Richardson Hospital

Tyrosine hydroxylase deficiency is an autosomal recessive disorder resulting from cerebral catecholamine deficiency. Tyrosine hydroxylase deficiency has been reported in fewer than 40 patients worldwide. To recapitulate all available evidence on clinical phenotypes and rational diagnostic and therapeutic approaches for this devastating, but treatable, neurometabolic disorder, we studied 36 patients with tyrosine hydroxylase deficiency and reviewed the literature. Based on the presenting neurological features, tyrosine hydroxylase deficiency can be divided in two phenotypes: an infantile onset, progressive, hypokinetic-rigid syndrome with dystonia (type A), and a complex encephalopathy with neonatal onset (type B). Decreased cerebrospinal fluid concentrations of homovanillic acid and 3-methoxy-4-hydroxyphenylethylene glycol, with normal 5-hydroxyindoleacetic acid cerebrospinal fluid concentrations, are the biochemical hallmark of tyrosine hydroxylase deficiency. The homovanillic acid concentrations and homovanillic acid/5-hydroxyindoleacetic acid ratio in cerebrospinal fluid correlate with the severity of the phenotype. Tyrosine hydroxylase deficiency is almost exclusively caused by missense mutations in the TH gene and its promoter region, suggesting that mutations with more deleterious effects on the protein are incompatible with life. Genotype-phenotype correlations do not exist for the common c.698G>A and c.707T>C mutations. Carriership of at least one promotor mutation, however, apparently predicts type A tyrosine hydroxylase deficiency. Most patients with tyrosine hydroxylase deficiency can be successfully treated with l-dopa.

Somatostatin-producing neuroendocrine tumors (SOM-NETs) of the duodenum and pancreas appear to be heterogeneous. To determine their clinicopathological profiles, respective data were analyzed on a series of 82 duodenal and 541 pancreatic NETs. In addition, the clinical records of 821 patients with duodenal or pancreatic NETs were reviewed for evidence of a somatostatinoma syndrome. Predominant or exclusive expression of somatostatin was found in 21 (26%) duodenal and 21 (4%) pancreatic NETs. They were classified as sporadic (n=31) or neurofibromatosis type 1 (NF1)-associated duodenal NETs (n=3), gangliocytic paragangliomas (GCPGs; n=6), or poorly differentiated neuroendocrine carcinomas (pdNECs; n=2). In addition, five duodenal and four pancreatic SOM-NETs were found in five patients with multiple endocrine neoplasia type 1 (MEN1). Metastases occurred in 13 (43%) patients with sporadic or NF1-associated SOM-NETs, but in none of the duodenal or pancreatic MEN1-associated SOM-NETs or GCPGs. Sporadic advanced (stage IV) SOM-NETs were more commonly detected in the pancreas than in the duodenum. None of the patients (including the 821 patients for whom only the clinical records were reviewed) fulfilled the criteria of a somatostatinoma syndrome. Our data show that somatostatin expression is not only seen in sporadic NETs but may also occur in GCPGs, pdNECs, and hereditary NETs. Surgical treatment is effective in most duodenal and many pancreatic SOM-NETs. MEN1-associated SOM-NETs and GCPGs follow a benign course, while somatostatin-producing pdNECs are aggressive neoplasms. The occurrence of the so-called somatostatinoma syndrome appears to be extremely uncommon.

AIMS: Extracts from pine tree bark containing a variety of flavonoids have been used in traditional medicine. Pycnogenol is a proprietary bark extract of the French maritime pine tree (Pinus pinaster ssp. atlantica) that exerts antioxidative, anti-inflammatory, and anti-platelet effects. However, the effects of Pycnogenol on endothelial dysfunction, a precursor of atherosclerosis and cardiovascular events, remain still elusive. METHODS AND RESULTS: Twenty-three patients with coronary artery disease (CAD) completed this randomized, double-blind, placebo-controlled cross-over study. Patients received Pycnogenol (200 mg/day) for 8 weeks followed by placebo or vice versa on top of standard cardiovascular therapy. Between the two treatment periods, a 2-week washout period was scheduled. At baseline and after each treatment period, endothelial function, non-invasively assessed by flow-mediated dilatation (FMD) of the brachial artery using high-resolution ultrasound, biomarkers of oxidative stress and inflammation, platelet adhesion, and 24 h blood pressure monitoring were evaluated. In CAD patients, Pycnogenol treatment was associated with an improvement of FMD from 5.3 ± 2.6 to 7.0 ± 3.1 (P < 0.0001), while no change was observed with placebo (5.4 ± 2.4 to 4.7 ± 2.0; P = 0.051). This difference between study groups was significant [estimated treatment effect 2.75; 95% confidence interval (CI): 1.75, 3.75, P < 0.0001]. 15-F(2t)-Isoprostane, an index of oxidative stress, significantly decreased from 0.71 ± 0.09 to 0.66 ± 0.13 after Pycnogenol treatment, while no change was observed in the placebo group (mean difference 0.06 pg/mL with an associated 95% CI (0.01, 0.11), P = 0.012]. Inflammation markers, platelet adhesion, and blood pressure did not change after treatment with Pycnogenol or placebo. CONCLUSION: This study provides the first evidence that the antioxidant Pycnogenol improves endothelial function in patients with CAD by reducing oxidative stress.

