Efficacy and tolerability of brivaracetam in patients with intellectual disability and epilepsy.

Patients with intellectual disability (ID) are often excluded from clinical trials, and little is known about the best approach to treat their epilepsy. Brivaracetam (BRV) is a new antiepileptic drug (AED) for adjunctive treatment in patients with focal-onset seizures with or without secondary generalization. We analyzed the efficacy and tolerability of BRV in patients with ID and epilepsy who either had or had not previously received treatment with levetiracetam (LEV). Data on efficacy and tolerability were retrospectively collected. After the initial start of BRV in our tertiary epilepsy center, we analyzed medical records at 0, 3, 6 and 12 months of follow-up. 116 patients were included (mean age = 34.9 years, 44% female). All had complete data of 3-month follow-up, 76 of 6-month follow-up, and 39 patients of 1-year follow-up. Median starting dose of BRV was 50.0 mg/day and the mean number of concomitant AEDs was 2.6. Seizure reduction and no side effects were reported in more than half of all patients. The most reported side effects were somnolence, dizziness and aggression. Retention rates for BRV were 84.4%, 75.5% and 58.1% after 3, 6 and 12 months, respectively. Seizure reduction and side effects did not differ significantly between the groups with or without previous LEV treatment. We demonstrate that BRV is effective and well tolerated in patients with epilepsy and ID, even in those where previous LEV treatment failed.

Nonambipolar Transport due to Electrons with 3D Resistive Response in the KSTAR Tokamak.

A small nonaxisymmetric (3D) magnetic field can induce nonambipolar transport of the particle species confined in a tokamak and thus a significant change of plasma rotation. This process can be in a favor of instability control in the region where the tokamak plasma is sufficiently collisional and resistive, as observed in the applications of n=1 resonant magnetic perturbations to the KSTAR tokamak. The plasma rotation can be globally accelerated due to radially drifting electrons and constrained to the electron root, if the radial transport is enhanced by an amplified 3D response. This mechanism is verified by a kinetically self-consistent magnetohydrodynamic modeling for both response and transport, which offers the quantitative explanations on the internal n=1 structure detected by electron-cyclotron-emission imaging and the cocurrent plasma spinning observed in the experiments.

Mood, anxiety, and perceived quality of life in adults with epilepsy and intellectual disability.

OBJECTIVE: Depression and anxiety symptoms are common among patients with epilepsy, but are relatively under-researched in patients with both epilepsy and intellectual disability (ID). The aim was to investigate whether epilepsy and ID characteristics are associated with mood, anxiety, and quality of life. MATERIALS AND METHODS: Adult patients with epilepsy and ID who rely on tertiary epilepsy care were included (N = 189). Mood, anxiety, and quality of life were assessed by standardized questionnaires. Epilepsy and ID characteristics were retrieved from patient charts or determined by psychometric instruments. RESULTS: Elevated levels of depressive and anxiety symptoms were present in 21.7% and 12.7%, respectively. Anxiety was significantly associated with a focal epilepsy type and ID domain discrepancy (substantial difference between two domains of adaptive behavior), but was negatively related to seizure frequency and drug load of mood-stabilizing antiepileptic drugs. Depressive symptoms were not significantly related to epilepsy characteristics, but a severe ID and ID domain discrepancy was associated with more depressive symptoms. Quality of life was significantly worse in those with multiple seizure types and ID domain discrepancy. CONCLUSION: Whereas anxiety and quality of life are associated with individual epilepsy characteristics, this could not be confirmed for depressive symptoms in patients with epilepsy and ID, despite its high prevalence.

Diagnostic exome sequencing in 100 consecutive patients with both epilepsy and intellectual disability.

