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Biomedical subjects

M Schulze

Publications and source records attributed to M Schulze.

At least 19 recordsLinked to original sources

Treatment of bendamustine and prednisone in patients with newly diagnosed multiple myeloma results in superior complete response rate, prolonged time to treatment failure and improved quality of life compared to treatment with melphalan and prednisone--a randomized phase III study of the East German Study Group of Hematology and Oncology (OSHO).

PURPOSE: This randomized phase III study compared bendamustine and prednisone (BP) to standard melphalan and prednisone (MP) treatment in previously untreated patients with multiple Myeloma (MM). PATIENTS AND METHODS: To be included, patients had to have histologically and cytologically proven stage II with progressive diseases or stage III MM. They were randomly assigned to receive BP (n=68) or MP (n=63). The primary endpoint was the time to treatment failure (TTF). Secondary endpoints included survival, remission rate, toxicity and quality of life. RESULTS: The overall response rate was 75% in the BP and 70% in the MP group. A significantly higher number of patients treated with BP achieved a complete remission than did patients receiving MP (32 vs. 13%; P=0.007), and the maximum response was achieved more rapidly in patients treated with BP compared to those receiving MP (6.8 vs. 8.7 cycles; P<0.02). TTF and remission duration were significantly longer in the BP group. Patients receiving BP had higher QoL scores and reported pain less frequently than patients receiving MP. CONCLUSION: BP is superior to MP with respect to complete remission rate, TTF, cycles needed to achieve maximum remission and quality of life and should be considered the new standard in first-line treatment of MM patients not eligible for transplantation.

Adult↗

[The position of laparoscopic surgery in pediatric urology].

With growing experience in laparoscopic techniques there is a switch in pediatrics from ablative surgery to reconstructive procedures. Besides the established procedures such as laparoscopic nephrectomy and orchidopexy, procedures like heminephrectomy and pyeloplasty have proven practicable and become standard therapies in children and infants. Due to technical advances, as shown for our own patients, the number of treated infants is still increasing. However, laparoscopic reconstructive procedures presuppose a good deal of experience in preparation and suture techniques, and remain reserved for centers with daily experience in laparoscopy. Daily experience with difficult urological laparoscopic procedures in adults will remain more common than in pediatric centres.

Child↗

Bendamustine, vincristine and prednisone (BOP) versus cyclophosphamide, vincristine and prednisone (COP) in advanced indolent non-Hodgkin's lymphoma and mantle cell lymphoma: results of a randomised phase III trial (OSHO# 19).

PURPOSE: The purpose of this study was to compare the efficacy and toxicity of bendamustine, vincristine + prednisone (BOP) with a standard regimen of cyclophosphamide, vincristine + prednisone (COP) in patients with previously untreated advanced indolent non-Hodgkin's lymphoma (NHL) and mantle cell lymphoma. METHODS: A total of 164 patients with follicular lymphoma (grade 1/2), mantle cell lymphoma or lymphoplasmacytic lymphoma (immunocytoma) was randomised to treatment with vincristine 2 mg (day 1) and prednisone 100 mg/m2 (days 1-5) + bendamustine 60 mg/m2 (days 1-5) or + cyclophosphamide 400 mg/m2 (days 1-5) for a total of eight 21-day cycles. RESULTS: The rate of complete remission was 22% with BOP and 20% with COP. The projected 5-year survival rate was 61% with BOP and 46% with COP. The BOP-associated 5-year survival advantage almost reached significance in the subgroup of patients who responded to therapy (74% vs. 56%; P = 0.05), and did reach significance in responders who did not receive interferon maintenance therapy (70% vs. 47%; P = 0.03). Toxicity was acceptable in both treatment groups, although alopecia and leucopenia were more severe with COP. CONCLUSIONS: Bendamustine can efficaciously and safely replace cyclophosphamide, as used in standard COP therapy, for the treatment of patients with indolent NHL and mantle cell lymphoma. Long-term survival data suggest a clinically significant benefit for patients treated with BOP.

Adult↗

Long term biventricular resynchronisation therapy in advanced heart failure: effect on neurohormones.

