Biomedical subjects
Publications and source records attributed to M Lorenz.
Patients receiving ongoing palliative pain therapy, either by intrathecal morphine application or a spinal cord stimulation system (SCS), should obtain functional tests of the implant and new diagnostic imaging if new symptoms of lumbar pain of changed quality appear. Six cases are presented in which a further operation of a recurrent disc herniation resulted in a significant reduction of preoperative complaints.
The aims of this study were (i) to determine and compare the concentration of reactive oxygen species (ROS) and total antioxidant status (TAS) in seminal plasma and sperm parameters of the male partners of patients undergoing IVF or intracytoplasmic sperm injection (ICSI) treatment and (ii) to establish the relationship between ROS and TAS concentrations and sperm quality and their effect on fertilization and pregnancy rate of patients who achieved a pregnancy and those who were unsuccessful. Twenty-six IVF and 22 ICSI patients were included in this study. The ROS concentration in seminal plasma and sperm concentration, vitality (eosin test), motility, morphology, membrane integrity (HOS test), maturity (chromomycin, CMA3) and DNA fragmentation (TUNEL) results and their relationship to fertilization and pregnancy were analysed. ROS concentrations were similar regarding the seminal plasma of male partners of patients who achieved a pregnancy and those who were unsuccessful. The other semen parameters, concentration, motility, vitality, membrane and DNA integrity, were comparable in both groups. However, both groups demonstrated a negative correlation between ROS concentration and sperm vitality, membrane integrity and morphology. Moreover, an inverse correlation was found between TUNEL, vitality, and membrane integrity. In conclusion, ROS concentration in seminal plasma affects the quality of spermatozoa. A negative correlation between the ROS concentration in seminal plasma and fertilization rate in both IVF/ICSI programmes was shown.
AIM: Aaslid's leg cuff method is a well validated technique to measure dynamic cerebral autoregulation. In the literature different protocols to choose cuff pressure have been described. The aim of this study is to find a technique as accurate as possible without un-necessary inconvenience for the patient. METHOD: The leg cuff test with bilateral cuffs was performed on 10 young healthy volunteers with three different protocols (cuff pressure at systolic level, doppler controlled and 30 mmHg above systolic level). For each examination the autoregulation index invented by Tiecks and Mahony was calculated. Statistical modelling of correlated data was done with Generalized Estimating Equations. RESULTS: The choice of the protocol influences the quality of the actual autoregulation test. The most reliable protocol is also the most inconvenient one for the patient. We found no systematic bias of the protocol on the autoregulation index, but the relation between induced blood pressure drop and resulting autoregulation index was close to statistical significance. CONCLUSION: For the leg cuff test with bilateral cuffs in awake patients we recommend to apply the protocol proposed by Tiecks. Additional report of the magnitude of induced blood pressure drop would be helpful to improve the results' comparability.
PURPOSE: To demonstrate that adding irinotecan to a standard weekly schedule of high-dose, infusional fluorouracil (FU) and leucovorin (folinic acid [FA]) can prolong progression-free survival (PFS). PATIENTS AND METHODS: Four hundred thirty patients with measurable or assessable metastatic colorectal cancer were randomly assigned to receive either FA 500 mg/m(2) as a 2-hour infusion and FU 2.6 g/m(2) by intravenous 24-hour infusion, both administered weekly for 6 weeks, followed by a 2-week rest (Arbeitsgemeinschaft für Internistische Onkologie [AIO] arm, n = 216), or a similar schedule but with FU 2.3 or 2.0 g/m(2) preceded by irinotecan 80 mg/m(2) administered over 30 minutes (experimental group, n = 214). RESULTS: The median PFS time in the experimental group was 8.5 months (95% CI, 7.6 to 9.9 months) compared with 6.4 months (95% CI, 5.3 to 7.2 months) in the AIO arm (P < .0001). The median overall survival time was increased from 16.9 to 20.1 months (P = .2779). The objective response rate was 62.2% (95% CI, 55.0% to 69.5%) in the experimental group and 34.4% (95% CI, 27.5% to 41.3%) in the AIO arm (P < .0001). CONCLUSION: The addition of irinotecan to the standard AIO FU/FA regimen was associated with a highly significant improvement in PFS and response rate and was well tolerated. The results of this study confirm that irinotecan in combination with high-dose infusional FU/FA is a reference first-line treatment.
