Search PubMed⌕ Search

Biomedical subjects

F M Debruyne

Publications and source records attributed to F M Debruyne.

At least 307 records · Page 17Linked to original sources
PubMed1991

Identification of high mobility group protein I(Y) as potential progression marker for prostate cancer by differential hybridization analysis.

One of the major problems in the diagnosis of localized prostatic tumors is to predict the aggressiveness of an individual tumor, which is presumably associated with chance to progression. In an attempt to find molecular markers that are specific for aggressive prostatic cancer cells, we compared steady-state mRNA levels of progressionally related prostatic tumors. The Dunning R-3327-H subline, a relatively benign rat prostatic tumor, was compared to the therefrom derived highly aggressive MatLyLu tumor by differential hybridization analysis. The differential screening revealed 26 complementary DNA clones that detected transcripts overexpressed in MatLyLu. Upon further screening on the entire panel of Dunning R-3327 sublines, it appeared that three clones (pBUS1, pBUS19, and pBUS30), detected transcripts specifically expressed in metastatic rat prostatic tumors. The expression pattern of pBUS19 and pBUS30 suggested a relation between these complementary DNAs. Nucleotide sequence analysis, however, could not yet substantiate this. Computer-assisted comparison of the DNA sequences revealed the presence of rat long terminal repeat-like repetitive elements in pBUS19. The differential expression of repetitive elements in progressionally related tumors is interesting, yet similar findings have not been reported in human malignancies. Nucleotide sequence analysis of pBUS1 indicated that this clone is identical or related to high mobility group protein I(Y), a non-histone nuclear protein. From recent studies it appeared that this protein might be implicated in replication and/or transcription processes and is induced in fast proliferating/undifferentiated cells. The overexpression of high mobility group protein I(Y) correlates rather with metastatic ability than with growth rate; hence it may serve as a valuable marker to identify progressionally advanced prostate cancer cells.

Animals↗
PubMed1991

Differential antiproliferative activities of alpha- and gamma-interferon and tumor necrosis factor alone or in combinations against two prostate cancer xenografts transplanted in nude mice.

We have investigated the antiproliferative effects of recombinant human alpha- and gamma-Interferon (IFN) and recombinant human Tumor Necrosis Factor alpha (TNF) against the hormone-independently growing PC3 and DU145 prostatic tumor lines. Subcutaneous, peritumoral administration of the drugs was started 24 hours after subcutaneous implantation of 1-2 mm3 tumor pieces. IFN was given three times per week and TNF five times per week. IFN-alpha (dose-range 0.5-5 ng/gram bodyweight) had significant growth-inhibiting effects against the PC3 tumor, but showed no significant antitumor effects against the DU145 tumor. IFN-gamma monotherapy (dose-range 8-80 ng/gram bodyweight) was less effective than IFN-alpha. 500 ng/gram TNF produced growth inhibition of both tumors, whereas the lower dose (50 ng/g) was only effective against the PC3 tumor. IFN-alpha and -gamma combination treatment had significant antiproliferative effects against the PC3 tumor, but not against the DU145 tumor. Combinations of IFN-alpha and TNF were very effective against both xenografts; some combinations resulted in complete growth inhibition. IFN-gamma and TNF combinations also showed significant antitumor effects against both tumor lines. We therefore conclude that cytokine combination treatment may provide a new approach in the treatment of hormone-escaped prostatic tumors.

Animals↗
PubMed1991

Leukocytes in the urine after intravesical BCG treatment for superficial bladder cancer. A flow cytofluorometric analysis.

Cellular immunologic reactions occurring in the bladder after intravesical treatment with bacillus Calmette-Guérin (BCG) were investigated by flow cytofluorometric analysis of leukocytes present in the urine. Urine specimens from 11 superficial bladder cancer patients were collected before and 5, 24, 48 and 72 h after repeated BCG instillations. Monoclonal antibodies specific for granulocytes, monocytes/macrophages, and T-and B-lymphocytes were used to characterize and quantify leukocyte subpopulations. The total number of cells in urine was found to be 2- to 485-fold increased 24 h after BCG administration. The predominant cell type present was the polymorphonuclear granulocyte, probably representing a defense mechanism against mycobacteria. The main mononuclear leukocytes in urine specimens were monocytes/macrophages and T-lymphocytes, indicating an ongoing immune response in the bladder wall. Although percentages of lymphocytes were low, T- and B-cells could be identified using a selective cell measurement procedure. In conclusion, a clear increase in the numbers of granulocytes, monocytes/macrophages and T-lymphocytes in urine after intravesical BCG administration was demonstrated, indicating local activation of the immune system.