OBJECTIVE: To assess prospectively the effect of cardiac resynchronisation therapy (CRT) on New York Heart Association (NYHA) functional class, cardiac function, cardiopulmonary exercise performance, and neurohormonal activation during 24 months' follow up. DESIGN: Controlled study. PATIENTS AND RESULTS: 124 patients with severe congestive heart failure (ejection fraction < 35%, NYHA III-IV) and left bundle branch block (QRS duration > 150 ms) were enrolled (control group, n = 59; CRT group, n = 65) and followed up at 1, 3, 12, and 24 months. Compared with the control group, CRT led to significant short and long term improvements in functional NYHA functional class (mean (SEM) 2.1 (0.4) v 2.8 (0.4) at 24 months, p < 0.05), mean ejection fraction (25.7 (4)% v 21.1 (5)% at 24 months, p < 0.05), peak Vo(2) (16.8 (3.9) v 12.6 (3.5) ml/kg x min at 24 months, p < 0.01), and Vo(2) at anaerobic threshold (14.4 (3.7) v 10.8 (3.2) ml/kg x min at 24 months, p < 0.05). In addition, CRT for one and 12 months significantly decreased the plasma concentrations of noradrenaline (norepinephrine) and N-terminal fragment of pro-brain natriuretic peptide, whereas no changes were observed for other neurohormones such as antidiuretic hormone, aldosterone, and endothelin. CONCLUSION: Long term CRT (<or= 24 months) results in significant improvement of NYHA class and cardiopulmonary exercise capacity and a short term decrease in neurohormonal activation.

Bundle-Branch Block↗

[Interdisciplinary diagnostics in the outpatient treatment department of an environmental medical centre - report on experience with 400 patients].

The medical diagnostics of 400 patients of an interdisciplinary environmental medical centre is presented. The basic diagnostics included a special environmental medical history using a questionnaire, physical examination, allergological examinations and human biomonitoring. The latter was carried out in order to quantify the internal exposure to environmental pollutants. The main focus was on the differential diagnostics which was supported by special medical divisions of the hospital. Allergic illnesses as well as results of human biomonitoring exceeding the reference ranges were found frequently. Unfortunately a link between external exposure, internal dose and symptoms can hardly be established in environmental medicine. However, in several cases we found a considerably increased internal exposure which allowed to identify the sources of exposure (for example, usage of dichlorobenzene, permethrin, pentachlorophenol). Eliminating the sources obviously improved the health status of some of the patients concerned.

Adolescent↗

Epidemiology and clinical features of imported dengue fever in Europe: sentinel surveillance data from TropNetEurop.

Travelers have the potential both to acquire and to spread dengue virus infection. The incidence of dengue fever (DF) among European travelers certainly is underestimated, because few centers use standardized diagnostic procedures for febrile patients. In addition, DF is currently not reported in most European public health systems. Surveillance has commenced within the framework of a European Network on Imported Infectious Disease Surveillance (TropNetEurop) to gain information on the quantity and severity of cases of dengue imported into Europe. Descriptions of 294 patients with DF were analyzed for epidemiological information and clinical features. By far the most infections were imported from Asia, which suggests a high risk of DF for travelers to that region. Dengue hemorrhagic fever occurred in 7 patients (2.4%) all of whom recovered. Data reported by member sites of the TropNetEurop can contribute to understanding the epidemiology and clinical characteristics of imported DF.

Adolescent↗

[Pyrethroid exposure following indoor treatments with a dog flea powder].

UNLABELLED: Pyrethroid exposure following indoor treatments with a dog flea powder. HISTORY: A 42 year old woman reported hair loss, gastrointestinal and non-specific symptoms. The patient has lived in a council flat and kept a dog who had been regularly treated with pyrethroid containing flea powder. INVESTIGATIONS: The biological monitoring of pyrethroid meta-bolites in urine was performed using gas chromatography-mass spectrometry. The values at admission and follow-up after 4 weeks were highly elevated. Inspection of the flat revealed a humid and cramped dwelling. TREATMENT: We recommended redevelopment and cleaning of the dwelling and the avoidance of ectoparasiticide use. CONCLUSION: To our knowledge this is the first documented case of high indoor pyrethroid exposure following the use of ectoparasiticides with domestic animals. Pyrethroids can cause neurotoxic symptoms and skin irritation. There are few data concerning chronic effects. The causal connection between pyrethroid exposure and symptoms remains unclear and poses a great problem in environmental medicine.

Adult↗

Imported Falciparum malaria in Europe: sentinel surveillance data from the European network on surveillance of imported infectious diseases.

