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Biomedical subjects

M Kirsch

Publications and source records attributed to M Kirsch.

At least 19 recordsLinked to original sources
PubMed2003

[Laser-induced thermotherapy (LITT) of lung metastases: description of a miniaturized applicator, optimization, and initial treatment of patients].

PURPOSE: A thin-caliber applicator system was developed for introducing a laser fiber under CT guidance into lung metastases with only minimal complications. MATERIALS AND METHODS: A space-saving 5.5 French Teflon cannula with a titanium trocar and connectors for a laser light guide (2 or 3 cm Dornier Diffusor-Tip H-6111-T2 or H-6111-T3 coupled to a Dornier Medilas Fibertom 5100 laser, wavelength of 1064 nm) and a perfusion line for physiologic saline solution were developed. After puncture the laser Diffusor-Tip remains in the cannula and is cooled during its tissue passage by slowly flowing saline solution. The miniaturized applicator system (Monocath) was calibrated in nonperfused bovine liver for maximum energy supply and necessary flow of the cooling saline solution in reference to a commercially available 9 French laser catheter with an 11.5 French inducer sheath (Power-Applicator). The new applicator system was used for treating lung metastases in 10 patients over a period of 21 months. RESULTS: The size of heat coagulation in bovine liver was 24 +/- 2 ml using the miniaturized system with application of 15 W for 20 min and a saline flow of 0.75 ml/min, in comparison to a size of 29 +/- 7 ml for the commercial applicator (30 W, 20 min, 60 ml/min). All metastases could be safely approached with the miniaturized applicator, except for two metastatic lesions at the lung base in two patients. A minor pneumothorax developed in three patients and intrapulmonary bleeding in two. Contrast-enhanced CT demonstrated necrosis of the treated metastatic areas in 6 patients. Follow-up of three patients after 5, 6, and 8 months showed complete tumor regression with minimal scarring in one patient. CONCLUSION: The miniaturized applicator system enables the introduction of a laser fiber into pulmonary metastases with only minor complications. Complete ablation seems to be achievable in suitable patients with the applied laser energy and a slow cooling fluid flow rate.

Adult↗
PubMed2002

Nasal nitric oxide levels in cystic fibrosis patients are associated with a neuronal NO synthase (NOS1) gene polymorphism.

Nitric oxide (NO) plays an important role in a number of physiological processes in the airways, including host defense. Although the exact cellular and molecular source of the NO formation in airways is unknown, there is recent evidence that neuronal NO synthase (NOS1) contributes significantly to NO in the lower airways of cystic fibrosis (CF) patients. NOS1 protein has been shown to be expressed in nasal epithelium, suggesting an involvement of NOS1-derived NO in upper airway biology. We here hypothesized that nasal NO concentrations in CF patients are related to genotype variants in the NOS1 gene. Measurements of nasal NO concentration and pulmonary function were performed in 40 clinically stable CF patients. Genomic DNA from all patients was screened for an intronic AAT-repeat polymorphism in the NOS1 gene using polymerase chain reaction and simple sequence length polymorphism (SSLP) analysis. The allele size at that locus was significantly (P = 0.001) associated with upper airway NO. Mean (+/- SD) nasal NO concentrations were 40.5 +/- 5.2 ppb in CF patients (n = 12) with high repeat numbers (i.e., both alleles > or =12 repeats) and 72.6 +/- 7.4 ppb in patients (n = 28) with low repeat numbers (i.e., at least one allele <12 repeats). Furthermore, in the group of CF patients harboring NOS1 genotypes associated with low nasal NO, colonization of airways with P. aeruginosa was significantly more frequent than in patients with NOS1 genotypes associated high nasal NO concentrations (P = 0.0022). We conclude that (1) the variability in CF nasal NO levels are related to naturally occurring variants in the NOS1 gene, and (2) that nasal NOS1-derived NO affects the susceptibility of CF airways to infection with P. aeruginosa.

Adolescent↗
PubMed2002

Magnetic resonance hydrometry: non-invasive quantification of the exocrine pancreatic function.

