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Biomedical subjects

C Hahn

Publications and source records attributed to C Hahn.

At least 73 records · Page 4Linked to original sources

Oral idarubicin, dexamethasone and vincristine (VID) in the treatment of multiple myeloma.

In order to replace the central venous line necessary for continuous infusion of vincristine and doxorubicin with high-dose dexamethasone (VAD) and to avoid hospitalization, we evaluated the efficacy and toxicity of oral idarubicin, vincristine and dexamethasone (VID) in patients with multiple myeloma. Vincristine (1.6 mg/m2, max 2 mg) was given as a bolus injection on day 1. Idarubicin was given in capsules 10 mg/m2/day for days 1-4 with an intraindividual dose escalation, 40 mg dexamethasone were given on days 1-4, 9-12, 17-20. Treatment cycles were repeated every 28 days. At this interim analysis, 53 patients have been entered into the ongoing trial; 46 patients are evaluable for toxicity. The median age was 60 years (interquartile range, 52-65). 46% were primary or secondary refractory, 20% had previously been treated with VAD and 30% had previously untreated disease, 4% had two or more relapses. Four patients died within 2 months from entry and were considered as early deaths (8.7%). 45% of the 42 patients evaluable for efficacy achieved a partial remission and 26% a minor remission. The median reduction of the M-component was 43% (interquartile range, 25-64%). VID is an effective and convenient alternative to VAD even in relapsed or refractory patients.

Administration, Oral↗

The direct effect of hepatic peroxisome proliferators on rat Leydig cell function in vitro.

A review of the literature indicates that some compounds which produce hepatic peroxisome proliferation in rats also appear to produce Leydig cell adenomas, and some also affect the serum concentrations of testosterone and estradiol. Previous studies with the peroxisome proliferator ammonium perfluorooctanoate showed a direct effect on Leydig cells to alter steroidogenesis. It was therefore proposed that peroxisome proliferators in general may directly affect Leydig cell function to produce Leydig cell tumors by some undetermined mechanism. The present study investigated whether the following peroxisome proliferators directly affect Leydig cell function in vitro: 2,4-dichlorophenoxyacetic acid, ammonium perfluorooctanoate, acetylsalicylic acid, clofibric acid, ciprofibrate, gemfibrozil, tiadenol, tibric acid, trichloroacetic acid, trichloroethylene, and Wyeth 14,643. Leydig cells, isolated from adult Crl:CDBR rats (12-16 weeks old), were treated with peroxisome proliferator for 21 hr and the medium was assayed for estradiol. The function of the treated Leydig cell was evaluated by measuring the release of testosterone in response to human chorionic gonadotropin (hCG). In general, the peroxisome proliferators reduced the hCG-stimulated release of testosterone and either reduced or had no effect on the baseline release of testosterone. Of the 11 peroxisome proliferators, 8 increased the release of estradiol from Leydig cells treated for 1 day. Two more compounds were found to increase estradiol production when the treatment period was extended to 2 days. These effects were seen at noncytotoxic doses and at concentrations similar to those achieved in rat serum in dietary studies. The results suggest that peroxisome proliferators, as a class of compounds, directly modify the steroidogenic function of Leydig cells in vitro. Some of these compounds are known to produce Leydig cell tumors in rats, but this association has yet to be established for other peroxisome proliferators. This suggests that compounds which directly affect Leydig cell function in vitro may also induce Leydig cell tumors in vivo. Further investigations are necessary to address the mechanism for the in vitro effects on Leydig cells and to clarify the apparent relationship between peroxisome proliferator-induced changes in Leydig cell function and the development of Leydig cell tumors.

2,4-Dichlorophenoxyacetic Acid↗

Relationship between the serum concentration of 7 alpha-hydroxycholesterol and fecal bile acid excretion in humans.

