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Biomedical subjects

D Krause

Publications and source records attributed to D Krause.

At least 37 records · Page 2Linked to original sources

[Transcatheter closure of atrial septal defects in adults. Practicality and safety of four different closure systems used in 102 patients].

BACKGROUND AND OBJECTIVE: Surgical closure of secundum atrial septal defect (ASD) or patent foramen ovale (PFO) is a procedure with few complications. But this surgical intervention can nowadays be avoided by transcatheter insertion of occluding devices. Such interventional methods must be judged against the results of surgical procedures. This report from one center presents the practicability and safety of different transcatheter occluder systems. PATIENTS AND METHODS: Transcatheter occlusion was undertaken in 102 patients (40 females, 62 males, aged between 17 and 76 years [median age 45]) with either an ASD (41pts.) or a PFO (60 pts.) or with both, in one patient. Four different systems were used: ASDOS (for ASD and PFO), PFO-STAR (for PFO), Amplatzer Septal Occluder (for ASD) or Amplatzer PFO Occluder (for PFO). Follow-up, including transoesophageal echocardiography took place 48 hours, 4 weeks, 6 months and 1 year after the interventional occluder placement. RESULTS: An occluder was successfully placed in the ASD or PFO in 99 of the 102 patients. In three patients the occluder ( ASDOS ASD) could not be correctly ancchored in the defect. In two other patients the same device was subsequently removed surgically because of mispositioning or a large resiudal shunt. Occluder-associated problems were: mild (41%) or extensive (11%) thrombus formation on the occluder without early embolization, residual shunt at one year (ASD 16%, PFO 29%); minor displacement (10%) or broken umbrella strut (6%) of no clinical relevance. One patient required emergency surgical intervention on the day of the transcatheter placement (PFO-STAR) because of pricardial tamponade. Primary complete occlusion was achieved in 71%. There was no case of cerebral emboli. CONCLUSION: Transcatheter occlusion of ASD and/or PFO is a reliable and safe procedure. Regarding peri- and/or postinterventional complications, primary results and practicability, the Amplatzer septal occluder and Amplatzer PFO occluder are particularly advantageous.

Adolescent↗

Percutaneous transluminal renal angioplasty in atheroma with renal failure: long-term outcomes in 99 patients.

The aim of this study was to evaluate renal function changes after percutaneous transluminal renal artery angioplasty (PTRA) done to treat atheromatous renal artery stenosis with renal failure. Between 1990 and 1995, PTRA was performed in 99 renal failure patients (creatinine clearance less than 80 ml/min) with atheromatous stenosis of one or more native renal arteries. Indications for PTRA were chronic renal failure with poorly controlled hypertension (group A, 67 patients) or rapidly deteriorating renal function (group B, 32 patients). Renal function changes after PTRA were evaluated based on the percentages of patients with improved, stabilized, and worsened serum creatinine and creatinine clearance values, and on mean differences between final and baseline creatinine clearances. At the end of follow-up (19+/-10 months), group A had a significantly smaller creatinine clearance gain (42.9 ml/min before PTA to 44.5 ml/min after PTA, D=1.6 ml/min, in group A, vs 24.1-28.4 ml/min, D=4.3, in group B, p=0.03), and a significantly smaller percentage of improved patients (36 vs 62%) than group B. Most stenoses in group B either were bilateral or occurred on a solitary kidney ( p=0.001). Percutaneous transluminal renal artery angioplasty combined with aggressive medical treatment may be useful in maintaining or improving renal function, particularly in patients with a recent, sharp deterioration in renal function.

Angiography↗

Suppes predicate for genetics and natural selection.

Patrick Suppes' slogan that "to axiomatize a theory is to present a set-theoretical predicate" was used in the synthetic theory of evolution. The system presented here extends the axiomatics of the evolutionary theory presented by M. Williams to encompass aspects of genetics. Some biological implications of the system are discussed, including the relationship between the Darwinian concept of fitness, as applied to organisms, and the concept of fitness as applied to genotypes, as it is normally used in population genetics. This paper should be viewed as an adjunct to the speculations on the logical-mathematical foundations of biological sciences.

Animals↗

Transient activation of Jun N-terminal kinases and protection from apoptosis by the insulin-like growth factor I receptor can be suppressed by dicumarol.