AIMS: To show the ability of magnetic resonance hydrometry (MRH) to quantify the pancreatic secretion after secretin stimulation in order to distinguish between physiological excretion and reduced output in chronic pancreatitis. METHODS: MRH images were acquired in a 1.0-T-clinical scanner using a body-array coil and a heavily T2-weighted standard single-shot TSE sequence. Thirty-one patients (14 male/17 female) who routinely underwent ERCP for suspected choledocholithiasis (n = 22), recurring abdominal pain (n = 1), icterus (n = 6 and suspected pancreatitis (n = 2) were included. During the investigation 1 CU/kg BW secretin were administered intravenously. Secreted volume of fluid, start of secretion, achievement of a plateau of secretion and a combined score of these parameters (MRH score) were assessed and evaluated. Sensitivity and specificity were calculated for these parameters. RESULTS: 27 patients had no pancreatic pathology, and four suffered from chronic pancreatitis. Patients without pancreatic disorders produced a mean pancreatic fluid volume of 183 plus minus 86 mL, whereas patients with chronic pancreatitis secreted 61 +/- 39 mL. Secretion started after a mean time of 95 +/- 94 seconds (no pancreatic impairment) and 62 +/- 13 seconds (chronic pancreatitis). The MRH score achieved a high accuracy in the detection of chronic pancreatitis. CONCLUSIONS: Our study demonstrated the feasibility of measuring pancreatic output by MRH after stimulation with secretin. Moreover, a distinction between normal secretion and patients with chronic pancreatitis is possible.

Adult↗
PubMed2002

[Secretin-stimulated MR cholangiopancreatography (MRCP): visualization of the normal pancreatic duct in comparison with ERCP].

PURPOSE: To determine whether the application of secretin improves the depiction of the normal pancreatic duct and to document the time course of any possible improved visualisation. PATIENTS AND METHODS: Twenty-eight patients with a normal pancreatic ductal system, proved by ERCP, were prospectively enrolled in our study. MRCP was carried out in a 1.0 Tesla unit using a thick slab single-shot turbo-echo sequence (TR: infinity, TE: 1100 ms, FA: 150 degrees, slab thickness: 65 mm). Following acquisition of a non-enhanced image, 1 clinical unit/kg bodyweight of secretin was injected intravenously. During the subsequent ten minutes the MR measurement was repeated every 30 seconds. The images were independently evaluated by two investigators. RESULTS: The improvement in quality after administration of secretin was statistically significant for both investigators (p < 0.05), but no significant difference was found between both investigators concerning the quality of the images (p = 0.49). Prior to the secretin application, the entire ductal system only be evaluated in ten cases (35.7 %) by both investigators, afterwards in 26 cases (92.9 %). Improvement was achieved after a mean time of 1.5 minutes and lasted until the ninth minute. CONCLUSION: Intravenous application of secretin improves image quality of MRCP also in patients with no pancreatic pathology. Improvement begins after 1.5 minutes and lasts for about seven minutes.

Adult↗
PubMed2001

Inhibition of peroxynitrite-induced nitration of tyrosine by glutathione in the presence of carbon dioxide through both radical repair and peroxynitrate formation.

Peroxynitrite (ONOO-/ONOOH) is assumed to react preferentially with carbon dioxide in vivo to produce nitrogen dioxide (NO2*) and trioxocarbonate(1-) (CO3*-) radicals. We have studied the mechanism by which glutathione (GSH) inhibits the NO2*/CO3*--mediated formation of 3-nitrotyrosine. We found that even low concentrations of GSH strongly inhibit peroxynitrite-dependent tyrosine consumption (IC50 = 660 microM) as well as 3-nitrotyrosine formation (IC50) = 265 microM). From the determination of the level of oxygen produced or consumed under various initial conditions, it is inferred that GSH inhibits peroxynitrite-induced tyrosine consumption by re-reducing (repairing) the intermediate tyrosyl radicals. An additional protective pathway is mediated by the glutathiyl radical (GS*) through reduction of dioxygen to superoxide (O2*-) and reaction with NO2* to form peroxynitrate (O2NOOH/O2NOO-), which is largely unreactive towards tyrosine. Thus, GSH is highly effective in protecting tyrosine against an attack by peroxynitrite in the presence of CO2. Consequently, formation of 3-nitrotyrosine by freely diffusing NO2* radicals is highly unlikely at physiological levels of GSH.

Antioxidants↗
PubMed2001

Poststernotomy mediastinitis due to Staphylococcus aureus: comparison of methicillin-resistant and methicillin-susceptible cases.

