Biomedical subjects

Georg Langebartels

Publications and source records attributed to Georg Langebartels.

5 recordsLinked to original sources

PubMed2006

Obesity is associated with a slower response to initial phenprocoumon therapy whereas CYP2C9 genotypes are not.

BACKGROUND: Initiation of phenprocoumon therapy is associated with a variable individual response. The CYP2C9 genotype has been shown to influence the response to warfarin therapy, but such an effect on phenprocoumon therapy remains uncertain. METHOD: Two hundred sixty hospital patients started on phenprocoumon were recruited for this study. Body mass index (BMI), waist and hip circumference, dietary habits, comorbidity, and comedication were initially assessed. A 5' exonuclease assay (TaqManR) was used to analyze the presence of five polymorphisms of the CYP2C9 gene in each of the study patients. Study endpoints included the time necessary to achieve the international normalized ratio (INR) target (INR >2) and the total drug amount required to attain target INR. For 250 of 260 patients, the subsequent required daily maintenance dose of phenprocoumon was also recorded. RESULTS: Both the necessary time and total dose required to attain target INR correlated significantly with BMI. The leaner the patient, the shorter the required time interval [BMI <22 (n=31), 5.48+/-2.49 days; BMI 22-25 (n=70), 6.09+/-2.40; BMI 25-30 (n=113), 6.76+/-3.61; BMI >30 (n=46), 8.50+/-5.75; p=0.001] and the lower the required dosage until the therapeutic range was achieved [BMI <22 (n=31), 23.8+/-12.1 mg; BMI 22-25 (n=70), 25.9+/-11.4 mg; BMI 25-30 (n=113), 29.6+/-25.2; BMI >30 (n=46), 35.8+/-19.7; p=0.027]. Overweight and waist circumference as a surrogate marker for abdominal fat were also associated significantly with these two parameters. Moreover, obesity was associated with a lower body-weight-adjusted maintenance dosage. All CYP2C9 genotypes that were tested failed to reveal an association with individual response variability. CONCLUSION: Patient obesity appears to directly correspond to the amount of phenprocoumon required during initiation of therapy. The CYP2C9 genotype was not shown to influence the necessary therapeutic dosage.

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PubMed2006

Quantification of aortic valve calcification using multislice spiral computed tomography: comparison with atomic absorption spectroscopy.

OBJECTIVES: Multislice spiral computed tomography (MSCT) allows the in vivo detection of valvular calcification. The aim of this study was to validate the quantification of aortic valve calcification (AVC) by MSCT with in vitro measurements by atomic absorption spectroscopy. METHODS: In 18 patients with severe aortic stenosis, 16 detector row MSCT (SOMATOM Sensation 16, Siemens, Forchheim, Germany with scan parameters as follows: 420 milliseconds tube rotation time, 12 x 0.75 mm collimation, tube voltage 120 KV) was performed before aortic valve replacement. Images were reconstructed at 60% of the RR interval with an effective slice thickness of 3 mm and a reconstruction increment of 2 mm. AVC was assessed using Agatston AVC score, mass AVC score, and volumetric AVC score. After valve replacement, the calcium content of the excised human stenotic aortic valves was determined in vitro using atomic absorption spectroscopy. RESULTS: The mean Agatston AVC score was 3,842 +/- 1,790, the mean volumetric AVC score was 3,061 +/- 1,406, and mass AVC score was 888 +/- 492 as quantified by MSCT. Atomic absorption spectroscopy showed a mean true calcification mass (Ca5(PO4)3OH) of 19 +/- 8 mass%. There was a significant correlation between in vivo AVC scores determined by MSCT and in vitro mean true calcification mass (r = 0.74, P = 0.0004 for mass AVC score, r = 0.79, P = 0.0001 for volumetric AVC score and r = 0.80, P = 0.0001 for Agatston AVC score) determined by atomic absorption spectroscopy. Linear regression analysis showed a significant association between the degree of hydroxyapatite (given in mass%) in the aortic valve and the degree of AVC (R = 0.74, F = 19.6, P = 0.0004 for mass AVC score, R = 0.80, F = 29.3, P = 0.0001 for Agatston AVC score and R = 0.79, F = 27.3, P = 0.0001 for volumetric AVC score) assessed by MSCT. CONCLUSION: MSCT allows accurate in vivo quantification of aortic valve calcifications.

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PubMed2006

Lower serum calcium levels are associated with greater calcium hydroxyapatite deposition in native aortic valves of male patients with severe calcific aortic stenosis.