Anderson-Fabry disease is a rare lysosomal storage disorder. It results from a deficiency of the lysosomal alpha-galactosidase A and leads to progressive accumulation of globotriaosylceramide in the endothelium and tissue cells of various organs. Some of the typical clinical findings such as tiredness, dry skin, myalgia and arthralgia as well as vague gastrointestinal complaints are also symptoms of hypothyroidism. Therefore, we studied the thyroid function in patients with Anderson-Fabry disease. Thyroid function was studied in 11 patients (6 female, 5 male) with Anderson-Fabry disease by measuring thyroid-stimulating hormone (TSH) and free thyroxine serum levels. Nine patients had chronic kidney disease with stage 1 and two with stage 5. Subclinical hypothyroidism (normal serum free thyroxine concentrations along with elevated serum TSH levels) was found in 4 of 11 patients (36.4%). Subclinical hypothyroidism was observed in both male and female patients as well as in patients with stage 1 and stage 5 kidney disease. Subclinical hypothyroidism is a common finding in patients with Anderson-Fabry disease, showing an excess prevalence as compared to the normal population. The high frequency seems to be relevant regarding the potential consequences of a hypothyroid state.
PURPOSE: To compare virtual with flexible bronchoscopy for the detection of bronchial stenoses. MATERIALS AND METHODS: In a retrospective study, we compared the results of 26 patients, who had clinical suspected pathologies of the tracheobronchial airways and underwent both flexible bronchoscopy and multislice CT with 3D surface rendering of the airways. Flexible bronchoscopy and virtual bronchoscopy were compared as to the rate of detecting bronchial stenoses. For statistical analysis, we divided the tracheobronchial tree in the following sections: trachea, 2 main bronchi, 6 lobar bronchi, 18 segmental bronchi and 36 subsegmental bronchi, corresponding to 63 bronchial sections for each patient (on average) and a total of 1638 bronchial sections for all 26 patients. We graded the bronchial stenosis as less than 50 %, as 50 to 95 % and as complete obstruction. RESULTS: Virtual bronchoscopy detected 25 bronchial stenoses, while flexible bronchoscopy only revealed 17 stenoses. Stenoses with a diameter less than 50 % were found with virtual bronchoscopy 14 times and with flexible bronchoscopy 10 times. Stenoses with a diameter between 50 and 95 % were detected 7 and 4 times, respectively, and complete obstructions 4 and 3 times, respectively. Tracheobronchial stenoses were well recognized with virtual bronchoscopy. Moreover, the virtual method enabled the visualization of high-grade stenoses and post-stenotic areas that could not be passed by the fiberoptic bronchoscope. Virtual bronchoscopy detected stenoses at a higher rate but the difference was not statistically significant (stenoses < 50 %: p = 0.352, 50 - 95 %: p = 0.339, complete obstruction: p = 0.696). CONCLUSION: Virtual bronchoscopy is a useful non-invasive method for the diagnostic evaluation of the tracheobronchial tree. In comparison with flexible bronchoscopy, virtual bronchoscopy is superior in revealing high-grade stenoses and visualizing post-stenotic areas.
