Pyometra is one of the most common diseases in female dogs, presenting as purulent inflammation a... more Pyometra is one of the most common diseases in female dogs, presenting as purulent inflammation and bacterial infection of the uterus. On average 20% of intact female dogs are affected before 10 years of age, a proportion that varies greatly between breeds (3–66%). The clear breed predisposition suggests that genetic risk factors are involved in disease development. To identify genetic risk factors associated with the disease, we performed a genome-wide association study (GWAS) in golden retrievers, a breed with increased risk of developing pyometra (risk ratio: 3.3). We applied a mixed model approach comparing 98 cases, and 96 healthy controls and identified an associated locus on chromosome 22 (p = 1.2 × 10–6, passing Bonferroni corrected significance). This locus contained five significantly associated SNPs positioned within introns of the ATP-binding cassette transporter 4 (ABCC4) gene. This gene encodes a transmembrane transporter that is important for prostaglandin transport. ...
Supplemental material, DS1_JVDI_10.1177_10406387187931681 for Evaluation of an ELISA for metaneph... more Supplemental material, DS1_JVDI_10.1177_10406387187931681 for Evaluation of an ELISA for metanephrines in feline urine by Thanikul Srithunyarat, Anna Svensson, Sofia Hanås, Odd V. Höglund, Ragnvi Hagman, Inger Lilliehöök, Ulf Olsson, Ingrid Ljungvall, Jens Häggström, Bodil Ström Holst, Ann Pettersson and Katja Höglund in Journal of Veterinary Diagnostic Investigation
Catecholamines can be used to evaluate neuroendocrine tumors, stress, and potentially pain, but c... more Catecholamines can be used to evaluate neuroendocrine tumors, stress, and potentially pain, but catecholamines degrade rapidly. Their metabolites normetanephrine (NME) and metanephrine (ME) have better stability in urine. In cats, urine sampling in a home environment would be beneficial to reduce effects of clinical stress and simplify sampling. We evaluated a human urine ELISA for analysis of NME and ME in feline urine, and investigated the effects of acidification, cat tray pellets, and storage time at room temperature up to 8.5 h. In 26 feline urine samples, mean NME concentration was 192 ± 80 ng/mL, mean intra- and inter-assay CV was 6.5% and 4.2%, respectively, and spike recovery was 98–101%, but dilutional recovery was unsatisfactory. For ME, mean intra- and inter-assay CV was 10.2% and 4.1%, respectively. Mean urine ME concentration was 32.1 ± 18.3 ng/mL, close to the kit’s lowest standard, and spike recovery was 65–90%; the ELISA could not be validated for ME. The stability ...
Selective breeding for desirable traits in strictly controlled populations has generated an extra... more Selective breeding for desirable traits in strictly controlled populations has generated an extraordinary diversity in canine morphology and behaviour, but has also led to loss of genetic variation and random entrapment of disease alleles. As a consequence, specific diseases are now prevalent in certain breeds, but whether the recent breeding practice led to an overall increase in genetic load remains unclear. Here we generate whole genome sequencing (WGS) data from 20 dogs per breed from eight breeds and document a ~10% rise in the number of derived alleles per genome at evolutionarily conserved sites in the heavily bottlenecked cavalier King Charles spaniel breed (cKCs) relative to in most breeds studied here. Our finding represents the first clear indication of a relative increase in levels of deleterious genetic variation in a specific breed, arguing that recent breeding practices probably were associated with an accumulation of genetic load in dogs. We then use the WGS data to ...
Lack of confidence and self-efficacy are the main causes of negative emotions experienced by vete... more Lack of confidence and self-efficacy are the main causes of negative emotions experienced by veterinary students when performing surgery. A surgical training model (STM) was developed to test the hypothesis that practical training on an STM before performing live surgery would enhance the students' confidence. In addition, low-cost and easily accessible materials were used for the construction. In the STM, neodymium magnets that were detached if too much traction was applied were used to ensure careful tissue handling during ligation of the ovarian pedicles and cervix. A pilot study was performed to evaluate veterinary undergraduate students' confidence when using the STM before performing their first live feline ovariohysterectomy (OHE) as lead surgeon. The results showed that the students rated their confidence level higher after performing feline OHE if they had practiced with the STM before surgery. Voluntary written comments revealed that live surgery as a learning situ...
