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Biomedical subjects

C Hahn

Publications and source records attributed to C Hahn.

At least 55 records · Page 3Linked to original sources
PubMed1998

Skin thermoregulation during local cooling in healthy volunteers and patients with systemic sclerosis--synchronous assessment of capillary red blood cell velocity, laser Doppler flux and skin temperature.

BACKGROUND: Patients with Raynaud's phenomenon due to systemic sclerosis exhibit a functional microangiopathy with endothelial cell damage. The aim of this study was to assess differences in the so-called nutritive and thermoregulative skin blood flow and to obtain further information by Fourier transformation and by nonlinear analysis of laser Doppler flux (LDF) time series. PATIENTS AND METHODS: A local cold stress test was performed in 10 patients and 10 age- and sex-matched healthy controls. Significant differences were detected between nutritive blood flow in the nailfold capillaries, assessed by capillary red blood cell velocity (CBV), and thermoregulatory blood flow, which was synchronously assessed by LDF. RESULTS: CBV was reduced during cooling, the drop being significantly larger in the patients than in the controls. In contrast, there was no significant difference in the decrease of LDF during cooling. The difference between the fall in CBV values and that in LDF was significantly more pronounced in patients. Further analysis of the LDF frequency spectrum by fast Fourier transformation revealed a significantly greater decrease in amplitude at the heart frequency level in healthy volunteers. A further analysis of the LDF signal revealed significant differences at rest and after cooling in fractal dimensions, suggesting an increased complexity of LDF signals in patients. SUMMARY: The patient's increased sensitivity towards local cold cn be observed best at the capillary level. But the changes of LDF in the frequency spectrum during cooling as calculated by fast Fourier transformation revealed significant differences. In addition differences in fractal dimensions of LDF time series suggest that an analysis of nonlinear dynamics may be a promising approach.

Adult↗
PubMed1997

[Symptoms, tumor stage and primary treatment in patients with colorectal carcinoma].

OBJECTIVE: To obtain population-related data, previously not available for Germany, regarding primary symptoms, diagnosis and treatment of patients with colorectal carcinoma. PATIENTS AND METHODS: During 1994, in the catchment area of Bonn (town of Bonn, districts of Euskirchen and Rhein-Sieg), there were 354 cases of newly diagnosed colorectal carcinoma. For all of them initial symptoms, primary diagnosis, cancer stage at time of diagnosis as well as surgical and conservative treatment were prospectively documented. By comparing entries from all relevant hospitals and doctors with those of the pathology institutes of the region, data of about 98% of all these patients were recorded. RESULTS: The average age of the patients was older (median of 69 for men, 72 for women) with more far metastases than in comparable groups reported by German university surgical departments. Only 4.6% of the group had occult blood in the stool as the only symptom. Most of the patients had local or regional metastases (T3-4: 63.9%; N1-3: 41%, respectively). Operations intended to be curative were possible in only 65.9% of the cohort. Adjuvant radiotherapy and/or chemotherapy was given to 11.7%, using current consensus recommendations.

Adenocarcinoma↗
PubMed1997

The Nck SH2/SH3 adaptor protein is present in the nucleus and associates with the nuclear protein SAM68.

SH2/SH3 adaptor proteins are essential components of the signal transduction pathways initiated by tyrosine kinases. Nck is a ubiquitously expressed adaptor protein whose function has been enigmatic. We performed confocal microscopy to localize Nck in NIH3T3 and A431 cells. Surprisingly, Nck was identified in the nucleus as well as the cytoplasm with no visible change in localization due to PDGF or EGF stimulation. Western blot analysis of nuclear and cytosolic fractions confirmed that there was no translocation in response to growth factor and that tyrosine phosphorylation was specific to only cytosolic Nck. Far Western blot analysis with either Nck, the SH2 domain, or the SH3 domains revealed differential binding in nuclear and cytosolic lysates, indicating specific binding partners for each subcellular location. The major target of c-Src during mitosis is SAM68, a RNA-binding protein ordinarily localized to the nucleus. SAM68 was identified as a nuclear specific binding partner of Nck in both nonmitotic and mitotic cells. Several tyrosine kinases can be found in the nucleus but their signal transduction remains undefined. The discovery of an adaptor protein in the nucleus suggests there are signal transduction mechanisms within the nucleus that recapitulate those found in the cytoplasm.

