Addisonin tautia sairastava potilas päivystyksessä

Vertaisarvioitu. Näin hoidan.Addisonin taudilla tarkoitetaan lisämunuaisten kuorikerroksen primaarista vajaatoimintaa. Sen hoitona käytetään gluko- ja mineralokortikoideja fysiologisina korvausannoksina. Stressitilanteessa, kuten akuutin sairauden yhteydessä, glukokortikoiditarve lisääntyy ja potilaita ohjeistetaan itse 2-3-kertaistamaan ylläpitoannos. Addisonin tautia sairastavan potilaan glukokortikoiditarpeen lisääntymisen nopea tunnistaminen päivystyspoliklinikassa on tärkeää. Liian vähäinen gluko- ja mineralokortikoidien saanti suhteessa niiden tarpeeseen voi johtaa hengenvaaralliseen Addisonin kriisiin. Sen laukaisee yleensä infektio tai muu stressitilanne. Kriisin tunnistaminen sekä nopea glukokortikoidi- ja nesteytyshoito ovat elintärkeitä. Potilailla tulisi olla SOS-passi, josta käyvät ilmi sairaus- ja lääkitystiedot

Probucol Prevents Early Coronary Heart Disease and Death in the High-Density Lipoprotein Receptor SR-BI/Apolipoprotein E Double Knockout Mouse

Mice with homozygous null mutations in the high-density lipoprotein receptor SR-BI (scavenger receptor class B, type I) and apolipoprotein E genes fed a low-fat diet exhibit a constellation of pathologies shared with human atherosclerotic coronary heart disease (CHD): hypercholesterolemia, occlusive coronary atherosclerosis, myocardial infarctions, cardiac dysfunction (heart enlargement, reduced systolic function and ejection fraction, and ECG abnormalities), and premature death (mean age 6 weeks). They also exhibit a block in RBC maturation and abnormally high plasma unesterified-to-total cholesterol ratio (0.8) with associated abnormal lipoprotein morphology (lamellar/vesicular and stacked discoidal particles reminiscent of those in lecithin/cholesterol acyltransferase deficiency and cholestasis). Treatment with the lipid-lowering, antiatherosclerosis, and antioxidation drug probucol extended life to as long as 60 weeks (mean 36 weeks), and at 5-6 weeks of age, virtually completely reversed the cardiac and most RBC pathologies and corrected the unesterified to total cholesterol ratio (0.3) and associated distinctive abnormal lipoprotein morphologies. Manipulation of the timing of administration and withdrawal of probucol could control the onset of death and suggested that critical pathological changes usually occurred in untreated double knockout mice between approximately 3 (weaning) and 5 weeks of age and that probucol delayed heart failure even after development of substantial CHD. The ability of probucol treatment to modulate pathophysiology in the double knockout mice enhances the potential of this murine system for analysis of the pathophysiology of CHD and preclinical testing of new approaches for the prevention and treatment of cardiovascular disease

Elevated serum squalene and cholesterol synthesis markers in pregnant obese women with gestational diabetes mellitus

Peer reviewe

Lecithin : cholesterol acyltransferase: symposium on 50 years of biomedical research from its discovery to latest findings

LCAT converts free cholesterol to cholesteryl esters in the process of reverse cholesterol transport. Familial LCAT deficiency (FLD) is a genetic disease that was first described by Kaare R. Norum and Egil Gjone in 1967. This report is a summary from a 2017 symposium where Dr. Norum recounted the history of FLD and leading experts on LCAT shared their results. The Tesmer laboratory shared structural findings on LCAT and the close homolog, lysosomal phospholipase A2. Results from studies of FLD patients in Finland, Brazil, Norway, and Italy were presented, as well as the status of a patient registry. Drs. Kuivenhoven and Calabresi presented data from carriers of genetic mutations suggesting that FLD does not necessarily accelerate atherosclerosis. Dr. Ng shared that LCAT-null mice were protected from diet-induced obesity, insulin resistance, and nonalcoholic fatty liver disease. Dr. Zhou presented multiple innovations for increasing LCAT activity for therapeutic purposes, whereas Dr. Remaley showed results from treatment of an FLD patient with recombinant human LCAT (rhLCAT). Dr. Karathanasis showed that rhLCAT infusion in mice stimulates cholesterol efflux and suggested that it could also enhance cholesterol efflux from macrophages. While the role of LCAT in atherosclerosis remains elusive, the consensus is that a continued study of both the enzyme and disease will lead toward better treatments for patients with heart disease and FLD.Peer reviewe

