Polyautoimmunity manifest as inflammatory myopathy, uveitis, and progressive cutaneous depigmentation in a mixed breed dog: a case report.

BACKGROUND: Polyautoimmunity is the expression of more than one autoimmune disease in a single patient. This report documents polyautoimmunity in a mixed breed dog with concurrent uveitis, cutaneous depigmentation, and inflammatory myopathy. CASE PRESENTATION: A 1-year-old male neutered mixed breed dog was presented for progressive generalized leukotrichia and leukoderma, bilateral panuveitis, and masticatory muscle atrophy. The latter progressed to myositis of lingual, pharyngeal, and masticatory muscles confirmed by biopsy. Temporalis muscle was completely replaced by adipose and fibrous tissue, and necrotic myofibers with extensive infiltration of mononuclear cells indicated active myositis of lingual muscle. Skin biopsies showed severe melanin clumping in epidermis, hair follicles, and hair shafts, and perifollicular pigmentary incontinence. Uveitis, depigmentation, and myositis affecting the masticatory, pharyngeal, and tongue muscles were diagnosed based on clinical, histological, and laboratory findings. CONCLUSIONS: To the authors' knowledge, this is the first report of concurrent uveitis, progressive cutaneous depigmentation, and inflammatory myopathy in a dog.

Periodic discharges in veterinary electroencephalography-A visual review.

First described in human EEG over 60 years ago, there are very few examples of periodic discharges in the veterinary literature. They are associated with a wide variety of etiologies, both intracranial and systemic, making interpretation challenging. Whether these patterns are indicative of ictal, interictal, or postictal activity is a matter of debate and may vary depending on the clinical features in an individual patient. Periodic discharges have a repeated waveform occurring at nearly regular intervals, with varying morphology of individual discharges from simple sharp waves or slow waves to more complex events. Amplitudes, frequencies, and morphologies of the discharges can fluctuate, occasionally evolving, or resolving over time. This study presents a visual review of several veterinary cases with periodic discharges on EEG similar to those described in human EEG, and discusses the current known pathophysiology of these discharges.

Case Report: MRI, Clinical, and Pathological Correlates of Bromethalin Toxicosis in Three Dogs.

Bromethalin toxicosis is an increasingly common clinical presentation in dogs that may be fatal depending on the extent of intoxication. Antemortem diagnosis of bromethalin toxicosis was achieved in three dogs by demonstration of the active metabolite desmethylbromethalin in fat or serum. Magnetic resonance imaging (MRI) findings were consistent with a diffuse leukoencephalopathy with restricted diffusion and prominent involvement of the corticospinal motor tracts on T2-weighted and diffusion-weighted sequences. Imaging findings were confirmed in one non-surviving dog at necropsy. Resolution of MRI abnormalities was demonstrated in one surviving dog that was consistent with the associated resolution of clinical signs. Initial findings in these dogs support further investigation of specific MRI patterns in cases of leukoencephalopathy to aid differential diagnosis. While antemortem detection of bromethalin and its metabolites confirms exposure, quantitation may be informative as a prognostic biomarker.

Whole genome sequencing for mutation discovery in a single case of lysosomal storage disease (MPS type 1) in the dog.

Mucopolysaccharidosis (MPS) is a metabolic storage disorder caused by the deficiency of any lysosomal enzyme required for the breakdown of glycosaminoglycans. A 15-month-old Boston Terrier presented with clinical signs consistent with lysosomal storage disease including corneal opacities, multifocal central nervous system disease and progressively worsening clinical course. Diagnosis was confirmed at necropsy based on histopathologic evaluation of multiple organs demonstrating accumulation of mucopolysaccharides. Whole genome sequencing was used to uncover a frame-shift insertion affecting the alpha-L-iduronidase (IDUA) gene (c.19_20insCGGCCCCC), a mutation confirmed in another Boston Terrier presented 2 years later with a similar clinical picture. Both dogs were homozygous for the IDUA mutation and shared coat colors not recognized as normal for the breed by the American Kennel Club. In contrast, the mutation was not detected in 120 unrelated Boston Terriers as well as 202 dogs from other breeds. Recent inbreeding to select for recessive and unusual coat colors may have concentrated this relatively rare allele in the breed. The identification of the variant enables ante-mortem diagnosis of similar cases and selective breeding to avoid the spread of this disease in the breed. Boston Terriers carrying this variant represent a promising model for MPS I with neurological abnormalities in humans.