PURPOSE: Comparison of MR images acquired as routine examinations at a field strength of 3.0 T and 1.5 T to determine whether and to which degree the image quality improves at the higher field strength of 3.0 T. MATERIALS AND METHODS: Routine MR images of 200 patients were examined retrospectively, with 100 images obtained at 1.5 T and 100 obtained at 3.0 T. The examinations were performed with a quadrature head coil and focused on the basal cisterns because of the abundance of small distinct structures in this region. We selected the T2-weighted 2D-FSE sequence in transverse direction for comparison. At both field strengths, the same section thickness of 5 mm and a matrix of 512 x 388 (FOV: 220 mm) were used. The quality of the images was evaluated with regard to depicting the cranial nerves N. III, V - X, the AICA and PICA. For comparison, image quality was rated with a score from 1 (well defined) to 5 (not depicted). RESULTS: A score of 1 was obtained in 46 % of the anatomic structures examined at 3.0 T and in only 9.2 % at 1.5 T. A score of 2 was given in 27.6 % of the anatomic structures at 3.0 T vs. 23.5 % at 1.5 T, a score of 3 in 17.2 % vs. 28.1 %, a score of 4 in 8.6 % vs. 28.7 %, and a score of 5 in 0.4 % vs. 10.3 %, respectively. The Mann-Whitney U test showed significance at p < 0.001 for the comparison of images at 1.5 and 3.0 Tesla. CONCLUSION: Routine magnetic resonance imaging using the same quadrature coil technique and similar acquisition times at 3.0 T and 1.5 T shows an improvement for T2-weighted images at the higher field strength.
Anaemia is a frequent complication among long-term renal transplant recipients. A prevalence of approximately 40% has been reported in several studies. If renal function declines to stage 5 kidney disease, the prevalence of anaemia in kidney transplants is even higher. A positive correlation between haemoglobin concentration and creatinine clearance has been reported, which is a function of endogenous erythropoietin production by the functioning graft. Inflammation related to a retained kidney graft may cause hypo-responsiveness to erythropoietic agents once kidney transplant recipients return to dialysis. Furthermore, the use of azathioprine, mycophenolate mofetil and sirolimus may be associated with post-transplant anaemia. Along with erythropoietin deficiency, depletion of iron stores is one of the major reasons for anaemia in the kidney transplant population. The proportion of hypochromic red blood cells appears to be a useful parameter to measure iron supply and utilization as well as to estimate mortality risks in kidney transplant recipients. While anaemia is an important cardiovascular risk-factor after transplantation, our data suggest that anaemia is not associated with mortality and graft loss. Nevertheless, inadequate attention is paid so far to the management of anaemia after renal transplantation. A promising future aspect for risk reduction of cardiovascular disease includes the effect of erythropoietic agents on endothelial progenitor cells.
UNLABELLED: Appropriate measurement of the glomerular filtration rate (GFR) is important for the assessment of renal function. This paper reviews the methods used to assess GFR in clinical trials of enzyme replacement therapy (ERT) in patients with Fabry disease, which include inulin clearance, 24-hour creatinine clearance, chromium ethylene diamine tetraacetate (51Cr-EDTA) clearance and cystatin C concentrations. GFR has also been estimated using calculations based on creatinine clearance (the Cockcroft-Gault formula) and the Modification of Diet in Renal Disease (MDRD) equation. Analysis of the results of these studies shows that there are striking discrepancies between estimated and measured GFR. For example, the MDRD equation overestimates GFR in patients with Fabry disease who have normal renal function. In addition, cystatin C has been shown to be of limited use for measuring renal function during ERT, because it is influenced by other factors such as age, gender and weight. CONCLUSION: The use of exact methods, such as inulin clearance, 124I-iothalamate, 99mTc-DTPA, 51Cr-EDTA and iohexol, appears to be mandatory for a robust evaluation of the effects of ERT on GFR in patients with Fabry disease.
Isolated ischemia of the cervical spinal cord is an uncommon but increasingly recognized complication of vertebral artery dissection (VAD). The authors report a young patient with congenital afibrinogenemia, who developed VAD with extensive unilateral spinal cord infarction, probably caused by local compression of spinal radicular feeders at their origin by vertebral artery hematoma.
