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  • 1
    Abstract: TP53 mutations confer subgroup specific poor survival for children with medulloblastoma. We hypothesized that WNT activation which is associated with improved survival for such children abrogates TP53 related radioresistance and can be used to sensitize TP53 mutant tumors for radiation. We examined the subgroup-specific role of TP53 mutations in a cohort of 314 patients treated with radiation. TP53 wild-type or mutant human medulloblastoma cell-lines and normal neural stem cells were used to test radioresistance of TP53 mutations and the radiosensitizing effect of WNT activation on tumors and the developing brain. Children with WNT/TP53 mutant medulloblastoma had higher 5-year survival than those with SHH/TP53 mutant tumours (100% and 36.6%+/-8.7%, respectively (p〈0.001)). Introduction of TP53 mutation into medulloblastoma cells induced radioresistance (survival fractions at 2Gy (SF2) of 89%+/-2% vs. 57.4%+/-1.8% (p〈0.01)). In contrast, beta-catenin mutation sensitized TP53 mutant cells to radiation (p〈0.05). Lithium, an activator of the WNT pathway, sensitized TP53 mutant medulloblastoma to radiation (SF2 of 43.5%+/-1.5% in lithium treated cells vs. 56.6+/-3% (p〈0.01)) accompanied by increased number of gammaH2AX foci. Normal neural stem cells were protected from lithium induced radiation damage (SF2 of 33%+/-8% for lithium treated cells vs. 27%+/-3% for untreated controls (p=0.05). Poor survival of patients with TP53 mutant medulloblastoma may be related to radiation resistance. Since constitutive activation of the WNT pathway by lithium sensitizes TP53 mutant medulloblastoma cells and protect normal neural stem cells from radiation, this oral drug may represent an attractive novel therapy for high-risk medulloblastomas.
    Type of Publication: Journal article published
    PubMed ID: 25539912
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  • 2
    ISSN: 1432-1041
    Keywords: cephalosporin ; creatinine ; diagnosis ; kidney function ; drug interference
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have carried out a study to evaluate the interference by cephalosporins with the measurement of creatinine by desk-top analyzers. The cephalosporins evaluated at concentrations of 0–250 mg/l were cefazolin sodium, cefoxitin sodium, cefotaxime sodium, and ceftazidime pentahydrate. The instruments evaluated were DT60 (Kodak, Rochester, USA), Seralyzer (Ames Division, Miles Laboratories, IN, USA), and Vision (Abbott Labs, Chicago, USA). All studies were done in plasma. None of the cephalosporins showed any interference with the DT60 analyzer. With the Vision and Seralyzer no interference was seen with cefotaxime or cefazolin. With cefazolin an increase of 10–20 µmol/l creatinine was seen for every 20 mg/l of drug; with cefoxitin there was an increase of 50–80 µmol/l of creatinine for every 100 mg/l of drug. Erroneous creatinine values may be found in patients taking cefazolin and cefoxitin and may lead to inappropriate clinical management.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-5195
    Keywords: Congenital hip dislocation ; Dysplasia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé Une enquête a été réalisée à Hong-Kong en 1975 afin de dépister les enfants, d'origine chinoise, porteurs d'une luxation congénitale de la hanche. L'analyse des statistiques précédentes, de 1960 à 1975, montrait que la fréquence de cette malformation était de dix fois inférieure au moins à celle observée chez les Caucasiens. La distribution selon le sexe et l'âge, les constations radiologiques et la prédominance du côté gauche étaient identiques à ce que l'on observe chez les Caucasiens porteurs d'une luxation congénitale de la hanche. Cependant, à l'inverse des enfants caucasiens, les chinois présentaient une luxation et non une dysplasie. Les mères des enfants atteints de luxation congénitale ont été comparées à un groupe témoin, ayant des enfants normaux, pour évaluer l'utilisation de la «position de Hong-Kong”, dans laquelle les enfants sont portés sur le dos de leurs mères, les hanches en abduction forcée. Comme la moitié seulement des enfants de chaque groupe étaient portés de cette façon, d'autres facteurs doivent être responsables de la faible fréquence de la luxation congénitale de la hanche chez les Chinois du Sud.
