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Biomedical subjects

H Navratil

Publications and source records attributed to H Navratil.

At least 37 records · Page 2Linked to original sources
PubMed1995

[Cancer of the prostate. 2. Physiology and cellular development].

Prostatic cancer is the second most frequent cancer in men in industrialised countries. The histological analysis of its initial development demonstrates the existence of precancerous lesions, PIN. The initial presence of several different cell populations accounts for the development of contingents of hormone-sensitive and hormone-resistant cells. The presence of numerous neuroendocrine cells appears to be a factor of poor prognosis. Hormones are intimately involved in the development of prostatic cancer and are an integral part of its treatment. Progress in molecular biology has furthered out knowledge of this disease. In particular, growth factors such as EGF and FGF are particularly involved and are starting to have a clinical application. The oncogene and anti-oncogene system is currently being explored (particularly p53 abd BCL 2). They are the basis for carcinogenesis and analysis of these factors will allow a better approach to the mechanisms of tumour induction and development.

Androgens↗
PubMed1995

[Effectiveness of and tolerance to intracavernous injection of moxisylyte in patients with erectile dysfunction: effect/dose relationship versus placebo].

The authors investigated the optima dose (efficacy and safety) of moxisylyte, an alpha-blocking agent, in a double-blind placebo-controlled crossover study in 30 patients. The origin of the erectile dysfunction was predominantly psychological in 14 patients and neurological in 16 patients. Each patient received 4 intracavernous injections in a randomized order (placebo, 10, 20, 30 mg of moxisylyte) at 7-day intervals. Regardless of the dose, moxisylyte induced significantly greater penile responses than placebo on all erection criteria. The frequency of responses allowing sexual intercourse appeared to be dose-dependent in the two aetiological groups. The erectile responses most frequently obtained were complete rigidity in the "neurological" group and tumescence in the "psychological" group. The safety was excellent for 95.6% of injections and no case of priapism was observed. One patient (neurological patient) experienced two prolonged erections after the dose of 20 mg and another patient (psychological patient) reported 2 headaches after the dose of 30 mg. No pain was experienced on injection. Moxisylyte is very well tolerated and is able to induce an erectile response from the dose of 10 mg. This dose appears to be sufficient in patients with central neurological erectile dysfunction; a dose of 20 mg tends to improve the quality of response in patients with a predominantly psychological disorder, although the differences observed between the doses were not statistically significant in this number limited of patients.

Adult↗
PubMed1994

Analysis of the whole CFTR coding regions and splice junctions in azoospermic men with congenital bilateral aplasia of epididymis or vas deferens.

Several recent studies have demonstrated the presence of mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene in healthy males with infertility caused by congenital absence of the vas deferens (CBAVD), previously recognized as an idiopathic genetic condition distinct from CF. In order to document further the genetic commonality of these two disorders, we undertook a double screening of the entire coding and flanking sequences of the CFTR gene, by using single-strand conformational polymorphism analysis and denaturing gradient gel electrophoresis in 12 unrelated infertile men with abnormalities of the vas deferens and/or epididymis. This strategy allowed us to identify 11 DNA sequence alterations considered as CF-causing mutations and several variations. Despite this double analysis, only two patients out of eight with CBAVD could be demonstrated as compound heterozygotes for CF mutations.

Adult↗
PubMed1994

Tissue-type plasminogen activator level is decreased in human seminal plasma with abnormal liquefaction.

OBJECTIVE: To determine plasminogen activators (PAs) and PA inhibitor levels in seminal plasma of patients attending an infertility clinic. DESIGN: Quantification by immunologic method of PAs in seminal plasma. SETTING: Patients of Department of Urology and Andrology, University Hospital, Nimes, France. PATIENTS: Ninety-two men attending for assessment because of infertility. INTERVENTIONS: Semen were collected by masturbation. Usual sperm parameters were determined; immediately after liquefaction, samples were snap-frozen at -85 degrees C until used for immunologic determination. MAIN OUTCOME MEASURES: Tissue-type PA antigen, urokinase-type PA antigen, and type 1 PA inhibitor antigen levels in seminal plasma. RESULTS: Median values of PA were 270 ng/mL (tissue-type PA) and 5.4 ng/mL (urokinase-type PA) in normozoospermia; 290 ng/mL (tissue-type PA) and 5.7 ng/mL (urokinase-type PA) in oligozoospermia; 325 ng/mL (tissue-type PA) and 3.5 ng/mL (urokinase-type PA) in oligoasthenozoospermia. Type 1 PA inhibitor antigen levels were often under detection limit. Tissue-type PA was 173.5 ng/mL in semen with abnormal liquefaction and 290 ng/mL in semen with normal liquefaction. CONCLUSION: The study confirmed the presence of both types of PAs in seminal plasma, tissue-type PA being largely predominant. No difference was found in tissue-type PA, urokinase-type PA, or type 1 PA inhibitor antigen levels between normal and oligozoospermic semen nor between normal and asthenozoospermic semen. On the other hand, semen with abnormal liquefaction had significantly lower tissue-type PA level than normal semen.

