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T Steiner

Publications and source records attributed to T Steiner.

At least 73 records · Page 4Linked to original sources

[Preclinical treatment of patients with stroke].

Stroke is the third leading cause of death and number one cause of disability in industrialised countries. Studies into the pathophysiology of acute ischaemic stroke have indicated that treatment options are likely to be optimized when early signs of stroke are recognized and treatment is initiated within 3 hours from symptom onset. Therefore, new conceptions heading towards early diagnosis, fast preclinical treatment, structured diagnostics, immediate initiation of acute therapy as well as early initiation of rehabilitation are required. It is well known that, for most patients, there is a long delay between the onset of symptoms and the start of therapy. Many factors are responsible for the time delay:signs and symptoms often go unrecognized and/or are minimized by patients, relatives and bystanders. Unlike trauma or myocardial infarction, stroke is not given a high priority by medical staff and/or emergency medical services (EMS). Although a small number of stroke patients is treated as emergency and attended to by the emergency medical services within this time window, this number could easily be increased by intensified public and emergency personnel education. At present the standard of care by the EMS personnel includes adequate cerebral oxygenation, treatment of cardiac arrhythmia, management of hypertension as well as therapy of hyperglycemia and hyperthermia. For the future, we hope that emergency medical services will be able to initiate therapies which must be administered within the first few hours of acute stroke after onset of symptoms. Early notification of hospitals would enable a particular stroke team to be present at the patient's admission.

Emergency Medical Services↗

Structural evidence for the aromatic-(i+1) amine hydrogen bond in peptides: L-tyr-L-tyr-L-Leu monohydrate.

In crystalline Tyr-Tyr-Leu monohydrate, an aromatic-(i+1) amine hydrogen bond is observed, that is a weak hydrogen-bond-type interaction between an aromatic side chain and N-H of the next peptide group in the main chain. Unlike the better investigated aromatic-(i+2) amine hydrogen bonds, which can adopt almost ideal geometries, the geometry of the discussed interaction is very distorted because of steric constraints. Presumably, this kind of weak hydrogen bond is only formed as a last resort if N-H finds it impossible to engage in the much stronger conventional hydrogen bonding with O-atom acceptors.

Amines↗

Water molecules hydrogen bonding to aromatic acceptors of amino acids: the structure of Tyr-Tyr-Phe dihydrate and a crystallographic database study on peptides.

The crystal structure of Tyr-Tyr-Phe dihydrate contains a hydrogen bond formed between a water molecule and the Phe side chain. The geometry is centered with a distance of 3.26 A between the water O atom and the aromatic centroid. In a database study on hydrated peptides, four related examples are found which exhibit a wide variability of hydrogen-bond geometries. The intermolecular surroundings of the water molecules are inspected, showing that they are typically involved in complex networks of conventional and non-conventional hydrogen bonds. Possible relevance for protein hydration is given.

Amino Acids↗

[Emergency and intensive care treatment after stroke. Recommendations of the European Consensus Group].

The concept of critical care in stroke is a controversial issue. The question of whether full-scale critical care management of stroke improves patient outcome is still open and probably depends on the definition adopted for critical care. At a second meeting of the European Ad Hoc Consensus Group, the following recommendations including specific problems for optimal emergency and critical care management of stroke patients were made.

Cerebrovascular Disorders↗

[Lymphocyte transformation test (LTT) as a model for evaluating cytokine-induced immunomodulation in renal cell carcinoma].

We investigated the immunomodulatory capacity of cytokines produced by renal cell carcinoma in vitro by analyzing their effects on mitogen-induced T-lymphocyte blast cell transformation. All of the tested 70 cell cultures, derived from 70 tumor areas in 33 patients, had immunomodulatory capacity. In addition to suppression in the lymphocyte transformation test (max. 44/70; 63%) there was also superinduction (max. 37/70; 53%). We found no significant correlation with the stage and grade of primary tumors. However, the suppression of mitogen-induced T-lymphocyte blast cell transformation was significant in multifocal tumors (0.08% TCM, P < 0.001) and non-significant in metastatic tumors. The production of the assayed cytokines IL-6, IL-10, IL-11, and TGF beta 1 was variable and there was no significant correlation to the immunomodulatory capacity of the tumors.