Administration, Intravesical↗
PubMed1991

Differential sensitivity of renal cell carcinoma xenografts towards therapy with interferon-alpha, interferon-gamma, tumor necrosis factor and their combinations.

Whereas cytokine therapy has proven efficacy in the treatment of metastatic renal cell carcinoma (RCC), many questions regarding the use of these drugs remain unanswered. In the present study we evaluated the antiproliferative effects of human recombinant alpha-interferon (IFN), gamma-interferon and tumor necrosis factor-alpha (TNF) on eight human RCC xenografts. In particular, the importance of the administration route, dosage and tumor load was investigated. Response to the cytokines differed widely amongst the different tumors. Of three tested routes of administration (i.v., i.p. and s.c. peritumoral), only the s.c. peritumoral route was effective against tumor growth. After 6 weeks of therapy consisting of 150 or 1,500 units IFN/g given s.c. peritumorally three times a week or 30,000 units TNF/g given five times a week, alpha-IFN treatment resulted in 2%-100% growth inhibition; gamma-IFN, in 7%-80%; and TNF, in 35%-75% as compared with the untreated control. Growth of five of eight tumor lines could be inhibited completely by combinations of IFN and TNF, whereby the tumor dimensions at the beginning of therapy were decisive for the results. In some cases IFNs had optimal doses; however, the antitumor effects of TNF were always dose-dependent. Our studies indicate that the doses at which the optimal direct effects of cytokines are measured are critically dependent on the tumor treated. Although direct effects are only one part of the mode of action of cytokines, our results indicate that dosage of cytokines may need individualisation.

Animals↗
PubMed1991

Presence of activated lymphocytes in the urine of patients with superficial bladder cancer after intravesical immunotherapy with bacillus Calmette-Guérin.

To study the mode of action of intravesical bacillus Calmette-Guérin (BCG) immunotherapy in the prevention and cure of superficial bladder cancer, flow-cytofluorometric analysis of the cellular immunological reaction in the urine of patients was performed. Fresh urine-derived leucocytes were obtained from eight patients before (t0) and 24 h (t24) and 48 h (t48) after repeated intravesical BCG instillations (at least 5 instillations). For two patients urine-derived leucocytes were investigated at the first BCG instillation. The number of leucocytes in the urine was markedly increased 24 h after repeated BCG instillations, indicating a local cellular immunological reaction induced by BCG. The mean number of cells per milliliter of urine at that time was 2.9 x 10(6) +/- 3.6 x 10(6) (n = 8). These leucocytes consisted mainly of granulocytes (75 +/- 11%, n = 8). In addition monocytes/macrophages (4 +/- 2%, n = 8) and T lymphocytes were present (1 +/- 1%, n = 5). The relative increase of monocytes/macrophages in the urine after BCG application tended to be higher compared to the other leucocyte subtypes. As T lymphocytes may play an important role in the BCG-mediated anti-tumour activity, subsets of lymphocytes were further characterized at t0, t24, and t48 after repeated BCG instillations. The lymphocyte population consisted mainly of T cells (86% CD3+, t0). Most of the T cells were CD4+ (helper/inducer) and were significantly decreased at 48 h (62 +/- 9% at t0 vs 49 +/- 6% at t48). Lymphocytes partly expressed HLA-DR antigens (44%, t0). The percentage of lymphocytes with interleukin-2 (IL-2) receptors (CD25+) was significantly increased at 24 h and 48 h, compared to pre-instillation values (19 +/- 11% and 10 +/- 4% vs 3 +/- 3% respectively). Natural killer cells (CD16+ and/or CD56+) and B cells (CD19+) were less numerous (10% and 19% at t0 respectively). After the first BCG instillation the increase in the number of leucocytes in urine seemed to be less compared to the numbers after repeated BCG instillations. Lymphocytes could not be detected in the urine collected before or after the first BCG instillation. In conclusion, we demonstrated the presence of considerable numbers of leucocytes in the urine 24 h after repeated BCG instillations, i.e. shortly after immunological activation. The antigen expression of the lymphocytes suggested that they may represent the lymphocytes in the bladder wall. Expression of HLA-DR and IL-2 receptors on lymphocytes indicated activation of T cells by the intravesical BCG treatment.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Intravesical↗
PubMed1991

Effects of high-energy shock waves combined with biological response modifiers in different human kidney cancer xenografts.

