Dataset Information

Association of Gallbladder Mucocele Histologic Diagnosis with Selected Drug Use in Dogs: A Matched Case-Control Study.

ABSTRACT:

Background

The cause of gallbladder mucocele (GBM) formation in dogs currently is unknown. Many available drugs represent a newer generation of xenobiotics that may predispose dogs to GBM formation.

Objective

To determine if there is an association between the histologic diagnosis of GBM in dogs and administration of selected drugs.

Animals

Eighty-one dogs with a histologic diagnosis of GBM and 162 breed, age, and admission date-matched control dogs from a single referral institution.

Methods

Medical records of dogs with GBM and control dogs from 2001 to 2011 were reviewed. Owner verification of drug history was sought by a standard questionnaire. Reported use of heartworm, flea, and tick preventatives as well as nonsteroidal anti-inflammatory drugs, analgesics, corticosteroids, or medications for treatment of osteoarthritis was recorded.

Results

Dogs with GBM were 2.2 times as likely to have had reported use of thyroxine (as a proxy for the diagnosis of hypothyroidism) as control dogs (95% confidence interval [CI], 0.949-5.051), 3.6 times as likely to have had reported treatment for Cushing's disease (95% CI, 1.228-10.612), and 2.3 times as likely to have had reported use of products containing imidacloprid (95% CI, 1.094-4.723). Analysis of a data subset containing only Shetland sheepdogs (23 GBM and 46 control) indicated that Shetland sheepdogs with GBM formation were 9.3 times as likely to have had reported use of imidacloprid as were control Shetland sheepdogs (95% CI, 1.103-78.239).

Conclusions and clinical importance

This study provides evidence for an association between selected drug use and GBM formation in dogs. A larger epidemiologic study of Shetland sheepdogs with GBM formation and exposure to imidacloprid is warranted.

SUBMITTER: Gookin JL

PROVIDER: S-EPMC4895658 | biostudies-literature | 2015 Nov-Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Association of Gallbladder Mucocele Histologic Diagnosis with Selected Drug Use in Dogs: A Matched Case-Control Study.

Gookin J L JL Correa M T MT Peters A A Malueg A A Mathews K G KG Cullen J J Seiler G G

Journal of veterinary internal medicine 20151018 6

<h4>Background</h4>The cause of gallbladder mucocele (GBM) formation in dogs currently is unknown. Many available drugs represent a newer generation of xenobiotics that may predispose dogs to GBM formation.<h4>Objective</h4>To determine if there is an association between the histologic diagnosis of GBM in dogs and administration of selected drugs.<h4>Animals</h4>Eighty-one dogs with a histologic diagnosis of GBM and 162 breed, age, and admission date-matched control dogs from a single referral i ...[more]

PMID: 26478445

Similar Datasets

Project description:To date studies have not investigated the culture-independent microbiome of bile from dogs, a species where aseptic collection of bile under ultrasound guidance is somewhat routine. Despite frequent collection of bile for culture-based diagnosis of bacterial cholecystitis, it is unknown whether bile from healthy dogs harbors uncultivable bacteria or a core microbiota. The answer to this question is critical to understanding the pathogenesis of biliary infection and as a baseline to exploration of other biliary diseases in dogs where uncultivable bacteria could play a pathogenic role. A pressing example of such a disease would be gallbladder mucocele formation in dogs. This prevalent and deadly condition is characterized by excessive secretion of abnormal mucus by the gallbladder epithelium that can eventually lead to rupture of the gallbladder or obstruction of bile flow. The cause of mucocele formation is unknown as is whether uncultivable, and therefore unrecognized, bacteria play any systematic role in pathogenesis. In this study we applied next-generation 16S rRNA gene sequencing to identify the culture-negative bacterial community of gallbladder bile from healthy dogs and gallbladder mucus from dogs with mucocele formation. Integral to our study was the use of 2 separate DNA isolations on each sample using different extraction methods and sequencing of negative control samples enabling recognition and curation of contaminating sequences. Microbiota findings were validated by simultaneous culture-based identification, cytological examination of bile, and fluorescence in-situ hybridization (FISH) performed on gallbladder mucosa. Using culture-dependent, cytological, FISH, and 16S rRNA sequencing approaches, results of our study do not support existence of a core microbiome in the bile of healthy dogs or gallbladder mucus from dogs with mucocele formation. Our findings further document how contaminating sequences can significantly contribute to the results of sequencing analysis when performed on samples with low bacterial biomass.

