Abstract
Background
Vestibular syndrome is often accompanied by nausea. Drugs currently approved for its treatment have been developed to stop vomiting but not nausea. The efficacy of 5-HT
3
receptor ...antagonists to reduce nausea has been described for chemotherapy, but not for nausea secondary to vestibular disorders.
Methods
Sixteen dogs with vestibular syndrome-associated nausea were included in the open-label, multicentre study. The intensity of nausea-like behaviour was analysed before ondansetron administration (0.5 mg/kg i.v.) and 2 h afterwards, using a validated 5-point-scale. The occurrence and frequency of salivation, lip licking, restlessness, vocalisation, lethargy, and vomiting were assessed.
Results
All dogs initially showed signs of nausea, whereas only 31% showed vomitus. The intensity of nausea was significantly reduced in all dogs (
p
≤ 0.0001) 2 h after ondansetron administration, including the clinical signs of nausea analysed in 11 dogs (salivation
p
= 0.0078, lip licking
p
= 0.0078, restlessness
p
= 0.0039, and lethargy
p
= 0.0078) except for vocalisation (
p
> 0.9999).
Conclusions
The results provide preliminary evidence of the potential benefit of ondansetron in the treatment of nausea, which was present in all examined dogs. Vomiting was only observed in 5 dogs indicating that nausea can occur separately and should not be perceived only as a preceding stimulation of the vomiting centre.
•Paroxysmal dyskinesia occurs in Welsh terrier dogs.•It is characterised by dystonia and choreoathetosis with normal mentation.•Age of onset varied and dogs were largely normal between ...episodes.•Prevalence is consistent with an inherited aetiology in Welsh terriers.
Breed specific paroxysmal dyskinesias are increasingly recognised in veterinary medicine. We aimed to characterise the phenomenology, clinical course and prevalence of a previously unreported paroxysmal dyskinesia in the Welsh terrier breed. Clinical records of five Welsh terriers with paroxysmal episodes were reviewed. Additionally, owners of Welsh terriers were invited to complete a questionnaire with the aim of characterising paroxysmal episodes in the wider breed population.
Clinical examinations (n = 5) and diagnostic investigations (n = 3) of affected Welsh terriers were within normal limits, apart from mild-moderate ventriculomegaly on cranial magnetic resonance imaging (n = 3). The survey of Welsh terrier owners revealed episodes consistent with a paroxysmal dyskinesia in 41 (22.8%) of 177 respondents. Median age of onset was 59 months. Episodes were predominantly characterised by sustained hypertonicity with periods of limb flexion, abnormal head and body posture, with preserved consciousness. Episode duration ranged from 30 s to 30 min (median, 3 min 30 s), with frequency varying widely between dogs. Affected dogs demonstrated a stable to improving clinical course in most cases. This study investigated a previously unreported paroxysmal dyskinesia in Welsh terriers. Similar clinical signs within the breed were potentially consistent with an inherited cause, worthy of further investigation.
Abstract
A subset of patients has long-lasting symptoms after mild to moderate Coronavirus disease 2019 (COVID-19). In a prospective observational cohort study, we analyze clinical and laboratory ...parameters in 42 post-COVID-19 syndrome patients (29 female/13 male, median age 36.5 years) with persistent moderate to severe fatigue and exertion intolerance six months following COVID-19. Further we evaluate an age- and sex-matched postinfectious non-COVID-19 myalgic encephalomyelitis/chronic fatigue syndrome cohort comparatively. Most post-COVID-19 syndrome patients are moderately to severely impaired in daily live. 19 post-COVID-19 syndrome patients fulfill the 2003 Canadian Consensus Criteria for myalgic encephalomyelitis/chronic fatigue syndrome. Disease severity and symptom burden is similar in post-COVID-19 syndrome/myalgic encephalomyelitis/chronic fatigue syndrome and non-COVID-19/myalgic encephalomyelitis/chronic fatigue syndrome patients. Hand grip strength is diminished in most patients compared to normal values in healthy. Association of hand grip strength with hemoglobin, interleukin 8 and C-reactive protein in post-COVID-19 syndrome/non-myalgic encephalomyelitis/chronic fatigue syndrome and with hemoglobin, N-terminal prohormone of brain natriuretic peptide, bilirubin, and ferritin in post-COVID-19 syndrome/myalgic encephalomyelitis/chronic fatigue syndrome may indicate low level inflammation and hypoperfusion as potential pathomechanisms.
•The aetiology of canine idiopathic vestibular syndrome is unclear.•No significant changes have previously been reported on magnetic resonance imaging.•Endolymph appearance were measured by a ...software determining grey values.•Study showed altered inner ear fluid appearance on magnet resonance imaging.•Unilateral decrease in inner ear signal correlated with direction of clinical signs.
