Canine GM2‐Gangliosidosis Sandhoff Disease Associated with a 3‐Base Pair Deletion in the HEXB Gene

Background

GM2‐gangliosidosis is a fatal neurodegenerative lysosomal storage disease (LSD) caused by deficiency of either β‐hexosaminidase A (Hex‐A) and β‐hexosaminidase B (Hex‐B) together, or the GM2 activator protein. Clinical signs can be variable and are not pathognomonic for the specific, causal deficiency.

Objectives

To characterize the phenotype and genotype of GM2‐gangliosidosis disease in an affected dog.

Animals

One affected Shiba Inu and a clinically healthy dog.

Methods

Clinical and neurologic evaluation, brain magnetic resonance imaging (MRI), assays of lysosomal enzyme activities, and sequencing of all coding regions of HEXA, HEXB, and GM2A genes.

Results

A 14‐month‐old, female Shiba Inu presented with clinical signs resembling GM2‐gangliosidosis in humans and GM1‐gangliosidosis in the Shiba Inu. Magnetic resonance imaging (MRI) of the dog's brain indicated neurodegenerative disease, and evaluation of cerebrospinal fluid (CSF) identified storage granules in leukocytes. Lysosomal enzyme assays of plasma and leukocytes showed deficiencies of Hex‐A and Hex‐B activities in both tissues. Genetic analysis identified a homozygous, 3‐base pair deletion in the HEXB gene (c.618‐620delCCT).

Conclusions and Clinical Importance

Clinical, biochemical, and molecular features are characterized in a Shiba Inu with GM2‐gangliosidosis. The deletion of 3 adjacent base pairs in HEXB predicts the loss of a leucine residue at amino acid position 207 (p.Leu207del) supporting the hypothesis that GM2‐gangliosidosis seen in this dog is the Sandhoff type. Because GM1‐gangliosidosis also exists in this breed with almost identical clinical signs, genetic testing for both GM1‐ and GM2‐gangliosidosis should be considered to make a definitive diagnosis.     

Contrast‐Enhanced Ultrasound Examination for the Assessment of Renal Perfusion in Cats with Chronic Kidney Disease

Background

Contrast‐enhanced ultrasound examination (CEUS) is a functional imaging technique allowing noninvasive assessment of tissue perfusion. Studies in humans show that the technique holds great potential to be used in the diagnosis of chronic kidney disease (CKD). However, data in veterinary medicine are currently lacking.

Objectives

To evaluate renal perfusion using CEUS in cats with CKD.

Animals

Fourteen client‐owned cats with CKD and 43 healthy control cats.

Methods

Prospective case‐controlled clinical trial using CEUS to evaluate renal perfusion in cats with CKD compared to healthy control cats. Time‐intensity curves were created, and perfusion parameters were calculated using off‐line software. A linear mixed model was used to examine differences between perfusion parameters of cats with CKD and healthy cats.

Results

In cats with CKD, longer time to peak and shorter mean transit times were observed for the renal cortex. In contrast, a shorter time to peak and rise time were seen for the renal medulla. The findings for the renal cortex indicate decreased blood velocity and shorter total duration of enhancement, likely caused by increased vascular resistance in CKD. Increased blood velocity in the renal medulla has not been described before and may be because of a different response to regulatory factors in cortex and medulla.

Conclusions and Clinical Importance

Contrast‐enhanced ultrasound examination was capable of detecting perfusion changes in cats with CKD. Further research is warranted to assess the diagnostic capabilities of CEUS in early stage of the disease process.     

Comparison of Single,Averaged, and Pooled Urine Protein:Creatinine Ratios in Proteinuric Dogs Undergoing Medical Treatment

Background

Monitoring urine protein:creatinine ratios (UPC ) in dogs with protein‐losing nephropathy (PLN ) is challenging because of day‐to‐day variation in UPC results.

Hypothesis/Objectives

Determine whether single, averaged, or pooled samples from PLN dogs receiving medical treatment yield comparable UPC s, regardless of degree of proteinuria.

Animals

Twenty‐five client‐owned PLN dogs receiving medical treatment.

Methods

UPC ratios were prospectively measured in each dog utilizing 3 methods: single in‐hospital sample (day 3), average sample (days 1–3), and pooled sample (equal pooling of urine from days 1–3). Bland‐Altman analysis was performed to evaluate agreement between methods for all dogs, as well as in subgroups of dogs (UPC ≤4 or UPC >4).

Results

For all dogs, Bland‐Altman log‐transformed 95% limits of agreement were ?0.07–0.18 (single versus pooled UPC ), ?0.06–0.16 (single versus average UPC ), and ?0.06–0.04 (pooled versus average UPC ). For dogs with UPC ≤4, Bland‐Altman 95% limits of agreement were ?0.42–0.82 (single versus pooled UPC ), ?0.38–0.76 (single versus average UPC ), and ?0.27–0.25 (pooled versus average UPC ). For dogs with UPC >4, Bland‐Altman 95% limits of agreement were ?0.17–2.4 (single versus pooled UPC ), ?0.40–2.2 (single versus average UPC ), and ?0.85–0.43 (pooled versus average UPC ).

