Presenting signs and clinical outcome in dogs with metaphyseal osteopathy: 39 cases (2009-2018).

OBJECTIVE: To describe the presenting signs, concurrent conditions, treatment and outcome of dogs with metaphyseal osteopathy. MATERIALS AND METHODS: Multi-centre retrospective review of medical records from January 2009 to September 2018 at four referral centres to identify dogs with a radiographic diagnosis of metaphyseal osteopathy. RESULTS: Thirty-nine dogs were identified. The median age at onset was 14 weeks old (range, 8 to 32 weeks old). There was a higher proportion of male dogs (29 of 39 male entire, nine of 39 female entire, one of 39 female neutered and no male neutered dogs). Where information was available, median time from the most recent vaccination was 20 days (range, 2 to 144 days). The most commonly recorded clinical signs were pyrexia (34 of 39), lethargy (32 of 39), pain (30 of 39), and being non-ambulatory (17 of 39). Thirty-five dogs required hospitalisation for analgesia and supportive care, 19 of 39 were discharged on prednisolone (median dose 2.0 mg/kg/day; range, 0.9 to 2.6 mg/kg/day), 18 of 39 were discharged on non-steroidal anti-inflammatories, two of 39 did not receive NSAIDs or prednisolone at any time point. The median duration of hospitalisation for those admitted was 5 days (range, 1 to 21 days). Where follow-up was available, relapse occurred in eight of 25 cases before reaching skeletal maturity. At the time of metaphyseal osteopathy diagnosis, five of 39 cases had concurrent conditions. Where follow-up was available, four of 25 developed future immune-mediated conditions. CLINICAL SIGNIFICANCE: Metaphyseal osteopathy should be considered in non-ambulatory painful young dogs. Some dogs developed future immune-mediated conditions, which may support the hypothesis that metaphyseal osteopathy is an autoinflammatory bone disorder. Further studies with a larger cohort are required to determine the clinical significance of this.

Point prevalence and clinical course of proteinuria in dogs with idiopathic non-erosive immune-mediated polyarthritis.

OBJECTIVES: To describe the point prevalence and clinical course of proteinuria in dogs diagnosed with idiopathic non-erosive immune-mediated polyarthritis. MATERIALS AND METHODS: Cases presenting to a single referral centre with a diagnosis of idiopathic non-erosive immune-mediated polyarthritis were retrospectively recruited from January 2009 to August 2018. Data including signalment, urinalysis, clinicopathological results, cytology from arthrocentesis, treatment and long-term follow-up were analysed. Dogs were defined as: non-proteinuric (UPC <0.2), borderline proteinuric (UPC 0.2-0.5) or overtly proteinuric (UPC >0.5). RESULTS: Fifty-eight dogs met the inclusion criteria. Twenty-two dogs were overtly proteinuric (38%), eight dogs were borderline proteinuric (14%) and 28 dogs were non-proteinuric (48%). Repeated urinalysis was performed in nine of 12 dogs with UPC greater than 2.0. The UPC decreased in all nine dogs, with the UPC decreasing to less than 0.5 in 44% of dogs. A greater than 50% decrease in UPC was noted in 44% of dogs, despite seven of nine (77%) receiving prednisolone as either monotherapy or in conjunction with an adjunctive immunosuppressive medication. CLINICAL SIGNIFICANCE: Proteinuria was common in this cohort of dogs diagnosed with primary idiopathic non-erosive immune-mediated polyarthritis. The use of prednisolone does not appear to be contraindicated in proteinuric dogs with idiopathic non-erosive immune-mediated polyarthritis.

Serological markers of gluten sensitivity in Border terriers with gall bladder mucocoeles.