The aetiology of canine idiopathic vestibular syndrome (IVS) remains unclear. In human medicine, characteristic magnetic resonance imaging (MRI) techniques are used to demonstrate differences in endolymph composition between affected and unaffected inner ears. The purpose of this study was to determine whether similar MRI techniques could help to detect changes in the inner ears of canine IVS patients. Medical records from two veterinary referral clinics were reviewed retrospectively. Dogs were included if they had a diagnosis of IVS, obvious lateralisation of clinical signs, and an MRI of the vestibular system. A region of interest (ROI) was manually outlined by defining the anatomical area of the inner ear in T2-weighted and fluid-attenuated inversion recovery (FLAIR) images. In order to calculate the ratio of FLAIR suppression of each ear, the mean grey value of the ROI was determined in both sequences. If a unilateral decrease in suppression was identified, it was compared with the direction of clinical signs.
In total, 80 dogs were included in the study. There was a significantly lower degree of suppression on the affected compared to the unaffected side (0.8886 vs. 0.9348, respectively; P = 0.0021). In 92.5% of cases, there was agreement between the most suppressed side on MRI and the direction of clinical signs. This study provides preliminary evidence about the appearance of endolymph on MRI of dogs with IVS. Further studies are needed to investigate associations between the severity of MRI changes and prognosis.
Epidemiological evaluation of canine epilepsy is an under-researched area. The objectives of this study were to estimate prevalence and investigate risk factors for epilepsy of unknown origin (EUO) ...among dogs attending primary veterinary practices in the UK. The clinical data analysed spanned a two-year period and included all dogs attending 92 primary veterinary clinics participating in the VetCompass project. Five hundred and thirty-nine EUO cases were identified giving a prevalence of 0.62% (95% CI 0.57% to 0.67%). Males were over 1.5 times as likely to have EUO compared with females (95% CI 1.44 to 2.06; P < 0.001). Of purebred dogs, the border terrier had 2.70 (95% CI 1.57 to 4.62; P < 0.001) and the German shepherd dog had 1.90 (95% CI 1.28 to 2.80; P=0.001) times increased odds of EUO compared with crossbred dogs. In addition, the West Highland white terrier had reduced odds (OR 0.23; 95% CI 0.08 to 0.62; P=0.004) of EUO compared with crossbred dogs (likelihood ratio test P < 0.0001). No association was found with neuter status, colour or weight. The current study highlights the clinical importance of epilepsy as a canine disorder in the UK. Increased awareness of sex and breed predispositions may assist clinicians with diagnosis. Further research is merited to evaluate the specific breed associations identified.
Cytomegalovirus (CMV) infections have a major impact on morbidity and mortality of transplant patients. Among the complex antiviral T‐cell response, CMV‐IE‐1 antigen‐specific CD8+ cells are crucial ...for preventing CMV disease but do not protect from recurring/lasting CMV reactivation. Recently, we confirmed that adoptive transfer of autologous IE‐1/pp65‐specific T‐cell lines was able to combat severe CMV disease; however, the control of CMV infection was only temporary. We hypothesized that CMV‐induced regulatory T cells (iTreg) might be related to recurring/lasting CMV infection.
In fact, kidney transplant patients with recurring CMV infections expressed enhanced suppression on CMV response. Analysis of in vitro expanded CD4+ epitope‐specific cells revealed that CMV‐specific CD4+CD25high Treg cells functionally suppress CD25low effector T cells (Teff) upon epitope‐specific reactivation. Their phenotype is similar to iTreg – CD39high/Helios‐/IL‐2low/IFNγhigh/IL‐10±/TGFß‐LAP±/FOXP3+ and methylated foxp3 locus. Remarkably, in vitro expanded CD4+CD25high iTreg share the same dominant TCR‐Vβ‐CDR3 clones with functionally distinct CD4+CD25low Teff. Moreover, the same clones were present in freshly isolated CD4+CD25high and CD4+CD25low T cells suggesting their in vivo generation. These findings directly demonstrate that Teff and iTreg can differentiate from one “mother” clone with specificity to the same viral epitope and indicate that peripheral iTreg generation is related to frequent antigen appearance.
This study relates the impact of cytomegalovirus (CMV)‐specific regulatory T cells on the quality of CMV‐specific T cell responses to frequent antigen appearance.
Assessment of donor‐specific alloreactive memory/effector T cell responses using an IFN‐γ Elispot assay has been suggested to be a novel immune‐monitoring tool for evaluating the cellular immune risk ...in renal transplantation. Here, we report the cross‐validation data of the IFN‐γ Elispot assay performed within different European laboratories taking part of the EU RISET consortium. For this purpose, development of a standard operating procedure (SOP), comparisons of lectures of IFN‐γ plates assessing intra‐ and interlaboratory assay variability of allogeneic or peptide stimuli in both healthy and kidney transplant individuals have been the main objectives. We show that the use of a same SOP and count‐settings of the Elispot bioreader allow low coefficient variation between laboratories. Frozen and shipped samples display slightly lower detectable IFN‐γ frequencies than fresh samples. Importantly, a close correlation between different laboratories is obtained when measuring high frequencies of antigen‐specific primed/memory T cell alloresponses. Interestingly, significant high donor‐specific alloreactive T cell responses can be similarly detected among different laboratories in kidney transplant patients displaying histological patterns of acute T cell mediated rejection. In conclusion, assessment of circulating alloreactive memory/effector T cells using an INF‐γ Elispot assay can be accurately achieved using the same SOP, Elispot bioreader and experienced technicians in kidney transplantation.
