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Arndt van Ophoven

Publications and source records attributed to Arndt van Ophoven.

12 recordsLinked to original sources
PubMed2007

The dual serotonin and noradrenaline reuptake inhibitor duloxetine for the treatment of interstitial cystitis: results of an observational study.

PURPOSE: We report an observational study to evaluate the efficacy and tolerability of duloxetine for interstitial cystitis. MATERIALS AND METHODS: A total of 48 women were prospectively treated for 2 months following an uptitration protocol to the target dose of 2 x 40 mg duloxetine per day. Patients received the target dose for 5 weeks. The efficacy of duloxetine treatment was assessed at week 8. The primary end point was a change in the overall well-being evaluated by a patient reported global response assessment. Secondary end points were changes in pain and urgency (visual analog scales), frequency and functional bladder capacity (48-hour voiding log), and changes in overall symptom severity (O'Leary-Sant index). RESULTS: There were 5 patients (10.4%) who were identified as responders and 17 patients (35.4%) who dropped out of the study exclusively due to side effects, with nausea present in all dropouts. No severe adverse events were reported. All 5 responders reported onset of symptom improvement but not until they had reached the target dose. Regarding secondary outcome parameters, duloxetine treatment did not result in statistically significant improvement of symptoms. Maximum urinary flow rate and residual volume were influenced more prominently in patients at the target dose, however, the changes did not appear to be clinically meaningful. CONCLUSIONS: Treatment of interstitial cystitis with duloxetine did not result in significant improvement of symptoms. The drug administration was safe but the tolerability of the drug was poor mainly due to nausea occurring with the starting dose of 20 mg per day. Based on the preliminary data of this observational trial we currently cannot recommend duloxetine as a therapeutic approach for interstitial cystitis.

Adrenergic Uptake Inhibitors↗
PubMed2006

Safety and efficacy of hyperbaric oxygen therapy for the treatment of interstitial cystitis: a randomized, sham controlled, double-blind trial.

PURPOSE: We conducted a double-blind, sham controlled study to evaluate the safety, efficacy and feasibility of hyperbaric oxygenation for interstitial cystitis. MATERIALS AND METHODS: A total of 21 patients with interstitial cystitis were randomized to 90 minutes treatment in a hyperbaric chamber pressurized with 100% O2 to 2.4 atmosphere absolute for 30 treatments sessions or 1.3 atmosphere absolute, breathing normal air in the control group. Moderate or marked improvement in a global response assessment questionnaire was defined as treatment response (primary outcomes). Secondary measurements included changes of pain and urgency evaluated by visual analog scales, functional bladder capacity and frequency. Changes in the O'Leary-Sant Interstitial Cystitis Index and rating of overall satisfaction with the therapeutic outcome were also reported. RESULTS: There were 3 of 14 patients on verum and no control patients who were identified as responders (p < 0.52) [corrected] At 12-month followup 3 patients (21.4%) still reported treatment response. Hyperbaric oxygenation resulted in a decrease of baseline urgency intensity from 60.2 +/- 15.0 to 49.9 +/- 35.2 mm at 3 months and decrease of pain intensity from 43.1 +/- 20.5 to 31.2 +/- 19.8 mm, respectively (p < 0.05). The Interstitial Cystitis Symptom Index score sum decreased from 25.7 to 19.9 points in patients on verum. Sham treatment did not result in improvement of the baseline parameters. CONCLUSIONS: A total of 30 treatment sessions of hyperbaric oxygenation appear to be a safe, effective and feasible therapeutic approach to interstitial cystitis. In the treatment responders application of hyperbaric oxygenation resulted in a sustained decrease of interstitial cystitis symptoms with a discordant profile regarding the peak amelioration of the various interstitial cystitis symptoms compared with a normobaric, normoxic sham treatment.

Adult↗
PubMed2005

The proteasome inhibitor MG-132 sensitizes PC-3 prostate cancer cells to ionizing radiation by a DNA-PK-independent mechanism.

BACKGROUND: By modulating the expression levels of specific signal transduction molecules, the 26S proteasome plays a central role in determining cell cycle progression or arrest and cell survival or death in response to stress stimuli, including ionizing radiation. Inhibition of proteasome function by specific drugs results in cell cycle arrest, apoptosis and radiosensitization of many cancer cell lines. This study investigates whether there is also a concomitant increase in cellular radiosensitivity if proteasome inhibition occurs only transiently before radiation. Further, since proteasome inhibition has been shown to activate caspase-3, which is involved in apoptosis, and caspase-3 can cleave DNA-PKcs, which is involved in DNA-double strand repair, the hypothesis was tested that caspase-3 activation was essential for both apoptosis and radiosensitization following proteasome inhibition. METHODS: Prostate carcinoma PC-3 cells were treated with the reversible proteasome inhibitor MG-132. Cell cycle distribution, apoptosis, caspase-3 activity, DNA-PKcs protein levels and DNA-PK activity were monitored. Radiosensitivity was assessed using a clonogenic assay. RESULTS: Inhibition of proteasome function caused cell cycle arrest and apoptosis but this did not involve early activation of caspase-3. Short-time inhibition of proteasome function also caused radiosensitization but this did not involve a decrease in DNA-PKcs protein levels or DNA-PK activity. CONCLUSION: We conclude that caspase-dependent cleavage of DNA-PKcs during apoptosis does not contribute to the radiosensitizing effects of MG-132.