BACKGROUND: We report the use of a new treatment modality in 2 patients with primary cutaneous B-cell lymphoma. In a 58-year-old woman with progressive nodular lesions on the scalp and face, several treatment attempts either failed or could not be used because of severe adverse effects and underlying epilepsy. The patient declined radiotherapy. A 30-year-old man presented with recurrence of tumor nodules occipitally, thoracically, on the arm, and on the right thigh after several excisions. OBSERVATIONS: Intralesional injection of rituximab, a chimeric antibody directed against the CD20 transmembrane antigen present in malignant and normal B cells, resulted in partial regression of tumor nodules. No adverse effects occurred except pain during or shortly after injection and, in one patient, a slight rise in body temperature. Due to the treatment a prolonged complete disappearance of B cells from peripheral blood samples was observed. CONCLUSION: Intralesional rituximab therapy is a nontoxic and effective treatment for cutaneous B-cell lymphoma that deserves further investigation in larger clinical trials.

BACKGROUND: Epithelial-to-mesenchymal transition (EMT) is a morphologic transdifferentiation of carcinomas, conferring increased tumour invasiveness, but may also be applied to the epithelioid versus sarcomatoid histotype of malignant pleural mesothelioma (MPM). Herein, we correlated proteins of a putative MPM-EMT axis, including periostin, epidermal growth factor receptor (EGFR), integrin beta1, phosphatase and tensin homologue (PTEN), integrin-linked kinase (ILK), p21 and p27, with clinico-pathologic parameters, in particular overall survival (OS). PATIENTS AND METHODS: A retrospective cohort of 352 mostly untreated patients with MPM was investigated by immunohistochemistry of a tissue microarray. Protein expression intensities were semi-quantitatively scored from 0 to 3 in their respective compartments, including peritumoural stroma as well as tumour cell plasma membrane, cytoplasm or nucleus. Data were correlated with histotype and survival outcome. RESULTS: A total of 32% of the tumours were diagnosed as epithelioid, 13% as sarcomatoid and 55% as biphasic histotype. High expression of membranous EGFR and integrin beta1 as well as nuclear p27 correlated with the epithelioid and high expression of cytoplasmic tumoural and stromal periostin with the sarcomatoid histotype. The median survival time of the 128 patients with complete follow-up data was 11.7 months. Univariate survival analysis revealed age, epithelioid histotype and any therapy as prognosticators for better OS. High expression of cytoplasmic PTEN or ILK as well as high expression of nuclear p21 or p27 correlated with increased, whereas high expression of cytoplasmic periostin with decreased OS (all p values <0.05). Multivariate Cox regression revealed any treatment, low cytoplasmic periostin and high cytoplasmic PTEN as independent prognosticators for better OS. CONCLUSION: Activation of periostin-triggered EMT is associated with the sarcomatoid histotype and has an impact on shorter survival of MPM patients. Finally, only the high expression of PTEN and the low expression of cytosolic periostin could be shown to be independent prognostic factors for longer OS.

To characterize newly arising replication of human immunodeficiency virus (HIV) type 1 in vivo at the cellular level, distinct viral RNA species in peripheral blood mononuclear cells (PBMCs) from HIV-1-infected patients were monitored during 2 weeks of structured treatment interruption (STI). HIV-1 RNA encoding tat/rev and PBMC-associated virions were almost completely depleted during antiretroviral therapy and emerged simultaneously after 2 weeks of STI, thus specifically reflecting productive viral infection at the cellular level. The magnitude of these correlates of reappearing cellular viral replication was predicted by during-therapy levels of nef transcripts in PBMCs. Significant rebound of plasma viremia, representing the progeny of a broader range of anatomical compartments, preceded and predicted productive infection in PBMCs. Thus, cellular viral rebound in PBMCs likely was primed before STI by the expression of nef in HIV-1-infected PBMCs that lacked virion production and was subsequently triggered by the plasma viremia that preceded the recurrence of productively infected PBMCs.