Lecithin:cholesterol acyltransferase:symposium on 50 years of biomedical research from its discovery to latest findings

LCAT converts free cholesterol to cholesteryl esters in the process of reverse cholesterol transport. Familial LCAT deficiency (FLD) is a genetic disease that was first described by Kaare R. Norum and Egil Gjone in 1967. This report is a summary from a 2017 symposium where Dr. Norum recounted the history of FLD and leading experts on LCAT shared their results. The Tesmer laboratory shared structural findings on LCAT and the close homolog, lysosomal phospholipase A2. Results from studies of FLD patients in Finland, Brazil, Norway, and Italy were presented, as well as the status of a patient registry. Drs. Kuivenhoven and Calabresi presented data from carriers of genetic mutations suggesting that FLD does not necessarily accelerate atherosclerosis. Dr. Ng shared that LCAT-null mice were protected from diet-induced obesity, insulin resistance, and nonalcoholic fatty liver disease. Dr. Zhou presented multiple innovations for increasing LCAT activity for therapeutic purposes, whereas Dr. Remaley showed results from treatment of an FLD patient with recombinant human LCAT (rhLCAT). Dr. Karathanasis showed that rhLCAT infusion in mice stimulates cholesterol efflux and suggested that it could also enhance cholesterol efflux from macrophages. While the role of LCAT in atherosclerosis remains elusive, the consensus is that a continued study of both the enzyme and disease will lead toward better treatments for patients with heart disease and FLD.</p

Cardiac Function, Perfusion, Metabolism, and Innervation following Autologous Stem Cell Therapy for Acute ST-Elevation Myocardial Infarction. A FINCELL-INSIGHT Sub-Study with PET and MRI

Purpose: Beneficial mechanisms of bone marrow cell (BMC) therapy for acute ST-segment elevation myocardial infarct (STEMI) are largely unknown in humans. Therefore, we evaluated the feasibility of serial positron emission tomography (PET) and MRI studies to provide insight into the effects of BMCs on the healing process of ischemic myocardial damage. Methods: Nineteen patients with successful primary reteplase thrombolysis (mean 2.4 h after symptoms) for STEMI were randomized for BMC therapy (2.9 × 106 CD34+ cells) or placebo after bone marrow aspiration in a double-blind, multi-center study. Three days post-MI, coronary angioplasty, and paclitaxel eluting stent implantation preceded either BMC or placebo therapy. Cardiac PET and MRI studies were performed 7–12 days after therapies and repeated after 6 months, and images were analyzed at a central core laboratory. Results: In BMC-treated patients, there was a decrease in [11C]-HED defect size (−4.9 ± 4.0 vs. −1.6 ± 2.2%, p = 0.08) and an increase in [18F]-FDG uptake in the infarct area at risk (0.06 ± 0.09 vs. −0.05 ± 0.16, p = 0.07) compared to controls, as well as less left ventricular dilatation (−4.4 ± 13.3 vs. 8.0 ± 16.7 mL/m2, p = 0.12) at 6 months follow-up. However, BMC treatment was inferior to placebo in terms of changes in rest perfusion in the area at risk (−0.09 ± 0.17 vs. 0.10 ± 0.17, p = 0.03) and infarct size (0.4 ± 4.2 vs. −5.1 ± 5.9 g, p = 0.047), and no effect was observed on ejection fraction (p = 0.37). Conclusion: After the acute phase of STEMI, BMC therapy showed only minor trends of long-term benefit in patients with rapid successful thrombolysis. There was a trend of more decrease in innervation defect size and enhanced glucose metabolism in the infarct-related myocardium and also a trend of less ventricular dilatation in the BMC-treated group compared to placebo. However, no consistently better outcome was observed in the BMC-treated group compared to placebo

