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Biomedical subjects

M Ziegler

Publications and source records attributed to M Ziegler.

At least 19 recordsLinked to original sources
PubMed2005

Elective nephron sparing surgery should become standard treatment for small unilateral renal cell carcinoma: Long-term survival data of 216 patients.

OBJECTIVES: Our experiences with elective nephron-sparing surgery (NSS) for renal cell carcinoma (RCC) in a consecutive series of 216 patients are presented. Clinicopathological features and long-term oncological outcome is compared to patients treated with radical nephrectomy (RN). METHODS: Between 1975 and 2002, NSS was performed in 488 patients; 311 of these patients had elective indications. Renal cell carcinoma was found in 241/311 patients (77.5%). Long-term follow up data could be obtained in 216/311 patients. Cancer-specific survival was estimated using the Kaplan-Meier method. Cox's regression analysis and log-rank tests were used to evaluate independent predictive values of different clinicopathological features. Survival data of the 216 patients after NSS surgery were compared to 369 patients with small RCC treated with RN. RESULTS: After a mean follow up of 66 months (median 64 months) 29 (13.4%) of 216 patients treated with NSS had died, 4 of them (1.8%) tumour-related. Tumour recurrence was detected in 12 patients (5.6%). 204 patients (94.4%) were free of tumour at last follow-up. Cancer specific survival rates at 5 and 10 years for patients treated with NSS (RN) were 97.8% (95.5%) and 95.8% (84.4%). CONCLUSIONS: Elective NSS surgery provides optimal long-term outcome in patients with small localized RCC. Compared to RN, renal parenchyma is preserved without any disadvantage in survival rates. Consequently elective NSS should be accepted as gold standard for small renal tumours.

Adult↗
PubMed2005

Transition from initiation to promoter proximal pausing requires the CTD of RNA polymerase II.

The C-terminal domain (CTD) of mammalian RNA polymerase II consists of 52 repeats of the consensus hepta-peptide YSPTSPS, and links transcription to the processing of pre-mRNA. Although Pol II with a CTD shortened to five repeats (Pol II Delta5) is transcriptionally inactive on chromatin templates, it is not clear whether CTD is required for promoter recognition in vivo. Here, we demonstrate that in the context of chromatin, Pol II Delta5 can bind to the c-myc promoter with the same efficiency as wild type Pol II. However, Pol II Delta5 does not form a stable initiation complex, and does not transcribe promoter proximal sequences. Fluorescence recovery after photobleaching (FRAP) experiments with cells expressing enhanced green fluorescent protein (EGFP)-tagged Delta5 or wildtype Pol II revealed a single, highly mobile Pol II Delta5 fraction whereas wildtype Pol II yielded less mobile fractions. These data suggest that CTD is not required for promoter recognition, but rather for subsequent formation of a stable initiation complex and isomerization to an elongation competent complex.

Binding Sites↗
PubMed2005

[Sports injuries and overuse syndromes].

The benefit of regularly performed physical activity as a fundamental component of a healthy lifestyle is uncontradicted. The number of persons who participate in sports in Germany is approximately more than 40 million people, whereof 27.5 million are organised in sport associations. Every year 1.5-2 million sports injuries occur in Germany, which represent 25-30% of all accidents. The costs for treatment amount to a total of 1.5 billion euros. It is estimated that 80% of all sports injuries could be prevented if training and competition were performed correctly. The patterns and risk of injuries differ between particular sport disciplines and are therefore difficult to estimate. Knowledge of specific injury risks is indispensable for prevention of sports injuries. Furthermore this knowledge facilitates both sports physicians' diagnosis and therapy and guidance of the patient. In this review epidemiological data of sport traumatology are surveyed, patterns of injuries of particular sports are described in detail and prevention strategies are given. In a separate section specifics of sports injuries in children are discussed.

Athletic Injuries↗
PubMed2005

[Exercise therapy as a therapeutic concept].

