Biomedical subjects

F M Debruyne

Publications and source records attributed to F M Debruyne.

At least 55 records · Page 3Linked to original sources

PubMed1999

[Chemotherapy of testicular cancer].

The incidence of testicular tumours is low. It is the most frequent tumour among men between the age of 15 and 44. A risk factor for a testicular tumour is abnormal development of a testicle, for example cryptorchidism. In case of doubt about the diagnosis a scrotal sonography is nearly 100% accurate. The treatment and final prognosis are determined by the histological type and presence or absence of retroperitoneal and/or lung metastasis. Two-thirds of the patients have a chance of cure of over 90%. Standard treatment for a patient with a metastasized non-seminoma and the more extensive forms of metastasized seminoma is chemotherapy with 4 courses of bleomycin, etoposide and cisplatin. Long-term side effects are limited to polyneuropathy in hands and feet in some of the patients. Reduction in fertility appears to be temporarily, the risk for offspring seems nil. In good prognosis patients toxicity can be decreased by reduction of the number of chemotherapy cycles or of the dose of bleomycin. In the poor prognosis subset new drugs may improve the prognosis but to date clear results are lacking. Second-line chemotherapy is only possible with attention for the cumulative bone marrow toxicity; autologous bone marrow rescue or growth factors can diminish this.

Adolescent↗

PubMed1999

Molecular analysis of multifocal prostate cancer lesions.

To analyse the origin of multifocal prostate cancer lesions, radical prostatectomy specimens from 17 patients were examined. As a marker of genetic lineage, the allelotype based on 33 microsatellite loci was compared between the different tumours present in a given case. Some results provide evidence suggestive of a clonal origin of multiple tumours in a subset of the prostates. In five cases, for example, comparison of multifocal tumour lesions within a given case revealed at least two concordant changes in allelic imbalance (AI) sequence dosages at different loci. In addition, considerable heterogeneity of allelotype was found within and among tumour foci of a given case. In five of the six tumours analysed for intratumour heterogeneity, for example, more than five discordant AI changes were found in one tumour region but not in the other. Conclusions regarding the clonality of such heterogeneous lesions are difficult to draw. A high frequency of AI changes in four lesions exhibiting prostatic intraepithelial neoplasia (mean 6.5 changes per lesion, range 3-6) was found, compared with eight primary tumours present in the same cases (mean 5.8 changes per lesion, range 3-6). The interpretation of AI associated with clinically detected prostate cancer remains a highly complex issue. The fact that no clear evidence was obtained for either a clonal or a non-clonal origin of multiple lesions in a given prostate indicates that several different mechanisms are likely to operate in establishing the allelotype and that additional evidence from unique mutations or selective gene inactivation may be necessary to obtain definitive results.

Humans↗

PubMed1999

Low reproducibility of maximum urinary flow rate determined by portable flowmetry.

To evaluate the reproducibility in maximum urinary flow rate (Qmax) in men with lower urinary tract symptoms (LUTSs) and to determine the number of flows needed to obtain a specified reliability in mean Qmax, 212 patients with LUTSs (mean age, 62 years) referred to the University Hospital Nijmegen, with various degrees of obstruction on pressure-flow studies, used a portable home-based uroflowmeter with 12 disposable beakers. Voided volume and maximum flow rate were recorded continuously during micturition. Flows with voided volumes of at least 100 ml and without possible artifacts were included. All analyses were repeated while excluding flows with voided volumes <150 ml. A coefficient of variation (CV) was calculated for each patient. The CV represents the standard deviation relative to the mean. All individual CVs were subsequently pooled into a population mean CV. This parameter was used to estimate the number of flows required to obtain a mean Qmax with specified reliability for an individual patient. All analyses were repeated, while successively excluding the first, the first two, and the first three flows, to assess a possible learning curve. A total of 1,854 flows was available for analyses, yielding an average of nine flows per patient. Mean Qmax was 13.2 ml/sec; the mean CV was 24%. To allow, for instance, a 10% deviation from the true mean Qmax (e.g., 15 ml/s +/- 1.5 ml/s), approximately 25 flows are necessary. The actual number of flows needed is in fact even higher due to the presence of small and artifactual flows. Using a 150 ml volume cutoff point, somewhat fewer flows are required, but the total number of flows needed (that is, valid, small, and artifactual flows) increases. There was no evidence of a learning curve. The boundaries of a confidence interval around a single Qmax measurement that is likely to contain the true mean Qmax, lie approximately 50% below or above that single Qmax measurement. To reduce this proportion down to 10%, approximately 25 flows are needed. Thus, to obtain reliable mean Qmax values, considerably more flows are required than are normally performed in urologic practice.

