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Biomedical subjects

F Di Silverio

Publications and source records attributed to F Di Silverio.

At least 55 records · Page 3Linked to original sources
PubMed1998

Hormonal profile of patients with Leydig cell tumors: a urologic cause of gynecomastia.

It is possible to hypothesize an alternative role for estrogens as a predisposing factor for testicular abnormalities: estrogen exposure during development in perinatal life may initiate cellular changes which would require estrogen and/or androgen later in life for promotion to hyperplasia or neoplasia. We reviewed the literature on Leydig cell tumors and the hormonal modifications they induce. In adult patients with Leydig cell tumors, although the serum estrogen (E2) and testosterone (T) varied, the T/E2 ratio was constantly low, and the chorionic gonadotropin administration produced an higher estrogen response than in normal men. Hormonal follow-up after orchidectomy for Leydig cell tumors has not been frequently described, and both normalization and lack of normalization of T, E2, gonadotropins and hCG have been reported. In the last part of the review we analyzed the principal urologic causes of gynecomastia in men. Testicular failure, either primary or secondary is a frequently found etiology for gynecomastia. Leydig cell tumors may elevate estrogen levels, and approximately 20% of patients with these tumors have gynecomastia.

Adult↗
PubMed1997

Multiple primary tumors: 17 cases of renal-cell carcinoma associated with primary tumors involving different steroid-hormone target tissues.

The aim of this study was to analyze the characteristics of 17 women with renal-cell carcinoma (RCC) associated with other primary neoplasms occurring in steroid-hormone target tissues. The reproductive history of these patients and the use of exogenous hormones were taken into consideration. In all, 10 RCCs were associated with breast carcinoma; 4, with endometrial carcinoma; and 3, with ovarian carcinoma. The presentation of a second primary tumor was described as synchronous or metachronous by evaluation of the interval between the discovery of the two neoplasms. Hormone and surgical treatment as well as pathologic findings for each primary tumor were also reported. In these 17 RCCs the overall rate of disease-specific survival recorded after a mean follow-up period of 32.7 months (range 9-66 months) was 58.8%; 7 patients died of metastatic disease after surviving for a mean of 14.7 months. In terms of the pathologic stage of RCC, a significant difference in mean survival was found between pN0 (mean survival 22.1 +/- 3.4 months) and pN1 RCCs (mean survival 13.7 +/- 3.5 months). A total of 13 (76.4%) women were postmenopausal at the time of diagnosis of the first primary tumor; the mean age of these women at menopause was 51.7 +/- 1.2 years. No prior use of oral contraceptives was reported by 12 (70.5%) of the 17 patients. Plasma 17-beta-estradiol and estrone levels were determined in only 7 patients at the diagnosis of each of the primary tumors. High plasma estrogen levels were found in 4 women with RCC and breast carcinoma and in 1 patient with RCC and endometrial carcinoma; in the remaining 2 patients low-normal values were found. A relationship appears to exist between certain reproductive and hormone-related factors and the risk of developing these tumor associations. Data emerging from the present study do not provide strong support for the hypothesis of hormone dependency of RCC; however, a role for estrogens in cases in which RCC is associated with other primary tumors involving steroid-hormone target tissues can be hypothesized.

Adult↗
PubMed1997

Surgical enucleation for renal cell carcinoma (RCC). Prognostic significance of tumour stage, grade and DNA ploidy.

This study reviews a total of 26 renal cell carcinoma (RCC) who underwent enucleation of the tumour with functionally and anatomically normal controlateral kidney and no evidence of systemic renal disease. At follow-up, after a mean of 62 months the disease specific survival rate for this series was 88.5%. Survival rates according to the pathologic stage, grading, tumour diameter and ploidy are reported. Local recurrences were documented in 4 of the 26 RCC. All 4 RCC were more than 5 cm in diameter and recurred in the remaining parenchyma. After local recurrence, three tumours with aneuploid DNA content underwent radical nephrectomy, whereas 1 with diploid DNA content was submitted to a new enucleation of the recurrence. To date the diploid case is still alive 3 years after the original resection of the primary tumour whereas the other 3 patients died for metastatic disease. In our experience the ideal candidate for renal sparing surgery in the presence of a normal opposite kidney is an asymptomatic patient that incidentally is brought to our attention with a small size (less than 5 cm in diameter), low stage (T1-T2) tumour, well surrounded by a pseudocapsule. DNA content is a valuable prognostic factor in patients submitted to conservative surgery. Diploid tumours have been seen to have a better prognosis and in case of local recurrence they may be reconsidered for a new enucleation of the recurrence.

