Persistent urinary incontinence in female Golden Retrievers following laser ablation of intramural ectopic ureters may be associated with the presence of historical urinary tract infection.

OBJECTIVE: To identify predictive factors for postoperative continence in female Golden Retrievers following cystoscopic-guided laser ablation of intramural ectopic ureters (CLA-EU). ANIMALS: 41 client-owned female entire Golden Retrievers with uni- or bilateral intramural ectopic ureter(s) were retrospectively enrolled. METHODS: Patients were diagnosed with ectopic ureters with a combination of ultrasonography and cystoscopy. CLA-EU was performed for all dogs so that each ureteral opening was considered to be in an appropriate position by a single operator. All dogs had short-term follow-up 4 weeks and long-term follow up > 10 weeks after the procedure via telephone, which included urinary continence scoring. Clinical factors and ultrasonographic and cystoscopic findings from initial presentation were evaluated to identify predictive factors for postoperative continence. RESULTS: Short-term urinary continence was achieved in 46.3% of dogs with no additional medical therapies. Presence of historical urinary tract infections prior to CLA-EU (OR, 0.130; 95% CI, 0.020 to 0.621; P = .018) was negatively correlated and ureteral dilatation (OR, 34.260; 95% CI, 1.813 to 2,143; P = .043) was positively correlated with likelihood of urinary continence. Long-term urinary continence was achieved in 63.4% of dogs, and presence of historical urinary tract infections was negatively prognostic (OR, 0.173; 95% CI, 0.023 to 0.856; P = .048). CLINICAL RELEVANCE: Female Golden Retrievers undergoing CLA-EU have similar outcomes to those reported for other mixed-breed cohorts with > 30% of dogs failing to regain urinary continence. Historical urinary tract infections were significantly associated with both short- and long-term urinary continence in our population.

Surgical management of a laryngeal rhabdomyosarcoma in a cat.

Case summary: An 11-year-old male castrated British Shorthair was referred for investigations into an upper respiratory tract mass. A partial laryngectomy was performed to excise the mass. Marginal resection of the mass involved excision of parts of the thyroid cartilage and left arytenoid cartilage. A tracheostomy tube was maintained for 48 h postoperatively. The cat recovered without complication and was discharged at 72 h postoperatively. Histopathology of the mass was deemed most consistent with a rhabdomyosarcoma (RMS). Relevance and novel information: Telephone follow-up 12 months postoperatively confirmed resolution of the clinical signs. To our knowledge, this is the first report of a laryngeal RMS in a cat. RMS should be considered a differential diagnosis for a laryngeal mass in a cat. This case demonstrates that resection via a partial laryngectomy may be a viable therapeutic option.

Serum cortisol assay performance following the 1 mg overnight dexamethasone suppression test.

BACKGROUND: The 1 mg overnight dexamethasone suppression test (ONDST) is recommended for the differential diagnosis of Cushing's syndrome and the investigation of adrenal incidentalomas. Despite documented variation in serum cortisol immunoassay performance, little has been published regarding its effect on the ONDST. AIMS: Assess the performance of three immunoassay platforms (Roche Elecsys II, Abbott Alinity & Siemens Centaur) when compared to a liquid chromatography tandem mass spectrometry (LC-MS/MS) method. METHODS: Samples (n = 77) sent to the laboratory as part of an ONDST were retrieved prior to disposal, anonymized, and analysed on all platforms. Samples with factors impacting immunoassay analysis quality were excluded. Results were statistically compared to an LC-MS/MS method that previously demonstrated excellent comparability to a candidate reference method. RESULTS: The Roche gen II showed a mean bias of -2.4 nmol/L and a Passing-Bablok fit of y = -0.9 + 0.97x. This was not affected by sex. The Abbott showed a mean bias -18.8 nmol/L, and a fit of y = -11.3 + 0.88x. This bias was -20.7 nmol/L in females versus -17.2 nmol/L in males. The Siemens had a mean bias of 2.3 nmol/L and a fit of y = 1.4 + 1.07x. This bias was 5.7 nmol/L in males versus -1.0 nmol/L in females. CONCLUSIONS: Clinicians should be aware of the method-dependent variation that exists within serum cortisol analysis during the ONDSTs. Roche and Siemens aligned more closely with LC-MS/MS while the Abbot may cause a reduction in ONDST sensitivity. This data supports assay-specific cut-offs for the ONDST.

