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Biomedical subjects

F Di Silverio

Publications and source records attributed to F Di Silverio.

At least 19 recordsLinked to original sources

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

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

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

Chlamydia trachomatis genitourinary infections: laboratory diagnosis and therapeutic aspects. Evaluation of in vitro and in vivo effectiveness of azithromycin.

Chlamydia trachomatis (C.t.) cell culture represents a sensitive method for the diagnosis of chlamydial infection and the only one which makes it possible to determine the susceptibility of an isolate to antibiotics so that an appropriate drug can be selected for individual treatment. In 11 patients, affected by urethroprostatitis and suspected of treatment failure with standard drug regimens, either due to lack of compliance with therapy or antibiotic resistance, C.t. was isolated in McCoy cell culture from urethral swabs, after prostatic massage. The in vitro activity of azithromycin against these isolates and the in vivo efficacy of the drug in the patients treated with a single 1 g dose have been evaluated. All the C.t. strains tested were susceptible to the action of azithromycin (MIC range 0.125-1.0 microgram/ml). Bactericidal values were one dilution higher (MBC range 0.25-2.0 microgram/ml). These in vitro results are consistent with clinical observations as all the patients treated had negative culture at a 4-week follow-up visit.

Azithromycin

Cost effectiveness in the management of benign prostatic hyperplasia: Italian data.

Several works in literature demonstrate that in some countries the economic considerations are as important as the clinical aspects of a disease; economic evaluation may be of help for decision making. The exact cost of the diagnosis and treatment of benign prostatic hypertrophy (BPH) patients is difficult to estimate. The total number of males in Italy is 27,982,144 (1991 data). In the last year 2,200,000 patients have been treated for BPH in Italy (surgically and pharmacologically); the overall cost for the therapy of BPH exceeded 46 million dollars per year. Currently surgery represents the standard treatment of BPH. In the USA alone over 350,000 surgical procedures are performed annually. In USA the cost per TURP is 12,000 dollars. In Italy the minimum direct cost is 3681 dollars; in most cases, however, the cost per TURP is over 5000 dollars. It is estimated that about 80% of patients with micturion problems prefer an alternative treatment before surgery. In our country 4,338,000 diagnoses of BPH have been performed in 1991. The number of prescriptions for BPH has been 4,867,000 and the number of drugs per prescription 1.16. It may be of interest to compare costs associated with different pharmacological therapies for BPH. Considering the direct costs, it has been estimated that the cost of 1 year's treatment with finasteride is 1833 dollars, while that of 1 year with plant extracts is 1151 dollars. The existing literature is deficient in defining the cost related to the therapeutical options for BPH.(ABSTRACT TRUNCATED AT 250 WORDS)

Cost-Benefit Analysis

[Prevention of renal calculosis: efficacy of Fiuggi water cure. Research Group on Renal Calculosis].

High fluid intake is the only nutritional modification that is universally agreed to be useful in all forms of nephrolithiasis. Particularly the use of oligomineral waters seems to be important as they can obtain a high urine volume with a low electrolytes concentration. The aim of this study was to evaluate the effects of an oligomineral water (Fiuggi) on some urinary parameters on different regimens of therapy. Out of 200 patients (118 M., 82 F., mean age 53 +/- 13 years), arrived to our outpatient Kidney Stone Center in Fiuggi, a random of 100 was submitted to water cure with more than 1500 ml/die of Fiuggi water for a period of 7 and 14 days, the other 100 patients to less than 1500 ml/die for the same periods. All the patients had a history of stone disease. Urinary values of calcium, phosphate, uric acid, magnesium, potassium, pH and density were measured in all groups of patients before and after water cure. Data were analyzed in unvaried method and were presented as mean +/- S.D. To evaluate the statistical differences between the values before and after therapy, the paired t test was used. Moreover, the percent changes of the considered parameters in relation to their basal values was considered. The 50-70% of all patients showed a reduction of the considered urinary parameters, with a statistical significance in patients who drunk more than 1500 ml of water. Urinary pH and Mg+/Ca++ ratio increased significantly in both groups of patients. The sex and the length of therapy didn't show any significant power on these results.

Adult

Relationship between epidermal growth factor and its receptor in human benign prostatic hyperplasia.

