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L Weissbach

Publications and source records attributed to L Weissbach.

At least 19 recordsLinked to original sources
PubMed2002

[How will urology cope with the new health care system?].

According to the report 2000 issued by the expert advisory committee on the health care system, improvement in performance requires, among other things, awareness of the need for more economic efficiency, better quality of medical care, and definition of targets. Disease prevention and early diagnosis are the main objectives of health policy and practice. Data mining becomes an important tool in epidemiological and clinical research. Urologists are called upon to engage in clinical studies to establish therapeutic standards and guidelines. Results of research must be put in to practice faster. Doctors ought to respond to changes in patients' attitudes.

Cost Control↗
PubMed2001

Evidence that HAX-1 is an interleukin-1 alpha N-terminal binding protein.

During studies aimed at understanding the function of the N-terminal peptide of interleukin-1 alpha (IL-1 NTP, amino acids 1-112), which is liberated from the remainder of IL-1 alpha during intracellular processing, we identified by yeast two-hybrid analysis a putative interacting protein previously designated as HAX-1. In vitro binding studies and transient transfection experiments confirmed that HAX-1 can associate with the IL-1 NTP. HAX-1 was first identified as a protein that associates with HS1, a target of non-receptor protein tyrosine kinases within haematopoietic cells. Recent data have also revealed interactions between HAX-1 and three disparate proteins, polycystin-2 (derived from the PKD2 gene), a protein linked to polycystic kidney disease, cortactin, and Epstein-Barr virus nuclear antigen leader protein (EBNA-LP). Sequence analysis of different HAX-1 binding domains revealed a putative consensus binding motif that is present in various intracellular proteins. Overlapping peptides comprising the IL-1 NTP were synthesized, and binding experiments revealed that discrete peptides were capable of interacting with HAX-1. HAX-1 may serve to retain the IL-1 NTP in the cytoplasm, and complex formation between the IL-1 NTP and HAX-1 may play a role in motility and/or adhesion of cells.

Adaptor Proteins, Signal Transducing↗
PubMed2001

[Palliation of urothelial carcinoma of the bladder].

Bladder cancer is a disease that occurs late in life (> 50% of the patients in Germany are 70 years or older). The general condition of the patients is frequently reduced, aggressive therapy of advanced tumours stages is therefore often contra-indicated. In this situation, palliative treatment is of extraordinary importance. Strangely enough, controlled prospective trials are lacking. They are, however, necessary in order to establish, or improve, standards of palliative treatment. Several smaller studies proved the potential of bladder irrigation and the embolisation of A. iliaca to stop bleeding from the tumourous bladder. If the tumour causes urinary retention, a permanent ureteral stent may in certain cases help to guarantee adequate flow. The assessment of palliative radiotherapy is not possible due to small numbers of (and highly selected) patients. It may have a potential in cases of hematuria, pain, and incontinence. New anti-tumour agents (e.g. Gemcitabine) may turn out to be a tolerable and effective palliative.

Aged↗
PubMed2001

Organ sparing surgery for malignant germ cell tumor of the testis.

PURPOSE: We evaluate the indication, technique and long-term outcome of organ preserving tumor resection rather than standard orchiectomy in 73 patients with bilateral testicular germ cell tumors or tumors of a solitary testicle. MATERIALS AND METHODS: Tumor resection was performed in 73 patients with 52 and 17 metachronous and synchronous bilateral testicular germ cell tumors, respectively, and 4 testicular germ cell tumors of a solitary testicle. Histology of the enucleated germ cell tumor revealed seminoma in 42 (57.5%) patients, embryonal carcinoma in 14 (19.2%), mature teratoma in 11 (15.1%), and mixed and combined germ cell tumors in 6 (8.2%). Mean tumor diameter was 15 mm. (range 5 to 30). Associated testicular intraepithelial neoplasia was diagnosed in 82% of patients who underwent local radiation with 18 Gy. RESULTS: After a median followup of 91 months (range 3 to 191) 72 (98.6%) patients had no evidence of disease and 1 died of systemic tumor progression. No local relapse occurred in 46 patients with associated testicular intraepithelial neoplasia treated with local radiation. However, local recurrence did develop in 4 patients after 3, 6, 12 and 165 months without radiation but all survived after undergoing inguinal orchiectomy. Testosterone levels were normal in 62 (84.9%) patients, hypogonadism developed in 7 (9.6%) and preoperative levels remained low in 4 (5.5%). Of the 10 patients who postponed local radiation for paternity reasons 5 had successfully fathered a child after organ sparing surgery. CONCLUSIONS: After a long-term followup of greater than 7 years organ sparing surgery represents a viable therapeutic approach to bilateral testicular germ cell tumor with an excellent postoperative outcome. Tumor enucleation might be considered a standard approach if the guidelines are respected, including cold ischemia, organ confined tumor less than 20 mm., multiple biopsies of the tumor bed, adjuvant local irradiation postoperatively to avoid local recurrence, close followup and high compliance.

Adult↗
PubMed2000

[Rational therapy].

