• A 10-year follow-up of snoring in men

      Lindberg, E; Taube, A; Janson, C; Gislason, T; Svärdsudd, K; Boman, G; Department of Lung Medicine and Asthma Research Centre, Uppsala University, Akademiska Sjukhuset, Sweden. (American College of Chest Physicians, 1998-10-01)
      STUDY OBJECTIVES: Little is known about the natural development of snoring, and this survey was conducted to study the development of snoring in men over a 10-year period. DESIGN: Population-based prospective survey. SETTING: The Municipality of Uppsala, Sweden. PARTICIPANTS AND MEASUREMENTS: In 1984, 3,201 randomly selected men aged 30 to 69 years answered a questionnaire on snoring and sleep disturbances. Of the 2,975 survivors in 1994, 2,668 (89.7%) answered a new questionnaire with identical questions to those used at baseline. Questions about smoking habits, alcohol, and physical activity were also added. RESULTS: Habitual snoring was reported by 393 men (15.0%) in 1984 and by 529 (20.4%) 10 years later. In both 1984 and 1994, the prevalence of snoring increased until age 50 to 60 years and then decreased. Risk factors for being a habitual snorer at the follow-up were investigated using multiple logistic regression with adjustments for previous snoring status, age, body mass index (BMI), weight gain, smoking habits, and physical activity. In men aged 30 to 49 years at baseline, the predictors of habitual snoring at the follow-up, in addition to previous snoring status, were as follows: persistent smoking (adjusted odds ratio, 95% confidence interval) (1.4, 1.1 to 1.9), BMI 1984 (1.1, 1.02 to 1.1/kg/m2) and weight gain (1.1, 1.03 to 1.2/kg/m2). Among men aged 50 to 69 years, after adjustments for previous snoring status and age, weight gain was the only significant risk factor for developing habitual snoring (1.2, 1.05 to 1.4/kg/m2). CONCLUSIONS: In men, the prevalence of snoring increases up to the age of 50 to 60 years and is then followed by a decrease. Weight gain is a risk factor for snoring in all age groups, while smoking is mainly associated with snoring in men <60 years of age.
    • 15q11.2 CNV affects cognitive, structural and functional correlates of dyslexia and dyscalculia.

      Ulfarsson, M O; Walters, G B; Gustafsson, O; Steinberg, S; Silva, A; Doyle, O M; Brammer, M; Gudbjartsson, D F; Arnarsdottir, S; Jonsdottir, G A; et al. (Nature Publishing Group, 2017-04-25)
      Several copy number variants have been associated with neuropsychiatric disorders and these variants have been shown to also influence cognitive abilities in carriers unaffected by psychiatric disorders. Previously, we associated the 15q11.2(BP1-BP2) deletion with specific learning disabilities and a larger corpus callosum. Here we investigate, in a much larger sample, the effect of the 15q11.2(BP1-BP2) deletion on cognitive, structural and functional correlates of dyslexia and dyscalculia. We report that the deletion confers greatest risk of the combined phenotype of dyslexia and dyscalculia. We also show that the deletion associates with a smaller left fusiform gyrus. Moreover, tailored functional magnetic resonance imaging experiments using phonological lexical decision and multiplication verification tasks demonstrate altered activation in the left fusiform and the left angular gyri in carriers. Thus, by using convergent evidence from neuropsychological testing, and structural and functional neuroimaging, we show that the 15q11.2(BP1-BP2) deletion affects cognitive, structural and functional correlates of both dyslexia and dyscalculia.
    • A [17F]-fluoromethane PET/TMS study of effective connectivity