Pharmacokinetics of Intravenous and Oral Phenobarbital Sodium in Healthy Goats.

Phenobarbital is a common drug used to manage epilepsy in goats. However, the recommended dose and dosing frequency are based on studies in dogs and horses. Studies describing the pharmacokinetics of phenobarbital when administered orally and assessing changes in behavior with concurrent electroencephalogram (EEG) readings are warranted in goats. The objectives of this study were to determine the bioavailability of orally administered phenobarbital and determine the effect of phenobarbital on brain activity using EEG in healthy goats. A cross-over design with 8 non-pregnant goats was performed. The goats were administered phenobarbital intravenously at 10 mg/kg, followed by a 2 week wash out period, and then administered phenobarbital, orally, at 10 mg/kg. Plasma sample determination of phenobarbital concentrations were collected at 13 time points. Continuous EEG readings with simultaneous video recording for 12 h was performed to determine the state of vigilance using a behavior scoring system prior to and after phenobarbital administration. Bioavailability of phenobarbital was 24.9%. Mean ± SD for half-life was similar between the oral (3.80 ± 0.826 h) and intravenous (4.0 ± 0.619 h) routes. Time to observed maximum concentration (Tmax), and maximum plasma concentration (Cmax) for the oral administration were 1.75 ± 0.46 h and 4,478.7 ± 962.4 ng/mL, respectively. Clearance was 152.5 ± 102.7 ml/h/kg. Area under the curve from zero to infinity (AUC0→∞) was 155,813 ± 218,448 and 38,763 ± 9,832 h*ng/mL for the intravenous and oral administration routes, respectively. Behavior score at 3 h after phenobarbital administration was different (P = 0.0002) from the score prior to administration for the oral administration route. In contrast, behavior scores before administration of phenobarbital and each time point after administration were not different (P >0.05) for the intravenous administration route or other oral administration route time points. Bioavailability of phenobarbital was poor, and the half-life was very short due to a high clearance. Doses >10 mg/kg should be considered when phenobarbital is administered orally in goats.

Prevalence of benign paroxysmal positional vertigo in the young adult population.

OBJECTIVE: To evaluate the prevalence of benign paroxysmal positional vertigo (BPPV), defined as positionally induced nystagmus (PIN) with associated symptoms on provocative testing, in the young healthy adult population. DESIGN: A prospective, cohort, screening study. SETTING: A community-based hospital located in a small midwestern city with a greater metropolitan population of approximately 125,000. PARTICIPANTS: One hundred ninety-eight young adults (99 men and 99 women), ages 18-34 years and not being treated for dizziness or balance problems, were recruited from November 2009 to April 2010. METHODS: The participants completed questionnaires that detailed demographics, medical and surgical history, sports and/or activity participation history, and baseline symptoms commonly associated with BPPV. The participants were screened for inclusion with an ocular motor assessment in room light, followed by a vestibular positional assessment for BPPV with infrared camera-equipped goggles recorded on digital video disk. MAIN OUTCOME MEASUREMENT: The prevalence of BPPV, defined as PIN, along with symptoms in study participants. RESULTS: The prevalence of BPPV was 9% in this young adult population. Symptoms during testing were reported in 14% of all subjects (22% of women, 5% of men). Of 22 women who reported symptoms, 12 had PIN (P = .519), whereas the 5 men who reported symptoms all had PIN (P = .001). PIN, characteristic of that seen in BPPV (with or without associated symptoms), was identified in 53% of subjects, with 43% of subjects having posterior canal involvement, 10% having anterior canal involvement, and 8% having horizontal canal involvement. Eleven percent of subjects had bilateral semicircular canal involvement. CONCLUSION: Nine percent of our young adult subjects were diagnosed with previously unrecognized BPPV, with provoked symptoms of dizziness, headache, nausea, or imbalance, symptoms that may cause significant physical and psychosocial limitations if left untreated. This is an important finding because BPPV is an often-overlooked diagnosis that has a known, very effective treatment.