Carcinoma, Renal Cell↗

Bilateral renal cell carcinoma in a horseshoe kidney: preoperative assessment with MRI and digital subtraction angiography.

Renal cell carcinoma in a horseshoe kidney is an unusual entity. To our knowledge, only 123 cases have been published to date. We report the first bilateral case of two clear-cell carcinomas in an asymmetrically fused kidney. Optimum preservation of renal function after radical tumor removal requires accurate preoperative imaging. Since the vascular supply in fusion anomalies is extremely variable, angiography is mandatory. Magnetic resonance imaging was most suitable to predict the tumor extent and localization, because it simultaneously gave the most comprehensive anatomical overview of the malformation.

Adenocarcinoma, Clear Cell↗

Acute ischaemic stroke: revascularizing therapy. Stroke Council of the American Heart Association.

The principal goals of thrombolytic therapy for stroke are early restitution of cerebral blood flow, reduction of ischaemia, and attenuation of neurological disability through lysis of an occluding thrombus and consequent rapid restoration of circulation in the affected territory. Therapy should be initiated as soon as possible, at least within 4-6 h of stroke onset, to prevent major infarction and to salvage the hypoperfused but potentially viable zone adjacent to the central ischaemic area known as the ischaemic penumbra. This survey focuses on the safety and efficacy of thrombolytic therapy in acute ischaemic stroke in clinical trials. The results of two successful major randomized studies using tissue plasminogen activator (t-PA) were recently published. Intravenous thrombolysis seemed to be effective in improving functional and neurological outcome in a clearly defined subgroup of patients meeting the inclusion criteria of the studies. However, the identification of those patients proved to be difficult and depended on expertise in recognizing the early infarction signs on initial computed tomography. Since treating ineligible patients is associated with an unacceptable risk of intracranial bleeding complications and death, intravenous thrombolysis should only be performed at selected centres in selected patients.

Cerebral Revascularization↗

Combination therapy with neuroprotectants and thrombolytics in acute ischaemic stroke.

A reduction in neuronal damage following acute ischaemic stroke can be achieved by two major strategies: restoration of cerebral blood flow through the use of thrombolytics, and inhibition of the pathophysiological cascade that occurs as a result of a decreased cerebral blood flow through the use of neuroprotective agents. Therefore, combination therapy with thrombolytic and neuroprotective agents may provide additional benefits to those that can be achieved using the individual agents alone. Indeed, such benefits have already been demonstrated in several animal studies. However, a number of problems in trial design and statistical methodology need to be overcome. Nevertheless, combination therapy offers the potential of reducing the cost of stroke in terms of both health care and social welfare, and as well as limiting disability.

Brain Ischemia↗

Increased transforming growth factor beta1 plasma level in patients with renal cell carcinoma: a tumor-specific marker?

PURPOSE: The most worrying problem with renal cell carcinoma (RCC) seems to be the prediction of metastases by means of tumor-specific markers. Therefore, much effort is committed to the development of new markers. MATERIALS AND METHODS: The level of latent transforming growth factor beta1 (TGF-beta1) was measured in plasma samples by ELISA. These samples were collected from patients with RCC before they underwent radical nephrectomy, from patients 1 h after extracorporeal lithotripsy, from patients with pyelonephritis, and from healthy controls. RESULTS: In all cases of RCC the levels of latent TGF-beta1 in plasma were much higher (n = 20, 41.0 +/- 13.9 ng/ml, range 19.3-78.1 ng/ml) than in healthy controls (n = 20, 3.8 +/- 2.9 ng/ml, range 0.6-9.9 ng/ml, p < 0.0001). The TGF-beta1 levels in plasma after extracorporeal lithotripsy (n = 20, 7.4 +/- 4. 64 ng/ml, range 2.9-21.7 ng/ml, p < 0.01) and in patients suffering from pyelonephritis (n = 20, 18.93 +/- 14.2 ng/ml, range 4.2-46.7 ng/ml, p < 0.001) were also higher than in healthy controls. CONCLUSION: We conclude that increased levels of latent TGF-beta1 are common in the plasma of RCC patients. The TGF-beta1 plasma level in RCC was found to be significantly higher than in cases of inflammation. Thus, TGF-beta1 is a possible tumor-prognostic marker in RCC.