Ultrasonography as a sensitive and specific diagnostic modality for the detection of ectopic ureters in urinary incontinent dogs.

Ultrasonography is a widely available diagnostic modality for the identification of dogs with suspected ureteral ectopia; however published studies detailing its sensitivity and specificity are currently lacking. The aim of this retrospective, descriptive, diagnostic accuracy study was to evaluate the sensitivity and specificity of ultrasonography for the diagnosis of ureteral ectopia in incontinent dogs presenting to a referral institution, using cystoscopy as the gold standard. Medical records of urinary incontinent dogs presenting to a single institution (n = 38) were retrospectively reviewed for the presence of ureteric insertion abnormalities and concurrent urinary tract abnormalities. Ultrasonographic findings were compared with those from cystoscopic examination to determine diagnostic accuracy. The relationship between the presence of concurrent urinary tract abnormalities and ureteral ectopia was assessed using an independent samples t-test and Mann-Whitney test. Statistical significance was set at P ≤ 0.05. Ultrasonography had a sensitivity of 93.5%, specificity of 100%, and diagnostic accuracy of 95% when identifying dogs with ureteral ectopia. When classifying individual ureters as ectopic or non-ectopic, sensitivity was 87.8% and specificity was 86.7%. Dogs with ureteral ectopia had significantly more concurrent urinary tract abnormalities on ultrasound than unaffected dogs (P = 0.004). Ectopic ureters were associated with significantly more concurrent ipsilateral upper urinary tract ultrasonographic abnormalities than unaffected ureters (P < 0.001). Ultrasonography performed by an experienced ultrasonographer is a sensitive and specific screening tool for canine ureteral ectopia, which eliminates the need for heavy sedation, general anesthesia, and advanced imaging, although it should not be relied upon as the sole diagnostic modality for the assessment of individual ureters.

Urinary incontinence secondary to a suspected congenital urethral deformity in a kitten.

CASE SUMMARY: A 5-month-old entire male domestic shorthair kitten was referred for investigation of a month-long history of urinary incontinence. Clinical examination, baseline blood work and imaging (plain radiography and ultrasonography) were unremarkable. Urinalysis documented a urinary tract infection and a retrograde urethrocystogram revealed an outpouching of the pelvic urethra. Surgical exploration revealed the absence of the dorsal portion of the urethral wall in this section of pelvic urethra, replaced by an epithelial lined expanded 'pouch'. The ventral aspect of the urethra appeared grossly normal. A modified perineal urethrostomy was performed to create an anastomosis of the urethral pouch to the skin of the perineum alongside conventional castration. The kitten made a full recovery and the incontinence resolved within 48 h. A congenital urethral diverticulum and secondary urinary tract infection were deemed the most likely aetiology in this case. RELEVANCE AND NOVEL INFORMATION: Urethral diverticuli are a rare condition in veterinary medicine. To our knowledge, it has only been reported in two dogs and presumptively in one cat, all of which made a complete recovery after surgical intervention. The present case reports an unusual urethral deformity as a potential differential diagnosis for lower urinary tract signs in a young cat.

Development of a total serum testosterone, androstenedione, 17-hydroxyprogesterone, 11ß-hydroxyandrostenedione and 11-ketotestosterone LC-MS/MS assay and its application to evaluate pre-analytical sample stability.

