Biomedical subjects
F Di Silverio
Publications and source records attributed to F Di Silverio.
[Renal calculosis: current and future therapeutic aspects].
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Immunoreactive EGF in human benign prostatic hyperplasia: relationships with androgen and estrogen receptors.
Benign prostatic hyperplasia (BPH) is a sex steroid dependent disease. Estrogens and androgens can modulate in different mammalian tissues epidermal growth factor (EGF) production and/or secretion. In order to clarify the relationships between estrogen and androgen receptor concentrations and those of immunoreactive EGF (irEGF), we have evaluated these parameters in 14 human BPH samples, by means of a dextran-coated charcoal method and radioimmunoassay, respectively. Cytosolic steroid receptors did not seem to correlate with irEGF. A linear significative relationship was evident between nuclear androgen receptor (ARn) levels and endogenous irEGF but not between nuclear estrogen receptors and irEGF: in ARn negative BPH samples, irEGF levels were lower than in ARn positive ones. Therefore, it is possible that androgens act at prostatic tissue level, through their own receptors, by modulating EGF production and/or secretion.
Use of terazosin in the medical treatment of benign prostatic hyperplasia: experience in Italy.
The purpose of this multicentre, randomised, placebo-controlled, double-blind study was to verify the safety and efficacy of terazosin, an alpha 1 adrenergic blocker, in patients with benign prostatic hyperplasia (BPH). This study involved 137 patients who were randomly assigned to receive either a designed dose of terazosin (2, 5 or 10 mg) or placebo. Response to treatment was measured objectively by uroflowmetric determinations. Subjective evaluation was based on the investigator's assessment of each patient's symptoms. The safety of this agent was monitored by haematological tests and urinalysis. In addition, systolic and diastolic blood pressures and pulse rates were recorded during each visit. The treatment of BPH with terazosin produced a significant improvement in mean flow rate and peak flow rate; there were no statistically significant differences in the analysis of symptomatic responses between the groups of patients treated with terazosin or placebo. Moreover, the safety of this alpha 1 blocker was thoroughly tested and clinically proven.
Evidence that Serenoa repens extract displays an antiestrogenic activity in prostatic tissue of benign prostatic hypertrophy patients.
A double-blind placebo-controlled study was performed in 35 benign prostatic hypertrophy (BPH) patients never treated before. The patients were randomized into two groups, the 1st (18 cases) receiving Serenoa repens extract (160 mg t.d.) for 3 months up to the day before the operation of transvesical adenomectomy and the 2nd (17 cases) receiving placebo. Steroid receptors were evaluated in the nuclear (n) and cytosolic (c) fraction using the saturation analysis technique (Scatchard analysis or single saturating-dose assay) for androgen (AR) and estrogen (ER) receptors and the enzyme immunoassay (EIA) for ER and progesterone receptors (PgR). Scatchard analysis of ERc and ERn revealed the presence of two classes of binding sites, one with high-affinity low-capacity binding and the other with low-affinity high-capacity binding. In the untreated BPH group, ER were higher in the n than in the c fraction: ERn were positive in 14 cases and ERc in 12 of 17 cases. In the BPH group treated with S. repens extract on the contrary, ERn were negative for both binding classes in 17 cases and ERc in 6 of 18 cases. Using EIA, ERn and ERc were detected in all 15 samples examined, but in the treated group, ERn were significantly (p less than 0.01) lower than in the untreated group, whilst ERc remained almost unchanged. Similar results were obtained measuring PgR: the n fraction of the treated group prostatic samples was significantly (p less than 0.01) lower than that of the untreated group.(ABSTRACT TRUNCATED AT 250 WORDS)
Prognostic role of flow cytometry in superficial bladder cancer.
Prognostic factors in superficial transitional cell carcinoma of the bladder were assessed with histopathological and flow cytometry analysis in a series of 61 patients operated transurethrally between 1988 and 1990. In particular, we evaluated the usefulness of flow cytometry in order to identify patients who require a more accurate clinical follow-up or a more aggressive therapy. A multivariate analysis was done in 61 cases, considering patient age and sex, stage, grade and number of lesions (unifocal or multifocal), post-TUR therapy (therapy or not), and DNA ploidy (diploid/aneuploid). DNA pattern and number of recurrences were determinant for selecting risk cases for progression.