In a time of scarce resources, the demand for a rational therapy is important in the present discussion to reform the health system. This article describes rational therapy and introduces practical approaches like drug therapy, evidence-based medicine, and clinical practice guidelines. The development of efficient cost-benefit relations may lead to more rationalization in the health sector. It is important to attain acceptance also among the patients that rationing in the health system is a necessary measure in diagnosis and therapy.

Cost Control↗
PubMed2000

[Early detection of prostatic carcinoma in urologic practice with digital rectal examination and prostate-specific antigen. Early Detection Project Group].

For the early detection of prostate cancer, a patient should undergo digital rectal examination (DRE) and PSA investigation. Follow-up of increased PSA levels detects nearly 80% of cancers. Positive predictive value of suspicious DRE and PSA is about 50%. Whereas in the first evaluation of this case-finding trial about 70% of the patients had organ-confined cancers, nearly all of the detected cancers in the follow-up investigation were organ confined. The increased number of organ-confined cancers detected in early periodical examinations can lead to a reduction of mortality and morbidity from prostate cancer.

Adult↗
PubMed2000

RPLND or primary chemotherapy in clinical stage IIA/B nonseminomatous germ cell tumors? Results of a prospective multicenter trial including quality of life assessment.

BACKGROUND: In order to reduce therapy-related morbidity in patients with nonseminomatous testicular germ cell tumors in clinical stage IIA/B, we performed a prospective multicenter trial comparing the standard retroperitoneal lymph node dissection (RPLND) +2 cycles of chemotherapy (arm A) with 3-4 cycles of primary chemotherapy (arm B). METHODS: From February 1991 to July 1995, 57 participating centers from Germany and Austria recruited 187 evaluable patients. 109 received primary RPLND and 78 primary chemotherapy. Two different chemotherapies were applied (PEB and CEB as adjuvant or inductive treatment). The quality of life (QoL), therapy-related morbidity, suspected predictive factors (histology and size of metastases), and outcome were assessed. RESULTS: In arm A, 12% had pathological stage (PS) I, 70% PS II A/B, and 18% PS II C/III. In arm B, 67% achieved complete remission with chemotherapy alone, 33% required a secondary RPLND. After a median follow-up of 36 months, 7% of the patients in arm A and 11% in arm B had relapsed. Two patients died due to complications of chemotherapy. Surgical complications amounted to 12% in arm A and 27% of 26 postchemotherapy RPLNDs (9% in arm B). Loss of ejaculation occurred in 32% in arm A, and 16% in arm B. Acute toxicity of chemotherapy was higher in the group receiving primary chemotherapy. CONCLUSION: We recommend primary RPLND because adjuvant chemotherapy can be spared in PS I, two cycles of chemotherapy are less toxic than 3 or 4 cycles, the primary operation is associated with less complications than that following chemotherapy and, with modern surgical procedures, ejaculation can be preserved in most of the patients, provided that the operation is carried out by an experienced surgeon. No statistically significant differences in the QoL outcome occurred between the treatment groups, suggesting that chemotherapy alone is not superior to primary or secondary RPLND in this respect.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

[Early recognition of prostate carcinoma. Initial results of a prospective multicenter study in Germany. Project Group for Early Detection DGU-BDU Laboratory diagnosis Professional Circle].

To compare the efficacy of digital rectal examination (DRE) and serum prostate specific antigen (PSA) in early detection of prostate cancer, we initiated a prospective multicenter screening trial. In 12,542 men choosen at random with a mean age of 62 (+/- 7.5) a suspect DRE or a PSA level > 4.0 ng/ml was found in 2343 (20%). Of the presently performed 744 biopsies, 157 revealed diagnosis of prostate cancer. Although further biopsies as well as the follow up of the 12,542 men are still missing, combination of DRE and PSA value > 4.0 ng/ml appears to be superior to DRE alone with a positive predictive value of 50% versus 19% in early detection of prostate cancer.

Aged↗
PubMed1999

[Medical guidelines].

Explore the source record for details and available documents.

Attitude of Health Personnel↗
PubMed1999

Homologous plasminogen N-terminal and plasminogen-related gene A and B peptides. Characterization of cDNAs and recombinant fusion proteins.

The cDNA corresponding to exons 2-4 of the processed human plasminogen (Pgn) gene, encoding the N-terminal peptide domain (NTP), has been cloned, expressed in Escherichia coli as a recombinant protein (r-NTP) containing a hexahistidine tag, and refolded to the native structure that contains two internal cystine bridges. RNA expression of the two Pgn-related genes, PRG A and PRG B, that potentially encode 9-kDa polypeptides having extensive similarity to the NTP has been investigated. Using RNA-based PCR with liver RNA as template, we demonstrate that PRG A encodes a detectable mRNA species. PRG A and PRG B have been found to be transcribed in the liver and yield virtually identical mRNAs. Neither of the PRGs are expressed in a variety of other normal tissues, as determined by Northern blot analysis. Factor-Xa digestion of the tagged r-NTP yields cleavage products which indicates that the expressed r-NTP domain of Pgn is endowed with a flexible conformation. Recombinant PRG B protein (r-PRG B) fused to a hexahistidine tag was purified and analyzed for structural integrity. Preliminary 1H-NMR spectroscopic data for r-NTP and r-PRG B indicate relatively fast amide 1H-2H exchange in 2H2O and close conformational characteristics for the two homologous polypeptides. Far ultraviolet-CD spectra for r-NTP and r-PRG B at pH 7.0 indicate similar defined secondary structure content for both domains, with 13-17% alpha-helix and 24-27% antiparallel beta-sheet. The fact that two transcriptionally active genes encode almost identical polypeptides supports the hypothesis that the Pgn NTP, together with the putative polypeptides encoded by the PRGs, may serve an important function, such as controlling the conformation of Pgn and thus its susceptibility to tissue activators.