Background Classically, serum testosterone (T) and androstenedione (A4) have been the mainstay for the biochemical assessment of hyperandrogenism. However, recent evidence suggests 11ß-hydroxyandrostenedione (11OHA4) and 11-ketotestosterone (11KT) may also be important. Here, we describe the development of a liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay for quantitation of total serum T, A4, 17-hydroxyprogesterone (17OHP), 11OHA4 and 11KT. In addition, we applied the method to assess pre-analytical stability. Methods An isotopically labelled internal standard was added to samples prior to supported liquid extraction (SLE). Extracts were analysed using LC-MS/MS to detect T/A4/17OHP/11OHA4 and 11KT along with their corresponding internal standards. Samples (n = 7) were collected from healthy volunteers (n = 14) and left incubated at 20 °C for up to 72 h. Tubes were retrieved at select time points, centrifuged, separated and frozen prior to analysis. Results The total run time was 4 min. For all analytes, intra- and inter-assay imprecision did not exceed 7.9% and 5.3%, respectively; matrix effects were negligible and mean recoveries ranged from 95.3 to 111.6%. The limits of quantitation (LOQs) were 0.25 nmol/L for T, A4 and 11OHA4, 0.50 nmol/L for 17OHP, and 0.24 nmol/L for 11KT. No significant change was observed in pre-centrifugation A4 or female T concentrations over 72 h. Significant increases (p < 0.01) in concentrations of 11KT, 17OHP, 11OHA4 and male T were observed after 2, 8, 12 and 24 h, respectively. Conclusions We developed a robust LC-MS/MS assay for the quantitation of total serum T/A4/17OHP/11OHA4 and 11KT. Applying the method to determine pre-analytical stability suggests samples requiring 11KT need separating from the cells within 2 h.

Evaluation of a pre-tied ligature loop for canine total lung lobectomy.

OBJECTIVE: To determine the ability of a pre-tied ligature loop (PLL) to create a seal against physiological airway pressures after total lung lobectomy and report outcomes in dogs requiring lung lobectomy. STUDY DESIGN: Ex vivo experimental randomized study and clinical case study. SAMPLE POPULATION: Thirty cadaveric canine lung lobes and 5 client-owned dogs. METHODS: Thirty canine lung lobes from dogs weighing 22.5-35 kg were randomized to lobectomy with stapler, PLL, or suture ligation. After lobectomy, each bronchial stump was submerged in water, and the mainstem airway pressure was increased to 80 mm Hg. Leakage was compared between techniques. The PLL was subsequently used in 5 dogs (17-25 kg) with neoplastic disease requiring total lung lobectomy. RESULTS: Two stapled and 4 sutured bronchial stumps leaked at supraphysiological pressures >15 mm Hg. One stapled bronchial stump failed at a physiological airway pressure (5 mm Hg). None of the PLL lobectomies leaked. The incidence of bronchial stump failures did not differ among techniques (P = .15). Lung lobectomy was performed successfully with the PLL in 5 clinical cases with no intraoperative or postoperative complications; median follow-up time was 6 months. CONCLUSION: Bronchial ligation with the PLL reliably resisted physiological airway pressures and performed comparably to current standard techniques in cadavers. The PLL provided an adequate air and vascular seal in 5 clinical cases undergoing total lung lobectomy. CLINICAL RELEVANCE: Pre-tied ligature loops provide an alternative method for total lung lobectomy in dogs.

Oestradiol measurement during fulvestrant treatment for breast cancer.

Biochemical evaluation of menopausal status is used to inform treatment decisions, including clinical trial eligibility in women with oestrogen receptor positive breast cancer. However, fulvestrant may interfere with oestradiol immunoassays and confound accurate assessment in this context. We conducted a service evaluation of two immunoassays and an LC-MS/MS assay to determine the extent of the interference. Serum oestradiol levels were analysed by two immunoassays (Siemens Centaur XP and Abbott Architect) and liquid chromatography-tandem mass spectrometry (LC/MS/MS). Immunoassay gave higher serum oestradiol results than LC-MS/MS at low concentrations, with improved analytical sensitivity demonstrated by LC-MS/MS. Cross-reactivity of fulvestrant was observed for each immunoassay. We have shown that two commonly used immunoassays do not demonstrate the required sensitivity or specificity for the measurement of oestradiol in a breast cancer population. For patients receiving fulvestrant, spurious results may be generated that could impact treatment decisions. LC-MS/MS is recommended in this setting.

Peas, please! Food familiarization through picture books helps parents introduce vegetables into preschoolers' diets.