Lack of exercise is a primary cause for today's level of morbidity and mortality in the Western world. Thus, exercise as a therapeutic modality has an important role. Beneficial effects of exercise have been extensively documented, specifically in primary and secondary prevention of coronary heart disease (CHD), diabetes mellitus, hypertension, disorders of fat metabolism, heart insufficiency, cancer, etc. A regular (at least 3 x per week) endurance training program of 30-40 min duration at an intensity of 65-70% of VO(2)max involving large muscle groups is recommended. The specific exercise activity can also positively affect individuals with orthopedic disease patterns, i.e., osteoporosis, back pain, postoperative rehabilitation, etc. Endurance strength training in the form of sequential training involving approx. 8-10 different exercises for the most important muscle groups 2 x per week is a suitable exercise therapy. One to three sets with 8-12 repetitions per exercise should be performed until volitional exhaustion of the trained muscle groups among healthy adults and 15-20 repetitions among older and cardiac patients. Apart from a positive effect on the locomotor system, this type of strength training has positive effects on CHD, diabetes mellitus, and cancer.

Coronary Disease↗
PubMed2005

Quantitative evaluation of a monoclonal antibody and its fragment as potential markers for pancreatic beta cell mass.

Antibodies, due to their high specificities and retention, represent potential beta cell imaging agents, however their slow clearance from the blood may preclude their use. Antibody fragments (Fabs) have much higher clearance and if they can be made with similar binding characteristics, would be more efficacious agents. An existing beta cell specific antibody (K14D10) and its Fab were evaluated with a previously developed screening assay. The Fab and the intact immunoglobulin (IgG) had similar affinities (6 - 20 nM), binding sites (300 000 - 700 000 sites/cell), and binding kinetics (t (1/2) = 8 - 18 minutes) for beta cells. However, the cellular specificity was far below the estimated requisite values needed to overcome the very low beta cell mass in the pancreas. The Fab cleared the blood twice as fast as the IgG, but did not preferentially accumulate into pancreas. Thus, generation of Fabs from IgGs with high beta cell binding and blood clearance appears feasible, but in order for molecules to be useful for tracking beta cell mass, antibodies of greater cellular specificity will have to be used.

Amino Acid Sequence↗
PubMed2005

Current TNM classification of renal cell carcinoma evaluated: revising stage T3a.

PURPOSE: : Recent studies of rare cases of pT3a renal cell carcinoma extending directly into the adrenal gland showed worse survival than in other pT3a cases and recategorization as stage pT4 was suggested. We assessed the prognostic validity of a stage pT3a diagnosis based on perirenal fat infiltration. MATERIALS AND METHODS: : The records of 1,794 patients with renal cell carcinoma who underwent surgical resection between 1975 and 2000 at our institution were analyzed retrospectively. Focusing on pT3a tumors, as defined by perirenal fat infiltration, numerous clinical and histopathological parameters were investigated by univariate and multivariate statistical methods with cancer specific survival as the primary end point. RESULTS: : We identified 237 of 1,794 patients with perirenal fat infiltration, classified as having pT3a disease. In patients with pT3a tumors tumor size was a significant parameter predicting survival. The most significant cutoff value for tumor size in pT3a disease was 7 cm. Patients with distant metastasis had a worse prognosis independent of T classification. Therefore, to assess the prognostic value of the current T classification in regard to T3a tumors we excluded patients with tumor stage cM+ for further subgroup analysis. Survival comparison of pT1 pNall, cM0 (744 of 1,794 cases) and pT3a pNall, cM0 7 cm or less (100 of 237) as well as pT2 pNall, cM0 (265 of 1,794) and pT3a pNall, cM0 greater than 7 cm (93 of 237) yielded similar results. After splitting pT3a into a modified T1/T2 classification a significant difference in 5-year survival analysis for a modified T1/T2 stage was found (pT1 plus pT3a less than 7 cm 90% vs pT2 plus pT3a greater than 7 cm 73%, p <0.001). Subsequently multivariate analysis in all 1,794 patients showed that modified T stage was an independent significant predictor of cancer specific survival. CONCLUSIONS: : We suggest revising the current pT3a classification based on perirenal fat infiltration but rendering a modified pT1/pT2 classification, which resolves pT3a cases without the loss of prognostic validity. Perirenal fat infiltration should not be used to assign T category. Tumors directly infiltrating the adrenal gland should be reclassified as T4.

