Biomedical subjects
Publications and source records attributed to H J Leisinger.
Doxazocin in association with finasteride is more efficient than doxazocin or finasteride alone to treat the urinary symptoms due to HBP. Finasteride alone or in combined treatment is more efficient than doxazocin on the prevention of the risk of acute urinary retention. Only finasteride in a long term use seems to reduce the need of surgery.
PURPOSE: Successful photodynamic therapy of epithelial cancer requires a specific photosensitization of malignant tissue. We evaluate the intensity and localization of protoporphyrin IX (PpIX) in superficial transitional cell carcinoma and nonmalignant cells of the human bladder following topical administration of its precursor, either aminolevulinic acid (ALA) or hexylester aminolevulinate (HAL). MATERIALS AND METHODS: Solutions of ALA or HAL were instilled into the bladder of 18 patients presenting with recurrent transitional cell carcinoma. The distribution of PpIX through the bladder wall was studied on frozen biopsies using fluorescence microscopy and correlated with pathological findings. RESULTS: Topical bladder instillation with 180 mmol (3%) ALA administered for 6 hours or 8 mmol (0.2%) HAL administered for 4 hours gave similar results regarding intensity and tissue distribution of PpIX fluorescence, whereas 8 mmol HAL administered for 2 hours followed by 2 hours of resting time (2+2 hours concept) induced a PpIX fluorescence twice as high. The fluorescence remained limited to cancer cells. Only a trace of PpIX fluorescence was observed in suburothelial connective tissue, that is chorion, but none in the bladder smooth muscle regardless of experiment conditions. CONCLUSIONS: HAL is an excellent precursor for PpIX synthesis in bladder cancer. With the 2+2 hour topical administration condition it yielded the highest PpIX fluorescence intensity and fluorescence contrast between normal and malignant urothelial cells. This approach allows us to optimize PpIX tissue distribution for photodynamic therapy in superficial bladder cancer.
Extracorporeal shock wave lithotripsy and ureteroscopy are minimal invasive techniques, both of which have definitively become essential for the treatment of ureteral stones resistant to conservative treatment. At the time of evidence-based medicine, no study makes it possible to recommend one of these methods rather than the other. For stones of identical size and location, this review of the literature shows that extracorporeal shock wave lithotripsy and ureteroscopy prove of comparable effectiveness and innocuousness. The urologist thus has two alternatives of which the technical control, the availability of the endoscopes or lithotriptors as well as the desire and comfort of the patients are the factors which condition his choice of the method for the treatment of ureteral stones.
Although intracytoplasmic sperm injection (ICSI) revolutionized treatment and prognosis of male infertility, checkup (case history, clinical and paraclinical examinations) practiced by urologist in infertile man keeps all its place. Varicocele, congenital or acquired seminal duct obstruction, urogenital tract infection, or ejaculation disorder must be sought, because these affections remain accessible to treatment.
Tumor-associated angiogenesis is emerging as an important prognostic factor and represents a hopeful potential therapeutic target for the cancer treatment. Bladder tumors, as all solid tumors, require an active angiogenesis to support their growth and progression. The angiogenic phenotype observed within a tumor is determined in large part by the balance between stimulatory and inhibitory inputs to the endothelial cells. Clinically, the importance of the angiogenic response observed within a tumor should be considered as an independent prognostic factor for superficial as well as invasive bladder tumors. The analysis of the angiogenic response could in the future influence the therapeutic strategy. Angiogenesis also represents a promising new therapeutic target, and is at the moment intensively tested in experimental and clinical trials. In this article, we will first review the mechanism of angiogenesis, and then its implication in bladder cancer, and as a potential therapeutic target.
Bladder transitional cell carcinoma, limited to the lamina propria, or superficial in 80% of the cases, is characterized by a high recurrence rate up to 70% in the three years following the first treatment. However, the constant evolution of the endoscopic techniques, useful to its diagnosis and treatment, contributed to reduce about by half this recurrence rate at three months. The actual development concerns new fluorescence detection methods, adapted to the standard endoscopic equipment. This new technique or fluorescence cystoscopy aims at improving the visual contrast between tumor and normal tissue in order to obtain a precise mapping of the diseased bladder. Thus, it allows to detect a carcinoma in situ (CIS) with a sensitivity around 80 to 90%. Its impact on the progression of the disease remains however to be demonstrated.
For many reasons, such as toxicity and lack of selectivity of photosensitisers, as well as complexity of technical procedures and inconstant therapeutic results, photodynamic therapy of highly recurrent superficial bladder cancer never gained wide acceptance in the urological community. However, the 25 years of experience combined with the recent discovery of new photosensitisers, such as protoporphyrin IX (PpIX) induced by 5-aminolevulinic acid (ALA) or ALA-derivatives or hypericin open new, very interesting perspectives in this therapeutic field.