Analysis of Variance↗

PubMed1999

Transient tenascin enhancement is an early event after androgen ablation in rat prostate.

Tenascin (tenascin-C), a mesenchymal glycoprotein, is expressed in many tissue remodeling processes. We evaluated tenascin expression during androgen-deprivation-related involution of the rat prostate. At set intervals following castration and subsequent testosterone repletion, prostates were removed in 30 adult rats. Each prostate was immunostained with a polyclonal antiserum against rat tenascin and keratin antibodies specifically directed against exocrine basal cells and luminal cells in the prostate glandular structure. Morphologic impressions were semiquantatively evaluated using a computer-assisted image analysis system. Rat prostates showed a transient increase in the periglandular tenascin expression directly following castration that reached a maximum at day 3. At day 6, tenascin expression was similar to control prostates. This was accompanied by a decrease of cells in the luminal cell layer. The weakest tenascin immunoreactivity was noted on day 14 after androgen withdrawal. This process was reversed by androgen repletion. This study shows that in the rat prostate tenascin expression may be androgen dependent and that during androgen deprivation-related involution tenascin expression is probably associated with tissue remodeling by stromal-epithelial interactions.

Androgens↗

PubMed1999

Lower-energy thermotherapy in the treatment of benign prostatic hyperplasia: long-term follow-up results of a multicenter international study.

The purpose of the present study was to evaluate the long-term results of lower-energy transurethral microwave thermotherapy (TUMT) and to determine predictors for a favorable treatment outcome in an international multicenter study. A total of 1092 patients treated between April 1990 and September 1993 in 6 different centers in different countries were evaluated. All patients were treated in a nonblinded, noncontrolled fashion with the Prostatron thermotherapy device using the lower-energy treatment protocol Prostasoft 2.0. Collected data included voiding parameters, Madsen symptom scores, retreatments, types of retreatment, and dates of retreatment. Instrumental retreatment served as the end point for further evaluation. The average age of our patients was 67 years. At baseline the average uroflow rate was 8.7 ml/s. After treatment the improvement in uroflow was 2-3 ml/s. This was maintained for up to 5 years after treatment for the patients remaining in follow-up. The overall improvement in the Madsen symptom score was 5-6 points for these patients. There was no significant difference between the different centers. During follow-up, however, the number of patients remaining in follow-up decreased rapidly. The absolute instrumental retreatment rate appeared to be 26%; however, when patients no longer in follow-up were taken into account, the calculated retreatment rate was 39.6% (Kaplan-Meier survival analysis). Patients undergoing retreatment were younger at baseline and had a higher Madsen score, a bigger prostate, and a greater postvoid residual. No major complication was seen. Lower-energy TUMT gives a sustained objective and subjective improvement in patients with moderate symptoms and a low-grade bladder outflow obstruction. Patients with bigger prostates, severe symptoms, low rates of maximal uroflow, and large residuals are prone to have a higher degree of prostatic obstruction and are not the ideal candidates for this treatment. The absolute instrumental retreatment rate after 5 years was 26%. Moreover, no significant international difference in treatment outcome was found.

Adult↗

PubMed1999

Sexual function following high energy microwave thermotherapy: results of a randomized controlled study comparing transurethral microwave thermotherapy to transurethral prostatic resection.

