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Biomedical subjects

Hans-Peter Schmid

Publications and source records attributed to Hans-Peter Schmid.

At least 19 recordsLinked to original sources
PubMed2006

Dendritic cell-based multi-epitope immunotherapy of hormone-refractory prostate carcinoma.

BACKGROUND: Dendritic cell (DC)-based immunotherapy is a promising approach to augment tumor antigen-specific T cell responses in cancer patients. However, tumor escape with down-regulation or complete loss of target antigens may limit the susceptibility of tumor cells to the immune attack. Concomitant generation of T cell responses against several immunodominant antigens may circumvent this potential drawback. In this trial, we determined the immunostimulatory capacity of autologous DC pulsed with multiple T cell epitopes derived from four different prostate-specific antigens in patients with advanced hormone-refractory prostate cancer. PATIENTS AND METHODS: Autologous DC of HLA-A*0201(+) patients with hormone-refractory prostate cancer were loaded with antigenic peptides derived from prostate stem cell antigen (PSCA(14-22)), prostatic acid phosphatase (PAP(299-307)), prostate-specific membrane antigen (PSMA(4-12)), and prostate-specific antigen (PSA(154-163)). DC were intradermally applied six times at biweekly intervals followed-in the case of an enhanced immune response-by monthly booster injections. Immune monitoring during the time of ongoing vaccinations (12-59 weeks) included ex vivo ELISPOT measurements, MHC tetramer analysis and in vitro cytotoxicity assays. RESULTS: Of the initial six patients, three qualified for long-term multi-epitope DC vaccination. This regime was tolerated well by all three patients. The vaccination elicited significant cytotoxic T cell responses against all prostate-specific antigens tested. In addition, memory T cell responses against the control peptides derived from influenza matrix protein and tetanus toxoid were efficiently boosted. Clinically, the long-term DC vaccination was associated with an increase in PSA doubling time. CONCLUSIONS: DC-based multi-epitope immunotherapy with repeated boosting in men with hormone-refractory prostate carcinoma is feasible and generates efficient cellular antitumor responses.

Acid Phosphatase↗
PubMed2006

Spontaneous priapism after radical retropubic prostatectomy.

We present the first case of priapism following radical prostatectomy. A 66-year-old man with normal erections underwent radical retropubic prostatectomy with unilateral nerve sparing. Pathology showed a pT2c pN0 Gleason score 3 + 3 = 6 prostate cancer and the postoperative course was uneventful. Ten days after surgery he recognized a spontaneous painful penile erection without sexual stimulation which occurred in a standing position and disappeared in a supine position. These episodes recurred several times during the next 3 weeks and then completely vanished. Pathophysiologically, we postulate intermittent position-depending venous obstruction due to local hematoma or thrombosis.

Aged↗
PubMed2006

Intermittent ureteral herniation--rare cause of flank pain.

Ureteral herniation is rare and difficult to diagnose, especially when intermittent, and ureterocystoneostomy using the psoas hitch or boari flap techniques have so far been used as therapeutic options. We describe ureterolysis in two cases as a successful alternative approach.

Aged↗
PubMed2005

Dendritic cells generated from patients with androgen-independent prostate cancer are not impaired in migration and T-cell stimulation.

BACKGROUND: Dendritic cell (DC)-based vaccination has been investigated as immunotherapy for several types of cancer. A potential drawback to vaccination with autologous monocyte-derived DCs (MoDCs) could be that MoDCs from patients are functionally impaired. In case of androgen-independent prostate cancer (CaP), the cancer itself, diverse prior therapies, and the hormone manipulation may affect the immune system. METHODS: MoDCs from patients suffering from androgen-independent CaP were generated according to a clinically applicable protocol to evaluate the phenotype, maturation capacity, migration, and T-cell stimulation of these cells compared with those generated from tumor-free donors. RESULTS: MoDCs generated from CaP patients could be fully matured and efficiently migrated towards the chemokine CCL21. They had a strong potency to activate allogeneic CD4+ and CD8+ T-cells and to present antigens to specific CTL. CONCLUSIONS: Our data suggest that MoDCs from patients with androgen-independent CaP are functionally intact and hence qualify as cellular vaccines for immunotherapy of advanced stage CaP.