      Ferrarelli, Fabio; Haraldsson, H Magnus; Barnhart, Todd E; Roberts, Andy D; Oakes, Terrence R; Massimini, Marcello; Stone, Charles K; Kalin, Ned H; Tononi, Giulio (Elsevier Science, 2004-08-30)
      We used transcranial magnetic stimulation (TMS) in combination with positron emission tomography (PET) to investigate the effective connectivity of four cortical regions within the same study. By employing [17F]-[CH3F] ([17F]-fluoromethane) as a radiotracer of blood-flow, we were able to obtain increased sensitivity compared to [15O]-H2O for both cortical and subcortical structures. The brain areas investigated were left primary motor cortex, right primary visual cortex, and left and right prefrontal areas. We found that each site of stimulation yielded a different pattern of activation/deactivation consistent with its anatomical connectivity. Moreover, we found that TMS of prefrontal and motor cortical areas gave rise to trans-synaptic activation of subcortical circuits.
    • [(18)F]Fluorodeoxyglucose-positron emission tomography/computed tomography response evaluation can predict histological response at surgery after induction chemotherapy for oligometastatic bladder cancer.

      Kollberg, Petter; Almquist, Helen; Bläckberg, Mats; Cwikiel, Magdalena; Gudjonsson, Sigurdur; Lyttkens, Kerstin; Patschan, Oliver; Liedberg, Fredrik; [ 1 ] Helsingborg Cty Hosp, Dept Urol, Helsingborg, Sweden Show the Organization-Enhanced name(s) [ 2 ] Lund Univ, Dept Translat Med, Lund, Sweden Show the Organization-Enhanced name(s) [ 3 ] Skane Univ Hosp, Dept Med Imaging & Physiol, Lund, Sweden Show the Organization-Enhanced name(s) [ 4 ] Skane Univ Hosp, Dept Oncol, Lund, Sweden Show the Organization-Enhanced name(s) [ 5 ] Landspitali Univ Hosp, Dept Urol, Reykjavik, Iceland Show the Organization-Enhanced name(s) [ 6 ] Skane Univ Hosp, Dept Urol, Malmo, Sweden (Taylor & Francis, 2017-08)
      Patients with limited metastatic and locally advanced bladder cancer have a poor prognosis, and no definite treatment recommendations exist. However, long-term survival is possible for selected patients if surgery is combined with multiple courses of chemotherapy (i.e. induction chemotherapy). Patients with tumours that are insensitive to chemotherapy probably have little to gain from subsequent extensive surgery. The aim of this study was to evaluate sequential FDG-PET/CT examinations as an indicator of chemotherapy response.
    • 2,8-dihydroxyadeninuria: are there no cases in Scandinavia?

      Arnadottir, Margret; Laxdal, Throstur; Halldorsdottir, Bergljot (Taylor & Francis, 2005-02-01)
      Homozygosity or mixed heterozygosity for mutations in the adenine phosphoribosyltransferase gene cause enzyme deficiency directing adenine through an alternative metabolic pathway. This results in the production of 2,8-dihydroxyadenine, which is actively secreted into the urine. 2,8-dihydroxyadenine is insoluble at physiological urinary pH but as marked supersaturation is possible the manifestations differ: there may be minimal consequences, there may be infiltration of the tubulointerstitial tissue with acute or chronic damage or there may be stone formation in the urinary tract. Effective treatment can be offered and therefore the prognosis depends upon the renal function at diagnosis. Treatment consists of adequate fluid intake, a low-purine diet and administration of allopurinol. Urinary 2,8-dihydroxyadenine crystals are easily recognized under a microscope. The diagnosis of 2,8-dihydroxyadeninuria can be confirmed by estimation of adenine phosphoribosyltransferase activity in erythrocyte lysates. More than 300 cases of 2,8-dihydroxyadeninuria have been diagnosed worldwide, most of them in Japan, France and Iceland. One case has been reported in Finland but there have been no reports from the Scandinavian peninsula or from Denmark. The relevant mutations may be very rare in these countries but underdiagnosis is also possible.
    • The 2-year course following detoxification treatment of substance abuse: the possible influence of psychiatric comorbidity