The insulin-like growth factor I receptor (IGF-IR) activated by its ligands insulin-like growth factor (IGF)-I or IGF-II mediates suppression of apoptosis and contributes to tumorigenesis and cell growth. Here we investigated the activation of the stress-activated protein kinases including Jun N-terminal Kinases and p38 MAPK by IGF-I in interleukin-3-dependent FL5.12 lymphocytic cells that overexpress the IGF-IR (FL5.12/WT). We have shown previously that IGF-I protects these cells from apoptosis induced by interleukin-3 withdrawal but does not promote proliferation. IGF-I induced a rapid and transient activation of JNK that peaked at 40 min that was paralleled by a transient and robust phosphorylation of c-Jun. p38 was constitutively phosphorylated in FL5.12/WT cells. Activation of the JNK pathway by IGF-I occurred in the presence of phosphatidylinositol 3-kinase inhibitors and could be enhanced by anisomycin. Analysis of a series of FL5.12 cells expressing mutated IGF-IRs and analysis of 32D/IGF-IR cells showed that neither the C terminus of the receptor nor IRS-1 and IRS-2 were required for JNK activation, although tyrosine 950 was essential for full activation. The JNK inhibitor dicumarol suppressed IGF-I-mediated activation of JNK and phosphorylation of c-Jun but did not affect p38 and IkappaB phosphorylation or activation of AKT. IGF-I-mediated protection from apoptosis in FL5.12/WT cells was completely suppressed by dicumarol and partially suppressed by a p38 inhibitor. In the breast carcinoma cell line MCF-7, treatment with dicumarol also induced apoptosis. These data indicate that transient activation of JNK by IGF-I is mediated by signals that are distinct from those leading to phosphatidylinositol 3-kinase and AKT activation. The data further suggest that the SAPK pathways contribute to suppression of apoptosis by the IGF-IR.

Anisomycin↗

Increased cytotoxicity and stability of Lipiodol-pirarubicin emulsion compared to classical doxorubicin-Lipiodol: potential advantage for chemoembolization of unresectable hepatocellular carcinoma.

There is no well-defined curative treatment for advanced and unresectable hepatocellular carcinoma. The widely used transarterial chemoembolization (TACE) with a doxorubicin-Lipiodol emulsion has not been shown to improve survival in randomized studies. Further, obstruction of the hepatic artery used in the procedure is badly tolerated in patients with cirrhosis. Drugs with a more rapid penetration into the cancer cells are likely to eliminate the need for obstruction of the hepatic artery. We therefore compared the cytotoxicity of another anthracycline pirarubicin with that of the commonly used doxorubicin. In this report, we show that pirarubicin has a greater in vitro cytotoxic effect than doxorubicin on the HepG2 and Hu-H7 human hepatoma cell lines. Pirarubicin emulsion with Lipiodol is more stable at 37 degrees C than doxorubicin-Lipiodol. Moreover, pirarubicin accumulates at a greater extent in the oil phase, permitting Lipiodol to act as a slow-releasing vector for the anthracycline. Further, amiodarone, a multidrug resistance inhibitor, was shown to decrease the intrinsic resistance of HepG2 and Hu-H7 cells to both anthracyclines, and the presence of polysorbate 80 in the amiodarone preparation increased the stability of the anthracycline-Lipiodol emulsions. We therefore conclude that pirarubicin is a better candidate for TACE than doxorubicin. The rapid and increased cytotoxicity of pirarubicin on hepatoma cancer cells and the stability of the pirarubicin-Lipiodol amiodarone emulsion could avoid the complete obstruction of the hepatic artery by Gelfoam sponges, and provide a better tolerated method of TACE in patients with latent liver insufficiency.

Amiodarone↗

Hepatic arterial infusion of cisplatin diluted in hypotonic 25 g/l glucose solution administered in balloon-occluded hepatic artery: experimental rationale and clinical pilot study.