PURPOSE: We evaluate changes in sexual function in patients treated with high energy transurethral microwave thermotherapy compared to transurethral resection of the prostate. MATERIALS AND METHODS: A total of 147 patients randomized to undergo transurethral microwave thermotherapy or transurethral resection of the prostate were asked to complete a self-administered questionnaire evaluating sexual function before, and 3 and 12 months after treatment. The questionnaire dealt with such items as social status, libido, quality of erection, ejaculation and overall satisfaction of sexual functioning. RESULTS: There was a statistically significant improvement of micturition in both groups. The improvement in the transurethral prostatic resection group was significantly better than in the transurethral microwave thermotherapy group. Antegrade ejaculation occurred at 3 months following treatment in 27% of the transurethral prostatic resection group compared to 74% of the transurethral microwave thermotherapy group and at 1 year in 37 and 67%, respectively. Significantly more patients undergoing transurethral prostatic resection (36%) had changes in sexual function compared to the transurethral microwave thermotherapy group (17%). The transurethral microwave thermotherapy group was more satisfied with the sex life. Of these patients 55% graded sex as very satisfying compared to 21% in the transurethral prostatic resection group. The severity of symptoms was not correlated with sexual function in this study. In general, older patients had sexual dysfunction more often, while younger patients had pain during sexual activities more frequently. CONCLUSIONS: Although clinically less effective, high energy transurethral microwave thermotherapy is a better therapeutic option than surgery for patients who want to preserve sexual function. In particular ejaculation is often preserved after transurethral microwave thermotherapy while there is significant deterioration following transurethral prostatic resection. In general, older patients have greater sexual dysfunction.

Aged↗

PubMed1999

How to select patients for high-energy transurethral microwave thermotherapy.

OBJECTIVES: To assist urologists in selecting patients for high-energy transurethral microwave thermotherapy (TUMT) on the basis of baseline characteristics. METHODS: Two hundred forty-seven patients with lower urinary tract symptoms and benign prostatic hyperplasia were treated with high-energy TUMT using the Prostatron device, software version 2.5. To evaluate outcome at 26 weeks, the World Health Organization response evaluation criteria were used. Multiple logistic regression models were created to identify the predictive value of baseline parameters and total amount of energy used. In addition, receiver operating characteristic curve and the best cutoff point for the prediction of a good response of each criterion under the condition of equal "costs" of misclassification to cases and noncases were calculated. RESULTS: For each of the three response evaluation criteria, graphs are presented to determine whether high-energy TUMT using the Prostatron can be justified. Only the total amount of energy delivered by the device has a major impact in all three criteria used. CONCLUSIONS: Graphs have been constructed from our analysis to assist urologists in making clinical recommendations for treatment on the basis of the expected outcome when using high-energy TUMT.

Aged↗

PubMed1999

Results of high-energy transurethral microwave thermotherapy in patients categorized according to the American Society of Anesthesiologists operative risk classification.

OBJECTIVES: To evaluate the relation between the American Society of Anesthesiologists (ASA) classification and response to transurethral microwave thermotherapy (TUMT) in patients with lower urinary tract symptoms and benign prostatic hyperplasia (BPH). METHODS: Two hundred forty-seven patients with symptomatic BPH treated with high-energy TUMT were scored retrospectively for ASA status. Student's t test was used to determine differences in improvement at each point of follow-up between patients classified as ASA 1 or 2 and patients classified as ASA 3 or 4. Logistic regression analysis was performed to assess the predictive value of ASA status for response using the World Health Organization response evaluation criteria for International Prostate Symptom Score, maximal flow rate, and urodynamic obstruction. RESULTS: There was a significant improvement in objective and subjective parameters at 12, 26, and 52 weeks of follow-up in both ASA 1 and 2 patients and ASA 3 and 4 patients. There was no difference in objective and subjective improvement between both groups at each point of follow-up. Objective and subjective improvement in ASA 3 and 4 patients with cardiovascular disease and ASA 3 and 4 patients with noncardiovascular disease was the same, although patients with cardiovascular disease received less energy during TUMT. Using logistic regression analysis, ASA classification was not predictive of response after high-energy TUMT. CONCLUSIONS: There is no relation between ASA classification and outcome after high-energy TUMT. Because these patients are considered at high risk of perioperative complications and postoperative morbidity, TUMT could contribute considerably to the treatment of BPH in this specific group of patients.

