Myeloma in an archaeological skeleton from Hofstadir in Mývatnssveit

Hægt er að lesa greinina í heild sinni með því að smella á hlekkinn View/OpenArchaeological investigations have been ongoing in the cemetery at Hofstadir in Mývatnssveit since the summer of 1999. To date, the remains of two chapels as well as 78 skeletons have been excavated, dated to between the 11th and 15th century. A skeleton was excavated in the summer of 2003 which showed pathological changes indicative of a malignant disease. Palaeopathological cases of malignancies are very rare, and it is therefore important to report on each case. Skeleton HST-027 was a female, aged 45-50 years at the time of death. Standard osteological methods were used to determine the sex, age and stature. Macroscopic analysis was carried out on the skeleton and all pathological changes on each bone described. The cranium, ribs, left os coxa and all left long bones were then radiographed to aid in the diagnosis. The analysis showed lytic lesions in all the flat bones, as well as the vertebrae, ribs and the proximal end of the left femur, all changes indicative of multiple myeloma. Palaeopathologically myeloma and metastatic cancer (then usually due to breast cancer in the case of women) are often difficult to distinguish. However there is no new bone formation surrounding the lesions, which means that metastatic cancer is unlikely to be the cause. Skeleton HST-027 from Hofstadir is the first published case of malignant disease in Iceland, and one of the clearer cases of myeloma in an archaeological specimen, but to date, approximately twenty cases have been reported world-wide.Fornleifauppgröftur hefur staðið yfir í kirkjugarðinum á Hofstöðum í Mývatnssveit frá því sumarið 1999. Nú þegar hafa leifar tveggja bænhúsa og 78 beinagrindur frá 11.-15. öld verið grafnar upp. Sumarið 2003 fannst beinagrind í kirkjugarðinum með meinafræðilegar breytingar sem bentu til illkynja meins. Slík fornleifafræðileg tilfelli eru mjög sjaldséð og þykir því vert að birta hvert einasta tilfelli. Beinagrindin sem um ræðir, HST-027, var úr konu sem hefur verið á aldrinum 45-50 ára þegar hún lést. Staðlaðar beinafræðilegar aðferðir voru notaðar til að greina kyn, lífaldur og líkamshæð. Fornmeinafræðileg rannsókn var gerð þar sem öllum sýnilegum breytingum á hverju einasta beini var lýst. Því næst voru höfuðkúpa, rifbein, vinstri mjaðmarspaði, og öll vinstri leggjarbein röntgenmynduð til að aðstoða við sjúkdómsgreiningu. Rannsókn leiddi í ljós beineyður í nánast öllum flötu beinum líkamans, auk hryggjarliða, rifbeina og efri hluta vinstri lærleggs, einkennandi fyrir mergæxli. Í fornleifafræðilegum tilfellum getur verið erfitt að greina á milli mergæxlis og meinvarps (þá líklegast frá brjóstakrabbameini, sérstaklega hjá konum), en ólíklegt er að um meinvarp sé að ræða þar sem engin merki eru um nýmyndun beins umhverfis vefskemmdirnar. Beinagrind HST-027 frá Hofstöðum er fyrsta birta tilfellið af illkynja meini á Íslandi og með öruggari greiningum af mergæxli í fornum beinum sem birt hafa verið almennt, en aðeins hafa um 20 tilfelli verið birt til þessa hvaðanæva úr heiminum

Association of Genetically Predicted Lipid Levels With the Extent of Coronary Atherosclerosis in Icelandic Adults.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadImportance: Genetic studies have evaluated the influence of blood lipid levels on the risk of coronary artery disease (CAD), but less is known about how they are associated with the extent of coronary atherosclerosis. Objective: To estimate the contributions of genetically predicted blood lipid levels on the extent of coronary atherosclerosis. Design, setting, and participants: This genetic study included Icelandic adults who had undergone coronary angiography or assessment of coronary artery calcium using cardiac computed tomography. The study incorporates data collected from January 1987 to December 2017 in Iceland in the Swedish Coronary Angiography and Angioplasty Registry and 2 registries of individuals who had undergone percutaneous coronary interventions and coronary artery bypass grafting. For each participant, genetic scores were calculated for levels of non-high-density lipoprotein cholesterol (non-HDL-C), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides, based on reported effect sizes of 345 independent, lipid-associated variants. The genetic scores' predictive ability for lipid levels was assessed in more than 87 000 Icelandic adults. A mendelian randomization approach was used to estimate the contribution of each lipid trait. Exposures: Genetic scores for levels of non-HDL-C, LDL-C, HDL-C, and triglycerides. Main outcomes and measures: The extent of angiographic CAD and coronary artery calcium quantity. Results: A total of 12 460 adults (mean [SD] age, 65.1 [10.7] years; 8383 men [67.3%]) underwent coronary angiography, and 4837 had coronary artery calcium assessed by computed tomography. A genetically predicted increase in non-HDL-C levels by 1 SD (38 mg/dL [to convert to millimoles per liter, multiply by 0.0259]) was associated with greater odds of obstructive CAD (odds ratio [OR], 1.83 [95% CI, 1.63-2.07]; P = 2.8 × 10-23). Among patients with obstructive CAD, there were significant associations with multivessel disease (OR, 1.26 [95% CI, 1.11-1.44]; P = 4.1 × 10-4) and 3-vessel disease (OR, 1.47 [95% CI, 1.26-1.72]; P = 9.2 × 10-7). There were also significant associations with the presence of coronary artery calcium (OR, 2.04 [95% CI, 1.70-2.44]; P = 5.3 × 10-15) and loge-transformed coronary artery calcium (effect, 0.70 [95% CI, 0.53-0.87]; P = 1.0 × 10-15). Genetically predicted levels of non-HDL-C remained associated with obstructive CAD and coronary artery calcium extent even after accounting for the association with LDL-C. Genetically predicted levels of HDL-C and triglycerides were associated individually with the extent of coronary atherosclerosis, but not after accounting for the association with non-HDL cholesterol. Conclusions and relevance: In this study, genetically predicted levels of non-HDL-C were associated with the extent of coronary atherosclerosis as estimated by 2 different methods. The association was stronger than for genetically predicted levels of LDL-C. These findings further support the notion that non-HDL-C may be a better marker of the overall burden of atherogenic lipoproteins than LDL-C.deCODE genetics/Amgen Inc