OBJECTIVES: To evaluate serological markers of gluten sensitivity in conjunction with cholecystokinin measurement in Border terriers with gall bladder mucocoeles. MATERIALS AND METHODS: Medical records from two referral hospitals were obtained between 2011 and 2019 to identify Border terriers with gall bladder mucocoeles, non-Border terriers with gall bladder mucocoeles and control Border terriers with non-biliary diseases. Enzyme-linked immunosorbent assays were performed on stored fasted serum samples for anti-gliadin IgG, anti-canine transglutaminase-2-IgA autoantibodies and cholecystokinin. Statistical analysis was performed using the Kruskall-Wallis test to identify differences between the groups. RESULTS: Fifteen Border terriers with gall bladder mucocoeles, 17 non-Border terriers with gall bladder mucocoeles and 14 control Border terriers with non-biliary diseases were recruited. Median transglutaminase-2-IgA autoantibodies in Border terriers with gall bladder mucocoeles was 0.73 (range: 0.18 to 1.67), which was significantly greater than in control Border terriers at 0.41 (0.07 to 1.14). Median cholecystokinin concentration in Border terriers with gall bladder mucocoeles was 13 pg/mL (6 to 45 pg/mL), which was significantly lower than in control Border terriers at 103 pg/mL (9 to 397 pg/mL). There was no difference in the anti-gliadin IgG between these groups. There was no difference observed in the non-Border terriers with gall bladder mucocoeles with either of the other groups. CLINICAL SIGNIFICANCE: Reduced cholecystokinin and increased transglutaminase-2-IgA autoantibodies was detected in Border terriers with gall bladder mucocoeles; which is in part homologous to gall bladder disease identified in human coeliac disease. The results suggest an immunological disease with impaired cholecystokinin release may be affecting gall bladder motility and possibly contributing to mucocoele formation in Border terriers.

Infiltrative laryngeal disease in dogs.

OBJECTIVES: To describe the clinical features and outcome of neoplastic and inflammatory infiltrative laryngeal disease in dogs. MATERIALS AND METHODS: Medical records at a single referral centre were retrospectively reviewed for dogs diagnosed with infiltrative laryngeal disease by CT or laryngoscopy. RESULTS: Fifteen dogs were included, with a median age of 6 years (range 1-14 years). Thirteen dogs were diagnosed with inflammatory disease including granulation tissue (n = 4) and neutrophilic (n = 2), septic neutrophilic (n = 2), eosinophilic (n = 1) lymphocytic/plasmacytic (n = 1) and mixed/unclassified (n = 3) inflammation. One dog was diagnosed with large cell lymphoma and one dog was diagnosed with mast cell tumour. Twelve dogs survived to discharge. Follow-up was available for 10 dogs diagnosed with inflammatory disease. Four had fully recovered (7, 10, 23 and 32 months) and one dog developed acute leukaemia and was euthanased at 2 months. Five dogs had recurrence of clinical signs at 1, 1, 5, 17 and 26 months. The dog with lymphoma was euthanased at 8 months and the dog with mast cell tumour died at 5 months. CLINICAL SIGNIFICANCE: In this cohort, infiltrative inflammatory lesions of the larynx were more common than neoplastic infiltration. For dogs that survived to discharge, outcome was fair although relapse was common.

Canine sterile steroid-responsive lymphadenitis in 49 dogs.

OBJECTIVES: To report clinical and laboratory features, treatment responses and outcome in dogs diagnosed with sterile steroid-responsive lymphadenitis in the United Kingdom. MATERIALS AND METHODS: Medical records of dogs diagnosed with sterile steroid-responsive lymphadenitis from 2009 to 2016 at six specialist referral centres were evaluated retrospectively. RESULTS: The study included 49 dogs. Springer spaniels appeared to be over-represented (16 of 49 dogs). Young dogs (median age: 3 years and 9 months) and females (31 of 49) were frequently affected. Clinical presentation was variable, with pyrexia (39 of 49), lethargy (35 of 49) and anorexia (21 of 49) the most commonly reported clinical signs. Lymph node cytology or histopathology demonstrated neutrophilic, pyogranulomatous, granulomatous or necrotising lymphadenitis without a detectable underlying cause in all cases. Because a sterile immune-mediated aetiology was suspected, all dogs received prednisolone, which was followed by rapid resolution of clinical signs and lymphadenopathy in most cases. CLINICAL SIGNIFICANCE: Sterile steroid-responsive lymphadenitis should be considered in dogs with pyrexia of unknown origin with inflammatory lymphadenopathy if no underlying cause can be found and often responds well to immunosuppressive corticosteroid therapy.