Reduced osmolarity in incubation medium was previously shown to increase in vitro cellular accumulation and cytotoxicity of cisplatin on cancer cells. We confirmed in the present work that cisplatin diluted in an hypotonic 25 g/l glucose solution (124 mOsm) was dramatically more cytotoxic in vitro than cisplatin diluted in normotonic 9 g/l NaCl (300 mOsm) on the human HT29 colon and MCF7 breast cancer cells. We conducted then a pilot clinical study on the administration of cisplatin diluted in hypotonic 25 g/l glucose solution given through the balloon-occluded hepatic artery for the treatment of liver metastases from colon or breast cancer tumors. Nine patients (5 men, 4 women; mean age 58, range: 44-71) with confirmed isolated, unresectable metastases from colorectal (7) or breast (2) tumors were included in this study and a total of 23 cycles were administered (2.55 per patient; range 1-5) with an average dose of 50 mg cisplatin (range: 12.5-100). Hepatic artery dissection due to balloon injury with partial or complete arterial obstruction were encountered in 2 patients. Pain in the liver and epigastric area was the main symptom which was constant and intense during the IAH cisplatin injection. Fever > 38 degrees C was observed in 15/23 cycles and increase of creatinine in 1/23 cycles. Transient increase of hepatic transaminases without change in prothrombin time was registered in all patients. However one patient who received the highest dose of 100 mg cisplatin developed a persistent but reversible clinical jaundice and a transient increase in prothrombin time. One patient achieved a partial response (12 weeks), 7 had stable disease (mean duration: 6 weeks) and one had a progressive disease. Hepatic arterial infusion of cisplatin diluted in hypotonic 25 g/l glucose solution and administered through the balloon-occluded hepatic artery is a feasible approach. Total dose of cisplatin in hypotonic glucose solution will not exceed 80 mg by cure in a further phase II study.

Adult↗

Rapid reconstitution of Epstein-Barr virus-specific T lymphocytes following allogeneic stem cell transplantation.

Epstein-Barr virus (EBV)-specific CD8 T lymphocytes are present at remarkably high frequencies in healthy EBV(+) individuals and provide protection from EBV-associated lymphoproliferative diseases. Allogeneic peripheral blood stem cell transplantation (allo-PBSCT) is a commonly used therapy in which T-cell surveillance for EBV is temporarily disrupted. Herein, human leukocyte antigen (HLA) class I tetramers were used to investigate the reestablishment of the EBV-specific CD8 T-cell repertoire in patients following allo-PBSCT. CD8(+) T cells specific for lytic and latent cycle-derived EBV peptides rapidly repopulate the periphery of matched sibling allo-PBSCT patients. The relative frequencies of T cells specific for different EBV peptides in transplantation recipients closely reflect those of their respective donors. Investigation of patients at monthly intervals following unmanipulated allo-PBSCT demonstrated that the frequency of EBV-specific T cells correlates with the number of EBV genome copies in the peripheral blood and that expansion of EBV-specific T-cell populations occurs even in the setting of immunosuppressive therapy. In contrast, patients undergoing T-cell-depleted or unrelated cord blood transplantation have undetectable EBV-specific T cells, even in the presence of Epstein-Barr viremia. The protective shield provided by EBV-specific CD8 T cells is rapidly established following unmanipulated matched sibling allo-PBSCT and demonstrates that HLA class I tetramers complexed with viral peptides can provide direct and rapid assessment of pathogen-specific immunity in this and other vulnerable patient populations. (Blood. 2000;96:2814-2821)

Adult↗

Mitochondrial DNA in the Central European population. Human identification with the help of the forensic mt-DNA D-loop-base database.

Sequencing of mtDNA is an advanced method for the individualisation of traces. Disadvantages of this method are expensive and time-consuming analysis and evaluation procedures as well as the necessary stock of population-genetic data which is still insufficient. Central European institutes of forensic medicine from Germany, Austria, and Switzerland have been working together since the beginning of 1998 to establish a mtDNA database. The aim is to build up a large stock of forensically established data and provide population-genetic data for frequency investigations, which will serve as a basis for expert opinions and scientific research. Good data quality is ensured by using original sequences only. Ring tests, which have been conducted to enhance analytical reliability, revealed a high correspondence rate of the analytical results obtained by the individual member institutes. Today 1410 sequences are available for comparison, of which 1285 sequences in the HV1 and HV2 regions cover the full ranges from 16051 to 16365 and from 73 to 340 (according to Anderson). The major part is formed by Central European sequences comprising 1256 data sets from Germany, Austria, and Switzerland. Today the database contains sequences from a total of 12 European, six African and three Asian countries including 100 sequences from Japan. This paper is aimed at discussing the individualisation potentials of mtDNA as well as the possibilities and limits of ethnic differentiation by means of pairwise sequence differences on the basis of the data stock available.

Austria↗

Efficiency of forensic mtDNA analysis. Case examples demonstrating the identification of traces.

