An examination of five spatial disease clustering methodologies for the identification of childhood cancer clusters in Alberta, Canada.

Cluster detection is an important part of spatial epidemiology because it may help suggest potential factors associated with disease and thus, guide further investigation of the nature of diseases. Many different methods have been proposed to test for disease clusters. In this paper, we study five popular methods for detecting spatial clusters. These methods are Besag-Newell (BN), circular spatial scan statistic (CSS), flexible spatial scan statistic (FSS), Tango's maximized excess events test (MEET), and Bayesian disease mapping (BYM). We study these five different methods by analyzing a data set of malignant cancer diagnoses in children in the province of Alberta, Canada during 1983-2004. Our results show that the potential clusters are located in the south-central part of the province. Although, all methods performed very well to detect clusters, the BN and MEET methods identified local as well as general clusters.

Breed and site predispositions of dogs with atopic dermatitis: a comparison of five locations in three continents.

The objectives of this multicentre study were to analyse and compare breed predispositions and lesion distributions of 552 dogs diagnosed with atopic dermatitis from five different dermatologic referral centres located in Australia, Germany (2) and the United States (2). Breeds were compared with the canine population in the respective locations. Breed predispositions varied from geographical site, although golden retrievers and German shepherd dogs were predisposed in three of five practices. Lesions were present most commonly on the paws (62%), ventrum (51%), ears (48%) and face (39%). Various breeds had specific site predilections. Based on this study, breed predispositions can vary greatly both between continents and also between different locations on the same continent. In addition, some breeds showed predispositions for certain body sites which also varied in some instances with the geographical location.

Comparison of variance estimation approaches in a two-state Markov model for longitudinal data with misclassification.

We examine the behaviour of the variance-covariance parameter estimates in an alternating binary Markov model with misclassification. Transition probabilities specify the state transitions for a process that is not directly observable. The state of an observable process, which may not correctly classify the state of the unobservable process, is obtained at discrete time points. Misclassification probabilities capture the two types of classification errors. Variance components of the estimated transition parameters are calculated with three estimation procedures: observed information, jackknife, and bootstrap techniques. Simulation studies are used to compare variance estimates and reveal the effect of misclassification on transition parameter estimation. The three approaches generally provide similar variance estimates for large samples and moderate misclassification. In these situations, the resampling methods are reasonable alternatives when programming partial derivatives is not appealing. With smaller chains or higher misclassification probabilities, the bootstrap method appears to be the best choice.

Effect of omega-3 fatty acids on canine atopic dermatitis.

Twenty-nine dogs were included in a double-blinded, placebo-controlled, randomised trial and were orally supplemented for 10 weeks with either flax oil (200 mg/kg/day), eicosapentaenoic acid (50 mg/kg/day) and docosahexaenoic acid (35 mg/kg/day) in a commercial preparation, or mineral oil as a placebo. For each dog, clinical scores were determined based on a scoring system developed prior to the trial. Total omega-6 and omega-3 intake and the ratio of omega-6:omega-3 (omega-6:3) were calculated before and after the trial. The dogs' clinical scores improved in those supplemented with flax oil and the commercial preparation, but not in the placebo group. No correlation was identified between total fatty acid intake or omega-6:3 ratio and clinical scores. Based on the results of this study, the total intake of fatty acids or the omega-6:3 ratio do not seem to be the main factors in determining the clinical response.

A review of general hepatitis C virus lookbacks in Canada.