Pyrexia in juvenile dogs: a review of 140 referred cases.

OBJECTIVES: To describe the presentation, influence of previous treatment and diagnosis in juvenile dogs presenting with pyrexia to a UK referral centre. MATERIALS AND METHODS: Clinical records of dogs aged 1 to 18 months presenting with a problem list including pyrexia (≥⃒39∙2°C) that was reproducible during referral hospitalisation were retrospectively reviewed. Signalment, history - including previous treatment, clinical examination findings and diagnosis were recorded. Diagnoses were categorised as non-infectious inflammatory, infectious, congenital, neoplastic and miscellaneous. The influence of previous treatment on the ability to reach a final diagnosis was analysed. RESULTS: A total of 140 cases was identified. Diagnosis was reached in 115 cases. Non-infectious inflammatory disease was identified in 91 cases (79%), infectious disease in 19 cases (17%), a congenital disorder in four dogs (3%) and neoplasia in one dog (1%). Breeds most commonly identified were Border collies (17/140; 12%), beagles (16/140; 11%), Labrador retrievers (11/140; 8%), springer spaniels (9/140; 6%) and cocker spaniels (8/140; 6%). Before presentation, most dogs had received antibiotics (83/140; 59%), non-steroidal anti-inflammatory drugs (84/140; 60%) or steroids (9/140; 6%), either alone or in combination. Neither antibiotics nor non-steroidal anti-inflammatory drugs influenced the ability to reach a diagnosis. Steroid-responsive meningitis-arteritis comprised 55 of 91 (60%) individuals of the non-infectious inflammatory cohort. All four dogs diagnosed with congenital disorders were Border collies. CLINICAL SIGNIFICANCE: Non-infectious inflammatory disease, particularly steroid-responsive meningitis-arteritis, immune-mediated polyarthritis and metaphyseal osteopathy, was commonly diagnosed in this population of pyrexic juvenile dogs.

Gall bladder mucoceles in Border terriers.

BACKGROUND: Gall bladder mucoceles (GBM) are a leading cause of biliary disease in dogs with several breeds, including the Shetland Sheepdog, American Cocker Spaniel, Chihuahua, Pomeranian, and Miniature Schnauzer apparently predisposed. OBJECTIVE: To determine risk factors, clinical features, and response to treatment of GBM in Border terriers (BT). ANIMALS: Medical records of 99 dogs (including 51 BT) with an ultrasonographic (±histopathologic) diagnosis of GBM from three referral centers in the United Kingdom were collected. A control group of 87 similar-aged BT with no ultrasonographic evidence of gall bladder disease was selected for comparison. METHOD: Retrospective case-control study. Odds ratios were calculated to establish breed predisposition. Signalment, presence of endocrine disease, clinicopathologic results, and outcome were compared between the BT, other breeds, and control BTs. RESULTS: The odds of identifying a GBM in a BT in this hospital population was 85 times that of all other breeds (95% confidence interval 56.9-126.8). BT had similar clinical signs and clinicopathologic changes to other breeds with GBM. There was no evidence that endocrinopathies were associated with GBM in BT. CLINICAL SIGNIFICANCE: A robust breed predisposition to GBM is established for the BT.

HIV testing in the critical care setting: views of patients, family members and health providers from urban South Africa.