CuInSe(2) (CIS) solar cells deposited on polyimide foil by the Solarion company in a web-coater-based process using sputter and evaporation techniques were investigated in the ion beam laboratory LIPSION of the University of Leipzig by means of Rutherford backscattering spectrometry (RBS) and particle-induced X-ray emission (PIXE) using high-energy broad ion beams and microbeams. From these measurements the composition of the absorber and the lateral homogeneity and film thicknesses of the individual layers could be determined on the basis of some reasonable assumptions. For the first time, quantitative depth profiling of the individual elements was performed by microPIXE measurements on a beveled section prepared by ion-beam etching of a CIS solar cell. Within the CIS absorber layer no significant concentration-depth gradients were found for Cu, In, and Se, in contrast with results from secondary neutral mass spectrometry (SNMS) depth profiling, which was applied to the same samples for comparison. Furthermore, both PIXE and SNMS showed the presence of a remarkable amount of Cd from the CdS buffer layer in the underlying absorber.
Proteolysis of extracellular matrix components is required for cell migration occurring in atherosclerotic lesion formation. In the present study, gene expression of the urokinase plasmingen activator receptor (uPAR) and underlying mechanisms were analyzed during the development of atherosclerosis in the aorta of apolipoprotein E-deficient mice (apoE(-/-)). A significant increase of uPAR expression was detected in the atherosclerotic tissue with advancing plaque-dimension. As uPAR gene transcription involves the transcription factor nuclear factor-kappaB (NF-kappaB), we analyzed nuclear NF-kappaB activity in vascular tissue of apoE-deficient mice. Congruent to uPAR, we could detect an increase in NF-kappaB activity, which underlines the chronic inflammatory component of the disease. Recently we reported that beta(3)-endonexin, a protein that modulates beta(3)-integrins, regulates uPAR expression through direct interaction with subunits of the NF-kappaB-complex. Herein we could show that beta(3)-endonexin protein is expressed in aortic tissue of mice. Moreover, in contrast to uPAR or NF-kappaB, the expression of beta(3)-endonexin was reduced in extracts of advanced atherosclerotic aortic tissue. The cytoplasmic protein beta(3)-endonexin regulates function of beta(3)-integrins. We revealed that integrin stimulation of endothelial cells led to an enhanced NF-kappaB activity and secretion of the NF-kappaB dependent chemokine monocyte chemoattractant protein-1 (MCP-1). The beta(3)-integrin dependent increase in MCP-1 was notedly reduced in cells that overexpressed beta(3)-endonexin. These results provide strong evidence that beta(3)-endonexin acts as a regulating factor in the integrin-mediated signal transduction and the present findings imply a pathophysiological role of beta(3)-endonexin in atherogenesis.
Anderson-Fabry disease is an X-linked recessive lysosomal storage disease resulting from deficient alpha-galactosidase A activity. The conception of the disease has changed within the last decade. Studies of the last years have shown that the disease is not limited to the classical full-blown manifestation in affected males, which is well known since more than a century, but may also occur in carrier females. The phenomenology may differ in severity and kind of organ manifestation. Cardiac and renal variants with solely disease manifestation of these organs have also been described in an increasing number. It is likely that a spectrum exists regarding alpha-galactosidase A activity in both genders on the one hand, and an additional one regarding the severity and the number of organs affected on the other. The purpose of this review is to sharpen physicians' perception of this disease. Early and accurate diagnosis is mandatory considering that this disorder is now, after introduction of the novel enzyme replacement therapy, a treatable disease.
