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Biomedical subjects

A Jungwirth

Publications and source records attributed to A Jungwirth.

At least 19 recordsLinked to original sources

One 10-core prostate biopsy is superior to two sets of sextant prostate biopsies.

OBJECTIVES: To compare the efficiency of different transrectal ultrasonography (TRUS)-guided prostate biopsy techniques for detecting prostate cancer. MATERIALS AND METHODS: In all, 81 prostates from radical prostatectomy were used and two consecutive sets of sextant biopsies and one 10-core biopsy taken in each specimen. The 10-core biopsy consisted of a sextant biopsy and four cores from the far lateral areas of the prostate. To simulate a transrectal biopsy procedure, all biopsies were taken under TRUS guidance. RESULTS: In the first set of sextant biopsies 44 prostate cancers (54%) were detected and in the second set 51 (63%). Combining both sets of sextant biopsies 57 (70%) of the carcinomas were detected. One set of 10-core biopsies detected 66 (82%) of all prostate cancers. Overall, with the 10-core biopsies 16% more prostate tumours were diagnosed than with two consecutive sets of sextant biopsies. To find the same number of prostate cancers as with the 10-core technique, 14% of patients undergoing sextant biopsy would require a second set and 11% at least a third set of biopsies. CONCLUSIONS: The 10-core prostate biopsy technique is superior to the commonly used sextant technique and could spare patients unnecessary repeated biopsy. Even after including a second set of sextant biopsies, the total detection rate with these 12 biopsies was inferior to the 10-core technique.

Biopsy, Needle↗

Acrosome reaction in Chlamydia-positive and negative patients.

Chlamydia trachomatis infections might have a detrimental effect on various sperm functions. Data concerning the effect of C. trachomatis on the capacitation activity of sperms are lacking. The study was undertaken to evaluate whether chlamydial infection influences acromsome reaction (AR). Three groups of men were investigated for ARs -Chlamydia negative (n = 46) and positive (n = 30) patients, and healthy men (n = 53) undergoing vasectomy. The fluorescence technique for the evaluation of AR was applied. The normal range for the induction of AR was assumed DeltaAR > 12.5% for this technique. Seminal plasma was examined for IgA antibodies against C. trachomatis. There was a significant difference in AR between healthy volunteers, Chlamydia-negative and Chlamydia-positive patients. DeltaARs were 15.8 +/- 1.6% in healthy volunteers versus 12.15 +/- 2.4% in Chlamydia-negative and 9.08 +/- 1.8% in Chlamydia-postive patients, respectively (P < 0.05). Significant elevated titres of C. trachomatis-specific IgA in seminal plasma showed a negative correlation with the AR of spermatozoa. AR seems to be a valuable marker, especially in couples with idiopathic infertility.

Acrosome Reaction↗

Association of DHEA-S and estradiol serum levels to symptoms of aging men.

OBJECTIVES: A number of interactions between age-related changes in serum levels of dehydroepiandrostendione sulfate (DHEA-S) and estradiol and symptoms of aging men have been proposed, yet data regarding this issue are scant. We therefore set up a prospective study to analyze these associations. METHODS: In a prospective, cross-sectional study, men aged 45-85 years were recruited. All men completed a questionnaire containing 38 items covering a number of aspects of the aging male. Questionnaires were compiled by using items from previously published and validated questionnaires. Several socioeconomic parameters were also determined. In parallel, serum levels of testosterone, free testosterone, luteinizing hormone (LH), follicle stimulating hormone (FSH), DHEA-S, estradiol, sex hormone binding globulin and prostate-specific antigen (PSA) were quantified by commercially available immunoassays. RESULTS: A total of 375 men with a mean age of 59.9 +/- 9.2 years (mean +/- standard deviation) were analyzed. Average DHEA-S and estradiol levels of 135.8 +/- 90.9 micrograms/dl and 29.7 +/- 14.6 pg/ml, respectively, were recorded. DHEA-S serum levels were negatively correlated to patient age, sexual function score, total score and PSA. Estradiol serum levels were positively correlated to testosterone and free testosterone. None of the other scores or questions revealed a correlation with DHEA-S or estradiol serum levels. CONCLUSION: This prospective study elucidates only small interactions between partial androgen deficiency of the aging male (PADAM)-related symptoms and serum levels of DHEA-S and estradiol. Nevertheless, the data suggest an impact of DHEA-S on sexual function.