BACKGROUND: Cough in the geriatric small breed dog with myxomatous mitral valve degeneration (MMVD), a large left atrium, and absence of heart failure often is attributed to compression of the left mainstem bronchus by the left atrium. Studies investigating this syndrome are lacking in dogs. HYPOTHESIS: Airway collapse is independent of left atrial enlargement. ANIMALS: A total of 16 dogs presenting with chronic cough in the absence of congestive heart failure. Group 1 dogs (n = 10) had moderate-to-severe left atrial enlargement based on an echocardiographically calculated left atrial:aortic surface area [LA:Ao(a)] > 6. Group 2 dogs (n = 6) had no to mild left atrial enlargement [LA:Ao(a) ≤ 6]. METHODS: Dogs were prospectively evaluated. CBC, biochemistry, urinalysis, cervical and thoracic radiographs, fluoroscopy, echocardiography, and bronchoscopy were performed. Bronchoscopic abnormalities were compared between groups using Fisher's Exact Test. P < .05 was considered significant. RESULTS: Fluoroscopy identified airway collapse in both groups. Bronchoscopic evidence of airway collapse >50% was observed in multiple bronchi with no difference between groups. All dogs had inflammation on airway cytology with respiratory infection in 1 dog in group 2. Left atrial size was interpreted radiographically as enlarged in 9 of 10 group 1 dog and in 2 of 6 group 2 dogs. VHS was above normal in both groups of dogs regardless of echocardiographic evidence of cardiomegaly. CONCLUSIONS: Results failed to identify an association between left atrial enlargement and airway collapse in dogs with MMVD, but did suggest that airway inflammation is common in dogs with airway collapse.

Abstract Competency in 21st-century health communication involves an understanding that the internet landscape has evolved from static webpages to applications that engage users. This evolution to “Web 2.0„ includes such applications as blogs, wikis, social-networking sites, and podcasts. This review presents trends in Web 2.0 internet usage, summarizes Web 2.0 applications as platforms for health promotion, discusses guidelines for using Web 2.0 applications, and identifies Web 2.0 learning outcomes. Greater awareness of Web 2.0 can provide health educators with new channels for health communication and will help stimulate additional research to further define best-practice models.

Death receptor targeting has emerged as one of the promising novel approaches of cancer therapy. The activation of one such prototypic death receptor, CD95 (Fas/APO-1), has remained controversial because CD95 agonistic molecules have exhibited either too strong toxicity or too little activity. The natural CD95 ligand (CD95L) is a cytokine, which needs to trimerize to mediate a cell death signal. Mega-Fas-Ligand, now referred to as APO010, is a synthetic hexameric CD95 agonist that exhibits strong antitumor activity in various tumor models. Here, we studied the effects of APO010 in human glioma models in vitro and in vivo. Compared with a cross-linked soluble CD95L or a CD95-agonistic antibody, APO010 exhibited superior activity in glioma cell lines expressing CD95 and triggered caspase-dependent cell death. APO010 reduced glioma cell viability in synergy when combined with temozolomide. The locoregional administration of APO010 induced glioma cell death in vivo and prolonged the survival of tumor-bearing mice. A further exploration of APO010 as a novel antiglioma agent is warranted.

OBJECTIVE: Cardiopulmonary bypass (CPB) surgery induces a transient rise in pro-inflammatory cytokines typically released by activated monocytes. The E4 variant of apolipoprotein E is a recognized risk factor for atherosclerosis. It has recently been shown that apolipoprotein E affects monocyte functions in vitro and leads to higher levels of median lipoprotein (a) in humans. The aim of the study is to investigate if the E4 genetic variant of apolipoprotein E affects cytokine release after CPB surgery. METHODS: 22 patients were operated on with standard coronary artery bypass grafting. Concentrations of interleukin 8 (IL-8) and tumor necrosis factor (TNF-alpha) were measured by automated Immulite immunoassay at regular intervals within 48 h after surgery. Total apparent cytokine outputs were calculated as area under the curve. Results are expressed as mean+/-standard deviation and compared by unpaired t-test. RESULTS: In the presented patient population 6 (27%) carried the E4 allele. Sixteen (63%) showed no E4 allele. Mean cross clamp time (CCT) was 56.2+/-13.5 min versus 55.7+/-12.1 min and CPB time was 91.8+/-17.5 versus 93.5+/-15.7 min. No statistical difference between E4-carriers and E4 non-carriers regarding CCT and CPB was observed. The total amount of IL-8 and TNF-alpha was higher in patients carrying the E4 genetic variant of apolipoprotein E in comparison to E4 non-carriers (P<0.08, P<0.039). CONCLUSION: The presence of the E4 allele is associated with increased release of IL-8 and TNF-alpha after CBP surgery. The preoperative determination of E4 in patients undergoing cardiac surgery may lead to additional perioperative measures for the treatment of an increased systemic inflammatory response.