Adult↗
PubMed1994

[Renal nephrogenic nephroma: an little known exceptional tumor. Apropos of a case disclosed by xanthogranulomatous pyelonephritis].

The authors report a new case of an exceptional benign renal tumour: nephronogenic nephroma, composed of differentiation of the blastema into primitive nephronic formations. It raises the problem of differential diagnosis with adult Wilms' tumour and renal blastematosis. In this patient, it was associated with segmental xanthogranulomatous pyelonephritis, presenting in the form of psoïtis and an abscess of the thigh. Total nephrectomy was performed.

Abscess↗
PubMed1993

Multiple-dose pharmacokinetics of moxisylyte after oral administration to healthy volunteers.

The pharmacokinetics of moxisylyte in plasma and urine was investigated after oral administration. Twelve subjects were treated orally, twice daily with 240 mg of the drug for 6 days; on day 7, the subjects received a last dose of 240 mg of moxisylyte. Moxisylyte was assayed in plasma and urine by a specific HPLC method with fluorimetric detection. Moxisylyte was absorbed rapidly and changed to its metabolites immediately after drug administration; unchanged moxisylyte was not found in plasma. Two metabolites were found in plasma and urine: conjugated desacetylmoxisylyte (DAM) and the conjugate of desmethylated DAM (MDAM). The pharmacokinetic parameters determined after the first oral administration were not modified on multiple dosing. The apparent elimination half-lives of conjugated DAM and MDAM were 2.3 and 3.5 h, respectively. Elimination of these two metabolites in urine averaged 50 and 10%, respectively.

Administration, Oral↗
PubMed1993

Adrenergic receptors on smooth muscle cells isolated from human penile corpus cavernosum.

The effect of the alpha-adrenergic blocker moxisylyte was examined on smooth muscle cells isolated from human corpus cavernosum, and compared with that of other adrenergic agents and papaverine. Isolated smooth muscle cells were shown to contract (reduction of the mean cell length) under noradrenaline and carbachol stimulations in a time-dependent and concentration-dependent manner (maximum at 30 seconds, EC50 [noradrenaline] = 5 nM., EC50 [carbachol] = 1 nM.). The contractile effect of noradrenaline was dose-dependently inhibited by moxisylyte (IC50 = 0.5 +/- 0.2 microM.) and by prazosin (IC50 = 0.9 +/- 0.2 microM.). The dose-response curves were parallel and no statistically significant difference could be shown between the IC50 values. The alpha 2-adrenergic antagonist tolazoline also inhibited noradrenaline-induced contraction, whereas the alpha-adrenergic agonist methoxamine did not change the mean cell length. As expected, isoproterenol caused relaxation of noradrenaline-precontracted cells by interaction with a beta 2-adrenergic receptor. Papaverine was also found to inhibit the contraction induced by noradrenaline in a dose-dependent manner (IC50 = 2 +/- 0.3 nM.). Tritiated-dihydroergocryptine (3H-DHE) specific binding was competitively inhibited by moxisylyte and prazosin with the same IC50 value of 0.01 microM. Methoxamine and tolazoline also inhibited this binding with lower affinity (IC50 = 0.1 +/- 0.02 microM.), while isoproterenol did not change specific binding. Scatchard plots from saturation experiments with 3H-DHE and with 3H-N-methyl scopolamine revealed the presence of 15 times more adrenergic than muscarinic binding sites (650,000 and 45,000 sites per cell, respectively). Together, these data support evidence for the presence of postsynaptic alpha 1-adrenergic receptors on smooth muscle cells from human corpus cavernosum. These receptors are coupled with the contraction of the cell and are blocked by the alpha 1-adrenergic antagonists moxisylyte or prazosin. They also show that the phosphodiesterase inhibitor papaverine and the beta-adrenergic agonist isoproterenol induced relaxation. This model constitutes a new approach to study the potential targets of the adrenergic agents in the erectile tissue.

Dose-Response Relationship, Drug↗
PubMed1993

Carboplatin and urothelial tumors.