      Tomasson, K; Vaglum, P; Department of Psychiatry, National University Hospital, Landspítalinn, Reykjavík, Iceland. (Springer, 1997)
      The influence of psychiatric comorbidity on the course and outcome in a nationwide representative sample (n = 351) of treatment-seeking substance users over a 28-month period was studied prospectively. The patients were administered the Diagnostic Interview Schedule and a questionnaire on drinking history. At 16 and 28 months after admission the patients returned a questionnaire on drinking history and mental health. In cases of those lacking information on either follow-up (45%), details on drinking status was obtained from informants. Completely abstinent were 16%. Generalized anxiety disorder and/or social phobia at the index admission predicted abstinence during the follow-up [odds ratio (OR) = 0.25], whereas onset of alcoholism among these patients after age 25 years predicted a worse prognosis (OR = 13.5). Also increasing number of social consequences related to abuse (OR = 1.3) and drinking more than the median (OR = 2.1) predicted a poor outcome. The abstinent group had significantly better mental health at follow-up. The patients with comorbid psychiatric disorders at admission were worse at follow-up. Although substance use disorders and comorbid psychiatric disorders have to a certain degree separate courses, there is nevertheless significant interaction between them. Early treatment and recognition of comorbid psychiatric disorders among substance abusers is necessary.
    • 20 years follow-up after the first microsurgical lumbar discectomies in Iceland

      Jensdottir, M; Gudmundsson, K; Hannesson, B; Gudmundsson, G (Springer Verlag, 2007-01-01)
      Background. Microsurgical discectomies are an established procedure in spinal surgery. This operating technique was first used in the Department of Neurosurgery in Iceland in 1981 and has become standard operative treatment for herniated lumbar discs. There is a great variability in outcome reports regarding recurrence rate and re-operation rate. Few articles are based on follow-up of more than 10 years. This article presents the results of a 20 years follow-up study. Methods. A retrospective study of all patients undergoing microsurgical discectomy for herniated lumbar disc, from June 1, 1981 to December 31, 1984. Outcome, based on recurrence rate, return to work and patient satisfaction was determined by a self-evaluation questionnaire, phone interviews and patient medical records. Findings. Of the 170 patients, 134 (78.8%) were included in the study (M:F, 58:42%). Preoperative symptoms: back pain with sciatica 108 (80.6%), sciatica 20 (14.9%), back pain 2 (1.5%). Mean follow-up time was 20.7 years (19.5-22.8). Recurrence rate was 12.7%. 19 patients (14.2%) underwent a subsequent lumbar operation at a different level or side. A majority of patients 108 (80.6%) returned to previous level of work, 26 (19.4%) lost some or all working capabilities. Patient satisfaction was high, 91.1% reporting excellent (68.7%) or good (22.4%) results. 5.2% of patients rated the outcome fair and 3.7% poor. Women reported worse outcome than men, excellent M:F 74.7:60.7%, and poor 7.1:1.3%. There was no significant difference in patient satisfaction in patients undergoing additional operations or those with recurrence of the herniated disc. Conclusions. Outcome was very good with 92.0% return to work and 91.1% patient satisfaction. The recurrence rate was 12.7% with a substantial number of cases occuring 10-20 years after operation. To conclude, microsurgical discectomies maintain a high success rate in the long-term.
    • 2017 EACTS Guidelines on perioperative medication in adult cardiac surgery

      Sousa-Uva*, Miguel; Head, Stuart J; Milojevic, Milan; Collet, Jean-Philippe; Landoni, Giovanni; Castella, Manuel; Dunning, Joel; Gudbjartsson, Tómas; Linker, Nick J; Sandoval, Elena; et al. (Oxford University Press, 2018-01)
    • 2018 EHRA expert consensus statement on lead extraction: recommendations on definitions, endpoints, research trial design, and data collection requirements for clinical scientific studies and registries: endorsed by APHRS/HRS/LAHRS

      Bongiorni, Maria G; Burri, Haran; Deharo, Jean C; Starck, Christoph; Kennergren, Charles; Saghy, Laszlo; Rao, Archana; Tascini, Carlo; Lever, Nigel; Kutarski, Andrzej; et al. (Oxford University Press, 2018-07)
    • 2018 update of the EULAR recommendations for the management of hand osteoarthritis.