Repeated taste exposure is an established means of increasing children's liking and intake of fruit and vegetables. However, parents find it difficult to offer children disliked foods repeatedly, often giving up after a few attempts. Studies show that familiarizing children to fruit and vegetables through picture books can increase their interest in tasting targeted foods. This study explored whether looking at picture books before providing foods to taste improved the outcomes of a home-delivered taste exposure regime. Parents of 127 toddlers (aged 21-24 months) identified two 'target' foods they wanted their child to eat (1 fruit, 1 vegetable). Families were randomly assigned to one of three groups. Parents and children in two experimental groups looked at books about either the target fruit or vegetable every day for two weeks; the control group did not receive a book. Parents in all three groups were then asked to offer their child both target foods every day during a 2-week taste-exposure phase. Parental ratings of children's liking and consumption of the foods were collected at baseline, immediately following taste-exposure (post-intervention), and 3 months later (follow-up). In all groups, liking of both foods increased following taste exposure and remained above baseline at follow-up (all ps < .001). In addition, compared to the control group who experienced only taste exposure, looking at vegetable books enhanced children's liking of their target vegetable post-intervention (p < .001) and at follow-up (p < .05), and increased consumption of the vegetable at follow-up (p < .01). Exposure to vegetable books was also associated with smaller increases in neophobia and food fussiness over the period of the study compared to controls (ps < .01), suggesting that picture books may have positive, long-term impacts on children's attitudes towards new foods.

Development of a rapid liquid chromatography tandem mass spectrometry method for the quantitation of serum dexamethasone and its clinical verification.

Background Measurement of serum dexamethasone during the overnight dexamethasone-suppression test has been recommended to reduce false-positive results when investigating Cushing's syndrome or increasingly commonly found adrenal incidentalomas. Despite this, there remains a paucity of well-validated dexamethasone methods currently available. Here, we describe the development of a rapid and sensitive liquid chromatography tandem mass spectrometry serum dexamethasone assay and verify its utility in a cohort of postmenopausal females. Method Isotopically labelled internal standard was added to samples prior to supported liquid extraction. Extracts were analysed using liquid chromatography tandem mass spectrometry in the positive electrospray ionization mode. Multiple reaction monitoring was used to detect dexamethasone and its corresponding internal standard transitions. Normal healthy postmenopausal women ( n = 95) were recruited and underwent an overnight dexamethasone suppression test, with serum dexamethasone and cortisol measurements at 09:00 after administration of oral dexamethasone 1 mg at 23:00 the night before. Results Mean intra- and inter-assay imprecision were 4.1% and 2.9%, respectively, for dexamethasone concentrations of 1.5, 6.0 and 12.0 nmol/L. Matrix effects were found to be negligible at 106-109% with recovery ranging from 96 to 100%. The limit of quantitation was 0.25 nmol/L, and structural analogue analysis proved the method to be robust against interferences. Applying a serum dexamethasone cut-off of >3.3 nmol/L was associated with a serum cortisol ≤50 nmol/L in 84/95 individuals. Conclusion We have developed a sensitive and robust liquid chromatography tandem mass spectrometry method for the quantitation of serum dexamethasone. The method can be used to identify false-positive results during the overnight dexamethasone suppression test or for pharmacokinetic studies.

Constitutively active follicle-stimulating hormone receptor enables androgen-independent spermatogenesis.

Spermatogenesis is regulated by the 2 pituitary gonadotropins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH). This process is considered impossible without the absolute requirement of LH-stimulated testicular testosterone (T) production. The role of FSH remains unclear because men and mice with inactivating FSH receptor (FSHR) mutations are fertile. We revisited the role of FSH in spermatogenesis using transgenic mice expressing a constitutively strongly active FSHR mutant in a LH receptor-null (LHR-null) background. The mutant FSHR reversed the azoospermia and partially restored fertility of Lhr-/- mice. The finding was initially ascribed to the residual Leydig cell T production. However, when T action was completely blocked with the potent antiandrogen flutamide, spermatogenesis persisted. Hence, completely T-independent spermatogenesis is possible through strong FSHR activation, and the dogma of T being a sine qua non for spermatogenesis may need modification. The mechanism for the finding appeared to be that FSHR activation maintained the expression of Sertoli cell genes considered androgen dependent. The translational message of our findings is the possibility of developing a new strategy of high-dose FSH treatment for spermatogenic failure. Our findings also provide an explanation of molecular pathogenesis for Pasqualini syndrome (fertile eunuchs; LH/T deficiency with persistent spermatogenesis) and explain how the hormonal regulation of spermatogenesis has shifted from FSH to T dominance during evolution.