As antiretroviral treatment has led to decreased morbidity, HIV testing policy has increasingly shifted towards routine, provider-initiated approaches. Yet, few studies have examined the acceptability of provider-initiated HIV testing in the intensive, or critical care setting, where knowledge of HIV status is likely to impact on clinical management but explicit consent for testing is difficult to obtain. We conducted qualitative research in an urban hospital and clinic in Johannesburg. In-depth interviews were conducted among HIV testing clients (n = 20), recently discharged critical care patients (n = 13) and family members of critical care patients (n = 14). One focus group discussion was held with health care providers (n = 10). HIV testing in critical care was viewed as acceptable but challenging to implement. An overarching theme of ambivalence emerged from patients and families, who saw HIV testing as a pre-requisite to appropriate clinical care, but were concerned about the quality of its delivery. While providers were aware of the current "no testing without consent" policy, they expressed frustration in cases when testing was in the patient's best interest but consent could not be obtained. Furthermore, providers found it stressful to weigh up patient confidentiality against medical necessity when assessing patients' "best interests". Without specific guidelines, they often developed pragmatic, ad hoc ways to resolve dilemmas around testing in critical care. Our findings suggest that HIV testing guidelines specific to the critical care setting may help providers do their jobs more ethically and transparently. Provider-initiated approaches are likely to be acceptable to patients and may improve clinical outcomes, but training and support in policy implementation and ethical decision-making are essential.

Phenotypic characterisation of canine epileptoid cramping syndrome in the Border terrier.

OBJECTIVES: To characterise the phenotype of Border terriers suspected to be affected by canine epileptoid cramping syndrome and to identify possible contributing factors. METHODS: Owners of Border terriers with suspected canine epileptoid cramping syndrome were invited to complete an online questionnaire. The results of these responses were collated and analysed. RESULTS: Twenty-nine Border terriers were included. Most affected dogs had their first episode before 3 years of age (range: 0·2 to 7·0 years). The majority of episodes lasted between 2 and 30 minutes (range: 0·5 to 150 minutes). The most frequent observations during the episodes were difficulty in walking (27 of 29), mild tremor (21 of 29) and dystonia (22 of 29). Episodes most frequently affected all four limbs (25 of 29) and the head and neck (21 of 29). Borborygmi were reported during episodes in 11 of 29 dogs. Episodes of vomiting and diarrhoea occurred in 14 of 29, with 50% of these being immediately before or after episodes of canine epileptoid cramping syndrome (7 of 14). Most owners (26 of 29) had changed their dog's diet, with approximately 50% (14 of 26) reporting a subsequent reduction in the frequency of episodes. CLINICAL SIGNIFICANCE: This study demonstrates similarities in the phenotype of canine epileptoid cramping syndrome to paroxysmal dystonic choreoathetosis, a paroxysmal dyskinesia reported in humans. This disorder appears to be associated with gastrointestinal signs in some dogs and appears at least partially responsive to dietary adjustments.

Teens with heavy prenatal cocaine exposure respond to experimental social provocation with escape not aggression.

Preclinical data show that, compared to no exposure, prenatal cocaine exposure (PCE) has age-dependent effects on social interaction and aggression. The aim of this clinical study was to determine how heavy/persistent PCE--after controlling for other prenatal drug exposures, sex and postnatal factors--predicts behavioral sensitivity to provocation (i.e., reactive aggression) using a well-validated human laboratory model of aggression. African American teens (mean=14.2 years old) with histories of heavy/persistent PCE (maternal cocaine use ≥ 2 times/week during pregnancy, or positive maternal or infant urine/meconium test at delivery; n=86) or none/some exposure (NON: maternal cocaine use < 2 times/week during pregnancy; n=330) completed the Point Subtraction Aggression Paradigm. In this task, teens competed in a computer game against a fictitious opponent. There were three possible responses: (a) earn points, to exchange for money later; or (b) "aggress" against the fictitious opponent by subtracting their points; or (c) escape temporarily from point subtraction perpetrated by the fictitious opponent. The PCE group responded significantly more frequently on the escape option than the NON group, but did not differ in aggressive or money-earning responses. These data indicate that PCE-teens provoked with a social stressor exhibit a behavioral preference for escape (negative reinforcement) than for aggressive (retaliatory) or appetitive (point- or money-reinforced) responses. These findings are consistent with preclinical data showing that social provocation of adolescent or young adult offspring after PCE is associated with greater escape behavior, inferring greater submission, social withdrawal, or anxiety, as opposed to aggressive behavior.