INTRODUCTION: In order to be able to influence and monitor future developments for urologists, strategies should be promoted in advance to guarantee the future of the speciality and to accommodate the inevitable changes. Faced with this challenge, the EAU, through its Strategy Planning Office (SPO), has prepared a document which is offered, here, in abbreviated form, to the European and international urological communities for general consideration. MATERIAL AND METHODS: A group of subjects, related to the domains and internal consistency of urology as a speciality, were selected and discussed among the members of the SPO and later submitted to open consultation among distinguished members of the urological community. The topics selected for discussion included: what is urology; urology in the university; sub-specialization in urology; training in urology; does kidney transplantation belong to urology, and others. RESULTS: It is shown that urology is going through an exciting and hazardous transition period. Urology has conflicting problems in its traditional domains due to changes in health care policy, and internal identification problems due to its permanent expansion and sub-specialization options. Weaker points are its relation with primary care medicine (shared care options), the presence and role of urology in institutions such as the university, department of surgery, children's hospitals, administration, etc.; the desegregating effect of the sub-specialities; the increasing encroachment of other specialities, and the increasing outpatient effect of technological progress. CONCLUSIONS: An action plan is proposed to confront these changes without losing manpower, internal consistency or social image and improving patient care quality, excellence of training and scientific progress.
INTRODUCTION: In order to be able to influence and monitor future developments for urologists, strategies should be promoted in advance to guarantee the future of the speciality and to accommodate the inevitable changes. Faced with this challenge, the EAU, through its Strategy Planning Office (SPO), has prepared a document which is offered, here, in abbreviated form, to the European and international urological communities for general consideration. MATERIAL AND METHODS: A group of subjects, related to the domains and internal consistency of urology as a speciality, were selected and discussed among the members of the SPO and later submitted to open consultation among distinguished members of the urological community. The topics selected for discussion included: what is urology; urology in the university; sub-specialization in urology; training in urology; does kidney transplantation belong to urology, and others. RESULTS: It is shown that urology is going through an exciting and hazardous transition period. Urology has conflicting problems in its traditional domains due to changes in health care policy, and internal identification problems due to its permanent expansion and sub-specialization options. Weaker points are its relation with primary care medicine (shared care options), the presence and role of urology in institutions such as the university, department of surgery, children's hospitals, administration, etc.; the desegregating effect of the sub-specialities; the increasing encroachment of other specialities, and the increasing outpatient effect of technological progress. CONCLUSION: An action plan is proposed to confront these changes without loosing manpower, internal consistency or social image and improving patient care quality, excellence of training and scientific progress.
Proper function of the wall of bladder requires gap junctional communication for coordinating the responses of smooth muscle (SMC) and urothelial cells exposed to urine pressure. In the rat bladder, Cx43 is expressed by SMC and urothelial cells, whereas Cx26 expression is restricted to the epithelium. We used a model of bladder outlet obstruction, in which a ligature is placed around the urethra to increase voiding pressure. Increased fluid pressure was associated with increased Cx43 and Cx26 mRNA expression and with the activation of a signaling cascade including the transcription factor c-Jun, which is a component of the AP-1 complex. The signaling pathway of the c-Jun NH2 terminal kinase (JNK) requires the presence of the scaffold protein Islet-Brain1/c-Jun amino-terminal kinase Interacting Protein-1 (IB1/JIP-1). Under stress conditions resulting from urine retention, we have found a reduced content of IB1/JIP-1 in urothelial cells, which in turn induced a drastic increase of JNK and AP-1 binding activities. The stress-induced activation of JNK was prevented by overexpressing IB1/JIP-1, using a viral gene transfer approach, a condition which also resulted in a decrease in Cx26 mRNA. The data show that: 1) mechanical stress of urothelial cells activates in vivo JNK, as a consequence of a regulated expression of IB1/JIP-1 and 2) that urothelial Cx26 may be directly regulated by the AP-1 complex.