Adult↗
PubMed1997

Safety profile of selective alpha-1 adrenoceptor antagonists in the treatment of benign prostatic hyperplasia.

Further identification of the alpha-1 adrenoceptor present in various tissues using pharmacological and molecular biological studies has revealed that there are three subtypes of the alpha-1 adrenoceptor. This raised the possibility that there could be one subset of alpha-1 adrenoceptors within the human prostate and these might differ from those in the vascular. Binding experiments defined the functionally important alpha-1 subtype in the human prostate. It has been postulated that a drug with relatively high affinity for the alpha-1 adrenoceptor may be "prostate-selective". Such a drug may be as effective as other alpha-1 adrenoceptor antagonists but may have less effect on blood pressure and cause fewer vasodilatory side effects. The safety profile of non-subtype selective and subtype selective long-acting alpha-1 blockers is considered. However, Quantitative analysis showed that the amount of alpha-1a receptor differs from biopsy to biopsy, suggesting that prostates will differ in their response to an alpha blocker even when it is alpha-1a selective. Polymerase chain reaction (PCR) technique can be used to determine quantitatively alpha-1a receptor in small amount of tissue; at present, however, no non invasive parameters have been tested.

Adrenergic alpha-Antagonists↗
PubMed1997

Peptide growth factors: clinical and therapeutic strategies.

The literature contains many accounts of studies in which tumour growth has been accelerated by administration of a particular mitogen and the response then inhibited by co-administration of the corresponding antagonist. Much effort has been focused on the development of cytokine or growth factor antagonists. Like most other cancer therapies, biological therapies will undoubtedly have undesirable toxicities because the proteins they target may not be unique to malignant cells. We reviewed the clinical and therapeutic potential of growth factor agonists and antagonists in some non urologic and urologic diseases. In a recent report we demonstrated that both androgen and antiandrogen treatments enhance the proliferation rate of the hormone-dependent prostate cancer cell line LNCaP, expressing a mutated androgen receptor. Simultaneous treatment with 1 nM R1881 and 100 nM OH-Flutamide, completely counteracted the androgen-induced increase of Epidermal Growth Factor (EGF) levels. Moreover we found that Testosterone, DHT and EGF are mainly concentrated in the periurethral zone in human BPH and long term treatment with Finasteride and with Flutamide modify the distribution and concentration of these factors. Some authors analyzed whether and addition of aurin tricarboxylic acid (ATA) can reduce the growth rate of basic FGF-dependent cells in a manner similar to suramin.

Animals↗
PubMed1997

Effects of short-term treatment with the alpha 1-blocker alfuzosin on urodynamic pressure/flow parameters in patients with benign prostatic hyperplasia.

OBJECTIVE: The objective of this double-blind, placebo-controlled urodynamic pressure/flow study was to assess the efficacy of short-term treatment with the alpha 1-blocker alfuzosin in outflow obstruction of patients with symptomatic benign prostatic hyperplasia (BPH). MATERIAL AND METHODS: Urodynamic pressure/flow parameters were assessed after 2 weeks of placebo run-in, 4 weeks of placebo (47 patients) or 2.5 mg t.i.d. alfuzosin treatment (47 patients), followed by an 8-week extension period with alfuzosin (single-blind). RESULTS AND CONCLUSION: Four weeks of alfuzosin treatment significantly increased maximum flow (+29.0%) and decreased detrusor pressure at maximum flow (-30.2%), detrusor opening pressure (-39.4%) and maximum detrusor pressure (-28.7%). Short-term alfuzosin treatment improved outflow conditions in BPH by reducing prostatic urethral obstruction.

Adrenergic alpha-Antagonists↗
PubMed1996

Effects of the lipidosterolic extract of Serenoa repens (Permixon) on human prostatic cell lines.

BACKGROUND: Permixon is a drug used in the treatment of benign prostatic hyperplasia. We studied its androgenic and antiandrogenic effects in the prostatic cell lines LNCaP and PC3, respectively responsive and unresponsive to androgen stimulation. METHODS: We performed FACScan analysis to investigate toxicity, 3H thymidine and 35S methionine incorporation to determine antiproliferative and metabolic effects, electron microscopy to study ultrastructural changes and cotransfection experiments to elucidate the role of wild type androgen receptor. RESULTS: In LNCaP cell line, Permixon induced a double proliferative/differentiative effect, not observed in PC3 cells. In PC3 cells cotransfected with wild-type androgen receptors and CAT reporter genes under the control of a androgen responsive element, the drug inhibited androgen-induced CAT transcription. CONCLUSIONS: Our data indicate a role of the androgen receptor in mediating the effects of Permixon in LNCaP cells. Cotransfection experiments in PC3 cells support a clear antiandrogenic action of the drug.