Age Factors↗

Effective long-term androgen suppression in men with prostate cancer using a hydrogel implant with the GnRH agonist histrelin.

OBJECTIVES: To evaluate the effectiveness of a hydrogel implant containing the gonadotropin-releasing hormone (GnRH) agonist histrelin in suppressing testosterone production in men with prostate cancer and to determine the effective dose (one, two, or four implants). METHODS: Forty-two men with prostate cancer and indications for androgen ablation were treated with one, two, or four implants. In two of the clinics, comprising 27 subjects, the treatment period was 12 months, with replacement with the same number of implants at 12-month intervals. In a third clinic, which treated 15 subjects, the implants were left in place for up to 30 months. The total experience was 605 treatment months. RESULTS: The histrelin levels were detected in serum proportional to the number of implants placed. The response, however, was similar among all three dose levels, with testosterone and luteinizing hormone essentially completely suppressed. Serum testosterone levels decreased from 21.9 +/- 17.6 nmol/L to 0.93 +/- 1.57 nmol/L within 1 month and were maintained at 0.55 +/- 0.24 nmol/L at 6 months and 0.60 +/- 0.28 nmol/L after 12 months of treatment. Of the 38 assessable patients, 35 (92%) had castrate levels of testosterone within 4 weeks of the initial implant placement. All patients followed for up for 12 months after placement of the initial set of implants maintained suppression of testosterone production while the implant was in place. CONCLUSIONS: The histrelin hydrogel implant provided adequate and reliable delivery of the potent GnRH agonist histrelin during at least 1 year using a single implant in men with prostate cancer. No apparent advantages were found in using more than one implant, and the question of the possible effectiveness of even lower doses remains open. This treatment modality appears to be both safe and effective.

Aged↗

Prostate cancer detection with two sets of ten-core compared with two sets of sextant biopsies.

OBJECTIVES: To compare the cancer detection of two consecutive sets of prostate biopsies using either the sextant or the 10-core technique. METHODS: Ninety-one specimens after radical prostatectomy were used and consecutive sets of biopsies were performed ex vivo on each prostate after the operation. The sextant biopsies were taken paramedian and midlobular, three per side. For the 10-core biopsies, two cores per side from the lateral areas of the prostate were added. We developed a realistic simulation of a transrectal sonographic biopsy procedure. RESULTS: In the first set of sextant biopsies, 55 prostate cancers (60.4%) were found; in the second set, 13 additional tumors were detected. Two consecutive sets of sextant biopsies thus found 68 tumors (74.7%). Using one 10-core biopsy led to cancer detection in 71 of the prostates (78%). A second 10-core biopsy revealed 11 additional tumors, for a cumulative cancer detection rate of 90.1%. We found that 9 (9.9%) of all the cancers were not diagnosed by two consecutive sets of this extended biopsy protocol. Eight of these cancers (88.9%) were clinically significant as determined by a tumor volume larger than 0.5 cm(3). CONCLUSIONS: Although the 10-core protocol is far superior to the commonly used sextant protocol, a significant number of prostate cancers can still be found on a second similar set of prostate biopsies. Even after two consecutive sets of 10-core biopsies, approximately 10% of the prostate tumors remained undetected. Most of them were clinically significant.

Biopsy, Needle↗

Clinical outcome of microsurgical subinguinal varicocelectomy in infertile men.

The present study assesses the clinical outcome of microsurgical subinguinal varicocelectomy in infertile men, especially with regard to sperm count, motility and fertility. Between June 1990 and October 1998, 272 patients had subinguinal microsurgical varicocelectomy operations for clinical varicoceles, and their long-term results were assessed. In nearly all the patients there was a significant improvement in sperm count and sperm motility after 3 and 6 months. Very few complications arose from this procedure. We concluded that microsurgical subinguinal varicocelectomy is an effective treatment for clinical varicoceles in infertile men. The significant improvement in the quality of spermatozoa, the low complication rates and the remarkably high pregnancy rates make this a valuable alternative to in vitro reproduction techniques.

Adolescent↗

[Physiology and pathophysiology of erectile dysfunction].