Aged↗
PubMed2005

Biological variation of total prostate-specific antigen: a survey of published estimates and consequences for clinical practice.

BACKGROUND: The objectives of this study were to determine whether a single result for total prostate-specific antigen (tPSA) can be used confidently to guide the need for prostate biopsy and by how much serial tPSA measurements must differ to be significant. tPSA measurements include both analytical and biological components of variation. The European Group on Tumor Markers conducted a literature survey to determine both the magnitude and impact of biological variation on single, the mean of replicate, and serial tPSA measurements. METHODS: The survey yielded 27 studies addressing the topic, and estimates for the biological variation of tPSA could be derived from 12 of these studies. RESULTS: The mean biological variation was 20% in the concentration range 0.1-20 microg/L for men over 50 years. The biological variation means that the one-sided 95% confidence interval (CI) of the dispersion for a single tPSA result is approximately 33%. Three replicate samples with one analysis on each narrow the one-sided 95% CI for the mean concentration to approximately 20% and facilitate decisions on prostate biopsy. During monitoring of serial measurements, the change needed for significance is approximately 50% (P <0.05). CONCLUSIONS: The biological variation of tPSA has implications for screening, diagnosis, and monitoring. Single measurements may not be sufficiently precise for screening and diagnosis. Replicate samples and calculation of the mean concentration may improve precision by reducing the dispersion. Monitoring of tPSA requires an estimate of either the change needed for significance or, alternatively, of the significance of the change.

Circadian Rhythm↗
PubMed2005

Novel use of fine needle aspiration of seminal vesicles for sperm retrieval in infertile men.

Fine needle aspiration of the seminal vesicles under transrectal ultrasound guidance was performed in a man with primary anorgasmy. The procedure included local anesthesia to the apex of the prostate and a 21-gauge needle for aspiration. A total of 3 mL of seminal fluid could be aspirated. Semen analysis showed a sperm count of 40 million/mL and 2% motility. Intracytoplasmic sperm injection was performed, pregnancy resulted, and a healthy girl was born. This is the first successful report of fine needle aspiration of the seminal vesicles in men whose infertility is caused by ejaculatory disorders or distal obstructive azoospermia. This finding could lead to an expansion of our armamentarium in assisted reproductive technology.

Adult↗
PubMed2005

A double-blind, placebo controlled comparison of the morphine sparing effect of oral rofecoxib and diclofenac for acute renal colic.

PURPOSE: We compared the morphine sparing effect of a single dose of 50 mg oral rofecoxib, 3, 8-hourly doses of 50 mg diclofenac and placebo for acute renal colic. MATERIALS AND METHODS: Patients who were 18 to 69 years old with clinically diagnosed acute renal colic and a visual analog scale (VAS) score of 40 mm or greater at hospital admission were randomized to receive 1 of the 3 treatment regimens, delivered in 3 identical encapsulated tablets. The primary end point was the mean total amount of intravenously administered morphine in the 24 hours following study medication dose 1. Secondary end points were mean VAS score and the number of treatment withdrawals due to pain. RESULTS: Of 400 patients admitted with acute flank pain 225 fulfilled the inclusion criteria, of whom 110 (49%) were eligible for evaluation and received rofecoxib (36), diclofenac (39) and placebo (35). Baseline characteristics in the 3 groups did not differ. Intent to treat analysis showed that mean morphine consumption was 13.6 mg in the rofecoxib group (95% CI 10.3 to 16.9), 10.2 mg in the diclofenac group (95% CI 7.7 to 12.7) and 11.5 mg in the placebo group (95% CI 8.8 to 14.3). The differences were not significant (p = 0.23). The same applied to mean VAS scores in the 3 groups (p = 0.22). There were no differences in the number of pain related treatment withdrawals (p = 0.64). CONCLUSIONS: No clinically relevant morphine sparing effect was seen in patients with renal colic treated with 50 mg oral diclofenac every 8 hours or a single dose of 50 mg rofecoxib as a representative of the specific inhibitors of cyclooxygenase-2.

Administration, Oral↗
PubMed2005

HcPro, a multifunctional protein encoded by a plant RNA virus, targets the 20S proteasome and affects its enzymic activities.

