The variety of phenotypes behind 'double outlet right ventricle': clinical and imaging presentations in four dogs and a cat.

This report describes five cases of double outlet right ventricle (DORV) in four dogs (aged 3-18 months, two males and two females) and a domestic shorthair cat (aged 6 months, female) who presented with various clinical signs including tachypnea (n = 5), exercise intolerance (n = 5), mucous cyanosis (n = 3), delayed growth (n = 2), and/or lethargy (n = 2). The represented canine breeds were poodle, Yorkshire terrier, Samoyed, and Shetland sheepdog. For all animals, echocardiography revealed marked aortic dextroposition with both arterial trunks totally arising from the right ventricle, associated with a ventricular septal defect and various other congenital abnormalities, including subvalvular aortic stenosis (n = 2), minor aortic insufficiency (n = 5), subvalvular pulmonic stenosis with pulmonary trunk hypoplasia (n = 1), patent ductus arteriosus (n = 1), minor mitral and/or tricuspid dysplasia (n = 3). Subsequent cardiac remodeling was characterized by marked right ventricular hypertrophy for all patients, associated with right ventricular and right atrial dilation for most of them (4/5). Two dogs died soon after the initial DORV diagnosis (i.e. after 24 h and two months). A surgical correction attempted for another dog confirmed the presence of a DORV associated with patent ductus arteriosus, but the animal died during the procedure from sudden cardiac arrest. The fourth dog underwent a contrast-enhanced retrospective electrocardiogram-gated multidetector computed tomography angiography under general anesthesia, which confirmed the conotruncal malformation. Despite episodes of exercise intolerance, this dog is still alive, at the age of 53 months, as is the cat at the age of 21 months.

Successful transcatheter pulmonary valve implantation in a dog: first clinical report.

Transcatheter pulmonary valve (TPV) implantation is a therapeutic approach approved by the United States Food and Drug Administration for human patients with failing pulmonary conduits in 2010 and for failing bioprosthetic surgical pulmonary valves in 2017. We report here the first successful transcatheter implantation of a stented valve in a pulmonary position in a dog with congenital pulmonary valve disease. A 3-year-old, 10.9 kg, client-owned Beagle dog was referred for a follow-up visit after a percutaneous balloon valvuloplasty performed 22 months before for treatment of a severe type A valvular pulmonary stenosis. The Doppler-derived peak pressure gradient was 348 mmHg before the procedure and 66 mmHg 24 h after. The dog was lethargic. Echocardiography revealed a mild pulmonary stenosis (pressure gradient-43 mmHg), severe pulmonary regurgitation, and secondary severe right ventricular and right atrial dilation. Worsening of right heart dilation was observed 2 months later despite medical therapy. A TPV implantation was performed using a prestented Melody bovine jugular bioprosthetic valve. The dog recovered uneventfully and was discharged 10 days after the procedure. Right heart dilation resolved within 15 days. The dog was doing well 7 months after valve implantation. This case demonstrates that TPV implantation with a stented valve is technically feasible in dogs with severe pulmonary valve disease. Stringent postoperative care, with particular attention to thrombosis and infectious endocarditis, and appropriate sizing and positioning of the valve stent are keys to the success of this procedure.

Humoral immunity response to human endogenous retroviruses K/W differentiates between amyotrophic lateral sclerosis and other neurological diseases.