3T3 Cells↗
PubMed1997

The low-dose monoethylglycinexylidide test: assessment of liver function with fewer side effects.

The hepatic metabolism of lidocaine (1 mg/kg intravenously) to its metabolite monoethylglycinexylidide (MEG-X) is the basis of the standard MEG-X test. To reduce the lidocaine-induced side effects, we evaluated the MEG-X formation after 0.5 and 1 mg/kg lidocaine intravenously in subjects with normal (n = 5) and severely impaired liver function (n = 7) (study I). From this study, a low-dose test (MEG-X concentration 30 minutes after 50 mg lidocaine intravenously [MEG-X30min] normalized to standard MEG-X test results) was developed. Sensory side effects from this low dose and from the standard MEG-X test were compared in a double-blind, randomized, cross-over study (study II) comprising 15 individuals with normal liver function and 45 patients with cirrhosis (15 Child A, 15 Child B, and 15 Child C). In study I, MEG-X formation rate was dose-independent in patients with severely impaired liver function. In study II, normalized MEG-X test results (ranging from < or = 4 to 120 microg/L) were virtually identical to the standard test results (mean difference: -1.9 microg/L; 95% confidence interval [CI]: -5.3; 1.5 microg/L). Fewer individuals experienced side effects (30% vs. 53%) with the low-dose test (P = .0013). In a multivariate analysis, the Child-Pugh score was inversely related to the occurrence of side effects. The low-dose MEG-X test gives almost identical results to the standard MEG-X test and is associated with fewer side effects, which occur less often in individuals with more severely compromised liver function.

Adult↗
PubMed1997

Rapid cooling contracture with cold cardioplegia.

BACKGROUND: Cold cardioplegia can induce rapid cooling contracture. The relations of cardioplegia-induced cooling contracture to myocardial temperature or myocyte calcium are unknown. METHODS: Twelve crystalloid-perfused isovolumic rat hearts received three 2-minute cardioplegic infusions (1 mmol/L calcium) at 4 degrees, 20 degrees, and 37 degrees C in random order, each followed by 10 minutes of beating at 37 degrees C. Finally, warm induction of arrest by a 1-minute cardioplegic infusion at 37 degrees C was followed by a 1-minute infusion at 4 degrees C. Indo-1 was used to measure the intracellular Ca2+ concentration in 6 of these hearts. Additional hearts received hypoxic, glucose-free cardioplegia at 4 degrees or 37 degrees C. RESULTS: After 1 minute of cardioplegia at 4 degrees, 20 degrees, and 37 degrees C, left ventricular developed pressure rose rapidly to 54% +/- 3%, 43% +/- 3%, and 18% +/- 1% of its prearrest value, whereas the intracellular Ca2+ concentration reached 166% +/- 23%, 94% +/- 4%, and 37% +/- 10% of its prearrest transient. Coronary flow was 5.7 +/- 0.2, 8.7 +/- 0.3, and 12.6 +/- 0.6 mL/min, respectively. Warm cardioplegia induction at 37 degrees C reduced left ventricular developed pressure and [Ca2+]i during subsequent 4 degrees C cardioplegia by 16% (p = 0.001) and 34% (p = 0.03), respectively. Adenosine triphosphate and phosphocreatine contents were lower after 4 degrees C than after 37 degrees C hypoxic, glucose-free cardioplegia. CONCLUSIONS: Rapid cooling during cardioplegia increases left ventricular pressure, [Ca2+]i and coronary resistance, and is energy consuming. The absence of rapid cooling contracture may be a benefit of warm heart operations and warm induction of cardioplegic arrest.

Animals↗
PubMed1997

Intraaortic balloon pumping for cardiac support: trends in practice and outcome, 1968 to 1995.