BACKGROUND: Serum levels of 7 alpha-hydroxycholesterol have been shown to reflect the activity of cholesterol 7 alpha-hydroxylase, the key enzyme of bite acid synthesis in the liver, but a comparison with direct measurements of bile acid synthesis rates has never been performed. METHODS: 7 alpha-Hydroxycholesterol was measured by gas-liquid chromatography/mass spectrometry and bile acid synthesis by the fecal balance method in 35 subjects. RESULTS: A significant correlation was found between 7 alpha-hydroxycholesterol concentration in serum and bile acid synthesis (r = 0.863, p < 0.001). Serum levels of 7 alpha-hydroxycholesterol in 20 patients treated with a 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor did not differ from levels obtained in healthy volunteers (78 +/- 7 ng/ml versus 63 +/- 5 ng/ml; NS). Treatment with fenofibrate reduced 7 alpha-hydroxycholesterol concentrations in six patients from 107 +/- 47 ng/ml to 61 +/- 12 ng/ml (p < 0.05). CONCLUSIONS: We conclude that the concentration of 7 alpha-hydroxycholesterol in serum is an indicator of bile acid synthesis and that serum levels of 7 alpha-hydroxycholesterol are not affected in patients treated with HMG-CoA reductase inhibitors but are affected in those treated with fenofibrate.

Acyl Coenzyme A↗

Considerations on developmental aspects of biocompatible dialysis membranes.

Modern strategies in developing new polymers for dialysis membranes aim to improve their blood compatibility. To achieve such a goal, two approaches have been successfully applied: existing cellulosic polymers were modified, either by introducing functional groups through ester or ether bonds, by mixing synthetic polymers with bulk additives, or by using copolymerization techniques. As a detailed example, the first synthetically modified cellulose membrane, Hemophan, was prepared by substituting some hydrogen atoms in the cellulosic glucose unit by diethyl-amino-ethyl groups with the modification having a considerable impact on the membrane's hemocompatibility. It is further known that the hemocompatibility of hydrophobic synthetic membranes is improved by rendering these materials partially hydrophilic. We tested the hypothesis, whether the hemocompatibility of a material, which is hydrophilic per se, such as unmodified cellulose, is changed after the introduction of hydrophobic substituents. For this purpose, the number and nature of substituents have been systematically varied in order to alter surface properties, and these variations have been subsequently related to blood compatibility parameters. As expected, thrombin generation as well as complement- and cell-activation depend on the number and nature of the substituents whereby some of the substituents show a very narrow optimum if their hemocompatibility is related to the degree of substitution. Changes in hemocompatibility can be followed by physical methods, such as surface angle analyses and zeta potential determinations. Data show that alterations in the lipophilic/hydrophilic balance on the polymer surface may explain substituent-related changes in polymer hemocompatibility.(ABSTRACT TRUNCATED AT 250 WORDS)

Biocompatible Materials↗

Serum concentration of 7 alpha-hydroxycholesterol as an indicator of bile acid synthesis in humans.

The serum concentration of 7 alpha-hydroxycholesterol as an indicator of total bile acid synthesis was investigated under different experimental conditions in humans. 7 alpha-Hydroxycholesterol was measured by gas-liquid chromatography-mass spectrometry, using [2H7]7 alpha-hydroxycholesterol and/or 5 alpha-cholestane-3 beta, 6 beta-diol as internal standards, and bile acid synthesis was estimated by the fecal balance method. Intraindividual variation was small when the concentration of 7 alpha-hydroxycholesterol was determined twice in the same subject 2 days to 11 months apart (7.3 +/- 6.5%, n = 52). In patients with advanced cirrhosis of the liver (n = 22) 7 alpha-hydroxycholesterol was 3.4-fold lower (22 ng/ml +/- 8) compared to matched controls (75 ng/ml +/- 19). Administration of cholestyramine (4 g b.i.d.) for 14 days increased 7 alpha-hydroxycholesterol concentration in five healthy volunteers from 40 +/- 11 ng/ml to 181 +/- 95 ng/ml (P = 0.02) and fecal excretion of acidic sterols from 254 +/- 60 mg/d to 1336 +/- 344 mg/d (P < 0.01). Although a significant correlation was found between 7 alpha-hydroxycholesterol in serum and bile acid synthesis in patients with hypercholesterolemia (r = 0.847, P < 0.001, n = 17), it was impossible to accurately determine bile acid synthesis from the serum levels of 7 alpha-hydroxycholesterol. Thus, determination of 7 alpha-hydroxycholesterol concentrations in serum can be used to assess changes in bile acid synthesis rates over short and long term periods under various experimental conditions, but not to calculate bile acid synthesis correctly.

