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Biomedical subjects

L Koch

Publications and source records attributed to L Koch.

At least 19 recordsLinked to original sources
PubMed2006

Lipoprotein(a), type 2 diabetes and vascular risk in coronary patients.

BACKGROUND: Lipoprotein(a) [Lp(a)] is an important cardiovascular risk factor in the general population. However, prospective data on the vascular risk conferred by Lp(a) in patients with diabetes mellitus are scarce and controversial. It is not known whether the diabetic state affects the association of Lp(a) with vascular events among coronary patients. DESIGN: We measured Lp(a) in 587 consecutive patients undergoing coronary angiography for the evaluation of coronary artery disease. The incidence of vascular events was recorded over 4 years. RESULTS: At baseline, Lp(a) was significantly lower in patients with type 2 diabetes (T2DM) (n = 136) than in nondiabetic individuals (11 (0.8-30) mg dL(-1) vs. 16 (0.8-51) mg dL(-1); P = 0.025). Prospectively, Lp(a) was a strong and independent predictor of vascular events in nondiabetic patients (standardized adjusted hazard ratio (HR) = 1.461 (1.121-1.904); P = 0.005), but not in patients with T2DM [HR = 0.812 (0.539-1.223); P = 0.320]. An interaction term diabetes x Lp(a) was significant (P = 0.008), indicating that Lp(a) was a significantly stronger predictor of vascular events in nondiabetic patients than in patients with T2DM. CONCLUSIONS: Lp(a) in diabetic coronary patients is low and not associated with the incidence of vascular events. Although measurement of Lp(a) provides useful information in nondiabetic coronary patients, it is of little value in coronary patients with T2DM.

Aged↗
PubMed2003

Effect of propranolol and depot lanreotide SR on postprandial and circadian portal haemodynamics in cirrhosis.

BACKGROUND: Long-acting somatostatin analogues have been suggested as an alternative to propranolol for the prevention of variceal rebleeding. AIM: To compare the effectiveness of lanreotide SR, a new depot formulation injected once-weekly, and propranolol in reducing circadian portal blood flow (PVF) and meal-stimulated hepatic venous pressure gradient (HVPG) in patients with liver cirrhosis. METHODS: Patients were randomized to receive either lanreotide SR intramuscularly (30 mg once weekly, n=12) or propranolol (n=12) orally. Hemodynamic measurements were performed on day 0 and on day 21 after a 3-week period of drug administration, while patients received three standard oral liquid test meals. On each study day 27 PVF measurements were performed over 24 h and eight measurements of HVPG during the first postprandial period. RESULTS: Propranolol was more effective than lanreotide SR in reducing baseline HVPG (-21.9 vs. -13.6%, P=0.04) and meal-stimulated HVPG (-16.6 vs. -3.8%, P=0.04). Propranolol reduced circadian PVF significantly by 9.3% (P=0.03) but not lanreotide SR. CONCLUSIONS: Long-term treatment with propranolol reduced baseline and postprandial HVPG and circadian PVF, while lanreotide SR did not. The results of our study do not encourage clinical testing of lanreotide SR 30 mg for the prevention of variceal haemorrhage.

Antihypertensive Agents↗
PubMed2001

Investigation of the oxygen isotopic composition in oxidic uranium compounds as a new property in nuclear forensic science.

The analysis of seized nuclear material aims at identifying the origin of the material. Determination of the n(18O)/n(16O) ratio for the uranium oxide adds another characteristic property to the pattern which enables location of the production area of the material. A method has been developed for n(18O)/n(16O) ratio measurement which uses thermal ionization mass spectrometric (TIMS) analysis of the 238UO+ species. It has been shown that uranium oxides of different geographic origin have significantly different n(18O)/n(16O) ratios, whereas different samples of the same origin have constant oxygen isotopes ratios.

Journal Article↗
PubMed2000

Development of daunorubicin resistance in tumour cells by induction of carbonyl reduction.