Amino Acid Sequence↗
PubMed1999

Prognostic factors in seminomas with special respect to HCG: results of a prospective multicenter study. Seminoma Study Group.

OBJECTIVE: In a prospective multicenter trial, it was our intention to elucidate clinical prognostic factors of seminomas with special reference to the importance of human chorionic gonadotropin (HCG) elevations in histologically pure seminomas. METHODS: Together with 96 participating urological departments in Germany, Austria, and Switzerland, we recruited 803 seminoma patients between 1986 and 1991. Out of 726 evaluable cases, 378 had elevated, while 348 had normal HCG values in the cubital vein. Histology was reviewed by two reference pathologists. HCG levels were determined in local laboratories and in a study laboratory. Standard therapy was defined as radiotherapy in stages I (30 Gy) and IIA/B (36 Gy) to the paraaortal and the ispilateral (stage I) and bilateral (stage IIA/B) iliac lymph nodes; higher stages received polychemotherapy and surgery in case of residual tumor masses. Statistics included chi-square tests, linear Cox regression, and log-rank test. RESULTS: The HCG elevation is associated with a larger tumor mass (primary tumor and/or metastases). HCG-positive and HCG-negative seminomas had no different prognostic outcome after standard therapy. The overall relapse rate of 6% and the survival rate of 98% after 36 months (median) indicate an excellent prognosis. The calculation of the relative risk of developing a relapse discovered only stage of the disease and elevation of the lactate dehydrogenase concentration and its prolonged marker decay as independent prognostic factors for seminomas. A more detailed analysis of the prognostic significance of the stage revealed that the high relapse rate in stage IIB seminomas after radiotherapy (24%) is responsible for this result. CONCLUSIONS: We conclude that HCG-positive seminomas do not represent a special entity. Provided standard therapy is applied, HCG has no influence on the prognosis. Patients with stage IIB disease should be treated with chemotherapy because of the demonstrated higher relapse rate outside the retroperitoneum.

Biomarkers, Tumor↗
PubMed1999

Guidelines for the diagnosis and therapy of testicular cancer and new developments.

The guidelines of testicular cancer were elaborated and agreed upon interdisciplinarily. Standard therapy of stage I seminoma is infradiaphragmatic radiotherapy. Possible alternatives are adjuvant carboplatin therapy (still in test procedure) and, in case of lacking risk factors, the watch-and-wait strategy. If small metastases of lymph nodes exist, radiotherapy requires a higher dose and a larger beam field. Standard therapy in clinical stage IIC-III is cisplatin-based multidrug chemotherapy. In regard to nonseminomatous germ cell tumor there are no universal recommendations: retroperitoneal lymphadenectomy (RLA) with protection of ejaculation function, watch-and-wait strategy as well as adjuvant chemotherapy have the same cure rate but differ in relapse rate and morbidity. Knowing the crucial risk factors - depending on the expected relapse rate - it will be possible to recommend adjuvant chemotherapy or wait-and-see strategy in the future. In case of lymph nodes up to 5 cm, three different therapeutic strategies are possible. They reach the same cure rate, but are associated with different morbidity: primary nerve-sparing RLA plus adjuvant chemotherapy, primary nerve-sparing RLA without adjuvant chemotherapy, and primary chemotherapy. Advanced stages are related to three different groups in reference to their prognosis. At present, they are still treated with three or four cycles of PEB. In current protocols, patients with 'poor prognosis' receive high-dose therapy afterwards. These results have to be taken in consideration when updating the guidelines. The present guidelines also give notes for the therapy of TIN, residual tumor resection (RTR), management of CNS metastases, and therapy of recurrences.

Carcinoma in Situ↗
PubMed1998

Binding of myosin essential light chain to the cytoskeleton-associated protein IQGAP1.

The 190 kD human IQGAP1 protein, by virtue of its N-terminal calponin-homology domain, is found associated with the actin cytoskeleton, and is capable of cross-linking actin filaments. IQGAP1 complexes with several proteins, including the Rho family GTPases Cdc42 and Rac, as well as calmodulin. It was previously noted that one of the IQ motifs of IQGAP1 displays significant similarity to a myosin heavy chain IQ motif responsible for binding the calmodulin-related myosin essential light chain (ELC). Employing the yeast two-hybrid methodology as well as in vitro binding experiments, we present evidence that a truncated version of IQGAP1 can interact with the myosin ELC. This interaction may have significant consequences for various cellular processes that involve actomyosin contractility, and suggests that the biological targets of the ELC may not be restricted to the myosin heavy chain.

Actins↗