. As SEP is a rare condition but life threatening, this detailed description of imaging findings in a short case series can be useful for a presumptive diagnosis and surgical planning.

Urodynamic and morphometric characteristics of the lower urogenital tract of male Beagle littermates from four months to two years of age.

OBJECTIVE: To describe functional and anatomic changes of the lower urogenital tract of healthy male dogs during the sexually immature period and up to 2 years of age by urodynamic and morphometric assessment. ANIMALS: 6 sexually intact male Beagle littermates. PROCEDURES: Dogs underwent electromyography-coupled urodynamic tests, CT-assisted retrograde urethrography, prostatic washes, and blood sampling monthly from 4 through 12 months of age and then at 3-month intervals. Urodynamic and morphometric variables and serum canine prostate-specific esterase concentrations were analyzed by statistical methods. RESULTS: Integrated pressure of the urethra was significantly increased beginning at 8 months of age, compared with earlier time points. Urethral pressure peak amplitudes varied among anatomic regions. During bladder filling, few electromyographic signals were concurrent with urethral pressure peaks; these were most commonly detected in the penile portion of the urethra. Urethral length and prostate gland volume were significantly greater from 7 to 24 months of age than at younger ages. Urethral length was approximately 26 to 27 cm after 9 months, and prostate gland volume was approximately 11 to 12 cm3 after 11 months of age. Serum canine prostate-specific esterase concentrations correlated with prostate gland volume. Urinary bladder threshold volume was significantly increased at 6 months of age, compared with that at 4 months, with a maximum of 197.7 mL at 24 months. CONCLUSIONS AND CLINICAL RELEVANCE: Urethral resistance was acquired at approximately 8 months of age, when growth of the lower urinary tract was incomplete. Electromyographic and integrated pressure measurement results and the distribution and amplitude of urethral pressure peaks highlighted the potential role of the prostate gland and possibly the bulbocavernosus muscles in control of continence.

Gallbladder and Liver Lobe Torsion in a Young Cat Presented with Hemoabdomen.

An 11 mo old domestic shorthair presented with acute lethargy. The cat was hypothermic and bradycardic and had pale pink mucous membranes, poor pulses, and a distended abdomen. Point-of-care ultrasound identified significant abdominal effusion, which was diagnosed to be a hemoabdomen. Bloodwork revealed hyperlactatemia, regenerative anemia, neutrophilia, hypoproteinemia, hypoalbuminemia, and increased alanine aminotransferase. The cat received an allotransfusion and a subsequent canine xenotransfusion and received further supportive therapy. After stabilization, abdominal ultrasonography diagnosed a gallbladder and liver lobe torsion with hemoabdomen. Exploratory laparotomy confirmed the torsion of the right medial and quadrate hepatic lobes together with the gallbladder. Cholecystectomy and lobectomy of the affected lobes were performed using a surgical stapler. The cat was discharged after 4 days. Histopathology confirmed hemorrhagic infarction of the liver lobes and gallbladder, consistent with the described torsion, and the hepatic pseudocyst. It also demonstrated a mucocele in the gallbladder. One month postoperatively, the cat had totally recovered. Hepatic lobe torsion without neoplasia is a rare disease in cats, with variable clinical signs. Gallbladder torsion is a hitherto unreported condition in cats. This is the first report of gallbladder and liver lobe torsion with secondary hemoabdomen in a cat, successfully treated by one-stage surgery.

Analysis of a cohort of 279 patients with hairy-cell leukemia (HCL): 10 years of follow-up.