Bile Acids and Salts↗

The hospital cost (fiscal year 1991/1992) of a simple perioperative allogeneic red blood cell transfusion during elective surgery at Duke University.

We sought to determine the actual cost to Duke University Medical Center of a perioperative red blood cell transfusion. A recent audit at Duke University Medical Center determined the base average direct and indirect hospital costs for providing a unit of red blood cells. The Transfusion Service's base cost for providing an allogeneic unit of red blood cells was $113.58. To obtain the actual hospital cost of transfusing a unit of red blood cells in the perioperative period, associated costs were calculated and added to the Transfusion Service's base cost. These associated costs included compatibility tests on multiple units per each unit transfused in the perioperative period, performing ABO and Rh typing and antibody screening on samples from patients who were not subsequently transfused, compatibility tests on units not issued, handling costs of units issued but not used, physically administering the blood, and the cost of the recipient contracting an infectious disease or developing a transfusion reaction. These associated costs increased the cost of transfusing an allogeneic unit of red blood cells in the perioperative period to $151.20. Perhaps the techniques described in the study can be used to quantify cost/benefit ratios associated with future changes in transfusion practice.

Blood Banks↗

Warm and cold blood cardioplegia. Comparison of myocardial function and metabolism using 31p magnetic resonance spectroscopy.

BACKGROUND: Standard myocardial protection during cardiac surgery uses hypothermic arrest, but warm heart surgery, recently introduced, is now used in many centers. We hypothesized that warm continuous blood cardioplegia (WCBC) would provide better myocardial preservation than cold continuous blood cardioplegia (CCBC). METHODS AND RESULTS: In isolated cross-perfused canine hearts, left ventricular (LV) function and myocardial O2 consumption (MVO2) were measured at constant LV volume, coronary perfusion pressure, and heart rate before and after 75 minutes of arrest at 37 degrees C or 10 degrees C. Metabolism was evaluated by 31P nuclear magnetic resonance spectroscopy. LV resting tone increased transiently after arrest by CCBC but not WCBC (38 +/- 3.9 versus 2.9 +/- 0.5 mm Hg, P < .0005). Myocardial ATP changed over time differently in the groups (P < .001), declining at the outset of CCBC and returning to control levels during the recovery period after CCBC or WCBC. Intracellular pH rose from 7.17 +/- 0.03 to 7.85 +/- 0.05 during CCBC (P < .0005 versus WCBC). MVO2 declined dramatically during arrest at either temperature but to a lower value during CCBC (P < .0005). LV pressure recovered to 86.1 +/- 5.1% of its prearrest value after CCBC and to 97.2 +/- 7.8% following WCBC (P = NS). After CCBC but not WCBC, there were small but significant increases in LV end-diastolic pressure (by 1.3 mm Hg, P < .05) and in the LV relaxation constant, tau (from 37.3 +/- 1.5 to 42.3 +/- 2.4 milliseconds, P < .05). CONCLUSIONS: The increase in intracellular pH during CCBC is largely accounted for by physicochemical factors. Group differences in ATP over time may be related to rapid cooling contracture during CCBC. The data suggest that CCBC mildly impairs LV function but that WCBC preserves function and metabolism at or near prearrest levels.

Adenosine Triphosphate↗

Allergic contact reaction to dexpanthenol: lymphocyte transformation test and evidence for microsomal-dependent metabolism of the allergen.

