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Biomedical subjects

F M Debruyne

Publications and source records attributed to F M Debruyne.

At least 199 records · Page 11Linked to original sources

Relationship between lower urinary tract abnormalities and disease-related parameters in multiple sclerosis.

Multiple sclerosis affects the lower urinary tract in many patients. The relationship between lower urinary tract abnormalities and disease-related parameters of multiple sclerosis is not well described. We screened urologically and neurologically 212 patients according to a standard protocol. Micturition complaints were noted in 52% of the patients and urodynamic abnormalities were found in 64%. A statistical correlation was found between detrusor hyperactivity and detrusor hypoactivity with disease-related parameters, that is disease duration, disability status, myelin basic protein concentration in the cerebrospinal fluid and neurophysiological investigations. No relationship was found between detrusor hypersensibility or detrusor hyposensibility and the aforementioned disease-related parameters. In 1 patient upper urinary tract abnormalities were noted in combination with urodynamic abnormalities. We conclude that lower urinary tract abnormalities can be found in every patient with multiple sclerosis unrelated to the state of the disease. Severe upper urinary tract abnormalities are rare.

Adolescent↗

Computer analysis of transrectal ultrasound images of the prostate for the detection of carcinoma: a prospective study in radical prostatectomy specimens.

PURPOSE: The reliability and objectivity of computer assisted transrectal ultrasound are examined. MATERIALS AND METHODS: Pathological examination of radical prostatectomy specimens was compared prospectively to automated cancer detection in corresponding transrectal ultrasound images. RESULTS: For automated cancer detection, a sensitivity of 0.75 and a specificity of 0.78 were obtained. Moreover, 74% of human interpretation of the percentage of malignancy in the analyzed images was equal to the actual calculated percentage (Pearson's product moment correlation coefficient 0.85). CONCLUSIONS: Comparing these results to those obtained with normal transrectal ultrasound, automated analysis provides additional information in the interpretation of transrectal ultrasound images by color coding them in an objective manner according to the probability of malignancy.

Aged↗

Semi-automated database design by the end-user.

An information system was developed to manage the data for a large number of research projects simultaneously. The system, called URIS, has facilitated the management of research data in an academic urological department. It enables end-users, who are not necessarily skilled computer scientists, to design their own databases semi-automatically, by supporting data entry screen design and the specification of research items. The system creates the database tables automatically after these activities. The specification of research items is the most important but also most difficult part in this process.

Computer Literacy↗

Comparison of biothesiometry and neuro-urophysiological investigations for the clinical evaluation of patients with erectile dysfunction.

In the literature the determination of the vibration sensitivity threshold of the penile glans by means of biothesiometry has been introduced as a cost-effective office test for the evaluation of penile neuropathy in impotent men. At our facility we have gained extensive experience with neuro-urophysiological tests for the evaluation of penile innervation. These neuro-urophysiological tests have the disadvantage of complexity, invasiveness and time consumption. In our study both methods were compared in 31 impotent patients. The results showed that penile glans biothesiometry yields consistent results when measurements are repeated during 1 session. However, no relationship was found between the outcome of penile glans biothesiometry and neuro-urophysiological tests of the dorsal penile nerve, which is probably due to the fact that vibration is not an adequate stimulus to the skin of the penile glans that contains free nerve endings (that is pain receptors) only, and hardly any vibration receptors. We conclude that biothesiometric investigation of penile glans innervation is unsuited for the evaluation of penile innervation and cannot replace neuro-urophysiological tests.

Erectile Dysfunction↗

A randomized study of intravesical mitomycin C, bacillus Calmette-Guerin Tice and bacillus Calmette-Guerin RIVM treatment in pTa-pT1 papillary carcinoma and carcinoma in situ of the bladder.

Results of a randomized prospective study are reported in which mitomycin C, Tice bacillus Calmette-Guerin (BCG) and RIVM-BCG were compared in 437 patients with primary or recurrent pTa and pT1 bladder tumors, including carcinoma in situ. The followup (or time in study) varied from 2 to 81 months (mean 36 months). After complete transurethral resection of all visible tumors the patients were treated with 30 mg. mitomycin C once a week for 4 consecutive weeks and thereafter every month for a total of 6 months, and 5 x 10(8) colony-forming units Tice BCG or RIVM-BCG once a week for 6 consecutive weeks. For papillary tumors mitomycin C and RIVM-BCG treatments were equally effective (p = 0.53), and mitomycin C was more effective than Tice BCG therapy (p = 0.01).

Administration, Intravesical↗

Comparison of P53 protein overexpression with P53 mutation in bladder cancer: clinical and biologic aspects.

