Browsing by Subject "CLINICAL-FEATURES"

Sort by: Order: Results:

Now showing items 1-20 of 21
  • Sofou, Kalliopi; De Coo, Irenaeus F. M.; Isohanni, Pirjo; Ostergaard, Elsebet; Naess, Karin; De Meirleir, Linda; Tzoulis, Charalampos; Uusimaa, Johanna; De Angst, Isabell B.; Lonnqvist, Tuula; Pihko, Helena; Mankinen, Katariina; Bindoff, Laurence A.; Tulinius, Mar; Darin, Niklas (2014)
  • Kyöstilä, Kaisa; Cizinauskas, Sigitas; Seppälä, Eija; Suhonen, Esko; Jeserevics, Janis; Sukura, Antti; Syrjä, Pernilla Elisabet Sofia; Lohi, Hannes (2012)
  • de Boo, Leonora W.; Jozwiak, Katarzyna; Joensuu, Heikki; Lindman, Henrik; Lauttia, Susanna; Opdam, Mark; van Steenis, Charlaine; Brugman, Wim; Kluin, Roelof J. C.; Schouten, Philip C.; Kok, Marleen; Nederlof, Petra M.; Hauptmann, Michael; Linn, Sabine C. (2022)
    Background The addition of adjuvant capecitabine to standard chemotherapy of early-stage triple-negative breast cancer (TNBC) patients has improved survival in a few randomised trials and in meta-analyses. However, many patients did not benefit. We evaluated the BRCA1-like DNA copy number signature, indicative of homologous recombination deficiency, as a predictive biomarker for capecitabine benefit in the TNBC subgroup of the FinXX trial. Methods Early-stage TNBC patients were randomised between adjuvant capecitabine-containing (TX + CEX: capecitabine-docetaxel, followed by cyclophosphamide-epirubicin-capecitabine) and conventional chemotherapy (T + CEF: docetaxel, followed by cyclophosphamide-epirubicin-fluorouracil). Tumour BRCA1-like status was determined on low-coverage, whole genome next-generation sequencing data using an established DNA comparative genomic hybridisation algorithm. Results For 129/202 (63.9%) patients the BRCA1-like status could be determined, mostly due to lack of tissue. During a median follow-up of 10.7 years, 35 recurrences and 32 deaths occurred. Addition of capecitabine appears to improve recurrence-free survival more among 61 (47.3%) patients with non-BRCA1-like tumours (HR 0.23, 95% CI 0.08-0.70) compared to 68 (52.7%) patients with BRCA1-like tumours (HR 0.66, 95% CI 0.24-1.81) (P-interaction = 0.17). Conclusion Based on our data, patients with non-BRCA1-like TNBC appear to benefit from the addition of capecitabine to adjuvant chemotherapy. Patients with BRCA1-like TNBC may also benefit. Additional research is needed to define the subgroup within BRCA1-like TNBC patients who may not benefit from adjuvant capecitabine.
  • Chen, Honglei; Wang, Keran; Scheperjans, Filip; Killinger, Bryan (2022)
    Idiopathic Parkinson's disease (PD) may take decades to develop, during which many risk or protective factors may come into play to initiate the pathogenesis or modify its progression to clinical PD. The lack of understanding of this prodromal phase of PD and the factors involved has been a major hurdle in the study of PD etiology and preventive strategies. Although still controversial, the Braak and dual-hit hypotheses that PD may start peripherally in the olfactory structures and/or the gut provides a theoretical platform to identify the triggers and modifiers of PD prodromal development and progression. This is particularly true for the search of environmental causes of PD as the olfactory structures and gut are the major human mucosal interfaces with the environment. In this review, we lay out our personal views about how the Braak and dual-hit hypotheses may help us search for the environmental triggers and modifiers for PD, summarize available experimental and epidemiological evidence, and discuss research gaps and strategies.