Malaria continues to have a high morbidity rate associated among European travelers. Thorough recording of epidemiological and clinical aspects of imported malaria has been helpful in the detection of new outbreaks and areas of developing drug resistance. Sentinel surveillance of data collected prospectively since 1999 has begun within TropNetEurop, a European network focusing on imported infectious diseases. TropNetEurop appears to cover approximately 10% of all patients with malaria seen in Europe. Reports of 1659 immigrants and European patients with Plasmodium falciparum malaria were analyzed for epidemiological information and data on clinical features. Regional data were quite diverse, reflecting local patterns of immigration and international travel. By far, the most infections were imported from West Africa. Europeans had more clinical complications; consequently, all deaths occurred in this group. Compared with European standards, the mortality rate was low (0.6% in Europeans). Data from TropNetEurop member sites can contribute to our understanding of the epidemiological and clinical findings regarding imported falciparum malaria.

Adolescent↗

Is first-line single-agent mitoxantrone in the treatment of high-risk metastatic breast cancer patients as effective as combination chemotherapy? No difference in survival but higher quality of life were found in a multicenter randomized trial.

BACKGROUND: To determine whether patients with high-risk metastatic breast cancer draw benefit from combination chemotherapy as first-line treatment. PATIENTS AND METHODS: A total of 260 women with measurable metastatic breast cancer fulfilling high-risk criteria, previously untreated with chemotherapy for their metastatic disease, were randomized to receive either mitoxantrone 12 mg/m(2) or the combination of fluorouracil 500 mg/m(2), epirubicin 50 mg/m(2) and cyclophosphamide 500 mg/m(2) (FEC) every 3 weeks. Treatment was continued until complete remission plus two cycles, or until disease progression. In the case of partial remission or stable disease, treatment was stopped after 12 cycles. Second-line treatment was vindesine, mitomycin and prednisolone. Gain from treatment was estimated using a modified Brunner's score composed of time to progression, patients' rating of the treatment benefit, alopecia, vomiting and performance status. RESULTS: After recruitment from 1992 to 1997 and observation from 1997 to 1999, the final evaluation showed that single-agent treatment with mitoxantrone does not differ significantly from combination treatment with FEC in terms of response, objective remission rate, remission duration, time to response, time to best response, time to progression or overall survival. There was, however, a significant difference in gain from treatment using a modified Brunner's score favoring the single-agent treatment arm. There was no evidence that any subgroup would fare better with combination treatment. CONCLUSIONS: No significant difference was detected between the treatment with mitoxantrone as a single agent and the combination of low-dose FEC in terms of response or survival; therefore, the imperative of the necessity of first-line combination chemotherapy for patients with high-risk metastatic breast cancer may be questioned. Since toxicity and quality of life score favored the single-agent mitoxantrone treatment arm, this treatment may be offered to patients preferring quality of life to a potential small prolongation of survival.

Adult↗

Human endostatin inhibits growth of human non-small-cell lung cancer in a murine xenotransplant model.

Overall prognosis in human NSCLC remains poor. Antiangiogenic treatment has become a promising concept for the treatment of solid malignancies. Our purpose was to evaluate the efficacy of recombinant HSENDO for the treatment of human NSCLC in an orthotopic murine xenotransplantation model. The efficacy of HSENDO was tested in vitro in cell-proliferation, cell-migration and tube-formation assays. In vivo, the effect of HSENDO on tumor growth was tested in s.c. xenotransplanted human NSCLC and on intrapulmonary induced human NSCLC. In vitro, HSENDO inhibited both human and rodent endothelial cell proliferation in a time- and dose-dependent fashion. Endothelial cell migration was inhibited by 97%. Tube formation of murine endothelial cells was inhibited and preexisting tubes degenerated after HSENDO exposure. In vivo, HSENDO delayed growth of s.c. xenotransplanted tumors. Immunohistochemic staining demonstrated no change in microvessel density but a significant reduction of proliferating tumor cells and an increase in bFGF and VEGF expression, reflecting the antiangiogenic effect of HSENDO. Intrapulmonary tumor induction caused death subsequent to metastatic disease. Systemic HSENDO application extended survival significantly. HSENDO was demonstrated to inhibit endothelial cell proliferation, migration and tube formation effectively. In vivo growth of s.c. transplanted tumors was delayed and survival extended by 32% and 69%, respectively, after intrapulmonary NSCLC induction.

Animals↗

Effective treatment of malignant pleural effusion by minimal invasive thoracic surgery: thoracoscopic talc pleurodesis and pleuroperitoneal shunts in 101 patients.