Traumatic bone fractures cause moderate to severe pain, which needs to be minimized for optimal r... more Traumatic bone fractures cause moderate to severe pain, which needs to be minimized for optimal recovery and animal welfare, illustrating the need for reliable objective pain biomarkers for use in a clinical setting. The objectives of this study were to investigate catestatin (CST) and vasostatin (VS) concentrations as two new potential biomarkers, and cortisol concentrations, scores of the short form of the Glasgow composite measure pain scale (CMPS-SF), and visual analog scale (VAS) in dogs suffering from traumatic bone fractures before and after morphine administration in comparison with healthy dogs. Fourteen dogs with hind limb or pelvic fractures and thirty healthy dogs were included. Dogs with fractures were divided into four groups according to analgesia received before participation. Physical examination, CMPS-SF, pain and stress behavior VAS scores were recorded in all dogs. Saliva and blood were collected once in healthy dogs and in dogs with fractures before and 35-70 mi...
Nova Scotia Duck Tolling Retrievers (NSDTRs) are a dog breed often affected by immune-mediated rh... more Nova Scotia Duck Tolling Retrievers (NSDTRs) are a dog breed often affected by immune-mediated rheumatic disease (IMRD), a disorder characterised by chronic stiffness and joint pain. Most, but not all, dogs with IMRD, have antinuclear antibodies (ANA), which are also commonly present in the autoimmune disease systemic lupus erythematosus (SLE). The clinical and diagnostic findings of IMRD indicate that it is an SLE-related disorder. C-reactive protein (CRP), an acute phase protein, is a quantitative marker of inflammation for many diseases and is used for diagnosing and monitoring systemic inflammation in both humans and dogs. However, in human SLE, CRP concentrations are often elevated but correlate poorly with disease activity; they can be low in individual patients with active disease. The aim of the study was to investigate CRP in a group of NSDTRs with the SLE-related disorder IMRD. The hypothesis was that CRP concentrations would be increased in dogs with IMRD compared to heal...
The neuroendocrine glycoprotein chromogranin A is a useful biomarker in humans for neuroendocrine... more The neuroendocrine glycoprotein chromogranin A is a useful biomarker in humans for neuroendocrine tumors and stress. Chromogranin A can be measured in both blood and saliva. The objective of this study was to investigate concentrations of and correlation between the chromogranin A epitopes catestatin and vasostatin in healthy dogs accustomed to the sample collection procedures. Blood and saliva samples were collected from 10 research Beagle dogs twice daily for 5 consecutive days, and from 33 privately-owned blood donor dogs in association with 50 different blood donation occasions. All dogs were familiar with sample collection procedures. During each sampling, stress behavior was scored by the same observer using a visual analog scale (VAS) and serum cortisol concentrations. Catestatin and vasostatin were analyzed using radioimmunoassays for dogs. The dogs showed minimal stress behavior during both saliva sampling and blood sampling as monitored by VAS scores and serum cortisol con...
Biomarkers representing sympathetic tone and the surgical stress response are measured to objecti... more Biomarkers representing sympathetic tone and the surgical stress response are measured to objectively evaluate surgical techniques and anaesthetic protocols. If a part of the intraoperative procedure is repeated on the contralateral organ, one animal may potentially serve as its own control and, if so, may minimize the problem of individual differences of the stress response to anaesthesia and surgery. This study aimed to investigate the use of chromogranin A for measurement of the intraoperative sympathetic tone. Additional aims were to investigate chromogranin A and cortisol as indicators of the intraoperative surgical stress response caused by repeated noxious stimuli in dogs subjected to ovariohysterectomy and thereby to investigate the possibility of one dog serving as its own control. Experiments were carried out on 10 dogs subjected to ovariohysterectomy. Perioperative blood samples (0-6) were collected after premedication, immediately before induction of anaesthesia (0), aft...