Aged↗

PubMed1999

Contrast-enhanced three-dimensional power Doppler angiography of the human prostate: correlation with biopsy outcome.

OBJECTIVES: To determine the feasibility of contrast-enhanced three-dimensional (3D) imaging of the prostatic vasculature using power Doppler imaging and to analyze whether semiquantitative judgments of 3D images with respect to symmetry and distribution of vascular structures correlated with biopsy outcome. METHODS: 3D power Doppler images were obtained before and after intravenous administration of 2.5 g Levovist. Subsequently, random and/or directed transrectal ultrasound (TRUS)-guided biopsies were performed. Vascular images were analyzed by two experts. Prostate vasculature was judged with respect to symmetry and vessel distribution using a (scale) grading system. RESULTS: Eighteen patients with a suspicion of prostate cancer either because of an elevated prostate-specific antigen (greater than 4.0 ng/mL; Tandem-R-assay) or an abnormal digital rectal examination were included in the study. Prostate cancer was detected in 13 patients. Vascular anatomy was judged abnormal in unenhanced images in 6 cases, of which 5 proved malignant. Enhanced images were considered suspicious for malignancy in 12 cases, including 1 benign and 11 malignant biopsy results. Sensitivity of enhanced images was 85% (specificity 80%) compared with 38% for unenhanced images (specificity 80%) and 77% for conventional gray-scale TRUS (specificity 60%). Of 6 patients who showed no B-mode abnormalities, vascular patterns were judged abnormal in 4 cases, of which 3 were malignant. CONCLUSIONS: Contrast-enhanced 3D power Doppler angiography is feasible in patients with suspicion of prostate cancer who are scheduled for prostate biopsies. The sensitivity of power Doppler 3D imaging for the detection of prostate malignancy increased from 38% (5 of 13) to 85% (11 of 13) after administration of intravascular microbubble contrast (Levovist), and specificity was found to be 80% (4 of 5) for both imaging modalities. Thus, the use of Levovist when combined with the power Doppler display mode and 3D image reconstruction offers a promising new research area that might prove useful in prostate cancer detection in the future.

Angiography↗

PubMed1999

Transrectal high-intensity focused ultrasound using the Ablatherm device in the treatment of localized prostate carcinoma.

OBJECTIVES: High-intensity focused ultrasound (HIFU) consists of focused ultrasound waves emitted from a transducer that are capable of inducing tissue damage. The histologic effects and clinical outcome of the HIFU treatment were studied in two different groups of men with prostate carcinoma. METHODS: The HIFU treatment was performed under regional or general anesthesia with the Ablatherm device. In one group, HIFU was performed 7 to 12 days before radical prostatectomy, and meticulous histopathologic examination of the radical prostatectomy specimens was performed. The second group consisted of patients with localized prostate carcinoma for whom radical prostatectomy was not an option and who received HIFU treatment alone. RESULTS: In 14 patients treated with HIFU before radical prostatectomy, complete necrosis was seen in the treated region in all cases. On the dorsal border, however, incomplete destruction of tissue was noted, and in 4 cases a small vital tumor focus was seen. In the second group, of those patients in whom the entire prostate was treated, a negative biopsy result and a prostate-specific antigen (PSA) level less than 4 ng/mL was obtained in 60% and a PSA nadir less than 0.5 ng/mL in 55% of patients. CONCLUSIONS: HIFU treatment results in the two groups clearly demonstrate the potential of this modality in the treatment of localized prostate carcinoma. This study showed that extensive coagulative necrosis can be obtained in the treated areas; however, exact targeting is crucial and a prerequisite for extended clinical application of HIFU.