BACKGROUND AND PURPOSE: Human endogenous retroviruses (HERV) K/W seem to play a role in fostering and exacerbation of some neurological diseases, including amyotrophic lateral sclerosis (ALS). Given these findings, the immunity response against HERV-K and HERV-W envelope surface (env-su) glycoprotein antigens in serum and cerebrospinal fluid (CSF) was investigated for ALS, multiple sclerosis (MS) and Alzheimer's disease patients and in healthy controls. METHODS: Four antigenic peptides derived respectively from HERV-K and HERV-W env-su proteins were studied in 21 definite or probable ALS patients, 26 possible or definite relapsing-remitting MS patients, 18 patients with Alzheimer's disease and 39 healthy controls. An indirect enzyme-linked immunosorbent assay was set up to detect specific antibodies (Abs) against env-su peptides. RESULTS: Amongst the measured levels of Abs against the four different HERV-K peptide fragments, only HERV-K env-su19-37 was significantly elevated in ALS compared to other groups, both in serum and CSF. Instead, amongst the Abs levels directed against the four different HERV-W peptide fragments, only HERV-W env-su93-108 and HERV-W env-su248-262 were significantly elevated, in the serum and CSF of the MS group compared to other groups. In ALS patients, the HERV-K env-su19-37 Abs levels were significantly correlated with clinical measures of disease severity, both in serum and CSF. CONCLUSIONS: Increased circulating levels of Abs directed against the HERV-W env-su93-108 and HERV-W env-su248-262 peptide fragments could serve as possible biomarkers in patients with MS. Similarly, increased circulating levels of Abs directed against the HERV-K env-su19-37 peptide fragment could serve as a possible early novel biomarker in patients with ALS.

Systemic arterial hypertension secondary to chronic kidney disease in two captive-born large felids.

Systemic arterial hypertension (SHT) has been widely described in the domestic cat (Felis catus). In these feline patients, SHT is considered as the most common vascular disorder of middle-aged to older animals, and secondary SHT related to chronic kidney disease (CKD) represents the most common form of the disease. We describe here the first two cases of spontaneous SHT in large felids, i.e. one 18-year old, 34.4 kg, male North-Chinese leopard (Panthera pardus japonensis, case #1) and one 20-year old, 28.7 kg, female snow leopard (Panthera uncia, case #2), both captive-bred and previously diagnosed with CKD. Both animals underwent complete echocardiographic examination under general anesthesia due to abnormal cardiac auscultation (heart murmur and/or gallop sound), and recurrent lethargy in case #1. The combination of left ventricular remodeling with moderate aortic regurgitation of high velocity was highly suggestive of SHT, which was confirmed by indirect blood pressure measurement (systolic arterial blood pressure of 183 mmHg for case #1 and 180 mmHg for case #2). Amlodipine was prescribed (0.35-0.70 mg/kg/day orally) for 31 and 6 months respectively after the initial diagnosis. In case #1, concurrent amlodipine and benazepril treatment was associated with decreased heart murmur grade and reduced aortic insufficiency severity. These reports illustrate that, similarly to domestic cats, SHT should be suspected in old large felids with CKD and that amlodipine is a well-tolerated antihypertensive drug in these species.

Antemortem diagnosis of a left auricular appendage herniation through a partial pericardial defect in a dog with degenerative mitral valve disease.

INTRODUCTION: A 14-year-old neutered male crossbreed dog was presented for weakness, cough and weight loss. Cardiac auscultation revealed tachycardia, arrhythmia and a grade V/VI left apical systolic heart murmur. Thoracic radiographs showed a large homogeneous soft tissue opacity in close contact with the cardiac silhouette in the left cranioventral mediastinum. Cardiac evaluation showed atrial fibrillation, degenerative mitral valve disease and a dilated left auricular appendage outside the pericardium consistent with herniation through a partial pericardial defect. Seven months after diagnosis, an atrial septal defect secondary to acquired atrial septal rupture was identified. The dog was euthanized thirteen months after initial presentation because of unresponsive clinical signs of congestive heart failure.

Involvement of IL-6 and IL-1 receptor antagonist on intellectual disability.

Imbalances in the regulation of pro-inflammatory cytokines have been increasingly correlated with several neurodevelopmental disorders and their role in neuronal development is being investigated. To assess the possible influence of cytokines on the onset of intellectual disability (ID), we studied the polymorphisms of thirteen proinflammatory cytokine genes in 81 patients and 61 healthy controls. We demonstrated a significant association of interleukin-6 (IL-6) single-nucleotide polymorphism (SNP) (-174 G/C and nt565 G/A), and interleukin-1 receptor antagonist (IL-1RA) (Mspa-I 11100) SNP with ID. Moreover, the IL-6 SNPs is an unfavorable genetic predisposition for females. The evaluation of circulating levels of IL-6 and IL-1RA showed that the serum concentrations of IL-6 were significantly higher in ID patients than in controls. These data suggest that functional cytokine gene polymorphisms may influence the development of ID.