Endovascular abdominal aortic aneurysm repair in nonagenarians--beyond limits?

Herein, we report a single institution's experience with endovascular abdominal aortic aneurysm repair in nonagenarians, over a 4-year period of time. We performed a retrospective study of cases, in which we documented patient demographics, symptoms, physical findings, surgical interventions, complications, and deaths. The survivors answered a questionnaire. Endovascular abdominal aneurysm repair was performed in 4 male nonagenarians (age range, 90-92 yr): 2 underwent repair of asymptomatic aneurysm and 2 underwent repair of symptomatic aneurysm. There was no in-hospital death, and patients were discharged after a median time of 11 days. Both patients with symptomatic abdominal aortic aneurysm died within 30 days, 1 of an occluded left femoral artery and the other of unknown cause. After follow-ups of 6 and 54 months, both survivors were in good physical condition and patient satisfaction appeared to be very high. We have shown that elective endovascular abdominal aneurysm repair in a small, selected group of nonagenarians was feasible and afforded acceptable short-term survival. In patients with symptomatic disease, however, the early postprocedural mortality rate appears to be high. Decision-making should focus chiefly on comorbidities, on subjective issues such as fear of rupture, and on ethical and financial considerations.

Eurytrema procyonis and pancreatitis in a cat.

A young adult male domestic shorthair cat was presented for physical examination, routine vaccinations, and a fecal examination. Physical examination revealed no significant abnormalities. Eggs of the raccoon pancreatic fluke Eurytrema procyonis were detected by fecal flotation. Results of a complete blood count and serum biochemistry panel were normal. Abdominal sonography revealed an enlarged hypoechoic pancreas with a hyperechoic rim, and a distended and thickened pancreatic duct. Serum pancreatic lipase immunoreactivity (PLI) was increased. These findings supported the possibility of fluke-associated pancreatitis. Treatment with praziquantel/pyrantel/febantel was associated with resolution of sonographic abnormalities and normalization of PLI.

Principles of neurological imaging of exotic animal species.

Because the central nervous system (CNS) is encased almost entirely in bone, the means by which the clinician can evaluate it are limited. Additionally, the small size of many exotic companion animals further complicates diagnostic evaluation of the brain and spinal cord. Knowledge of the advantages and limitations of different imaging modalities, along with the neuroanatomical localization and assessment of likely causes of disease, will permit the clinician to choose the most appropriate imaging method for the patient. This article discusses the basic imaging principles of radiology, myelography, CT, and MRI of the nervous system of companion exotic animals to aid exotic animal clinicians in selecting imaging modalities and interpreting the results.

Discrimination between six species of canine microfilariae by a single polymerase chain reaction.

Canine dirofilariasis caused by Dirofilaria immitis is usually diagnosed by specific antigen testing and/or identification of microfilariae. However, D. immitis and at least six other filariae can produce canine microfilaremias with negative heartworm antigen tests. Discriminating these can be of clinical importance. To resolve discordant diagnoses by two diagnostic laboratories in an antigen-negative, microfilaremic dog recently imported into the US from Europe we developed a simple molecular method of identifying different microfilariae, and subsequently validated our method against six different filariae known to infect dogs by amplifying ribosomal DNA spacer sequences by polymerase chain reaction using common and species-specific primers, and sequencing the products to confirm the genotype of the filariae. We identified the filaria in this dog as D. repens. This is the first case of D. repens infection in the United States. Additionally, we examined microfilariae from five additional antigen-negative, microfilaremic dogs and successfully identified the infecting parasite in each case. Our diagnoses differed from the initial morphological diagnosis in three of these cases, demonstrating the inaccuracy of morphological diagnosis. In each case, microfilariae identified morphologically as A. reconditum were identified as D. immitis by molecular methods. Finally, we demonstrated that our PCR method should amplify DNA from at least two additional filariae (Onchocerca and Mansonella), suggesting that this method may be suitable for genotyping all members of the family Onchocercidae.