BACKGROUND AND OBJECTIVES: This article reviews the Canadian experience with general hepatitis C virus (HCV) lookback programmes. MATERIALS AND METHODS: Comprehensive literature searches were conducted in PubMed, Medline, HealthSTAR and EMBASE. In addition, bibliographic searches were performed on all retrieved articles, and provinces were contacted to determine whether they had performed general HCV lookbacks. RESULTS: Of the seven Canadian general HCV lookbacks identified, two focused specifically on the paediatric population. The proportion of transfused patients presumed to be alive varied from 48.9 to 97.5%. Between 55.3 and 99.1% of letters were successfully delivered. The proportion of patients tested for HCV and subsequently found to be HCV positive varied considerably (66.2-80.4% and 0.9-5.0%, respectively). Newly diagnosed patients represented 42-58% of cases identified. CONCLUSIONS: The Canadian general HCV lookback experience successfully identified previously undiagnosed HCV-positive patients, but the resources required to notify patients are high and the yield is relatively low. The effectiveness may be greatest in the paediatric population.

Zinc-responsive dermatosis in dogs: 41 cases and literature review.

Forty-one cases of zinc-responsive dermatosis in the dog are described. The Siberian husky was the predominant breed affected. Periocular crusts were the most common clinical sign and parakeratosis was noted in the skin biopsy specimens of all dogs. Treatment with oral zinc ameliorated the clinical signs in most dogs, but cases necessitating other treatments such as parenteral zinc or retinoids are reported. The authors recommend a starting dose of 2-3 mg kg-1 elemental zinc per day in the treatment of this disorder.

Clinicopathologic findings, sensitivity to house dust mites and efficacy of milbemycin oxime treatment of dogs with Cheyletiella sp. infestation.

Twenty-three dogs with positive skin scrapings for Cheyletiella sp. were treated with milbemycin oxime using a protocol approximating 2 mg kg-1 orally once weekly for three weeks. Nineteen of these dogs belonged to a household of 41 dogs and two dogs were in households with one other dog. All in-contact dogs were treated. Pre-treatment intradermal skin tests showed positive reactions to D. farinae in 13 dogs and to D. pteronyssinus in 12 dogs; these became negative post-treatment in four and seven dogs, respectively. All dogs showed a dramatic reduction in clinical signs one week after the third treatment. Eighteen dogs no longer had mites on skin scrapings, three had dead mites and two had deformed eggs. Recurrence of clinical signs necessitated two additional courses of the protocol in the multiple dog household and for a dog receiving immunosuppressive treatment for pemphigus foliaceus. Possible adverse reactions to the milbemycin (vomiting, lethargy) were noted once in two dogs.

Thiopurine methyltransferase in red blood cells of dogs, cats, and horses.

Our objective was to determine if thiopurine methyltransferase (TPMT), the enzyme important in the metabolism of azathioprine in human beings, is detectable in red blood cell lysates (RBCL) of healthy dogs, cats, and horses. Values for TPMT activity were determined from blood collected from 20 healthy dogs, cats, and horses. The TPMT activity in each animal's RBCL was determined using a radioenzymatic end point involving TPMT-facilitated metabolism of 6-mercaptopurine to 6-methylmercaptopurine (6-MMP). One unit of TPMT activity represents the formation of 1 nmol of 6-MMP per milliliter of packed red blood cells per hour of incubation at 37 degrees C. TPMT activity in RBCL was detectable in all species, with mean RBC values +/- standard deviation of 17.9 +/- 3.79 U/mL in dogs; 2.76 +/- 0.70 U/mL in cats; and 2.185 +/- 0.36 U/mL in horses. Values for TPMT in the 3 species were significantly (P < .05) different from one another. TPMT values for dogs were significantly higher than the other species, and TPMT values for cats were significantly higher than those for horses. We conclude that RBCL TPMT values are measurable in dogs. cats, and horses and that dogs have higher values than cats or horses. These findings are consistent with the lower tolerance for azathioprine in cats as compared with dogs. It remains to be determined whether RBCL TPMT values in these species correlate with TPMT activity in the liver, where most of the metabolization of azathioprine is believed to occur.

Pharmacokinetics of exogenous corticotropin in normal dogs, hospitalized dogs with non adrenal illness and adrenopathic dogs.