BACKGROUND: For effective palliation of patients with malignant pleural effusion due to advanced neoplastic disease, any proposed treatment should have low procedure-related mortality and morbidity. METHODS: The clinical outcome of 119 thoracoscopies in 101 patients (56 women, 45 men), from 42 to 91 years of age (mean, 68 +/- 9 years) with malignant pleural effusions was evaluated in a retrospective study. Video-assisted thoracoscopy (VATS) talc pleurodesis was done in 105 instances, and a pleuroperitoneal shunt was performed 14 times as an alternative when complete expansion of the lung could not be achieved due to tumor implants on the visceral pleura. RESULTS: The VATS talc pleurodesis resulted in clinically significant improvement of dyspnea in 92.2% of the patients. Thirty-day mortality was 2.8% and morbidity was 2.8%. The mean duration of postoperative survival was 6.7 months. Recurrent pleural effusion occurred in 5.7% of patients after a mean interval of 6 months. Clinical relief of dyspnea was obtained in 73% of the patients treated with pleuroperitoneal shunts. Thirty-day mortality in this group was 21% and morbidity was 14.3%. The mean duration of survival was 4.2 months. CONCLUSIONS: The VATS talc pleurodesis is appropriate for palliation of patients with malignant pleural effusions and should be performed once the diagnosis has been confirmed. Patients with lungs trapped by visceral carcinomatosis may benefit from placement of a pleuroperitoneal shunt as an alternative.

Adult↗

Gene expression by human articular chondrocytes cultured in alginate beads.

Culture of articular chondrocytes in alginate beads offers several advantages over culture in monolayer; cells retain their phenotype for 8 months or longer. Earlier studies of chondrocytes cultured in alginate concentrated on collagen and proteoglycan synthesis. However, gene expression by in situ hybridization (ISH) has not been investigated. The purposes of the present study on human chondrocytes were (a) to modify the ISH procedure for the alginate beads to examine the mRNA expression of alpha1 (II) procollagen, aggrecan, and two matrix metalloproteinases (MMP-3 and MMP-8) thought to be involved in cartilage matrix degradation, and (b) to compare expression in cultured chondrocytes with that in chondrocytes of intact human cartilage. The modifications made for ISH include the presence of CaCl2 and BaCl2 in the fixation and washing steps and exclusion of cetyl pyridinium chloride. By ISH we show that aggrecan, MMP-3, and MMP-8 are continuously expressed during 8 months of culture. The alpha1 (II) procollagen gene is expressed only during the first 2 months of culture and after 3 months its expression is undetectable, which is consistent with its absence in adult articular cartilage. By Western blotting, Type II collagen protein had been synthesized and deposited in both the cell-associated and further-removed matrix compartments at 7 and 14 days of culture. These data indicate that chondrocytes cultured in alginate beads could be preserved for immunohistochemistry and ISH and that culture of human chondrocytes in alginate beads may serve as a good model for studying cartilage-specific phenotype as well as factors that influence cartilage matrix turnover.

Adult↗

[Adult human chondrocytes in alginate culture. Preservation of the phenotype for further use in transplantation models].

Successful and cartilage-specific cultivation of chondrocytes requires a stable phenotype during the in vitro culture period. This is based on a differentiated extracellular matrix synthesis. The alginate system as a three-dimensional support is a useful system to culture chondrocytes and to analyze the biochemical processes in this system. Talar cartilage from the talocrural joints of 40 different donors were obtained through the Regional Organ Bank of Illinois within 24 hours of death. In 65% of the tissues the cartilage was classified as being undamaged. In these studies we were interested in the results of short-term culture over 14 days. Cell proliferation, total collagen content and total proteoglycan content were measured in the different matrix compartments and were visualized by histology and immunohistochemistry. Already after 7 days in culture the adult human chondroctes looked intact and formed a stable and cell-associated cartilage-specific extracellular matrix in the presence of 10% calf serum. This could be also demonstrated in the presence of IGF-I. With regards to the collagen content IGF-I at a concentration of 50 ng/ml seemed to induce an equal effect to 10% serum; with regards to the proteoglycan content IGF-I at a concentration of 20 ng/ml was equivalent. These encouraging preliminary results may lead to a new approach in tissue engineering for chondrocyte transplantation in combination with their extracellular matrix.

Adult↗

[Value of synovial analysis for prognosis of matrix synthesis of transplanted chondrocytes].