In a patient with contact dermatitis, dexpanthenol was found to be the causative allergen. There was a positive reaction to dexpanthenol on patch testing. Controls did not show any positive reactions to dexpanthenol on patch testing. Additionally, an LTT was performed. After preincubation with dexpanthenol-modified microsomes, we observed an increase in lymphocyte proliferation to dexpanthenol, in comparison to dexpanthenol without microsomes, suggesting that microsomal metabolism plays a rôle in the pathogenesis of dexpanthenol sensitization, because microsomes are known to possess drug metabolizing enzymes such as cytochrome P450.

Cell Division↗

[Contrast-enhanced CT of the mediastinum in lymph node diagnosis].

In mediastinal lymphoadenopathy diagnostic problems arise if lymphomas are of the same density as cardial or vascular structures. For this reason, CT based on contrast enhancement must definitely ensure a significantly greater enhancement of vascular structures than of non-vascular ones during the entire scan period. We studied 4 groups of 20 patients each employing standardised CT examinations employing 100 ml. contrast medium in different concentrations (200 and 300 mg. iodine/ml., respectively) and an injection flow rate of 0.7 and 2.0 ml/s. The results show that higher iodine concentrations produce a significantly greater enhancement in the aorta than a lower iodine concentration independent of the flow rate. Although a lower flow rate slightly delayed the enhancement increase, this was nevertheless higher than 60 HU within a period of 4 minutes. Hence, we recommend to perform contrast enhanced CT of the mediastinum using lower flow rates (0.5-1.0 ml/s.) and a higher contrast medium concentration (300 mg. iodine/ml.).

Adult↗

SWAT team approach to ventricular assistance.

In 1986, the Cardiovascular Research Institute in Sion, Switzerland, created a flying bridge-to-cardiac transplantation team. This team, consisting of two physicians, a physicist, a biomedical engineer, and two intensive care nurses, has participated in 23 bridges to cardiac transplantation in 11 cardiovascular surgery centers in Europe. The cardiac function of all patients was 100% supported by paracorporeal pneumatic biventricular Pierce-Donachy devices. Twenty of the 23 patients have had transplantation, and 11 are alive and well. The bridge-to-cardiac transplantation team, which travels with a transportable driver and the ventricle sets, supervises the bridged patients 24 hours a day until cardiac transplantation is performed.

Adolescent↗

[Investigations on methods of quantitative polarization optical estimation of neutral carbohydrates in extracellular matrix].

By means of the fluorescence PAS-reaction using a Schiff-type reagent substituted with acriflavine, the neutral carbohydrates were demonstrable selectively in the human trophoblast basement membrane. The reaction product is characterized by a typical birefringence that can be measured in the polarized light. The results obtained from ascertainment of the dispersion of the birefringence before and after the histochemical reaction, as well, gave further evidence for specificity and a definite improvement of the measurement of path differences.

Acriflavine↗

Partial nucleotide sequence of St. Louis encephalitis virus RNA: structural proteins, NS1, ns2a, and ns2b.

cDNA clones of the St. Louis encephalitis (SLE) virus genome have been obtained and the nucleotide sequence of 4.7 kb corresponding to the 5' terminal half of the genome determined. The genome contains a 5' noncoding region of 98 nucleotides followed by a single continuous open reading frame that encodes three structural proteins in the order capsid (C), membrane precursor (prM)-membrane (M), and envelope (E). Immediately following the C-terminus of E are located nonstructural proteins NS1 through NS3. The SLE amino acid sequence homology with yellow fever (YF), Murray Valley encephalitis (MVE), West Nile (WN), and dengue-2 (DEN) viruses over the sequenced region is 39, 66, 64, and 43%, respectively. The start of each SLE protein has been assigned on the basis of N-terminal sequence data and potential proteolytic cleavage sites homologous with YF and MVE viruses. Flaviviruses have conserved glycosylation sites in prM and NS1 proteins, although only one of the two glycosylation sites in the SLE E protein is conserved in MVE and DEN viruses. An evolutionary tree showing relationships of SLE, MVE, WN, YF, and DEN-2 flaviviruses is proposed on the basis of the amino acid sequences of the C proteins.

Base Sequence↗