OBJECTIVE: Epilepsy is highly prevalent among patients with intellectual disability (ID), and seizure control is often difficult. Identification of the underlying etiology in this patient group is important for daily clinical care. We assessed the diagnostic yield of whole exome sequencing (WES). In addition, we evaluated which clinical characteristics influence the likelihood of identifying a genetic cause and we assessed the potential impact of the genetic diagnosis on (antiepileptic) treatment strategy. METHODS: One hundred patients with both unexplained epilepsy and (borderline) ID (intelligence quotient ≤ 85) were included. All patients were evaluated by a clinical geneticist, a (pediatric) neurologist, and/or a specialist ID physician. WES analysis was performed in two steps. In step 1, analysis was restricted to the latest versions of ID and/or epilepsy gene panels. In step 2, exome analysis was extended to all genes (so-called full exome analysis). The results were classified according to the American College of Medical Genetics and Genomics guidelines. RESULTS: In 58 patients, the diagnostic WES analysis reported one or more variant(s). In 25 of the 100 patients, these were classified as (likely) pathogenic, in 24 patients as variants of uncertain significance, and in the remaining patients the variant was most likely not related to the phenotype. In 10 of 25 patients (40%) with a (likely) pathogenic variant, the genetic diagnosis might have an impact on the treatment strategy in the future. SIGNIFICANCE: This study illustrates the clinical diagnostic relevance of WES for patients with both epilepsy and ID. It also demonstrates that implementing WES diagnostics might have impact on the (antiepileptic) treatment strategy in this population. Confirmation of variants of uncertain significance in (candidate) genes may further increase the yield.

Challenging behavior in adults with epilepsy and intellectual disability: An analysis of epilepsy characteristics.

PURPOSE: The study aimed to describe the frequency and severity of self-injurious, stereotyped, and aggressive/destructive behavior in adults with both epilepsy and intellectual disability (ID) who reside at a tertiary epilepsy center and to investigate the associations between challenging behavior and epilepsy and ID characteristics. METHOD: The frequency and severity of self-injurious, (motoric) stereotyped, and aggressive/destructive behavior among 189 patients was assessed using the Behavior Problem Inventory. Comparisons were made with an adult reference population with ID, based on gender, to determine whether the behavior was clinically deviant. Epilepsy characteristics, including age at onset, epilepsy type, seizure types, seizure frequency, and use of antiepileptic drugs (AEDs), were retrieved from patient files. The level of ID was classified using the Diagnostic and Statistical Manual of Mental Disorders - Fifth Edition (DSM-5) and an ID domain discrepancy was allocated if there was a substantial difference between two domains of adaptive behavior within a subject. RESULTS: Self-injurious behavior was present in 35% of subjects, stereotyped behavior in 60%, and aggressive/destructive behavior in 63%. The behavior exceeded clinical norms in 7%, 18%, and 12%, respectively. Aggression was the behavior evaluated most often as being problematic, despite its reported frequency being the lowest. When adjusting for level of ID and use of psychotropic medication, logistic regression analyses showed that self-injurious behavior was significantly associated with a lower number of AEDs (odds ratio (OR) = 0.4); that stereotyped behavior was significantly associated with a higher number of seizure types (OR = 1.4) and a lower number of AEDs (OR = 0.4); and that aggression was significantly associated with the presence of an ID domain discrepancy (OR = 3.1). CONCLUSION: Challenging behavior is a serious issue among adults with epilepsy and ID. Although some of the epilepsy and ID characteristics seemed to contribute independently to these types of challenging behavior, the effects of epilepsy-related characteristics are modest when compared with ID.

Psychogenic nonepileptic seizures in adults with epilepsy and intellectual disability: A neglected area.

PURPOSE: To describe the main characteristics of psychogenic nonepileptic seizures (PNES) in adults with epilepsy and intellectual disability (ID), and to analyse the differences regarding psychosocial functioning, epilepsy severity and ID between patients with PNES and a control group without PNES. METHODS: Medical records of adults with ID and epilepsy living at an epilepsy care facility (N = 240) were screened for PNES and evaluated by a neurologist. A control group consisting of patients with epilepsy and ID, without PNES, was matched according to age, sex and level of ID. Characteristics of PNES and epilepsy were provided by the subject's nursing staff or retrieved from patient charts, psychosocial data were collected by standardised questionnaires and level of ID was individually assessed using psychometric instruments. RESULTS: The point prevalence of PNES was 7.1%. The patients with PNES (n = 15) were most often female and had a mild or moderate level of ID. Compared to controls, they showed more depressive symptoms, experienced more negative life events and had more often an ID discrepancy (ID profile with one domain particularly more impaired than another). Stress-related triggers were recognised in a large majority by the nursing staff. CONCLUSION: PNES appears to be a relatively rare diagnostic entity among inpatients with both epilepsy and ID. However, the complexity of diagnosing PNES in this population, and the similarities in stress-related triggers for PNES in patients with and without ID, suggest that PNES may be underdiagnosed in the ID population. Diagnostic challenges of PNES and, as subcategory, reinforced behavioural patterns are discussed.