  • Gershony, Liza C.; Belanger, Janelle M.; Hytonen, Marjo K.; Lohi, Hannes; Famula, Thomas R.; Oberbauer, Anita M. (2020)
    Background Primary hypoadrenocorticism (or Addison's disease, AD) is an autoimmune disease that results in destruction of the adrenal cortex and consequent adrenal insufficiency. The disease has been described in purebred and mixed breed dogs, although some breeds, including the Bearded Collie, are at increased risk for AD. Candidate gene approaches have yielded few associations that appear to be breed-specific. A single other genome-wide association study reported no significant regions of association for AD in Standard Poodles. The present study aimed to identify genomic regions of association for canine AD in Bearded Collies. Results Our study consists of the first genome-wide association analysis to identify a genome-wide significant region of association with canine AD (CFA18). Peaks of suggestive association were also noted on chromosomes 11, 16 and 29. Logistic regression analysis supported an additive effect of risk genotypes at these smaller effect loci on the probability of disease associated with carrying a risk genotype on CFA18. Potential candidate genes involved in adrenal steroidogenesis, regulation of immune responses and/or inflammation were identified within the associated regions of chromosomes 11 and 16. The gene-poor regions of chromosomes 18 and 29 may, however, harbor regulatory sequences that can modulate gene expression and contribute to disease susceptibility. Conclusion Our findings support the polygenic and complex nature of canine AD and identified a strongly associated locus on CFA18 that, when combined with three other smaller effect loci, was predictive of disease. The results offer progress in the identification of susceptibility loci for canine AD in the Bearded Collie. Further studies are needed to confirm association with the suggested candidate genes and identify actual causative mutations involved with AD susceptibility in this breed.
  • Abolhassani, Hassan; Azizi, Gholamreza; Sharifi, Laleh; Yazdani, Reza; Mohsenzadegan, Monireh; Delavari, Samaneh; Sohani, Mahsa; Shirmast, Paniz; Chavoshzadeh, Zahra; Mahdaviani, Seyed Alireza; Kalantari, Arash; Tavakol, Marzieh; Jabbari-Azad, Farahzad; Ahanchian, Hamid; Momen, Tooba; Sherkat, Roya; Sadeghi-Shabestari, Mahnaz; Aleyasin, Soheila; Esmaeilzadeh, Hossein; Al-Herz, Waleed; Bousfiha, Ahmed Aziz; Condino-Neto, Antonio; Seppänen, Mikko; Sullivan, Kathleen E.; Hammarstrom, Lennart; Modell, Vicki; Modell, Fred; Quinn, Jessica; Orange, Jordan S.; Aghamohammadi, Asghar (2020)
    Introduction During the last 4 decades, registration of patients with primary immunodeficiencies (PID) has played an essential role in different aspects of these diseases worldwide including epidemiological indexes, policymaking, quality controls of care/life, facilitation of genetic studies and clinical trials as well as improving our understanding about the natural history of the disease and the immune system function. However, due to the limitation of sustainable resources supporting these registries, inconsistency in diagnostic criteria and lack of molecular diagnosis as well as difficulties in the documentation and designing any universal platform, the global perspective of these diseases remains unclear. Areas covered Published and unpublished studies from January 1981 to June 2020 were systematically reviewed on PubMed, Web of Science and Scopus. Additionally, the reference list of all studies was hand-searched for additional studies. This effort identified a total of 104614 registered patients and suggests identification of at least 10590 additional PID patients, mainly from countries located in Asia and Africa. Molecular defects in genes known to cause PID were identified and reported in 13852 (13.2% of all registered) patients. Expert opinion Although these data suggest some progress in the identification and documentation of PID patients worldwide, achieving the basic requirement for the global PID burden estimation and registration of undiagnosed patients will require more reinforcement of the progress, involving both improved diagnostic facilities and neonatal screening.