PURPOSE: Prostate cancer is the most commonly diagnosed cancer in the United States. The diagnosis or followup of prostate cancer in men older than 50 years is based on digital rectal examination, measurement of the free-to-total prostatic specific antigen ratio and transrectal ultrasound assisted needle biopsy of the prostate. We developed and evaluated a noninvasive method for diagnosing prostate cancer based on the measurement of telomerase activity after prostatic massage in fresh voided urine or after urethral washing. MATERIALS AND METHODS: We obtained 36 specimens of cells after prostatic massage in the fresh voided urine of 16 patients who subsequently underwent radical prostatectomy and after urethral washing in 20 who underwent prostate needle biopsies. Ethylenediaminetetraacetic acid was immediately added to the collected urine or washing to a final concentration of 20 mM. After protein extraction by CHAPS buffer each specimen was tested for telomerase activity in a 2-step modified telomeric repeat amplification protocol assay. The 2 prostate cancer cell lines PC-3 and LNCaP with high telomerase activity were used as a positive control. RESULTS: Telomerase activity was detected in 14 of 24 samples with known prostate cancer (sensitivity 58%). In contrast, no telomerase activity was found in the 12 cases without histological evidence of prostate tumor (specificity 100%). Eight of 9 poorly differentiated cancers expressed telomerase activity (89%), while only 6 of 15 well and moderately differentiated cancers showed telomerase activity (40%). CONCLUSIONS: Our data illustrate that telomerase activity may be detected in voided urine or washing after prostatic massage in patients with prostate cancer. Sensitivity was higher for poorly differentiated tumors. This approach is not currently available for detecting prostate cancer in clinical practice. However, these results are promising and further studies are ongoing.
Phage display is a powerful method of isolating of antibody fragments from highly diverse naive human antibody repertoires. However, the affinity of the selected antibodies is usually low and current methods of affinity maturation are complex and time-consuming. In this paper, we describe an easy way to increase the functional affinity (avidity) of single chain variable fragments (scFvs) by tetramerization on streptavidin, following their site-specific biotinylation by the enzyme BirA. Expression vectors have been constructed that enable addition of the 15 amino acid biotin acceptor domain (BAD) on selected scFvs. Different domains were cloned at the C-terminus of scFv in the following order: a semi-rigid hinge region (of 16 residues), the BAD, and a histidine tail. Two such recombinant scFvs directed against the carcinoembryonic antigen (CEA) were previously selected from human non-immune and murine immune phage display libraries. The scFvs were first synthesized in Escherichia coli carrying the plasmid encoding the BirA enzyme, and then purified from the cytoplasmic extracts by Ni-NTA affinity chromatography. Purified biotinylated scFvs were tetramerized on the streptavidin molecule to create a streptabody (StAb). The avidity of various forms of anti-CEA StAbs, tested on purified CEA by competitive assays and surface plasmon resonance showed an increase of more than one log, as compared with the scFv monomer counterparts. Furthermore, the percentage of direct binding of 125I-labeled StAb or monomeric scFv on CEA-Sepharose beads and on CEA-expressing cells showed a dramatic increase for the tetramerized scFv (>80%), as compared with the monomeric scFv (<20%). Interestingly, the percentage binding of 125I-labeled anti-CEA StAbs to CEA-expressing colon carcinoma cells was definitely higher (>80%) than that obtained with a reference high affinity murine anti-CEA mAb (30%). Another advantage of using scFvs in a StAb format was demonstrated by Western blot analysis, where tetramerized anti-CEA scFv could detect a small quantity of CEA at a concentration 100-fold lower than the monomeric scFv.
For economic reasons, the tendency in western communities is to simplify the investigations for a given pathology. This case is typically the one where some more money has to be invested to achieve the correct diagnosis.
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We report a case of renal metastases from prostate cancer to show that the possibility of tumor metastasis, although rare, should always be considered in the differential diagnosis of renal mass.
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Germ cell tumours (GCT) of the testis are the most common malignant tumours occurring in young adults. In view of the young age of patients, the increasing incidence of GCT and the overexpression of wild-type p53 observed in a majority of tumours, the possibility of the involvement of a virus in the development of this cancer was considered. Testicular GCT were analysed for the presence of cytomegalovirus and Epstein-Barr virus (EBV), which are known to cause overexpression of wild-type p53 protein, and parvovirus B19. The testicular tissue of 39 patients with testicular GCT and 12 patients with healthy testicular tissues was tested for presence of viral DNA by PCR. Neither cytomegalovirus nor EBV DNAs were detected in the 39 tumours analysed, but parvovirus B19 DNA sequences were demonstrated in the testicular tissue of 85% (33/39 cases) of patients with GCT. The sera of 16 of the 39 patients with GCT were tested for the presence of parvovirus B19 IgM and IgG. B19-specific IgG was detected in the sera of 11 patients (69%). Only one case was positive for parvovirus B19 IgM, which was also shown to have B19 genome sequences in the serum by PCR, indicating that in a majority of cases an acute B19 infection can be excluded as being the source of the B19 DNA sequences in the testis. B19 DNA could not be detected in normal testicular tissue and thus parvovirus B19 could play a role, direct or indirect, in the development of testicular GCT or have tropism for the tumour cells.
Day surgery in urology is in full growth actually. The present report is based on our first 120 patients. Low post-operative complication rate, patients' satisfaction and economical savings are the main factors for the important increase in this type of surgery.