The paper presents results of forensic mitochondrial DNA analyses which were aimed at typing the traces caused by touching or abrasion of skin cells. Five cases of strangulation tool investigation are summarised. Two cases of homicide could be cleared up by identifying the mtDNA of both the victim and the suspect on cables which had obviously been used as strangulation tools. In eight of 10 cases, weapons could be reliably assigned to their users. The mtDNA of the users could be even detected on cartridges after firing. In one case, evidence of a suicide could be provided by means of mtDNA sequencing of the wiping traces on a suicide note.

DNA Fingerprinting↗

Induction of basal cell carcinomas and trichoepitheliomas in mice overexpressing GLI-1.

Basal cell carcinoma is the most prevalent cancer in the western world, showing a rapid increase in incidence. Activation of the Sonic hedgehog/Patched (PTCH) signaling pathway because of PTCH1 inactivation is a key event in sporadic and familial basal cell carcinoma development in humans and is associated with transcriptional activation of specific target genes, including PTCH1 itself. These changes are analogous to the situation in Drosophila where hedgehog activates the zinc-finger transcription factor Cubitus interruptus, leading to increased transcription of target genes. In the present study, we show that mice ectopically expressing the human Cubitus interruptus homolog GLI-1 in the skin develop tumors closely resembling human BCCs as well as other hair follicle-derived neoplasias, such as trichoepitheliomas, cylindromas, and trichoblastomas. Furthermore, examination of the tumors revealed wild-type p53 and Ha ras genes. These findings firmly establish that increased GLI-1 expression is central and probably sufficient for tumor development and suggest that GLI-1-induced tumor development does not depend on additional p53 or Ha ras mutations.

Animals↗

Response to methotrexate treatment is associated with reduced mortality in patients with severe rheumatoid arthritis.

OBJECTIVE: This study investigated whether efficacious methotrexate (MTX) treatment has an impact on mortality of patients with severe rheumatoid arthritis (RA). METHODS: In this prospective, observational, one-center study, patients with severe RA refractory to other disease-modifying antirheumatic drugs started MTX treatment between 1980 and 1987. Patients were divided into 4 different groups according to their response to MTX treatment after 1 year (>50% improvement [n = 99], 20-50% improvement [n = 70], no improvement [n = 52], and discontinued treatment [n = 35]). After a followup of 7.5-15.3 years (mean 10 years), the numbers of deaths were assessed in the different groups. Standardized mortality ratios (SMR) were calculated by comparing the number of observed deaths in the study with the number of expected deaths in an age- and sex-matched sample of the general population. RESULTS: Two hundred seventy-one patients entered the study between 1980 and 1987. In 1995/1996, outcomes for 256 patients (94.5%) could be documented; 88 patients (34.4%) had died. In patients with >50% improvement after 1 year, the SMR was 1.47, while in patients with 20-50% improvement, the SMR was 1.85. In both groups combined, the SMR was 1.64 (95% confidence interval [95% CI] 1.11-2.17), compared with 4.11 (95% CI 2.56-5.66) in patients without improvement. Patients who had discontinued MTX treatment during the first year had an SMR of 5.56 (95% CI 3.29-7.83). CONCLUSION: Patients with severe RA who do not respond to MTX treatment have a poor prognosis, with >4-fold increased mortality compared with the general population, while RA patients who respond to MTX treatment have only a moderately increased mortality rate.

Antirheumatic Agents↗

Preoperative intraarterial thrombolysis before surgical revascularization for popliteal artery aneurysm with acute ischemia.

Because a popliteal artery aneurysm (PAA) generates emboli that progressively deteriorate the distal arterial network, they can constitute limb-threatening lesions. In 20 to 40% of cases, discovery of PAA coincides with sudden occlusion and resulting acute ischemia. In 40 to 60% of these patients, surgical revascularization fails and amputation is required. The objective of this prospective study was to assess the value of intraarterial thrombolysis to restore distal runoff before surgical revascularization. Between January 1, 1992 and December 31, 1996, we treated 15 PAA causing acute ischemia in 15 male patients with a mean age of 66.7 years (range, 44 to 87 years). Diagnosis was documented by clinical examination and ultrasound imaging. Intraarterial thrombolysis was performed under arteriographic control through a multiperforated catheter inserted by the anterograde femoral route to the thrombus. After an initial bolus of 100,000 U of urokinase, 600,000 to 1,600,000 U was continuously infused over a period of 6 to 18 hr. Heparin sodium was administered throughout thrombolysis. Surgical revascularization was performed within 1 to 4 days (mean, 2 days) after thrombolysis by exclusion and bypass in 14 cases and percutaneous transluminal angioplasty with stenting in 1 case. The ensuing results showed that, if performed carefully, intraarterial thrombolysis can safely prepare patients presenting with occluded PAA with acute ischemia for surgical revascularization to restore distal runoff. We use this combined technique routinely in our department. Morbidity is low in comparison with the risks of amputation.