A resistant descendant of the human stomach carcinoma cell line EPG85-257 was selected in the presence of increasing concentrations of daunorubicin (DRC). To avoid the expression and activity of P-glycoprotein (P-gp) and multidrug resistance-associated protein (MRP), cells were cultured in the presence of verapamil. The resulting cells were used to evaluate an induced carbonyl reduction as a new determinant in DRC resistance. The MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl tetrazolium bromide) toxicity assay was performed to estimate sensitivity to DRC in both cell lines. IC50 values of DRC increased almost 8-fold in the resistant descendants compared to the parental cell line. P-gp transcripts were detectable in both cell lines at only very low levels, and no significant alterations between sensitive and resistant cells were observed. MRP mRNA expression was markedly higher compared to P-gp mRNA, but, as was the case with P-gp, MRP mRNA levels in sensitive and resistant cells showed no alteration. This was probably due to the effect of the presence of verapamil during cell selection. Another known drug resistance factor, the lung resistance-related protein (LRP), was not at all detectable. Interestingly, resistant cells possessed 6-fold higher levels of DRC carbonyl-reducing activity, leading to the less toxic 13-hydroxy metabolite daunorubicinol (DRCOL). The 6-fold higher DRCOL formation roughly parallels the 8-fold increase in DRC IC50 values during cell selection, and therefore may account for DRC resistance in these cells. The determination of specific carbonyl reducing enzymes, known to be involved in DRC detoxification, revealed that mRNA expression of carbonyl reductase (EC 1.1.1.184), aldose reductase (EC 1.1.1.21), and dihydrodiol dehydrogenase 2 (EC 1.3.1.20) increased in the resistant descendant. In contrast, the phase II-conjugating enzyme activities of glutathione S-transferases were significantly lower in resistant than in sensitive cells, whereas those of glucuronosyl transferase were not detectable in either cell line. Apparently, conjugating enzymes are not involved in DRC resistance in human stomach carcinoma cells. These studies indicate that DRC resistance in human stomach carcinoma cells may appear as a result of an induction of metabolic DRC inactivation via carbonyl reduction to the less active 13-hydroxy metabolite DRCOL.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2000

X-ray densitometry for the measurement of regional myocardial perfusion.

The evaluation of regional myocardial blood flow (RMBF) during cardiac catheterization is of particular diagnostic interest. The purpose of this investigation was to validate x-ray densitometric parameters for the evaluation of RMBF. In five anesthetized dogs, arterial flow in the circumflex coronary artery was measured continuously with an electromagnetic flowmeter, and RMBF was determined by colored microspheres. Five different perfusion levels were created by mechanical obstruction of the coronary artery or by intravenous infusion of adenosine. At each steady-state perfusion level, digital subtraction coronary angiograms were obtained for densitometric analysis. Results documented a close correlation between the related time parameters 1/Mean Transit Time (1/MTT, r2 = 0.969), and 1/Rise Time (1/RT, r2 = 0.965) and RMBF over a wide range between 0.36 ml/(min x g) and 11.16 ml/(min x g). Maximum myocardial contrast density (Imax) also showed a good, but inverse correlation (r2 = 0.889) with RMBF and, therefore, did not reflect vascular volume. Contrast medium Appearance Time (AT) showed no correlation to RMBF (r2 = 0.017). Repeat densitometric measurements for different perfusion levels revealed a good reproducibility for MTT (accuracy: 0.001 s; precision: 0.447 s or 6.7 %) and RT (accuracy: 0.014 s; precision: 0.202 s or 10.4 %), while AT (accuracy: 0.072 s; precision: 0.420 s or 68.5%) and Imax (accuracy: 0.022 GL; precision: 1.197 GL or 44.5%) showed substantial variation. Myocardial perfusion reserve (MPR) calculated from RT (r2 = 0.90) or MTT (r2 = 0.94) showed better correlations to RMBF reserve than MPR calculated from AT (r2 = 0.04). In conclusion, only 1/MTT and 1/RT showed a good reproducibility and a close correlation to RMBF. Therefore, only these parameters can be recommended for calculations of RMBF and its reserve under clinical conditions.

Absorptiometry, Photon↗
PubMed1999

High-linear energy transfer (LET) alpha versus low-LET beta emitters in radioimmunotherapy of solid tumors: therapeutic efficacy and dose-limiting toxicity of 213Bi- versus 90Y-labeled CO17-1A Fab' fragments in a human colonic cancer model.