Aged↗

PubMed1999

The tolerability of urodynamic studies and flexible cysto-urethroscopy used in the assessment of men with lower urinary tract symptoms.

OBJECTIVE: To determine the overall tolerability of urodynamic studies used in the assessment of men with lower urinary tract symptoms (LUTS), by assessing the objective and subjective morbidity experienced during and after urodynamic studies, and to assess the voiding complaints caused by the combination of urodynamic studies with flexible cysto-urethroscopy. PATIENTS AND METHODS: A total of 103 men with LUTS, who underwent a urodynamic study combined with flexible cysto-urethroscopy, completed a questionnaire designed to assess objective and subjective symptoms and degree of bother, with emphasis on the urodynamic study. In addition, a urine specimen was analysed and cultured. In all, 78 patients who underwent a second urodynamic study completed the questionnaire twice. RESULTS: The results of the first questionnaire showed that more than half of the patients experienced some urge after the urodynamic study and cysto-urethroscopy (56%); 35% of the patients experienced little and 19% experienced severe voiding discomfort after the combined investigations, compared with 24% and 5%, respectively, after a urodynamic study alone. Three patients (3%) had a symptomatic urinary tract infection. Haematuria, increased voiding frequency and increased nocturia occurred occasionally. Most of the patients found the urodynamic study less bothersome than they had expected (64%) and only 9% found it worse than expected. The overall degree of discomfort, experienced during and after the urodynamic study combined with cysto-urethroscopy, was low, and after a second urodynamic study was even lower. CONCLUSION: In contrast with earlier results, this clinic-based urodynamic investigation was associated with a low proportion of urinary tract infection, and low objective and subjective morbidity. The combination of a urodynamic study with a flexible cysto-urethroscopy does not cause significant additional voiding complaints. Most patients find urodynamic studies tolerable and not very bothersome.

Antibiotic Prophylaxis↗

PubMed1999

A computer model for describing the effect of urethral afferents on simulated lower urinary tract function.

A computer model of mechanical properties of the bladder, the urethra and the rhabdosphincter, as well as their neural control is presented in this paper. The model has a rather simple design and processes sensory information from both the bladder wall tension and urethral stretch. It is assumed that afferent signals from the urethra are involved in a sacral excitatory reflex and a supraspinal inhibitory reflex. Pressure and flow signals that resemble experimentally measured normal human behaviour could be simulated with this model. From these simulations the relation between the neural control mechanisms used in the model and the neural control mechanism in vivo cannot be judged entirely because similar behaviour could be simulated with models that are bas ed on different neural control mechanisms. Also behaviour that resembles detrusor overactivity was simulated with our model after an externally induced rise in detrusor pressure was added. Detrusor overactivity, sometimes in combination with urethral relaxation, can occur during a urodynamic investigation. A possible explanation for this detrusor overactivity might be that the micturition reflex is triggered by unknown disturbances and is inhibited immediately after by the same mechanism that normally ceases voiding. The described model provides such a mechanism. Based on these simulations, therefore, it is concluded that urethral afferent signals might be important in lower urinary tract control.

Afferent Pathways↗

PubMed1999

Contrast angiosonography: a technology to improve Doppler ultrasound examinations of the prostate.