Intramuscular mast cell tumors in 7 dogs.

Mast cell tumors (MCTs) are commonly encountered in dogs and have been reported in cutaneous, conjunctival, oral mucosal, and gastrointestinal locations, but not in an intramuscular location. Medical records at 2 referral centers in the UK were examined to find cases of MCTs in this location. Seven dogs were identified as having an intramuscular MCT by a combination of fine-needle aspirate cytology and computed tomography or ultrasound. None of the dogs had evidence of local lymph node metastasis. Six dogs had no evidence of distant metastasis and surgery was carried out as the primary treatment option. Three of those dogs also had adjunctive chemotherapy due to a high Ki67 value or high mitotic index. All 6 dogs that had had surgery were alive at follow-up with a minimum elapsed time of 7 months. One dog had a course of chemotherapy due to the location, size, and evidence of biological activity of the tumor and died 23 days afterwards. The prognosis of intramuscular mast cell tumors appears to be favorable in most cases.

Tumeurs à mastocytes intramusculaires chez sept chiens. Les tumeurs à mastocytes (MCT) sont couramment observées chez les chiens et elles sont signalées à des emplacements cutanés, conjonctivaux, gastrointestinaux et dans les muqueuses orales, mais non dans des régions intramusculaires. Les dossiers médicaux de deux centres spécialisés du Royaume-Uni ont été examinés afin de trouver des cas de MCT à cet endroit. Sept chiens ont été identifiés comme ayant un MCT intramusculaire en utilisant une combinaison de cytologie par aspiration à l'aiguille fine et de tomodensitométrie ou d'échographie. Aucun des chiens ne présentait des signes de métastase des ganglions lymphatiques locaux. Six chiens ne manifestaient aucun signe de métastase distante et la chirurgie a été réalisée comme option de traitement primaire. Trois de ces chiens ont aussi subi une chimiothérapie d'appoint en raison d'une valeur élevée de Ki67 ou d'un indice mitotique élevé. Les six chiens qui avaient subi la chirurgie étaient vivants au suivi avec un délai écoulé de 7 mois. Un chien a subi un traitement de chimiothérapie en raison de l'emplacement, de la taille et de signes d'activité biologique de la tumeur et est mort 23 jours plus tard. Le pronostic de tumeurs à mastocytes intramusculaires semble être favorable dans la plupart des cas.(Traduit par Isabelle Vallières).

Evaluation of an Axial Pattern Flap Based on the Cranial Cutaneous Branch of the Saphenous Artery: A Cadaveric Perfusion Study.

OBJECTIVES: To confirm the anatomic location of the cranial cutaneous branch of the saphenous artery (CCSA), delineate the angiosome of the CCSA, and provide guidelines for clinical use of an axial pattern flap based on the CCSA. STUDY DESIGN: Anatomic study. ANIMALS: Greyhound cadavers (n=10). METHODS: Shortly after euthanasia, the CCSA was identified and isolated in each hindlimb. Methylene blue and radiographic perfusion studies were performed. The skin was freed from the thigh for photographic and radiographic images. The dimensions of the skin area suitable for use as an axial pattern flap were related to anatomical landmarks. Mock surgical elevation and transposition of the flap in 2 dogs allowed assessment of flap mobility and ease of donor site closure for clinical use. RESULTS: The CCSA was reliably identified in all dogs branching from the saphenous artery as it became superficial to the sartorius muscle, immediately distal to the caudal cutaneous branch and proximal to the genicular branches. Genicular branches were variably paired or singular. Perfusion studies defined the CCSA angiosome as the area cranial to the saphenous artery and caudal to the cranial border of the thigh, extending proximally from the level of the medial tibial condyle to two-thirds of the distance to the inguinal ring. CONCLUSION: An axial pattern flap based on the CCSA could be expected to cover skin defects of the cranial aspect of the distal thigh and stifle, the popliteal region caudal to the stifle, and the proximal medial crus.