PURPOSE: This trial was conducted to determine whether high-dose fluorouracil (FU) given as a weekly 24-hour infusion is more active than bolus FU + leucovorin (LV), and whether high-dose infusional FU can be modulated by LV. PATIENTS AND METHODS: A total of 497 patients with previously untreated metastatic colorectal cancer were randomly assigned to receive bolus FU 425 mg/m2 intravenously + LV 20 mg/m2 on days 1 to 5 and repeated on day 28 (FU + LV), or FU 2600 mg/m2 as a 24-hour infusion alone (FU24h) or in combination with 500 mg/m2 LV (FU24h + LV)-all given weekly x6 followed by a 2-week rest period. Survival was the major study end point. RESULTS: With a median follow-up of more than 3 years, survival did not differ among the treatment groups (median FU + LV, 11.1 months [95% CI, 10.2 to 15.0 months]; FU24h, 13.0 months [95% CI, 10.4 to 15.4 months]; FU24h + LV, 13.7 months [95% CI, 12.0 to 16.4 months]; P =.724). Progression-free survival (PFS) was significantly longer for FU24h + LV (median FU + LV, 4.0 months [95% CI, 3.4 to 4.9]; FU24h, 4.1 months [95% CI, 3.4 to 5.0]; FU24h + LV 5.6 months [95% CI, 4.4 to 6.7]; P =.029). The response rates in the subgroup of patients with measurable disease were 12%, 10%, and 17% for FU + LV, FU24h, and FU24h + LV, respectively (not significant). Occurrence of grade 3 and 4 diarrhea was higher in the FU24h + LV arm (22%) compared with the FU24h (6%) or FU + LV (9%) arms; however, stomatitis (11% in FU + LV v 3% in FU24h v 5% in FU24h + LV arms) and hematologic toxicity were higher in the bolus FU + LV arm. Global quality of life did not differ within the three arms. CONCLUSION: Neither FU24h + LV nor FU24h prolong survival, relative to bolus FU + LV. Leucovorin increases PFS if added to FU24h, but increases toxicity.
Laparoscopic cholecystectomy (LC) has become the treatment of choice for patients with symptomatic cholecystolithiasis. But with the introduction of this technique, the incidence of bile duct injuries has increased. We report the case of a 33-year-old man who was transferred from an affiliated hospital to our department for the treatment of a bile duct injury 2 weeks after LC. Prior to transfer, a laparotomy had been performed, with insertion of a T-tube and a Robinson drain on day 5 after LC. Endoscopic retrograde cholangiography (ERC) on admission day revealed an extensive defect of the right biliary system, which could not be treated endoscopically. An emergency laparotomy had to be performed at night for acute bleeding from the portal vein. Due to massive inflammation in the porta hepatis and intraparenchymal destruction of the right bile duct, liver resection was performed 2 days later, after the patient had stabilized in the intensive care unit (ICU). The patient had a prolonged postoperative course, but he finally recovered well from these operations. In conclusion, the management of bile duct injuries should include ultrasound to detect and drain fluid collections and ERC to classify the injury. Emergency laparotomy should never be performed without these examinations, since the majority of bile duct injuries can be treated endoscopically. Surgery for this serious complication should always be performed at specialized centers for hepatobiliary surgery.
The data of 825 consecutive patients with ischemic stroke or TIA were retrospectively reviewed for ultrasound findings of stenoses or occlusions of the middle cerebral artery (MCA). Using survival statistics,we studied the influence of various factors on the prognosis of MCA findings. We identified 90 subjects with MCA stenosis or occlusion. Microembolic signals were demonstrated in 33% and spontaneous flow variations in 7%. Symptomatic MCA findings normalized more quickly than asymptomatic findings. Microembolic signals occurred only in symptomatic stenoses. Spontaneous flow variations strongly predicted the disappearance of a stenosis. Atherogenic risk factors were associated with stable ultrasound findings. These data suggest that different types of MCA findings exist: (1) dynamic, emboligenic stenoses or occlusions with early normalization and a high risk for ischemic events and (2) static, nonemboligenic stenoses with rare normalization and a low risk of ischemic events. A high percentage of the former may be of embolic origin, and the latter may be atherosclerotic plaques.