Successful transplantation of autologous chondrocytes for repair of articular cartilage defects requires an undisturbed matrix-synthesis of the transplanted cells. This, in turn, is dependent on the composition of the synovial fluid (SF) of the respective joint. We addressed the question whether analysis of a patient's SF can predict the rate of matrix-synthesis of articular cartilage exposed to this SF in vitro. SF was obtained from 115 patients with disorders of the knee, including gonarthrosis (n = 44), meniscal tears (n = 10), rheumatoid arthritis (n = 53), and reactive arthritides (n = 8). In the SF, the following parameters were determined: Interleukin-1 beta, IL-6, IL-8, IL-1-RA, TNF alpha, Insulin-like growth-factor I (IGF-I), IGF-II, IGF-binding protein-2 (IGFBP-2), IGFBP-3 as well as total proteinase activity and total collagenase activity. To assess the effect of SF on the matrix synthesis of articular chondrocytes, bovine cartilage was incubated in the presence of SF, and the rate of proteoglycan synthesis subsequently determined. In some cases, a monoclonal antibody directed against IGF-I was added. SF from patients with OA or trauma, respectively, stimulated PG-synthesis of bovine cartilage more markedly than did SF from patients with rheumatic arthritides. On the average, 60 percent of the SF-induced increase of cartilage matrix synthesis could be titrated out by an anti-IGF-I-AB. The best predictor for the SF-effects on PG-synthesis of exposed cartilage was the proportion of free IGF-I (r = 0.573, p < 0.001, Spearman rank correlation) followed by the SF-concentrations of IGF-I (with a positive sign), IGFBP-3, IL-1 beta, and TNF alpha (all with a negative sign). According to our data, IGF-I is the most important anabolic factor in human SF with respect to cartilage PG-synthesis. The proportion of free IGF-I seems to be of special importance in this regard. Low SF-levels of free IGF-I could be identified as a possible risk-factor for a sub-optimal protoeglycan synthesis of chondrocytes exposed to this synovial milieu.

Adult↗

On-line determination of mercury in river water at the German monitoring station Schnackenburg/Elbe.

A monitor is described which provides the on-line determination of mercury in river water at concentrations from 20 to 1000 ng/L. The measurement includes an on-line digestion with Br-/BrO3- and UV-radiation. Each determination is controlled by an on-line addition of 50 and 100 ng/L mercury carried out by pre-dilution of a 500 and 1000 ng/L stock solution using sequential injection analysis (SIA). One cycle of analysis takes 20 min and results in nine signals. A five days stand-alone operation has been performed successfully. Details are also published at web page: "http/www.rzbd.fh-hamburg.de/-prmercol".

Environmental Monitoring↗

Bioartificial cartilage.

Cartilage is a highly differentiated tissue. Its three-dimensional composition of cells and matrix is able to resist intensive mechanical loads. The capacity of cartilage tissue for regeneration is limited. Chondrocytes are responsible for matrix production of cartilage tissue. Enzymatic isolation and expansion of chondrocytes with cell culture techniques has been improved in the last years. These cells can be cultured on different three-dimensional culture systems suitable for transplantation to repair localized cartilage defects. Two types of bioresorbable polymer fleece matrices (PLLA and a composite fleece of polydioxanone and polyglactin) and lyophilized dura as a biological carrier are tested. Phenotypic and morphological appearance of the cultured articular rabbit chondrocytes is preserved on all three types of transport media. Production of glycosaminoglycans has been shown by Alcian blue staining, production of collagen by azan staining. Chondroitin 4- and 6-sulfate are detected immunohistochemically in the created constructs. The different carriers have specific characteristics regarding their suitability for the creation of bioartificial cartilage. This tissue is transplantable into articular cartilage defects and could, therefore, improve the minor intrinsic healing capacity of cartilage tissue.

Animals↗

[Tissue engineering for therapy of osteochondral cartilage lesions].

Cartilage defects still represent an unsolved problem in joint surgery. The intrinsic healing capacity of cartilage is insufficient and at best leads to reparative tissue like fibrous cartilage or cartilage like tissue regardless of the therapy applied. Cell culture techniques and generation of tissue specific matrix tread new paths to treat traumatic cartilage lesions. This technology referred to as tissue engineering allows for formation of constructs consisting of chondrocytes capable of production of cartilage specific matrix in combination with three-dimensional cell carriers. Polymers such as polylactid, co-polymers like polydioxanon with polyglactin and lyophilized dura have been used successfully to create such constructs with chondrocytes of different animal species. Cartilage specific compounds can be detected by histological and immunohistochemical techniques. To apply these constructs in humans, the distinguishing characteristics and problems of cell culture with human chondrocytes have to be considered. A further improvement of the artificially created tissue is conceivable using growth factors even including genetic manipulation of the applied cells.

Animals↗