Accuracy of WISC-III and WAIS-IV short forms in patients with neurological disorders.

The assessment of intellectual abilities is intensive, time-consuming, and might be considered burdensome for patients. We examined psychometric qualities of short forms (SFs) of the Wechsler Intelligence Scales for Children (WISC-third edition) and for adults (WAIS-fourth edition), in children (n = 986; Mage = 10.9) and adults (n = 324; Mage = 40.9) with neurological disorders. SF estimates were compared with Full Scale IQ (FSIQ), obtained by a complete administration, for the entire sample and for the subgroups FSIQ < 80 and FSIQ ≥ 80. The FSIQ was correctly identified within ± 7 points in 86% of children and 87% of adults. There were, however, some differences regarding the optimal SF subtest combination between subgroups. Although clinical inferences should not be made, SFs may be useful in research settings to obtain a global estimate of intelligence, and in clinical settings to screen periodically for possible intellectual deterioration.

Evaluation of perampanel in patients with intellectual disability and epilepsy.

INTRODUCTION: Initial registration studies of perampanel (PMP), an AMPA receptor antagonist, have now been followed up by 'clinical' studies that confirmed its efficacy and safety in patients with refractory epilepsy. Publications on the use of PMP among patients with intellectual disability (ID) are still limited. This study extends our knowledge with respect to the relevance of PMP for patients with both ID and epilepsy, and furthermore specifies the behavioral side effects of PMP in this specific population. METHODS: Retrospective evaluation of medical records at 3, 6 and 12months of follow-up after the initial start of PMP. RESULTS: 62 patients were included. 21 patients (33.9%) were female. All patients had complete data of 6months follow-up and we were able to review 42 patients with a 1-year follow-up. Level of ID varied from borderline to profound, and mild ID was most common (43.5%). The mean maximum daily dosage of PMP was 5.6mg (range 1-12mg). Retention rates for PMP were 87.1% and 67.7% after three and six months. A trend indicated a longer mean retention time in patients with a more severe ID (borderline-mild-moderate ID: 205days, severe-profound ID: 275days). Seizure reduction was achieved in 53.2%. 36 patients (58.1%) experienced adverse effects, 80.6% of those within 3months. 45.2% of the patients experienced somatic adverse effects. Most common were fatigue & sleep problems, motor problems & unsteadiness, and gastrointestinal problems. Behavioral adverse effects were present in 40.3%. Most common were aggression, agitated behavior, disruptive behavior, and mood symptoms. Reasons for discontinuation of PMP were lack of efficacy in 14.8%, intolerable adverse effects in 44.4%, and a combination of both in 40.7%. Altogether, 24.2% (15/62) of the patients achieved seizure reduction without experiencing adverse effects, though none reached seizure freedom. CONCLUSIONS: The use of PMP might lead to an effective seizure reduction without adverse effects in a minority of patients with both epilepsy and ID. Pre-existing behavioral problems or polypharmacy do not predict the occurrence of additional behavioral adverse effects, implying that these patients need not be excluded from the introduction of PMP when clinically indicated. Patients should, ideally, be monitored at a multidisciplinary clinic.

A systematic review of neuropsychiatric comorbidities in patients with both epilepsy and intellectual disability.

Epilepsy is a neurological condition that is particularly common in people with intellectual disability (ID). The care for people with both epilepsy and ID is often complicated by the presence of neuropsychiatric disorders, defined as psychiatric symptoms, psychiatric disorders, and behavioral problems. The aim of this study was to investigate associations between epilepsy or epilepsy-related factors and neuropsychiatric comorbidities in patients with ID and between ID and neuropsychiatric comorbidities in patients with epilepsy. We performed a systematic review of the literature, published between January 1995 and January 2015 and retrieved from PubMed/Medline, PsycINFO, and ERIC and assessed the risk of bias using the SIGN-50 methodology. Forty-two studies were identified, fifteen of which were assessed as having a low or acceptable risk-of-bias evaluation. Neuropsychiatric comorbidities were examined in relation to epilepsy in nine studies; in relation to epilepsy-related factors, such as seizure activity, seizure type, and medication in four studies; and in relation to the presence and degree of ID in five studies. We conclude that the presence of epilepsy only was not a clear determinant of neuropsychiatric comorbidity in patients with ID, although a tendency towards negative mood symptoms was identified. Epilepsy-related factors indicating a more severe form of epilepsy were associated with neuropsychiatric comorbidity as was the presence of ID as compared to those without ID in patients with epilepsy, although this should be validated in future research. A large proportion of the studies in this area is associated with a substantial risk of bias. There is a need for high quality studies using standardized methods to enable clear conclusions to be drawn that might assist in improving the quality of care for this population.