Recent studies suggest that radioimmunotherapy (RIT) with high-linear energy transfer (LET) radiation may have therapeutic advantages over conventional low-LET (e.g., beta-) emissions. Furthermore, fragments may be more effective in controlling tumor growth than complete IgG. However, to the best of our knowledge, no investigators have attempted a direct comparison of the therapeutic efficacy and toxicity of a systemic targeted therapeutic strategy, using high-LET alpha versus low-LET beta emitters in vivo. The aim of this study was, therefore, to assess the toxicity and antitumor efficacy of RIT with the alpha emitter 213Bi/213Po, as compared to the beta emitter 90Y, linked to a monovalent Fab' fragment in a human colonic cancer xenograft model in nude mice. Biodistribution studies of 213Bi- or 88Y-labeled benzyl-diethylene-triamine-pentaacetate-conjugated Fab' fragments of the murine monoclonal antibody CO17-1A were performed in nude mice bearing s.c. human colon cancer xenografts. 213Bi was readily obtained from an "in-house" 225Ac/213Bi generator. It decays by beta- and 440-keV gamma emission, with a t(1/2) of 45.6 min, as compared to the ultra-short-lived alpha emitter, 213Po (t(1/2) = 4.2 micros). For therapy, the mice were injected either with 213Bi- or 90Y-labeled CO17-1A Fab', whereas control groups were left untreated or were given a radiolabeled irrelevant control antibody. The maximum tolerated dose (MTD) of each agent was determined. The mice were treated with or without inhibition of the renal accretion of antibody fragments by D-lysine (T. M. Behr et al., Cancer Res., 55: 3825-3834, 1995), bone marrow transplantation, or combinations thereof. Myelotoxicity and potential second-organ toxicities, as well as tumor growth, were monitored at weekly intervals. Additionally, the therapeutic efficacy of both 213Bi- and 90Y-labeled CO17-1A Fab' was compared in a GW-39 model metastatic to the liver of nude mice. In accordance with kidney uptake values of as high as > or = 80% of the injected dose per gram, the kidney was the first dose-limiting organ using both 90Y- and 213Bi-labeled Fab' fragments. Application of D-lysine decreased the renal dose by >3-fold. Accordingly, myelotoxicity became dose limiting with both conjugates. By using lysine protection, the MTD of 90Y-Fab' was 250 microCi and the MTD of 213Bi-Fab' was 700 microCi, corresponding to blood doses of 5-8 Gy. Additional bone marrow transplantation allowed for an increase of the MTD of 90Y-Fab' to 400 microCi and for 213Bi-Fab' to 1100 microCi, respectively. At these very dose levels, no biochemical or histological evidence of renal damage was observed (kidney doses of <35 Gy). At equitoxic dosing, 213Bi-labeled Fab' fragments were significantly more effective than the respective 90Y-labeled conjugates. In the metastatic model, all untreated controls died from rapidly progressing hepatic metastases at 6-8 weeks after tumor inoculation, whereas a histologically confirmed cure was observed in 95% of those animals treated with 700 microCi of 213Bi-Fab' 10 days after model induction, which is in contrast to an only 20% cure rate in mice treated with 250 microCi of 90Y-Fab'. These data show that RIT with alpha emitters may be therapeutically more effective than conventional beta emitters. Surprisingly, maximum tolerated blood doses were, at 5-8 Gy, very similar between high-LET alpha and low-LET beta emitters. Due to its short physical half-life, 213Bi appears to be especially suitable for use in conjunction with fast-clearing fragments.

Animals↗
PubMed1999

[Voluntary testing procedures of farm animal housing equipment according to the Animal Welfare Act of 1998].

Before its broad application in practice, housing equipment should be tested, in particular with regard to animal welfare. The differing positions of the German Federal Council (Bundesrat) and the German Federal Parliament (Bundestag), whether such testing should be mandatory or voluntary, have been conciliated in the amended animal welfare act by empowering the Federal Ministry of Food, Agriculture and Fisheries (BML) to fix official standards for voluntary testing procedures by regulation. On request of the BML, a report as scientific basis for a draft regulation is currently prepared by the scientific animal welfare committee of the German Agricultural Society (DLG). The scientific animal welfare committee has been appointed by the DLG in order to provide support in the effort to strengthen animal welfare aspects in the DLG-utility testing procedure of housing equipment, which is in place since 1953. The committee elaborates standards concerning testing methods, assessment criteria and the necessary size of investigations. As required, the scientific animal welfare committee may support the DLG-testing bodies in the implementation of the animal welfare part of the testing procedure. It will, moreover, be involved in the welfare assessment based on the testing results. The amendments of the already established testing procedure will help to fulfill the general requirements on an acceptable animal welfare testing procedure. While keeping in mind that there are certain limits in what can be achieved by a voluntary testing procedure, the enhanced consideration of animal welfare aspects within the DLG-utility testing procedure has the advantage to be relatively unbureaucratic and in line with EU legislation, and is, therefore, an appropriate tool for a contibrution to improved animal welfare in livestock housing.

