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Biomedical subjects

F Debruyne

Publications and source records attributed to F Debruyne.

At least 19 recordsLinked to original sources

Adjuvant chemotherapy for superficial transitional cell bladder carcinoma: long-term results of a European Organization for Research and Treatment of Cancer randomized trial comparing doxorubicin, ethoglucid and transurethral resection alone.

PURPOSE: We compared the efficacy of transurethral resection alone or transurethral resection followed by bladder instillations of doxorubicin or ethoglucid for 1 year in patients with superficial bladder carcinoma, and followed them long term for the incidence of progression to muscle invasion. MATERIALS AND METHODS: A total of 443 patients with superficial transitional cell carcinoma of the bladder was randomized. After randomization of 206 patients the control arm was closed to patient entry based on the results of an interim analysis showing a significant difference in favor of those receiving adjuvant chemotherapy. RESULTS: Final analysis of treatment results for recurrence included 432 patients at a median followup of 3.4 years for time to first recurrence, 5 years for analysis of time to invasion (Category T2 disease or worse) and 10.7 years for duration of survival. Time to first recurrence was significantly prolonged by both drugs compared to transurethral resection alone (doxorubicin versus transurethral resection alone p < 0.001 and ethoglucid versus control p < 0.001). Recurrence rate per year was 0.30 for both adjuvant treatment arms and 0.68 for the resection only group. Progression to muscle invasion was rare (15.1% of cases) and not apparently different in the 3 treatment arms. Of the 423 patients death from any cause in 199 and from malignant disease in 59 was not correlated with treatment. However, there was a strong correlation between death from malignant disease, and T category and tumor grade. CONCLUSIONS: In regard to time to first recurrence and recurrence rate per year this study indicates that adjuvant chemotherapy with doxorubicin and ethoglucid using the indicated schedule is superior to transurethral resection alone. However, progression in stage or survival was not influenced by the treatment regimen.

Aged

Evaluation and follow-up of patients with N1-3 M0 or NXM1 prostate cancer in phase III trials.

OBJECTIVES: The aim of this discussion is to review the design and conduct of phase III trials in metastatic prostate cancer, to seek ways of improving their study design, accuracy, relevance to clinical practice, acceptability to patients, and ease of participation by clinicians. We also aim to try to set uniform definitions for the evaluation of the different endpoints used in clinical trials on metastasized prostate cancer. METHODS: The work was started by correspondence between the participants in the group for the year before the consensus meeting. Two comprehensive questionnaires were circulated and the answers were distributed to all the members of the group. The statements were finalized during the consensus meeting. RESULTS: There were some differing opinions concerning the methods of evaluation of endpoints for follow-up, such as time to tumor progression and time to treatment failure. After the consensus conference, there were no major disagreements within the group. CONCLUSIONS: The aim of phase III trials is to influence clinical management. To obtain a credible result they require a sound statistical basis with appropriate power and encompassing patients from small urologic practices as well as large or academic institutions. However, deviation from routine practice may affect the accrual rate, and the trial procedure should therefore be as similar as possible to routine management. Trials inevitably involve extra work and cost. Both should be kept to a minimum to encourage participation and hasten a timely conclusion. It is mandatory to create uniform ways of designing and evaluating clinical trials in prostate cancer.

Clinical Trials, Phase III as Topic

Distribution of the solitary adenoma over the parathyroid glands.

One hundred and ten patients with primary hyperparathyroidism were studied, in which a normal parathyroid gland was found on the same side as an adenoma (both confirmed by histological examination), and the upper or lower location could clearly be defined during surgery. The distribution of the adenomas over the upper and lower glands was unequal: 61.8 per cent in the superior versus 38.2 per cent in the inferior position. Statistical analysis revealed that this is not a random distribution (p = 0.013). The explanation of this relative predilection is unknown. The finding should not influence the surgical procedure for primary hyperparathyroidism.

Adenoma

Changes in spectral measures and voice-onset time with age: a cross-sectional and a longitudinal study.

In this study, we searched for changes in spectral features (during the sustained vowels [a] and [i]) and the voice onset time (VOT, of [pa] and [ka]) of the ageing voice. A longitudinal study (on 20 participants) and a cross-sectional study (on 265 participants) were conducted. The spectral parameters under consideration were: the difference in amplitude between the first and the second harmonic, the energy difference between the frequency band below 1 kHz and 2-4 kHz, and the energy difference between < 1 kHz and 4-5 kHz. The VOT was also measured. Comparing five age bands of men and women, the cross-sectional study revealed a stronger H2 relative to H1 for women above 60 years pronouncing both vowels [a] and [i]. A relatively stronger spectral level was found between 4 and 5 kHz in elderly men and women (60+) for [i] compared to young men and women (20-29 years). Significant differences in the longitudinal study were not identical to those of the cross-sectional study. After a time interval of 30 years, 20 men produced a relatively weaker 2- to 4-kHz part of the spectrum and the VOT became much longer. It was impossible to attribute the changes purely to the process of ageing. Situations and emotions also play an important role and contribute to the different findings of the two groups of participants under consideration.