Are the Oxford(®) medial unicompartmental knee arthroplasty new instruments reducing the bearing dislocation risk while improving components relationships? A case control study.

INTRODUCTION: The recently introduced Microplasty(®) system is an upgrade of conventional phase III instrumentation. However, little is known of its impact on the position of the implant following the Oxford(®) mobile-bearing unicompartmental knee arthroplasty (UKA). This study investigated whether the Microplasty(®) instrumentation system can improve the positioning of the implant and reduce the rate of early failure. HYPOTHESIS: Microplasty(®) provides a better positioning and decreases the rate of dislocation. MATERIALS AND METHODS: The medical records and radiographs of 82 consecutive Oxford(®) UKAs were reviewed retrospectively. The radiographic parameters and prevalence of early failure of 41 UKAs performed with the Microplasty(®) system and 41 UKAs using the conventional instrumentation system were compared. Both groups were comparable in terms of demographics and preoperative status. RESULTS: The femoral components in the Microplasty(®) group were more contiguously placed and more convergent in relation to the tibial components compared to the conventional instrumentation system (P<0.01). The frequency of bearing dislocation was lower in the Microplasty(®) group (P=0.04). A wide gap and the angle between components were associated with an increased risk of bearing dislocation. CONCLUSION: The Microplasty(®) instrumentation system consistently placed the femoral and tibial components in more contiguous and convergent positions. Such changes in position decreased the risk of bearing dislocations by reducing the space available for bearing rotation. LEVEL OF EVIDENCE: Level III, case control study.

Structural analysis of muscarinic acetylcholine receptor type 1 intracellular loop 3 by hydrogen/deuterium exchange mass spectrometry.

G protein-coupled receptors (GPCRs) perform vital signaling functions and are involved in various diseases, making GPCRs major drug targets. GPCRs have seven α-helical transmembrane domains connected by three extracellular loops (ECLs) and three intracellular loops (ICLs). Among the three ICLs, ICL3 has been reported to have a critical function in interacting with downstream signaling molecules. Despite its important role in GPCR signaling, the structure of ICL3 has not been fully defined. In the present study, we used muscarinic acetylcholine receptor type 1 (M1) as a model system to analyze the structure of ICL3. Optimized purification conditions for M1_ICL3 comprised His-tag affinity purification and solubilization with n-dodecyl-b-D-maltopyranoside. Purified M1_ICL3 was analyzed using circular dichroism and hydrogen/deuterium exchange mass spectrometry; the results of these analyses suggested that M1_ICL3 is disordered and flexible.

Vitamin D supplementation in children with epilepsy and intellectual disability.

BACKGROUND: Children with epilepsy and intellectual disability have an increased risk of vitamin D deficiency. In this patient group, it is neither clear which factors are associated with the level of 25-hydroxyvitamin D nor what the therapeutic results are when Dutch guidelines are followed. METHODS: This retrospective study included 30 patients who, in October 2012, were residents of the children's wards of a tertiary epilepsy center in The Netherlands (Kempenhaeghe). From November 2012 onward they received cholecalciferol supplementation in doses that met or exceeded Dutch guidelines. At baseline, after 6, and 15 months, serum 25-hydroxyvitamin D concentration was measured. RESULTS: At baseline, the vitamin D status in 11 (36.7%) residents was found to be deficient, in 10 (33.3%) to be insufficient and in 9 (30.0%) sufficient. Supplementation dose, diet, body mass index, intellectual disability, and mobility were significantly associated with baseline 25-hydroxyvitamin D concentrations. The mean 25-hydroxyvitamin D concentration increased significantly from 57.40 ± 22.00 nmol/L at baseline to 89.47 ± 26.77 nmol/L after 15 months (P < 0.001). In spite of supplementation ranging from 400 to 1200 IU/day, 64% of the residents in the deficient category and 30% of those with an insufficient level at baseline failed to attain a sufficient vitamin D status after 15 months. CONCLUSIONS: Not all residents reached a sufficient vitamin D status after supplementation at least equal to the amount recommended by the Dutch guidelines. In a high-risk population, such as our residents, we advise monitoring 25-hydroxyvitamin D concentrations, adjusting supplementation accordingly and following patients to ensure they reach sufficiency.