Agriculture↗
PubMed1999

Studies on the red marrow dosimetry in radioimmunotherapy: an experimental investigation of factors influencing the radiation-induced myelotoxicity in therapy with beta-, Auger/conversion electron-, or alpha-emitters.

Usually, the red marrow (RM) is the first dose-limiting organ in radioimmunotherapy. However, several studies have obtained only poor correlations between the marrow doses and the resulting toxicities. Furthermore, RM doses are mostly not determined directly but are derived from blood doses by assuming a ratio that is, over time for the respective conjugates, more or less constant between blood and marrow activities. The aim of this study was to determine, in a mouse model, this RM:blood activity ratio for various immunoconjugates, to investigate whether there may be differences between complete IgG and its fragments with various labels ((125/131)I versus (111)In, (88/90)Y, or 213Bi), and to analyze, in more detail, factors other than just total dose, such as dose rate or relative biological effectiveness factors, that may influence the resulting myelotoxicity. The maximum tolerated activities (MTAs) and doses (MTDs) of several murine, chimeric, and humanized immunoconjugates as complete IgG or fragments (F(ab)2 and Fab), labeled with beta(-)-emitters (such as 131I or 90Y), Auger electron-emitters (such as 125I or (111)In), or alpha-emitters (such as 213Bi) were determined in nude mice. Blood counts were monitored at weekly intervals; bone marrow transplantation was performed to support the assumption of the RM as dose-limiting. The radiation dosimetry was derived from biodistribution data of the various conjugates, accounting for cross-organ radiation; besides the major organs, the activities in the blood and bone marrow (and bone) were determined over time. Whereas no significant differences were found for the RM:blood ratios between various IgG subtypes, different radiolabels or various time points, differences were found between IgG and bi- or monovalent fragments: typically, the RM:blood ratios were approximately 0.4 for IgG, 0.8 for F(ab')2, and 1.0 for Fab'. Nevertheless, at the respective MTAs, the RM doses differed significantly between the three conjugates: e.g., with 131I-labeled conjugates, the maximum tolerated activities were 260 microCi for IgG, 1200 microCi for F(ab)2, and 3 mCi for Fab, corresponding to blood doses of 17, 9, and 4 Gy, respectively. However, initial dose rates were 10 times higher with Fab as compared to IgG, and still 3 times higher as compared to F(ab)2; interestingly, all three deliver approximately 4 Gy within the first 24 h. The MTDs of all three conjugates were increased by BMT by approximately 30%. Similar observations were made for 90Y-conjugates. Higher RM doses were tolerated with Auger-emitters than with conventional beta(-)-emitters, whereas the MTDs were similar between alpha- and beta(-)-emitters. In accordance to dose rates never exceeding those occurring at the single injection MTA, two subsequent injections of two doses of 80% of the single shot MTA of 131I- or 90Y-labeled Fab' and two doses of 100% of the single shot MTA of 213Bi-labeled Fab' were tolerated without increased lethality, if administered 24-48 h apart. In contrast, reinjection of bivalent conjugates was not possible within 6 weeks. These data suggest that the RM:blood activity ratios differ between IgG and fragments, although there is no anatomical or physiological explanation for this phenomenon at this point. In contrast to the current opinion, indication for a strong influence of the dose rate (or dose per unit time), not only total dose, on the resulting toxicity is provided, whereas the influence of high-linear energy transfer (alpha and Auger/conversion electrons) versus low-linear energy transfer (beta and gamma) type radiation seems to be much lower than expected from previous in vitro data. The lower myelotoxicity of Auger-emitters is probably due to the short path length of their low-energy electrons, which cannot reach the nuclear DNA if the antibody is not internalized into the stem cells of the RM.