Systolic arterial blood pressure in small-breed dogs with degenerative mitral valve disease: a prospective study of 103 cases (2007-2012).

The objective of this prospective observational study was to assess systolic arterial blood pressure (SABP) in small-breed dogs with degenerative mitral valve disease (MVD) from different International Small Animal Cardiac Health Council (ISACHC) heart failure classes. For this purpose, 103 client-owned dogs weighing <20 kg (mean ± standard deviation, 8.5 ± 3.0 kg; aged 9.8 ± 2.9 years) and presenting with MVD diagnosed by echo-Doppler examination were enrolled. Nineteen healthy dogs (9.9 ± 2.3 years; 8.7 ± 4.2 kg) were concurrently recruited as controls. SABP was measured in unsedated dogs using the Doppler method according to the recommendations in the American College of Veterinary Medicine consensus statement. SABP was significantly increased in dogs in ISACHC class 1 (n=53; median, interquartile range 140 mmHg, 130-150 mmHg) and class 2 (n=21; 140 mmHg, 130-150 mmHg), compared to the control group (n=19; 130 mmHg, 120-140 mmHg; P<0.01 and P<0.05, respectively), but remained within the reference interval (≤ 160 mmHg). Conversely, dogs in ISACHC class 3 showed a significantly lower SABP (n=29, 120 mmHg, 110-130 mmHg) than those from all other ISACHC classes (P<0.001) and the controls (P<0.05). Additionally, SABP<120 mmHg was recorded in 13/103 dogs (13%). The 13 dogs were all ISACHC class 3 (3a or 3b) and were under medical treatment for heart failure. In conclusion, MVD was often associated with SABP values that were within the reference interval, but at its upper end. However, a significant decrease in SABP was observed in dogs with ISACHC heart failure class 3. Whether such low SABP values resulted from an MVD-related decrease in cardiac output, an afterload reduction owing to cardiac treatment, or both, remains to be determined.

Effects of dietary salt intake on renal function: a 2-year study in healthy aged cats.

BACKGROUND: Increasing salt intake to promote diuresis has been suggested in the management of feline lower urinary tract disease. However, high dietary salt intake might adversely affect blood pressure and renal function. OBJECTIVES: The objective of this study was to assess the long-term effects of increased salt intake on renal function in healthy aged cats. METHODS: This study was controlled, randomized, and blinded. Twenty healthy neutered cats (10.1 ± 2.4 years) were randomly allocated into 2 matched groups. One group was fed a high salt diet (3.1 g/Mcal sodium, 5.5 g/Mcal chloride) and the other a control diet of same composition except for salt content (1.0 g/Mcal sodium, 2.2 g/Mcal chloride). Clinical examination, glomerular filtration rate, blood pressure measurement, cardiac and kidney ultrasonography, and urinary and blood tests were performed before and over 24 months after diet implementation. Statistics were performed using a general linear model. RESULTS: Sixteen cats completed the 2 year study. The only variables affected by dietary salt intake were plasma aldosterone and urinary sodium/creatinine ratio, respectively, higher and lower in the control group all over the study period and urinary specific gravity, lower in the high salt diet group at 3 months. CONCLUSIONS AND CLINICAL IMPORTANCE: Glomerular filtration rate (GFR), blood pressure, and other routine clinical pathological variables in healthy aged cats were not affected by dietary salt content. The results of this 2 year study do not support the suggestion that chronic increases in dietary salt intake are harmful to renal function in older cats.

Comparative echocardiographic and clinical features of hypertrophic cardiomyopathy in 5 breeds of cats: a retrospective analysis of 344 cases (2001-2011).