Pheochromocytomas (PCCs) are rare tumors that arise from chromaffin tissue in the adrenal medulla, but can also occur in the abdomen outside the adrenals and are then called sympathetic paragangliomas (sPGLs). According to the literature, between 15 and 25% of apparently sporadic adrenal PCC and sPGL are caused by germline mutations in RET, von Hippel-Lindau disease (VHL), succinate dehydrogenase subunit B (SDHB), or subunit D SDHD. However, few studies have addressed the mutationfrequency of these candidate genes in selected subgroups of PCC andsPGL, such as bilateral adrenal PCC or extra-adrenal sPGL, and none have looked at somatic mutations by analyzing tumor tissue. Therefore, we have investigated the occurrence of germline and somatic mutations in RET, VHL, SDHB, and SDHD in comparatively large series of bilateral adrenal PCC (n = 33 patients) and sPGL (n = 26 patients), with the aim of determining the mutation frequency of each of these genes and to establish a genetic testing algorithm. Twenty-one RET, two VHL germline, and one SDHD mutations were found in the patients with bilateral adrenal PCC. In sPGL, one novel SDHB germline and one novel SDHB somatic mutation were observed. In addition, two SDHD germline mutations were found. We conclude that germline RET mutations are predominantly found in bilateral PCC, and that somatic and germline SDHB and SDHD mutations usually occur in sPGL, which has practical consequences for genetic testing algorithms. We suggest that sequential mutation analysis should be directed first at RET, followed by VHL and SDHD for patients with bilateral adrenal PCC at diagnosis, and at SDHB and SDHD for patients with sPGL.

BACKGROUND: Animals with chronic cough can have normal bronchoalveolar lavage fluid cytology when small airway disease is absent. Cytology of a tracheobronchial brushing can detect inflammation in larger airways; however, evaluation of this technique has been limited in veterinary medicine. OBJECTIVE: To compare airway brush cytology to bronchoalveolar lavage fluid analysis in dogs and cats with chronic cough. ANIMALS: Forty dogs and five cats undergoing bronchoscopic investigation of chronic cough. METHODS: Prospective study. Bronchoscopy and bronchoalveolar lavage were performed followed by tracheobronchial brushing of central airways. Results of cytologic assessment of BAL fluid and brush cytology were compared for the presence or absence of inflammation and concordance of inflammatory cell type. RESULTS: Brush cytology detected central airway inflammation in 34 of 40 (85%) dogs with inflammatory BAL fluid. However, the type of inflammation reported differed in 23 of 34 dogs. In five cats with inflammation in BAL fluid, brush cytology detected inflammation in four; the type of inflammation was discordant in all cats. CONCLUSIONS AND CLINICAL RELEVANCE: Brush cytology has good agreement with BAL regarding the presence of inflammation, although the type of inflammation detected with the different sampling techniques commonly varies. Brush cytology can provide supplementary information to BAL, and additional studies will provide further information on the role of tracheobronchial brush cytology in the diagnosis and management of respiratory conditions.

