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Biomedical subjects

M Schneider

Publications and source records attributed to M Schneider.

At least 91 records · Page 5Linked to original sources
PubMed2003

Long-term efficacy and safety of infliximab in the treatment of ankylosing spondylitis: an open, observational, extension study of a three-month, randomized, placebo-controlled trial.

OBJECTIVE: Treatment of ankylosing spondylitis (AS) with infliximab, an anti-tumor necrosis factor alpha monoclonal antibody, was shown to be efficacious in patients with active disease during a 3-month treatment period. The purpose of this study was to evaluate the efficacy and safety of infliximab treatment of AS for a 1-year period. METHODS: This study was an open, observational, extension study of a 3-month, randomized, placebo-controlled trial. All patients who had tolerated infliximab (infliximab/infliximab group) or placebo (placebo/infliximab 12-week crossover group) therapy for 3 months entered the open extension trial (n = 65). Infliximab was administered at a dosage of 5 mg/kg every 6 weeks after the induction phase (weeks 0, 2, and 6). The primary end point was a 50% improvement in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). RESULTS: At week 54, a total of 54 of the 69 patients (78%) continued to take infliximab. The intent-to-treat primary efficacy analysis at week 54 showed that 47% of patients in the infliximab/infliximab group (95% confidence interval 31-63) and 51% of the patients in the placebo/infliximab group (95% confidence interval 36-67) achieved 50% improvement in BASDAI scores. In the analysis of those who completed the study, the mean BASDAI scores improved between weeks 0 and 54 in both treatment groups: from 6.6 to 2.4 in the infliximab/infliximab group and from 6.3 to 2.6 in the placebo/infliximab group. The dosage of nonsteroidal antiinflammatory drugs was reduced in approximately 70% of the patients. There were significant improvements in measures of functioning, metrologic parameters, and quality of life. Between weeks 12 and 54, a total of 4 patients had serious adverse events that were possibly related to infliximab and resulted in their discontinuing the study. CONCLUSION: Infliximab therapy in AS patients resulted in a rapid and significant improvement in BASDAI scores (>50% improvement) and a durable response for 1 year. The safety profile of infliximab in AS was comparable to that observed in the postmarketing experience for the approved indications.

Acute-Phase Proteins↗
PubMed2003

Adolescents and eating disorders: an examination of a day treatment program.

OBJECTIVE: In this study, we report on our day treatment program (DTP) for adolescents and young adults with eating disorders (EDs). METHOD: Data for the 82 female patients in DTP were examined, compared across ED diagnosis and by age (adolescents vs. young adults). At admission, patients completed the Eating Disorder Inventory-2 (EDI-2) and the Beck Depression Inventory (BDI) and the Family Adaptability and Cohesion Evaluation Scale- II (FACES-II). RESULTS: Forty-nine percent of patients successfully completed the day program and 13% required hospitalization following day treatment. Overall, there were no significant differences between the adolescents and adults at discharge of the day program. DISCUSSION: With shortened inpatient (IP) hospitalizations, DTPs can provide the long-term care required by many adolescent patients for psychological and physical recovery. This may be particularly important for the development of children and adolescents.

Adolescent↗
PubMed2003

[Imaging beyond conventional radiography: mini arthroscopy, duplex ultrasonography and positron emission tomography].

Imaging procedures, such as ultrasound and magnetic resonance imaging have broadened the diagnostic spectrum by "visualization" of pathomorphologic changes in rheumatic diseases. The advantages of these techniques are sectional imaging and three dimensional illustration, which enhance the exact detection of inflammatory soft tissue alterations and the sensitive and early detection of bony changes. Most current techniques and methods such as mini arthroscopy, color and power Doppler ultrasonography and positron emission tomography (PET) complete the set of diagnostic tools for rheumatologists, when other diagnostics reach their limits. Doppler ultrasonography and PET detect and assess inflammatory changes of systemic diseases locally and on the whole, which were not visible by standard diagnostic procedures. Mini arthroscopy furnishes, besides the direct evaluation of the joint, access to the pathomorphologic substrate itself with the opportunity of tissue sampling and further molecular biological analysis. These new diagnostic techniques open a widespread goal for rheumatologists in terms of etiopathogenesis, early diagnosis and monitoring of inflammatory rheumatic diseases.