  • Kuula, Laura S.M.; Backman, Janne; Blom, Marja (2022)
    The aim of this study was to estimate healthcare costs and mortality associated with serious fluoroquinolone-related adverse reactions in Finland from 2008 to 2019. Serious adverse reaction types were identified from the Finnish Pharmaceutical Insurance Pool's pharmaceutical injury claims and the Finnish Medicines Agency's Adverse Reaction Register. A decision tree model was built to predict costs and mortality associated with serious adverse drug reactions (ADR). Severe clostridioides difficile infections, severe cutaneous adverse reactions, tendon ruptures, aortic ruptures, and liver injuries were included as serious adverse drug reactions in the model. Direct healthcare costs of a serious ADR were based on the number of reimbursed fluoroquinolone prescriptions from the Social Insurance Institution of Finland's database. Sensitivity analyses were conducted to address parameter uncertainty. A total of 1 831 537 fluoroquinolone prescriptions were filled between 2008 and 2019 in Finland, with prescription numbers declining 40% in recent years. Serious ADRs associated with fluoroquinolones lead to estimated direct healthcare costs of 501 938 402 (sic), including 11 405 ADRs and 3,884 deaths between 2008 and 2019. The average mortality risk associated with the use of fluoroquinolones was 0.21%. Severe clostridioides difficile infections were the most frequent, fatal, and costly serious ADRs associated with the use of fluoroquinolones. Although fluoroquinolones continue to be generally well-tolerated antimicrobials, serious adverse reactions cause long-term impairment to patients and high healthcare costs. Therefore, the risks and benefits should be weighed carefully in antibiotic prescription policies, as well as with individual patients.
  • Nordal, Ellen; Rypdal, Veronika; Christoffersen, Terje; Aalto, Kristiina; Berntson, Lillemor; Fasth, Anders; Herlin, Troels; Nielsen, Susan; Peltoniemi, Suvi; Straume, Bjorn; Zak, Marek; Rygg, Marite; Nordic Study Grp Pediat Rheumatolo (2017)
    Background: The incidence of uveitis associated with juvenile idiopathic arthritis (JIA) varies around the world. Our aim was to investigate the incidence and predictors of uveitis in a Nordic population-based cohort. Methods: Consecutive JIA cases from defined geographical areas in Denmark, Finland, Sweden and Norway with disease onset between January 1997 to June 2000 were followed for median 98 months in this prospective longitudinal cohort study. Potential clinical and immunological predictors of uveitis were identified with logistic regression analysis. Results: Uveitis occurred in 89 (20.5%) of the 435 children with regular ophtalmologic follow-up among the 500 included. Chronic asymptomatic uveitis developed in 80 and acute symptomatic uveitis in 9 children. Uveitis developed at a median interval of 0.8 (range - 4.7 to 9.4) years after onset of arthritis. Predictors of uveitis were age <7 years at JIA onset (Odds ratio (OR) 2.1, 95% confidence interval (CI) 1.3 to 3.5), presence of antihistone antibodies (AHA) > 15 U/ml (OR 4.8 (1.8 to 13.4)) and antinuclear antibodies (ANA) (OR 2.4 (1.5 to 4.0)). Mean combined IgM/IgG AHA was significantly higher in the uveitis group (19.2 U/ml) than in the non-uveitis group (10.2 U/ml) (p = 0.002). Young age at JIA onset predicted uveitis in girls (p <0.001), but not in boys (p = 0.390). Conclusion: Early-onset arthritis and presence of AHA in girls, as well as presence of ANA in both genders, were significant predictors of chronic uveitis. The high incidence of uveitis in this long-term Nordic JIA cohort may have severe implications in a lifelong perspective.