Carcinoma, Renal Cell↗
PubMed2005

Effects of dyskinesias in Parkinson's disease on quality of life and health-related costs: a prospective European study.

The treatment of Parkinson's disease (PD) with l-DOPA leads to involuntary movements (dyskinesias). This 6-month observational study in three European countries in PD patients with various degrees of motor complications examined the effects of dyskinesias on the quality of life (QoL) of patients and health care costs. Retrospective and prospective health economic data were collected, and QoL of patients was measured using the Short Form-36 (SF-36) and the PD Quality of Life (PDQL) Scale. Regression analysis was used to estimate the adjusted effects of dyskinesias on QoL and costs, whilst accounting for the potentially confounding effects of disease progression, motor fluctuations and country. Increasing dyskinesia scores on either the Unified PD Rating Scale or the Goetz Dyskinesia Rating Scale were associated with significant reductions in QoL scores on the SF-36 and PDQL Scale. Increasing dyskinesia severity was also associated with increased depression scores on the Montgomery-Asberg Depression Rating Scale along with significant increases in health care costs. The effects of dyskinesia on QoL, depression and costs decreased but remained significant after adjustment for the confounding effects of disease progression and motor fluctuations. In conclusion, dyskinesias may adversely affect QoL and increase health care costs in patients with PD. Future studies should evaluate the potentially beneficial effects in terms of QoL and health care costs of strategies to delay the onset of, or the treatment of, dyskinesias.

Activities of Daily Living↗
PubMed2004

[The role of jogging in the prevention and treatment of cardiovascular disease].

Lack of exercise and poor eating habits are considered to be major causes of most diseases of civilization. In consequence, endurance sports, but also an integration of physical activity in everyday life, are gaining in importance. Positive effects of regular physical exercise have been described for CAD, arterial hypertension, lipid metabolic disorders, type 2 diabetes mellitus and the metabolic syndrome. In order to achieve an optimal training effect, exercise intensity should be oriented to the individual anaerobic threshold. As a rule of thumb, 30 minutes of endurance training--ideallyevery day--is considered necessary. Prior testing of a person's ability to undertake such activities should include ECG and blood pressure measurements, spirometry and lactate determination, and contraindications must be taken into account.

Anaerobic Threshold↗
PubMed2004

Pro- and anti-inflammatory cytokine production by autoimmune T cells against preproinsulin in HLA-DRB1*04, DQ8 Type 1 diabetes.