In total, 279 patients with hairy-cell leukemia (HCL) were analyzed, with a median follow-up of 10 years. Data were collected up to June 2018. We analyzed responses to treatment, relapses, survival, and the occurrence of second malignancies during follow-up. The median age was 59 years. In total, 208 patients (75%) were treated with purine analogs (PNAs), either cladribine (159) or pentosatin (49), as the first-line therapy. After a median follow-up of 127 months, the median overall survival was 27 years, and the median relapse-free survival (RFS) was 11 years. The cumulative 10-year relapse incidence was 39%. In patients receiving second-line therapy, the median RFS was 7 years. For the second-line therapy, using the same or another PNA was equivalent. We identified 68 second malignancies in 59 patients: 49 solid cancers and 19 hematological malignancies. The 10-year cumulative incidences of cancers, solid tumors, and hematological malignancies were 15%, 11%, and 5.0%, respectively, and the standardized incidence ratios were 2.22, 1.81, and 6.67, respectively. In multivariate analysis, PNA was not a risk factor for second malignancies. HCL patients have a good long-term prognosis. PNAs are the first-line treatment. HCL patients require long-term follow-up because of their relatively increased risk of second malignancies.

Long-term outcome of the transobturator vaginal tape inside out for the treatment of urethral sphincter mechanism incompetence in female dogs.

OBJECTIVE: To evaluate the long-term efficacy of the transobturator vaginal tape inside out (TVT-O) in female dogs with urethral sphincter mechanism incompetence (USMI). STUDY DESIGN: Retrospective study. ANIMALS: Incontinent spayed female dogs (n = 12). METHODS: TVT-O tape was inserted in 12 incontinent bitches diagnosed with USMI. Follow-up information was evaluated by a telephone questionnaire, and a continence score was attributed. RESULTS: One year after surgery, 7 of 12 (58%) dogs were completely continent. Two dogs were removed from the long-term analysis (1 dead and 1 lost). At a median follow-up time of 85 months (range, 28-95), 4 of 10 dogs were completely continent without medical treatment. Incontinence recurred in 6 dogs at a median time of 2 months after surgery (range 1-20). Among these 6 dogs, 4 regained continence, and 2 had sporadic episodes of incontinence with additional medical treatment. No postoperative complications were encountered. CONCLUSION: TVT-O alone was successful in maintaining long-term continence in 40% of the dogs. Additional postoperative medical treatment was effective in restoring continence in another 40% of the dogs. CLINICAL SIGNIFICANCE: TVT-O provides an alternative treatment of USMI in female dogs that is safe and less invasive than standard surgical techniques.

Surgical management of ectopic ureters in dogs: Clinical outcome and prognostic factors for long-term continence.

OBJECTIVE: To determine outcomes after surgical correction of ectopic ureters (EU) and identify prognostic factors for long-term continence. STUDY DESIGN: Retrospective study. ANIMALS: Forty-seven dogs (36 females and 11 males). METHODS: Medical records (1999-2016) of dogs with surgical correction of EU were reviewed. A continence score (1 = incontinent, 2 = sporadic incontinence, 3 = continent) was attributed preoperatively, at discharge, 1 month postoperatively, and at long-term evaluation. RESULTS: Twenty-eight dogs had unilateral and 19 dogs had bilateral EU (57 intramural and 9 extramural). Nineteen dogs had a pelvic bladder. Neoureterostomy with dissection (n = 50), ureteroneocystotomy (n = 9), or nephroureterectomy (n = 7) were performed. Thirty-three dogs were neutered: 32 before or during the surgery and 1 after surgery. Colposuspension was performed during surgical correction in 15 dogs. Adjuvant medical treatment improved postoperative continence scores. Median continence scores were greater at discharge (3), at 1 month postoperatively (3), and at long-term evaluation (3) than before surgery (1). At long-term evaluation (mean 46.1 months), a score of 1 was observed in 19%, a score of 2 in 7%, and a score of 3 in 74% of the dogs. CONCLUSION: Overall, good (score 2) to excellent (score 3) long-term outcome was achieved in 81% of dogs. Long-term continence was improved with medical treatment and neutering was not associated with an increased risk of recurrence of incontinence in this population of dogs.

Role of IRF4 in resistance to immunomodulatory (IMid) compounds® in Waldenström's macroglobulinemia.