Biological and clinical implication of cellular DNA content in renal cell carcinomas.
DNA flow cytometric analysis (FCM) was performed on surgical bioptic samples taken from 82 renal cell carcinomas. FCM has evidenced that 35% (29/82) of renal carcinomas resulted diploid, 65% (53/82) aneuploid and of the latter 22% (12/53) multiclonal. Our results do not indicate any relationship among cytometric ploidy, Fuhrman grading, Robson and pTNM staging. A possible interesting increase of aneuploidy frequency was observed between the NMV (66%) subgroup and the no zero NMV (90%) subgroup, while in diploid patients these values were 40% and 10%, respectively. Follow-up data evidence a significant difference in survival pattern of patients between diploid and aneuploid groups. In conclusion, our results show that cytometric ploidy is a potential important prognostic parameter in survival term.
New ultrasensitive assay development by using monoclonal antibodies for detecting prostate-specific antigen.
The Serono Maia Clone prostatic-specific antigen (PSA) kit incorporates an immunoradiometric assay for the measurement of PSA in the serum. The method can be used over a range of 0-100 ng/ml without dilution. Standard concentrations are 0, 0.4, 1, 5, 20, and 100 ng/ml. Up to date, 373 normal men, 89 normal women, 117 prostatic carcinoma, 98 other carcinoma, and 85 benign prostatic hypertrophy have been tested. The aim of this study is to evaluate the sensitivity and specificity of a new immunoassay method for the determination of PSA, that could be able to evaluate low levels of PSA, resulted undetectable with other methods. This ability could be useful in patients treated with hormone-suppressive therapy or after radical prostatectomy. We have collected all low values present in samples examined. With the Serono Maia Clone PSA kit only 26.7% of these have been evaluated as 'out' values as opposed to 46.5% with the Hybritech kit.
The prognostic value of DNA content in patients with prostatic carcinoma.
In 80 patients with pathologically proven prostatic cancer, DNA content was correlated to grade, stage and survival. The survival curve and duration of response to therapy in these patients was examined. At the end of follow-up the cumulative survival curve in the aneuploid patients was 0.40, according to the Kaplan-Meier method, while in the diploid population it was 0.65. Differences between the two groups, aneuploid and diploid, were observed within the various histological subgroups: survival in the G2 population was 0.57 for the diploid and 0.30 for the aneuploid whereas in the G3 patients it was respectively 0.69 for the diploid and 0.05 for the aneuploid patients.
Transbrachial approach in spermatic phlebography.
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Colonoscopic control of uretero-enteric anastomoses in internal urinary diversion.
Twenty-four patients with internal urinary diversion following total bladder ablation underwent colonoscopic control of the uretero-enteric anastomoses. The techniques performed were: rectal bladder with colostomy according to Mauclaire (11 patients); rectal bladder with abdomino-perineal pull-through according to Heitz-Boyer/Hovelacque (6); ureterosigmoidostomy (7). The uretero-enteric anastomoses were divided into 3 categories according to the colonoscopic appearance: "nipple-like", nearly flat and flat anastomosis. Urographic examinations were carried out in all patients and the results demonstrated that the "nipple-like" anastomosis was the most successful for the preservation of upper urinary tract integrity.
Cellular DNA content and proliferative activity evaluated by flow cytometry versus histopathological and staging classifications in human bladder tumors.
Flow cytometric analysis of cellular DNA content was performed on 78 biopsy bladder samples obtained from 61 patients with bladder tumors. All 6 normal tissue samples and 1 benign papilloma exhibited a cytometrically diploid DNA distribution, while 39 of 60 bladder carcinomas exhibited at least one aneuploid cell subpopulation. Furthermore, 13 of 39 aneuploid tumors were characterized by the presence of more than one aneuploid cell subpopulation. The results indicate a significant relationship between cytometric ploidy and morphological classification and stage: the occurrence of subpopulations with abnormal DNA content is associated with the increase in differentiation grade and stage. A significant statistical difference in the survival pattern between the diploid and aneuploid groups was observed. The percent of S cells extracted from DNA content distribution histograms indicates a statistically significant difference (p less than 0.01) between normal tissue (3.7 +/- 1.8), diploid tumor (8.4 +/- 3.9) and aneuploid tumor (14.9 +/- 6.0). Moreover the percent of S-phase cells increases with grade in only the aneuploid subgroup. Our results suggest that cytometric parameters in association with morphological and clinical criteria can contribute to a more accurate characterization of bladder tumors in prognostic terms.