Human benign prostatic hyperplasia (BPH) samples were analyzed to evaluate the presence of immunoreactive epidermal growth factor (irEGF) and EGF receptor (EGFR). In all BPH samples examined both peptide and its receptor were present. Scatchard analysis of binding data of [125I]EGF showed two classes of binding sites with high and low affinity. Intratissular irEGF concentrations showed a significant inverse linear correlation with EGFR levels. Two groups of samples can be identified: the first showing high irEGF concentrations and low levels of EGF binding sites; the second low irEGF and high concentrations of EGFR. The simultaneous presence of EGF and its receptor in BPH samples indicates that this growth factor may act in an autocrine/paracrine manner in human prostatic tissue. The inverse relationship between EGF and the two sites of EGFR lead one to hypothesize that EGF itself could play a central role in determining receptor cell surface availability.

Aged

[Pharmacological combinations in the treatment of benign prostatic hypertrophy].

In the development of the obstructive symptomatology of benign prostatic hypertrophy (BPH), two components may be identified, mechanical and dynamic. In the mechanical component, the interaction of a stromal and a epithelial compartment determines prostatic mass growth. The dynamic component involves smooth muscle tone in the prostate and urethra. The consideration that prostatic disease is not only epithelial in origin, but also stromal, leads to the association of an antiandrogen (which acts on the epithelial component) and an antiestrogen (active on the stromal component) in the medical therapy of BPH. In 1985 we carried out a randomized study on 256 BPH patients treated with Cyproterone acetate (CPA) plus Tamoxifen (TAM). Recently, we performed a multicenter double blind study on BPH patients treated with the association CPA plus Serenoa Repens. A statistically significant difference in prostate volume reduction between the groups treated with the combinations and those with the monotherapies was observed. The development of new compounds, such as 5 alpha reductase and aromatase inhibitors, consents to introduce a combination therapy with less side effects. A second pharmacological association may be obtained with drugs acting on the mechanical and others acting on the dynamic (alpha blockers) component of BPH. This combination may associate the early symptomatic effect of alpha blockers with the long term results of a 5 alpha reductase inhibitor, antiestrogen or aromatase inhibitor.

Bromocriptine

Pathology of BPH.

Much research has been conducted to determine which tissue (epithelium or stroma) in the prostate gives rise to benign prostatic hyperplasia (BPH). Considering that BPH displays two structural compartments, stromal and epithelial and that the periurethral and transitional regions are particularly involved, the immunohistochemical and regional evaluation of steroid receptors concentration, 5 alpha reductase, DHT and estrogen activity, may show important data on the role of these factors in BPH development. We started a immunohistochemical study on the epidermal growth factor (EGF) concentrations in the periurethral, central and pericapsular zones of BPH samples, considering the stroma-epithelium ratio; investigations are performed on BPH patients submitted to transvesical prostatectomy. Considering that the periurethral zone is particularly involved in BPH, the presence of high concentration of growth factors in this region, may support the concept of their involvement in BPH.

Adult

Plant extracts in BPH.

In Italy plant extracts represent 8.6% of all pharmacological prescriptions for Benign Prostatic Hyperplasia (data from 1991). This review evaluates all the suggested mechanisms of action for plant extracts. Recently we demonstrated an antiestrogenic effect of Serenoa Repens in BPH patients. Clinical trials with plant extracts have yielded conflicting results. In a recent review by Dreikorn and Richter, only five placebo controlled studies were found. Moreover, as opposed to chemically defined drugs, it is possible that for these extracts the active ingredients are not known; consequently pharmacodynamic and pharmacokinetic data are often missing. The International Consultation of Benign Prostatic Hyperplasia (Paris, June 1991) concluded that, to date, phytotherapeutic agents must be considered as a symptomatic treatment. Now more adequate pharmacological and clinical studies, placebo controlled, should determine the exact role of these drugs in the treatment of BPH.

5-alpha Reductase Inhibitors

Distant disease.

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Androgen Antagonists

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.

Aged

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.

Adrenergic alpha-Antagonists

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)

Aged

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.

Carcinoma, Transitional Cell

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.

Carcinoma, Renal Cell