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      • KCI등재

        Hemoglobin Andrew-Minneapolis: Hemolytic Erythrocytosis and Severe Iron Overload in Toxic Liver Cirrhosis

        Berndt Zur,Birgit Stoffel-Wagner,Michael Ludwig 대한진단검사의학회 2012 Annals of Laboratory Medicine Vol.32 No.6

        We report this case involving a 50-yr-old man of Central European descent who presented at our outpatient department with psoriasis. The known preexisting conditions in this case included alcohol-related toxic liver cirrhosis and untreated type 2 diabetes. The patient had an HbA1c level of 6.2%, which was determined during a routine diabetic monitoring visit. We also assessed HbA1c levels via HPLC (Variant; Bio-Rad, Hercules, CA, USA) and noted an anomaly in the HbA fraction. Subsequent chromatographic, electrophoretic, and genetic examinations confirmed Hb Andrew-Minneapolis, a rare genetic Hb anomaly. always been present in this patient, yet the possible causes of its occurrence had not been investigated. On analysis of the patient’s Hb on HPLC, we found an obvious peak of 39.1%. Distinct bands were also noted in the acidic and alkaline hemoglobin electrophoresis (Hydrasys; Sebia, Norcross, GA, USA) results. Capillary zone electrophoresis (Capillarys; Sebia, Norcross, GA,USA) showed an obvious peak of 24.9%. Hemogram analyses (XE-5000; Sysmex, Kobe, Japan) on EDTA-anticoagulated blood (Hb=18.3 g/dL, reference range: 13.5-17.2 g/dL) revealed hyperchromia, macrocytosis (mean corpuscular Hb=37 pg/cell, refernce range: 27-33.5 pg/cell; mean corpuscular volume=103 fL, reference range: 80-99 fL) and reticulocytosis (2.8%, reference range: 0.5-2.0%). Arterial blood gas analysis (Rapidlab 1265; Siemens, Munich, Germany) revealed that the partial pressure of oxygen was 68.5mmHg, slightly lower than the reference range of 70-100 mmHg. The p50 value also decreased, measuring 19 mmHg (reference value: >27 mmHg). Serum sample analysis (Dimension Vista 1500; Siemens, Munich, Germany) indicated that hemolysis (free Hb=386 mg/L, reference value: ≤50 mg/L) was occurring, and the patient had a reduced haptoglobin level of 0.17 g/L (reference range: 0.3-2 g/L). Additionally, the ferritin level distinctly increased to 1,206 ng/mL (reference range: 13-252 ng/mL) and was accompanied by 100% transferrin saturation (reference level: ≤45%). The soluble transferrin receptor level also increased to 1.92 mg/L (reference value: 0.83-1.76 mg/L). Hemochromatosis was excluded via PCR (Lightcycler; Roche, Basel, Switzerland). Gamma-glutamyltransferase (γ-GT), ALT, and AST levels were all slightly elevated. Scleral icterus was visible and the total bilirubin level was 8.3 mg/dL (reference range: 0.2-1.0 mg/dL). Vitamin B12 and folic acid deficiencies were ruled out. Gene sequencing (Applied Biosystems, Carlsbad, CA, USA) revealed the presence of a beta-globin mutation that results in Hb Andrew-Minneapolis [beta 144 (HCl)Lys→Asn]. The polymorphism Hb F-Sardinia [A gamma (E19)Ile→Thr] was also detected. Hb Andrew-Minneapolis is a rare anomaly that results in the formation of a Hb molecule with high oxygen affinity. This results in a left shift of the Hb-oxygen dissociation curve and consecutive erythrocytosis [1]. Only limited reports of falsely high HbA1c levels exist [2, 3]. We suspect that our patient had falsely low HbA1c levels because fasting glucose values were repeatedly >200 mg/dL, and daily blood glucose levels were always pathologically high. The patient presented with hyperchromic macrocytic erythrocytosis with marked hemolysis, indicating an instability of this Hb variant. This anomaly has not been described previously. Likewise, no reports exist substantiating possible iron overload in this variant. Existing liver cirrhosis must obviously be taken into account, as secondary iron overload can occur in alcohol-related toxic liver cirrhosis [4]. However, tranferrin saturation of this high of a level has not been previously described. Misjudgements of the patient’s type 2 diabetes were due to falsely low results of HbA1c levels. Interestingly, only falsely high HbA1c levels have been reported [2, 3]. Hemoglobinopathy with increased oxygen affinity is a rare, yet important, condition in the differential diagnosis of erythrocytosis. To...