BACKGROUND: Immunomodulatory drugs, IMid compounds, are active in Waldenström's macroglobulinemia (WM), although in a lesser extent than multiple myeloma, where it was initially developed. We hypothesized WM tumour cells might develop mechanisms of resistance, and sought to identify and describe these mechanisms. MATERIAL AND METHOD: MM and WM-derived cell lines, and Waldenström's CD19+ cells were treated using both lenalidomide and pomalidomide. Stable CRBN expressing cells were generated. RESULTS: WM-derived cells were resistant to IMid compounds. We demonstrated a modulation of the downstream targets of IRF4, despite low expression of cereblon, and hypothesized IRF4 was the cause for resistance to IMid compounds. We ruled out the role of various IRF4 regulatory mechanisms, and other pathways activating WM tumor cells, such as B cell activators. CONCLUSION: This study demonstrated that mechanisms of resistance to IMid compounds could be not related to cereblon. IRF4 was identified as the potential mechanism of resistance to lenalidomide and pomalidomide in WM. It potentially explains the lesser activity observed in the clinic in WM. Interestingly, some WM patients benefited strongly to lenalidomide and pomalidomide, and future studies will have to describe the indirect mechanisms of IMid compounds in WM, possibly related to an immune-mediated process.

Urodynamic investigation by telemetry in Beagle dogs: validation and effects of oral administration of current urological drugs: a pilot study.

BACKGROUND: Vesico-urethral function may be evaluated in humans and dogs by conventional urodynamic testing (cystometry and urethral pressure profilometry) or by electromyography. These techniques are performed under general anaesthesia in dogs. However, anaesthesia can depress bladder and urethral pressures and inhibit the micturition reflex. The primary objective of this pilot study was to evaluate the use of telemetry for urodynamic investigation in dogs. We also aimed to determine the applicability of telemetry to toxicologic studies by assessing the repeatability of telemetric recordings. RESULTS: Conventional diuresis cystometry was performed in six continent adult female Beagle dogs prior to surgical implantation of telemetric and electromyographic devices. In the first phase of the telemetric study, continuous recordings were performed over 8 days and nights. Abdominal, intravesical and detrusor threshold pressures (Pdet th), voided volume (Vv), urethral smooth muscle electrical activity and involuntary detrusor contractions (IDC) were measured during the bladder filling phase and during micturition episodes.Vv recorded during telemetry was significantly lower than bladder volume obtained by diuresis cystometry. Repeatability of telemetric measurements was greater for observations recorded at night. IDC frequency and Pdet th were both lower and Vv was higher at night compared to values recorded during daytime.In the second phase of the telemetric study, phenylpropanolamine, oestriol, bethanechol, oxybutynin or duloxetine were administered orally for 15 days. For each drug, continuous recordings were performed overnight for 12 hours on days 0, 1, 8 and 15. Electromyographic urethral activity was significantly increased 8 days after oestriol or duloxetine administration. No significant changes in bladder function were observed at any time point. CONCLUSIONS: In dogs, the high repeatability of nocturnal telemetric recordings indicates that this technique could provide more informative results for urologic research. Urethral smooth muscle electrical activity appears to be modified by administration of drugs with urethral tropism. In this pilot telemetric study, bladder function was not affected by oral administration of urological drugs at their recommended clinical dosages. Experimental studies, (pharmacokinetic and pharmacodynamic) and clinical studies are warranted to further define the effects of these drugs on vesico-urethral function in dogs.

Urodynamic and morphometric characteristics of the lower urogenital tracts of female Beagle littermates during the sexually immature period and first and second estrous cycles.