BACKGROUND: Primary hypertrophic cardiomyopathy (HCM) is the most common feline heart disease and has been demonstrated to be inherited in some breeds. However, few studies have compared HCM phenotypes and survival according to breed. OBJECTIVES: To compare epidemiological characteristics, clinical findings, left ventricular (LV) geometric patterns, and survival in several breeds of cats with HCM. ANIMALS: Three hundred and forty-four cats from 5 different breeds (Persian, Domestic Shorthair [DS], Sphynx, Maine coon [MC], and Chartreux) with primary HCM diagnosed by conventional echocardiography. METHODS: Retrospective study. Cats were classified according to breed and clinical status. RESULTS: Age at the time of diagnosis was lower (P < .001) in MC (median age, 2.5 years) and Sphynx (3.5 years) than in other breeds (OB), ie, 8.0, 8.0, and 11.0 years for DS, Chartreux, and Persians, respectively. The prevalence of LV outflow tract obstruction was higher (P < .001) in Persians (23/41; 56%) than in OB (115/303; 38%). Age at the first cardiac event was lower (P < .01) in MC (median age, 2.5 years) than in OB (7.0 years). All cats surviving > 15 years of age were DS, Persians, or Chartreux. Sudden death (representing 24% of all cardiac deaths) was observed only in 3 breeds (DS, MC, and Sphynx). CONCLUSION AND CLINICAL IMPORTANCE: As in humans, feline HCM is characterized by marked phenotypic variability with several breed-dependent features regarding epidemiology, LV geometric patterns, and clinical course (ie, age at diagnosis, 1st cardiac event, and cause of death).

Renal resistive index in 55 dogs with degenerative mitral valve disease.

BACKGROUND: Azotemia occurs frequently in dogs with degenerative mitral valve disease (DMVD). It could indicate changes in renal hemodynamics. HYPOTHESIS/OBJECTIVES: To assess the renal resistive index (RI) in dogs with DMVD, and the statistical link between heart failure class, azotemia, echo-Doppler parameters, several plasma variables, and RI. ANIMALS: Fifty-five dogs with naturally occurring DVMD were used (ISACHC class 1 [n = 28], 2 [n = 19], and 3 [n = 8]). METHODS: Observational, blinded study, performed under standardized conditions. Physical examination, renal ultrasonography, and echo-Doppler examinations were performed in awake dogs. The RI of the renal, interlobar, and arcuate arteries were measured. Plasma creatinine, urea, and N-terminal pro-B-type natriuretic peptide concentrations (NT-proBNP) were determined. Statistical links between variables and RI were tested by means of a general linear model. RESULTS: Although the RI of renal and arcuate arteries were unaffected by ISACHC class, the left interlobar RI increased (P < .001) from 0.62 ± 0.05 (mean ± SD) in class 1 to 0.76 ± 0.08 in class 3. It was also higher (P < .001) in azotemic (0.74 ± 0.08) than in non-azotemic (0.62 ± 0.05) dogs. Similar findings were observed for right interlobar RI. Univariate analysis showed a positive statistical link between NT-proBNP (P = .002), urea (P < .001), creatinine (P = .002), urea-to-creatinine ratio (P < .001), left atrium-to-aorta ratio (P < .001), regurgitation fraction (P < .001), systolic pulmonary arterial pressure (P < .001), shortening fraction (P = .035), and RI. CONCLUSION AND CLINICAL IMPORTANCE: In dogs with DMVD, interlobar RI increases with heart failure severity and azotemia but a cause and effect relationship remains to be established.

Echocardiographic and tissue Doppler imaging alterations associated with spontaneous canine systemic hypertension.