Lipoprotein(a) Concentration and Risks of Cardiovascular Disease and Diabetes

Publisher's version (útgefin grein)Background: Lipoprotein(a) [Lp(a)] is a causal risk factor for cardiovascular diseases that has no established therapy. The attribute of Lp(a) that affects cardiovascular risk is not established. Low levels of Lp(a) have been associated with type 2 diabetes (T2D). Objectives: This study investigated whether cardiovascular risk is conferred by Lp(a) molar concentration or apolipoprotein(a) [apo(a)] size, and whether the relationship between Lp(a) and T2D risk is causal. Methods: This was a case-control study of 143,087 Icelanders with genetic information, including 17,715 with coronary artery disease (CAD) and 8,734 with T2D. This study used measured and genetically imputed Lp(a) molar concentration, kringle IV type 2 (KIV-2) repeats (which determine apo(a) size), and a splice variant in LPA associated with small apo(a) but low Lp(a) molar concentration to disentangle the relationship between Lp(a) and cardiovascular risk. Loss-of-function homozygotes and other subjects genetically predicted to have low Lp(a) levels were evaluated to assess the relationship between Lp(a) and T2D. Results: Lp(a) molar concentration was associated dose-dependently with CAD risk, peripheral artery disease, aortic valve stenosis, heart failure, and lifespan. Lp(a) molar concentration fully explained the Lp(a) association with CAD, and there was no residual association with apo(a) size. Homozygous carriers of loss-of-function mutations had little or no Lp(a) and increased the risk of T2D. Conclusions: Molar concentration is the attribute of Lp(a) that affects risk of cardiovascular diseases. Low Lp(a) concentration (bottom 10%) increases T2D risk. Pharmacologic reduction of Lp(a) concentration in the 20% of individuals with the greatest concentration down to the population median is predicted to decrease CAD risk without increasing T2D risk.Peer Reviewe

Eighty-eight variants highlight the role of T cell regulation and airway remodeling in asthma pathogenesis

Publisher's version (útgefin grein)Asthma is one of the most common chronic diseases affecting both children and adults. We report a genome-wide association meta-analysis of 69,189 cases and 702,199 controls from Iceland and UK biobank. We find 88 asthma risk variants at 56 loci, 19 previously unreported, and evaluate their effect on other asthma and allergic phenotypes. Of special interest are two low frequency variants associated with protection against asthma; a missense variant in TNFRSF8 and 3‘ UTR variant in TGFBR1. Functional studies show that the TNFRSF8 variant reduces TNFRSF8 expression both on cell surface and in soluble form, acting as loss of function. eQTL analysis suggests that the TGFBR1 variant acts through gain of function and together with an intronic variant in a downstream gene, SMAD3, points to defective TGFβR1 signaling as one of the biological perturbations increasing asthma risk. Our results increase the number of asthma variants and implicate genes with known role in T cell regulation, inflammation and airway remodeling in asthma pathogenesis.We thank the individuals who participated in this study and the staff at the Icelandic Patient Recruitment Center and the deCODE genetics core facilities. Further to all our colleagues who contributed to the data collection and phenotypic characterization of clinical samples as well as to the genotyping and analysis of the whole-genome association data. This research has been conducted using the UK biobank Resource under Application Number ‘24711’.Peer Reviewe