Adult

The ageing voice: changes in fundamental frequency, waveform stability and spectrum.

In the present study we searched for age dependent acoustic changes in the voice of 205 men and women divided in four age groups from 60 to 99 years old. Sixty young men and women served as a comparison group. The findings cover three domains of acoustic features. Firstly, the voice pitch of males and females congruate one to another, while range and variability both increase. The values of jitter, shimmer and harmonics-to-noise ratio (measures of microstability of frequency, amplitude and waveform resp.) reflect a growing voice instability. From all spectral characteristics, only the difference between the first and the second harmonic differs significantly when comparing young to old women.

Acoustics

Labyrinthine fistulae: a retrospective analysis.

A retrospective analysis has been conducted of 57 labyrinthine fistulae found in 375 cholesteatoma cases, primarily treated by removal of the matrix of the cholesteatoma and covering the fistula with a mixture of bone paste and fibrin glue. CT-scan with slices of 1 mm demonstrated the fistula in almost 90% of the cases. Eighteen percent of the ears were pre-operatively totally deaf. Large fistulae are riskier than smaller ones for post-operative perceptive losses, but even in very large and multiple fistulae the hearing may be preserved in most cases.

Bone Cements

Temporary voice changes after uncomplicated thyroidectomy.

Voice characteristics were studied before and after thyroidectomy in patients with intact vocal fold motility. The speaking voice was acoustically analysed in 47 patients and phonetograms were made in 17 patients. Eight parameters were measured and the pre- and postoperative values compared. The results show that the most affected parameter was the pitch of the speaking voice. The fourth postoperative day there was, on average, a lower SFo and a smaller Fo range during speaking. Postoperatively a progressive normalisation took place. After three months there were no more statistical differences and, looking at the individual measures, the SF0 of all patients fell within 2 semitones from their preoperative level. Vocal quality was also altered in the first postoperative examination, as shown by the higher jitter and smaller harmonics. These measures normalised after two weeks. In the same way, the evaluation of the limits of the voice by means of the phonetogram, showed that the maximal performances in the intensity and pitch domain were decreased in the earliest postoperative period. Information about temporary voice change is useful in patients undergoing thyroidectomy.

Female

Prostatic neuroendocrine cells have a unique keratin expression pattern and do not express Bcl-2: cell kinetic features of neuroendocrine cells in the human prostate.

We investigated the keratin phenotype and bcl-2 immunoreactivity of neuroendocrine cells in the human prostate to determine whether the postmitotic status of these cells is associated with protection from apoptosis by bcl-2 protein expression and to elucidate the possible cell kinetic relationship between neuroendocrine cells and the other epithelial components of the prostate. Tissue specimens were selected from prostates of 19 patients harboring normal secretory glands (n = 15) and glandular benign prostatic hyperplasia (n = 10). Using a novel sequentially selective destaining immunoenzymatic cytochemical technique we were able to demonstrate the distribution of neuroendocrine cells, keratin markers identifying either basal, luminal, or intermediate cells, and the bcl-2 protein in single sections. Basal cell keratins were expressed in the minority of the neuroendocrine cells. In most of the cells, intermediate and luminal cell keratins were found and bcl-2 was constantly negative. Our findings indicate that neuroendocrine cells and other epithelial cells in the human prostate share a common keratin phenotype and probably originate from a common epithelial precursor. From the absence of bcl-2 we infer that the neuroendocrine cells have no progenitor cell characteristics.

Aged

Tinnitus maskers in the treatment of tinnitus. The MICROTEK 321Q.

Traditional tinnitus maskers are generators that deliver a grossly inaccurate broad band high energy noise which most tinnitus patients find an excessive noise intrusion, unacceptable and intolerable. Audiometric analysis defines tinnitus in terms of frequency and intensity. The 321Q-minimum energy narrow band microtek maskers (Mikrotek, Medical, Inc. Columbus) deliver a variable width and a low energy noise that is programmable to any frequency within the audible spectrum. We studied one hundred consecutive tinnitus patients. All patients underwent thorough ENT-analysis and audiometry. Only eight of them could be provided with the masking device and only four found some relief with its use. No correlation in the parameters could be found to discriminate between satisfied and unsatisfied patients.

Acoustic Stimulation

Basic research.

Basic research is currently investigating the molecular cascade associated with bladder cancer development. Many new findings are potential leads towards the improvement of the diagnosis and prognosis of this disease. Special care, however, should be taken in the design of protocols for clinical evaluation of the value of these markers. Some initial guidelines have been put forward in this report.