Serum Cortisol: An Up-To-Date Assessment of Routine Assay Performance.

BACKGROUND: Accurate serum cortisol quantification is required for the correct diagnosis and management of adrenal pathologies. Presently, most laboratories use immunoassay to measure serum cortisol with proficiency schemes demonstrating a wide dispersion of results. Here, we investigate the effects of sex, matrix, and antibody specificity on serum cortisol quantification in 6 routine assays. METHODS: Surplus serum was obtained before disposal and the following cohorts were created: males, nonpregnant females, pregnant patients, and patients prescribed either metyrapone or prednisolone. Samples were anonymized and distributed to collaborating laboratories for cortisol analysis by 6 routine assays. Cortisol was also measured in all samples using an LC-MS/MS candidate reference measurement procedure (cRMP); cortisol-binding globulin (CBG) was measured in the nonpregnant and pregnant female cohorts. RESULTS: Considerable inter- and intraassay variation was observed across the male and nonpregnant female cohorts relative to the cRMP. Four immunoassays underrecovered cortisol in the pregnancy cohort, and CBG was found to be significantly higher in this cohort than in the nonpregnant females. In the metyrapone and prednisolone cohorts, all immunoassays overestimated cortisol. The first generation Roche E170 and Siemens Centaur XP were particularly prone to overestimation. In all cohorts the routine LC-MS/MS assay aligned extremely well with the cRMP. CONCLUSIONS: Despite the clinical importance of serum cortisol, the performance of routine immunoassays remains highly variable. Accurate quantification is compromised by both matrix effects and antibody specificity. Underpinning this study with a cRMP has highlighted the deficiencies in standardization across routine cortisol immunoassays.

Canine Ovariohysterectomy: A Survey of Surgeon Concerns and Surgical Complications Encountered by Newly Graduated Veterinarians.

The objective of this study was to document newly qualified veterinarians' concerns and surgical complications encountered during canine ovariohysterectomy (cOVH) during the first year of general practice. A questionnaire investigating concerns about cOVH procedures was sent to all final-year veterinary students (group 1) enrolled at five UK universities. Participants were later asked to complete a similar questionnaire 6 months (group 2) and 12 months (group 3) after graduation, which involved grading their concern about different aspects of the cOVH procedure and reporting surgical complications encountered after completing three cOVHs. Responses were compared between different time points. There were 196 respondents in group 1, 55 in group 2, and 36 in group 3. Between groups 1 and 2, there was a statistically significant reduction in the respondents' levels of concern in every aspect of cOVH (p<.05). Between groups 2 and 3, there was no statistically significant change in respondents' levels of concern in any aspect of cOVH (p≥.21). There was a significant reduction in the number of complications encountered by veterinarians in group 3 (39/102, 38.2%) compared to those in group 2 (117/206, 56.8%) (p=.002). Employers should anticipate high levels of concern regarding all aspects of cOVHs in new graduates, and supervision during the first 6 months may be particularly useful.

Evaluation of cumulative cognitive deficits from electroconvulsive therapy.

BACKGROUND: Electroconvulsive therapy (ECT) is the most effective acute treatment for severe depression, but widely held concerns about memory problems may limit its use. AIMS: To find out whether repeated or maintenance courses of ECT cause cumulative cognitive deterioration. METHOD: Analysis of the results of 10 years of cognitive performance data collection from patients who have received ECT. The 199 patients had a total of 498 assessments, undertaken after a mean of 15.3 ECT sessions (range 0-186). A linear mixed-effect regression model was used, testing whether an increasing number of ECT sessions leads to deterioration in performance. RESULTS: The total number of previous ECT sessions had no effect on cognitive performance. The major factors affecting performance were age, followed by the severity of depression at the time of testing and the number of days since the last ECT session. CONCLUSIONS: Repeated courses of ECT do not lead to cumulative cognitive deficits. This message is reassuring for patients, carers and prescribers who are concerned about memory problems and confusion during ECT.