OBJECTIVES: A feasibility study to evaluate whether analysis techniques adapted from X-ray angiography can be used to analyze the transient enhancement of prostate blood flow patterns in color Doppler maps as obtained after administering ultrasound contrast agents. METHODS: Injections of ultrasound contrast agents were given to dogs and humans, and color Doppler blood flow patterns in fixed transverse sections through the prostate were recorded on video tape. Computer assistance of Doppler signals over time is used to evaluate the transient enhancement of flow patterns obtained with contrast-enhanced Doppler ultrasound. Results are compared to indicator dilution curve theory as used in, e.g., X-ray angiography. RESULTS: Administering a contrast agent to improve color Doppler evaluation of prostate blood flow resulted in clear enhancement of Doppler signal intensities without unwanted side effects. Using the computer, the perfused area of the prostate could be obtained quantitatively over time showing profiles of individual heartbeats. Averaging the perfused area over one heartbeat resulted in an indicator dilution curve, and correlation with dilution theory indicated the feasibility of applying wash-in and wash-out analysis of contrast agents in color Doppler images. CONCLUSION: Frame-by-frame interpretation by the computer indicated the feasibility of analyzing the transient enhancement of blood flow visibility in the Doppler image over time using techniques such as wash-in and wash-out time. This technology provides researchers in the field of ultrasound evaluation of the prostate the opportunity to apply a new diagnostic tool, contrast angiosonography, in their research. This method for analysis of prostatic blood flow can be helpful in any application that affects the blood supply of the prostate such as heat treatments and hormonal treatments.

Aged↗

PubMed1999

Metastasectomy in renal cell carcinoma: A multicenter retrospective analysis.

OBJECTIVE: In 60-70% of patients with renal cell carcinoma (RCC), metastases develop in the course of the disease. In the present analysis, the surgical management of metastases is described, and survival data are presented. This retrospective analysis may help in the management of future cases. Due to the retrospective nature of the data, no comparison between surgical and nonsurgical management is possible. METHODS: Between 1985 and 1995, 152 resections of RCC metastases were performed in 101 patients at four Dutch Hospitals. Thirty-five and 6 patients had metastases resected 2 and 3 times, respectively. In most patients, the primary tumor was resected (n = 95). Resections were performed for metastases at different locations: lung n = 54, bone n = 42, lymph nodes n = 18, cerebrum n = 12 and locations in the spinal canal, thyroid, bowel, and testis. Skin excisions were excluded from the analysis. Solitary metastases were resected in 40 patients. RESULTS: Median survival after the initial metastasectomy was 28 months. Initial tumor stage, grade, or size were not related to metastasis location or survival. The number of initially resected pulmonary metastases was of no influence on survival, however, multiple consecutive resections were related with longer survival. Patients with solitary metastases (n = 40) did not show longer survival after the first metastasectomy compared to no solitary lesions. Better survival was found for lung metastases compared to other tumor locations (p = 0.0006, log rank test) and for patients that were clinically tumor free after metastasectomy (p = 0.0230, log rank test). Additional immuno- or radiotherapy did not independently influence survival. Time interval between primary tumor resection and metastasectomy correlated positively with survival: a tumor-free interval of more than 2 years between primary tumor and metastasis was accompanied by a longer disease-specific survival after metastasectomy. Eleven patients were free of disease after metastasectomy with a median time of 47 (14-65) months. The median time of hospital admittance for metastasectomy was 9 days (4-64). Lethal complications were found in 2 patients. Long-term (>5 years) disease-free survival was achieved in 7% of patients whereas 14% of patients were free of disease with a minimal follow-up of 45 months. CONCLUSIONS: (1) Surgical management of metastases could be performed with short hospital stay, and low complication rates were found. (2) Disease-free survival was found in 14 and 7%, with follow-ups of at least 45 and 60 months, respectively. (3) The longest survival was found after surgery for pulmonary lesions. (4) Resection of solitary metastases did not result in longer survival compared to resection of nonsolitary lesions. (5) An interval shorter than 2 years between primary tumor and metastases was correlated with a shorter disease-specific survival.

Carcinoma, Renal Cell↗

PubMed1999

Results of a European comparative randomized study comparing oral bropirimine versus intravesical BCG treatment in BCG-naive patients with carcinoma in situ of the urinary bladder. European Bropirimine Study Group.