OBJECTIVE: To compare values of lower urogenital tract urodynamic and morphometric variables determined during the prepubertal (sexually immature) period and first and second estrous cycles in healthy female Beagle littermates to determine functional and anatomic changes of the lower urogenital tract during those periods. ANIMALS: 5 female Beagle littermates. PROCEDURES: Urethral pressure profilometry, diuresis cystometry, and vaginourethrography were performed when dogs were 3.5, 4.5, 5, 6, 7, 8, 8.5, and 9 months old and during proestrus; estrus; early, middle, and late diestrus; and early and late anestrus of the first and second estrous cycles. RESULTS: At the end of the prepubertal period, values of urodynamic and morphometric variables increased significantly, compared with values at earlier times. Maximum bladder capacity developed when dogs were 9 months old. In all dogs, the bladder was intermittently located in an intrapelvic position during the prepubertal period; the bladder was intra-abdominal from the time dogs were 9 months old until the end of the study. Urethral pressure decreased significantly during estrus and early diestrus of the first and second estrous cycles. Bladder capacity increased significantly during diestrus of both estrous cycles. Urethral and vaginal lengths were significantly longer during proestrus and estrus than they were during anestrus. CONCLUSIONS AND CLINICAL RELEVANCE: Values of lower urogenital tract urodynamic and morphometric variables were influenced by age and phases of the estrous cycle of immature and young adult Beagles in this study. Age of dog and phase of estrous cycle should be considered when interpreting urodynamic and vaginourethrography data.

Urodynamic and haemodynamic effects of a single oral administration of ephedrine or phenylpropanolamine in continent female dogs.

This study investigated the effects of a single oral administration of ephedrine (2 mg/kg) or phenylpropanolamine (PPA) (1.5 mg/kg) on the vesico-urethral and cardiovascular functions in continent female dogs. Urethral pressure profilometry (UPP), arterial blood pressures and heart rate were measured in five control dogs and after single-dose treatment with ephedrine or PPA at T(0), T(2h), T(4h), T(6h), T(12h), T(18h) and T(24h). UPPs were performed under propofol anaesthesia and other measurements were performed on awake dogs. A telemetric urodynamic investigation was performed on three additional dogs for 24 h after the administration of each drug. Urethral pressures increased over 4-6 h and urethral functional lengths increased 2-6h after administration of both drugs. During micturition, a decrease in detrusor pressure coupled with an increase in bladder volume was observed after ephedrine administration and there was also an increase in bladder volume after PPA had been given. With both drugs increased arterial blood pressures at 4-6 h were compensated by a decreased heart rate over 12 h. Urethral function was improved after both ephedrine and PPA, and bladder function also improved during micturition following ephedrine.

Clinical evaluation of a single daily dose of phenylpropanolamine in the treatment of urethral sphincter mechanism incompetence in the bitch.

The objective of this retrospective study was to determine the efficacy of a single daily oral dose of phenylpropanolamine (PPA) in the treatment of urethral sphincter mechanism incompetence (USMI) in bitches. Nine bitches diagnosed with USMI were treated with a single daily dose [1.5 mg/kg body weight (BW)] of PPA for at least 1 month. Urethral pressure profiles (UPP) were performed in 7 dogs before treatment and repeated in 4 of them after treatment. Treatment with PPA resulted in long-term continence in 8/9 bitches. One dog did not respond to PPA and was treated surgically later. Recheck UPPs showed a significant increase in maximal urethral closure pressure in the 4 bitches after treatment with PPA compared to before treatment. In conclusion, long-term continence can be achieved in bitches affected with USMI after administration of a single daily dose of PPA (1.5 mg/kg BW).

Acquired urinary incontinence in the bitch: update and perspectives from human medicine. Part 2: The urethral component, pathophysiology and medical treatment.

Various pathologies can affect the bladder and/or urethral contractility causing signs of urinary incontinence. In this second part of a three-part review, the pathophysiology of impaired urethral contractility (including urethral hyper- and hypotonicity) in the bitch and in women is discussed. Urethral sphincter mechanism incompetence (USMI) is the most common form of acquired urinary incontinence in bitches and is characterized by a decreased urethral tone. The pathophysiology and current recommended medical treatment options for USMI and cases of modified urethral tonicity due to a neurological disorder or functional outlet obstruction are discussed. Treatment options in human medicine in cases of impaired urethral contractility are described.

Acquired urinary incontinence in the bitch: update and perspectives from human medicine. Part 1: The bladder component, pathophysiology and medical treatment.