Clinical diagnostic criteria for sepsis (systemic inflammatory response syndrome caused by infect... more Clinical diagnostic criteria for sepsis (systemic inflammatory response syndrome caused by infection) are unspecific and, therefore, biomarkers for sepsis diagnosis are needed for appropriate treatment and patient survival. Pyometra, a common disease caused by bacterial infection of the uterus, results in sepsis in nearly 60% of cases in dogs. We used dogs with pyometra as a natural model for sepsis and collected serum samples from 39 dogs, of which 22 with pyometra and 17 healthy controls. Dogs with pyometra were further grouped into dogs with sepsis (n=18) and without sepsis (n=4). Serum concentrations of a panel of cytokines, including keratinocyte-derived chemokine (KC)-like, granulocyte-macrophages colony stimulating factor (GM-CSF), interleukin (IL)-2, IL-4, IL-6, IL-7, IL-8, IL-10, IL-15, IL-18, chemokine C-X-C motif ligand (CXCL)10 and tumor necrosis factor (TNF)-α, were measured using multiplex analyses. Serum C-reactive protein (CRP) levels were determined using an automated immunoturbidimetric assay. In addition to physical examination hematological and serum biochemical analyses were performed to evaluate the overall status of the dogs. Significantly higher concentrations of KC-like (757 vs 304pg/ml) were detected in dogs with pyometra as compared to healthy dogs. Within the pyometra group, dogs with sepsis compared to dogs without sepsis had a higher KC-like concentration (873 vs 300pg/ml). Hemoglobin levels were significantly lower in dogs with pyometra compared to healthy dogs, regardless of the presence or absence of sepsis, and correlated negatively with KC-like. KC-like concentrations correlated positively with CRP, number of hospitalization days, number of monocytes, concentrations of IL-8, and percentage band neutrophils. Our data suggest that bacterial infection triggers the expression of KC-like and further studies are warranted of KC-like as a possible biomarker for diagnosing sepsis and uterine bacterial infection in dogs.
Pyometra is one of the most common diseases in female dogs, presenting as purulent inflammation a... more Pyometra is one of the most common diseases in female dogs, presenting as purulent inflammation and bacterial infection of the uterus. On average 20% of intact female dogs are affected before 10 years of age, a proportion that varies greatly between breeds (3–66%). The clear breed predisposition suggests that genetic risk factors are involved in disease development. To identify genetic risk factors associated with the disease, we performed a genome-wide association study (GWAS) in golden retrievers, a breed with increased risk of developing pyometra (risk ratio: 3.3). We applied a mixed model approach comparing 98 cases, and 96 healthy controls and identified an associated locus on chromosome 22 (p = 1.2 × 10–6, passing Bonferroni corrected significance). This locus contained five significantly associated SNPs positioned within introns of the ATP-binding cassette transporter 4 (ABCC4) gene. This gene encodes a transmembrane transporter that is important for prostaglandin transport. ...
Supplemental material, DS1_JVDI_10.1177_10406387187931681 for Evaluation of an ELISA for metaneph... more Supplemental material, DS1_JVDI_10.1177_10406387187931681 for Evaluation of an ELISA for metanephrines in feline urine by Thanikul Srithunyarat, Anna Svensson, Sofia Hanås, Odd V. Höglund, Ragnvi Hagman, Inger Lilliehöök, Ulf Olsson, Ingrid Ljungvall, Jens Häggström, Bodil Ström Holst, Ann Pettersson and Katja Höglund in Journal of Veterinary Diagnostic Investigation
Catecholamines can be used to evaluate neuroendocrine tumors, stress, and potentially pain, but c... more Catecholamines can be used to evaluate neuroendocrine tumors, stress, and potentially pain, but catecholamines degrade rapidly. Their metabolites normetanephrine (NME) and metanephrine (ME) have better stability in urine. In cats, urine sampling in a home environment would be beneficial to reduce effects of clinical stress and simplify sampling. We evaluated a human urine ELISA for analysis of NME and ME in feline urine, and investigated the effects of acidification, cat tray pellets, and storage time at room temperature up to 8.5 h. In 26 feline urine samples, mean NME concentration was 192 ± 80 ng/mL, mean intra- and inter-assay CV was 6.5% and 4.2%, respectively, and spike recovery was 98–101%, but dilutional recovery was unsatisfactory. For ME, mean intra- and inter-assay CV was 10.2% and 4.1%, respectively. Mean urine ME concentration was 32.1 ± 18.3 ng/mL, close to the kit’s lowest standard, and spike recovery was 65–90%; the ELISA could not be validated for ME. The stability ...