Antiandrogens: clinical applications.
Antiandrogens, preventing androgen action at target tissue level, are used in the treatment of various androgen-dependent diseases. Pharmacologically these substances have either a steroidal structure, like cyproterone acetate (CPA) and spironolactone (SPL), or a non-steroidal structure, like flutamide (FLU). In women with hyperandrogenism (PCO syndrome, idiopathic hirsutism, acne), clinical benefit may be obtained with CPA, which also displays a progestational activity and an antigonadotropic effect. CPA (25-50 mg/day) is used in combination with ethinyl-estradiol (EE) (20-30 micrograms/day) in reversed sequential regimen. SPL, less effective than CPA may be employed in moderate hirsutism and acne at dosages of 100-200 mg/day. During SPL treatment menstrual irregularities are frequent: in this case an association with oral contraceptives is indicated. SPL + bromocriptine (2.5-5 mg/day) has been experienced with success in PCO syndrome. The pure antiandrogen FLU, inducing progressive increase in LH and testosterone secretion, may be used only in combination with oral contraceptives. In men antiandrogens have been tested in BPH and prostatic carcinoma. In BPH the decrease in nuclear receptors and DHT nuclear content during CPA or FLU may represent the rational base of the medical treatment. An improvement in urinary obstructive manifestation has been observed with CPA alone or associated with tamoxifen (100 mg + 100 mg day). In advanced prostatic carcinoma antiandrogens represent a good alternative to estrogen therapy with less side effects and in combination with surgical or medical castration (LH-RH analogues) achieve a complete androgen blockade. An increase in the percentage of remissions and survival has been reported.
Blood cellular and biochemical changes after extracorporeal shock wave lithotripsy.
The present study deals with blood cell behaviour and related hematochemical changes occurring in man after exposure to extracorporeal shock wave lithotripsy (ESWL). The following parameters have been investigated, before and after treatment, in a longitudinal study carried out on 58 patients of our Center: RBC count, Ht, Blood Hb, Plasma Hb, autohemolysis after 72 hours, bilirubinemia, WBC count, platelet count, in vitro platelet aggregation, beta-TG, sideremia and urinary post-exposure transferrin concentration. After exposure to ESWL, with pulse numbers ranging from 350 to 3,000, 18-20 KV, direct and indirect evidences of hemolysis have been found when number of SW exceeded 1,000. The hemolysis rate in different models of in vitro exposure to ESWL of blood samples was also investigated. Increase of WBC count, and changes of the platelet in vitro aggregation patterns were also observed. Changes in sideremia values have been related to urinary loss of transferrin.
Staghorn calculi of the kidney: classification and therapy.
Following the introduction of new techniques, the reclassification of staghorn calculi is indicated in order to establish the most suitable form of treatment. Of 269 patients with staghorn calculi treated over a 3-year period, 56% underwent extracorporeal shockwave lithotripsy (ESWL) monotherapy; 16% required open surgery and the remaining 28% underwent percutaneous nephrolithotripsy (PCNL) with ultrasound in association with ESWL. The latter group has been reviewed, taking into account invasiveness, results, complications and cost effectiveness. A combination of PCNL and ESWL was beneficial in patients in whom percutaneous access through a single tract removed more than 70% of the stone. As a result of these findings, the authors propose a revised classification of staghorn calculi.
Advanced prostatic cancer: clinical and hormonal response to flutamide in patients pretreated with LHRH analogue and cyproterone acetate.