Arthritis, Rheumatoid↗
PubMed2003

Reversible inhibitors of TAFIa can both promote and inhibit fibrinolysis.

The plasma carboxypeptidase activated thrombin-activable fibrinolysis inhibitor (TAFIa), is thermally unstable at 37 degrees C, with a half-life of 8 or 15 min depending on the isoform. The arginine analog, 2-guanidinoethylmercaptosuccinate (GEMSA), not only inhibits TAFIa but also slows the spontaneous inactivation of the enzyme, thereby reducing the activity of TAFIa, while extending its apparent half-life. Because, as shown in previous work, the ability of TAFIa to prolong clot lysis can be more dependent on its half-life than its concentration, in this study we determined whether reversible inhibitors of TAFIa could paradoxically prolong clot lysis. Potato tuber carboxypeptidase inhibitor (PTCI) or GEMSA were titrated into normal pooled human plasma, in the presence of soluble thrombomodulin. Both inhibitors mediate a biphasic antifibrinolytic effect, prolonging clot lysis at lower concentrations and enhancing clot lysis at higher concentrations. The antifibrinolytic effect of GEMSA is maximized at 1 mmol L-1, increasing clot lysis time from 100 min to 350 min. The antifibrinolytic effect of PTCI is maximized at 100 nmol L-1, increasing clot lysis time from 100 min to 240 min. To further characterize the nature of this biphasic effect, TAFI at various concentrations was added to TAFI-immunodepleted human plasma in the presence of PTCI or GEMSA. The magnitude of the effect depends on the concentration of TAFIa, the concentration of inhibitor, and the potency of the inhibitor. We propose that the biphasic antifibrinolytic effect is mediated by the dynamic equilibrium of free TAFIa that inactivates quickly, and TAFIa bound to inhibitor that inactivates slowly. TAFIa inhibitors used as therapeutic agents might not only enhance lysis at higher concentrations, but also stabilize fibrin clots at intermediate concentrations.

Animals↗
PubMed2003

Ex situ resection of primary cardiac tumors.

The prognosis of malignant heart tumors is pessimistic; 50% of patients die within 6 months. No optimal therapy has been established, and standardized therapeutic concepts have not been developed due to the low incidence of this disease. In most cases, chemotherapy and radiotherapy have not shown any survival benefit compared to surgical treatment. Obviously, radical resection of the tumor is the most important determinant for long-term survival. Here, we report on two patients in whom radical resection of heart tumors could be accomplished only after explantation of the heart.

Adult↗
PubMed2003

Results of randomised phase II studies comparing S16020 with methotrexate in patients with recurrent head and neck cancer.

BACKGROUND: The purpose of this study was to carry out two randomised phase II trials of S16020, a new olivacine derivative, tested as a single agent in patients with recurrent head and neck cancer, using methotrexate as the control arm to validate the results. PATIENTS AND METHODS: S16020 at either 80 or 100 mg/m2 was administered as a 3-h infusion every 3 weeks. Methotrexate, 40 or 50 mg/m2, was given by bolus injection, weekly for a minimum of 6 weeks. In total, 36 patients were entered in the randomised studies (25 in an initial study, 11 in a confirmatory study) of whom 24 received S16020 and 12 received methotrexate. RESULTS: A scheduled interim analysis showed one patient having a non-confirmed objective response with S16020 and three patients having a confirmed objective response with methotrexate. In the methotrexate group, there were no patients with severe non-haematological toxicity. With S16020, there was a high incidence of severe non-haematological toxicities, including asthenia, oedema of the face, oedema and pain at the tumour sites and erythematous rash; consequently, both studies were stopped. CONCLUSIONS: Both studies were stopped due to the poor anticipated benefit/risk ratio for S16020, although time to progression and overall survival time were similar in both treatment arms.

Adult↗
PubMed2003

Phase I and pharmacokinetic study of the association of capecitabine-cisplatin in head and neck cancer patients.