Corticotropin (ACTH) pharmacokinetics was assessed in 10 normal dogs receiving exogenous ACTH (0.5 U/kg, i.v.). A two-compartment open model was most appropriate for description of exogenous ACTH pharmacokinetics. The apparent distribution and elimination rate constants (alpha and beta) were 7.4 +/- 2.7 x 10(-2) min(-1) and 5.5 +/- 3.8 x 10(-3) min(-1), respectively. Area under the concentration-time curve (AUC) was 2.91 +/- 0.78 x 10(4) pg x min/mL, mean residence time (MRT) was 45.0 +/- 12.2 min, the distribution half-life (t1/2alpha) was 9.4 min (harmonic mean), and the elimination half-life (t1/2beta) was 128 min (harmonic mean). The total body clearance of ACTH (ClB) was 1.83 +/- 0.46 x 10(4) mL x min/kg and volume of distribution (Vd(area)) was 30 +/- 15 L/kg. Corticotropin pharmacokinetics was also assessed in 12 client owned dogs, six dogs with non adrenal illness (NAI) and six dogs with hyperadrenocorticism (HAC), receiving exogenous ACTH (0.5 U/kg, i.v.). For these patients, data was best fitted to a one-compartment open model. In dogs with NAI, the AUC was 6.23 +/- 0.62 x 10(5) pg x min/mL, MRT was 38.7 +/- 12 min, the apparent elimination rate constant (k(el)) was 0.26 +/- 0.0017 min(-1) elimination half-life was 26.7 min, ClB was 0.84 +/- 0.1 x 10(4) mL/min/kg, and Vd(area) was 31.9 +/- 5.7 L/kg. In dogs with HAC, AUC was 4.74 +/- 0.23 x 10(5) pg x min/mL, MRT was 20.4 min, k(el) was 0.034 +/- 0.009 min(-1), half-life was 20.4 min, CIB was 1.06 +/- 6.0 x 10(4) mL/min/kg and Vd(area) was 29.7 +/- 6.7 L/kg. Dogs with pituitary-dependent hyperadrenocorticism showed more rapid elimination and clearance of exogenous corticotropin than dogs with NAI.

The effect of levothyroxine treatment on resting energy expenditure of hypothyroid dogs.

Thirty adult, client-owned dogs were diagnosed with hypothyroidism based on history, physical examination findings, hematologic and biochemical abnormalities, thyrotropin (TSH) response testing, endogenous canine thyrotropin (cTSH) concentration, or both, and total serum thryoxine concentration. All dogs received levothyroxine (L-thyroxine) at an initial dose of 22 micrograms/kg PO sid in either a tablet (13 dogs) or chewable form (17 dogs). Energy expenditure of each dog during apparent rest was estimated with an open-flow indirect calorimetry system by determining the rates of carbon dioxide production and oxygen consumption. Energy expenditure of apparent rest (EE) was lower in untreated hypothyroid dogs compared with reference values for EE. After treatment with L-thyroxine, EE of the hypothyroid dogs was significantly (P < .05) higher than pretreatment values.

Primary cutaneous coccidioidomycosis and subsequent drug eruption to itraconazole in a dog.

Three weeks after traveling to Arizona, a 13-month-old, female Labrador retriever developed draining tracts in the right hind limb. Primary cutaneous coccidioidomycosis was diagnosed. Initial treatment with itraconazole resulted in exacerbation of clinical signs. Histopathology was suggestive of a cutaneous drug eruption. Discontinuation of the itraconazole caused resolution of the drug eruption. Successful treatment of the fungal infection was achieved using ketoconazole.

Surveillance of clustering near point sources.