Alpha Particles↗
PubMed1998

[Oncogenetics: a new activity between research and medicine].

The on-going development of predictive tests for common cancers--as breast and colorectal cancers--is potentially introducing fundamental changes in medical practices, and, therefore, changes in the role and meaning of medicine in society. In this context, analysing the conditions of emergence and development of cancergenetics activities, and their potential implications, appears as an issue of particular interest for sociology. The study conducted at Inserm unit 379 in Marseille, in collaboration with physicians from institut Paoli-Calmettes, led us, firstly, to identify a set of factors as decisive for the future of these activities. In addition, this analysis highlights the diversity of the conditions of introduction of genetic tests, depending on the pathologies and the context of existing clinical practices. Considering these elements, we argue for the setting of adequate modalities of regulation so as to permit a managed and responsible introduction of genetic testing in medicine and society.

Adenomatous Polyposis Coli↗
PubMed1997

Bacterial endocarditis: results of a survey in a children's hospital in France.

OBJECTIVE: To identify and analyse the risk factors for infective endocarditis. DESIGN: Retrospective survey over a 12-year period. SETTING: Department of Paediatric Cardiology, Nancy, France. SUBJECTS: 43 children attending during 1970-1992 who were diagnosed with infective endocarditis in accordance with Von Reyn's classification. RESULTS: 45 episodes of infective endocarditis were recorded (2 children had 2 episodes). Congenital cardiac disease was the most frequent predisposing factor for infective endocarditis. The causes of bacteraemia found were frequently, but not exclusively, of dental origin (30.5%). Among the dental causes were: poor oral health, inappropriate treatments and lack of antibiotic prophylaxis. CONCLUSIONS: Children diagnosed with a cardiac disorder should be examined by a dentist. Modern principles of antibiotic therapy and accepted dental procedures must be performed as soon as possible and parents informed of the current preventive recommendations.

Adolescent↗
PubMed1997

[Laser angioplasty and recanalization].

Percutaneous transluminal coronary balloon angioplasty (PTCA) still is the most frequently applied interventional technique for treatment of coronary artery disease. Plastic deformation of the obstructive plaque with creation of splits, intimal tears and dissections is the main mechanism of PTCA for lumen widening. As a result, acute complications due to flow limiting dissections and acute vessel closure can unpredictably occur resulting in myocardial infarction, urgent bypass surgery and death. Furthermore, long-term success of PTCA is limited by restenosis. In order to overcome these limitations of PTCA, alternative interventional techniques were developed, which instead of deforming the obstructive plaque ablate this tissue. These techniques include high and low speed rotational angioplasty, directional atherectomy, the transluminal extraction catheter, ultrasound angioplasty and laser (Light Amplification by Stimulated Emission of Radiation) angioplasty. 308 nm XeCl excimer laser angioplasty today is the laser technique of choice for clinical application. This pulsed laser requires direct contact to the obstructive plaque. It creates fast (< 200 microseconds) expanding gas bubbles which induce plaque ablation. Main indications for 308 nm XeCl excimer laser angioplasty are diffuse and long coronary lesions and total coronary occlusions. Despite promising initial results this technique showed no better acute and long-term results in comparison to PTCA for the treatment of these types of lesions ("Amsterdam-Rotterdam" Study, "Excimer Rotational Balloon Angioplasty Comparison" Study). As a result, this interventional technique was rarely applied for patient treatment. More recently, the concept of plaque ablation by 308 nm XeCl excimer laser angioplasty was renewed for the treatment of in-stent restenosis. This indication is being investigated in the "Laser Angioplasty of Restenosed Stents" trial. First results document the practicability and safety of this approach. Long-term results are awaited. With ongoing miniaturization, laser guidewires were developed for the recanalization of chronic total occlusions. The randomized multicenter "Total Occlusion Trial with Angioplasty assisted by Laser guidewire "Study documented a success rate of laser wire recanalization in up to 66% in contrast to 47.5% for mechanical wires only. Long-term results are still awaited. Technical and procedural progress including saline flush during laser application, homogeneous light distribution and the concept of smooth laser ablation is pushed foreward to make excimer laser angioplasty safer, more predictable and more effective.