OBJECTIVES: This European phase III clinical trial was part of an intercontinental study which was closed prematurely by the sponsor. The study was designed to compare the effects of oral bropirimine with intravesical BCG, the current standard treatment in patients with newly diagnosed bladder carcinoma in situ (CIS). METHODS: A total of 55 BCG-naive patients with bladder CIS were randomized to receive bropirimine (n = 27) or BCG (n = 28). Bropirimine was orally administered at a dose of 3 g/day for 3 consecutive days with a 4-day drug-free interval for up to 1 year. BCG-Tice instillations were administered weekly for 2 x 6 weeks. Both biopsies and cytology had to be negative for the patient to be considered a complete responder (CR). RESULTS: The percentage of dropouts for all of the adverse events was 4% for bropirimine and 14% for BCG. The most frequently reported local events in the bropirimine- versus the BCG-treated group were irritative complaints, 64 vs. 89% (p = 0.03) and hematuria, 24 vs. 61% (p < 0.01). The most frequently reported systemic events in the bropirimine- versus the BCG-treated group were fever 4 vs. 21%, flu syndrome 24 vs. 7%, headache 28 vs. 11% and nausea 24 vs. 11% (all p > 0.05). A total of 92% of the patients treated with bropirimine had a CR with a mean duration of 12.6 months (95% CI 9.2-15.9). In the BCG group, all of the patients had a CR with a mean of 12.3 months (95% CI 8.5-16.0). CONCLUSIONS: This study shows that bropirimine, an orally administered drug that can be self-administered to outpatients with more acceptable local toxicity compared to BCG, could be an effective first-line therapy in patients with CIS of the urinary bladder. Continued investigation of bropirimine is warranted to increase its clinical utility.

Adjuvants, Immunologic↗

PubMed1999

Clinical experience in Europe with uroselective alpha1-antagonists.

alpha1-Adrenoreceptors are thought to be involved in prostate smooth muscle contractions and could hence play a role in the dynamic component of intravesical obstruction associated with symptomatic BPH. Consequently, since the mid-eighties alpha receptor blocking agents have been used for the treatment of BPH. Non-selective alpha blockers are usually associated with systemic side-effects which resulted in an exclusion or withdrawal of many patients from this form of treatment. With the availability of so-called uroselective alpha blockers the management picture has changed since it was anticipated that these compounds cause lesser side-effects with at least the same, or even better, efficacy. Comparative clinical studies are essential for determining the eventual advantages of the uroselective alpha1-antagonists and a large number of such studies have been performed worldwide studying the various available compounds. European studies with terazosin showed clear superiority of the drug over the placebo while causing only limited side-effects. Various other studies using alpha-blocking agents such as doxazosin, tamsulosin and alfuzosin yielded identical results. Especially with tamsulosin and alfuzosin, the side-effects were comparable with those encountered in the placebo group. About 7% of the patients using tamsulosin experienced retrograde ejaculation in one study which did not occur in the alfuzosin studies. Important studies in Europe have also investigated the value of a combination of an alpha blocker with a 5alpha-reductase inhibitor. Comparable studies in which both alfuzosin and doxazosin were combined with the 5alpha-reductase inhibitor Proscar have shown that a combination is not superior to a blocker monotherapy and especially in the ALFIN study the results show that alfuzosin monotherapy is superior to Proscar in the management of symptomatic BPH. European studies have evaluated Quality of Life, sexuality as well as socio-economical outcome of the treatment with alpha1 receptor antagonists. These studies completed the spectrum of clinical research in Europe in the important field of management of symptomatic BPH with uroselective alpha1 antagonists.

Adrenergic Antagonists↗

PubMed1999

In vivo and in vitro characterizations of three 99mTc-labeled monoclonal antibody G250 preparations.