Antineoplastic Agents↗
PubMed2005

Hyperthermia-induced proteasome inhibition and loss of androgen receptor expression in human prostate cancer cells.

Prostate cancer is the second leading cause of death in men in western countries and is usually treated by surgery and/or radiotherapy. More recently, hyperthermia has been introduced into clinical trials investigating a possible effect in the first-line treatment of prostate cancer. However, the molecular mechanisms of hyperthermia are not completely understood. In this study, we investigated the effects of hyperthermia on proteasome function and its significance for signal transduction, cell death and androgen receptor (AR) expression in PC-3, LnCaP, and DU-145 human and TRAMP-C2 murine prostate cancer cells. Hyperthermia caused apoptosis and radiosensitization and decreased 26S proteasome activity in all three human cell lines to about 40% of untreated control cells. 20S proteasome activity was not affected by heat. Heat treatment inhibited constitutive and radiation-induced activation of nuclear factor kappaB caused by stabilization of IkappaB. Although stabilization of AR by proteasome inhibitors has been reported previously, AR protein levels in LnCaP cells decreased dramatically after heat. Our data suggest that inhibition of proteasome function and dependent signal transduction pathways might be a major molecular mechanisms of heat-induced apoptosis and radiosensitization. Hyperthermia abrogates AR expression in androgen-dependent cells and might thus promote malignant progression of prostate cancer.

Animals↗
PubMed2005

Safety and efficacy of concurrent application of oral pentosan polysulfate and subcutaneous low-dose heparin for patients with interstitial cystitis.

OBJECTIVES: To conduct a prospective controlled study assessing the safety and efficacy of the additional administration of subcutaneous low-dose heparin in patients receiving oral pentosan polysulfate (PPS) medication for interstitial cystitis. METHODS: A total of 41 patients with interstitial cystitis who reported efficacy of oral PPS medication were divided into three groups (major, intermediate, and minor PPS response), according to their therapeutic response to PPS. Patients received 3 x 5000 IU/day heparin for 2 days, followed by 2 x 5000 IU/day for 12 days. The maintenance dose was 5000 IU/day heparin. We used 17 patients randomly taking PPS alone as the control group. The primary endpoint was a change in overall well-being. Secondary endpoints were changes in pain, urgency, frequency, functional bladder capacity, and the O'Leary-Sant index. RESULTS: Overall, 10 patients were identified as responders at 3 months (24.4%) and 9 patients at 6 months (21.9%) compared with no responders in the control group (P < or = 0.001). At 3 months, 7 (31.8%) of 22 patients in the minor response group reported a statistically significant overall improvement in their well-being compared with 1 (12.5%, P < or = 0.001) of 8 patients of the intermediate group and 2 (18.2%, P < or = 0.001) of 11 patients of the major response group. A significant amelioration of pain intensity was observed in the minor response group at 3 and 6 months. CONCLUSIONS: The concurrent administration of low-dose heparin and oral PPS appears to be a safe and efficacious treatment modality. The subcutaneous administration of heparin appeared to be predominantly of value for patients with interstitial cystitis and an initial minor response to PPS.

Administration, Oral↗
PubMed2005

Long-term results of amitriptyline treatment for interstitial cystitis.

PURPOSE: We performed a prospective, open label study to examine the safety and efficacy of the long-term administration of the tricyclic antidepressant amitriptyline in patients with interstitial cystitis (IC). MATERIALS AND METHODS: A total of 94 patients were stratified into 2 groups, namely a National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) group of those who fulfilled NIDDK criteria for IC and a nonNIDDK group of those who presented with characteristic IC symptoms but met at least 1 NIDDK exclusion criterion. Amitriptyline was received strictly at bedtime following an established self-titration protocol without a limitation of the maximum daily dose. Patients reporting improvement in a global response assessment questionnaire were considered treatment responders. Further efficacy measures were changes in pain and urgency, functional bladder capacity and frequency. Changes in the O'Leary-Sant IC index and rating of overall satisfaction with the therapeutic outcome were also reported. RESULTS: Mean study followup +/- SD was 19.0 +/- 12.5 months. The response rate was 64% (60 patients). The overall mean dose was 55 mg (range 12.5 to 150). Side effects occurred in 79 patients (84%), including dry mouth in 79% and weight gain in 59%. Patient overall satisfaction with the therapeutic result was excellent or good in 43 (46%). The dropout rate was 31% (29 patients) after a mean treatment period of 6 weeks at a mean dose of 70 mg. Nonresponse to treatment was the primary reason for dropout in all cases, while side effects contributed to dropout in 25 (86%). Improvement in the various IC symptoms was statistically significant compared with baseline. CONCLUSIONS: Long-term administration of amitriptyline is a feasible, safe and effective treatment for IC, provided that the drug is used judiciously to minimize adverse effects. The therapeutic response to amitriptyline was uniformly observed in patients fulfilling NIDDK criteria and in those with the pure clinical diagnosis of IC.