      Kloppenburg, Margreet; Kroon, Féline Pb; Blanco, Francisco J; Doherty, Michael; Dziedzic, Krysia S; Greibrokk, Elsie; Haugen, Ida K; Herrero-Beaumont, Gabriel; Jonsson, Helgi; Kjeken, Ingvild; et al. (BMJ, 2019-01-01)
      Since publication of the European League Against Rheumatism (EULAR) recommendations for management of hand osteoarthritis (OA) in 2007 new evidence has emerged. The aim was to update these recommendations. EULAR standardised operating procedures were followed. A systematic literature review was performed, collecting the evidence regarding all non-pharmacological, pharmacological and surgical treatment options for hand OA published to date. Based on the evidence and expert opinion from an international task force of 19 physicians, healthcare professionals and patients from 10 European countries formulated overarching principles and recommendations. Level of evidence, grade of recommendation and level of agreement were allocated to each statement. Five overarching principles and 10 recommendations were agreed on. The overarching principles cover treatment goals, information provision, individualisation of treatment, shared decision-making and the need to consider multidisciplinary and multimodal (non-pharmacological, pharmacological, surgical) treatment approaches. Recommendations 1-3 cover different non-pharmacological treatment options (education, assistive devices, exercises and orthoses). Recommendations 4-8 describe the role of different pharmacological treatments, including topical treatments (preferred over systemic treatments, topical non-steroidal anti-inflammatory drugs (NSAIDs) being first-line choice), oral analgesics (particularly NSAIDs to be considered for symptom relief for a limited duration), chondroitin sulfate (for symptom relief), intra-articular glucocorticoids (generally not recommended, consider for painful interphalangeal OA) and conventional/biological disease-modifying antirheumatic drugs (discouraged). Considerations for surgery are described in recommendation 9. The last recommendation relates to follow-up. The presented EULAR recommendations provide up-to-date guidance on the management of hand OA, based on expert opinion and research evidence.
    • 2019 EACTS/EACTA/EBCP guidelines on cardiopulmonary bypass in adult cardiac surgery.

      Wahba, Alexander; Milojevic, Milan; Boer, Christa; De Somer, Filip M J J; Gudbjartsson, Tomas; van den Goor, Jenny; Jones, Timothy J; Lomivorotov, Vladimir; Merkle, Frank; Ranucci, Marco; et al. (Oxford University Press, 2020-02)
    • 2019 EACTS/EACTA/EBCP guidelines on cardiopulmonary bypass in adult cardiac surgery.

      Puis, Luc; Milojevic, Milan; Boer, Christa; De Somer, Filip M J J; Gudbjartsson, Tomas; van den Goor, Jenny; Jones, Timothy J; Lomivorotov, Vladimir; Merkle, Frank; Ranucci, Marco; et al. (Oxford University Press, 2020-02)
    • 2019 EACTS/EACTA/EBCP guidelines on cardiopulmonary bypass in adult cardiac surgery.