UNLABELLED: In previous clinical studies, excellent visualization of tumor lesions has been observed with 131I-labeled monoclonal antibody (mAb) G250 in patients with renal cell carcinoma (RCC). In several cases, 131I-cG250 immunoscintigraphy disclosed tumor lesions that were not visualized by radiography or CT. To improve image quality, we aimed to develop a 99mTc-labeled mAb G250 preparation for radioimmunodetection of RCC. We studied in vitro stability, biodistribution and imaging potential of three 99mTc-labeled G250 preparations in nude mice with subcutaneous RCC xenografts.125I-G250 and the nonspecific mAb 131I-MN14 were used as control antibodies. METHODS: The mAb G250 was labeled with 99mTc according to three methods using: (a) S-hydrazinonicotinamide (HYNIC), (b) S-benzoylmercaptoacetyltriglycine (MAG3) and (c) a direct labeling method (Schwarz method). The stability of all preparations was tested in serum at 37 degrees C during 48 h. In addition, diethylenetriamine pentaacetic acid, cysteine and glutathione challenge assays were performed. RESULTS: All preparations showed good stability in serum during the 48-h incubation period. 99mTc-G250 (Schwarz) showed release of the radiolabel at a 100-fold or higher molar excess of cysteine and at a 10,000-fold or higher molar excess of glutathione. 99mTc-MAG3-G250 showed release of the radiolabel at a 10,000-fold molar excess of cysteine. 99mTc-HYNIC-G250 was stable under all conditions. Tumors were clearly visualized with all preparations. 99mTc-G250 (Schwarz) showed significantly lower blood levels (3.8 %ID/g) compared with all other preparations (11.2, 13.4 and 13.4 %ID/g for 99mTc-HYNIC-G250, 99mTc-MAG3-G250 and 125I-G250, respectively, 48 h postinjection). At 48-h postinjection, mean tumor uptake was very high with all mAb G250 preparations: 92.4 (99mTc-HYNIC-G250), 125.9 (99mTc-MAG3-G250), 29.4 (99mTc-G250 Schwarz) and 75.4 (125I-G250) %ID/g. Mean tumor uptake of the nonspecific 131I-MN14 mAb was 6.6 %ID/g. CONCLUSION: In this study, 99mTc-HYNIC-G250 showed excellent in vitro stability and tumor targeting. Moreover, this preparation could be labeled with high efficiency (>95%) at room temperature within 15 min. Therefore, 99mTc-HYNIC-G250 seems to be an ideal candidate for radioimmunodetection of RCC.

Animals↗

PubMed1999

Phase I radioimmunotherapy of metastatic renal cell carcinoma with 131I-labeled chimeric monoclonal antibody G250.

Clinical tumor targeting studies with chimeric monoclonal antibody G250 (cG250) in renal cell carcinoma (RCC) patients indicated the potential use of this antibody for radioimmunotherapy. Here we report on a phase I activity dose escalation study to determine the safety, the maximum tolerable dose (MTD), and the possible therapeutic potential of 131I-labeled cG250 in patients with progressive metastatic RCC. All patients (n = 12) received a diagnostic i.v. infusion of 5 mg of cG250 labeled with 222 MBq of 131I. If accumulation of the antibody in metastatic lesions was observed, patients were hospitalized and a second, therapeutic, i.v. infusion of 5 mg of cG250 labeled with a high dose of 131I was administered (n = 8). Three patients per dose level were entered, starting at 1665 MBq/m2. If no dose-limiting toxicity occurred, the study continued at the next dose level (555 MBq/m2 increase). Most patients experienced mild nausea without vomiting. No other complaints were reported during hospitalization. In two of two patients who received a dose of 2775 MBq/m2, grade IV hematological toxicity was observed, which was defined as dose limiting. Thus, the MTD was set at 2220 MBq/m2. In one patient (2220 MBq/m2), stable disease (lasting 3-6 months) was achieved, whereas another patient (2220 MBq/m2) showed a partial response that is ongoing (>9 months). The minor responses observed in this phase I trial in patients with an advanced stage of RCC are encouraging and warrant further study in a phase II setting at the MTD to determine the efficacy of radioimmunotherapy for metastatic RCC.

Adult↗