      • KCI등재

        A Study on High Performance Fine-Grained Concrete Containing Rice Husk Ash

        Ha Thanh Le,Sang Thanh Nguyen,Horst-Michael Ludwig 한국콘크리트학회 2014 International Journal of Concrete Structures and M Vol.8 No.4

        Rice husk ash (RHA) is classified as a highly reactive pozzolan. It has a very high silica content similar to that of silica fume (SF). Using less-expensive and locally available RHA as a mineral admixture in concrete brings ample benefits to the costs, the technical properties of concrete as well as to the environment. An experimental study of the effect of RHA blending on workability, strength and durability of high performance fine-grained concrete (HPFGC) is presented. The results show that the addition of RHA to HPFGC improved significantly compressive strength, splitting tensile strength and chloride penetration resistance. Interestingly, the ratio of compressive strength to splitting tensile strength of HPFGC was lower than that of ordinary concrete, especially for the concrete made with 20 % RHA. Compressive strength and splitting tensile strength of HPFGC containing RHA was similar and slightly higher, respectively, than for HPFGC containing SF. Chloride penetration resistance of HPFGC containing 10?15 % RHA was comparable with that of HPFGC containing 10 % SF.

      • Telomere shortening and inactivation of cell cycle checkpoints characterize human hepatocarcinogenesis

        Plentz, Ruben Raphael,Park, Young Nyun,Lechel, André,Kim, Haeryoung,Nellessen, Friederike,Langkopf, Britta Heike Eva,Wilkens, Ludwig,Destro, Annarita,Fiamengo, Barbara,Manns, Michael Peter,Ronca Wiley Subscription Services, Inc., A Wiley Company 2007 Hepatology Vol.45 No.4

        <P>Telomere shortening and inactivation of cell cycle checkpoints characterize carcinogenesis. Whether these molecular features coincide at specific stages of human hepatocarcinogenesis is unknown. The preneoplasia–carcinoma sequence of human HCC is not well defined. Small cell changes (SCC) and large cell changes (LCC) are potential precursor lesions. We analyzed hepatocellular telomere length, the prevalence of DNA damage, and the expression of p21 and p16 in biopsy specimens of patients with chronic liver disease (n = 27) that showed different precursor lesions and/or HCC: liver cirrhosis (n = 25), LCC (n = 26), SCC (n = 13), and HCC (n = 13). The study shows a decrease in telomere length in nondysplastic cirrhotic liver compared with normal liver and a further significant shortening of telomeres in LCC, SCC, and HCC. HCC had the shortest telomeres, followed by SCC and LCC. Hepatocytes showed an increased p21 labeling index (p21-LI) at the cirrhosis stage, which remained elevated in most LCC. In contrast, most SCC and HCC showed a strongly reduced p21-LI. Similarly, p16 was strongly expressed in LCC but reduced in SCC and not detectable in HCC. γH2AX-DNA-damage-foci were not detected in LCC but were present in SCC and more frequently in HCC. These data indicate that LCC and SCC represent clonal expansions of hepatocytes with shortened telomeres. Conclusion: The inactivation of cell cycle checkpoints coincides with further telomere shortening and an accumulation of DNA damage in SCC and HCC, suggesting that SCC represent more advanced precursor lesions compared with LCC. (HEPATOLOGY 2007;45:968–976.)</P>

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