      Kunst, Gudrun; Milojevic, Milan; Boer, Christa; De Somer, Filip M J J; Gudbjartsson, Tomas; van den Goor, Jenny; Jones, Timothy J; Lomivorotov, Vladimir; Merkle, Frank; Ranucci, Marco; et al. (Elsevier Science, 2019-12)
      Disclaimer 2019: The EACTS/EACTA/EBCP Guidelines represent the views of the EACTS, the EACTA and EBCP and were produced after careful consideration of the scientific and medical knowledge and the evidence available at the time of their dating. The EACTS, EACTA and EBCP are not responsible in the event of any contradiction, discrepancy and/or ambiguity between the EACTS, EACTA and EBCP Guidelines and any other official recommendations or guidelines issued by the relevant public health authorities, in particular in relation to good use of healthcare or therapeutic strategies. Health professionals are encouraged to take the EACTS, EACTA and EBCP Guidelines fully into account when exercising their clinical judgement as well as in the determination and the implementation of preventive, diagnostic or therapeutic medical strategies; however, the EACTS, EACTA and EBCP Guidelines do not, in any way whatsoever, override the individual responsibility of health professionals to make appropriate and accurate decisions in consideration of each patient's health condition and, where appropriate and/or necessary, in consultation with that patient and the patient's care provider. Nor do the EACTS, EACTA and EBCP Guidelines exempt health professionals from giving full and careful consideration to the relevant official, updated recommendations or guidelines issued by the competent public health authorities, in order to manage each patient's case in light of the scientifically accepted data pursuant to their respective ethical and professional obligations. It is also the health professional's responsibility to verify the applicable rules and regulations relating to drugs and medical devices at the time of prescription. The article has been co-published with permission in the British Journal of Anaesthesia, the European Journal of Cardio-Thoracic Surgery and the Interactive CardioVascular and Thoracic Surgery. All rights reserved in respect of the European Journal of Cardio-Thoracic Surgery and the Interactive CardioVascular and Thoracic Surgery. (C) European Association for Cardio-Thoracic Surgery 2019, published by Oxford University Press, and in respect of the British Journal of Anaesthesia (C) 2019 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.
    • 25-hydroxyvitamin D and cardiovascular disease in patients with systemic lupus erythematosus: data from a large international inception cohort.

      Lertratanakul, Apinya; Wu, Peggy; Dyer, Alan; Urowitz, Murray; Gladman, Dafna; Fortin, Paul; Bae, Sang-Cheol; Gordon, Caroline; Clarke, Ann; Bernatsky, Sasha; et al. (Wiley-Blackwell, 2014-08)
      An association between 25-hydroxyvitamin D (25[OH]D; vitamin D) deficiency and increased cardiovascular (CV) risk factors and CV disease (CVD) has been shown in general population studies. Vitamin D deficiency has been noted in systemic lupus erythematosus (SLE), and CVD is a major cause of morbidity and mortality in SLE. The objectives of this study were to estimate the associations of 25(OH)D levels with CV risk factors and to determine whether low baseline 25(OH)D levels predict future CV events in patients participating in an international inception cohort.
    • 3D False Color Computed Tomography for Diagnosis and Follow-Up of Permanent Denervated Human Muscles Submitted to Home-Based Functional Electrical Stimulation.

      Carraro, Ugo; Edmunds, Kyle J; Gargiulo, Paolo; 1IRRCS Fondazione Ospedale San Camillo , Venezia, Italy. 2Institute for Biomedical and Neural Engineering, Reykjavik University; Landspítali, Reykjavík, Iceland. (PagePress, 2015-03-11)
      This report outlines the use of a customized false-color 3D computed tomography (CT) protocol for the imaging of the rectus femoris of spinal cord injury (SCI) patients suffering from complete and permanent denervation, as characterized by complete Conus and Cauda Equina syndrome. This muscle imaging method elicits the progression of the syndrome from initial atrophy to eventual degeneration, as well as the extent to which patients' quadriceps could be recovered during four years of home-based functional electrical stimulation (h-b FES). Patients were pre-selected from several European hospitals and functionally tested by, and enrolled in the EU Commission Shared Cost Project RISE (Contract n. QLG5-CT-2001-02191) at the Department of Physical Medicine, Wilhelminenspital, Vienna, Austria. Denervated muscles were electrically stimulated using a custom-designed stimulator, large surface electrodes, and customized progressive stimulation settings. Spiral CT images and specialized computational tools were used to isolate the rectus femoris muscle and produce 3D and 2D reconstructions of the denervated muscles. The cross sections of the muscles were determined by 2D Color CT, while muscle volumes were reconstructed by 3D Color CT. Shape, volume, and density changes were measured over the entirety of each rectus femoris muscle. Changes in tissue composition within the muscle were visualized by associating different colors to specified Hounsfield unit (HU) values for fat, (yellow: [-200; -10]), loose connective tissue or atrophic muscle, (cyan: [-9; 40]), and normal muscle, fascia and tendons included, (red: [41; 200]). The results from this analysis are presented as the average HU values within the rectus femoris muscle reconstruction, as well as the percentage of these tissues with respect to the total muscle volume. Results from this study demonstrate that h-b FES induces a compliance-dependent recovery of muscle volume and size of muscle fibers, as evidenced by the gain and loss in muscle mass. These results highlight the particular utility of this modality in the quantitative longitudinal assessment of the responses of skeletal muscle to long-term denervation and h-b FES recovery.
    • 5-year incidence of age-related maculopathy in the Reykjavik Eye Study