The proteasome is a multicatalytic complex involved in many cellular processes in eukaryotes, such as protein and RNA turnover, cell division, signal transduction, transcription and translation. Intracellular pathogens are targets of its enzymic activities, and a number of animal viruses are known to interfere with these activities. The first evidence that a plant virus protein, the helper component-proteinase (HcPro) of Lettuce mosaic virus (LMV; genus Potyvirus), interferes with the 20S proteasome ribonuclease is reported here. LMV infection caused an aggregation of the 20S proteasome to high-molecular mass structures in vivo, and specific binding of HcPro to the proteasome was confirmed in vitro using two different approaches. HcPro inhibited the 20S endonuclease activity in vitro, while its proteolytic activities were unchanged or slightly stimulated. This ability of HcPro, a pathogenicity regulator of potyviruses, to interfere with some of the catalytic functions of the 20S proteasome suggests the existence of a novel type of defence and counter-defence interplay in the course of interaction between potyviruses and their hosts.

Chromatography, Affinity↗
PubMed2004

Update on screening for prostate cancer with prostate-specific antigen.

Serum prostate-specific antigen (PSA) determination in conjunction with digital rectal examination (DRE) is recommended by the majority of clinical guidelines for early detection(opportunistic screening) of prostate cancer provided the patient is well informed and has a life-expectancy of at least 10 years. The major disadvantage of PSA is its lack of specificity. Various static and dynamic concepts have been developed to improve the diagnostic performance of PSA of which free/total PSA ratio and PSA doubling time seem to be the most promising. Apart from early detection, population screening(mass screening) is a distinct topic. The effect of the latter one with regard to reduction of prostate cancer specific mortality and quality of life issues is not yet clear. Several national and international prospective trials are currently being conducted to answer these important questions but results will only be available in a few years.

Biomarkers, Tumor↗
PubMed2003

Problems with prostate-specific antigen screening: a critical review.

The effect of population screening with regard to reduction of prostate cancer specific mortality and quality of life issues is not yet clear. Several national and international prospective studies are currently being conducted to answer these important questions. They include the trials in the Federal State of Tyrol, Austria and in the Quebec City area, Canada, as well as the Prostate, Lung, Colorectal and Ovarian (PLCO) trial in the United States and the European Randomized Study of Screening for Prostate Cancer (ERSPC). In the meantime, individual case finding (opportunistic screening) is recommended for men with a life-expectancy of at least 10 years.

Humans↗
PubMed2003

Bicycle riding has no important impact on total and free prostate-specific antigen serum levels in older men.

OBJECTIVES: To investigate whether bicycle riding significantly alters total prostate-specific antigen (tPSA), free PSA (fPSA), and percent free PSA (%fPSA) serum concentrations in potential candidates for prostate cancer screening. METHODS: Thirty-three men, ranging in age from 50 to 74 years (mean 61 +/- 8), rode a 13-mile bicycle course. Blood samples for PSA analysis were drawn immediately before and 1 hour after cycling for 90 minutes. The precycling and postcycling tPSA, fPSA, and %fPSA values were compared using the Wilcoxon matched-pairs test, with P = 0.01 set as the significance level. RESULTS: Changes between precycling and postcycling values for tPSA (P = 0.517), fPSA (P = 0.048), and %fPSA (P = 0.166) were not statistically significant. CONCLUSIONS: Physical activity combined with perineal pressure as induced by a 13-mile bicycle tour has no diagnostic impact on PSA values.

Aged↗
PubMed2003

Prostate specific antigen doubling time as auxiliary end point in hormone refractory prostatic carcinoma.