Micturition disorders are commonly encountered in veterinary medicine and can be divided into two main categories, namely, urinary incontinence and urinary retention. Various pathologies can affect the bladder and/or urethral contractility causing symptoms of urinary incontinence. In this first part of a three-part review, the different causes of urinary incontinence, the physiology of the lower urinary tract and impaired bladder contractility are reviewed. Since urinary incontinence due to overactive bladder syndrome or detrusor atony is described in both dogs and humans, the different therapeutic targets in the treatment of impaired bladder contractility in human and veterinary medicine are discussed.

Combined pharmacokinetic and urodynamic study of the effects of oral administration of phenylpropanolamine in female Beagle dogs.

This study investigated the differences in pharmacokinetic, urodynamic and haemodynamic parameters after administration of two dosages of phenylpropanolamine (PPA) in female Beagle dogs. Blood was collected and urethral pressure profiles were performed over 24 h periods following single or three times daily (T(0),T(6h),T(12h)) administration of PPA. The maximal concentration (C(max)) was reached 2 h after PPA administration (T(max)) and the half-life (T((1/2))) was 4 h. Three times daily administration induced an increase in C(max) due to bioaccumulation. A significant increase in urethral resistance, compared to the control group, was observed at T(max) after 1 week of once daily administrations, but not when PPA was administered every 6 h during the day, despite higher plasma concentrations following more frequent dosing. An increase in mean arterial pressure was compensated by a decreased heart rate. Clinical efficacy with the temporary increase in urethral resistance following single daily administration of PPA in dogs suffering from urethral sphincter mechanism incompetence (USMI) needs to be further investigated in a randomised clinical trial.

Acquired urinary incontinence in the bitch: update and perspectives from human medicine. Part 3: The urethral component and surgical treatment.

Urethral sphincter mechanism incompetence (USMI) is the most common cause of urinary incontinence in dogs. Surgery may be recommended if the animal does not respond to medical treatment or becomes refractory. In this third part of a three-part review, surgical options for the treatment of USMI are described. Colposuspension is the most frequently described procedure and offers a fair prognosis, with about 50% of the dogs being continent after surgery and most of the reminder being improved or more responsive to medical treatment. Urethropexy offers a similar success rate, but with a higher rate of complications. Endoscopic injection of collagen is an attractive technique due to its minimally invasive nature and low risk of adverse effects. Initial results may however deteriorate with time. Other procedures have been reported, but involve a low number of cases and have resulted in variable success rates. In women, stress urinary incontinence is mainly treated by minimally invasive procedures involving vaginal placement of sub-urethral slings.

Risks assessment of water pollution by pesticides at local scale (PESTEAUX project): study of polluting pressure.

Pollution of water resources (surface waters and ground waters) by pesticide uses is one of the key point of the European policy with the implementation of the Water Frame Work Directive (2000/60/EC) and the thematic Strategy on the Sustainable use of pesticides. According to this legislation, the Member States must initiate measures to limit environmental and toxicological effects caused by pesticide uses. The Agricultural Research Centre of Wallonia (CRA-W) emphasized the need of a tool for spatial risk analysis and develOPs it within the framework of PESTEAUX project. The originality of the approach proposed by the CRA-W is to generate maps to identify the risk of pollution at locale scale (agricultural parcel). The risk will be assessed according to the study of different factors, grouped under 3 data's layers: polluting pressure, vulnerability of the physical environment (soil) and meteorological data. This approach is directly based on the risk's definition which takes into account the polluting pressure, linked to the human activities, and the vulnerability of the soil, defined by factors of physical environment which characterize the water flow in the parcel. Moreover, meteorological data influence the intensity and likelihood flow of water, and indirectly pesticide by leaching or runoff. The PESTEAUX's approach to study the pollution is based on the model "source-vector-target". The source is the polluting pressure, in other words, the pesticides which could reach the targets. The main vector is the water which vehicles the pesticide on and trough the soil until the target which are the surface waters or ground waters. In this paper we introduce the factors contributing to the polluting pressure. These factors are linking to the human activities and more precisely, to the pesticide uses. The factors considered have an influence on pesticide's transport by water (in its solid state or in dissolved state by leaching, run-off, or erosion) but also on a set of process controlling pesticide behavior in the environment such as degradation, sorption,....