      Jonasson, Fridbert; Arnarsson, Arsaell; Peto, Tunde; Sasaki, Hiroshi; Sasaki, Kazuyuki; Bird, Alan C (Elsevier, 2005-01-01)
      PURPOSE: To examine the age- and gender-specific 5-year incidence of age-related maculopathy (ARM) and age-related macular degeneration (AMD) in citizens of Reykjavik. DESIGN: Population-based, prospective cohort study. PARTICIPANTS: The cohort was a population-based random sample of citizens 50 years and older. Of 1379 eligible subjects, 1045 had a baseline examination in 1996; 846 of the 958 survivors (88.2%) had a 5-year follow-up examination in 2001. METHODS: The incidence of various characteristics of drusen and pigmentary changes that are typical of ARM were determined using the international classification and grading system for ARM and AMD. MAIN OUTCOME MEASURES: Early ARM and AMD were assessed by masked grading of stereo fundus photographs. RESULTS: Hypopigmentation developed at 5 years in 10.7% of people 50 to 59 years of age (95% confidence interval [CI], 6.9-14.4) and in 25.7% those 70 to 79 years of age (95% CI, 18.4-33.0) at baseline. Age-related macular degeneration developed in no one who was 50 to 59 years of age at baseline. Geographic atrophy (GA) developed in 4.6% (95% CI, 1.2-7.9) and exudative AMD in none of those who were 70 years and older at baseline. CONCLUSIONS: Geographic atrophy is the predominant type of AMD in Iceland, and the ratio of GA to neovascular AMD is higher than in racially similar populations.
    • 52 Genetic Loci Influencing Myocardial Mass.

      van der Harst, Pim; van Setten, Jessica; Verweij, Niek; Vogler, Georg; Franke, Lude; Maurano, Matthew T; Wang, Xinchen; Mateo Leach, Irene; Eijgelsheim, Mark; Sotoodehnia, Nona; et al. (Elsevier Biomedical, 2016-09-27)
      Myocardial mass is a key determinant of cardiac muscle function and hypertrophy. Myocardial depolarization leading to cardiac muscle contraction is reflected by the amplitude and duration of the QRS complex on the electrocardiogram (ECG). Abnormal QRS amplitude or duration reflect changes in myocardial mass and conduction, and are associated with increased risk of heart failure and death.
    • 6-Bromoindole Derivatives from the Icelandic Marine Sponge : Isolation and Anti-Inflammatory Activity.