Inactivation of the lpcC gene alters surface-related properties and symbiotic capability of Bradyrhizobium japonicum.

UNLABELLED: We investigated the role of the Bradyrhizobium japonicum lpcC gene, encoding a mannosyl transferase, involved in the lipopolysaccharide (LPS) biosynthesis. The inactivation of the lpcC gene considerably altered the LPS structure and the cell surface properties. LPS analysis showed that the lpcC mutant JS715 had an abnormal LPS structure deficient in O-antigen. The cell surface hydrophobicity increased approximately threefold in JS715 compared to the wild type. The increased cell surface hydrophobicity is likely to be related with cell aggregation in the mutant culture. For the growth comparison, JS715 showed slower growth rate than the wild type. The motility of JS715 decreased in soft agar plates, but it showed enhanced biofilm-forming ability. Interestingly, JS715 was not able to nodulate the host legume soybean (Glycine max). This study shows not only that lpcC is involved in the biosynthesis of O-antigen in the B. japonicum LPS, but also that inactivation of the lpcC gene affects symbiotic capability of B. japonicum and surface-related properties such as cell hydrophobicity, biofilm formation and motility. SIGNIFICANCE AND IMPACT OF THE STUDY: This study demonstrates the role of the B. japonicum lpcC in nodulation with soybean and importance of cell surface hydrophobicity. The results also highlight that intact LPS is required for successful symbiosis between B. japonicum and soybeans. Our findings not only support previous studies emphasizing the necessity of LPS on the interaction between the two symbiotic partners, but also contribute to a better understanding of the symbiotic mechanisms.

Inhibition of Hedgehog signaling sensitizes NSCLC cells to standard therapies through modulation of EMT-regulating miRNAs.

BACKGROUND: Epidermal growth factor receptor- tyrosine kinase inhibitors (EGFR-TKIs) benefit Non-small cell lung cancer (NSCLC) patients, and an EGFR-TKIi erlotinib, is approved for patients with recurrent NSCLC. However, resistance to erlotinib is a major clinical problem. Earlier we have demonstrated the role of Hedgehog (Hh) signaling in Epithelial-to-Mesenchymal transition (EMT) of NSCLC cells, leading to increased proliferation and invasion. Here, we investigated the role of Hh signaling in erlotinib resistance of TGF-ß1-induced NSCLC cells that are reminiscent of EMT cells. METHODS: Hh signaling was inhibited by specific siRNA and by GDC-0449, a small molecule antagonist of G protein coupled receptor smoothened in the Hh pathway. Not all NSCLC patients are likely to benefit from EGFR-TKIs and, therefore, cisplatin was used to further demonstrate a role of inhibition of Hh signaling in sensitization of resistant EMT cells. Specific pre- and anti-miRNA preparations were used to study the mechanistic involvement of miRNAs in drug resistance mechanism. RESULTS: siRNA-mediated inhibition as well as pharmacological inhibition of Hh signaling abrogated resistance of NSCLC cells to erlotinib and cisplatin. It also resulted in re-sensitization of TGF-ß1-induced A549 (A549M) cells as well the mesenchymal phenotypic H1299 cells to erlotinib and cisplatin treatment with concomitant up-regulation of cancer stem cell (CSC) markers (Sox2, Nanog and EpCAM) and down-regulation of miR-200 and let-7 family miRNAs. Ectopic up-regulation of miRNAs, especially miR-200b and let-7c, significantly diminished the erlotinib resistance of A549M cells. Inhibition of Hh signaling by GDC-0449 in EMT cells resulted in the attenuation of CSC markers and up-regulation of miR-200b and let-7c, leading to sensitization of EMT cells to drug treatment, thus, confirming a connection between Hh signaling, miRNAs and drug resistance. CONCLUSIONS: We demonstrate that Hh pathway, through EMT-induction, leads to reduced sensitivity to EGFR-TKIs in NSCLCs. Therefore, targeting Hh pathway may lead to the reversal of EMT phenotype and improve the therapeutic efficacy of EGFR-TKIs in NSCLC patients.