We have studied the effects of high-energy shock waves (HESW) alone or in combination with biological response modifiers on the growth of five human kidney cancer xenografts in mice. Exposure of the tumors to three sessions of 800 shock waves every 48 hours with 18.4 kV, 37.5 MPa, on the commercially available Lithostar resulted in a temporary growth delay. The sensitivity for HESW was related to the doubling time of the tumor. Several days after stopping the HESW administration, the tumors regained their original growth potential with the same doubling time. The systemic application of Tumor Necrosis Factor-alpha (TNF-alpha, 500 ng/g body weight, 5 times/week) and/or Interferon-alpha (IFN-alpha, 5.0 ng/g body weight, 3 times/week) subcutaneously around the tumor also had a limited effect on the growth of these established tumors (60-80 mm3). The combination of HESW with TNF-alpha and IFN-alpha resulted in an almost complete cessation of tumor growth in the NU-1 human kidney xenograft and had an additive antitumor effect in the NU-3. Synergism was also seen in the NU-1 and NU-3 with the combination of HESW and TNF-alpha, while the combination with IFN-alpha had only a limited effect on tumor growth. So TNF-alpha was the active agent, that enhanced the antiproliferative effects of shock waves. In the NC-65 tumor (same doubling time as the NU-1 and NU-3, but less well vascularized), the antiproliferative effect of HESW was not potentiated by TNF-alpha.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Early metabolic response to high energy shock waves in a human tumor kidney xenograft monitored by 31P magnetic resonance spectroscopy.

The effects of electromagnetically generated high-energy shock waves (HESW, Siemens Lithostar) on the phosphate metabolite levels of the NU-1 human kidney cancer xenograft implanted under the skin of the hind limb of nude mice were monitored by 31P magnetic resonance spectroscopy (MRS). Administration of 200 and 800 HESW (18.1 kV, P(+) = 37.5 MPa, P(-) = 5.2 MPa, tr = 30-120 nsec, tw = 340 nsec, freq. = 1.25 Hz), focused on the tumor centre, resulted in an immediate tumor decline; 2 h after exposure to the HESW, the high-energy phosphate resonances had decreased drastically. This decline in energy rich molecules was accompanied by a concomitant increase in the inorganic phosphate resonance and a decrease in pH of the tumor. During the following period, a dose-time dependent recovery of the original high-energy phosphate resonance intensities was observed. These changes are qualitatively similar to those produced by ischemic inhibition of energy metabolism and are correlated with early histological features like vascular disruption, stasis within capillaries, and focal thrombosis. These results demonstrate that experimental HESW treatment of the NU-1 kidney tumor is effective in provoking a temporary reduction of both high-energy phosphate metabolism and tissue pH of the tumor. The data presented here strongly suggest that these effects are predominantly indirect by affecting tumor vascularity. Overall, this study shows that MRS is a powerful technique for longitudinal investigations of HESW-induced effects and can provide information about its mode of action.

Animals↗
PubMed1991

Urethroplasty using the pedicled island flap technique in complicated urethral strictures.

Many techniques have been described for the repair of recurrent urethral strictures. Experience with 1-stage correction of hypospadias and epispadias, using a vascularized island flap technique, has led to its increased application for complicated adult urethral strictures. The advantage of the vascularized island flap technique is that reconstruction can be completed with only 1 operation, and it provides good subjective and objective results. Analysis of 50 consecutive cases treated by this approach has proved its validity. Of the 50 cases fistulas occurred in 20%, of which 12% required surgical correction, and stricture recurred in 32%. The largest proportion of recurrence was noted in patients who were primarily treated with 3 or more urethrotomies within a short time. Therefore, we recommend open surgical repair when 1 or 2 internal urethrotomies fail to produce a good result.

Adolescent↗
PubMed1991

The use of local anesthesia in second generation extracorporeal shock wave lithotripsy: eutectic mixture of local anesthetics.