The objective of the study was to compare the outcome of poststernotomy mediastinitis (PSM) caused by methicillin-resistant and methicillin-susceptible Staphylococcus aureus (MRSA and MSSA, respectively). Hospital records of 41 patients with S. aureus PSM who were all treated by closed drainage from 1 April 1996 through 1 February 2000 were reviewed. PSM was caused by MRSA in 15 patients and by MSSA in 26. Follow-up (+/-SD) averaged 12.5+/-14.0 months per patient. Both groups had similar perioperative characteristics. Patients with MRSA PSM had a significantly lower actuarial survival rate than did patients with MSSA PSM (60.0%+/-12.6%, 52.5%+/-3.4%, and 26.3%+/-19.7% versus 84.6%+/-7.1%, 79.0%+/-8.6%, and 79.0%+/-8.65 at 1 month, and at 1 and 3 years, respectively; values are +/- SD; P=.04). PSM-related death and treatment failure were significantly higher in the MRSA group than in the MSSA group (P=.03 and.02, respectively). Logistic regression analysis revealed that MRSA was the only independent risk factor for overall mortality. In conclusion, the clinical outcome of PSM caused by MRSA is poorer than that caused by MSSA.

Adult↗
PubMed2001

Comparative genomic hybridization-aided unraveling of complex karyotypes in human hematopoietic neoplasias.

The information obtained by conventional cytogenetics (CC) in human leukemias is sometimes limited, in particular by complex karyotypes with many marker chromosomes. While CC is restricted to metaphases with a good quality, interphase fluorescence in situ hybridization (I-FISH) is also capable of analyzing specific anomalies in the interphase nuclei. Comparative genomic hybridization (CGH) gives additional information about the imbalanced karyotype changes in the whole genome. The aim of this study was to assess the contribution of CGH to the unraveling of complex GTG karyotypes, which are difficult to evaluate by banding analysis, and to compare these results with those by CC and FISH. Thirteen bone marrow samples and one sample obtained from peripheral blood of 13 leukemia patients were examined by CC, FISH and CGH. The GTG banding analysis showed complex karyotypes with many marker chromosomes. The most frequent abnormalities were numerical and structural aberrations on chromosomes 5 and 7. In 12 of the 14 samples, the CGH analysis was able to detect chromosomal imbalances with losses of material on chromosome 5 and 7 as the most frequent aberrations. In all 14 samples, additional FISH analyses were performed. For most of the studied neoplasias, a close correlation between CC, FISH and CGH data was observed. CGH was considerably helpful in adding additional information to classical karyotyping, if the low quality or number of metaphases was insufficient for a reliable CC analysis. Even in cases where whole chromosome painting could be applied, it added information on the breakpoints of the observed rearrangements. In only 2 of the studied 14 samples, neither CGH nor I-FISH could improve the result of karyotyping. CGH, nevertheless, can be regarded as a powerful additional technique in leukemias with unsuccessful CC, incomplete, or complex karyotypes with many marker chromosomes. A systematic analysis by three techniques such as CC, FISH and CGH guarantees an optimal genetic characterization of the neoplasias.

Acute Disease↗
PubMed2001

Closed drainage using redon catheters for poststernotomy mediastinitis: results and risk factors for adverse outcome.

BACKGROUND: Several different surgical techniques have been described for the treatment of poststernotomy mediastinitis. The present study was undertaken to evaluate the midterm results of primary closed drainage using Redon catheters and to identify risk factors for adverse outcome. METHODS: Hospital records of 72 patients in whom poststernotomy mediastinitis developed and who underwent closed drainage with Redon catheters between April 1, 1996, and December 31, 1999, were reviewed. Follow-up was complete and averaged 11.8 +/- 11.5 months. RESULTS: Of the 25 deaths (34.7%) recorded, 15 were directly attributable to mediastinitis. Actuarial estimates for freedom from mediastinitis-related death were 80.1% at 1 month and 77.4% at 1 year, 2 years, and 3 years. Logistic regression identified older age (odds ratio, 1.1; 95% confidence interval, 1.02 to 1.18), incubation time of 14 days or less (6.5; 1.33 to 31.4), and methicillin-resistant Staphylococcus aureus (5.8; 1.2 to 27.2) as independent risk factors for mediastinitis-related death. Reintervention for recurrent mediastinitis was necessary in 9 patients (12.5%) and occurred at a mean interval of 18.7 +/- 13.5 days from the first debridement. Actuarial estimates for freedom from reintervention were 87.1% at 1 month and 85.2% at 1 year, 2 years, and 3 years. The combined end point of treatment failure (mediastinitis-related death or reintervention) was recorded in 9 patients (26.4%). Actuarial estimates for freedom from treatment failure were 74.3% at 1 month and 72.7% at 1 year, 2 years, and 3 years. Logistic regression identified older age (1.01; 1.02 to 1.18), preoperative renal insufficiency (6.8; 1.04 to 44.5), and methicillin-resistant S aureus infection (4.8; 1.04 to 22.33) as independent risk factors for treatment failure (includes mediastinitis-related death and reintervention [with or without death]). CONCLUSIONS: Primary closed drainage using Redon catheters is an effective and simple treatment for most patients in whom poststernotomy mediastinitis develops. However, patients with methicillin-resistant S aureus infection or recurrent mediastinitis may benefit from a more aggressive approach.