Poor sensitivity of field rapid HIV testing: implications for mother-to-child transmission programme.

We validated rapid HIV tests among pregnant women in a clinical setting. Field testing was performed using First Response 1,2,3 or Standard Diagnostic and Pareekshak tests. Results were confirmed by third generation HIV ELISA. Discordant or negative, specimens were confirmed by RNA PCR and a fourth generation ELISA test. Sensitivity and specificity were 94.5% (CI: 85.8-98.2) and 100% for First Response; 87.5% (CI: 46.7-99.3) and 100% (CI: 87.7-100%) for Standard Diagnostic and 90.2% (CI: 81.2-95.4) and 100% (CI: 98-100%) for Pareekshak. These sensitivities were lower than laboratory validation which approached 100%. The low-field sensitivity results have implications for Prevention of Mother-to-Child Transmission services.

Incidence of nevirapine-associated hepatitis in an antenatal clinic.

OBJECTIVE: To describe the incidence, clinical presentation and management of nevirapine-associated hepatitis among antiretroviral-naïve pregnant women treated with nevirapine-based antiretroviral therapy at a dedicated antenatal antiretroviral clinic. METHODS: Retrospective analysis of pregnant women initiated on nevirapine-based highly active antiretroviral therapy at a dedicated antenatal antiretroviral clinic between July 2004 and December 2006. RESULTS: Three hundred and ninety women were included in the analysis. Median age was 29 (interquartile range (IQR) 26-32) years and median pre-treatment CD4 cell counts was 157 (IQR 104-193) cells/microl. Baseline alanine transaminase (ALT) was elevated in 2.8% of women (11/390). After initiation of nevirapine-based ART 8% (31/390) experienced an ALT elevation. Three of these patients developed clinical hepatitis with jaundice (0.8%, 3/390). The mean and median time to clinical presentation was 5 weeks. Hepatitis resolved following discontinuation of ART. Non-nevirapine regimens were initiated following biochemical and symptomatic improvement; symptoms did not recur. CONCLUSIONS: Among pregnant women, nevirapine-containing ART has a favourable safety profile, with a low incidence of serious hepatic events.

The detection of urethritis pathogens among patients with the male urethritis syndrome, genital ulcer syndrome and HIV voluntary counselling and testing clients: should South Africa's syndromic management approach be revised?

OBJECTIVES: To determine the prevalence of urethritis pathogens amongst male symptomatic urethritis (MUS) patients, genital ulcer (GUS) patients without urethritis symptoms and men requesting HIV testing at a voluntary counselling and testing (VCT) clinic. METHODS: A prospective study was conducted in Johannesburg, South Africa. Men from the three groups were screened for urethritis pathogens using molecular tests. Culture for Neisseria gonorrhoeae and, initially, trichomoniasis was performed. Antimicrobial susceptibility testing was undertaken for ciprofloxacin on all gonococcal isolates; ciprofloxacin resistant isolates were screened for ceftriaxone resistance. RESULTS: 664 participants were recruited (438 MUS, 76 GUS and 158 VCT) over 2 years. Gonorrhoea was detected in 62.3% MUS, 15.8% GUS and 3.2% VCT participants. Chlamydial infection was detected in 19.3% MUS, 13.2% GUS and 8.2% VCT participants. Trichomoniasis was detected in 4.9% MUS, 19.7% GUS and 3.8% VCT participants. Mycoplasma genitalium infection was detected in 14.4% MUS, 13.2% GUS and 7.0% VCT participants. Ciprofloxacin resistance increased from 13.0% in the first year to 26.3% in the second year; all resistant isolates were susceptible to ceftriaxone. CONCLUSIONS: Urethritis pathogens, including Trichomonas vaginalis, should be covered in syndromic management treatment of genital ulcers in the absence of clinical urethritis. Consideration should be given to adding metronidazole to existing MUS treatment. Ciprofloxacin can no longer be relied upon to treat presumptive gonococcal infections in South Africa.