Biomarkers, Tumor↗

Dichotomized efficacy end points and global end-point analysis applied to the ECASS intention-to-treat data set: post hoc analysis of ECASS I.

BACKGROUND AND PURPOSE: It is not yet known which end points are the most suitable for evaluation of the effects of acute stroke intervention. The European Cooperative Acute Stroke Study (ECASS) I study used 2 primary end points. The study was powered to detect a 15% improvement of the median of each primary end point. The study failed to show this effect and was negative in the intention-to-treat analysis. The National Institute of Neurological Disorders and Stroke (NINDS) study used 4 dichotomized end points and applied a global end-point analysis. This study was positive and led to FDA approval of thrombolytic therapy for acute ischemic stroke. This study was undertaken to answer the question of whether a different statistical design may have shown a positive results of the ECASS I trial. METHODS: We performed a retrospective analysis of the ECASS I intention-to-treat data set (615 randomized and treated patients, rtPA treatment versus placebo) and post hoc application of the NINDS trial statistical methodology (global end-point analysis). The scores of the modified Rankin Scale (mRS), Barthel Index (BI), and the National Institutes of Health Stroke Scale (NIHSS) were dichotomized according to the criteria used in the NINDS trial. Favorable outcome was defined as a score of 0 or 1 on mRS, a score of 95 or 100 on BI, and a score of 0 or 1 on NIHSS. RESULTS: The number of patients reaching favorable outcome were higher in all 3 end points in the rtPA-treated group. The effect sizes were 8% for mRS, 6% for BI, and 14% for NIHSS, respectively. The differences are statistically significant for the mRS (P=0.044; odds ratio [OR], 1. 4; 95% confidence interval [CI], 1.0 to 2.0) and the NIHSS (P=0.001; OR, 1.9; 95% CI, 1.4 to 2.8), while for the BI significance was missed (P=0.102; OR, 1.3; 95% CI, 0.9 to 1.8). The global end-point statistics, however, shows a significant increase (P=0.008; OR, 1.5; 95% CI, 1.1 to 2.0) of favorable outcome in the rtPA-treated patient group. CONCLUSIONS: Using the global end-point analysis, ECASS is positive in the intention-to-treat analysis. This may indicate that the time window for thrombolysis may be as long as 6 hours. Looking at the 3 dichotomized end points, the effect sizes for 2 end points, mRS and BI, are smaller in the ECASS 6-hour intention-to-treat population compared with the NINDS trial, whereas the effect size for the NIHSS is larger. While in the NINDS trial all 3 end points reveal statistically significant results, in ECASS only 2 of the 3 corresponding end points, mRS and NIHSS, were statistically significant. This finding underlines an important difference of a global end-point approach: it may show a positive overall result although one of the end points is not positive.

Cerebrovascular Disorders↗

Early hemicraniectomy in patients with complete middle cerebral artery infarction.