Adult↗
PubMed2001

Risk factors for post-cardiopulmonary bypass vasoplegia in patients with preserved left ventricular function.

BACKGROUND: Although vasodilatory shock (VS) is one of the main complications of cardiopulmonary bypass (CPB), its pathophysiologic basis remains unclear. The aim of this study was to identify predisposing factors for the development of VS after CPB independent of ventricular function. METHODS: Thirty-six patients undergoing coronary artery bypass grafting who developed VS were compared with 72 control patients without post-CPB cardiogenic or vasoplegic shock, in a 2:1 case control study. Patients and controls underwent the same anesthetic protocol and were matched by age, sex, operation date, and left ventricle ejection fraction. RESULTS: Preoperative and intraoperative patient characteristics were not significantly different between the two groups. Preoperative use of angiotensin-converting enzyme inhibitors and intravenous heparin were independent predictors for post-CPB VS by multivariate analysis (relative risk of 2.26 and 2.78, respectively). Intensive care unit stay and hospital stay were significantly longer in VS cases than controls, without any difference in early postoperative mortality. CONCLUSIONS: The only independent risk factors for postoperative VS identified were preoperative use of angiotensin-converting enzyme inhibitors and intravenous heparin. These risk factors were independent of age, gender, anesthetic protocol, and left ventricle ejection fraction.

Aged↗
PubMed2001

The freestyle stentless aortic bioprosthesis: more about the subcoronary technique.

Two years after aortic valve replacement with a Freestyle stentless aortic xenograft using the partial scallop inclusion technique, late prosthetic valve endocarditis developed with abscess formation in the space between the porcine and native human aortic wall. The presence of such a periprosthetic dead space exposes the patient to increased postoperative pressure gradients and the risk of superinfection.

Aged↗
PubMed2001

Norepinephrine release after acute brain death abolishes the cardioprotective effects of ischemic preconditioning in rabbit.

OBJECTIVE: Brain death (BD) abolishes the infarct-limiting effect of ischemic preconditioning (IP) in rabbits. We wished to define the role of the norepinephrine storm in this observation. METHODS: Rabbits were randomized into six groups of ten animals each. In control group (CTRL), anaesthetized rabbits were subjected to 30 min left coronary marginal branch occlusion and 90 min reperfusion. In CTRL+IP group, anaesthetized rabbits were preconditioned with a 5-min ischemia and 5-min reperfusion sequence before coronary occlusion. In CTRL+NE+IP group, anaesthetized rabbits received a 10 microg/kg norepinephrine injection 90 min before IP. In BD group, rabbits were subjected to 90 min of BD before coronary occlusion. In BD+IP group, brain-dead rabbits were preconditioned before coronary occlusion. In BD+LA+IP group, rabbits received an intra-arterial bolus injection of an alpha and beta adrenoreceptor blocking agent (labetolol, 1 mg/kg) prior to brain death induction and subsequent preconditioning. BD was induced by rapid inflation of an intracranial balloon. At termination of the experiment, left ventricular volume (LVV), myocardial volume at risk (VAR) and infarct volume (IV) were determined with methylene blue and tetrazolium staining, and measured using planimetry. RESULTS: LVV was not significantly different among groups. Myocardial VAR/LVV was not significantly different between groups (CTRL, 22.5+/-6.9%; CTRL+IP, 23.3+/-2.2%; CTRL+NE+IP, 25.9+/-12.7%; BD, 19.9+/-4.8%; BD+IP, 21.7+/-3.1%; BD+LA+IP, 23.4+/-5.8%; P=NS). IV/VAR was significantly reduced in the CTRL+IP group as compared with CTRL and CTR+NE+IP groups (12.2+/-1.2 vs. 49.7+/-1.7 and 49.3+/-4.7%; P<0.0001). There was no significant difference in IV/VAR between BD and BD+IP groups. In contrast, IV/VAR was reduced in BD+LA+IP compared to BD and BD+IP groups (13.9+/-5.4 vs. 50.0+/-1.4 and 49.6+/-1.5%; P<0.001). CONCLUSION: The loss of infarct-limiting effect of IP in brain-dead rabbits is related to the massive release of norepinephrine that occurs as a consequence of BD.

Animals↗
PubMed2001

Immunologic events and long-term survival after combined heart and kidney transplantation: a 12-year single-center experience.