Alleles

A randomised comparison of monotherapy with Casodex 50 mg daily and castration in the treatment of metastatic prostate carcinoma. Casodex Study Group.

Casodex (Bicalutamide, ICI 176,334) is a potent, non-steroidal, selective anti-androgen with a long half-life allowing once-daily oral administration. In this randomised, open, multicentre study, Casodex 50 mg monotherapy was compared with castration (medical, using goserelin acetate, [Zoladex], or surgical) in 245 patients with advanced prostate cancer. Primary end-points were time to treatment failure, time to objective progression and survival. Subjective responses, quality of life and tolerability were also evaluated. There was no significant difference between the groups in terms of objective progression or subjective responses. Treatment failed in 59 of 119 patients (50%) randomised to Casodex and in 61 of 126 patients (48%) randomised to castration (no statistically significant difference). An updated analysis showed that survival was similar in the two groups. Casodex was well tolerated with a low incidence of diarrhoea and sexual dysfunction. On the basis of this study, Casodex monotherapy is an effective alternative to castration in the treatment of metastatic prostate cancer.

Aged

The prediction of clinical outcome from transurethral microwave thermotherapy by pressure-flow analysis: a European multicenter study.

A total of 100 patients treated with a single session of microwave thermotherapy at 4 European centers was stratified according to 2 different types of obstruction (constrictive and compressive) and compared to clinical outcome at 6 months. Patients had a Madsen-Iversen score of 8 or more, maximum flow rate of 15 ml. per second or less and residual urine volume of 300 ml. or less at entry. The change in Madsen-Iversen score was the same in the 2 groups. Maximum flow rate increased from 8.71 +/- 2.62 to 14.73 +/- 4.04 ml. per second in the constrictive group, and from 8.54 +/- 2.26 to 10.41 +/- 4.52 in the compressive group (p < or = 0.0001). Residual urine decreased from 96.00 +/- 72.85 to 40.34 +/- 56.33 ml. in the constrictive group and from 109.86 +/- 67.09 to 84.65 +/- 81.45 ml. in the compressive group (p < or = 0.0001). Success, as defined by an increase of 50% or more in maximum flow rate and Madsen-Iversen score, was noted in 68% of the constrictive but only 15% of the compressive groups (p < or = 0.0001 chi-square test for trend). Selection by pressure-flow criteria for patients being considered for thermotherapy should improve the overall clinical results.

Diathermy

Bracken fern-induced bladder tumors in guinea pigs. A model for human neoplasia.

We have induced tumors by feeding guinea pigs with a diet containing 25 or 30% dried bracken fern for 100 or 150 days. A high incidence of bladder tumors was obtained. All but one animal had preneoplastic or neoplastic lesions after 4 months; after one year, 24 or 25 exposed animals had carcinoma. Bladder tumors obtained were essentially pure transitional cell carcinomas, although 4 cases (7% of the exposed animals and 10% of the 39 transitional cell carcinoma observed) showed areas of focal squamous metaplasia. Immunohistological detection of cytokeratins 10, 13, and 18 confirmed the transitional nature of these tumors. Tumor development can be followed by ultrasonography and cytology. Bladder tumors arose through several steps. Dysplasia and preneoplastic hyperplasia were seen after 4 months and papillary carcinomas appeared after 6 months, whereas muscle-invasive carcinomas required 1 year. Thus this model reproduces the full spectrum of preneoplastic and neoplastic bladder lesions observed in humans. Interestingly, when tumors were induced in older guinea pigs, none of them progressed to a muscle-invasive stage. This phenomenon should provide the opportunity to study the molecular mechanisms associated with these two different growth patterns, a major issue in understanding human bladder tumor progression.

Animals

Acoustic analysis of tracheo-oesophageal versus oesophageal speech.

In order to evaluate the vocal quality of tracheo-oesophageal and oesophageal speech, several objective acoustic parameters were measured in the acoustic waveform (fundamental frequency, waveform perturbation) and in the frequency spectrum (harmonic prominence, spectral slope). Twelve patients using tracheo-oesophageal speech (with the Provox valve) and 12 patients using oesophageal speech for at least two months, participated. The main results were that tracheo-oesophageal voices more often showed a detectable fundamental frequency, and that this fundamental frequency was fairly stable; there was also a tendency to more clearly defined harmonics in tracheo-oesophageal speech. This suggests a more regular vibratory pattern in the pharyngo-oesophageal segment, due to the more efficient respiratory drive in tracheo-oesophageal speech. So, a better quality of the voice can be expected, in addition to the longer phonation time and higher maximal intensity.

Evaluation Studies as Topic