Selective breeding for desirable traits in strictly controlled populations has generated an extra... more Selective breeding for desirable traits in strictly controlled populations has generated an extraordinary diversity in canine morphology and behaviour, but has also led to loss of genetic variation and random entrapment of disease alleles. As a consequence, specific diseases are now prevalent in certain breeds, but whether the recent breeding practice led to an overall increase in genetic load remains unclear. Here we generate whole genome sequencing (WGS) data from 20 dogs per breed from eight breeds and document a ~10% rise in the number of derived alleles per genome at evolutionarily conserved sites in the heavily bottlenecked cavalier King Charles spaniel breed (cKCs) relative to in most breeds studied here. Our finding represents the first clear indication of a relative increase in levels of deleterious genetic variation in a specific breed, arguing that recent breeding practices probably were associated with an accumulation of genetic load in dogs. We then use the WGS data to ...
Lack of confidence and self-efficacy are the main causes of negative emotions experienced by vete... more Lack of confidence and self-efficacy are the main causes of negative emotions experienced by veterinary students when performing surgery. A surgical training model (STM) was developed to test the hypothesis that practical training on an STM before performing live surgery would enhance the students' confidence. In addition, low-cost and easily accessible materials were used for the construction. In the STM, neodymium magnets that were detached if too much traction was applied were used to ensure careful tissue handling during ligation of the ovarian pedicles and cervix. A pilot study was performed to evaluate veterinary undergraduate students' confidence when using the STM before performing their first live feline ovariohysterectomy (OHE) as lead surgeon. The results showed that the students rated their confidence level higher after performing feline OHE if they had practiced with the STM before surgery. Voluntary written comments revealed that live surgery as a learning situ...
Traumatic bone fractures cause moderate to severe pain, which needs to be minimized for optimal r... more Traumatic bone fractures cause moderate to severe pain, which needs to be minimized for optimal recovery and animal welfare, illustrating the need for reliable objective pain biomarkers for use in a clinical setting. The objectives of this study were to investigate catestatin (CST) and vasostatin (VS) concentrations as two new potential biomarkers, and cortisol concentrations, scores of the short form of the Glasgow composite measure pain scale (CMPS-SF), and visual analog scale (VAS) in dogs suffering from traumatic bone fractures before and after morphine administration in comparison with healthy dogs. Fourteen dogs with hind limb or pelvic fractures and thirty healthy dogs were included. Dogs with fractures were divided into four groups according to analgesia received before participation. Physical examination, CMPS-SF, pain and stress behavior VAS scores were recorded in all dogs. Saliva and blood were collected once in healthy dogs and in dogs with fractures before and 35-70 mi...
Nova Scotia Duck Tolling Retrievers (NSDTRs) are a dog breed often affected by immune-mediated rh... more Nova Scotia Duck Tolling Retrievers (NSDTRs) are a dog breed often affected by immune-mediated rheumatic disease (IMRD), a disorder characterised by chronic stiffness and joint pain. Most, but not all, dogs with IMRD, have antinuclear antibodies (ANA), which are also commonly present in the autoimmune disease systemic lupus erythematosus (SLE). The clinical and diagnostic findings of IMRD indicate that it is an SLE-related disorder. C-reactive protein (CRP), an acute phase protein, is a quantitative marker of inflammation for many diseases and is used for diagnosing and monitoring systemic inflammation in both humans and dogs. However, in human SLE, CRP concentrations are often elevated but correlate poorly with disease activity; they can be low in individual patients with active disease. The aim of the study was to investigate CRP in a group of NSDTRs with the SLE-related disorder IMRD. The hypothesis was that CRP concentrations would be increased in dogs with IMRD compared to heal...