Weekly paclitaxel improves pathologic complete remission in operable breast cancer when compared with paclitaxel once every 3 weeks.

PURPOSE: To determine the impact a change in schedule of paclitaxel administration from once every 3 weeks to frequent administration would have on the pathologic complete response (pCR) rate in the breast and lymph nodes for patients with invasive breast cancer treated with primary systemic chemotherapy (PST). PATIENTS AND METHODS: Patients with clinical stage I-IIIA breast cancer were randomly assigned to receive PST of paclitaxel doses administered either weekly (for a total of 12 doses of paclitaxel) or once every 3 weeks (four cycles), followed by four cycles of fluorouracil/doxorubicin/cyclophosphamide (FAC) in standard doses every 3 weeks. Two different doses of paclitaxel were used based on lymph node status defined by ultrasound and fine needle aspiration. Clinical response and extent of residual disease in the breast and lymph nodes was assessed after completion of all chemotherapy. RESULTS: A total of 258 patients were randomly assigned to receive doses of paclitaxel administered either weekly or once every 3 weeks, followed by FAC. Of these 258 patients, 110 patients had histologic lymph node involvement and 148 patients had clinical N0 disease. Weekly paclitaxel followed by FAC was administered to 127 patients and once-every-3-weeks paclitaxel followed by FAC was administered to 131 patients. Clinical response to treatment was similar between groups (P = .25). Patients receiving weekly paclitaxel had a higher pCR rate (28.2%) than patients treated with once-every-3-weeks paclitaxel (15.7%; P = .02), with improved breast conservation rates (P = .05). CONCLUSION: The change in schedule of paclitaxel from once every 3 weeks to a more frequent administration significantly improved the ability to eradicate invasive cancer in the breast and lymph nodes.

Total RNA yield and microarray gene expression profiles from fine-needle aspiration biopsy and core-needle biopsy samples of breast carcinoma.

BACKGROUND: Gene expression profiling should be applicable to needle biopsy samples if microarray technology is to become practically useful for clinical research or management of breast carcinoma. This study compared gene expression profiles derived from fine-needle aspiration biopsy (FNAB) and from core needle biopsy (CBX). METHODS: Total RNA was extracted from single FNAB and CBX samples. Corresponding pairs of FNAB and CBX were analyzed for similarity of gene expression profiles using cDNA microarrays that contain 30721 human sequences. A subset of genes that distinguished CBX samples from FNAB samples was evaluated in a larger group of needle biopsy samples and in a published genomic database derived from 78 sporadic breast carcinomas with known clinical outcome. RESULTS: Sixty-eight patients with newly diagnosed breast carcinoma were included in the current study. Sixty-five patients underwent FNAB (17 had both FNAB and CBX) and 3 underwent CBX only. Extracted RNA was of suitable quality for hybridization in 46 (71%) FNABs and 15 (75%) CBXs. Total RNA yield in those samples was similar for single-pass FNAB (mean = 3.6 microg and median = 2.2 microg; n = 46) and CBX (mean = 2.8 microg and median = 2.0 microg; n = 15), with 1 microg or more of total RNA in all cases. Transcriptional profiling was performed successfully in all cases when it was attempted, in a total of 50 samples (38 FNABs and 12 CBXs), including matched FNAB and CBX samples from 10 patients. There were differences in gene expression profiles in 10 matched FNAB and CBX sample pairs. Genes that were expressed differently in CBX samples, compared with FNAB samples, were recognized as being predominantly from the endothelium, fibroblasts, myofibroblasts or smooth muscle, and histiocytes. Corresponding microscopic cell counts from FNABs demonstrated means of 80% tumor cells, 15% lymphocytes, and 5% stromal cells, whereas CBXs contained 50% tumor cells, 20% lymphocytes, and 30% stromal cells. Considering that CBXs are approximately six-fold richer in nonlymphoid stromal cells than FNABs and that CBXs differentially express a set of recognized stromal genes, the authors used these biopsies to define a transcriptional profile of breast carcinoma stroma. A set of 120 genes differentially expressed in CBXs was assessed independently in a published breast carcinoma genomic database to classify breast carcinomas based on stromal gene expression. Subgroups of tumors with low or high stromal signal were identified, but there was no correlation with the development of systemic metastases within 5 years. CONCLUSIONS: Both FNAB and CBX yield a similar quality and quantity of total RNA and are suitable for cDNA microarray analyses in approximately 70-75% of single-pass samples. Transcriptional profiles from FNAB and CBX of the same tumor generally are similar and are driven by the tumor cell population. The authors concluded that each technique has relative advantages. The FNABs provide transcriptional profiles that are a purer representation of the tumor cell population, whereas transcriptional profiles from CBXs include more representation from nonlymphoid stromal elements. Selection of the preferred needle biopsy sampling technique for genomic studies of breast carcinomas should depend on whether variable stromal gene expression is desirable in the samples.