Androgen Antagonists↗
PubMed1996

Comparison of phytotherapy (Permixon) with finasteride in the treatment of benign prostate hyperplasia: a randomized international study of 1,098 patients.

BACKGROUND: Controversy regarding the relative efficacy of treatments for the relief of the symptoms of benign prostatic hyperplasia (BPH). METHODS: This was a 6-month double-blind randomized equivalence study that compared the effects of a plant extract (320 mg Permixon) with those of a 5 alpha-reductase inhibitor (5 mg finasteride) in 1,098 men with moderate BPH using the International Prostate Symptom Score (IPSS) as the primary end-point. RESULTS: Both Permixon and finasteride decreased the IPSS (-37% and -39%, respectively), improved quality of life (by 38 and 41%), and increased peak urinary flow rate (+25% and +30%, P = 0.035), with no statistical difference in the percent of responders with a 3 ml/sec improvement. Finasteride markedly decreased prostate volume (-18%) and serum PSA levels (-41%); Permixon improved symptoms with little effect on volume (-6%) and no change in PSA levels. Permixon fared better than finasteride in a sexual function questionnaire and gave rise to less complaints of decreased libido and impotence. CONCLUSIONS: Both treatments relieve the symptoms of BPH in about two-thirds of patients but, unlike finasteride, Permixon has little effect on so-called androgen-dependent parameters. This suggests that other pathways might also be involved in the symptomatology of BPH.

Aged↗
PubMed1996

Incidence and prediction of stone recurrence after lithotripsy in idiopathic calcium stone patients: a multivariate approach.

In order to evaluate the recurrence of calcium kidney stones, 520 patients (275 males and 245 females), aged 14-79 years, previously treated with lithotripsy were followed up for 23 months on average (median = 24 months; range = 12-48 months), and 101 relapses (10%/year) were recorded. Among the possible predictors of recurrence, measured at the beginning of the follow-up and analyzed in univariate and multivariate statistical ways, age was inversely related with occurrence of event (multivariate t value = -2.12) whereas urinary calcium (UC; t = 2.78), alkaline phosphatase (AP; t = 3.55) and history of previous relapses (t = 2.07) were directly related to the recurrence. The levels of UC were not correlated to those of AP (linear correlation coefficient r = 0.0032), but the combination of their high levels increased the risk of recurrences. The contribution of the other considered factors to stone formation were not significant (sex, family history of stone disease, gallstone, renal failure, serum calcium, phosphate, uric acid, sodium and proteins, urinary phosphate, sodium, magnesium and uric acid.

Adolescent↗
PubMed1996

DNA ploidy, Gleason score, pathological stage and serum PSA levels as predictors of disease-free survival in C-D1 prostatic cancer patients submitted to radical retropubic prostatectomy.

We report our experience with 85 prostatic cancer patients aged 51-79 years, who underwent radical retropubic prostatectomy from 1989 to December 1994 (mean follow-up 35 months). In order to get a more relevant analysis we chose to describe in detail only pathological C-D1 cases and to subdivide the patients, according to the Gleason sum, into G2-G5 and G6-G10 groups. Means of pre- and postsurgery PSA levels were ranked by DNA ploidy and presence or absence of recurrence: aneuploid patients showed lower levels of PSA production that may be due to cell dedifferentiation. However, in patients who developed recurrence, postsurgery PSA levels were higher (p < 0.005). The influence of DNA ploidy on disease-free survival was evaluated: the cumulative survival proportion was better in diploid (0.3581) than in aneuploid patients (0.2996). Using the Cox proportional hazard model with age, Gleason sum, DNA ploidy and presurgery PSA levels as covariates, we demonstrated that, in our series, only the presurgery PSA level was an important and significant predictor of recurrences (p < 0.005). Considering global recurrences with age, Gleason sum and presurgery PSA levels kept fixed, DNA aneuploidy conferred a relative risk 2.3 times higher than diploidy. When, in the same analysis, we introduced postsurgery PSA levels, only DNA ploidy and the latter variable kept statistical significance with a relative risk of 2.5. Considering only local and distant recurrences (with exclusion of those identified by elevated PSA levels) the relative risk was 3.9 and 3.8, respectively. These data support the critical role of nuclear DNA analysis as predictor of outcome after surgery even in this discussed subset of patients (C-D1).