    Notes: Summary In 19 75 we carried out a survey in Hong Kong to locate Chinese children with congenital dislocation of the hip. Analysis of the available records between 1960 and 1975 gave an observed incidence which was at least 10 times less than found in Caucasians. The age and sex distribution, radiographic findings and the left-sided predominence were similar to Caucasians with congenital dislocation of the hip. However, unlike Caucasian children, the Chinese presented with dislocation and not dysplasia. The mothers of children with congenital dislocation of the hip were compared with a control group with normal children to assess their use of the “Hong Kong” position, in which the children are carried on the back of their mother with their hips in a position of wide abduction. Since only half of the children in either group were carried in this manner, other factors must be responsible for the low incidence of congenital dislocation of the hip in southern Chinese.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background : Occult biliary stones escape detection on conventional investigations, and clinico-biochemical systems proposed for predicting biliary pancreatitis has low predictive values.Aim : To evaluate the accuracy of clinico-biochemical parameters for prediction of biliary pancreatitis in patients undergoing endoscopic ultrasonography.Methods : Early endoscopic ultrasonography was performed on 139 patients presenting with acute pancreatitis within 24 h of admission. The aetiologies of all patients were determined after complete evaluations, and clinico-biochemical characteristics of patients with a biliary cause (biliary group) and non-biliary causes (non-biliary group) were compared.Results : Biliary pancreatitis was diagnosed in 107 patients and 32 patients had non-biliary causes. The biliary group belonged to a significantly older age group, had a female predominance, significantly more derangement of liver function and a higher incidence of severe attack of acute pancreatitis. On multivariate analysis, female sex, age 〉58 years and serum alanine aminotransferase 〉150 U/L were independent predictive factors for biliary cause of acute pancreatitis. Using these three factors for prediction of biliary cause, the sensitivity was 93% and overall accuracy was 85%.Conclusion : Clinico-biochemical prediction for biliary cause of acute pancreatitis improves in the era of endoscopic ultrasonography with a higher sensitivity and overall accuracy. In centres where endoscopic ultrasonography is inaccessible or local expertise is unavailable, clinico-biochemical prediction of biliary cause of acute pancreatitis may provide a useful alternative in the initial management of this group of patients.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0703
    Source: Springer Online Journal Archives 1860-2000
    Topics: Energy, Environment Protection, Nuclear Power Engineering , Medicine
    Notes: Abstract. An atomic absorption spectrometric (AAS) method has been developed for determining μg/L levels of Sb in samples of water and blood. The AAS method is based on the concept of stabilized temperature platform furnace atomization (STPF) realized through the use of a transversely heated graphite atomizer (THGA) furnace, longitudinal Zeeman-effect background correction, and matrix modification with palladium nitrate-magnesium nitrate-nitric acid. The method of standard additions is not mandatory. The detection limit (3 standard deviations of the blank) is 2.6 μg Sb/L for the water, red blood cells (RBCs), and serum samples. Data are presented on the degree of accuracy and precision. The THGA-AAS method is simple, fast, and contamination-free because the entire operation from sampling to AAS measurement is carried out in the same tube. The method has been applied to the determination of Sb in some leachate tap water samples derived from a static copper plumbing system containing Sn/Sb solders, and in small samples (0.5 ml) of RBCs and serum derived from rats given Sb-supplemented drinking water.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background : Patients undergoing transarterial chemoembolization for hepatocellular carcinoma have advanced tumour or severe cirrhosis and frequently have associated protein-calorie malnutrition. The role of nutritional supplements for such patients is unclear.Aim : To investigate, in a randomized controlled trial, any benefit of the long-term administration of branched chain amino acids in patients undergoing chemoembolization for hepatocellular carcinoma.Methods : Forty-one patients received oral branched chain amino acids for up to four courses of chemoembolization and 43 patients did not receive any nutritional supplement. Morbidity, liver function, nutritional status, quality of life and long-term survival were compared between the two groups.Results : The administration of branched chain amino acids resulted in a lower morbidity rate compared with the control group (17.1% vs. 37.2%, P = 0.039). In particular, the group given branched chain amino acids showed a significantly lower rate of ascites (7.3% vs. 23.2%, P = 0.043) and peripheral oedema (9.8% vs. 27.9%, P = 0.034). Significantly higher serum albumin, lower bilirubin and a better quality of life were observed after chemoembolization in the group given branched chain amino acids. However, there was no significant difference in survival between the two groups.Conclusions : Nutritional supplementation with oral branched chain amino acids is beneficial in increasing the serum albumin level, reducing the morbidity and improving the quality of life in patients undergoing chemoembolization for inoperable hepatocellular carcinoma.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Aim : To compare the clinico-pathological features of hepatitis B virus-related hepatocellular carcinoma in young and old patients.Methods : The clinico-pathological characteristics of hepatitis B virus-related hepatocellular carcinoma were compared in 1863 consecutive patients (121 patients, ≤40 years; 1742 patients, 〉 40 years) seen at a single institution over the last 13 years.Results : Young patients presented more often with pain (P 〈 0.0001), hepatomegaly (P = 0.01) and ruptured hepatocellular carcinoma (P = 0.02), whereas old patients presented with ankle oedema (P = 0.001), ascites (P = 0.002) and by routine screening (P = 0.035). Liver function, Child–Pugh grading and indocyanine green test were better preserved in young patients. They also had a higher α-foetoprotein concentration (P = 0.001), larger tumour size (P = 0.001) and more frequent metastasis (P = 0.008), but a similar surgical resection rate (33.6% vs. 28%), to old patients. There was no difference between the two groups in the overall post-resection survival rate, but there was a shorter survival in young patients with unresectable disease (3.6 months vs. 4.6 months, P = 0.004).Conclusion : Young patients with hepatocellular carcinoma often show a later presentation, but a higher resectability rate and similar survival rates, than old patients. The screening programme should include young hepatitis B virus carriers, even in the absence of cirrhosis.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 0005-2787
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1435-4373
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 0005-2736
    Keywords: ESR ; Fatty acid ; Fluidity ; Lipid modulation ; Phospholipid ; Plasma membrane
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Medicine , Physics
    Type of Medium: Electronic Resource
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