  • Halonen, Pia; Jakobsson, Maija; Heikinheimo, Oskari; Gissler, Mika; Pukkala, Eero (2020)
    The incidence pattern of lichen planus (LP) and LP-related mortality are unknown. The aim of this study was to assess these factors, based on Finnish nationwide registry data including 13,378 women with LP diagnosed during 1969 to 2012. The incidence rate for LP in 2003 to 2012 was 28 per 100,000 woman-years age-adjusted to the European Standard Population. Mortality was assessed using the standardized mortality ratio (SMR) with national mortality rates as the reference. All-cause mortality was increased (SMR 1.07, 95% confidence interval (95% CI) 1.02-1.11), with excess mortality from Hodgkin lymphoma (SMR 6.73, 95% CI 1.83-17.2), non-Hodgkin lymphoma (SMR 1.68, 95% CI 1.11-2.44), cancer of the oral cavity (SMR 10.5, 95% CI 5.99-17.0), cancer of the tongue (SMR 7.25, 95% CI 3.13-14.3), infections (SMR 1.78, 95% CI 1.14-2.64), respiratory diseases (SMR 1.31, 95% CI 1.07-1.57), and diseases of the digestive system (SMR 1.39, 95% CI 1.09-1.75). In conclusion, LP is a common disease and patients seem to have an impaired long-term prognosis.
  • INTERACT2 Investigators; Kaste, Markku; Tatlisumak, Turgut (2017)
    Objective: To clarify associations between intracerebral hemorrhage (ICH) location and clinical outcomes among participants of the main phase Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT2). Methods: Associations between ICH sites and poor outcomes (death [6] or major disability [3-5] of modified Rankin Scale) and European Quality of Life Scale (EQ-5D) utility scores at 90 days were assessed in logistic regression models. Results: Of 2,066 patients included in the analyses, associations were identified between ICH sites and poor outcomes: involvement of posterior limb of internal capsule increased risks of death or major disability (odds ratio [OR] 2.10) and disability (OR 1.81); thalamic involvement increased risks of death or major disability (OR 2.24) and death (OR 1.97). Involvement of the posterior limb of the internal capsule, thalamus, and infratentorial sites were each associated with poor EQ-5D utility score ( Conclusion: Poor clinical outcomes are related to ICH affecting the posterior limb of internal capsule, thalamus, and infratentorial sites. The highest association with death or major disability and poor EQ-5D utility score was seen in ICH encompassing the thalamus and posterior limb of internal capsule.
  • Männistö, Jonna M. E.; Jääskeläinen, Jarmo; Otonkoski, Timo; Huopio, Hanna (2021)
    Context: The management of congenital hyperinsulinism (CHI) has improved. Objective: To examine the treatment and long-term outcome of Finnish patients with persistent and transient CHI (P-CHI and T-CHI). Design: A population-based retrospective study of CHI patients treated from 1972 to 2015. Patients: 106 patients with P-CHI and 132 patients with T-CHI (in total, 42 diagnosed before and 196 after year 2000) with median follow-up durations of 12.5 and 6.2 years, respectively. Main outcome measures: Recovery, diabetes, pancreatic exocrine dysfunction, neurodevelopment. Results: The overall incidence of CHI (n = 238) was 1:11 300 live births (1972-2015). From 2000 to 2015, the incidence of P-CHI (n = 69) was 1:13 500 and of T-CHI (n = 127) 1:7400 live births. In the 21st century P-CHI group, hyperinsulinemic medication was initiated and normoglycemia achieved faster relative to earlier. Of the 74 medically treated P-CHI patients, 68% had discontinued medication. Thirteen (12%) P-CHI patients had partial pancreatic resection and 19 (18%) underwent near-total pancreatectomy. Of these, 0% and 84% developed diabetes and 23% and 58% had clinical pancreatic exocrine dysfunction, respectively. Mild neurological difficulties (21% vs 16%, respectively) and intellectual disability (9% vs 5%, respectively) were as common in the P-CHI and T-CHI groups. However, the 21st century P-CHI patients had significantly more frequent normal neurodevelopment and significantly more infrequent diabetes and pancreatic exocrine dysfunction compared with those diagnosed earlier. Conclusions: Our results demonstrated improved treatment and long-term outcome in the 21st century P-CHI patients relative to earlier.
  • Savolainen, Marika; Pekkola, Johanna; Mustanoja, Satu; Tyni, Tiina; Hernesniemi, Juha; Kivipelto, Leena; Tatlisumak, Turgut (2020)
    Moyamoya angiopathy (MMA) is a chronic progressive disorder, but imaging changes observed over time are not yet characterized in European populations. We analyzed the progression of MMA with magnetic resonance imaging and angiography (MRI and MRA) in our Finnish MMA registry. Stage classification based on MRA findings was used to evaluate the progress of the disease.