The combination of cisplatin and 5-fluorouracil (5-FU) is considered to be the standard treatment in induction chemotherapy for patients with squamous cell carcinoma of the head and neck. Capecitabine (Xeloda) is an oral fluoropyrimidine that is preferentially activated at the tumoral level, exploiting the higher thymidine phosphorylase activity in tumoral tissue. This phase I trial was conducted in patients with locally recurrent or metastatic head and neck carcinoma. The treatment plan included cisplatin on day 1 every 21 days, followed by capecitabine twice daily from day 2 to day 15, with a 1-week rest period. Pharmacokinetic investigations concerned plasma measurement of unchanged capecitabine, 5'-deoxy-5-fluorocytidine, 5'-doxifluridine and 5-FU using an optimized high performance liquid chromatography method, and cisplatin measurement in plasma using a limited sampling procedure. Twenty-one patients were included (mean age 61 years, range 46-76 years). Dose (mg/m(2)) increments for cisplatin and capecitabine (b.i.d.), respectively, were as follows: level 1, 80 and 1000 (three patients); level 2, 100 and 1000 (12 patients); and level 3, 100 and 1125 (five patients). Dose-limiting toxicities occurring during the first cycle (grade >/= 3) were observed on level 2 (one patient with diarrhea, nausea, vomiting, hand-foot syndrome, one toxic death due to renal failure and neutropenia, one patient with neutropenia) and on level 3 (one patient with diarrhea, one patient with hand-foot syndrome and one patient with neutrothrombocytopenia). Due to delayed side-effects, 14 patients (67%) had repeated cycles every 28 days instead of 21 days as initially planned. Objective response was obtained in seven patients (three complete responses and four partial responses). There was no evidence of pharmacokinetic-pharmacodynamic relationships with the drugs and metabolites investigated. Combination of capecitabine and cisplatin is feasible, with a very promising response rate. The recommended doses for further phase II studies are those of level 2 with cisplatin 100 mg/m(2) on day 1 and capecitabine 1000 mg/m(2) b.i.d. on days 1-14, every 28 days.

Administration, Oral↗
PubMed2003

Human seminal plasma displays significant phospholipid transfer activity due to the presence of active phospholipid transfer protein.

The lipid composition of germ cell membranes is considerably modified during spermatogenesis, sperm maturation and capacitation. Some of these modifications are caused by exchanges between soluble lipid donors or acceptors and cell membranes. The aim of this study was to assess whether significant lipid transfers between lipoprotein structures are detectable in human seminal plasma. Phospholipid and cholesteryl ester (CE) transfer activities were measured by specific fluorescence and isotopic assays. Seminal plasma samples did not display significant CE transfer. Substantial levels of phospholipid transfer activity were detected in all samples studied, levels were approximately 25% of the phospholipid transfer activity measured in human blood plasma. Concordantly, CE transfer protein was not detected in seminal plasma, while the presence of the phospholipid transfer protein (PLTP) was confirmed by Western blot analysis. Enzyme-linked immunosorbent assay indicated that seminal PLTP concentrations represented 25% of the concentration measured in blood plasma. Blockade of phosphatidylcholine and phosphatidyl-ethanolamine transfer by a 60 min, 56 degrees C heating step or with anti-PLTP antibody revealed that PLTP accounts for almost 80% of the phospholipid transfer activity present in seminal plasma. As shown by gel-permeation chromatography and Western blot analysis, seminal PLTP activity was partially associated with prostasomes. Significantly higher PLTP activity levels were measured in seminal plasma samples with low seminal vesicle secretions. The latter observation may reflect the sustained secretion of active PLTP that is diluted in a variable volume of PLTP-free seminal vesicle secretion. In conclusion, human seminal plasma displays significant phospholipid transfer activity due to the presence of active PLTP.

Carrier Proteins↗
PubMed2002

Degree of threat to the biological diversity in the Ilha Grande State Park (RJ) and guidelines for conservation.