BACKGROUND AND AIM OF THE STUDY: The study aim was to evaluate the relationship between serum calcium levels and the degree of calcification found in stenotic aortic valves. METHODS: Using atomic absorption spectroscopy, the hydroxyapatite content of 228 excised human stenotic aortic valves was determined and expressed as a percentage of valve mass. Left heart catheterization preceded valve replacement. In addition, serum levels of calcium and creatinine were determined before native calcific aortic valve excision. RESULTS: Valves from male patients contained more hydroxyapatite than those of female patients (26 +/- 9 versus 22 +/- 9 mass%; p < 0.001). Patients presenting with lower serum calcium levels showed a slight trend towards higher levels of valve calcification (r = -0.15, p = 0.026), but this association appeared only within the subgroup of male patients. Male patients with lowest serum calcium levels displayed greatest valvular hydroxyapatite deposition (1st calcium tertiary: 29.5 +/- 8.9 mass% versus 2nd calcium tertiary 26.4 +/- 7.8 mass% versus 3rd calcium tertiary 21.4 +/- 8.9 mass%; n = 122; p = 0.001; r = -0.25; p = 0.006). This association was even more distinct in male patients with normal serum creatinine levels. Furthermore, serum calcium was inversely and significantly associated with serum C-reactive protein in male patients (r = - 0.34; p < 0.001). CONCLUSION: Serum calcium levels appear to be inversely related to valve calcification in patients with severe calcific aortic stenosis (AS). This finding indicates the importance of systemic calcium metabolism in calcific AS, independent of manifest disorders of calcium metabolism or renal function. Interestingly, this association was evident only in male patients, suggesting a gender-dependent pathogenesis.

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PubMed2004

The amount of calcium-deficient hexagonal hydroxyapatite in aortic valves is influenced by gender and associated with genetic polymorphisms in patients with severe calcific aortic stenosis.

AIMS: The study evaluated the relationship between cardiovascular risk factors (CRF), gene polymorphism, calcification and fibrosis of stenotic aortic valves. METHODS AND RESULTS: The calcium content of 187 excised stenotic aortic valves was determined using atomic absorption spectroscopy. Hydroxyproline content was quantified. Left-heart catheterization was performed. CRF and genotypes of the interleukin 10, connective tissue growth factor (CTGF) and chemokine receptor 5 (CCR5) polymorphisms were assessed. Calcification consisted of Ca-deficient hexagonal hydroxyapatite, Ca(10 - x)(HPO4)x(PO4)(6 - x)(OH)(2 - x); with 0<or=x<or=1. Calcification (quintiles) was positively associated with the mean gradient across the aortic valve (44 +/- 14, 52 +/- 17, 54 +/- 16, 60 +/- 15, 68 +/- 19 mm Hg; p<0.001). Males (n=101) had a higher degree of calcification (26.1 +/- 8.9 vs 20.8 +/- 9.2 mass%; p<0.001), despite the same mean gradient across the aortic valve (56 +/- 17 vs 56 +/- 19 mm Hg; p=0.958). CRF were not, whereas interleukin 10 polymorphisms -1082, -819, and -592 were significantly associated with the degree of calcification. Furthermore, if certain allele carriers had additionally the rare CCR5 or CTGF allele the degree of calcification was higher. CONCLUSION: Calcification of stenotic aortic valves consists of Ca-deficient hexagonal hydroxyapatite. Gender and genetic polymorphisms have an impact on the degree of aortic valve calcification.

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PubMedDate not supplied

Experimental testing of a new left ventricular assist device--the microdiagonal blood pump.

All existing ventricular assist devices are associated with a considerable number of serious complications. This article reports on the first animal tests with a newly developed microdiagonal blood pump (MDP). Six adult female sheep weighing 80 to 90 kg underwent implantation of the microdiagonal blood pump. The inflow and outflow conduits were anastomosed to the left atrium and the descending aorta. Pump flow was adjusted to 2-3 L/minute. Hemodynamic and echocardiographic data, as well as blood samples, were measured over the entire test period of 7 days. All internal organs and the pump were explanted for thorough examination at the end of the trial. Mean arterial (range 88.5 +/- 13.1-103.7 +/- 10.7 mm Hg) and mean pulmonary arterial (18.3 +/- 2.7-21.6 +/- 20.5 mm Hg) pressures, as well as the pulmonary capillary wedge pressure (14.2 +/- 3.0 - 16.6 +/- 4.0 mm Hg), remained stable during the whole test period. Cardiac output (4.9 +/- 0.7 --> 3.2 +/- 0.5 L/minute) decreased postoperatively caused by partial unloading of the heart. Left ventricular end diastolic (4.1 +/- 0.5 --> 3.6 +/- 0.3 cm) and end systolic (3.2 +/- 0.4 --> 2.8 +/- 0.5 cm) diameters, as well as the ejection fraction (57 +/- 9 --> 42 +/- 5%), decreased after MDP implantation and did not change during the test period. Mean number of platelets (428 +/- 54 --> 286 +/- 66 x 10(3)/microL) and hemoglobin (9.8 +/- 1.3 --> 6.3 +/- 0.8 g/dL) decreased perioperatively because of surgical reasons and increased continuously in the postoperative course (platelet count and hemoglobin on day 7:441 +/- 74 x 10(3)/microL and 7.2 +/- 1.1 g/dL, respectively). Free hemoglobin was not enhanced in the postoperative course (mean value during the test period: 18.8 mmoL/L). Histologic examination of the organs did not demonstrate any infarctions of internal organs other than typical operative sequelae such as chronic pericarditis and some degree of atelectasis of the left lungs. These results demonstrate that the microdiagonal pump may be a promising alternative to the currently used ventricular assist devices, if long-term trials support these results.

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