OBJECTIVES: A total of 4756 cases of intraaortic balloon pump support have been recorded at the Massachusetts General Hospital since the first clinical insertion for cardiogenic shock in 1968. This report describes the patterns of intraaortic balloon use and associated outcomes over this time period. METHODS: A retrospective record review was conducted. RESULTS: Balloon use has increased to more than 300 cases a year at present. The practice of balloon placement for control of ischemia (2453 cases, 11.9% mortality) has become more frequent, whereas support for hemodynamic decompensation (congestive heart failure, hypotension, cardiogenic shock) has been relatively constant (1760 cases, 38.2% mortality). Mean patient age has increased from 54 to 66 years, and mortality has fallen from 41% to 20%. Sixty-five percent (3097/4756) of the total patient population receiving balloon support underwent cardiac surgery. Placement before the operation (2038 patients) was associated with a lower mortality (13.6%) than intraoperative (771 patients, 35.7% mortality) or postoperative use (276 patients, 35.9% mortality). Independent predictors of death with balloon pump support were insertion in the operating room or intensive care unit, transthoracic insertion, age, procedure other than angioplasty or coronary artery bypass, and insertion for cardiogenic shock. Independent predictors of death with intraoperative balloon insertion were age, mitral valve replacement, prolonged cardiopulmonary bypass, urgent or emergency operation, preoperative renal dysfunction, complex ventricular ectopy, right ventricular failure, and emergency reinstitution of cardiopulmonary bypass. CONCLUSIONS: Balloons are being used more frequently for control of ischemia in more patients who are elderly with lower mortality. An institutional bias toward preoperative use of the balloon pump appears to be associated with improved outcomes.

Age Distribution↗
PubMed1997

Promising survival with three-dimensional conformal radiation therapy for non-small cell lung cancer.

PURPOSE: Local failure is a major obstacle to the cure of locally advanced non small-cell lung cancer. Three-dimensional conformal radiation therapy (3-DCRT) selects optimal treatment parameters to increase dose to tumor and reduce normal tissue dose, potentially representing an enhancement of the therapeutic ratio of radiation therapy for lung cancer. We performed this analysis of 45 non-small cell lung cancer patients treated with 3-DCRT alone, to evaluate the ability of computer derived lung dose volume histograms to predict serious pulmonary toxicity, to assess the feasibility of this approach, and to examine the resulting survival. METHODS: There were 28 males (62%) and 17 females (38%). The median age was 65 (range: 38-82). Tumor stage was Stage I/II in 13%, IIIa in 42%, and IIIb in 44%. The histology was squamous in 44%, adenocarcinoma in 36%, and other non-small cell histologies in the others. Only 47% of patients. had combined favorable prognostic factors (i.e. KPS < or = 80, and < or = 5% wt. loss). The median dose of radiation to gross disease was 70.2 Gy (range: 52.2-72 Gy) delivered in fractions of 1.8 Gy, 5 days per week. RESULTS: Seven patients did not complete 3-DCRT due to disease progression outside the port. Follow-up data are mature: the median follow up of the 6 survivors is 43.5 months (35-59). Thoracic progression occurred in 46%. Median survival (all 45 patients.) is 15.7 months and survival is 32% at 2 years and 12% at 59 months. Pulmonary toxicity > or = grade 3 occurred in 9% of patients. Dose volume histograms were available in 31 patients and showed a correlation between risk of pulmonary toxicity and indices of dose to lung parenchyma. Grade 3 or higher pulmonary toxicity occurred in 38% (3/8) of patients with > 30% of lung volume receiving > or = 25 Gy, versus 4% (1/23) of patients with < or = 30% lung receiving > or = 25 Gy (P = 0.04). Grade 3 or higher pulmonary toxicity occurred in 29% (4/14) of patients with a predicted pulmonary normal tissue complication probability of 12% or higher versus 0% (0/17) in patients with a predicted probability of less than 12% (P = 0.03). CONCLUSIONS: Despite adverse prognostic criteria median survival is encouraging and may be higher than some combined modality approaches. Dose volume histogram parameters may be useful to determine the maximum dose for individual patients and thereby permit avoidance of toxicity.

Adult↗
PubMed1997

KAMEDIN: a telemedicine system for computer supported cooperative work and remote image analysis in radiology.