Carbonic anhydrase IX in oligodendroglial brain tumors

Background Carbonic anhydrase IX is a hypoxia-induced enzyme that has many biologically important functions, including its role in cell adhesion and invasion. Methods This study was set out to investigate the role of CA IX in a series of 86 oligodendroglial brain tumors (71 primary and 15 recurrent; 48 pure oligodendrogliomas and 40 mixed oligoastrocytomas). Results 80% of the tumors showed CA IX expression by immunohistochemistry. Tumors with moderate or strong CA IX expression had decreased level of cell proliferation compared to weak or no CA IX expression (median 2.9 vs. 5.8, p = 0.015). CA IX correlated with two antioxidative enzymes, manganese superoxide dismutase (MnSOD) and regulatory gammaglutamylcysteine synthetase (GLCL-R): CA IX expression was significantly higher in MnSOD-positive tumors (p = 0.008) and decreased in GLCL-R-positive tumors (p = 0.044). In Cox multivariate analysis CA IX expression, patient age and histological component (pure oligodendroglioma vs. mixed oligoastrocytoma) showed independent prognostic values (p = 0.009, p = 0.003 and p = 0.022, respectively), CA IX positivity predicting poorer outcome. Conclusion CA IX was proved to be an independent prognostic indicator in oligodendroglial brain tumors, and it also correlates reversely with cell proliferation. It may have a role in the biology of oligodendrogliomas, and most interestingly, as it is mainly expressed in tumor tissue, CA IX could serve as a target molecule for anticancer treatments.BioMed Central Open acces

Denial of long-term issues with agriculture on tropical peatlands will have devastating consequences