Acute Disease↗

Expression of the plasminogen activator system and the inhibitors PAI-1 and PAI-2 in posttraumatic lesions of the CNS and brain injuries following dramatic circulatory arrests: an immunohistochemical study.

Plasminogen activators as inducible extracellular serine proteases are involved in a variety of processes, such as the degradation of brain structures. In regions of brain degradation, an increase in the expression of genes encoding cytokines and proteinases has recently been demonstrated. We tested the hypothesis, whether the plasminogen activator system as well as the plasminogen activator inhibitors are expressed and possibly involved in a proteolytic cascade that breaks down the extracellular matrix as a result of ischemic or posttraumatic brain destructions. To study this supposition, we investigated immunohistochemically the expression of tPA, uPA and its receptor, the plasminogen activator inhibitors PAI-1 and PAI-2, tetranectin as well as the laminin breakdown as an event of secondary brain injury. Brain tissue from 21 autopsy cases with severe brain injuries, material from 14 ischemic infarcts and 11 controls with acute hypoxia were used. All components of the plasminogen activator system studied were over-expressed immunohistochemically in reactive astrocytes, microglia and endothelial cells around the lesion zone. Tetranectin showed an analogous distribution to the plasminogen activator system. A reduced immunoreactivity of laminin within the identical region of destruction was detected concomitant with laminin remnants in perivascular macrophages, so that a remarkable role of the plasmin cascade in the degradation of extracellular matrix proteins in the brain is taken into consideration.

Adult↗

Schizophrenia with onset before the age of eleven: clinical characteristics of onset and course.

This study reports on the long-term course of 11 patients (6 girls, 5 boys) with childhood onset schizophrenia (COS, age at onset < 10 years). Patients were examined twice (mean follow-up period 38 years after onset). The premorbid development is assessed in terms of the Modified Premorbid Adjustment Scale (M-PAS) and additionally described by distinct psychopathological categories. The psychopathology at the onset of psychosis and at the second follow-up examination was assessed by categorical application of the Positive and Negative Syndrome Scale (PANSS). The outcome was rated with the Disability Assessment Score (DAS). The course of psychotic episodes and intervals between them is presented according to DSM-IV subtype classifications. Ten of 11 patients presented premorbid developmental peculiarities that were not adequately covered by the M-PAS subscales. Whereas in the 4 patients with acute onset of psychosis the positive PANSS-type was predominant, in the 7 patients with an insidious onset the negative PANSS-type prevailed. The nature of the diagnostic subtypes varied markedly across the course of the illness. In case of a continuous predominant catatonic symptomatology the outcome was poor. Detailed case descriptions help to illuminate the heterogeneous psychopathology of COS. Various temporary premorbid behavioral peculiarities were precursors of COS. A differentiation between premorbid and prodromal signs proved to be arbitrary. Our results contradict the assumption that COS is characterized only by a negative symptomatology.

Age Factors↗

Regulation of survival signals from the insulin-like growth factor-I receptor.

Suppression of apoptosis by survival factors is important for the maintenance of normal tissue homoeostasis and the response to infection or injury. Survival factors such as insulin-like growth factor-I (IGF-I) initiate a signalling cascade that starts by tyrosine phosphorylation of substrates leading to the activation of serine kinases that modulate the activity of members of the Bcl-2 family, which regulates the apoptotic machinery in most cells. Tumour cells often have enhanced survival mechanisms due either to up-regulation of the IGF-I receptor and its ligands or to loss of function of a phosphatase (PTEN) that regulates part of this survival pathway. The C-terminus of the IGF-I receptor appears to be a regulatory domain for the anti-apoptotic activity of this receptor, and certain residues within the C-terminus are essential for this regulatory activity. Knowledge of the proteins and pathways, which interact with these C-terminal domains, should lead us to ways of modulating IGF-I-mediated survival in tumours.

Animals↗