      Di, Xiaxia; Rouger, Caroline; Hardardottir, Ingibjorg; Freysdottir, Jona; Molinski, Tadeusz F; Tasdemir, Deniz; Omarsdottir, Sesselja; 1 Faculty of Pharmaceutical Sciences, University of Iceland, Hagi, Hofsvallagata 53, IS-107 Reykjavik, Iceland. xid1@hi.is. 2 Department of Immunology and Centre for Rheumatology Research Landspitali-The National University Hospital of Iceland, Hringbraut, IS-101 Reykjavik, Iceland. xid1@hi.is. 3 GEOMAR Centre for Marine Biotechnology (GEOMAR-Biotech), Marine Natural Products Chemistry Research Unit, GEOMAR Helmholtz Centre for Ocean Research Kiel, Am Kiel-Kanal 44, 24106 Kiel, Germany. caroline.rouger@u-bordeaux.fr. 4 Department of Immunology and Centre for Rheumatology Research Landspitali-The National University Hospital of Iceland, Hringbraut, IS-101 Reykjavik, Iceland. ih@hi.is. 5 Faculty of Medicine, Biomedical Center, University of Iceland, Vatnsmyrarvegur 16, IS-101 Reykjavik, Iceland. ih@hi.is. 6 Department of Immunology and Centre for Rheumatology Research Landspitali-The National University Hospital of Iceland, Hringbraut, IS-101 Reykjavik, Iceland. jonaf@landspitali.is. 7 Faculty of Medicine, Biomedical Center, University of Iceland, Vatnsmyrarvegur 16, IS-101 Reykjavik, Iceland. jonaf@landspitali.is. 8 Department of Chemistry and Biochemistry and Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92093, USA. tmolinski@ucsd.edu. 9 GEOMAR Centre for Marine Biotechnology (GEOMAR-Biotech), Marine Natural Products Chemistry Research Unit, GEOMAR Helmholtz Centre for Ocean Research Kiel, Am Kiel-Kanal 44, 24106 Kiel, Germany. dtasdemir@geomar.de. 10 Department of Marine Sciences, Faculty of Mathematics and Natural Sciences, Kiel University, Christian-Albrechts-Platz 4, 24118 Kiel, Germany. dtasdemir@geomar.de. 11 Faculty of Pharmaceutical Sciences, University of Iceland, Hagi, Hofsvallagata 53, IS-107 Reykjavik, Iceland. sesselo@hi.is. (MDPI, 2018-11-08)
      An UPLC-qTOF-MS-based dereplication study led to the targeted isolation of seven bromoindole alkaloids from the sub-Arctic sponge Geodia barretti. This includes three new metabolites, namely geobarrettin A⁻C (1⁻3) and four known compounds, barettin (4), 8,9-dihydrobarettin (5), 6-bromoconicamin (6), and l-6-bromohypaphorine (7). The chemical structures of compounds 1⁻7 were elucidated by extensive analysis of the NMR and HRESIMS data. The absolute stereochemistry of geobarrettin A (1) was assigned by ECD analysis and Marfey's method employing the new reagent l-Nα-(1-fluoro-2,4-dinitrophenyl)tryptophanamide (l-FDTA). The isolated compounds were screened for anti-inflammatory activity using human dendritic cells (DCs). Both 2 and 3 reduced DC secretion of IL-12p40, but 3 concomitantly increased IL-10 production. Maturing DCs treated with 2 or 3 before co-culturing with allogeneic CD4⁺ T cells decreased T cell secretion of IFN-γ, indicating a reduction in Th1 differentiation. Although barettin (4) reduced DC secretion of IL-12p40 and IL-10 (IC50 values 11.8 and 21.0 μM for IL-10 and IL-12p40, respectively), maturing DCs in the presence of 4 did not affect the ability of T cells to secrete IFN-γ or IL-17, but reduced their secretion of IL-10. These results indicate that 2 and 3 may be useful for the treatment of inflammation, mainly of the Th1 type.
    • 64,XX, SRY-, and ZFY-negative Icelandic horse likely to be true hermaphrodite

      Bodvarsdottir, S K; Imsland, F; Thorisson, B; Steinarsdottir, M; Eyfjord, J E (W. B. Saunders Co., 2009-10-01)
      A 4-year-old Icelandic horse, considered to be a mare, showed stallion-like behavior in a group of mares. On clinical examination, the horse turned out to have an enlarged erectable phallic clitoris. Ultrasound examination showed a normal-sized left ovary covered with numerous small follicular cysts and a compact testis-like tissue in place of the right ovary. The karyotype was normal for a mare (64,XX), and the horse was found to be negative for the Y chromosome-specific markers SRY, ZFY, and EIF1AY. This case indicates that the intersexual phenotype may be caused by autosomal recessive mutation, resulting in defects in cortisol biosynthesis rather than transferal of Y chromosome male-specific genes. This is the first report of an intersexual phenotype in an Icelandic horse that is likely to be a true hermaphrodite because of female sex chromosomes and a mixture of female and male gonads and external genitals.