Gastric cancer is highly refractory to DNA-damaging therapies. We therefore studied both gene mutation and protein expression of p53 and Bax in a cohort of 116 patients with gastric cancer who underwent R0-resection with a curative intent. Bax mutation was independent from severe microsatellite instability (MSI), that is, global mismatch repair deficiency as determined by analysis of BAT-25/BAT-26 microsatellite markers. Thus, Bax-frameshift mutation is a feature of tumors with low MSI. In contrast and as expected, no p53 mutations were observed in the microsatellite instable tumors. p53 Mutation or p53 overexpression did not have an impact on disease prognosis. p53-Inactivation was, however, associated with an extremely poor prognosis in the subgroup of patients with Bax-mutated tumors. Thus, we show for the first time that the combined mutation of p53 and Bax, two key regulators of the mitochondrial apoptosis pathway, results in an extremely aggressive tumor biology and poor clinical prognosis.
PURPOSE: Comparison of the performance of virtual and conventional colonoscopy for the detection of colorectal polyps and inflammatory colon diseases using a 16-slice spiral CT scanner. Furthermore, presentation of the first experiences with a new three-dimensional reconstruction mode ("colon-dissection") that dissects the colonic wall like a pathologic-anatomic preparation to increase the sensitivity. MATERIALS AND METHODS: Forty patients were studied using a 16-slice spiral CT (Lightspeed 16, General Electric Medical Systems, Milwaukee, Wisconsin 53201, USA). The examination was performed after standard oral preparation for colonoscopy. The colonic distension was achieved with room air and intravenous butylscopolamine. Images were obtained in supine and prone position using a detector configuration of 16 x 0.625 mm, pitch 1.7, rotation time 0.5 s, 160 mAs and 120 kV. Axial reconstruction with a slice thickness of 0.625 mm. The CT data were assessed by two radiologists on an Advantage Workstation (Volume Analysis 2, USA) using a software with the capabilities of axial, multiplanar and volume rendering, virtual endoscopy, and colon dissection. Conventional colonoscopy was used to determine the sensitivity. RESULTS: A total of 30 polyps were found in 8 patients and a carcinoma was detected in two patients. Colonography identified 4 polyps with a diameter of 10 mm or more, 6 polyps with a diameter of 5 mm to 9.9 mm, 11 polyps with a diameter of 3 to 4.9 mm and 9 polyps with a diameter of 3.0 mm or less. There were two false negative findings (one polyp of 3 mm and one of 4 mm had been overseen) and two false positive findings for polyps (polyps of 4 mm and 6 mm). The sensitivity and specificity for the detection of colonic polyps were 93% and 94% with the "colonic-dissection" mode, 87 % and 94 % with the "virtual-endoscopy" mode and 63 % and 97 % with multi-planar reconstruction, respectively. Depending on the diameter of the colonic polyps, the "colon-dissection" mode ("virtual-coloscopy") had a sensitivity and specificity of 100 % and 100 % for polyps with a diameter over 5.0 mm, 91 % and 82 % for polyps with a diameter from 3.0 to 4.9 mm and 89 % and 78 % for polyps with a diameter under 3.0 mm, respectively. Inflammatory colon diseases presented as thickening of the colon wall over 5 mm. CONCLUSIONS: Virtual colonoscopy with 16-slice spiral CT allows accurate detection of colonic polyps, including small polyps below a diameter of 3 mm. In comparison with the 2D- and 3D-"virtual-endoscopic" reconstruction, the 3D-reconstruction software "colon-dissection" achieves the highest sensitivity for the detection of colonic masses. Therefore, the combination of a 16-slice spiral CT and the "colon-dissection" reconstruction software provides a high resolution in the z-axis for detecting colonic masses and polyps down to a diameter of less than 2 mm, with a sensitivity of about 90 %. This sensitivity is much higher than the sensitivity achievable with 4-slice spiral CT and without "colon-dissection" mode. A thickened colon wall over 5 mm indicates inflammatory colon disease.