The aim of the present investigation was to establish whether in advanced prostatic carcinoma in relapse treated with LHRH analogues combined with cyproterone acetate (CPA), substitution of this antiandrogen with another compound such as flutamide (FLU) might lead to further subjective and objective improvement. The present randomized study was carried out on 100 patients in relapse treated with long acting LHRH analogue + CPA: 52 patients were submitted to combination therapy with FLU, whilst the remaining 48 cases continued with CPA treatment. Plasma levels of gonadotropin FSH-LH, androstenedione and dehydroepiandrosterone sulphate were significantly reduced by both treatments, testosterone fell to castration values, but prolactin showed no change. Progress of the disease was confirmed in all the patients who continued with CPA treatment with a median survival rate of 9.3 +/- 2 months from the start of the second cycle of CPA. In the FLU-treated group, the overall objective response differed significantly in relation to the stage of the disease. In fact, in stage D2, the response was poor with a median survival of 12 +/- 2 months, which is almost comparable to that in the CPA group. In stage D1, a clinical improvement, even if of short duration, was observed in almost 50% of the cases with a median survival of 18 +/- 3 months. Good results were also obtained in undifferentiated tumours, FLU probably acting as an antimitotic agent. Moreover, FLU also exerted an analgesic effect, with relief of bone pain in 65% of the cases in stage D2.(ABSTRACT TRUNCATED AT 250 WORDS)
Incidental prostatic carcinoma: four-year follow-up after treatment with cyproterone acetate.
This report is a retrospective clinical randomized study carried out on 114 cases of incidental prostatic carcinoma aged 55-87 years, 58 untreated and 56 treated with cyproterone acetate (CPA 200 mg/day) for 6 months, immediately after surgery. 78 cases were staged A1 and the remaining 36 A2. In stage A1, 75 cases were histologically graded G1, and 3 G2, whereas in stage A2, 7 cases were G1, 19 G2 and 10 G3. Moreover, flow cytometric DNA analysis showed in A1 20 G1 carcinomas with nuclear diploidy and 3 G2 with nuclear aneuploidy, in stage A2, 4 G3 tumors with nuclear aneuploidy. During the 4-year follow-up, 25/28 patients of the untreated group and 15/56 of the CPA-treated group were found in progression. In A1, progression was found in 6/37 untreated patients and 5/41 CPA-treated, whilst in A2 progression was observed in 19/21 untreated patients and in 10/15 treated with CPA. The critical period for progression was between the 2nd and 3rd year of follow-up. In A1, therefore, 6 months of therapy with CPA does not modify the progression rate, which is significantly improved in A2 (66% in the treated and 90% in the untreated group) during the first 30 months of follow-up. The prognosis may probably be further improved by continuing endocrine therapy.
Zoladex vs. Zoladex plus cyproterone acetate in the treatment of advanced prostatic cancer: a multicenter Italian study.
A collaborative multicenter trial was conducted by 17 Italian groups to verify whether the so-called total androgen blockade obtained with luteinizing hormone releasing hormone (LHRH) analogs combined with antiandrogens is more effective than conventional monotherapy in the treatment of advanced prostatic cancer. A total of 328 previously untreated patients were evaluated: 163 patients received Zoladex depot alone, 3.6 mg subcutaneously every 28 days, and 165 patients received Zoladex depot plus cyproterone acetate (CPA), 200 mg/day orally. The follow-up period ranged from 41-251 weeks. Treatment was well tolerated, and side-effects in both groups mainly comprised loss of libido and erections, hot flashes and breast swelling and tenderness. There was no significant difference in objective response after 6, 12 and 24 months of treatment between the 2 groups. Median time to disease progression was comparable in both groups: 55 weeks in the Zoladex group and 54 weeks in the Zoladex plus CPA group. The time to disease progression and the survival distribution was comparable in both groups. Although there were no significant differences in the overall subjective response to both treatments, a faster improvement, with respect to pain and performance status was noted in the Zoladex plus CPA group (8 weeks) compared to Zoladex alone (12 weeks). The addition of antiandrogen, by inhibiting the initial elevation of plasma testosterone, may prevent the disease flare-up which occurs in a small number of patients during the first few days of treatment with LHRH analogs alone.(ABSTRACT TRUNCATED AT 250 WORDS)