Ozone affects gas exchange, growth and reproductive development in Brassica campestris (Wisconsin fast plants).

Exposure to ozone (O(3)) may affect vegetative and reproductive development, although the consequences for yield depend on the effectiveness of the compensatory processes induced. This study examined the impact on reproductive development of exposing Brassica campestris (Wisconsin Fast Plants) to ozone during vegetative growth. Plants were exposed to 70 ppb ozone for 2 d during late vegetative growth or 10 d spanning most of the vegetative phase. Effects on gas exchange, vegetative growth, reproductive development and seed yield were determined. Impacts on gas exchange and foliar injury were related to pre-exposure stomatal conductance. Exposure for 2 d had no effect on growth or reproductive characteristics, whereas 10-d exposure reduced vegetative growth and reproductive site number on the terminal raceme. Mature seed number and weight per pod and per plant were unaffected because seed abortion was reduced. The observation that mature seed yield per plant was unaffected by exposure during the vegetative phase, despite adverse effects on physiological, vegetative and reproductive processes, shows that indeterminate species such as B. campestris possess sufficient compensatory flexibility to avoid reductions in seed production.

PGE2/TXB2 imbalance in neonatal hypoxemic respiratory failure.

BACKGROUND: An imbalance of vaso-constrictor and -dilator mediators has been implicated in the pathogenesis of the pulmonary hypertension accompanying neonatal hypoxemic respiratory failure (NHRF). AIM: To characterize plasma PGE2, TXB2 and their ratio in normal newborns and in those with NHRF. METHODS: Twenty newborns with NHRF received inhaled PGE1 (IPGE1) by jet nebulizer in doses of 25, 50, 150 and 300 ng/kg/min followed by weaning. Blood for PGE2 and TXB2 assay using EIA was available in 8 neonates with NHRF prior to IPGE1. Umbilical cord arterial samples were also obtained at delivery from 10 normal newborns to serve as controls. RESULTS: Compared to normal newborns, those with NHRF had significantly lower PGE2/TXB2 ratios after controlling for preterm gestation (< 37 weeks) and postnatal age (p < 0.05). Notably, all subjects except one in the NHRF group had a value of < 1.0 (range 0.1-1.2) compared to a value of > 1.0 in all subjects in the Control group (range 1.1-5.2). CONCLUSIONS: Lower PGE2/TXB2 ratio in subjects with NHRF compared with controls reflects a predominance of vaso-constrictor activity in these patients as the basis of pulmonary hypertension. Plasma PGE2/TXB2 ratio may have important implications for the diagnosis and treatment of NHRF.

Cholesterol and steroid synthesizing smooth endoplasmic reticulum of adrenocortical cells contains high levels of translocation apparatus proteins.

Steroid-secreting cells possess abundant smooth endoplasmic reticulum whose membranes contain many enzymes involved in sterol and steroid synthesis. In this study we demonstrate that adrenal smooth microsomal subfractions enriched in these membranes also possess high levels of proteins belonging to the translocation apparatus, proteins previously assumed to be confined to morphologically identifiable rough endoplasmic reticulum (RER). We further demonstrate that these smooth microsomal subfractions are capable of effecting the functions of these protein complexes: co-translational translocation, signal peptide cleavage and N-glycosylation of newly synthesized polypeptides. We hypothesize that these elements participate in regulating the levels of ER-targeted membrane proteins involved in cholesterol and steroid metabolism in a sterol-dependent and hormonally-regulated manner.