Conclusions and Clinical Importance

UPC ratios from all methods were comparable in PLN dogs receiving medical treatment. In PLN dogs with UPC >4, more variability between methods exists likely because of higher in‐hospital results, but whether this finding is clinically relevant is unknown.

     

The Gastrointestinal Microbiome: A Review

The gastrointestinal microbiome is a diverse consortium of bacteria, archaea, fungi, protozoa, and viruses that inhabit the gut of all mammals. Studies in humans and other mammals have implicated the microbiome in a range of physiologic processes that are vital to host health including energy homeostasis, metabolism, gut epithelial health, immunologic activity, and neurobehavioral development. The microbial genome confers metabolic capabilities exceeding those of the host organism alone, making the gut microbiome an active participant in host physiology. Recent advances in DNA sequencing technology and computational biology have revolutionized the field of microbiomics, permitting mechanistic evaluation of the relationships between an animal and its microbial symbionts. Changes in the gastrointestinal microbiome are associated with diseases in humans and animals including inflammatory bowel disease, asthma, obesity, metabolic syndrome, cardiovascular disease, immune‐mediated conditions, and neurodevelopmental conditions such as autism spectrum disorder. While there remains a paucity of data regarding the intestinal microbiome in small animals, recent studies have helped to characterize its role in host animal health and associated disease states. This review is intended to familiarize small animal veterinarians with recent advances in the field of microbiomics and to prime them for a future in which diagnostic tests and therapies will incorporate these developments into clinical practice.     

Retrospective Evaluation of the Effect of Heart Rate on Survival in Dogs with Atrial Fibrillation

Background

Atrial fibrillation (AF) usually is associated with a rapid ventricular rate. The optimal heart rate (HR) during AF is unknown.

Hypothesis/Objectives

Heart rate affects survival in dogs with chronic AF.

Animals

Forty‐six dogs with AF and 24‐hour ambulatory recordings were evaluated.

Methods

Retrospective study. Holter‐derived HR variables were analyzed as follows: mean HR (meanHR, 24‐hour average), minimum HR (minHR, 1‐minute average), maximum HR (maxHR, 1‐minute average). Survival times were recorded from the time of presumed adequate rate control. The primary endpoint was all‐cause mortality. Cox proportional hazards analysis identified variables independently associated with survival; Kaplan‐Meier survival analysis estimated the median survival time of dogs with meanHR <125 bpm versus ≥125 bpm.

Results

All 46 dogs had structural heart disease; 31 of 46 had congestive heart failure (CHF), 44 of 46 received antiarrhythmic drugs. Of 15 dogs with cardiac death, 14 had CHF. Median time to all‐cause death was 524 days (Interquartile range (IQR), 76–1,037 days). MeanHR was 125 bpm (range, 62–203 bpm), minHR was 82 bpm (range, 37–163 bpm), maxHR was 217 bpm (range, 126–307 bpm). These were significantly correlated with all‐cause and cardiac‐related mortality. For every 10 bpm increase in meanHR, the risk of all‐cause mortality increased by 35% (hazard ratio, 1.35; 95% CI, 1.17–1.55; P < 0.001). Median survival time of dogs with meanHR<125 bpm (n = 23) was significantly longer (1,037 days; range, 524‐open) than meanHR ≥125 bpm (n = 23; 105 days; range, 67–267 days; P = 0.0012). Mean HR was independently associated with all‐cause and cardiovascular mortality (P < 0.003).

Conclusions and Clinical Importance

Holter‐derived meanHR affects survival in dogs with AF. Dogs with meanHR <125 bpm lived longer than those with meanHR ≥ 125 bpm.     

Computed Tomographic Angiography of the Pancreas in Cats with Chronic Diabetes Mellitus Compared to Normal Cats

Background

Diabetes mellitus (DM) is a common endocrinopathy in cats. No known diagnostic test or patient characteristic at the time of diagnosis can predict likely disease course, unlike in people in whom computed tomographic angiography (CTA) is used. No published data exist regarding the CTA appearance of the pancreas in cats with DM, and thus, it is unknown what if any CTA variables should be further assessed for associations with pancreatic endocrine function.

Hypothesis/Objectives

A significant difference in pancreatic attenuation, volume, and size will be identified between normal cats and those with chronic DM on CTA.

Animals

Ten healthy control cats and 15 cats with naturally occurring DM present for >12 months.