Administration, Oral↗
PubMed2004

Hyperbaric oxygen for the treatment of interstitial cystitis: long-term results of a prospective pilot study.

OBJECTIVE: We conducted a prospective pilot study to assess the safety and efficacy of hyperbaric oxygen (HBO) for the treatment of interstitial cystitis (IC). METHODS: Six patients underwent 30 sessions of 100% oxygen inhalation in a hyperbaric chamber and were followed up over 15 months. The measures of efficacy were changes in pain and urgency (visual analog scales), alteration in the patient's assessment of overall change in his well-being (Patient Global Assessment Form), and changes in frequency and functional bladder capacity (48-hours voiding log). Evaluation of symptom severity regarding pain and voiding problems was done using the O'Leary-Sant index. RESULTS: Four patients rated the therapeutic result as either excellent or good and assessed their well-being after HBO treatment as improved. Two patients showed only short-term amelioration of some of their symptoms. At 12 months follow-up the baseline functional bladder capacity increased from 37-161 ml (range) to 160-200 ml in the responder group. The 24-hour voiding frequency decreased from 15-27 to 6-11 voids per day, a pain scale improvement from 20-97 mm at baseline to 3-30 mm at 12 months follow-up and an urgency scale improvement from 53-92 mm to 3-40 mm, respectively was observed at 12 month follow-up. The symptom and pain index score decreased from 23-35 at baseline to 3-17 at 12 months follow-up. CONCLUSION: HBO appears to be effective to treat IC patients. Treatment was well tolerated and resulted in a sustained decrease of pelvic pain and urgency, improvement of voiding patterns and increase of functional bladder capacity for at least 12 months.

Adult↗
PubMed2004

A prospective, randomized, placebo controlled, double-blind study of amitriptyline for the treatment of interstitial cystitis.

PURPOSE: We conducted a prospective study to examine the safety and efficacy of the tricyclic antidepressant amitriptyline in patients with interstitial cystitis (IC). MATERIALS AND METHODS: The study comprised 44 women and 6 men who all met the symptom criteria of the National Institute of Diabetes, Digestive and Kidney Diseases for IC. The patients were randomly assigned to amitriptyline or placebo. Patients were prospectively treated for 4 months with a self-titration protocol that allowed them to escalate drug dosage in 25 mg increments in 1 week-intervals (maximum dosage 100 mg). The change from baseline in the O'Leary-Sant IC symptom and problem index was the primary outcome parameter. Changes in functional bladder capacity and frequency (48-hour voiding log), and intensity of pain and urgency (visual analog scales) were chosen as secondary outcome parameters. RESULTS: Two patients (1 on amitriptyline, 1 on placebo) dropped out of the study due to side effects. Thus, the data of 48 patients (24 patients in each group) were available for evaluation. Mean symptom score decreased from 26.9 to 18.5 in the amitriptyline group compared with 27.6 to 24.1 in the placebo group (p = 0.005). Pain and urgency intensity improved statistically significantly in the amitriptyline group compared with the placebo group (p <0.001). The frequency and functional bladder capacity improved to a much greater degree in the amitriptyline group but the differences were not statistically significant (p = 0.063, p = 0.083). Anticholinergic side effects were reported by all except 2 patients in the amitriptyline group (92%) and by 5 patients in the placebo group (21%). Mouth dryness was the most frequent side effect reported in the amitriptyline group (79%). CONCLUSIONS: Amitriptyline therapy for 4 months is safe and effective for treating IC. A statistically significant change in the symptom score and statistically significant improvement of pain and urgency intensity compared with placebo were observed. Anticholinergic side effects constitute the major drawback of amitriptyline treatment for IC.

Adult↗
PubMed2002

Long-term results of trigone-preserving orthotopic substitution enterocystoplasty for interstitial cystitis.