The neuroendocrine glycoprotein chromogranin A is a useful biomarker in humans for neuroendocrine... more The neuroendocrine glycoprotein chromogranin A is a useful biomarker in humans for neuroendocrine tumors and stress. Chromogranin A can be measured in both blood and saliva. The objective of this study was to investigate concentrations of and correlation between the chromogranin A epitopes catestatin and vasostatin in healthy dogs accustomed to the sample collection procedures. Blood and saliva samples were collected from 10 research Beagle dogs twice daily for 5 consecutive days, and from 33 privately-owned blood donor dogs in association with 50 different blood donation occasions. All dogs were familiar with sample collection procedures. During each sampling, stress behavior was scored by the same observer using a visual analog scale (VAS) and serum cortisol concentrations. Catestatin and vasostatin were analyzed using radioimmunoassays for dogs. The dogs showed minimal stress behavior during both saliva sampling and blood sampling as monitored by VAS scores and serum cortisol con...
Biomarkers representing sympathetic tone and the surgical stress response are measured to objecti... more Biomarkers representing sympathetic tone and the surgical stress response are measured to objectively evaluate surgical techniques and anaesthetic protocols. If a part of the intraoperative procedure is repeated on the contralateral organ, one animal may potentially serve as its own control and, if so, may minimize the problem of individual differences of the stress response to anaesthesia and surgery. This study aimed to investigate the use of chromogranin A for measurement of the intraoperative sympathetic tone. Additional aims were to investigate chromogranin A and cortisol as indicators of the intraoperative surgical stress response caused by repeated noxious stimuli in dogs subjected to ovariohysterectomy and thereby to investigate the possibility of one dog serving as its own control. Experiments were carried out on 10 dogs subjected to ovariohysterectomy. Perioperative blood samples (0-6) were collected after premedication, immediately before induction of anaesthesia (0), aft...
Clinical diagnostic criteria for sepsis (systemic inflammatory response syndrome caused by infect... more Clinical diagnostic criteria for sepsis (systemic inflammatory response syndrome caused by infection) are unspecific and, therefore, biomarkers for sepsis diagnosis are needed for appropriate treatment and patient survival. Pyometra, a common disease caused by bacterial infection of the uterus, results in sepsis in nearly 60% of cases in dogs. We used dogs with pyometra as a natural model for sepsis and collected serum samples from 39 dogs, of which 22 with pyometra and 17 healthy controls. Dogs with pyometra were further grouped into dogs with sepsis (n=18) and without sepsis (n=4). Serum concentrations of a panel of cytokines, including keratinocyte-derived chemokine (KC)-like, granulocyte-macrophages colony stimulating factor (GM-CSF), interleukin (IL)-2, IL-4, IL-6, IL-7, IL-8, IL-10, IL-15, IL-18, chemokine C-X-C motif ligand (CXCL)10 and tumor necrosis factor (TNF)-α, were measured using multiplex analyses. Serum C-reactive protein (CRP) levels were determined using an automated immunoturbidimetric assay. In addition to physical examination hematological and serum biochemical analyses were performed to evaluate the overall status of the dogs. Significantly higher concentrations of KC-like (757 vs 304pg/ml) were detected in dogs with pyometra as compared to healthy dogs. Within the pyometra group, dogs with sepsis compared to dogs without sepsis had a higher KC-like concentration (873 vs 300pg/ml). Hemoglobin levels were significantly lower in dogs with pyometra compared to healthy dogs, regardless of the presence or absence of sepsis, and correlated negatively with KC-like. KC-like concentrations correlated positively with CRP, number of hospitalization days, number of monocytes, concentrations of IL-8, and percentage band neutrophils. Our data suggest that bacterial infection triggers the expression of KC-like and further studies are warranted of KC-like as a possible biomarker for diagnosing sepsis and uterine bacterial infection in dogs.
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