Erectile dysfunction is an entity associated with age but is not necessarily a consequence of aging. During erection the penis acts as a capacitor--accumulating blood under pressure. Erectile function is, therefore, dependent on the integration and regulation of functional interplay between psychologic, neurologic, endocrine and vasoactive factors. Any imbalance in the integration of these factors will result in erectile dysfunction. Trabecular smooth muscle is an important structure, which contributes to control of detumescence and erection. The smooth muscle tone is mediated by many hormones and vasoactive factors (e.g. norepinephrine, acetylcholine, NO, VIP, prostaglandins etc.) but its functioning is also dependent on a sufficient oxygenation to prevent the fibrosis of this important structure. This oxygenated state is achieved during erections. So we can conclude: Erections are good for erections.

Adult↗

Inhibition of the growth of Caki-I human renal adenocarcinoma in vivo by luteinizing hormone-releasing hormone antagonist Cetrorelix, somatostatin analog RC-160, and bombesin antagonist RC-3940-II.

BACKGROUND: Metastatic or recurrent renal cell carcinoma (RCC) is a therapeutic challenge because it is resistant to chemotherapy and external radiotherapy. No uniformly effective therapeutic agents are available for the management of patients with RCC. Hormones and growth factors may play a role in promoting the transformation and/or proliferation of kidney neoplasms. METHODS: Luteinizing hormone-releasing hormone (LH-RH) antagonist Cetrorelix (SB-75), somatostatin analog RC-160, and bombesin antagonist RC-3940-II were tested for their effects on the growth of the Caki-I renal adenocarcinoma cell line xenografted into nude mice. RESULTS: After 4 weeks of treatment, tumor volume was significantly (P < 0.01) decreased in animals receiving RC-160, to 167.5 +/- 34.2 mm3, compared with the control group (485.7 +/- 77.2 mm3). LH-RH antagonist SB-75 and bombesin antagonist RC-3940-II also significantly reduced the volume of Caki-I tumors, to 159.9 +/- 18.1 and 234.7 +/- 81.8 mm3, respectively. Somatostatin analog RC-160 decreased serum levels for growth hormone (GH) and insulin-like growth factor-I compared with controls. Treatment with RC-160, Cetrorelix, and RC-3940-II significantly reduced the number of high-affinity receptors for epidermal growth factor on Caki-I tumors. CONCLUSIONS: LH-RH antagonist Cetrorelix, somatostatin analog RC-160, and bombesin antagonist RC-3940-II effectively inhibit the growth of human Caki-I renal adenocarcinomas in nude mice. These peptide analogs should be considered for the therapy of patients with metastatic or recurrent RCC.

Animals↗

[A pill for the man? Current status of fertility control in the man].

Taking all facts into consideration from animal experiments and clinical studies with regard to the development of a male contraceptive you must be aware that the 'pill for men' will hardly be available in this century. Because of the increasing interest of the industry and the effort of the WHO and other similar institutions, like the Population Council of New York, to develop a male pill the stagnation of the past 20 years could be overcome, and it may be possible to have an adequate method in 2005. In all probability this will be a combination of hormones either from a gestagen plus testosterone preparation or a potent LHRH agonist and/or antagonist, also in combination with a long-acting testosterone preparation, with testosterone levels within the normal range. Nowadays it cannot be said which role gossypol will finally play. There are studies going on with gossypol with some promising results.

Contraceptive Agents, Male↗

Decrease in the level and mRNA expression of LH-RH and EGF receptors after treatment with LH-RH antagonist cetrorelix in DU-145 prostate tumor xenografts in nude mice.

Using radioligand binding, RT-PCR, and Southern blot analyses, we evaluated whether agonist [D-Trp6]LH-RH and antagonist Cetrorelix could affect the levels of receptors for LH-RH and EGF and expression of mRNA for these receptors in DU-145 human androgen-independent prostate cancers xenografted into nude mice. Radioligand binding studies showed the presence of specific high affinity receptors for LH-RH and EGF in DU-145 prostate tumors. Cetrorelix, but not [D-Trp6]LH-RH significantly inhibited tumor growth. The concentration of LH-RH receptors was reduced by 22% (p<0. 05) and 67% (p<0.01) after 4 weeks of treatment with [D-Trp6]LH-RH and Cetrorelix respectively. The concentration of EGF receptors fell by 48% (p<0.05) in the [D-Trp6]LH-RH group, whereas Cetrorelix led to a 66% reduction (p<0.01). The expression of LH-RH and EGF receptor mRNA was investigated by RT-PCR analysis followed by Southern blotting. Densitometric analysis of the developed bands showed that the antagonist Cetrorelix decreased the expression of LH-RH receptor mRNA by 55% (p<0.01) compared to control group while the 20% reduction after treatment with the LH-RH agonist was non-significant. Treatment with [D-Trp6]LH-RH and Cetrorelix also reduced the expression of EGF receptor mRNA by 35% and 68% respectively (both, p<0.01) compared to control group. In conclusion, these data demonstrate that growth inhibition of DU-145 prostate tumors induced by prolonged administration of LH-RH antagonist Cetrorelix is accompanied by a marked decrease in the concentration of LH-RH and EGF receptors as well as in their mRNA levels.