PURPOSE: Interstitial cystitis is a chronic debilitating condition mainly affecting women. Conservative treatment often produces unsatisfactory results and the identification of the best surgical treatment modality is difficult. We evaluate retrospectively the long-term results of trigone-preserving cystectomy followed by orthotopic substitution enteroplasty for women suffering from interstitial cystitis. MATERIALS AND METHODS: The study comprised 18 women with a mean age of 55.9 years. All surgical interventions were performed by 1 surgeon. All patients completed a voiding log and were interviewed about symptoms. Renal ultrasonography was done to evaluate the upper urinary tract. Followup data also comprised blood chemistry studies, including vitamin B12 blood levels and blood gas analysis. Pain and lower urinary tract problems were measured using a validated self-assessment symptom index. RESULTS: Ileocoecal augmentation was performed in 10 women and ileal substitute was done in 8. After a mean followup of 57 months 14 patients are completely pain-free, 12 void spontaneously and 15 report complete resolution of dysuria. Three patients perform intermittent self-catheterization and 1 woman prefers a suprapubic catheter for control of urinary hypercontinence. These 4 patients underwent ileoplasty. Surgery failed to relieve symptoms in 2 of the 18 patients. Surgery achieved a statistically highly significant improvement of diurnal and nocturnal voiding frequencies, functional bladder capacity and symptom index score. CONCLUSIONS: Substitution enterocystoplasty is a valuable and safe therapeutic option for patients with intractable interstitial cystitis resistant to conservative therapy. In our series use of the ileocecal bowel segment showed better functional results.

Adult↗
PubMed2002

Interstitial cystitis: an update.

PURPOSE OF REVIEW: Interstitial cystitis is a chronically progressive, severely debilitating, heterogeneous syndrome affecting the urinary bladder, mainly associated with urgency, frequency and pain. Though known for over a century, its etiology is poorly understood and universally effective treatments are lacking. This review focuses on recently published literature on the disorder. RECENT FINDINGS: Appropriate diagnostic tests for interstitial cystitis remain uncertain. The diagnostic criteria developed by the US National Institutes of Health represent research definitions which are subject to controversial debate for their overenthusiastic clinical application. The diagnosis is made clinically and by cystoscopy with hydrodistention and sometimes biopsy when other pathologies have been excluded. In symptomatic patients, glomerulations upon bladder distension are indicative but not pathognomonic for nonulcerative interstitial cystitis. Patients with ulcerative disease represent a separate subgroup with distinct characteristics and treatment implications. The role of bladder permeability tests remains controversial. Promising noninvasive markers for interstitial cystitis have been described but are not yet clinically available. Validated symptom scores are appropriate to assist in diagnostics and to monitor disease course and treatment efficacy. Lately investigated hypotheses for causative factors include occult or resistant microorganisms, urothelial hyperpermeability, neurogenic or hormonal pathomechanisms, and mast cell activation. Increasing evidence for a genetic susceptibility is emerging. SUMMARY: Among the multitude of oral, intravesical, interventional and complementary treatments suggested few studies have high levels of evidence. Newly proposed agents must await further controlled studies. Treatment remains empiric until radical surgical procedures should ultimately be considered for severe refractory cases.

Animals↗
PubMedDate not supplied

Phase I trial of antigen-specific gene therapy using a recombinant vaccinia virus encoding MUC-1 and IL-2 in MUC-1-positive patients with advanced prostate cancer.

MUC-1 is overexpressed on many tumor cells. In addition, aberrant glycosylation of MUC-1 on human tumors leads to exposure of cryptic peptide epitopes that play a role in tumor immunity. As such, it has been identified as a potential target for immunotherapy. The purpose of this phase 1 clinical trial was to determine the maximum tolerated dose, safety of a multiple-dose regimen, and the immunologic effect of vaccinia virus expressing MUC-1 and IL-2 genes (VV/MUC-1/IL-2) in patients with advanced prostate cancer. Five x 10(5), 5 x 10(6), and 5 x 10(7) plaque-forming units (pfu) of vaccinia viruses were used in the dose-escalating study. Viruses were given via intramuscular injection, and clinical response and immune function modulation were analyzed. No grade 3 or 4 toxicity was observed. Objective clinical response was observed after the fourth injection (0.3 ng/mL) in only one patient who received an intermediate dose of virus. Systemic immune modulation in this patient included (1) up-regulation of IL-2 (CD25) and T cell (TcR alphabeta) receptors, (2) increase in the CD4/CD8 ratio (2.5-fold) (3) augmentation of T-helper type 1 cell (TH1) (interferon-gamma and tumor necrosis factor-alpha) but not TH2 (IL-4) cytokine mRNA expression, (4) induction of natural killer cell activity and MHC independent MUC-1 specific cytotoxic T-cell activity, and (5) normalization of mRNA expression of T-cell-associated signal transduction molecules TcR-zeta and p56lck. These results suggest that VV/MUC-1/IL-2 gene therapy with a maximum tolerated dose of 5 x 10(7) pfu is safe and well tolerated.

Aged↗