Aged↗
PubMed1996

In vitro study of a double infection by herpes simplex virus type 2 and Chlamydia trachomatis.

Sexually transmitted diseases (STDs) may recognize multiple etiological agents. Among them, Chlamydia trachomatis (Ct) and herpes simplex virus type 2 (HSV-2) cause symptomatic, subclinical and asymptomatic infections of the urogenital tract which can lead to serious sequelae. In the present study the coinfection and superinfection by Ct and HSV-2 in epithelial cultured cells from human cervix (HeLa 229) are described. A double infection, followed by the intracellular synthesis of chlamydial and viral antigens, was established. Both synergistic and interfering phenomena were recorded: viral antigen synthesis resulted increased whereas Ct inclusion bodies were produced to a lower extent.

Antigens, Bacterial↗
PubMed1996

[Comparative effects of transurethral incision (TUIP) and the combination of TUIP and LHRH agonists in the treatment of benign prostatic hypertrophy].

Between December 1991 and December 1993, 74 BPH patients with an increased operative risk and concomitant diseases such as diabetes mellitus and hypertension were submitted to a transurethral incision of the prostate (TUIP). After TUIP, patients were randomized to two different groups: group 1 was followed without additional treatment and group 2 received an LHRH analogue for the first 6 months of follow-up. With respect to transurethral resection of the prostate (TURP), TUIP has been shown to demonstrate a lower perioperative morbidity. This advantage has lent further support to this technique as a valid alternative for patients in poor general conditions who are at high risk with more invasive procedures. One of the limits of TUIP is the long-term effectiveness. Aim of this study was to ascertain whether in patients with BPH and an increased operative risk who require immediate and definitive treatment but with a low perioperative morbidity, the long-term effectiveness of TUIP can be stabilized by the administration of an LHRH analogue. At present postoperative follow-up ranges from a minimum of 24 months to a maximum 48 months (mean 38.4 months). Perioperative morbidity rate associated with TUIP was 8.1%. In the group randomized to combination therapy (TUIP + LHRH analogue), the clinical condition of the patients was not modified by LHRH analogue treatment and none of the patients withdrew from treatment. Loss of sexual potency occurred in all patients on LHRH analogue, however, none of these patients discontinued treatment for this reason. At the end of the cycle of hormone treatment, sexual potency returned to pretreatment values in 69.5% of patients after a mean of 3.2 months. In this study the objective efficacy of the treatment was evaluated using flow rate measurements, and the subjective assessment of outcomes, using the International Prostate Symptom Score. Statistically significant differences between the two groups (TUIP alone or TUIP + LHRH analogue) (p < 0.01) were reported at 6 months and were still maintained at 24 months of follow up. Results emerging from this investigation confirm that TUIP may be considered extremely safe procedure with low operative risk. In selected BPH patients who are at high risk, with a more invasive procedure and who must be submitted to immediate and definitive treatment, the association of an LHRH analogue seems to increase the long-term effectiveness of TUIP. Five year follow-up studies are still in progress.

Aged↗
PubMed1995

Androgenic and antiandrogenic control on epidermal growth factor, epidermal growth factor receptor, and androgen receptor expression in human prostate cancer cell line LNCaP.

Both androgen and antiandrogen treatments enhance the proliferation rate of the hormone-dependent prostate cancer cell line LNCaP, expressing a mutated androgen receptor (AR). We studied the modification of the expression of epidermal growth factor (EGF), of its receptor (EGF-R), and of androgen receptor (AR) in the LNCaP cell line, under basal conditions and during androgen (R1881) and antiandrogen hydroxy-flutamide (OH-FLU) treatment. After prolonged R1881 administration, a marked increase of EGF release was observed, completely blocked by the addition of OH-FLU. The Scatchard plot analysis of EGF-R binding revealed two classes of binding sites with high and low affinity. The administration of OH-FLU alone or combined with R1881 did not modify the affinity constants, while the low-affinity component disappeared after androgen administration. Both androgen and antiandrogen administration led to a significant increase of the EGF-R high-affinity component. AR mRNA and protein levels were downregulated by R1881 treatment. Following OH-FLU administration, AR mRNA was slightly downregulated, and there was not a strict parallelism between AR mRNA levels and AR binding capacity. When combined with R1881, OH-FLU partially counteracted the androgen-induced AR downregulation. Our data show that EGF-R binding capacity is the only parameter constantly raised in cell proliferation with respect to quiescent cells, and highlights the nonunivocal action of OH-FLU on androgen-induced effects.