BACKGROUND: Alterations of the tumor suppressor gene p53 are known to occur in bladder cancer. Although p53 overexpression is associated with mutation of the p53 gene, a substantial discrepancy between molecular genetic alteration in p53 and overexpression of the protein has been found. EXPERIMENTAL DESIGN: Tumor specimens of 39 bladder cancer patients were immunohistochemically analyzed for p53 overexpression, and the results were compared with the presence of a mutation as assessed by single strand conformation polymorphism (SSCP) and direct sequencing. Both clinical and biologic aspects were studied. RESULTS: A significant correlation between p53 overexpression and poor survival in the whole group studied was found (p < 0.01). No association between p53 overexpression and decreased survival was found for invasive tumors in contrast with other studies. Differences in treatment of the patients and different Ab and scoring systems used might explain these differences. In our study, the Kaplar-Meier curves showed the same result for p53 overexpression and p53 mutation when the whole group and the invasive tumors were studied. However, in the group of superficial tumors, which was unfortunately too small for statistical analysis, we found p53 overexpression in three tumors, and no p53 mutations were found. A good concordance between p53 mutation and p53 overexpression was found (p < 0.02). However, two out of eight tumors with an SSCP-proven p53 mutation showed no p53 immunoreactivity, probably as a result of loss of the nuclear localization signal. Twenty three percent (7/31) of the tumors showed p53 overexpression without any sign of a mutation. CONCLUSIONS: Our results indicate that, despite good concordance between p53 mutation and p53 overexpression, there is no direct casual relationship between mutation and protein accumulation. Apparently, other events than mutation can trigger p53 stability.

Adult↗

Immunization with anti-idiotype monoclonal antibodies bearing the internal image of the renal-cell carcinoma-associated antigen G250 induces specific cellular immune responses.

We have previously isolated and characterized 6 anti-idiotype antibodies (Ab2s) directed against monoclonal antibody G250 (MAbG250) which reacts with a tumor-associated antigen (TAA) expressed in a large proportion of human renal-cell carcinomas (RCC). These 6 Ab2s (NUH31, 51, 71, 82, 91: IgG1, NUH44: IgG2a) showed MAbG250 binding site specificity and induction of anti-TAA antibody resembling MAbG250 (so-called AbI') in rabbits, indicating that they are internal image antibodies. To investigate whether these Ab2s could induce G250-TAA-specific cell-mediated immunity, delayed-type hypersensitivity (DTH) tests were carried out with G250 antigen-positive and/or -negative cells in the ears of BALB/c mice. Mice primed with Ab2 showed antigen-specific DTH responses, whereas no significant DTH response was observed with G250-negative cells. This antigen-specific DTH could be transferred to naive mice by lymphocytes harvested from Ab2-sensitized mice. In addition to the classical DTH responses observed 24 and 48 hr after tumor challenge, an early-phase antigen-specific hypersensitivity response was seen 2 hr after challenge. This early component of the specific hypersensitivity reaction but not the classical DTH could be transferred to naive mice by serum from Ab2-sensitized mice, indicating that the early reaction was due to serum factors. These findings demonstrate that all Ab2s induced tumor-specific cellular immune responses directed against human RCC, and suggest that they may be useful as RCC-TAA surrogates, i.e., as tumor vaccines for RCC patients.

Animals↗

[Transurethral microwave-thermotherapy in the treatment of benign prostatic hyperplasia].

OBJECTIVE: Determining the therapeutic efficacy of transurethral microwave thermotherapy (TUMT) in benign prostatic hyperplasia (BPH). DESIGN: Prospective. SETTING: Department of Urology, University Hospital Nijmegen, the Netherlands. METHOD: In the outpatient clinic, 130 BPH patients (mean age: 65.9 years (SD: 6.9); mean prostatic volume 50.2 cm3 (SD: 18.4)) received TUMT in a single session lasting 60 min. The prostate was heated to above 45 degrees C by a microwave antenna in a urethral catheter, resulting in tissue necrosis. In the first year after treatment the Madsen symptom score, maximal flow, residual volume, prostatic volume and concentration of prostate-specific antigen in blood were collected. RESULTS: After 1 year 98 patients could be evaluated; of the other 32, 16 withdrew from follow-up, 10 underwent transurethral prostate resection and 6, other treatment. The maximal flow increased by 1.2 ml/s (SD: 4.0). The residual volume decreased by 15.8 ml (SD: 55.6). Symptom scores improved by 5.9 points (SD: 5.0). A 50% increase in symptom score was seen in 49.5% of all patients; 24.3% showed no improvement of complaints. There was no change in prostatic volume, whereas PSA concentration showed a transient increase in the first week after TUMT. Preliminary results after 6 months' follow-up of a randomised placebo-controlled study in 50 patients showed subjective and objective improvement of miction. CONCLUSION: TUMT results in distinct subjective improvement. Urodynamic findings show a less pronounced improvement.