  • PRIDE Consortium Investigators; Venkatesan, Sudhir; Myles, Puja R.; Bolton, Kirsty J.; Linko, Rita; Mikic, Dragan (2020)
    Background. The effect of neuraminidase inhibitor (NAI) treatment on length of stay (LoS) in patients hospitalized with influenza is unclear. Methods. We conducted a one-stage individual participant data (IPD) meta-analysis exploring the association between NAI treatment and LoS in patients hospitalized with 2009 influenza A(H1N1) virus (A[H1N1]pdm09) infection. Using mixed-effects negative binomial regression and adjusting for the propensity to receive NAI, antibiotic, and corticosteroid treatment, we calculated incidence rate ratios (I RRs) and 95% confidence intervals (CIs). Patients with a LoS of Results. We analyzed data on 18 309 patients from 70 clinical centers. After adjustment, NAI treatment initiated at hospitalization was associated with a 19% reduction in the LoS among patients with clinically suspected or laboratory-confirmed influenza A(H1N1)pdm09 infection (IRR, 0.81; 95% CI, .78-.85), compared with later or no initiation of NAI treatment. Similar statistically significant associations were seen in all clinical subgroups. NAI treatment (at any time), compared with no NAI treatment, and NAI treatment initiated Conclusions. When patients hospitalized with influenza are treated with NAIs, treatment initiated on admission, regardless of time since symptom onset, is associated with a reduced LoS, compared with later or no initiation of treatment.
  • Sofou, Kalliopi; de Coo, Irenaeus F. M.; Ostergaard, Elsebet; Isohanni, Pirjo; Naess, Karin; De Meirleir, Linda; Tzoulis, Charalampos; Uusimaa, Johanna; Lönnqvist, Tuula; Bindoff, Laurence Albert; Tulinius, Mar; Darin, Niklas (2018)
    Background Leigh syndrome is a phenotypically and genetically heterogeneous mitochondrial disorder. While some genetic defects are associated with well-described phenotypes, phenotype-genotype correlations in Leigh syndrome are not fully explored. Objective We aimed to identify phenotype-genotype correlations in Leigh syndrome in a large cohort of systematically evaluated patients. Methods We studied 96 patients with genetically confirmed Leigh syndrome diagnosed and followed in eight European centres specialising in mitochondrial diseases. Results We found that ataxia, ophthalmoplegia and cardiomyopathy were more prevalent among patients with mitochondrial DNA defects. Patients with mutations in MT-ND and NDUF genes with complex I deficiency shared common phenotypic features, such as early development of central nervous system disease, followed by high occurrence of cardiac and ocular manifestations. The cerebral cortex was affected in patients with NDUF mutations significantly more often than the rest of the cohort. Patients with the m. 8993T> G mutation in MT-ATP6 gene had more severe clinical and radiological manifestations and poorer disease outcome compared with patients with the m. 8993T> C mutation. Conclusion Our study provides new insights into phenotype-genotype correlations in Leigh syndrome and particularly in patients with complex I deficiency and with defects in the mitochondrial ATP synthase.