BACKGROUND AND PURPOSE: Malignant, space-occupying supratentorial ischemic stroke is characterized by a mortality rate of up to 80%. Several reports indicate a beneficial effect of hemicraniectomy in this situation. However, whether and when decompressive surgery is indicated in these patients is still a matter of debate. METHODS: In an open, prospective trial we performed hemicraniectomy in 63 patients with acute complete middle cerebral artery infarction. Initial clinical presentation was assessed by the Scandinavian Stroke Scale (SSS) and the Glasgow Coma Scale (GCS). All survivors were reexamined 3 months after surgical decompression, with the clinical evaluation graded according to the Rankin Scale (RS) and Barthel Index (BI). We analyzed the influence of early decompressive surgery (<24 hours after symptom onset, based on clinical status at admission and initial CT findings) versus late surgery (>24 hours after first reversible signs of herniation) on mortality, functional outcome, and the length of time of critical care therapy was needed. RESULTS: In total, 46 patients (73%) survived. Despite complete hemispheric infarction, no survivor suffered from complete hemiplegia or was permanently wheelchair bound. In patients with speech-dominant hemispheric infarction (n=11), only mild to moderate aphasia was present. The mean BI score was 65, and RS score revealed severe handicap in 13% of the patients. In 31 patients with early decompressive surgery, mortality was 16% and BI score 68.8. Early hemicraniectomy led to a significant reduction in the length of time critical care therapy was needed (7.4 versus 13.3 days, P<0.05). CONCLUSIONS: In general, the outcome of patients treated with craniectomy in severe ischemic hemispheric infarction was surprisingly good. In addition, early decompressive surgery may further improve outcome in these patients.

Adult↗

An integrated approach for a knowledge-based clinical workstation: architecture and experience.

Today, the demand for medical decision support to improve the quality of patient care and to reduce costs in health services is generally recognized. Nevertheless, decision support is not yet established in daily routine within hospital information systems which often show a heterogeneous architecture but offer possibilities of interoperability. Currently, the integration of decision support functions into clinical workstations is the most promising way. Therefore, we first discuss aspects of integrating decision support into clinical workstations including clinical needs, integration of database and knowledge base, knowledge sharing and reuse and the role of standardized terminology. In addition, we draw up functional requirements to support the physician dealing with patient care, medical research and administrative tasks. As a consequence, we propose a general architecture of an integrated knowledge-based clinical workstation. Based on an example application we discuss our experiences concerning clinical applicability and relevance. We show that, although our approach promotes the integration of decision support into hospital information systems, the success of decision support depends above all on an adequate transformation of clinical needs.

Artificial Intelligence↗

[Criteria for clinical studies exemplified by immuno- and immunochemotherapy of renal cell carcinoma].

Clinical trials of phase I to III are the basis of testing drugs before their wide use among patients. In order to provide high quality treatment in oncology, particularly in palliative care of tumour patients, it is of critical importance to pay attention both to study characteristics and to the relevant German laws for clinical drug testing. For more than 20 years interleucin-2 and interferon-alpha based immunotherapy of metastatic renal cell carcinoma has been in controversy. In spite of various clinical protocols no consensus concerning the value of these concepts has been reached. Therefore, high quality oncological studies are necessary to determine the effectiveness of this type of immunotherapy and to avoid an uncritical application of a toxic and expensive treatment.

Antineoplastic Combined Chemotherapy Protocols↗

[Thrombolytic therapy in ischemic infarct].

Thrombolytic therapy in acute ischemic stroke is safe and effective in a defined subgroup of stroke patients. Until now, different fibrinolytic substances including urokinase, streptokinase and recombinant tissue plasminogen activator (rt-PA) have been tested regarding safety, efficacy, dosage and economic parameters in patients suffering from both carotid and basilar artery territory strokes. Recently, two large multicenter placebo-controlled intravenous rt-PA studies were published. The results show that thrombolysis of acute carotid territory strokes (European Cooperative Acute Stroke Study) and of strokes with a deficit measurable on the NIH Stroke Scale (National Institute of Neurological Disorders and Stroke rt-PA Stroke Study) improves clinical and economic outcome parameters in patients who were treated within 6 hours of the onset of symptoms and had that no signs of extended early infarction on the initial CT-scan. The occurrence of intracranial hemorrhages is more frequent after thombolytic therapy, but the majority of bleeding complications referred to petechial or more confluent hemorrhage limited to the infarcted tissue, without clinical deterioration. However, the identification of the appropriate patients is difficult and depends on the level of clinical and diagnostic experience. In vertebrobasilar artery territory stroke, local intraarterial thrombolysis with urokinase or streptokinase is performed in most cases. Thrombolytic treatment within twelve hours of the onset of symptoms was associated with significantly better results concerning both survival and neurological recovery.