Efficacy of light-emitting diode photomodulation in reducing erythema after fractional carbon dioxide laser resurfacing: a pilot study.

BACKGROUND: The most common side effects of fractional carbon dioxide (CO2 ) laser resurfacing are erythema and edema of the treated skin. Light-emitting diode (LED) devices have been shown to stimulate fibroblast activity and hasten wound healing. The current study was designed to evaluate the efficacy of such LED devices in treating post-laser therapy erythema. OBJECTIVES: To evaluate the clinical efficacy of LED photomodulation in reducing erythema resulting from ablative fractional CO2 laser resurfacing. MATERIALS AND METHODS: Randomly selected facial halves of 10 Korean subjects (Fitzpatrick skin type III-IV) were treated using a 635-nm wavelength LED array immediately after full-face fractional laser skin resurfacing. Each participant was subsequently treated with LED daily for the following 7 days. Clinical photographs, subjective physician assessment, and chromometer erythema index were used to track the results, with clinical improvement assessed using a 5-point grading scale. RESULTS: The postlaser erythema resolved faster on the experimental side than the control side, with improvements noted according to physician assessment and chromometer erythema index. Statistically significant improvements between the two sides were first noted on day 4. CONCLUSION: Treatment using a 635-nm-wavelength LED array decreases the intensity and duration of post-fractional CO2 laser treatment erythema.

Targeting the Hedgehog signaling pathway for cancer therapy.

INTRODUCTION: Hedgehog (Hh) signaling pathway plays key roles in embryonic development, formation and maintenance of cancer stem cells (CSCs) and acquisition of epithelial-to-mesenchymal transition (EMT). Since CSCs and EMT are important biological factors responsible for cancer cell invasion, metastasis, drug resistance and tumor recurrence, the Hh signaling pathway is believed to be an important target for cancer therapy. AREAS COVERED: In recent years, small-molecule inhibitors of Hh signaling have been synthesized for cancer treatment. Clinical trials using these inhibitors are being conducted to determine their toxicity profiles and efficacies. In addition, nutraceuticals (such as isoflavones, curcumin, vitamin D, etc) have been shown to inhibit cancer growth through downregulation of Hh signaling. EXPERT OPINION: Inhibition of Hh signaling is important for suppression of cancer growth, invasion, metastasis and recurrence in cancer therapy. However, targeting only one molecule in Hh signaling may not be sufficient to kill cancer cells because cancers show deregulation of multiple signals. Therefore, utilizing new technologies to determine alterations in Hh and other signals for individuals and designing combination strategies with small-molecule Hh inhibitors, nutraceuticals and other chemotherapeutics in targeted personalized therapy could have a significant effect on improving the overall survival of patients with cancers.

Production of an anticanine globulin (polyspecific) reagent for laboratory investigation.

OBJECTIVES: Canine allo- or autoantibodies are clinically important, but attachment of these immunoglobulin G (IgG) antibodies does not produce observable haemagglutination. Antibody to canine globulins is required to demonstrate sensitisation of red blood cells. Commercial reagents are available, but these often differ in sensitivity and specificity. Rabbit anticanine globulins (polyspecific) were produced for use in canine blood compatibility testing and in the investigation of immune-mediated haemolytic anaemia. METHODS: Canine sera was pooled, IgG was purified and subsequently used to immunise rabbits. A rising titre of anticanine IgG was demonstrated by indirect enzyme-linked immunosorbent assay. Rabbit anticanine complement was isolated and investigated by agglutination of complement-coated canine red blood cells. Both antibodies were purified and checked for crossreactivity before being combined to polyspecific anticanine globulins. The obtained reagent was used to indicate sensitised canine red blood cells and free antibodies in three different types of clinical samples, including blood for compatibility testing and that for investigation of immune-mediated haemolytic anaemia and screening for post-transfusion alloantibodies and was also compared to commercial Coombs' reagent. RESULTS: The product provided results in accordance with those from commercial Coombs' reagent. The sensitivity for canine crossmatching was 100% and specificity for diagnosing immune-mediated haemolytic anaemia was 87%. CLINICAL SIGNIFICANCE: This product is helpful for canine crossmatching purposes and in the investigation of immune-mediated haemolytic anaemia.