OBJECTIVE: In hormone refractory prostatic carcinoma (HRPCa), the majority of patients have bone metastases only, which are by definition non-measurable. This makes objective evaluation of chemotherapeutic agents difficult. Prostate specific antigen (PSA) as a dynamic model was analyzed as potential auxiliary end point in HRPCa. METHODS: In the framework of a master protocol, the Swiss Group for Clinical Cancer Research (SAKK) is evaluating cytotoxic drugs in HRPCa since 1991. These prospective phase II trials include uniform requirements with regard to response, toxicity and quality of life. From the entire pool of patients, 40 with bidimensionally measurable metastases (lymph nodes, visceral organs) could be identified. PSA doubling time was calculated in patients with a rising PSA during therapy. RESULTS: Objective best response to any given chemotherapeutic agent was: partial remission (PR) in six patients (15%), stable disease (SD) in 13 (32%) and progressive disease (PD) in 21 (53%). PSA remained stable or decreased in four of six patients with PR (67%), seven of 13 with SD (54%) but only in four of 21 with PD (19%) (Cochran-Armitage test for trend; p=0.015). The median PSA doubling time for patients with a rising PSA was 238 days in PR and 224 days in SD, compared to 113 days in PD (Wilcoxon test; p=0.002). CONCLUSIONS: PSA doubling time is a potential auxiliary end point in the evaluation of cytotoxic drugs in HRPCa. Thus, also patients with non-measurable (bone) metastases could be included in analysis of response.

Aged↗
PubMed2003

Semi-quantitative immunochromatographic test for prostate specific antigen in whole blood: tossing the coin to predict prostate cancer?

OBJECTIVES: A strip test for the semi-quantitative determination of prostate specific antigen (PSA) based on whole blood was evaluated by the Working Group on Laboratory Diagnostics of the German Urological Association. METHODS: In 301 men (156 volunteers and 145 referred patients, mean ages 57 years and 64 years) handling and capability of the strip test to predict PSA serum concentrations (Access Hybritech, Beckman Coulter, Inc., Fullerton, CA, USA) relative to a cutoff of 4 micro g/l were investigated. For patients, the strip test was performed by investigators, volunteers accomplished it according to leaflet instructions. Each test result was interpreted by both, the patient/volunteer and an investigator. RESULTS: 24% of the volunteers required assistance with test performance. The overall agreement between Access PSA (range 0.1-29.7) and strip test was 76% (read by participants) and 79% (read by investigators). Within the PSA ranges 0.1-3, 3.1-5 and 5.1-10, participants yielded agreement rates of 89%, 40% and 56%, respectively. Studying the 2.1-10 PSA range most relevant for prostate cancer screening, agreement rate (53%), sensitivity (50%) and specificity (67%) were barely superior to random chance. Volunteers alone (PSA range 0.1-11.3 micro g/l) yielded a specificity of 92%, however, all PSA values above the cutoff (n=8) went unrecognized and all positive strip tests (n=12) were incorrect (sensitivity 0%, positive predictive value 0%). CONCLUSIONS: Test handling and interpretation was difficult. The rate of false strip test results is disappointing even for PSA ranges remote from the cutoff. In its present form the strip test fails to meet the clinical requirements and its launch to the market was therefore discontinued.

Diagnostic Errors↗
PubMed2003

Substrate affinity and substrate specificity of proteasomes with RNase activity.

We have partially reconstituted 20S proteasome/RNA complexes using oligonucleotides corresponding to ARE (adenosine- and uridine-rich element) (AUUUA)4 and HIV-TAR (human immunodeficiency virus-Tat transactivation response element), a stem-loop structure in the 5' UTR (untranslated region) of HIV-mRNAs. We demonstrate that these RNAs which associate with proteasomes are degraded by proteasomal endonuclease activity. The formation of these 20S proteasome/RNA substrate complexes is rather specific since 20S proteasomes do not interfere with truncated TAR that is not cleaved by proteasomal endonuclease. In addition, affinity of proteasomes for (AUUUA)4 is much stronger as it is for HIV-TAR. These results provide further arguments for our hypothesis that proteasomes could be involved in the destabilisation of cytokines mRNAs containing AUUUA sequences as well as viral mRNAs.

Animals↗
PubMed2003

Accurate control of the superficial and deep dorsal veins during radical retropubic prostatectomy: the Münster clamp technique.