Aged↗

Vaccination with anti-idiotype antibodies mimicking a renal cell carcinoma-associated antigen induces tumor immunity.

We have previously isolated and characterized 6 different internal image mouse monoclonal anti-idiotype antibodies (Ab2) directed against the paratope of mouse monoclonal antibody G250 (MAbG250, Ab1), which specifically reacts with human renal cell carcinoma (RCC). These Ab2s (NUH31, 44, 51, 71, 82 and 91) demonstrated specificity for the combining site of Ab1, and appeared to recognize 2 partly overlapping idiotopes on Ab1. In this study, we further characterize the fine specificity of the Ab2, investigate whether the immunogenicity of Ab2 could be enhanced by conjugation to a carrier and investigate the anti-tumor efficacy of Ab3 sera in mice challenged with RCC. Immunization of animals with Ab2 conjugated to keyhole limpet hemocyanin as carrier protein resulted in a 2-fold increase in antigen-specific anti-anti-idiotype antibodies (Ab3) as compared with immunization using Ab2 alone. Specific reactivity was observed with antigen-positive cell lysates, and all Ab3 sera contained immunoglobulin resembling Ab1 (Ab1'), as shown by competitive Ab1-antigen binding assays. Fine-specificity studies of Ab3 sera revealed that the Ab2s can be divided into 4 mutually exclusive groups, showing that the 6 Ab2s recognize 4 slightly different idiotopes in the Ab1 binding pocket. Treatment of RCC-challenged mice with Ab3 sera resulted in significant tumor growth inhibition and lower tumor take rates as compared with control groups. Ab3 sera obtained from NUH-91-immunized animals showed superior characteristics as compared to the other Ab3 sera: no tumors remained after 5 weeks of Ab3-NUH91 treatment. Our findings indicate that the Ab2 elicit powerful anti-tumor effects in immune-competent animals.

Adjuvants, Immunologic↗

Decreased E-cadherin expression is associated with poor prognosis in patients with prostate cancer.

Decreased levels of the cell-cell adhesion molecule E-cadherin are associated with loss of differentiation in a number of human carcinomas. However, the value of E-cadherin as a prognostic marker in these cancers is largely undetermined. A previous study of E-cadherin levels in prostate cancer revealed that almost 50% of tumors examined had reduced or absent levels of this protein (Umbas et al., Cancer Res., 52: 5104-5109, 1992). To determine the potential prognostic significance of this finding, prostate cancer specimens from 89 patients were evaluated immunohistochemically for E-cadherin expression, and the results were related to histopathological grade, tumor stage, presence of metastases, and survival. As previously observed, a significant inverse correlation was found between E-cadherin expression and tumor grade. Importantly, we also found significant correlations between E-cadherin expression and tumor stage and overall survival. Sixty-three percent of the tumors that extended beyond the prostate capsule (T3-4) versus 33% of the tumors confined to the prostate (T1-2) had aberrant expression (chi 2 = 8.1, P < 0.005). Seventy-six percent of the primary tumors from patients that presented with metastases showed aberrant staining compared to 32% from patients without metastases (chi 2 = 14.9; P < 0.001). The life table analysis showed a significantly higher survival rate for patients with normal staining compared to patients with aberrant expression (chi 2 = 20.4, P < 0.001 by log rank test). Moreover, abnormal expression of E-cadherin correlated significantly with progression after radical prostatectomy (P < 0.005). These results suggest that E-cadherin expression can serve as a prognostic indicator for the biological potential of prostate cancer.

Adult↗

Internal image anti-idiotype antibodies related to renal-cell carcinoma-associated antigen G250.

The potential usefulness of internal-image anti-idiotype antibodies (Ab2s) in modulating hosts' immune responses to tumor-associated antigen (TAA) have stimulated considerable interest in the development and characterization of Ab2s. Six different mouse monoclonal Ab2s (NUH31, 44, 51, 71, 82 and 91) were generated against murine monoclonal antibody G250 (MAbG250) which recognizes a human renal-cell carcinoma-associated antigen. All 6 Ab2s showed specificity for the MAbG250 paratope in Western-blot analysis. In inhibition assays, all Ab2s were able to compete with the nominal antigen, albeit with differing efficiency. Based on cross-blocking studies for idiotope mapping, the Ab2s could be divided into 2 groups (group I; NUH31, 51, 71, group 2; NUH44, 82, 91). However, cross-reactivity between these 2 groups was observed, indicating that they recognized partly overlapping epitopes on the paratope of MAbG250. Sera from rabbits immunized with Ab2s showed reactivity with G250 antigen-positive cell lysates, but not with antigen-negative cell lysates. Additional studies revealed that all Ab2s were able to induce anti-anti-idiotype antibodies resembling MAbG250 (Ab1'). These findings suggest that the Ab2s functionally mimic the original G250 antigen and may be of use in the immunotherapy of human renal-cell carcinoma.