With increased focus on quality assurance, a complete axillary lymph node dissection (ALND) has been defined as the removal of 10 or more lymph nodes (LN). The objective of this study was to determine which patient, physician, and geographic factors predict the adequacy of ALND in breast cancer patients. The University of Louisville Breast Cancer Sentinel Lymph Node Study is a multicenter, prospective study of 4,131 patients, all of whom had a sentinel node biopsy and completion ALND. Univariate and multivariate analyses were performed to determine which factors were independently associated with the removal of 10 or more LN. Of the 4,131 patients in this study, the median number of LN removed was 11 (range; 3-45). Ten or more LN were removed in 3,213 (77.8%) patients. The median patient age in this study was 60 (range; 27-100), with a median tumor size of 1.5 cm (range; 0.1-11.0 cm). On univariate analysis, patient age, tumor size, and palpability were correlated with adequacy of ALND. Academic affiliation and percentage of breast practice were significant physician factors predictive of adequacy of ALND. Both geographic region and community size were significantly correlated with adequacy of ALND. On multivariate analysis, patient age (p = 0.024), surgeon academic affiliation (p < 0.001), percentage breast practice (p < 0.001), and community size (p = 0.003) were significant determinants of adequacy of ALND. Younger patients were more likely to have an adequate ALND. Surgeons in academic practice had a higher rate of adequate ALND, as did those practicing in larger communities. Surgeons with a more breast experience had a lower rate of adequate ALND. Patient age, surgeon academic affiliation, and breast experience, as well as community size are all significant factors predictive of adequacy of ALND.

The Inter Face Project was a pilot study to improve race relationships between supervisors and employees in South African industry. The ultimate intent of this project was to find a path for more extensive research aimed at improving inter‐racial attitudes and behavior in South Africa, especially in work situations. Nevertheless, this project is only a small step in the direction of improved inter‐race relationships in that country. Behavior modeling training was the vehicle for attempting to change the behaviors. Several measures were used because it was uncertain how change would be found. However, performance records were incomplete and therefore not useful. A questionnaire and expectation scale did not reveal significant change, possibly because of the small sample size and the reluctance on the part of supervisors to be candid. Structured interviews, however, indicated dramatic improvements in inter‐race attitudes and observations for both supervisors and employees. Second post‐test improvements (20 weeks after training) were, in fact, even greater than improvements noted at the first post‐test (six weeks after training). Before and after training comments by employees and supervisors provided strong evidence of the extent of change that occurred. Several suggestions for follow‐up research were outlined.

Abstract Cook Inlet beluga whales (CIBWs; Delphinapterus leucas ), are an isolated and declining endangered population in Alaska, USA. Their critical habitat has been broadly defined, with little empirical data on habitat use to direct management actions. This article examines data collected during surveys for a long‐term photo‐ID study to gain insight into the use of critical habitat by CIBW groups and individuals, with a focus on areas where belugas were observed feeding, calving, rearing young, and in transit. It also describes patterns of group distribution, size, and composition, according to sex and age class, in order to better understand how CIBWs are distributed throughout critical habitat during the ice‐free season. The results are presented according to survey month and survey zone, so that patterns of habitat use are accessible in a useful format to aid managers in evaluations of how timing and location of human activities occurring in CIBW critical habitat may overlap with CIBW occurrence and use of these areas. There were 575 beluga groups encountered during 477 photo‐ID surveys conducted in CIBW critical habitat 2005–2017. CIBW locations were mapped, and models were developed to test for temporal and spatial patterns. Approximately 400 individual whales were identified, and their sighting histories were compiled to examine residency and movement patterns. CIBWs were found seasonally in distinct areas, where they aggregate in large groups of both sexes and all age classes while rearing calves and feeding. These areas, and the general corridors connecting them, represent important beluga habitat that warrant focused management attention and protection efforts. Whales travelling among distinct areas of Cook Inlet increase their likelihood of exposure to multiple, localized threats. Habitat protection and the regulation of anthropogenic activities should consider cumulative effects of all activities in the range of CIBWs and their potential to affect the entire population.

CASE REPORT: A normolipaemic 7-year-old female spayed Domestic Shorthair was initially presented with a history of pruritus for several years and diagnosed with concurrent atopic dermatitis, flea bite hypersensitivity and adverse food reaction. The hypersensitivities were controlled with cyclosporin, allergen-specific immunotherapy, topical flea control and a restricted diet. Five months after initial presentation, the cat developed a non-healing nodular ulcerated cutaneous lesion in the left axilla and also developed immune-mediated haemolytic anaemic (IMHA). The IMHA was stabilised, but the axillary lesion persisted and progressed to a diffuse, firm, yellowed subcutaneous swelling over the ventral body approximately 20 months later. Histopathology was consistent with cutaneous xanthoma. The cat was normolipaemic and being fed a home-prepared diet of lean kangaroo meat and pumpkin to manage pruritus associated with adverse food reactions. No underlying malignancy was detected on routine screening tests. CONCLUSION: A diffuse, planar form of cutaneous xanthoma occurring without associated lipaemia has not been previously reported in cats.