BACKGROUND: In this study we compare the incidence of cardiac rejection and long-term survival after combined heart and kidney transplantation (HK) and single heart transplantation (H). Combined HK transplantation is a surgical option for patients with irreversible cardiac and renal failure. However, long-term results of combined HK transplantation on immunologic events and patient survival remain unknown. METHODS: Between 1988 and 1997, 12 consecutive patients underwent combined HK transplantation (HK group) at a single institution. A control group (H group) of 24 single heart transplant recipients operated on within the same period was matched for age, pre-operative pulmonary vascular resistance, hepatic insufficiency and gender mismatch. Recipients and donors were ABO compatible without HLA antigen matching. All patients received immediate triple immunosuppression that included cyclosporine. Because of early renal dysfunction, cyclosporine was switched to anti-thymocyte globulin in 5 patients from the HK group and in 1 patient from the H group (p = 0.01). RESULTS: Actuarial freedom from heart rejection at 6 months and at 1 year following transplantation averaged 90 +/- 9% and 70 +/- 14% in the HK group, and 65 +/- 10% and 49 +/- 11% in the H group, respectively (p = 0.023). Actuarial survival at 1, 5 and 12 years was not significantly different between groups, at 66%, 55% and 28% in the HK group, and 66%, 44% and 32% in the H group, respectively (p = 0.66). CONCLUSION: The incidence of cardiac rejection was significantly lower. Long-term survival in the HK group was similar to that in the H group. Putative mechanisms of decreased cardiac rejection in the HK group include allogeneic stimulation, donor-derived dendritic cells and induction by anti-thymocyte globulins. The need for long-term immunosuppression may be reduced after combined heart and kidney transplantation.

ABO Blood-Group System↗
PubMed2001

NAD(P)H, a directly operating antioxidant?

Endogenous oxygen- and nitrogen-centered free radicals are considered to play a decisive role in a variety of diseases such as neurodegenerative disorders, atherosclerosis, or cancer. Directly operating antioxidants limit the action of freely diffusing radicals by scavenging the attacking, oxidizing radical and re-reducing the oxidized biomolecule, i.e., the biomolecule-derived radical. From textbooks of biochemistry it is understood that NAD(P)H acts as a hydride (hydrogen anion) donor in a variety of enzymatic processes. One example is the re-reduction of GSSG to GSH, catalyzed by glutathione reductase. Because of this reaction, NADPH has been suggested to also act as an indirectly operating antioxidant, thus maintaining the antioxidative power of glutathione. To the best of our knowledge, however, neither NADPH nor NADH has been considered to be directly operating antioxidants. Based on recently published data, new experiments, and theoretical considerations, we propose that NAD(P)H represents a decisive, directly operating antioxidant that should be considered of major importance in the mitochondrial compartment. NAD(P)H fulfills this task both by scavenging toxic free radicals and repairing biomolecule-derived radicals.

Animals↗
PubMed2001

Bilateral cerebellar infarctions caused by a stenosis of a congenitally unpaired posterior inferior cerebellar artery.

Bilateral symmetrical cerebellar infarcts in the territory supplied by the medial posterior inferior cerebellar artery (PICA) branches are extremely rare. In the few cases published, it has not been possible to clearly pinpoint the cause of this infarct pattern. The authors present the case history of a 58-year-old man who had acute headaches accompanied by pronounced rotatory vertigo with nausea and vomiting. The neurological examination revealed bilateral cerebellar signs. Cranial magnetic resonance imaging showed bilateral, nearly symmetrical infarcts in the territory of the medial branches of both PICAs. These bilateral PICA infarctions were caused by a stenosis of an unpaired PICA originating from the left vertebral artery supplying both cerebellar hemispheres.

Arterial Occlusive Diseases↗
PubMed2001

Therapeutic anti-angiogenesis for malignant brain tumors.

Malignant brain tumors, especially malignant gliomas, have a poor prognosis, a fact which has remained unchanged over the last decades despite the employment of multimodal therapeutic approaches. Malignant gliomas are among the most vascularized tumors known and the amount of vascularization has been correlated to their prognosis. Since tumor growth is dependent on concomitant vascularization, recent experimental studies have focused on the use of anti-angiogenic molecules as a novel strategy in brain tumor therapy. Angiogenesis inhibitors target at proliferating endothelial cells and suppress the formation of a sufficient vascular bed. Inhibitors such as TNP-470, suramin and angiostatin have shown their therapeutic potential in experimental studies. In a clinical setting, they could be applied for the treatment of multiple tumors or postsurgically as an adjuvant therapy to prevent recurrence. This article discusses presently available anti-angiogenic agents, emphasizing on substances already in clinical trials.

Angiogenesis Inhibitors↗