Methods

Prospective cross‐sectional study comparing pancreatic attenuation, enhancement pattern, size, volume, pancreatic volume‐to‐body weight ratio (V:BW), pancreatic arterial: portal phase ratio (A:P), time‐to‐arterial enhancement, and time‐to‐peak portal enhancement on CTA between sedated healthy control cats and those with chronic DM.

Results

The pancreas in cats with chronic DM was significantly larger, had higher volume, higher V:BW, and shorter time‐to‐peak portal enhancement on CTA when compared to normal cats.

Conclusions and Clinical Importance

Peak portal enhancement time, pancreatic size, pancreatic volume, and V:BW can be used to differentiate normal sedated cats from those with chronic DM by CTA. These variables warrant further investigation to identify possible associations with endocrine function.     

Spectrophotometry and Ultracentrifugation for Measurement of Plasma Lipids in Dogs with Diabetes Mellitus

Background

There are conflicting reports of plasma lipoprotein lipid content in dogs with diabetes mellitus (DM).

Objectives

To determine lipoprotein lipid content of plasma of dogs with DM by spectrophotometry and ultracentrifugation; to compare lipoprotein lipid content in diabetic and healthy dogs; and to quantify apolipoprotein B‐100 (ApoB) in dogs with DM.

Animals

22 dogs with DM and 9 healthy dogs.

Methods

Cross‐sectional study. Triglyceride (TG), total cholesterol (TC), and high‐density lipoprotein cholesterol (HDL‐C) concentrations were measured by spectrophotometry. Very low‐density lipoprotein cholesterol (VLDL‐C) and low‐density lipoprotein cholesterol (LDL‐C) concentrations were calculated after ultracentrifugation. Non‐HDL‐C cholesterol was calculated by subtracting HDL‐C from TC. ApoB was quantified by ELISA. The Mann‐Whitney test was used for comparison of median lipoprotein concentrations, and Spearman's correlation was used to assess associations between ApoB and lipoprotein fractions.

Results

All values are reported in mg/dL. Median TG (122), TC (343.5), HDL‐C, (200), VLDL‐C, (27) LDL‐C (68), non‐HDL‐C (114), and ApoB (320) were significantly higher in dogs with DM, compared to healthy dogs (57, 197, 168, 12, 16, 31, and 258, respectively, P‐values 0.0079, <0.001, 0.029, 0.011, <0.001, <0.001, 0.025, respectively). A significant association was found between ApoB and LDL‐C (Spearman's rho = 0.41, P = 0.022) and between ApoB and non‐HDL‐C (Spearman's rho = 0.40, P = 0.027).

Conclusions and Clinical Importance

Dyslipidemia of dogs with DM is characterized by pronounced increases in LDL‐C and non‐HDL‐C concentrations, although all lipoprotein fractions are significantly increased. Knowledge of specific lipoprotein fraction alterations in dogs with DM can enhance treatment options for diabetic dyslipidemia in dogs.     

Finding best exotic breed proportion in crossbred lactating sheep kept under farmers’ conditions in Ethiopia determined by use of nested Legendre polynomials with limited data

ABSTRACT

The present study was conducted to estimate milk production performance and fit lactation curves for groups of ewes of Local and of Awassi crosses, with a variable blood level, reared under farmer’s environment. The Weigh-Suckle-Weigh method plus hand milking was used to estimate milk yield for ewes. A total of 466 observations from 115 ewes were used. Estimated least-squares adjusted means for the milk production over 120 days were 0.56?kg day^?1 (Local), 0.67 (<30% Awassi), 0.86 (30–50% Awassi), and 0.96 (>50% Awassi). Groups with 30–50% Awassi and >50% Awassi ewes produced significantly (p?<?0.05) more milk than Local ewes. Significant differences were observed between <30% Awassi and >50% Awassi crossbred groups. The best crosses (>50% Awassi) produced over 70% more milk than the local ewes which demonstrates the potential that exists in increasing milk production through the initiated crossbreeding programme with sheep in Ethiopia.     

Effects of three short-term pasture allocation methods on milk production,methane emission and grazing behaviour by dairy cows

Two short-term grazing experiments were conducted with Norwegian Red cows. In Exp 1, 24 cows were randomly assigned to one of the following three pasture allocation methods (PAM): weekly pasture allowance (7RG), grazing 1/7 of 7RG each day (1SG), or grazing as 1SG but had access to grazed part of the paddock within one week (1FG). In Exp 2, 7RG was shortened to 5 days (5RG). We hypothesized that PAM will affect sward quality, quantity, intake and production differently. Pasture chemical composition changed with advancing grazing days but were not different between treatments. Pasture intake, milk yield, and methane emission were not affected by PAM. In Exp 1, 7RG cows spent less time on grazing, whereas in Exp 2, 1FG cows spent longer on grazing than others. Patterns observed in sward quality, and behavioural and physiological adaptations of cows to short-term changes in nutrient supply may explain the observed effects.