A detailed evaluation of cardiac toxicity: a phase II study of doxorubicin and one- or three-hour-infusion paclitaxel in patients with metastatic breast cancer.

PURPOSE: This Phase II study was designed to determine the efficacy and toxicity of combination doxorubicin and paclitaxel as front-line treatment for metastatic breast cancer. EXPERIMENTAL DESIGN: Eligible patients had no prior anthracycline or taxane therapy and normal cardiac function. They were treated with bolus doxorubicin 60 mg/m2, followed by paclitaxel 200 mg/m2, as either 1- or 3-h infusions for six to seven cycles. Single-agent paclitaxel was continued thereafter. Serial multiple gated acquisition scans were performed, and endomyocardial biopsies were performed for consenting patients. RESULTS: Eighty-two patients were enrolled with a median age of 53 years (range, 32-78 years). Of 79 evaluable patients, 58.2% had an objective response (3.8% complete response + 54.4% partial response), 34.2% had stable disease, and 7.6% had progressive disease. With median follow-up of 37.5 months, median time to progression was 7 months; median survival was 31 months. Multiple gated acquisition scans were performed in 82 of 82 patients at baseline, 75 of 82 patients at a total doxorubicin dose of 60-180 mg/m2, 62 of 68 patients at 200-300 mg/m2, 18 of 52 patients at 310-360 mg/m2, and 4 of 8 patients at 420 mg/m2. Median ejection fractions were 62.5, 60, 57.5, 52.5, and 32%, respectively. Fifteen of 82 (18.3%) patients had a decrease in ejection fraction > or = 15% to an absolute ejection fraction < or = 50%. Eight of these 15 patients (53%) developed clinical congestive heart failure: 4 of 8 (50%) who received a total doxorubicin dose of 420 mg/m2 versus 4 of 74 (5.4%) who received a dose < or = 360 mg/m2 (P = 0.002). CONCLUSIONS: When the doxorubicin dose exceeds 360 mg/m2, the combination of bolus doxorubicin and paclitaxel presents unacceptable cardiac risk.

Juvenile myelomonocytic leukemia: analyses of treatment results in the EORTC Children's Leukemia Cooperative Group (CLCG).

Forty-six children with juvenile myelomonocytic leukemia (JMML) diagnosed between 1978 and 1993 in 12 centers were retrospectively studied. There is no evidence that any conventional treatment influences the long-term evolution of JMML. Among 28 patients treated without bone marrow transplantation (BMT), 26 died (median survival: 17 months), two are alive, one in complete remission (CR) after intensive chemotherapy. Allogenic BMT is the best treatment: 18 patients underwent BMT, 11 are in CR (at 9, 15, 22, 25, 41, 45, 49, 53, 66, 90 and 108 months). Conditioning regimens using chemotherapy alone may cure some patients (3/6) occasionally despite autologous reconstitution (1/3); if relapse occurs, a second BMT may be curative (2/3). Among the 12 patients conditioned immediately with TBI, six are in CR, one is in relapse, five died (one of them in durable autologus CR from Schwannoma). It is our opinion that splenectomy is of therapeutic value and seems not to have influenced the incidence of infections complications. We found no argument in favor of intensive chemotherapy before conditioning. Results with HLA-matched unrelated donors are satisfactory. One patient relapsed at 4 months after an unrelated BMT and entered a new CR after discontinuation of cyclosporine.