  • Bersano, Anna; Guey, Stephanie; Bedini, Gloria; Nava, Sara; Herve, Dominique; Vajkoczy, Peter; Tatlisumak, Turgut; Saarela, Marika; van der Zwan, Albert; Klijn, Catharina J. M.; Braun, Kees P. J.; Kronenburg, Annick; Acerbi, Francesco; Brown, Martin M.; Calviere, Lionel; Cordonnier, Charlotte; Henon, Hilde; Thines, Laurent; Khan, Nadia; Czabanka, M.; Kraemer, Markus; Simister, Robert; Prontera, Paolo; Tournier-Lasserve, E.; Parati, Eugenio; European Moyamoya Dis Initiative (2016)
    Background: The pathogenesis of moyamoya disease (MMD) is still unknown. The detection of inflammatory molecules such as cytokines, chemokines and growth factors in MMD patients' biological fluids supports the hypothesis that an abnormal angiogenesis is implicated in MMD pathogenesis. However, it is unclear whether these anomalies are the consequences of the disease or rather causal factors as well as these mechanisms remain insufficient to explain the pathophysiology of MMD. The presence of a family history in about 9-15% of Asian patients, the highly variable incidence rate between different ethnic and sex groups and the age of onset support the role of genetic factors in MMD pathogenesis. However, although some genetic loci have been associated with MMD, few of them have been replicated in independent series. Recently, RNF213 gene was shown to be strongly associated with MMD occurrence with a founder effect in East Asian patients. However, the mechanisms leading from RNF213 mutations to MMD clinical features are still unknown. Summary: The research on pathogenic mechanism of MMD is in its infancy. MMD is probably a complex and heterogeneous disorder, including different phenotypes and genotypes, in which more than a single factor is implicated. Key Message: Since the diagnosis of MMD is rapidly increasing worldwide, the development of more efficient stratifying risk systems, including both clinical but also biological drivers became imperative to improve our ability of predict prognosis and to develop mechanism-tailored interventions. (C) 2016 S. Karger AG, Basel
  • Gilchrist, James J.; Rautanen, Anna; Fairfax, Benjamin P.; Mills, Tara C.; Naranbhai, Vivek; Trochet, Holly; Pirinen, Matti; Muthumbi, Esther; Mwarumba, Salim; Njuguna, Patricia; Mturi, Neema; Msefula, Chisomo L.; Gondwe, Esther N.; MacLennan, Jenny M.; Chapman, Stephen J.; Molyneux, Malcolm E.; Knight, Julian C.; Spencer, Chris C. A.; Williams, Thomas N.; MacLennan, Calman A.; Scott, J. Anthony G.; Hill, Adrian V. S. (2018)
    Nontyphoidal Salmonella (NTS) is a major cause of bacteraemia in Africa. The disease typically affects HIV-infected individuals and young children, causing substantial morbidity and mortality. Here we present a genome-wide association study (180 cases, 2677 controls) and replication analysis of NTS bacteraemia in Kenyan and Malawian children. We identify a locus in STAT4, rs13390936, associated with NTS bacteraemia. rs13390936 is a context-specific expression quantitative trait locus for STAT4 RNA expression, and individuals carrying the NTS-risk genotype demonstrate decreased interferon-gamma (IFN gamma) production in stimulated natural killer cells, and decreased circulating IFN gamma concentrations during acute NTS bacteraemia. The NTS-risk allele at rs13390936 is associated with protection against a range of autoimmune diseases. These data implicate interleukin-12-dependent IFN gamma-mediated immunity as a determinant of invasive NTS disease in African children, and highlight the shared genetic architecture of infectious and autoimmune disease.
  • Ibaid, Ibtihag; Hussien, Mohammed; Kaukinen, Katri; Sabir, Omayma; Elmekki, Miskelyemen; Musa, Azza; Abdelhadi, Nasreldein; El Hussein, Abdel Rahim; Saavalainen, Paivi (2022)
    Objective The aim of the study was to determine the prevalence of coeliac disease (CD) and to recognise Human leukocyte antigen (HLA)-associated hereditary susceptibility to Sudanese CD patients with type 1 diabetes mellitus (DM1). Design Antitissue transglutaminase IgA (anti-TG IgA) was measured in the serum of 373 children affected with DM1 aged 1-19-year old and in 100 serum samples from non-diabetic control children. Histological examination was performed in 19 children seropositive for anti-TG IgA (17 DMI and 2 controls). Additionally, PCR-based analysis of Major histocompatibility complex, class II, DO beta 1 (HLA-DQB1) genotyping was implemented in three study population groups as follows: group 1 (n=25) (+ve DM1 and +ve CD), group 2 (n=63) (-ye DM1 and +ve CD) and control group 3 (n=2) (+ve CD). Results Twenty-six Sudanese children with DM1 out of 373 (6.97%) were seropositive for anti-TG IgA. Duodenal biopsy revealed Marsh 2 and 3 in 13 out of 17 (76.47%) seropositive anti-TG IgA patients with DM1. Significant association (p Conclusions Anti-TG IgA titre of greater than 10 times upper limit of normal (>= 10x ULN) can be useful for detecting CD in children with type 1 diabetes without duodenal biopsy. HLA testing in children with DM1 appears to provide little added benefit given the high prevalence (96%) of HLA DQ2/DQ8 in children with DM1.