Health authorities are often alerted to suspected cancer clusters near the vicinity of potential point sources by members of the public. A surveillance system, where administrative regions around the potential point sources are regularly monitored for high disease rates, would allow for responses which are easier to obtain, timelier, and less expensive than individual thorough investigations. The monitoring could be done by using the so-called 'focused' tests for detecting disease clustering. However, these tests, generally designed to detect clusters of a fixed size around the foci, are not particularly effective when dealing with administrative regions with substantial differences in populations. In this work, an approach which overcomes the problem to a certain extent is described. Here the selected cluster sizes are based on the populations of the administrative regions under examination. The approach is used to investigate whether cancer clustering appears in the vicinity of the pulp and paper mills in British Columbia for the years 1983-1989. The results indicate that the approach performs reasonably well in identifying cancer sites for which elevated risks have also been suggested in the epidemiologic literature. Consequently, this methodology could be utilized to provide guidance for further investigation even in the absence of local reports. Similarly, it could be readily utilized to provide timely responses to local reports.

Monoclonal gammopathy in a dog with chronic pyoderma.

A monoclonal gammopathy composed of immunoglobulin G, with concurrent light-chain proteinuria and generalized lymph node plasmacytosis, was associated with chronic pyoderma in a dog. A uniform population of plasma cells was observed cytologically and histologically in multiple lymph node specimens. A diagnosis of monoclonal gammopathy of unknown significance was eventually made by exclusion of other known causes of monoclonal gammopathy, resolution after antibiotic therapy, and no evidence of lymphoproliferative disease after 11 months of follow-up and subsequent necropsy. This report expands the diagnostic considerations for monoclonal gammopathies in the dog.

Sebaceous adenitis in dogs and results of treatment with isotretinoin and etretinate: 30 cases (1990-1994).

Medical records of 30 dogs with histologically confirmed sebaceous adenitis that were treated with isotretinoin or etretinate were reviewed. Akitas and Standard Poodles were overrepresented, compared with the general hospital population. Thirteen dogs had concurrent pyoderma. The retinoids were administered for a minimum of 2 months. Dosage for the 13 dogs treated with isotretinoin only ranged from 0.8 to 3.5 mg/kg of body weight/d (mean, 1.4 mg/kg/d). Dosage for the 10 dogs treated with etretinate only ranged from 0.7 to 1.8 mg/kg/d (mean, 1.1 mg/kg/d). Two dogs were first given isotretinoin (mean dosage, 1.5 mg/kg/d) and, when they did not respond, were subsequently given etretinate (mean dosage, 0.85 mg/kg/d). Five dogs were first given etretinate (mean dosage, 1 mg/kg/d) and, when they did not respond, were subsequently given isotretinoin (mean dosage, 1.6 mg/kg/d). For the 20 dogs treated with isotretinoin, 1 was lost to follow-up; 9 of the remaining 19 had a successful outcome (> 50% reduction in severity of scaling and extent of alopecia, compared with pretreatment appearance). For the 17 dogs treated with etretinate, 9 had a successful outcome. Outcome could not be predicted on the basis of clinical signs or histologic findings, and a prognosis could not be determined on the basis of whether sebaceous glands were evident histologically.

Management of otitis externa.

Otitis externa represents one of the most common reasons that pets are presented for veterinary attention. They are also some of the more frustrating entities practitioners are called on to deal with. Successful management depends on an understanding of the primary, predisposing, and perpetuating factors involved in the pathogenesis of otitis externa. Emphasis is then placed on establishing a diagnosis through physical examination, cytologic examination, culture and sensitivity testing, radiographs and biopsies. The general goals of management are to resolve, remove, or control primary factors, clean and dry the ear, reduce inflammation and resolve secondary infections. These goals are achieved through various cleaning techniques, topical, and systemic therapies. Therapeutic alternatives are given for otitis involving bacteria, Malassezia, otodectes, demodex, allergies, ceruminous disorders, the idiopathic inflammatory/hyperplastic otitis externa of cocker spaniels, "Swimmer's Ear", contact/irritant reactions, overtreatment, and concurrent otitis media.

Llama dermatology.