BACKGROUND: Feline systemic arterial hypertension (SHT) is associated with a wide spectrum of left ventricular (LV) geometric patterns as well as diastolic, and to a lesser extent, systolic myocardial dysfunction. However, little is known about SHT-related cardiac changes in dogs. HYPOTHESIS: SHT in dogs is responsible for morphological and functional cardiac alterations. ANIMALS: Thirty dogs with spontaneous untreated SHT and 28 age- and body weight-matched healthy dogs as controls. METHODS: Prospective observational study. Conventional echocardiography and 2-dimensional color tissue Doppler imaging were performed in SHT dogs by trained observers and compared with controls. RESULTS: Forty-seven percent of SHT dogs (14/30) had diffuse concentric hypertrophy. None had left atrial dilatation and 10/30 (33%) had aortic insufficiency (AoI) associated with proximal aortic dilatation. Longitudinal diastolic left ventricular free wall (LVFW) motion was altered in all SHT dogs at the base (early to late diastolic wave ratio, E/A = 0.5 ± 0.1 versus 1.3 ± 0.3 for controls, P < .0001) and the apex (E/A = 1.6 ± 1.7 versus 3.9 ± 3.1, P < .05). Longitudinal motion of the interventricular septum at the base (E/A = 0.7 ± 0.4 versus 1.1 ± 0.1, P < .01) and radial LVFW motion in the subendocardium (E/A = 0.9 ± 0.5 versus 1.6 ± 0.3, P < .01) were also altered in dogs with SHT. Longitudinal LVFW systolic velocities and gradients were also significantly decreased (P < .05) in SHT dogs. CONCLUSION AND CLINICAL IMPORTANCE: As in SHT in cats, SHT in dogs is associated with myocardial dysfunction independently of the presence of myocardial hypertrophy. However, unlike feline SHT, it results in a homogeneous LV geometric pattern with a relatively high prevalence of AoI.

Attention-deficit hyperactivity disorder and intellectual disability: a study of association with brain-derived neurotrophic factor gene polymorphisms.

Symptoms of attention-deficit hyperactivity disorder (ADHD) have been found in several studies of children with intellectual disabilities (ID) but the two diseases are not always associated. Several lines of evidence implicate the involvement of brain-derived neurotrophic factor (BDNF) in ADHD, and it may also be relevant in ID due to its known involvement in the development of the central nervous system (CNS) and in learning/memory functions. We genotyped paediatric patients with ADHD and ID for the Val66Met and 270 C/T polymorphisms in BDNF. Diagnosis of ADHD and ID was confirmed by the clinicians in accordance with DSM-IV criteria. The G/A genotype of the Val66Met SNP was associated with both ADHD and ID, and the G allele was significantly associated with ADHD. The C/C genotype of the C270T SNP was significantly overrepresented in both ADHD and ID groups compared with the controls. Data suggest that both BDNF polymorphisms could play a role in the etiology of ADHD. In addition, we present the first results suggesting that these BDNF SNPs are significantly associated with ID.

Investigation on the possible relationship existing between the HLA-DR gene and attention deficit hyperactivity disorder and/or mental retardation.

This study examines the possible relationship existing between the HLA-DR gene and attention deficit hyperactivity disorder (ADHD) and/or mental retardation (MR). The diagnosis of ADHD and mental retardation were established through clinical interviews with the parents, children and teachers, according to the criteria in DSM-IV. HLA-DRB1 genotyping was performed both by polymerase chain reaction-sequence specific primers (PCR-SSP) and by sequence based typing (SBT) in a cohort of 81 affected children and a sample of 100 healthy controls. Here, we report a positive association of HLA-DR4 with ADHD but not with MR. The study adds confirmation to the role of the HLA-DRB1 in the etiology of some types of childhood neuropsychiatric illnesses.

Executive function impairment in early-treated PKU subjects with normal mental development.