The prognosis of advanced-stage bladder cancer is poor. Chemotherapy, particularly regimens including platinum salts, appears to increase survival moderately but at the cost of severe, mainly renal toxicity. Platinum is a major factor in this toxicity, and new platinum salts (chiefly carboplatin) have therefore been developed. Carboplatin has no renal toxicity at usual doses, and its use does not require concomitant hyperhydration. Its gastrointestinal, otologic, and general tolerability is excellent. In contrast, most patients develop thrombocytopenia, which can be important, but which is always transitory. The platelet count reaches its nadir (grade 2 or 3) at around day 20, and the leukocyte nadir (grade 2 or 3) occurs about day 19. Anemia is rare. The literature on the use of carboplatin for the treatment of advanced-stage urothelial tumors is reviewed. Carboplatin is used at doses varying between 200 and 400 mg/m2, administered in 28-day courses. Dose adjustment is based on serum creatinine level, creatinine clearance, nadir blood cell levels, or previous treatment, reflecting the wide disparity between different studies. Used alone, carboplatin achieved objective responses (ORs) in 14% of patients (3% complete responses, CRs, and 11% partial responses, PRs) in a total group of 327 patients included in 13 trials. In polychemotherapy various combinations of carboplatin with other agents have been reported, most frequently carboplatin/methotrexate/vinblastine; the OR rate was 63% (CR rate 19% and PR rate 44%) among 88 patients in four studies. These results confirm the relative efficacy of carboplatin in the treatment of advanced-stage urothelial tumors, particularly when it is combined with other agents. Its efficacy is similar to that of cisplatin, but it is far less toxic. A prospective, comparative trial will be necessary to confirm these data. The pharmacokinetic behaviors of the two platinum salts are markedly different, as carboplatin does not undergo tubular metabolism. The efficacy of carboplatin could be optimized by adapting the dosage to the glomerular filtration rate, which is a more accurate method than extrapolation from the serum creatinine or creatinine clearance values. This has been shown in the case of nonseminomatous germ cell tumors. Calculation of the optimum carboplatin dose should now be applied to urothelial tumors. The general and renal tolerability of a platinum salt is an important element of choice when the efficacies are equivalent. These considerations fully warrant further clinical trials of carboplatin.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Is the volume injected a parameter likely to influence the erectile response observed after intracavernous administration of an alpha-blocking agent?

In 12 impotent patients with spinal cord injury, we assessed the erectile response induced by intracavernous administration of 20 mg moxisylyte dissolved in 4 different volumes of solvent. We tested successively in each patient 0.4, 0.8, 1.2 ml and the volume usually injected of 2 ml, with a 7-day interval between 2 injections. The reduction in the volume from 2 to 0.4 ml did not thwart the quality of erection obtained by the intracorporeal administration of 20 mg moxisylyte. Indeed, for each erectile parameter (rigidity, abdominopenile angle, length and circumference of the penis), no statistically significant difference arose between the 4 tests. All patients achieved full rigidity. Neither priapism nor prolonged erection occurred. These results suggest that discreet and easily handled small-sized injection pens, containing little solution, could be conceived for autoinjection therapy.

Adult↗
PubMed1993

Quantitative topographic distribution of epithelial and mesenchymal components in benign prostatic hypertrophy.

Excised tissue of benign prostatic hyperplasia from 15 men 60-89 years old was investigated by immunohistochemistry and specific histological staining. For each adenoma, 10 tissue sections (2-5 specimens per lobe according to its volume) were analyzed by computer-assisted image analysis (SAMBA 2002). There was evidence for a high ratio of stroma to glands: the mean proportions of glandular, muscular and fibrous areas were respectively 30.4, 14.9 and 54.7%. Each adenoma presented a homogeneous structure, but the proportions of the three tissue components differed significantly among adenomas (p < 0.001). These findings incite us to consider biopsy as a possible investigation of the morphology of benign prostatic hyperplasia, and thus we could choose an adequate therapy according to histologic composition.

Aged↗
PubMed1992

Moxisylyte plasma kinetics in humans after intracavernous administration.