OBJECTIVE: To better control the superficial and deep dorsal veins during radical retropubic prostatectomy and, thus, to reduce blood loss. PATIENTS AND METHODS: A surgical technique is described which introduces a modified Babcock clamp to fully encompass all tissue above the prostatic capsule. In a prospective protocol, 30 consecutive patients (median age 64.5, range 57-76 years) were randomly assigned to either the standard technique or the Münster clamp method. Blood loss was estimated for the entire phase from teasing away the periprostatic fat until the apex had been mobilized. RESULTS: Median hemorrhage was 950 (range 300-2,100) ml for the standard technique and 800 (range 200-1,750) ml for the clamp procedure (Wilcoxon rank sum test, p = 0.17). CONCLUSIONS: The Münster clamp technique can reduce hemorrhage during radical retropubic prostatectomy. This method is easy to apply and is also suitable for cystoprostatectomy.

Hemostasis, Surgical↗
PubMed2003

A new modification of the Chiron ACS assay for total prostate-specific antigen achieves equimolar response characteristics and improves the detection of prostate cancer.

Nonequimolar-response assays for prostate-specific antigen (PSA) are criticized for overestimating total PSA in some men without prostate cancer (PCA), and underestimating total PSA in some men with PCA. We recently studied three nonequimolar-response PSA assays that had undergone modifications. While two of the studied assays achieved equimolar-response characteristics with improved areas under receiver operating characteristic (ROC) curves (AUC), the modification of the Chiron ACS PSA assay (ACS PSA2, Chiron) failed to achieve this. Recently, the ACS assay underwent another modification (ACS PSA, Bayer), which we investigated. Sera from 305 men (155 without and 150 with PCA, PSA > or = 2 and < or = 30 microg/l, Tandem-E) were measured using both modifications of the ACS assay and equimolar-response reference methods (Tandem-R free and Tandem-E, Hybritech). Molar response relative to the reference method and clinical performance (comparison of AUCs) between the previous and new ACS assay modifications were studied. The new modification of the ACS assay (ACS PSA, Bayer) achieved equimolar-response characteristics but reported lower values (average 10%) than the Tandem-E assay. Compared to the previous modification (ACS PSA2, Chiron), a 3% improvement in AUC (p = 0.01) was found. Using results of the redesigned equimolar-response assay (ACS PSA, Bayer), we calculated that 6 of 155 men without PCA in this sample set could be spared unnecessary biopsy compared with the previous nonequimolar-response assay (ACS PSA2, Chiron) without missing additional PCA (90% sensitivity). These data provide additional evidence for clinical advantages of equimolar-response over nonequimolar-response PSA assay formats.

Case-Control Studies↗
PubMed2002

Combining free and total prostate specific antigen assays from different manufacturers: the pitfalls.

OBJECTIVES: We investigated the impact of interchanging free prostate specific antigen (f-PSA) concentrations from 10 different assays over a reference total PSA (t-PSA) on predicting prostate histology with free-to-total PSA ratios (f/t-PSA). METHODS: Archival sera from 80 t-PSA- and age-matched pairs of histologically confirmed prostate cancer (PCA) and benign prostatic hyperplasia (BPH) patients with t-PSA levels between 2 and 25 microg/l were investigated. Serum aliquots were analyzed for t- and f-PSA using a reference method (Access, Beckmann-Coulter Hybritech) and 10 commercially available f-PSA assays. Passing Bablok and linear regression were performed to investigate the interassay agreement between f-PSA assays. To compare diagnostic performance, ROC curves for PCA detection were calculated for the 10 f/t-PSA combinations using the reference t-PSA as denominator. Sensitivities, specificities and f/t-PSA cut-offs were calculated for varying points of the ROC curve. RESULTS: Despite good correlation of all 10 f-PSA assays with the reference method 4 showed significantly lower mean f-PSA levels. For f/t-PSA as a predictor of prostate histology, areas under the ROC curve (AUC) varied between 0.65 and 0.71 and, if compared to the reference method (AUC=0.70), were significantly lower in three cases. Ensuring 80% specificity, sensitivities ranged between 34% and 54% (reference method: 53%) and f/t-PSA cutpoints differed considerably depending on the f-PSA assay used (range: 0.15-0.24; reference: 0.15). Similar variations were noted at 95% specificity and 80% and 95% sensitivity. CONCLUSIONS: Arbitrary combinations of f- and t-PSA assays should not be used to calculate f/t-PSA ratios unless adequate studies have validated the diagnostic performance and cut-offs of that particular assay choice.

Aged↗