  • Forsgård, Johanna A.; Metsähonkala, Liisa; Kiviranta, Anna-Mariam; Cizinauskas, Sigitas; Junnila, Jouni J. T.; Laitinen-Vapaavuori, Outi; Jokinen, Tarja S. (2019)
    Background: Stress, sleep deprivation, and infectious diseases are important seizure-precipitating factors in human epilepsy patients. However, these factors have not been thoroughly studied in epileptic dogs. Objective: Seizure-precipitating factors are common in dogs with idiopathic epilepsy and the occurrence of these factors associate with the dogs' signalment, personality, and epilepsy-related factors. Animals: Fifty dogs with diagnosed idiopathic epilepsy from the hospital populations of University Veterinary Teaching Hospital of University of Helsinki and Referral Animal Hospital Aisti. Methods: In a retrospective cross-sectional observational study, owners were interviewed about their dogs' possible seizure-precipitating factors according to a predefined questionnaire. The dogs were identified and selected by searching the medical records of the participating animal hospitals. Results: The prevalence of seizure-precipitating factors in the study population was 74% (37/50). The most frequently reported factors included stress-related situations, sleep deprivation, weather, and hormonal factors. In dogs with focal onset seizures, the number of precipitating factors was 1.9 (95% CI 1.1-3.4) times higher compared to dogs with generalized seizures. Conclusions and Clinical Importance: Seizure-precipitating factors are common in dogs with idiopathic epilepsy, and the nature of these factors is consistent with those of human patients. Aside from antiepileptic medication, acknowledging and avoiding seizure-precipitating factors could help veterinarians achieve better treatment outcomes.
  • Nordberg, Janne; Mpindi, John Patrick; Iljin, Kristiina; Pulliainen, Arto Tapio; Kallajoki, Markku; Kallioniemi, Olli; Elenius, Klaus; Elenius, Varpu (2012)
  • Hominickn, Devon; Silva, Asitha; Khurana, Noor; Liu, Ying; Dechow, Paul C.; Feng, Jian Q.; Pytowski, Bronislaw; Rutkowski, Joseph M.; Alitalo, Kari; Dellinger, Michael T. (2018)
    Patients with Gorham-Stout disease (GSD) have lymphatic vessels in their bones and their bones gradually disappear. Here, we report that mice that overexpress VEGF-C in bone exhibit a phenotype that resembles GSD. To drive VEGF-C expression in bone, we generated Osx-tTA; TetO-Vegfc double-transgenic mice. In contrast to Osx-tTA mice, Osx-tTA; TetO-Vegfc mice developed lymphatics in their bones. We found that inhibition of VEGFR3, but not VEGFR2, prevented the formation of bone lymphatics in Osx-tTA; TetO-Vegfc mice. Radiological and histological analysis revealed that bones from Osx-tTA; TetO-Vegfc mice were more porous and had more osteoclasts than bones from Osx-tTA mice. Importantly, we found that bone loss in Osx-tTA; TetO-Vegfc mice could be attenuated by an osteoclast inhibitor. We also discovered that the mutant phenotype of Osx-tTA; TetO-Vegfc mice could be reversed by inhibiting the expression of VEGF-C. Taken together, our results indicate that expression of VEGF-C in bone is sufficient to induce the pathologic hallmarks of GSD in mice.