Androgen Antagonists↗
PubMed1995

Benefits and complications of laparoscopic pelvic lymphadenectomy for detection of stage D1 prostate cancer: a multicenter experience.

One hundred fifty-eight consecutive patients with clinically localized prostate cancer were submitted to staging laparoscopic pelvic lymphadenectomy (LPL) at 5 cooperative centers with one or more of the following conditions which were considered as risk factors for nodal disease: clinical stage C (or T3) disease, serum prostate-specific antigen > 20 ng/ml, Gleason sum > 6. The mean number of lymph nodes removed was 11 (range 2-29). Metastases from prostate cancer were found in 41 patients (25.9%). The proportion of lymph node-positive patients increases significantly with the presence of one, two or three of the conditions considered as risk factors (p < 0.00005). The benefit of LPL is limited to the lymph node-positive patients who can be spared a second operation.

Humans↗
PubMed1995

Is medical therapy an expensive way for delaying surgery in BPH patients?

Nowadays, no medical therapy can be considered as a real and definitive alternative to surgery in the management of BPH patients. We considered pharmacologic approach as a treatment that may delay the need for surgery for BPH. In some cases a delayed therapy may continue for all patient life, excluding the need for TURP. The questions that we propose in the present review are: Is there always a role for a delayed medical therapy in the treatment of BPH patients? In which BPH patients a delayed medical therapy and in which instead an immediate surgery may be chosen? Which factors may influence this decision? A delayed medical therapy cannot be chosen in all BPH cases. Two factors can influence the evolution of the disease and the decision of the therapy: the first, natural history of BPH is related to BPH progression, and the second to patient characteristics. The role of growth factors in the natural history of BPH is investigated. Age of patient, his health condition and the presence of concomitant diseases are characteristics that may influence the therapeutic choice. In a young patient with good health condition and no concomitant diseases, the specific clinical phase of BPH is crucial to determinate the need for surgery of for medical delayed therapy. If there is a worsening health status or concomitant diseases as diabetes and hypertension that can increase the risk related to surgery in the future or can determine a more rapid evolution of BPH, TURP may be immediately recommended in all clinical phases of prostatic hyperplasia. The role of age in this therapeutic decision must be carefully examined.

Age Factors↗
PubMed1995

Is there always a role for radical prostatectomy in the treatment of localized prostate cancer?

The efficacy of radical prostatectomy on localized prostate cancer is well documented. However if a high risk for patients suffering from prostate cancer and effectiveness of treatment would be documented, the advantage of the therapy on the natural history of the disease must be demonstrated. Johansson et al. analyzed the natural history of 223 untreated localized prostate cancer with a mean follow up of 123 months. Only 8.5% of the patients died of prostate cancer. The 10 year disease specific survival rate was 86.8%. The progression free survival rate was 53.1%. Zincke et al. reported that the disease specific survival of the T1 T2 submitted to radical prostatectomy at 15 years was 93% and the survival free of disease was 70%. Our data on localized prostate cancer submitted to radical prostatectomy showed that the disease specific survival and the progression free survival after 5 years of follow-up were 99% and 85.7% respectively. Fleming, focusing on life expectancy, demonstrated that radical prostatectomy provides some benefit compared with watchful waiting for patients younger than 70 years. The greatest marginal benefits of treatment arise when we assume higher metastatic rates and higher treatment efficacy. In fact in this case, radical prostatectomy offers 3.5 years of improvement in quality of life adjusted survival in younger patients with moderately or poorly differentiated tumors. Radical prostatectomy can particularly benefit selected groups of patients with localized prostate cancer. The grade of differentiation has been shown to be the most powerful predictor in several series. DNA ploidy and tumor volume may be other reliable prognostic factors. Among all the parameters considered, the two with greatest effect in determining the outcome of treatment compared to watchful waiting were the rate of progression to metastatic disease in untreated patients and the estimated efficacy of treatment in reducing the metastatic rate.

Age Factors↗
PubMed1994

Cystinuria caused by mutations in rBAT, a gene involved in the transport of cystine.

Cystinuria is a classic heritable aminoaciduria that involves the defective transepithelial transport of cystine and dibasic amino acids in the kidney and intestine. Six missense mutations in the human rBAT gene, which is involved in high-affinity transport of cystine and dibasic amino acids in kidney and intestine, segregate with cystinuria. These mutations account for 30% of the cystinuria chromosomes studied. Homozygosity for the most common mutation (M467T) was detected in three cystinuric siblings. Mutation M467T nearly abolished the amino acid transport activity induced by rBAT in Xenopus oocytes. These results establish rBAT as a cystinuria gene.

Adolescent↗