Extracorporeal shock wave lithotripsy (ESWL&) can be painful. Of our population of patients treated with a Siemens Lithostar device 51.4% needed intravenous analgesia. A eutectic mixture of local anesthetics, a hydrophylic cream containing 25 mg. lidocaine and 25 mg. prilocaine per gm., proved to be effective for local analgesia. Therefore, we investigated its effectiveness during ESWL. With randomized, double-blind application the eutectic mixture of local anesthetics and placebo were evaluated in 83 patients according to the percentage of patients who required intravenous analgesia during ESWL. Of 40 patients treated with the eutectic mixture of local anesthetics 12 (30%) needed supplementary fentanyl citrate, compared to 23 of 43 (53%) placebo treated patients. Although there is no statistical significance (p = 0.32), the eutectic mixture of local anesthetics does decrease pain during ESWL and it should be particularly useful for patients in whom intravenous analgesia is contraindicated.

Adult↗
PubMed1991

The possible influence of antibiotics on results of bacillus Calmette-Guérin intravesical therapy for superficial bladder cancer.

Intravesical treatment with Bacillus Calmette-Guérin is an established treatment of carcinoma in situ and an effective prophylaxis for the prevention of recurrence of transitional cell carcinoma. During instillation therapy oral antibiotics may be used to prevent or to treat urinary tract infections. Tuberculostatic agents are employed to prevent or to treat local irritative symptoms and systemic side effects caused by Bacillus Calmette-Guérin. We investigated the susceptibility of four different Bacillus Calmette-Guérin preparations to 18 antibiotics and to 11 tuberculostatic agents in vitro. All preparations were equally susceptible to most of the commonly used antibiotics and to all of the tuberculostatic agents with the exception of pyrazinamide. Our results suggest that in the absence of cystitis, instillations should not be accompanied by antibiotics because of the possible inhibition of antitumor efficacy by eradication of living Bacillus Calmette-Guérin organisms. The same inhibition may occur when tuberculostatic agents are used to prevent local and systemic complications of Bacillus Calmette-Guérin instillation therapy.

Administration, Intravesical↗
PubMed1991

Penile sensory disorders in erectile dysfunction: results of a comprehensive neuro-urophysiological diagnostic evaluation in 123 patients.

A total of 123 patients with complaints of erectile dysfunction and no clinically overt neurological disease underwent a comprehensive neuro-urophysiological diagnostic evaluation. The results were compared with those obtained in 50 healthy volunteers. Data gathered consisted of somatosensory evoked potentials from the posterior tibial nerve (tibial evoked potential) and from the dorsal penile nerve (pudendal evoked potential). Also, 2 sacral reflex latencies were measured (bulbocavernosus reflex and urethro-anal reflex). A total of 58 patients (47%) had at least 1 abnormal neuro-urophysiological measurement. Neuro-urophysiological abnormalities were found more frequently in older patients. The tibial evoked potential was abnormal in 30 patients (24%), pudendal evoked potential in 21 (17%), bulbocavernosus reflex in 26 (21%) and urethro-anal reflex in 32 (26%). It was concluded that somatosensory disturbances constitute an important part of neuro-urophysiological abnormalities. Our results suggest a relationship between erectile dysfunction and subclinical, age-related (penile) sensory disorders. Our study corroborates the importance of penile sensibility for erectile (patho)physiology as suggested by others and supports the concept of sensory deficit impotence as an important cause of erectile dysfunction.

Adolescent↗
PubMed1991

Comparison of the diagnostic value of pump and gravity cavernosometry in the evaluation of the cavernous veno-occlusive mechanism.

We performed cavernosometry in 96 patients with erectile dysfunction. Two different techniques were compared: pump cavernosometry using a roller pump as the inflow source and gravity cavernosometry using an infusion set as the inflow source. We conclude that the diagnostic value of both techniques is comparable. In pump cavernosometry maintenance flow is the most accurate parameter of veno-occlusive function. Gravity cavernosometry has the advantages of simplicity, cost-effectiveness and a lower complication rate. Incomplete cavernous smooth muscle relaxation appeared to be limiting the diagnostic value of both techniques.

Adult↗
PubMed1991

Cytotoxic effects of high energy shock waves in different in vitro models: influence of the experimental set-up.