AIMS/HYPOTHESIS: Preproinsulin is a target T cell autoantigen in human Type 1 diabetes. This study analyses the phenotype and epitope recognition of preproinsulin reactive T cells in subjects with a high genetic risk of diabetes [HLA-DRB1*04, DQ8 with Ab+ (autoantibody-positive) or without islet autoantibodies (control subjects)], and in HLA-matched diabetic patients. METHODS: A preproinsulin peptide library approach was used to screen for cytokine profiles and epitope specificities in human peripheral blood lymphocytes, and CD4(+)CD45RA(-) and CD4(+)CD45RA(+) T cell subfractions, representing memory and naive and recently primed T cells respectively. RESULTS: In CD4(+) T cell subsets we identified immunodominant epitopes and cytokine production patterns that differed profoundly between patients, Ab+ subjects and non-diabetic HLA-matched control subjects. In Ab+ subjects, a C-peptide epitope C13-29 and insulin B-chain epitope B11-27 were preferentially recognised, whereas insulin-treated Type 1 diabetic patients reacted to native insulin and B-chain epitope B1-16. In peripheral blood lymphocytes of Ab+ subjects, an increase in T helper (Th) 1 (IFNgamma, IL-2) and Th2 (IL-4) cytokines was detectable, wheras in CD45RA(+) and CD45RA(-) subsets, IL-4 and IL-10 phenotypes dominated, compatible with the contribution of non-CD4 cells to IFNgamma content. In insulin-treated Type 1 diabetic patients, naive and recently primed CD4(+) cells were characterised by increasd IFNgamma, TNFalpha, and IL-5. CONCLUSIONS/INTERPRETATION: Our data show that T cell reactivity to preproinsulin in CD45RA subsets is Th2-dominant in Ab+ subjects, challenging the Th1 paradigm in Type 1 diabetes. Characteristic immunodominant epitopes and cytokine patterns distinguish diabetic patients and Ab+ subjects from HLA-matched healthy individuals. This could prove useful in monitoring of T-cell immunity in clinical diabetes intervention trials.

Adolescent↗
PubMed2004

[Glossary on patient safety -- a contribution to on-target-definition and to appreciate the subjects of "patient safety"].

Since the release of the report "To Err is Human" by the American Institute of Medicine (IOM) the subject "Medical Risks, Errors and Patient Safety" has gained increasing interest in literature. In Germany, neither extensive statistics nor generally significant epidemiological studies regarding common errors associated with damages caused to patients' health exist. In recent years the subject has become increasingly interesting both in specialist discussion and it the lay press; it has become evident that the different use of terms, especially those originating from the Anglo-Saxon language, can lead to misunderstandings. Hence, as one of the first steps of its action programme, the expert panel "Patient Safety" of the German Agency for Quality in Medicine has compiled a glossary of technical terms to provide adequate support to the discussion this important subject of nomenclature.

Germany↗
PubMed2004

Adrenal metastases in 1635 patients with renal cell carcinoma: outcome and indication for adrenalectomy.

PURPOSE: Routine removal of the ipsilateral adrenal gland in patients with renal cell carcinoma who undergo nephrectomy has been a matter of dispute. In a retrospective study we screened for subgroups of patients with renal cell carcinoma from a large single center patient population who may have benefited from ipsilateral adrenalectomy. MATERIALS AND METHODS: Radical nephrectomy was performed in 1635 patients at a single institution between 1980 and 2000. A total of 1010 patients underwent radical nephrectomy plus ipsilateral adrenalectomy, whereas in 625 no simultaneous adrenalectomy was performed. Numerous clinical and histopathological parameters were investigated by univariate and multivariate statistical methods for their predictive value in regard to cancer specific survival. RESULTS: Metastases in the adrenal gland were found in 5.5% of patients (56 of 1010) undergoing nephrectomy with adrenalectomy. Of 30 patients with adrenal metastasis and preoperative computerized tomography/magnetic resonance imaging 23 were found to have histological evidence of cancer, approaching a false-negative rate of 23.3%. All patients with false-negative computerized tomography/magnetic resonance imaging had a primary tumor of greater than 4 cm. Patients with adrenal metastases predominately had pT3 or greater tumor stage (82%). Cancer specific survival rates (75% vs 73% for adrenalectomy vs no adrenalectomy) and postoperative complications rates (7% vs 8%) did not differ significantly between the 2 groups. The prognosis in patients with a solitary adrenal metastasis (18 of 56) was more favorable than in patients with additional metastatic sites (38 of 56). CONCLUSIONS: Adrenal metastases from primary renal cell carcinoma were found significantly more often in patients with advanced tumor stages. Ipsilateral adrenalectomy should be recommended for all resectable renal cell carcinoma with a primary tumor of greater than 4 cm or with nonorgan confined tumor stages (T3 or greater) since a false-negative rate of about 20% can be expected with current imaging techniques.