Brain Ischemia↗

Hemicraniectomy with dural augmentation in medically uncontrollable hemispheric infarction.

Surgical decompression to alleviate raised intracranial pressure has been reported repeatedly in the past decades in small series of patients. Only recently have there been indications from larger trials that surgical decompression may be beneficial in treating space-occupying hemispheric infarction. However, surgical requirements for the procedure to be effective have not yet been defined. Based on theoretical criteria, the authors operated on 43 patients with medically uncontrollable hemispheric infarctions. The craniectomies were planned to be as large as possible and performed in combination with a subtemporal decompression. Postoperative computerized tomography scans were evaluated for these criteria. The mean survival rate for the group of 43 patients was 72.1% and no surviving patient ended up in a vegetative state. The mean area of craniectomy was found to be 84.3 +/- 16.5 cm2 and the mean distance of the inferior craniectomy margin to the middle fossa was 1.8 +/- 1.3 cm. Comparison of survivors and nonsurvivors failed to show a significant difference in the size of craniectomy or the distance to the floor of the middle fossa. Compared with the reported 80% fatality rate for medically treated stroke patients, in this subgroup the outcome (72.1% survival rate) is remarkably good. The authors conclude that decompressive craniectomy is an effective treatment, able to reduce mortality, and to improve neurological outcome in patients with space-occupying cerebral infarction if the size of craniectomy is large enough. Nevertheless, there is a need for further investigation to identify patients who will benefit from surgery and predictors to optimize the timing of surgical intervention.

Journal Article↗

Computational support for the suggested contribution of C-H...O=C interactions to the stability of nucleic acid base pairs.

Ab inito quantum chemical calculations are performed to quantify the stabilizing role of long C-H...O=C contacts in nucleic acid base pairing, which was suggested by Leonard, McAuley-Hecht, Brown & Hunter [(1995). Acta Cryst. D51, 136-139]. For the Watson-Crick adenine-uracil pair, a contribution of about 6% to the total bond energy is obtained. This weakly bonding effect is primarily a result of electrostatic attraction between the total positive charge of adenine C(2)-H and the negative end of the dipole uracil O(2)=C.

Journal Article↗

Renal cell carcinomas produce IL-6, IL-10, IL-11, and TGF-beta 1 in primary cultures and modulate T lymphocyte blast transformation.

We investigated the immunomodulatory capacity of primary cultures of renal cell carcinomas (RCC) by assessing production of cytokines and modulation of mitogen-induced T lymphocyte blast transformation. The results clearly show that immunomodulatory capacity is a common feature of RCC and that in vitro these tumors can produce interleukin-10 (IL-10) up to 20 ng/ml, IL-6 up to 35 micrograms/ml (> 250 kU/ml in the B9 system), IL-11 up to 15 micrograms/ml, and transforming growth factor-beta 1 (TGF-beta 1) up to 22 ng/ml. Furthermore, these tumors have the capacity to modulate T cell blast transformation over two orders of magnitude in each direction. The correlations of the immunologic properties of tumor cell cultures with the conventional classification of tumors (histology, cytology, staging, grading, presence of metastases, and secondary tumors) are analyzed. The significance of these findings for modulation of local immunity by RCC as well as for patient outcome is discussed.

Adjuvants, Immunologic↗