Project description:Gallbladder mucocele formation is an emerging disease in dogs characterized by increased secretion of condensed granules of gel-forming mucin by the gallbladder epithelium and formation of an abnormally thick mucus that can culminate in obstruction of the bile duct or rupture of the gallbladder. The disease is associated with a high morbidity and mortality and its pathogenesis is unknown. Affected dogs have a significantly increased likelihood of concurrent diagnosis of hyperadrenocorticism, hypothyroidism, and hyperlipidemia. Whether these endocrinopathies represent coincidental primary disease processes that exacerbate gallbladder mucocele formation in predisposed dogs or reflect a concurrent disruption of endocrine and lipid metabolism is unclear. In this study, we investigated a hypothesis that dogs with gallbladder mucocele formation would have a high prevalence of occult and atypical abnormalities in adrenal cortical and thyroid gland function that would suggest the presence of endocrine disruption and provide deeper insight into disease pathogenesis. We performed a case-control study of dogs with and without ultrasonographic diagnosis of gallbladder mucocele formation and profiled adrenal cortical function using a quantitative mass spectrometry-based assay of serum adrenal-origin steroids before and after administration of synthetic cosyntropin. We simultaneously profiled serum thyroid hormone concentrations and evaluated iodine sufficiency by measurement of urine iodine:creatinine ratios (UICR). The studies were complemented by histological examination of archival thyroid tissue and measurements of thyroid gland organic iodine from dogs with gallbladder mucocele formation and control dogs. Dogs with gallbladder mucocele formation demonstrated an exaggerated cortisol response to adrenal stimulation with cosyntropin. A prevalence of 10% of dogs with gallbladder mucocele formation met laboratory-based criteria for suspect or definitive diagnosis of hyperadrenocorticism. A significantly greater number of dogs with gallbladder mucocele formation had basal serum dehydroepiandrosterone (DHEAS) increases compared to control dogs. A high percentage of dogs with gallbladder mucocele formation (26%) met laboratory-based criteria for diagnosis of hypothyroidism, but lacked detection of anti-thyroglobulin antibodies. Dogs with gallbladder mucocele formation had significantly higher UICRs than control dogs. Examination of thyroid tissue from an unrelated group of dogs with gallbladder mucocele formation did not demonstrate histological evidence of thyroiditis or significant differences in content of organic iodine. These findings suggest that dogs with gallbladder mucocele formation have a greater capacity for cortisol synthesis and pinpoint DHEAS elevations as a potential clue to the underlying pathogenesis of the disease. A high prevalence of thyroid dysfunction with absent evidence for autoimmune thyroiditis suggest a disrupted thyroid hormone metabolism in dogs with gallbladder mucocele formation although an influence of non-thyroidal illness cannot be excluded. High UICR in dogs with gallbladder mucocele formation is of undetermined significance, but of interest for further study.

Project description:Gallbladder mucocele (GBM) is a common biliary disorder in dogs. Gallbladder hypokinesia has been proposed to contribute to its formation and progression. The specific cause of gallbladder stasis in dogs with GBM as well as viable treatment options to resolve dysmotility remains unknown. Vitamin D deficiency is one of the many potential causes of gallbladder hypokinesia in humans and repletion results in complete resolution of stasis. Improving our understanding of the relationship between serum vitamin D and GBM could help identify dogs as a model for humans with gallbladder hypokinesia. Furthermore, this relationship could provide insight into the pathogenesis of GBM and support the need for future studies to investigate vitamin D as a novel treatment target. Therefore, goals of this study were i) to determine if serum 25-hydroxyvitamin(OH)D concentrations were decreased in dogs with GBM, ii) if serum 25(OH)D concentrations were different in clinical versus dogs subclinical for GBM, and iii) to determine if serum 25(OH)D concentrations could predict the ultrasonographic type of GBM. Sixty-two dogs (clinical, n = 26; subclinical, n = 36) with GBM and 20 healthy control dogs were included in this prospective observational study. Serum 25(OH)D concentrations were measured with a competitive chemiluminescence immunoassay. Overall, dogs with GBM had lower serum 25(OH)D concentrations than control dogs (P = 0.004). Subsequent subgroup analysis indicated that this difference was only significant in the subclinical group compared to the control dogs (P = 0.008), and serum 25(OH)D concentrations did not significantly differ between dogs clinical for GBM versus subclinical or control dogs, indicating that inflammatory state in clinical dogs was not the major constituent of the observed findings. Decreasing serum 25(OH)D concentrations, but not clinical status, was associated with a more advanced developmental stage of GBM type determined by ultrasonography. Our results indicate that vitamin D has a role in dogs with GBM. Additional studies are needed to assess if reduced vitamin D in dogs with GBM is a cause or effect of their biliary disease and to investigate if vitamin D supplementation could be beneficial for dogs with GBM.