Animals↗

Effects of high energy shock waves on tumor blood flow and metabolism: 31P/1H/2H nuclear magnetic resonance study.

The effects of high energy shock waves (HESW) on tumor cell metabolism and tumor blood flow were studied in the NU-1 kidney cancer xenograft by multinuclear 1H/2H/31P magnetic resonance spectroscopy. Tumor xenografts were exposed to 800 HESW using an experimental electromagnetic shock wave emitter based on the Siemens Lithostar Plus, which is used for clinical lithotripsy. Exposure of tumors to 800 HESW resulted in a temporary decrease of tumor blood flow (TBF) determined by the 2H NMR monitoring of the 2HO1H wash-out after intratumoral injection. By concomitant recording of 31P and 1H NMR spectra, tumor pH, high-energy phosphates and lactate levels were followed. Tumor treatment with HESW transiently resulted in acidification, ATP decrease, P(i) increase and lactate increase. In contrast, HESW administration adjacent to the tumor did not significantly influence TBF, tumor pH, high-energy phosphates or lactate levels, showing that the observed alterations are caused by an interaction of HESW and tumor tissue. The most likely explanation for these observations is that HESW administration causes local vascular malfunctioning followed by a reduction in oxygen and nutrient supply to the tumor which leads to a decreased aerobic energy metabolism. The results of this study may be used to aid the design of HESW-based therapies.

Animals↗

Magnetic resonance spectroscopy detects metabolic differences between seven Dunning rat prostate tumor sublines with different biological behavior.

In this study, it was investigated whether prostate tumor biological parameters correlate with metabolic profiles. 1H and 31P magnetic resonance spectra were acquired from perchloric acid extracts of seven Dunning R-3327 prostate tumor sublines. Several metabolic ratios, for example, phosphocholine/total phosphate, choline/total creatine, and inositol/total creatine, did not correlate specifically with one biological characteristics but, based on each of these ratios, the well-differentiated, nonmetastatic, and hormone-dependent sublines could be discriminated from the poorly differentiated or anaplastic, metastatic, and hormone-independent sublines. The glycerophosphoethanolamine/total phosphate, glycerophosphocholine/total phosphate, and phosphocreatine/total phosphate ratios correlated with differentiation grade, and the differences in glycerophosphorylglycerol/total phosphate ratio between metastatic and nonmetastatic sublines was highly significant. No correlation for hormonal sensitivity with any of the metabolites measured could be found, neither by 31P nor by 1H MRS.

Animals↗

Molecular prognostic factors in bladder cancer.

In this paper the predictive value of molecular prognostic parameters for bladder cancer is discussed. DNA ploidy has additional prognostic value for grade 2 tumors, irrespective of stage, with aneuploid tumors having a poor prognosis. Overexpression of the epidermal growth factor receptor (EGFR) can be used as a prognostic factor for the group of superficial tumors. Both abnormal E-cadherin and retinoblastoma (RB) expression have additional prognostic value for invasive tumors. The exact predictive value for the superficial tumors needs further study. The results with respect to p53 are conflicting and its exact role especially in the progression of pT1g3 tumors has to be clarified. In view of the discordance concerning its prognostic value, c-erbB-2 overexpression also needs further study. It appears that at this moment only a few molecular markers seem to have potential prognostic value, but their precise clinical relevance has to be studied more extensively. In particular the value of progression markers in the superficial TCC needs more attention.

Aneuploidy↗

Intravesical therapy in superficial bladder cancer.

OBJECTIVE: To identify the appropriate characteristics of superficial bladder cancer that allow the physician to predict tumor behavior. METHODS: We analyzed 1,745 patients with primary superficial bladder cancer with regard to disease and patient characteristics. RESULTS: With the characteristics we found, the population can be described and prognostic factors can be found. Moreover, with the use of these factors, it appears to be possible to predict tumor behavior on a group level. Prediction on an individual level, however, remains far from ideal. CONCLUSIONS: Three treatment options can be chosen: follow-up after initial transurethral resection, additional instillations with intravesical chemotherapy, or instillations with bacillus Calmette-Guerin (BCG). In case instillations are indicated, most (but not all) superficial bladder cancer trials show superiority of BCG over intravesical chemotherapy, although at the cost of more side effects. However, with intravesical BCG, it seems possible to influence the natural history of superficial bladder cancer, which means that we can delay progression and improve survival.

Administration, Intravesical↗