The purpose of this article is to add information to the many dermatologic topics initially discussed in the 1989 issue on llama medicine (normal anatomy; bacterial, fungal, ectoparasitic, immune-mediated, and zinc-responsive disease) and make mention of newly recognized diseases. Since 1989, it appears that one of the most common and perplexing groups of dermatoses seen at Colorado State University are hyperkeratotic/inflammatory dermatoses. These remain poorly understood. Idiopathic hyperkeratosis (zinc-responsive dermatosis) may be a true zinc deficiency or a keratinizing disorder responsive to supraphysiologic dosages of zinc supplementation. Idiopathic nasal/perioral hyperkeratotic/ inflammatory dermatosis (munge) and idiopathic necrolytic/neutrophilic/hyperkeratotic dermatosis bear clinical, histologic, and therapeutic similarities, and may be subsets of the same disease. Further studies (e.g., looking for metabolic derangements) are necessary to better answer these questions.

Use of isotretinoin and etretinate for the treatment of benign cutaneous neoplasia and cutaneous lymphoma in dogs.

The purpose of this study was to evaluate the synthetic retinoids isotretinoin and etretinate to treat dogs with intracutaneous cornifying epitheliomas (ICE), other benign skin neoplasias, and cutaneous lymphoma. Twenty-four dogs were used. All tumors were diagnosed by histologic examination. Ten dogs with multiple (at least 5) benign skin tumors (7 with ICE, 1 each with inverted papillomas, sebaceous adenomas and epidermal cysts) were treated with isotretinoin (n = 7) and/or etretinate (n = 5). Twelve dogs with cutaneous lymphoma were treated with isotretinoin, and 2 dogs with cutaneous lymphoma were initially treated with etretinate. Successful treatment with isotretinoin was achieved in 1 dog with ICE, 1 with inverted papillomas, and 1 with epidermal cysts. Partial improvement with isotretinoin was seen in 2 dogs with ICE. Successful treatment was achieved with etretinate in 4 dogs with ICE (Norwegian Elkhound was the predominant breed with ICE). Remission was achieved in 6 of the 14 dogs with cutaneous lymphoma. Adverse effects developed in 7 of the 24 dogs, so treatment was stopped in 2 dogs.

Feline gingivitis-stomatitis-pharyngitis.

Inflammatory conditions of the feline mouth are commonly encountered in small animal practice. Although the majority can be attributed to dental disease and a small percentage are due to autoimmune diseases, the eosinophilic granuloma complex, neoplasia, and other miscellaneous syndromes, many cases appear to be due to a gingivitis-stomatitis-pharyngitis complex, which is likely multifactorial in origin. Viruses, bacterial infection, diet, dental disease, oral conformation, genetic predisposition, hypersensitivities, immunoinsufficiencies, and other defects in oral defense mechanisms may all be contributory. The complexities of this syndrome have made it one of the most challenging diagnostic and therapeutic problems in feline medicine.

Investigation of antibodies to extractable nuclear antigens in dogs.

Determination of antibodies to specific nuclear antigens, termed extractable nuclear antigen (ENA), was investigated in healthy dogs and in dogs with autoimmune, inflammatory, and neoplastic diseases. Using a counterimmunoelectrophoresis method, the dogs' sera were tested for antibodies against the nuclear antigens single-stranded DNA, Sm, Ro, La, ribonucleoprotein, Scl, and proliferating cell nuclear antigen. Antibodies to the Ro antigen were found in 1 dog with discoid lupus erythematosus, in 1 dog with pemphigus erythematosus, and in 1 dog with facial pyoderma and chronic superficial keratitis. In 15 dogs, antibodies were detected to ENA, but the precipitin lines were too weak to identify the specific ENA. These antibodies were found in some dogs with systemic lupus erythematosus, discoid lupus erythematosus, pemphigus erythematosus, dermatomyositis, vitiligo, lymphoma; in the dog with facial pyoderma and chronic superficial keratitis; and in 1 healthy dog. The highest percentage of dogs with antibodies to ENA in a large series (greater than 8) of this study was in dogs with systemic lupus erythematosus (4 of 13; 31%).