Abstract Mortality is a demographic metric crucial for understanding the dynamics of endangered populations such as Cook Inlet beluga whales (CIBWs, Delphinapterus leucas ), but patterns of mortality are currently not well understood for CIBWs, making decisions about recovery actions challenging. We combined long‐term photo‐ID data from approximately 420 individual belugas identified during the period 2005–2017 with stranding data from 95 dead belugas to identify patterns of mortality with respect to age, sex, geographic range, cause of death, and to estimate minimum mortality rates. Reported mortality was greatest for adults of reproductive age, followed by calves, with fewer subadults and no adults older than 49 years in the stranding data set despite lifespans of 70+ years reported in other beluga populations. Dead females and males were evenly represented. Live stranding was the predominant assigned cause of death but represented only ~33% of deaths of known cause. Causal factors for the majority of deaths and live strandings are unknown. Annual mortality estimated from reported carcasses relative to total population size averaged 2.2%. Our analysis advances our current understanding of mortality patterns in CIBWs but linking a greater proportion of carcasses to photo‐ID individuals would further improve our understanding; we conclude with recommendations for achieving this.

PURPOSE: To identify trends in chronic obstructive pulmonary disease (COPD) diagnoses among active duty U.S. military personnel based on deployment history and whether International Classification of Disease, 9th edition (ICD-9) coding meet criteria for the diagnosis of COPD. METHODS: A retrospective chart review using the electronic medical system was conducted for military personnel diagnosed with COPD based on ICD-9 codes for emphysema or chronic obstructive lung disease with at least three qualifying outpatient COPD-coded encounters. Clinical symptoms, smoking history, pulmonary function testing, and radiographs obtained during the diagnostic workup were reviewed. The established diagnosis of COPD was analyzed in relation to deployment. RESULTS: A total of 371 patients were identified during the study period (2005-2009). Of these patients, 194 (52.3%) deployed, whereas 177 (47.7%) did not deploy to Southwest Asia since 2003. Thirty-four percent had no documented smoking history despite the diagnosis of COPD. Airway obstruction was identified by spirometry in only 67% of individuals diagnosed with COPD. No statistically significant differences in pulmonary function testing values were identified between those deployed and nondeployed individuals. CONCLUSION: Despite evidence of increased respiratory symptoms in deployed military personnel, the impact of deployment on increased diagnosis of COPD or severity of disease appears minimal.

BACKGROUND: Cerebrospinal fluid (CSF) lactate concentrations increase after seizure activity in many human patients independent of the underlying disease process. The effect of seizure activity on CSF lactate concentration in dogs is unknown. HYPOTHESIS/OBJECTIVES: Cerebrospinal fluid lactate concentration is unaffected by seizure activity in dogs and is more dependent on the underlying disease process causing the seizures. ANIMALS: One-hundred eighteen client-owned dogs with seizure disorders. METHODS: Case series. Cerebrospinal fluid lactate concentration was determined using a commercially available lactate monitor. Seizure semiology, time from last seizure to CSF collection, number of seizures within the 72 hours preceding CSF collection, and clinical diagnosis were recorded. RESULTS: Dogs with focal seizures had higher CSF lactate concentrations than did those with generalized seizures (P = .03). No differences in lactate concentrations were found among dogs with single seizures, cluster seizures or status epilepticus (P = .12), among dogs with CSF collection at different time points after the last seizure activity (P = .39) or among dogs having different numbers of seizures within the 72 hours preceding CSF collection (P = .42). A significant difference (P = .001) was found in CSF lactate concentrations among diagnostic groups, and dogs with inflammatory and neoplastic disease had higher concentrations than did dogs with idiopathic or unknown epilepsy. CONCLUSIONS AND CLINICAL IMPORTANCE: Cerebrospinal fluid lactate concentration is minimally affected by seizure activity in dogs and increased concentrations are more likely associated with the underlying disease process.

Abstract Interactions between different species of predators are not uncommon, yet they are generally understudied in North America. Across their range, gray wolves ( Canis lupus ) and wolverines ( Gulo gulo ) occupy similar habitats and dietary niches. However, due to the elusiveness and relatively low density of these two species, interactions between them are not well documented. Here, we describe three instances of a single wolf pack killing a wolverine in the span of 13 months. None of the wolverines killed by wolves were consumed, suggesting that food was not the primary motivation behind the killings. Alternatively, defense of a food resource, territoriality, interspecific competitive killing, or some combination of those behaviors appear to be the cause of these actions. Documentation of these occurrences improves our understanding of wolf and wolverine ecology, interspecific predator interactions, and potential future changes to this aspect of community ecology.