Myeloma in an archaeological skeleton from Hofstadir in Mývatnssveit

Hægt er að lesa greinina í heild sinni með því að smella á hlekkinn View/OpenArchaeological investigations have been ongoing in the cemetery at Hofstadir in Mývatnssveit since the summer of 1999. To date, the remains of two chapels as well as 78 skeletons have been excavated, dated to between the 11th and 15th century. A skeleton was excavated in the summer of 2003 which showed pathological changes indicative of a malignant disease. Palaeopathological cases of malignancies are very rare, and it is therefore important to report on each case. Skeleton HST-027 was a female, aged 45-50 years at the time of death. Standard osteological methods were used to determine the sex, age and stature. Macroscopic analysis was carried out on the skeleton and all pathological changes on each bone described. The cranium, ribs, left os coxa and all left long bones were then radiographed to aid in the diagnosis. The analysis showed lytic lesions in all the flat bones, as well as the vertebrae, ribs and the proximal end of the left femur, all changes indicative of multiple myeloma. Palaeopathologically myeloma and metastatic cancer (then usually due to breast cancer in the case of women) are often difficult to distinguish. However there is no new bone formation surrounding the lesions, which means that metastatic cancer is unlikely to be the cause. Skeleton HST-027 from Hofstadir is the first published case of malignant disease in Iceland, and one of the clearer cases of myeloma in an archaeological specimen, but to date, approximately twenty cases have been reported world-wide.Fornleifauppgröftur hefur staðið yfir í kirkjugarðinum á Hofstöðum í Mývatnssveit frá því sumarið 1999. Nú þegar hafa leifar tveggja bænhúsa og 78 beinagrindur frá 11.-15. öld verið grafnar upp. Sumarið 2003 fannst beinagrind í kirkjugarðinum með meinafræðilegar breytingar sem bentu til illkynja meins. Slík fornleifafræðileg tilfelli eru mjög sjaldséð og þykir því vert að birta hvert einasta tilfelli. Beinagrindin sem um ræðir, HST-027, var úr konu sem hefur verið á aldrinum 45-50 ára þegar hún lést. Staðlaðar beinafræðilegar aðferðir voru notaðar til að greina kyn, lífaldur og líkamshæð. Fornmeinafræðileg rannsókn var gerð þar sem öllum sýnilegum breytingum á hverju einasta beini var lýst. Því næst voru höfuðkúpa, rifbein, vinstri mjaðmarspaði, og öll vinstri leggjarbein röntgenmynduð til að aðstoða við sjúkdómsgreiningu. Rannsókn leiddi í ljós beineyður í nánast öllum flötu beinum líkamans, auk hryggjarliða, rifbeina og efri hluta vinstri lærleggs, einkennandi fyrir mergæxli. Í fornleifafræðilegum tilfellum getur verið erfitt að greina á milli mergæxlis og meinvarps (þá líklegast frá brjóstakrabbameini, sérstaklega hjá konum), en ólíklegt er að um meinvarp sé að ræða þar sem engin merki eru um nýmyndun beins umhverfis vefskemmdirnar. Beinagrind HST-027 frá Hofstöðum er fyrsta birta tilfellið af illkynja meini á Íslandi og með öruggari greiningum af mergæxli í fornum beinum sem birt hafa verið almennt, en aðeins hafa um 20 tilfelli verið birt til þessa hvaðanæva úr heiminum

Recurrent bilateral cellulitis of lower extremeties : case of the month

Neðst á síðunni er hægt að nálgast greinina í heild sinni með því að smella á hlekkinn View/OpenNetjubólga á útlimum er tiltölulega algengt vandamál sem læknar glíma við. Algengast er að staphylokokkar og streptókokkar valdi þessari sýkingu þó fjöldi annarra baktería geti valdið svipaðri sjúkdómsmynd. Ónæmisbældir einstaklingar eru í aukinni áhættu á því að fá sýkingar af ýmsu tagi og þarf því að hafa vakandi auka með þeim. Hér er lýst tilviki af þrálátri netjubólgu hjá sjúklingi með meðfæddan mótefnaskort. Með vaxandi tíðni ónæmisbældra sjúklinga þurfa læknar að hafa augu opin fyrir sjaldséðum sýkingum og sérkennilegum birtingarformum þeirra

Recurrent bilateral cellulitis of lower extremeties : case of the month

Neðst á síðunni er hægt að nálgast greinina í heild sinni með því að smella á hlekkinn View/OpenNetjubólga á útlimum er tiltölulega algengt vandamál sem læknar glíma við. Algengast er að staphylokokkar og streptókokkar valdi þessari sýkingu þó fjöldi annarra baktería geti valdið svipaðri sjúkdómsmynd. Ónæmisbældir einstaklingar eru í aukinni áhættu á því að fá sýkingar af ýmsu tagi og þarf því að hafa vakandi auka með þeim. Hér er lýst tilviki af þrálátri netjubólgu hjá sjúklingi með meðfæddan mótefnaskort. Með vaxandi tíðni ónæmisbældra sjúklinga þurfa læknar að hafa augu opin fyrir sjaldséðum sýkingum og sérkennilegum birtingarformum þeirra