Obtaining and sustaining an erection are common problems for the male spinal cord injury patient. Intracavernous injection of vasoactive substances offers a new treatment option but it must be approached with caution in this population. In this work, the use of an alpha-adrenergic blocking agent, moxisylyte, after intracavernous administration for complete paraplegic patients with erectile impotence is described. During this study, the pharmacokinetic profile of moxisylyte has been defined. Unchanged moxisylyte is not found in plasma, this drug is immediately metabolized after administration. Three metabolites were found in plasma: desacetylmoxisylyte (DAM), conjugated DAM, and conjugates of desmethylated DAM (MDAM). Maximum plasma levels of 72.3 ng ml-1, 301.4 ng ml-1, and 88.8 ng ml-1 are obtained 0.22 h, 0.9 h, and 2.08 h after drug administration for these three metabolites, respectively. The elimination half-lives are 0.89 h, 2.16 h, and 5.32 h and the MRT, 1.38 h, 3.23 h, and 8.45 h, respectively. No side-effects were noted, only one patient presented sleepiness. Successful erections (10 to 25 min) were obtained in all patients and no priapism was noted.

Adult↗
PubMed1992

Disposition of roxithromycin in the epididymis after repeated oral administration.

The epididymal penetration of roxithromycin was studied in order to evaluate the drug for use in the treatment of epididymo-orchitis. Seventeen patients hospitalized for surgery as part of treatment for prostatic adenoma or prostatic cancer were premedicated orally with roxithromycin 150 mg bd for three days followed by 150 mg pre-operatively (3 h before surgical incision). Roxithromycin concentrations in serum and epididymis were determined by microbiological assay. The mean epididymal concentrations were 6.48 +/- 4.88 and 5.98 +/- 3.92 mg/kg for left and right epididymis respectively and the corresponding mean tissue/serum ratios 0.88 +/- 0.57 and 0.84 +/- 0.53. The wide intersubject variation in the concentration of roxithromycin found in serum and tissue is commonly seen with other macrolide antibiotics. The concentrations observed in this study in serum and tissue were greater than the MIC90s for Chlamydia trachomatis (0.25 to 1 mg/L), and Ureaplasma urealyticum (0.5 mg/L).

Adenoma↗
PubMed1992

Clinical study of the longitudinal deformation of the flaccid penis and of its variations with aging.

The length changes of the flaccid penis provoked by a maximum manual stretching of the glans have been measured in 905 men in order to study its biomechanical qualities. Our study shows that the flaccid penis is deformable, extensible and elastic in its longitudinal axis. The analysis of the variations of these biomechanical properties with aging shows a significant decrease. Thus, the biomechanical behavior of the flaccid penis during stretching is highly different in young men and old men. This distortion difference according to age proves the physiological importance of the penile distortion since impotence significantly increases with age. As the vascular mechanisms may be disregarded during flaccidity, these penile physical features of the flaccid penis are only due to tissue mechanisms. Consequently, any distortion loss would reflect a tissue impairment, very likely a progressive senile fibrosis of cavernous tissues.

Adolescent↗
PubMed1992

[Therapeutic indications and complementary explorations in benign prostatic hypertrophy: significance of simultaneous recordings].

Dysuria due to obstruction by benign prostatic hypertrophy causes an increase in the bladder work and constitutes the origin of alterations in the bladder wall. Although initially reversible, the progression towards fibrosis makes recovery increasingly incomplete the longer the treatment is delayed. The detection and evaluation of increased bladder work in the presence of early obstruction allows treatment to be instituted early in the natural history of the disease. Although clinical examination may be suggestive of bladder neck obstruction, it is neither characteristic of the bladder repercussions nor sufficient to define a population at risk. Similarly, voiding urethrography, uroflowmetry or cystomanometry, taken separately, are unable to assess bladder work early in the disease. However, bladder work can be studied by recording the voiding intravesical pressure (measured by a suprapubic catheter) in relation to the urine flow (measured by uroflowmetry). By studying the variations in voiding pressure in relation to initiation of micturition, a parameter can be defined which is useful for the therapeutic indication: the PVOP (pre-voiding opening pressure of the bladder neck), which is able to distinguish 2 mechanisms of obstruction: "compression" characterised by a raised PVOP, as in the case of benign prostatic hypertrophy, and "stenosis", with an unchanged PVOP, as in the case of urethral stricture. Re-evaluation after prostatectomy shows a return to normal of the PVOP. The difficulty of routinely inserting a suprapubic catheter has led to the development of indirect approaches, particularly voiding hydrodynamic morphological or transrectal ultrasonographic methods.

Humans↗
PubMed1992

[Postoperative rectoprostatic fistulas. Report of 2 cases. Review of the literature].

The authors report two cases of acquired prostatorectal fistulae after TURP, which were treated by a Kraske approach. They review the literature of iatrogenic fistulae and all of the techniques of approaching the prostatorectal region. If the bladder drainage is always necessary and may be sufficient in as much as 34% of the patients, the need for a colostomy and the choice of the approach is discussed.

Aged↗