The software system KAMEDIN (Kooperatives Arbeiten und MEdizinische Diagnostik auf Innovativen Netzen) is a multimedia telemedicine system for exchange, cooperative diagnostics, and remote analysis of digital medical image data. It provides components for visualisation, processing, and synchronised audio-visual discussion of medical images. Techniques of computer supported cooperative work (CSCW) synchronise user interactions during a teleconference. Visibility of both local and remote cursor on the conference workstations facilitates telepointing and reinforces the conference partner's telepresence. Audio communication during teleconferences is supported by an integrated audio component. Furthermore, brain tissue segmentation with artificial neural networks can be performed on an external supercomputer as a remote image analysis procedure. KAMEDIN is designed as a low cost CSCW tool for ISDN based telecommunication. However it can be used on any TCP/IP supporting network. In a field test, KAMEDIN was installed in 15 clinics and medical departments to validate the systems' usability. The telemedicine system KAMEDIN has been developed, tested, and evaluated within a research project sponsored by German Telekom.

Humans↗
PubMed1997

Inactivation of the small GTPase Rho disrupts cellular attachment and induces adhesion-dependent and adhesion-independent apoptosis.

Rho small GTPases regulate a variety of cellular signaling pathways involved in cell growth and transformation. In this study, we examined potential roles for Rho in adhesion-dependent and -independent pathways regulating apoptosis. Rho GTPases are specifically inactivated by exoenzyme C3 (C3) of Clostridium botulinum. Using a novel Sindbis virus-based gene expression system, we created a double subgenomic recombinant (dsSIN:C3) capable of expressing active C3 in intact cells. Infection of L929 fibroblasts with dsSIN:C3 caused essentially complete ADP-ribosylation of intracellular Rho within 1 h. dsSIN:C3-infected cells also became rounded within 1-2 h and detached by 5 h post-infection. Infection of L929 in suspension with dsSIN:C3 disrupted the ability for normal cellular attachment and spreading. Infection of primary cell explants of chicken embryo fibroblasts (CEF) and rat aortic smooth muscle cells (RSM) with dsSIN:C3 caused cytoskeletal effects similar to those seen in L929. We also observed that C3 markedly decreased the basal phosphorylation state of focal adhesion kinase (FAK). Most intriguingly, we found that dsSIN-based expression of C3 or loss of function mutants of Rho could each induce apoptosis and, in RSM, this effect was observed to be adhesion-independent. Rho GTPases, therefore, appear to regulate signal pathways that are required for cell survival and growth that are separate from, but likely overlap with, Rho-dependent pathways involved in cellular adhesion.

ADP Ribose Transferases↗
PubMed1997

Nonreplacement operations for mitral valve regurgitation.

Mitral valve reconstruction offers patients an important alternative to the traditional method for treating severe mitral regurgitation--mitral valve replacement. Over the last 15 years, surgical techniques have evolved for treating mitral regurgitation occurring from various anatomic mechanisms--annular dilatation, abnormal leaflet motion due to a variety of causes, or leaflet perforation. Currently, over 90% of regurgitant mitral valves of varying etiologies are amenable to nonreplacement therapy by reconstruction, with good intermediate- and long-term results. Reconstruction obviates the need for long-term anticoagulation, and thus, there has evolved a trend toward reconstruction earlier in the course of this disease, before fixed atrial fibrillation and ventricular dilatation occur.

Heart Valve Prosthesis↗
PubMed1997

Image transfer and computer-supported cooperative diagnosis.

The KAMEDIN system was designed as a low-cost communication tool as part of a computer-supported cooperative work project that included synchronized user interaction, telepointing and audioconferencing. During a five-month field trial, it was used for medical image transfer and cooperative diagnosis in 14 clinics and medical departments in Germany. During the field test, 297 teleconsultations were performed via ISDN and 875 MByte of data were transferred. An image compression ratio of 2-3 was obtained, so that the total quantity of data transferred corresponded to 14,000-21,000 magnetic resonance images or 3500-5250 computerized tomography images. Furthermore, 694 local sessions were conducted for the preparation of teleconsultations and the review of transferred images. Participants learned to handle the KAMEDIN system in a few hours. This was mainly owing to the design of the user-oriented graphical user interface and the restriction of the system to a set of essential image-processing functions.

Computers↗
PubMed1997

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1995

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↗
PubMed1995

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↗