Using a set of standardized operating procedures investigators can accurately assess circulating alloreactive memory/effector T cells in the context of kidney transplantation. See more in the CTOT series, pages 1859–1904.
Cytomegalovirus (CMV) infection influences both short and long term outcomes in immunosuppressed organ transplant recipients. The aim of this study was to evaluate the effect of different induction ...immunosuppression regimens on CMV specific T cell response in patients with already established CMV immunity. In 24 seropositive living donor kidney recipients, the frequency of CMV specific T cells was determined by ELISPOT (Enzyme-Linked ImmunoSpot) assay prior and 6 months after transplantation. Recipients' peripheral blood mononuclear cells were stimulated with immediate-early (IE1) and phosphoprotein 65 (pp65) CMV-derived peptide pools and the number of cells producing interferon gamma (IFN-gamma) was assessed. Patients received quadruple immunosuppression based either on depletive rabbit antithymocyte globulin (rATG) or non-depletive basiliximab induction and tacrolimus/mycophenolate mofetil/steroids. Patients with rATG induction received valgancyclovir prophylaxis. No effects of different induction agents on CMV specific T cell immunity were found at sixth month after kidney transplantation. There were no associations among dialysis vintage, pretransplant CMV specific T cell immunity, and later CMV DNAemia. Similarly, no effect of CMV prophylaxis on CMV specific T cell immunity was revealed. This study shows no effect of posttransplant immunosuppression on CMV specific T cell immunity in living donor kidney transplant recipients with CMV immunity already established, regardless of lymphocyte depletion and CMV prophylaxis.
Abstract There is a complex bidirectional relationship between stress and epilepsy. Stressful stimuli and subsequent cortisol release act as a trigger for seizure activity in some individuals with ...epilepsy, and seizure activity itself may act as a stressor to the affected individual. Epilepsy is the most common chronic neurological condition in domestic dogs and requires chronic management by their human carers, impacting upon the quality of life of both dog and carer. Seizures occur unpredictably and may be stressful for carers to witness and manage. In the present study we investigated the role of seizure activity as a stressor, measuring the effect of spontaneously occurring seizure activity in dogs with epilepsy upon their own cortisol levels and that of their carers. Furthermore, we tested whether individual differences in HPA reactivity were associated with owner personality characteristics and the quality of the dog–carer relationship. Saliva samples were obtained from sixteen dog-carer dyads in the home setting 20 and 40 minute post-seizure, and at time-matched points on the following (non-seizure) day. Significant differences in cortisol levels were found in dogs at 40 minute post-seizure (265.1% increase), and at 20 minute post-seizure in their carers (40.5% increase). No associations were found between cortisol reactivity and the strength of the dog-carer bond. Carers with higher neuroticism scores exhibited higher cortisol levels at both post-seizure sampling points. As there was a gender bias in the carer sample (15/16 were female), and there are known sex differences in cortisol reactivity in response to psychological stress, the conclusions of this study may be limited to female carers. These findings are the first to objectively demonstrate the acutely stressful effects of seizures in dogs with epilepsy and their carers.
Quantification of the humoral alloimmune response is generally achieved by measuring serum HLA antibodies, which provides no information about the cells involved in the humoral immune response. ...Therefore, we have developed an HLA‐specific B‐cell ELISPOT assay allowing for quantification of B cells producing HLA antibodies. We used recombinant HLA monomers as target in the ELISPOT assay. Validation was performed with human B‐cell hybridomas producing HLA antibodies. Subsequently, we quantified B cells producing HLA antibodies in HLA‐immunized individuals, non‐HLA‐immunized individuals and transplant patients with serum HLA antibodies. B‐cell hybridomas exclusively formed spots against HLA molecules of corresponding specificity with the sensitivity similar to that found in total IgG ELISPOT assays. HLA‐immunized healthy individuals showed up to 182 HLA‐specific B cells per million total B cells while nonimmunized individuals had none. Patients who were immunized by an HLA‐A2‐mismatched graft had up to 143 HLA‐A2‐specific B cells per million total B cells. In conclusion, we have developed and validated a highly specific and sensitive HLA‐specific B‐cell ELISPOT assay, which needs further validation in a larger series of transplant patients. This technique constitutes a new tool for quantifying humoral immune responses.
The authors show that peripheral blood B cells of defined HLA specificity can be enumerated using a novel, monomeric HLA molecule‐based assay.
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