Animals↗

Luteinizing hormone-releasing hormone antagonist Cetrorelix (SB-75) and bombesin antagonist RC-3940-II inhibit the growth of androgen-independent PC-3 prostate cancer in nude mice.

BACKGROUND: Hormones like bombesin (BN)/gastrin-releasing peptide (GRP) and luteinizing hormone-releasing hormone (LH-RH) and growth factors such as epidermal growth factor (EGF) might be involved in the relapse of prostate cancer under androgen ablation therapy. Interference with receptors for BN/GRP, LH-RH, or EGF might provide a therapeutic approach to inhibit tumor growth of androgen-independent prostate cancer. METHODS: LH-RH antagonist Cetrorelix (SB-75) and the BN/GRP antagonist RC-3940-II were tested for their effects on the growth of the androgen-independent PC-3 human prostate cancer cell line xenografted into nude mice. Tumor growth, serum hormone levels, and receptor concentrations for BN/GRP and EGF were measured. RESULTS: When the treatment was started, tumor volume in all groups was 70-80 mm3. After 4 weeks, tumor volume in the control animals injected with saline was 871 +/- 233 mm3 and that of animals treated with Cetrorelix only 197 +/- 61 mm3. The BN/GRP antagonist RC-3940-II also significantly reduced PC-3 tumor volume in nude mice to 122 +/- 20 mm3. The combination of Cetrorelix and RC-3940-II produced no additional inhibition. High-affinity receptors for EGF were detected in the tumor membranes and their number was significantly decreased after administration of Cetrorelix or RC-3940-II. CONCLUSIONS: These findings demonstrate that LH-RH antagonists and BN/GRP antagonists inhibit the growth of the androgen-independent prostate cancer cell line PC-3 in vivo. Both analogs may exert a direct inhibitory effect on tumor growth through a down-regulation of EGF receptors.

Animals↗

Effect of active immunization against luteinizing hormone-releasing hormone on the androgen-sensitive Dunning R3327-PAP and androgen-independent Dunning R3327-AT2.1 prostate cancer sublines.

BACKGROUND: The objective of this study was to determine the effect of active immunization against LHRH on the growth characteristics and histology of subcutaneously implanted tumors of the androgen-sensitive Dunning R3327-PAP and androgen-independent R3327-AT2.1 rat prostate adenocarcinoma sublines. RESULTS: We herein demonstrate that 1) active immunization with an LHRH-diphtheria toxoid-conjugate (LHRH-DT) leads to the downregulation of gonadotropins and testosterone and consequently the atrophy of testosterone-dependent organs such as the testes, prostate, and androgen-sensitive Dunning R3327-PAP tumors, 2) growth inhibition of Dunning R3327-PAP tumors is caused by suppression of cell division rather than by an increase in cell death and is associated with an increase of the tumor stroma content, and 3) volume increase of the androgen-independent Dunning R3327-AT2.1 tumor is slightly but significantly reduced, indicating a local stimulatory LHRH loop within this tumor cell line.

Analysis of Variance↗

Growth hormone-releasing hormone antagonist MZ-4-71 inhibits in vivo proliferation of Caki-I renal adenocarcinoma.