The State Park of Ilha Grande is only a part (5,594 hectares) of the entire island (19,300 hectares) which is located off the south coast of Rio de Janeiro state, between the cities of Mangaratiba and Angra dos Reis. Approximately half of the Park area (47%) is covered by dense Atlantic forest. The secondary forest growth is in a process of ecological succession close to attaining maturity (43%) and the remaining part (10%) is composed of human-altered areas (1%), rocky outcrops with herbaceous vegetation (7%), mangroves and beaches (2%). The fauna is well represented but already shows signs of degradation with introduced species. The analysis of the degree of threat has shown that the dense forest habitat has a relatively stable status of conservation while the secondary forest, the mangrove and the herbaceous vegetation on rocky outcrops (and their fauna) are categorized as vulnerable. The area altered by human occupation is considered threatened. Since the coastal area where Ilha Grande is located is well known for its beautiful scenery (known as the green coast, because of the contrast between the ocean and the Atlantic forest covering the Serra do Mar mountain chain). There is a strong possibility for tourism to become the means in which to achieve economic sustainability for conservation. Contradictorily, tourism is also the major threat to local biodiversity and its landscape units. Because tourism is not organized and controlled, during high season the numbers grow above local capacity, giving rise to a proliferation of hotels, guesthouses and camping grounds. The resulting untreated open sewage, random garbage disposal and other harmful activities form the major threats to biodiversity.

Animals↗
PubMed2002

Treatment of active ankylosing spondylitis with infliximab: a randomised controlled multicentre trial.

UNLABELLED: BACKGROUND Treatment options for patients with ankylosing spondylitis are few. We aimed to assess the effectiveness of infliximab, an antibody to tumour necrosis factor (TNF)-alpha, in treatment of such patients. METHODS: In this 12-week placebo-controlled multicentre study, we randomly assigned 35 patients with active ankylosing spondylitis to intravenous infliximab (5 mg/kg) and 35 to placebo at weeks 0, 2, and 6. One patient in the infliximab group was withdrawn from the study. Our primary outcome was regression of disease activity of at least 50%. To assess response, we used validated clinical criteria from the ankylosing spondylitis assessment working group, including disease activity (BASDAI), functional indices (BASFI), metrology (BASMI), and quality of life (short form 36). Analyses were done by intention to treat. FINDINGS: 18 (53%) of 34 patients on infliximab had a regression of disease activity at week 12 of at least 50% compared with three (9%) of 35 on placebo (difference 44% [95% CI 23-61], p<0.0001). Function and quality of life also improved significantly on infliximab but not on placebo (p<0.0001 and p<0.0001, respectively). Treatment with infliximab was generally well tolerated, but three patients had to stop treatment because of systemic tuberculosis, allergic granulomatosis of the lung, or mild leucopenia. INTERPRETATION: Our results show that treatment with infliximab is effective in patients with active ankylosing spondylitis. Since there are some potentially serious adverse effects, we recommend that this treatment mainly be used in co-operation with rheumatological centres.

Adult↗
PubMed2002

A polyhydroxybutyrate biodegradable stent: preliminary experience in the rabbit.

PURPOSE: The lifelong persistence of foreign bodies within the arteries may contribute to restenosis. Thus, biodegradable devices might decrease recurrence rates. METHODS: Eleven polyhydroxybutyrate biodegradable stents and 13 tantalum stents were implanted into the iliac arteries of New Zealand white rabbits for up to 30 weeks. After killing the animals, the specimens were harvested, fixed in formalin, processed in paraffin, and stained. RESULTS: Polyhydroxybutyrate instigated intense inflammatory and proliferative reactions with an increase in collagen (2.4- to 8-fold vs native segments), thrombosis and in-stent lumen narrowing (375.5-606.6 mm vs 655.6 +/- 268.8 mm in native segments). The elastic membranes were destroyed in all specimens. The tantalum stents increased the in-stent lumen progressively (769.7 +/- 366.6 mm vs 1309.9 +/- 695.3 mm), penetrated the external elastic membrane, and increased mural collagen content (6- to 8.6-fold vs native segments). Neither restenoses nor thromboses occurred. CONCLUSIONS: In the rabbit iliac artery, polyhydroxybutyrate stents caused intensive inflammatory vascular reactions which ban them from clinical use.

Animals↗
PubMed2002

[Evidence-based guidelines--what is the present situation?].

Guidelines have proven to be an important tool for improving quality of health care. Evidence-based guidelines are particularly well accepted and have a high degree of credibility based on the transparent process of their development and the explicit use of clinical patient-oriented research, on which the recommendations are based. The goal of the guidelines "Management of early rheumatoid arthritis", currently developed by an interdisciplinary working group, is to minimize out existing deficiencies in the provision of health care.

Arthritis, Rheumatoid↗