Non peer reviewe

Evaluation of prognostic factors in glial tumors

Uusia aivokasvaimia löydetään Suomessa vuosittain noin 600. Näistä yleisimpiä ovat aivojen tukisolukasvaimet, glioomat. Glioomien selkeästi suurimman alaluokan muodostavat astrosytoomat. Seuraavaksi yleisimpiä ovat oligodendroglioomat. Sekamuotoisista kasvaimista suurimman ryhmän muodostavat oligoastrosytoomat, missä on piirteitä molemmista edellä mainituista kasvaintyypeistä. Eri kasvainten toisistaan erottaminen on erittäin vaikeaa ja erityisesti oligodendroglioomien tunnistamiseen on jo kauan kaivattu apuvälineitä. Oligodendroglioomien todelliseksi määräksi arvioidaan jopa kolmannesta kaikista glioomista nykyisin diagnosoidun 6% sijaan. Täsmällinen diagnoosi on välttämätön sillä kasvainten hoito ja niiden reagointi eri hoitoihin poikkeaa huomattavasti. Toisin kuin astrosytoomat, oligodendroglioomat ovat useimmiten kemosensitiivisiä. Tässä tutkimuksessa on etsitty immunohistokemiallisin värjäyksin ja mRNA in situ hybridisaatiota käyttäen luotettavia rutiinikäyttöön soveltuvia apuvälineitä kasvainten ennusteen täsmällistä arviointia ja erotusdiagnostiikkaa varten. Tärkeimpiä löydöksiämme olivat perifeerisen bentsodiatsepiini reseptorin määrän lisääntyminen astrosytoomien malignisoituessa. Tämä tarjoaa mahdollisuuden käytännön sovellutuksille aivokasvainten kuvantamisdiagnostiikassa. Tuumorisupressori proteiini p16:n määrä puolestaan väheni sekä astrosytoomissa että oligodendroglioomissa näiden malignisoituessa. Potilaiden, joiden kasvaimet olivat p16 immunopositiivisia, ennuste oli merkittävästi parempi kuin niiden potilaiden, joiden kasvaimet olivat immunonegatiivisia. Tuumorisupressori proteiinien p53 ja p21 määrä puolestaan lisääntyi oligodendroglioomien malignisoituessa. Jälkimmäinen oli itsenäinen ennustetekijä multivariaattianalyysissä. Topoisomeraasi IIa on DNA:n kahdentumisessa ja näin ollen solun jakautumisessa tärkeä entsyymi. Lisäksi se on useiden sytostaattien kohdemolekyyli. Entsyymin määrän todettiin lisääntyvän oligodendroglioomien ja oligoastrosytoomien malignisoituessa. Lisäksi määrä oli merkittävästi suurempi oligoastrosytoomien oligodendrogliooma- kuin astrosytoomakomponentissa. Havainnoilla on huomattava käytännön merkitys ennusteen määrittämisen ja mahdollisesti optimaalisen hoidon valinnan kannalta.Gliomas, are the most common type of intracranial tumors. Diffuse astrocytomas are the most frequent gliomas followed by oligodendrogliomas. Oligoastrocytomas, consisting of a mixture of oligodendroglioma and astrocytoma cells, are the most common type of mixed gliomas. The classification of gliomas is difficult and controversial especially in case of oligodendrocytic tumors. It has been suggested that oligodendrogliomas are underdiagnosed and that they may actually represent 25-33% of all glial tumors in contrast to the reported 6%. The exact histopathological diagnosis is of crucial importance because glioma types respond differently to treatments. Oligodendrogliomas are among the most chemosensitive solid malignancies whereas most astrocytic tumors are resistant to chemotherapy. This study focused on finding new potential molecular biological markers to help prognostication, differential diagnosis and selection of treatment. The amount of peripheral benzodiazepine receptor (PBR) immunopositivity associated significantly with histological grade and proliferation rate of the studied astrocytic tumors. Diazepam binding inhibitor (DBI) was observed to localize in the same cells with PBR. Intense PBR expression predicted poor survival but however, did not reach significance in multivariate analysis. CDKN2/p16 immunoreactivity decreased with increasing malignancy grade in both oligodendrocytic and astrocytic tumors. Lack of CDKN2/p16 immunoreactivity was closely associated with poor patient survival in both astrocytoma and oligodendroglioma patients. The expression of tumor supressors p53 and p21 increased with malignancy in oligodendrocytic tumors. The amount of pRb expression was found have significant effect on cell proliferation rate, whereas p21 immunopositivity had independent prognostic value in multivariate analysis suggesting use for p21 immunostaining in routine neuropathology. Topoisomerase IIa immunoreactivity increased with proliferation and malignancy grade in oligodendrocytic tumors. Multivariate analysis showed that topoIIa had an independent prognostic value for patient survival high expression predicting poor outcome. TopoIIa, being a target for multiple cytotoxic drugs, may offer a tool for selecting therapy for patients with oligodendrocytic tumors. These two qualities make it a potential tool for clinical use

Effect of gestational diabetes mellitus on newborn cholesterol metabolism

Background and aims: Impaired glucose metabolism during pregnancy may associate with changes in fetal cholesterol metabolism. We investigated if gestational diabetes mellitus (GDM) affects newborn cholesterol metabolism as determined by cord blood squalene and non-cholesterol sterols. Furthermore, we examined potential correlations between cord blood and maternal serum non-cholesterol sterols. Methods: Pregnant women at risk for GDM (BMI>30 kg/m(2)) were enrolled from maternity clinics in Finland. GDM was determined from the results of an oral glucose tolerance test. Serum samples were taken in the third trimester of pregnancy, and cord blood samples collected from their newborns at birth. Squalene and non-cholesterol sterols were analyzed from serum and cord blood by gas liquid chromatography. All women with GDM were in good glycaemic control. Results: The ratios of squalene and non-cholesterol sterols to cholesterol (100 x mu mol/mmol of cholesterol) in cord blood did not differ between the infants born to mothers with GDM (n = 15) or mothers with normal glucose tolerance (n = 13). The ratios of sitosterol and campesterol to cholesterol in the cord blood correlated with the corresponding maternal serum ratios (r = 0.70, p <0.0001) in both groups. Conclusions: In obese women under good glycaemic control, GDM did not affect newborn cholesterol metabolism. Cord blood sitosterol and campesterol ratios to cholesterol correlated with the corresponding maternal serum ratios thus potentially reflecting maternal-fetal cholesterol transport. (C) 2018 Elsevier B.V. All rights reserved.Peer reviewe