In view of evidence that growth hormone (GH) and insulin-like growth factors (IGF) may play a role in the development of renal cell carcinoma (RCC), we investigated the effects of growth hormone-releasing hormone (GH-RH) antagonist MZ-4-71 on the proliferation of the human renal adenocarcinoma cell line Caki-I in vitro and in vivo. Male nude mice bearing xenografts of human Caki-I RCC were treated for 4 weeks with MZ-4-71 injected s.c. twice daily at a dose of 20 microg per animal. Tumor growth, serum, liver, and tumor IGF levels and IGF-I receptor concentrations in Caki-I cell membranes were measured. After 4 weeks of therapy, the final volume of Caki-I tumors in nude mice treated with MZ-4-71 was significantly (P < 0.01) decreased to 52.6 +/- 12.3 mm3 as compared with controls that measured 504.2 +/- 104.1 mm3. Treatment with GH-RH antagonist also significantly reduced tumor weight, serum levels of GH and IGF-I, liver concentrations of IGF-I, and tumor levels of IGF-I and IGF-II. High-affinity binding sites for IGF-I were detected in the cell membranes of Caki-I tumors. IGF-I and IGF-II stimulated the proliferation of Caki-I cells in tissue cultures. Antagonist MZ-4-71 could inhibit in vitro growth of Caki-I cells, but only at high concentrations. Our findings demonstrate that GH-RH antagonist MZ-4-71 can significantly inhibit the growth of Caki-I RCC. MZ-4-71 may exert its suppressive effect on tumor growth through a reduction in GH release from the pituitary and the subsequent decrease in the production of IGF-I in the liver and IGF-I and II by the tumors. The efficacy of MZ-4-71 suggests that this compound could be considered for the therapy of recurrent or metastatic RCC.

Animals↗

Follicle-stimulating hormone activates a cAMP-dependent chloride conductance in TM4 Sertoli cells.

The effect of follicle-stimulating hormone (FSH) on the electrical properties of TM4-Sertoli cells was investigated. Addition of 5 IU/ml FSH caused a dose-dependent and reversible depolarization of the resting membrane potential by +15.3 +/- 1.0 mV accompanied by a decrease of the input resistance. The depolarization was completely abolished in chloride-free solutions. The reversal potential of the effect was close to the calculated reversal potential for chloride. We conclude that FSH activates a chloride conductance in cultured TM4 Sertoli cells.

Animals↗

Inhibition of growth of androgen-independent DU-145 prostate cancer in vivo by luteinising hormone-releasing hormone antagonist Cetrorelix and bombesin antagonists RC-3940-II and RC-3950-II.

The aim of this study was to test the antagonist of LH-RH (Cetrorelix), agonist [D-Trp6]LH-RH (triptorelin) and new bombesin antagonists RC-3940-II and RC-3950-II for their effect on the growth of an androgen-independent prostate cancer cell line, DU-145, xenografted into nude mice. Xenografts were grown in male nude mice, and after 4 weeks, the animals were treated either with saline (control) or with one of the analogues. One group of mice was given a combination of Cetrorelix and RC-3950-II. Treatment was given for 4 weeks. Tumour and body weights, and tumour volumes were measured. At sacrifice, tumours were dissected for histological examination and receptor studies. Serum was collected for measurement of hormone levels. The final tumour volume in control animals injected with saline was 577 +/- 155 mm3 and that of animals treated with Cetrorelix only 121.4 +/- 45 mm3 (P < 0.01). Bombesin antagonists RC-3940-II and RC-3950-II also significantly reduced DU-145 tumour volume in nude mice to 84.9 +/- 19.9 and 96.8 +/- 28 mm3, respectively. Agonist [D-Trp6]LH-RH did not significantly inhibit tumour growth. Serum levels of LH were decreased to 0.08 +/- 0.02 ng/ml (P < 0.05) in the Cetrorelix treated group as compared to 1.02 +/- 0.1 ng/ml for the controls, and testosterone levels were reduced to castration levels (0.01 +/- 0.01 ng/ml). Specific receptors for EGF and LH-RH in DU-145 tumours were significantly downregulated after treatment with Cetrorelix, RC-3940-II and RC-3950-II. Although LH-RH could be a local regulator of growth of prostate cancer, the fall in LH-RH receptors is not fully understood and the inhibitory effects of Cetrorelix and bombesin antagonists on DU-145 tumour growth might be attributed at least in part to a downregulation of EHF receptors. Since Cetrorelix and bombesin antagonists inhibit growth of androgen-independent DU-145 prostate cancers, these compounds could be considered for the therapy of advanced prostate cancer in men, especially after relapse.

Animals↗