Executive functions were studied in 14 early and continuously treated PKU subjects (age 10.8 years, range 8-13) in comparison with controls matched for IQ, sex, age and socioeconomic status. Brain MRI examination was normal in all PKU patients. Neuropsychological evaluation included Wisconsin Card Sorting Test, Rey-Osterreith Complex Figure Test, Elithorn's Perceptual Maze Test, Weigl's Sorting Test, Tower of London, Visual Search and Motor Motor Learning Test. Whatever the IQ, PKU subjects performed worse than controls in tests exploring executive functions. Subgrouping the PKU subjects according to the quality of dietary control for the entire follow-up period (using 400 micromol/L as cut-off value for blood phenylalanine (Phe) concentration) showed that patients with worse dietary control performed more poorly than both the PKU group with the best dietary control and the control group. However, a mild impairment of executive functions was still found in PKU patients with a good dietary control (Phe <400 micromol/L) compared to controls. Concerning the PKU group as a whole, no linear correlation was found between neuropsychological performance and historical and concurrent biochemical parameters. We conclude that (a) PKU patients, even when treated early, rigorously and continuously, show an impairment of frontal lobe functions; (b) a protracted exposure to moderately high levels of Phe can affect frontal lobe functions independently of the possible effect of the same exposure on IQ; (c) in order to reduce the risk of frontal lobe dysfunction, the target of dietary therapy should be to maintain blood Phe concentration below 400 micromol/L.

Nature of phonological delay in children with specific language impairment.

This study investigated the nature of phonological delay in a group of children with specific language impairment. It was asked whether phonological errors in this group of children were generated by a slow but normal language learning process or whether they reflected a selective impairment in some representations that enhance normal acquisition and use of a language phonology. A group of 10 children with SLI (mean age = 5.1) was compared with three groups of normal children who were matched in age (age control group, mean age = 5.1), in sentence comprehension and recalling (grammar control group, mean age = 3.7), or who exhibited a phonological performance lower than the age average (group with low phonological performance, mean age = 4.4). The four groups of children were assessed in terms of: (1) responses to a mispronunciation detection task; and (2) error profiles with complex and simple syllabic structures. Performance on the mispronunciation detection task showed that the group with SLI could distinguish a target lexical item from acoustic non-word stimuli that were highly similar to it in terms of phonetic characteristics. An analysis of overall error rate at this task showed, however, that four children with SLI had a much lower performance than normal children of the same age, even when the auditory stimuli were tokens of the target word, or non-words that were phonetically different from the target. A difficulty in coordinating vocal actions in an articulatory plan accounted for error profiles with simple syllabic structures both for some children with SLI and normal children with phonological performance lower than the age average. A severe difficulty with representing complex syllabic structures was a homogeneous characteristic of the group with SLI and worked as the main indicator of impaired, rather than simply slow, phonological development.

Reading strategies in children with learning disabilities and minor neurological dysfunction.

The connexions between minor neurological dysfunction (MND) and learning disabilities (LD) are analysed in 48 children with LD with and without MND. The two groups did not differ in a set of reading/writing tests or in neuropsychological tests. What proved to be different were the profiles of correlation internal to reading and between reading and presupposed neuropsychological functions. The results highlight the importance of studying the connexions between MND and LD and the need to take neuromotor parameters into account in the construction of clinical subtypes of learning disabilities.

Abnormalities of visual evoked potentials by checkerboards in children with specific reading disability.

Visual evoked potentials by checkerboards of varying check sizes were recorded in the two hemispheres of 16 specific reading disabled and 8 normal children. In most of the disabled subjects a gross hemisphere asymmetry was assessed, while in the control group the usual evoked potential symmetry was observed. In some disabled subjects the evoked potentials had a larger amplitude in the right hemisphere, while in others the amplitude was larger in the left hemisphere. In a small subgroup the evoked potentials were symmetrical, but they had a smaller amplitude than in the control subjects. The results, giving evidence of a dysfunction in basic visual processing, are discussed in the context of current literature on clinical subgroups and the interhemispheric relationship in the dyslexic syndrome.

Language disorders and prognosis for reading disabilities in developmental age.

2 groups of language-disordered children were studied regarding the reading levels reached at the end of the first year of school. The first group was composed by children with language retardation mainly on phonological level, the second group was composed by children with retardation also on semantic-syntactic level. The results confirmed the strong association between reading disability and language disorders and yielded significant differences between the two groups: the reading achievement seemed to be associated mainly to semantic and syntactic competences.