Angioplasty, Balloon, Coronary↗
PubMed1996

Importance of calibration for diameter and area determination by intravascular ultrasound.

BACKGROUND: Intravascular ultrasound (IVUS) permits quantitative assessment of the lumen diameter and area of coronary arteries. The experimental study was performed to evaluate the accuracy of diameter and area measurements. METHODS AND RESULTS: Lumen quantitation (lumen diameter D and cross-sectional area A) in lucite tubes (lumen diameter 2.5 to 5.7 mm, Plexiglas) was performed using a mechanical IVUS system (HP console, 3.5 F catheter, Boston Scientific, 30 MHz). The influence of fluid type (blood, water and saline solution), fluid temperature (20 degrees C/37 degrees C), catheter to catheter variation, gain setting and ultrasound frequency (12, 20 and 30 MHz) was determined. In blood at 20 degrees C there was a constant deviation of the measured diameter from the true luminal diameter of -0.29 +/- -0.04 mm (p < 0.06). In water and saline solution at 20 degrees C the mean deviation from true diameter was -0.21 +/- -0.06 mm (p < 0.06). At 37 degrees C, the deviation in blood was greater than at 20 degrees (-0.34 +/- -0.02 mm) which is > 10% in a 3 mm tube (p < 0.06). Three of the ten catheters tested in water at 20 degrees C underestimated true diameter by more than -0.3 mm. The deviation from true diameter (5 mm tube) with varying gain settings was -0.14 mm to -0.23 mm compared to -0.19 mm at standard settings (p > 0.288). At 12 MHz diameter measured was over-estimated. The error in absolute area estimation increased with increasing diameter tested in blood at 37 degrees C (-1.21 to -2.72 mm2), whereas the relative error ([Measured Area-True Area]/True Area x 100 [%]) was more striking at smaller diameters (up to -25% in the 2.5 mm tube). CONCLUSION: Luminal diameters and areas are underestimated by this particular IVUS system. When IVUS imaging and measurements are made during coronary interventions this error should be taken into account with regard to appropriate sizing of the device and the assessment of the postprocedure result. Because systematic errors might also occur in other IVUS system (not tested in this study), it is advisable to ensure that each system is validated prior to clinical use, especially when exact measurements are required.

Calibration↗
PubMed1996

Detection of trace radioisotopes in soil, sediment and vegetation by glow discharge mass spectrometry.

The possibility for the determination of some radioisotopes of cesium, strontium, plutonium, uranium and thorium by glow discharge mass spectrometry (GDMS) in soils, sediments and vegetations is investigated. The preparation of samples is described as a combination of the use of a conductive host matrix and a secondary cathode in order to decrease the dilution effect of the blending material for the trace level determination and to gain a stable discharge. Effects of interferences arising from the nature of the conductive host matrix and of the secondary cathode on the sensitivity of the method are discussed. The determination of (137)Cs and (90)Sr has been attempted and the results obtained were in agreement with those from other analytical techniques. Accuracy, internal and external precisions have been also evaluated. GDMS is shown to be a helpful technique for the determination of radioisotopes in environmental samples. Radioisotopes can be determined according to the matrix of the sample (e.g. grass), also in presence of isobaric interferences. However, limitations still exist on the application of GDMS.

Journal Article↗
PubMed1996

Isotopic abundance measurements on solid nuclear-type samples by glow discharge mass spectrometry.

A double-focusing Glow Discharge Mass Spectrometer (GDMS) installed in a glovebox for nuclear sample screening has been employed for isotopic measurements. Isotopic compositions of zirconium, silicon, lithium, boron, uranium and plutonium which are elements of nuclear concern have been determined. Interferences arising from the matrix sample and the discharge gas (Ar) for each of these elements are discussed. The GDMS results are compared with those from Thermal Ionization Mass Spectrometry (TIMS). For boron and lithium at microg/g-ng/g levels, the two methods gave results in good agreement. In samples containing uranium the isotopic composition obtained by GDMS was in agreement with those from TIMS independently of the enrichment. Attempts for the determination of plutonium isotopic composition were also made. In this case, due to the interferences of uranium at mass 238 and americium at mass 241, the GDMS raw data are complementary with those values obtained from physical non-destructive techniques.

Journal Article↗