Adrenal Gland Neoplasms↗
PubMed2004

[Dynamics of some postreplication DNA repair proteins in carcinogen-damaged mammalian cells].

Many types of DNA lesions in template strands block DNA replication and lead to a stalling of replication forks. This block can be overcome (bypassed) by special DNA polymerases (for example, DNA polymerase eta, Pol eta) that perform translesion synthesis on damaged template DNA. The phenomenon of completing DNA replication, while DNA lesions remain in the template strands, has been named post-replication repair (PRR). In yeast Saccharomyces cerevisiae, PRR includes mutagenic and error-free pathways under the regulation of the RAD6/RAD18 complex, which induces ubiquitylation of PCNA. In mammalian cells, Pol eta accumulates in replication foci but the mechanism of this accumulation is not known. Pol eta possesses a conserved PCNA binding motif at the C terminal and phosphorylation of this motif might be essential for its interaction with PCNA. We have shown previously that staurosporine, an inhibitor of protein kinases, inhibits PRR in human cells. In this study we examined whether the accumulation of Pol eta in replication foci after DNA damage is dependent on phosphorylation of the PCNA binding motif. We also studied DNA damage-induced phosphorylation of GFP-tagged human Rad18 (hRad18) and its accumulation in replication foci. Our data indicate that (1) Pol eta is not phosphorylated in response to UV irradiation or MMS treatment, but its diffusional mobility is slightly decreased, and (2) hRad18 accumulates in MMS-treated cells, and considerable amount of the protein co-localizes with detergent insoluble PCNA in replication foci; these responses are sensitive to staurosporine. Our data suggest that hRad18 phosphorylation is the staurosporine-sensitive PRR step.

Amino Acid Motifs↗
PubMed2003

[Percutaneous carotid angioplasty with stent implantation and protection device against embolism--a prospective study of 100 consecutive cases].

BACKGROUND AND OBJECTIVE: Percutaneous transluminal angioplasty and stenting of internal carotid artery stenosis has been increasingly practiced as an alternative to carotid embolectomy, particularly since the development of cerebral protection devices. 100 consecutive elective percutaneous carotid stenting procedures were carried out in our centre. We here present the clinical outcome and follow-up of these patients. PATIENTS AND METHODS: 69 men and 22 women, average age 69 +/- 10 years with symptomatic (41 %) or asymptomatic and progressive (59 %) > 80 % stenosis of the internal carotid artery were treated. There was a high rate of co-morbidity and a high vascular risk. 64 % would have been excluded from the NASCET trial because of one, 31 % because of two or more contraindications. In 84 % of the patients symptomatic coronary artery disease was present, in 13 % a significantly reduced left ventricular function (LVEF < 40 %).Pre- and post-procedure all patients were given aspirin and clopidogrel and examined by an independent neurologist. 99 stents were placed with the use of an embolic protection device (28 times with distal balloon occlusion, 72 times with a filter device).The follow-up period averaged 10.4 +/- 8.2.(1 - 29 months). RESULTS: The angiographic success rate was 99 %. During the procedure transient neurological symptoms were experienced by 4 % of patients (2x TIA,2x PRIND) and a minor stroke resulted in two. In 90 % of the interventions debris was collected from the embolic protection device. The maximum diameter of particles was 311+/-431 (30 - 1850) micro m. There was some correlation between patients' symptoms prior to stent implantation and maximum particle size (p < 0,04),but none with any other angiographic or clinical parameters. The combined endpoint (death and any stroke) after 30 days occurred 5 times (5 %). A subacute stent thrombosis occurred once, restenosis in two patients. CONCLUSION: Carotid artery stenting with use of a distal embolic protection device is a feasible new alternative to carotid endarterectomy. Our results indicate high success rate and low complication rates, even in patients with severe co-morbidity. The results compare well with surgical figures. Our favourable results are supported by data emerging from current randomized multicenter trials and a large therapy registry. However, long-term follow-up will still be required.

Adult↗