High energy shock waves (electromagnetically generated, Siemens Lithostar) were studied for their effects in vitro on different (tumor) cell types. Cells were exposed to the shock waves as a single cell suspension or as a cell pellet on the bottom of a test tube. In both cases, a dose dependent direct cytotoxicity, established by trypan blue dye exclusion, was observed after treatment with 1000 or 2000 shock waves. Also, the antiproliferative capacity as determined by clonogenic potential (double layer soft agar) and growth rate (plastic) were affected in this way. However, comparing the results after treatment in suspension or pellet, a discrepancy was evident. The cell lines showed a different susceptibility in pellet vs. suspension. Also the differential sensitivity of the cell types varied in these two treatment models. Furthermore the outcome depended on the cell concentration; direct cytotoxicity in a cell suspension was more pronounced at higher cell concentrations, while in a pellet this was increased by decreasing the number of cells. Finally, no shock wave induced cytotoxicity could be seen after fixation of cells in gelatine or by placing the pellet on a bottom layer of gelatine. Pressure measurements revealed no adequate explanation for this phenomenon. These results indicate that in vitro effects depend on the way cells are exposed to the shock waves and can be greatly influenced by changing the conditions of the microenvironment. Therefore, precise descriptions of the experimental set-up and careful interpretations of their outcome are obligatory.

Carcinoma↗
PubMed1991

Extracorporeal shock wave lithotripsy for large renal calculi: the role of ureteral stents. A randomized trial.

Ureteral stents reduce complications after extracorporeal shock wave lithotripsy (ESWL*) and contribute to successful stone passage. However, some reports note complications that are attributed to indwelling ureteral stents. We randomized 64 patients with large renal calculi (stone burden more than 200 mm.2) for in situ treatment or treatment with a prophylactically inserted stent. We used a 6Ch round stent with single-coiled ends or a triangular shaped stent with double-coiled ends. Patients were treated with a Siemens Lithostar lithotriptor. After 3 months we evaluated the results of treatment and post-ESWL morbidity. Of the in situ group (23 patients) treatment complications consisted of fever in 3, pyelonephritis in 1 and steinstrasse in 3. After 3 months 8 patients (35%) were free of stones. Of the stented population (41 patients) treatment complications consisted of fever in 7, pyelonephritis in 1, steinstrasse in 6 and bladder discomfort in almost half of the patients. Stent calcification and stent migration were also seen in 7 and 10 patients, respectively. Calcified stents had been in situ longer than noncalcified stents. The round stents migrated and calcified more often than the more rigid triangular stents. After 3 months 18 of the stented patients were stone-free (44%). We conclude that ureteral stents do not reduce post-ESWL complications. They are clearly associated with morbidity and do not improve stone passage markedly. Therefore, patients with a stone burden of more than 200 mm.2 should be treated in situ without auxiliary stenting.

Adolescent↗
PubMed1991

Evidence for early lower urinary tract dysfunction in clinically silent multiple sclerosis.

The occurrence of micturition complaints as late sequelae of multiple sclerosis is well studied and documented. However, no reports exist on urologically asymptomatic patients with a relatively short disease duration. In a prospective study of 40 patients with definite multiple sclerosis (mean disease duration 5 years), urodynamic investigations (cystometry and pressure-flow study) were combined with neuro-urophysiological measurements (cortical evoked potentials and sacral reflex latencies). Patients with (13) and without (27) micturition complaints were investigated. Neurourodynamic abnormalities were seen in 35 of 40 patients (88%). The lower urinary tract proved to be afflicted by multiple sclerosis at an early stage of the disease. Early neurourodynamic investigations had clinical implications. All of the complaining and half of the noncomplaining patients showed urodynamic abnormalities upon which the need for further followup and eventual therapeutic intervention was based. We conclude that neurourodynamic testing of a urinary functional system can be worthwhile as part of the initial diagnostic evaluation in patients with proved multiple sclerosis.

Adult↗
PubMed1991

Value of the patient's case history in diagnosing urinary incontinence in general practice.

What is the value of the case history in diagnosing urinary incontinence in general practice? A total of 103 women with urinary incontinence presented to their general practitioner (GP) and underwent a standard history-taking, physical examination and urodynamic testing. The urodynamic diagnoses were analysed against symptoms and symptom complexes. Symptoms of stress incontinence in the absence of symptoms of urge incontinence had a sensitivity of 78%, specificity of 84% and predictive value of 87%. Symptoms of urge incontinence in the absence of symptoms of stress incontinence excluded genuine stress incontinence. Information on age, parity, enuresis, nocturia, frequency, urgency, cystocele, prolapse and hysterectomy did not contribute to a correct diagnosis. It was concluded that urodynamics are unnecessary in most women presenting with urinary incontinence in general practice.

Adult↗