Project description:Mucocele formation is characterized by secretion of abnormally thick mucus by the gallbladder epithelium of dogs that may cause obstruction of the bile duct or rupture of the gallbladder. The disease is increasingly recognized and is associated with a high morbidity and mortality. The cause of gallbladder mucocele formation in dogs is unknown. There is a strong breed predisposition and affected dogs have a high incidence of concurrent endocrinopathy or hyperlipidemia. These observations suggest a significant influence of both genetic and metabolic factors on disease pathogenesis. In this study, we investigated a theory that mucocele formation is associated with a syndrome of metabolic disruption. We surmised that a global, untargeted metabolomics approach could provide unique insight into the systemic pathogenesis of gallbladder mucocele formation and identify specific compounds as candidate biomarkers or treatment targets. Moreover, concurrent examination of the serum and hepatic duct bile metabolome would enable the construction of mechanism-based theories or identification of specific compounds responsible for altered function of the gallbladder epithelium. Abnormalities observed in dogs with gallbladder mucocele formation, including a 33-fold decrease in serum adenosine 5'-monophosphate (AMP), lower quantities of precursors required for synthesis of energy transporting nucleotides, and increases in citric acid cycle intermediates, suggest excess metabolic energy and a carbon surplus. Altered quantities of compounds involved in protein translation and RNA turnover, together with accumulation of gamma-glutamylated and N-acetylated amino acids in serum suggest abnormal regulation of protein and amino acid metabolism. Increases in lathosterol and 7?-hydroxycholesterol suggest a primary increase in cholesterol synthesis and diversion to bile acid formation. A number of specific biomarker compounds were identified for their ability to distinguish between control dogs and those that formed a gallbladder mucocele. Particularly noteworthy was a significant decrease in quantity of biologically active compounds that stimulate biliary ductal fluid secretion including adenosine, cAMP, taurolithocholic acid, and taurocholic acid. These findings support the presence of significant metabolic disruption in dogs with mucocele formation. A targeted, quantitative analysis of the identified serum biomarkers is warranted to determine their utility for diagnosis of this disease. Finally, repletion of compounds whose biological activity normally promotes biliary ductal secretion should be examined for any therapeutic impact for resolution or prevention of mucocele formation.

Project description:ObjectivesThis study investigated patterns in health service usage among older adults with dementia and matched controls over a 10-year span from 5 years before until 5 years after diagnosis.DesignPopulation-based retrospective matched case-control study.SettingAdministrative health data of individuals in Saskatchewan, Canada from 1 April 2008 to 31 March 2019.ParticipantsThe study included 2024 adults aged 65 years and older living in the community at the time of dementia diagnosis from 1 April 2013 to 31 March 2014, matched 1:1 to individuals without a dementia diagnosis on age group, sex, rural versus urban residence, geographical region and comorbidity.Outcome measuresFor each 5-year period before and after diagnosis, we examined usage of health services each year including family physician (FP) visits, specialist visits, hospital admissions, all-type prescription drug dispensations and short-term care admissions. We used negative binomial regression to estimate the effect of dementia on yearly average health service utilisation adjusting for sex, age group, rural versus urban residence, geographical region, 1 year prior health service use and comorbidity.ResultsAdjusted findings demonstrated that 5 years before diagnosis, usage of all health services except hospitalisation was lower among persons with dementia than persons without dementia (all p<0.001). After this point, differences in higher health service usage among persons with dementia compared to without dementia were greatest in the year before and year after diagnosis. In the year before diagnosis, specialist visits were 59.7% higher (p<0.001) and hospitalisations 90.5% higher (p<0.001). In the year after diagnosis, FP visits were 70.0% higher (p<0.001) and all-type drug prescriptions 29.1% higher (p<0.001).ConclusionsFindings suggest the year before and year after diagnosis offer multiple opportunities to implement quality supports. FPs are integral to dementia care and require effective resources to properly serve this population.

Dataset Information

Association of Gallbladder Mucocele Histologic Diagnosis with Selected Drug Use in Dogs: A Matched Case-Control Study.

Background

Objective

Animals

Methods

Results

Conclusions and clinical importance

Publications

Association of Gallbladder Mucocele Histologic Diagnosis with Selected Drug Use in Dogs: A Matched Case-Control Study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets