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Biomedical subjects

F Pagano

Publications and source records attributed to F Pagano.

At least 55 records · Page 3Linked to original sources
PubMed1997

Gene expression and autoradiographic localization of endothelin-1 and its receptors A and B in the different zones of the normal human prostate.

PURPOSE: To investigate the gene expression and tissue distribution of prepro Endothelin-1 (ET-1), Endothelin Converting Enzyme (hECE-1), and ETA and ETB receptors in the central (CZ), transition (TZ) and peripheral (PZ) zones of normal human prostates. MATERIALS AND METHODS: Sections of the different zones of histologically normal prostates from 35 year-old men were obtained and autoradiographically studied with 125I ET-1 with and without the ETA antagonist BQ-123, the ETB agonists sarafotoxin 6C, and excess cold ET-1. Specimens from PZ and CZ and DU145 and PC3 human prostate cancer cell lines were also investigated by reverse transcription (RT)-PCR. RESULTS: The mRNAs of all genes were detected in all specimens examined. No ETB expression was found in either cell lines. Specific intense 125I ET-1 binding with clear-cut differences among zones was found. In the CZ the main subtype in the glandular stroma and epithelium was the ETA and ETB, respectively, in the PZ the opposite was true. In PZ, the ETA receptors were detected on the glandular epithelium; in the TZ both receptor subtypes were only in the stroma. CONCLUSIONS: These receptors' zonal distribution differences may be relevant for the pathogenesis of BPH and prostatic cancer.

Adult↗
PubMed1997

[Vesica ileale Padovana (VIP): surgical technique, long-term functional evaluation, complications and management].

OBJECTIVE: An original technique for complete bladder replacement using an ileal segment--the VIP pouch--is described. The long-term functional results and early and late complications are presented. METHODS: The records of 209 VIPs performed following radical cystectomy for invasive bladder cancer from 1987 through 1995 were reviewed. Follow-up ranged from 6 to 87 months (mean: 24 mo.); the age of the patients ranged from 35 to 76 years (mean: 59.6 yrs.). RESULTS: 188 patients with a follow-up of at least 6 months have been evaluated. There was 1 postoperative death from massive pulmonary embolism, 23 pts. died from tumor progression and 4 are still alive with metastases. Early complications were observed in 10.5% of the pts., comprising 9 cases of prolonged ileus (5 functional and 4 obstructive), 3 pelvic hematomas, 2 deep venous thrombosis and 2 fistulas between the enteric anastomosis and the VIP pouch. Late complications were observed in 39.5%, in particular, 28 uretero-ileal stenosis (15%), 21 urethro-ileal stenosis (11%) and 15 laparoceles (8%). Clinically relevant metabolic disturbance has not been observed. Complete daytime continence was achieved in more than 90% of the cases and night-time continence was observed in 75% of the patients. The mean VIP manometric capacity was around 400 ml with low pressure during reservoir emptying; 39 patients (20%), showed voiding problems with a mean postmicturition residual of 150 ml (3 pts. require clean intermittent self-catheterization). CONCLUSIONS: VIP offers a simple and easy-to-perform surgical technique to provide a good capacity, low pressure, non refluxing reservoir employing only a 40 cm. ileal segment. The clinical and urodynamic results are good and offer high quality of life to patients undergoing cystectomy. The overall rate of late complications is fairly high, although conservative management is effective in most cases.

Adult↗
PubMed1996

Cytoskeletal and cytocontractile protein composition of stromal tissue in normal, hyperplastic, and neoplastic human prostate. An immunocytochemical study with monoclonal antibodies.

Monoclonal antibodies specific for protein markers of smooth muscle and nonmuscle cell differentiation were applied to cryosections of normal, hyperplastic, and neoplastic human prostate specimens in order to determine whether differences in the distribution of target antigens could be detected among the various tissues. Immunofluorescence assays showed that vimentin, desmin, smooth-muscle-type alpha-actin, and both smooth muscle and nonmuscle myosin heavy chains do not change their patterns of labeling in the stromas of normal, BPH, and carcinomatous prostates. By contrast, cytokeratin 18, a differentiation marker of simple epithelia, and to a lesser extent cytokeratin 8, was consistently found in stromal tissue of the "transition zone", but only scarcely in the stroma of the "peripheral zone" from normal prostate, and was completely unexpressed in benign hyperplasia. Prostatic carcinoma from the "peripheral zone" expressed this cytoskeletal component only in trace amounts. Moreover, in prostate showing coexistence of hyperplasia and neoplasia (in the "peripheral zone"), the stroma of BPH closely resembled the stroma surrounding the carcinoma; that is, it was completely unreactive with the anti-cytokeratin 18 antibody. Expression of cytokeratins in extraepithelial tissues has been previously correlated with the achievement of a proliferative state, notably in embryogenesis, in tissue regeneration, and in various pathological forms of proliferation and growth, including some tumors of mesenchymal origin. Our results indicate the following: (1) cells in the stromal tissue of normal prostate are of smooth muscle type and are heterogeneous as concerns cytokeratin distribution; (2) we show, for the first time, the existence of a marker that is differentially distributed in the "transition" versus "peripheral" zone; (3) the expression of cytokeratins in the stroma is lost with the development of hyperplasia and only partially recovers with neoplasia; (4) the pattern of stromal tissue, concerning cytokeratin 18 expression, does not change with different BPH locations ("transition" versus "peripheral" zone); and (5) contrary to expectations, cytokeratin 18 expression disappears in conditions presumably involving stromal cell proliferation.

Adult↗
PubMed1996

Proliferation of submesothelial mesenchymal cells during early phase of serosal thickening in the rabbit bladder is accompanied by transient keratin 18 expression.

Partial outlet obstruction of the rabbit bladder induces serosal thickening and smooth muscle (SM) hypertrophy. Within thickened serosa, submesothelial (mesenchymal) cells differentiate into SM cells after 30 days of obstruction[S. Buoro et al. Lab. Invest. 69, 589-602, 1993]. Here, we show that submesothelial cells transiently express keratin (K) 18 but not K8 soon after obstruction. We investigated a possible relationship between keratin expression and cell proliferation/differentiation in vivo and in vitro. The results of this study indicate that expression of K18 is spatiotemporally related to the pattern of cell proliferation with respect to the localization of an elastic membrane which divides the thickened serosa into an "extrinsic" and an "intrinsic" region. Moreover, K18 is not present in bladder mesenchyma during early development, indicating that its expression in the adult is not attributable to a dedifferentiation process. However, simultaneous K18, K8, and desmoplakin (DP) expression can be induced in normal and thickened serosa upon treatment with bromo-deoxyuridine. Our results indicate that K18 is a marker of proliferating mesenchymal cells in rabbit serosa, whereas the combined expression of K18, K8, and DP might be related to the hypothesized alterations in the stability of gene expression. A model is proposed in which keratin-containing submesothelial cells can act as a "transit" cell phenotype involved in both regenerating mesothelial cells and formation of SM cells.

Animals↗
PubMed1996

Characterization of in vitro relaxant mechanisms in erectile tissue from rabbits of different ages.

In the present study we investigated the in vitro relaxant response of erectile tissue obtained from rabbits of different ages (3, 7 and 24 months) in order to detect the progression with age of cavernosal activity in response to substances acting via endothelium-dependent or -independent mechanisms. Noradrenaline induced a concentration-dependent contraction (0.1 microM-3 mM), with an increase in the contractility in the 24-month-old group. Acetylcholine produced a concentration-dependent relaxant effect in the three age groups, with a reduction of the maximal relaxant effect in older animals. ATP (10 microM-1 mM) and adenosine (10 microM-1 mM) induced a concentration-dependent relaxant effect that was higher in the older group. The presence of the NO2-synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) (0.1 mM) or of the P2-purinoceptor antagonist suramin did not affect ATP relaxation. Relaxation induced by sodium nitrite and nifedipine was reduced in older animals. In conclusion, aging selectively alters the in vitro responsiveness of rabbit erectile tissue. Purinergic system remains more active despite a decrease in the maximal endothelial cholinergic activity and the direct smooth muscle relaxant component.

Acetylcholine↗
PubMed1996

Chronic treatment with cyclosporine A in New Zealand rabbit: aortic and erectile tissue alterations.

Transplanted patients frequently present erectile impotence. In order to test any interference by cyclosporine A (CsA), which is commonly used in the post-transplantation management, we investigated the in vitro contractile and relaxant responses of corpus cavernosum and aorta from rabbits chronically treated with CsA. Male New Zealand White rabbits 6 months of age were treated with CsA (25 mg/kg per day s.c.) or solvent (corn oil) for 3 weeks. Descending thoracic aorta and erectile tissue were studied in vitro at the end of treatment. Isometric tension was recorded. In thoracic aorta, noradrenaline (0.1-30 mM) induced a concentration-dependent contraction with no difference between the two groups. Acetylcholine (30 nM-3 mM) produced relaxation (52 +/- 4% at 1 mM) that was significantly reduced in comparison to controls (67 +/- 4%, P < 0.05). ATP (3-10 mM) relaxation was not significantly different (maximal 78 +/- 10% and 62 +/- 12% in CsA-treated and controls). The relaxation produced by sodium nitrite was reduced in CsA-treated rabbits (at 10 mM and 0.1 mM concentrations). In erectile tissue, no significant variation in the response of isolated erectile tissue to the above drugs was observed between CsA-treated and control animals. These data indicate that chronic treatment with CsA in rabbits, despite alteration of the in vitro response of thoracic aorta, does not directly influence the function of penile tissue with relaxants.

Animals↗
PubMed1996

Nutritional assessment: a primary component of multidimensional geriatric assessment in the acute care setting.

OBJECTIVE: To test the prognostic role of nutritional variables as a component of geriatric multidimensional assessment and to study the effect of hospitalization on nutritional status. DESIGN: Validation cohort study: multidimensional assessment on admission and at discharge and a weekly nutritional assessment. SETTING: General Medicine and Geriatrics wards in an acute-care university hospital. PATIENTS: A consecutive sample of 302 patients aged 79 +/- 6 years, range 70-96 years. MAIN OUTCOME MEASURES: Mortality, longstay (> 29 days), loss of lean body mass as expressed by a negative change in mid-arm muscle circumference (MAMC). RESULTS: Incidence of mortality, longstay, and decreased MAMC was 6.9%, 24.8%, and 64.2%, respectively. According to logistic regression analysis, mortality was independently predicted by preadmission dependency in at least one Activity of Daily Living (odds ratio = 2.08, confidence limits = 1.19-3.65), clinical diagnosis of malnutrition (OR = 1.89, CL = 1.11-3.21), serum albumin < 3.5 g/dL (OR = 1.82, CL = 1.06-3.14). This predictive model allowed us to recognize 75% of the patients at risk of death by targeting 23% of the population. Longstay was independently predicted by stroke (OR = 1.54, CL = 1.01-2.35), clinical diagnosis of malnutrition (OR = 1.41, CL = 1.04-1.93), and more than five comorbid diseases (OR = 1.39, CL = 1.01-1.94). Dependency in at least one ADL was the only independent predictor of decreased MAMC (OR = 1.71, CL = 1.27-2.30). CONCLUSIONS: Nutrition variables are a cardinal component of multidimensional assessment in the acute-care setting. Nutritional status deteriorates during the hospital stay, mostly in physically dependent patients.

Activities of Daily Living↗
PubMed1996

Randomized open labelled comparative study of the efficacy, safety and tolerability of leuprorelin acetate 1M and 3M depot in patients with advanced prostatic cancer.

OBJECTIVES: In a European, prospective, 1:2 randomized phase II multicentre study, 237 patients with advanced or metastatic prostate cancer were treated with either the 1M- (80 patients) or 3M-depot formulation (157 patients) of leuprorelin acetate for 9 months to compare efficacy and safety. METHODS: Standard clinical investigations and methods were employed in the study. Leuprorelin levels were determined using a specially modified RIA. RESULTS: The two formulations produced virtually identical effects with a pronounced fall in testosterone and gonadotropin serum levels and a marked reduction in PSA levels. After 9 months' treatment, PSA was normalized (< or = 4 ng/ml) in 65.2 and 66.1% of the 1M and 3M depot patients, respectively. The best response to 1M vs. 3M depot during the study was as follows: complete remission in 5 vs. 5.7%, partial remission in 36.3 vs. 33.8% and stabilization in 40.0 vs. 40.8%. The main side effects of both formulations were related to androgen deprivation. CONCLUSIONS: Comparable results were recorded for the two formulations of leuprorelin acetate in terms of clinical response, endocrine effects and tolerability. The newly developed leuprorelin acetate 3M depot, as a refinement of the established 1M depot, offers an opportunity to improve patient compliance and provides individualized and optimized, patient-orientated treatment by reducing the number of injections to four per year.

Aged↗
PubMed1996

Is stage pT4a (D1) reliable in assessing transitional cell carcinoma involvement of the prostate in patients with a concurrent bladder cancer? A necessary distinction for contiguous or noncontiguous involvement.

PURPOSE: A series of patients with concurrent transitional cell carcinoma involvement of the prostate and bladder is reviewed to define the impact of prostate involvement pathways and the degree of prostate invasion on survival rate. MATERIALS AND METHODS: A total of 72 patients who underwent radical cystectomy for pathological stage pT4a (D1) cancer was divided into contiguous--stage pT4a, transitional cell carcinoma of the bladder extended into the prostate through the bladder wall and noncontiguous--stage pT4a simultaneous transitional cell carcinoma of the prostate and bladder carcinoma that did not directly infiltrate into the prostate through the bladder wall. In the latter group the degree of prostate invasion was classified as urethral mucosal involvement, ductal/acinar involvement, stromal invasion and extracapsular extension. The survival rate was estimated by the Kaplan-Meier and Cox proportional hazards methods. Comparisons between curves were performed by univariate log rank and multivariate L-ratio tests. RESULTS: The overall 5-year survival rate for stage pT4a was 21.5% (median followup 64 months). Furthermore, 46% and 7% of patients in noncontiguous and contiguous pT4a groups, respectively, were estimated to be alive (p < 0.000). Those with positive nodes experienced a poor outcome in both groups. Of patients with noncontiguous pT4a stage 100% with urethral mucosal involvement, 50% with ductal/acinar involvement and 40% with stromal invasion were estimated to be alive. The major prognostic factors were bladder tumor stage, nodal involvement and degree of prostate invasion. CONCLUSIONS: The invasion pathways of the prostate in patients with transitional cell bladder carcinoma have a statistically significant prognostic role. Contiguous and noncontiguous involvements are 2 distinct clinicopathological features and they should not be included in the same stage. In the noncontiguous stage pT4a group bladder and prostate transitional cell carcinoma should be separately staged, and prostate involvement also should be staged according to invasion degree.

Carcinoma, Transitional Cell↗
PubMed1996

Physiological aging and penile erectile function: a study in the rat.

Erectile function of adult (8-month-old) and aged (27-month-old) rats was investigated by in vivo and in vitro assays. Reflexogenic tonic erections were evoked in vivo by electrostimulation of the dorsal nerve of the penis. Aged rats developed tendentially low intracavernosal pressures, and the kinetics of erection and detumescence were significantly lower than in adult animals. The erectile tissue isolated from aged rats exhibited poor response to papaverine. When precontracted with norepinephrine, aged tissues required a 3-fold increase of papaverine concentration to full relaxation. Functional measurements were coupled with morphological analysis of elastic fibres of the tunica albuginea. Light microscopy showed degenerative signs of elastic fibres of aged rat specimens. Taken together, the present findings show that physiological aging is associated with penile tissue stiffness and abnormal corporal compliance.

Aging↗
PubMed1996

Self-injection devices for intracavernosal pharmacotherapy: operational classification and safety considerations.

Several self-injection devices have been recently proposed as an aid to home intracavernosal self-injection treatment for erectile dysfunction, with the purpose of allowing an easier drug administration, decreasing the artificiality of intracavernosal pharmacotheraphy, with the overall goal of increasing the acceptability of this treatment. We propose a classification of these devices according to the type of mechanical impact on the cavernosal tissue: self-injection pens, allowing for manual needle insertion and manual drug delivery; autoinsertors, with automatic needle insertion and manual drug delivery, and autoinjectors, that provide both automatic needle insertion and automatic drug delivery. The use of autoinjectors bears two theoretical risks: extra-corporal drug delivery in cases of wrong injection site, and trabecular damage due to high delivery pressure. In one device pressures 15 times higher the values reached by manual injection, and statistically higher than pressures obtained by maximal strength manual injection, were observed in an in-vitro investigation. Specific studies are needed to define a threshold pressure value for trabecular damage in the flaccid state; accordingly, information on autoinjector developed pressures should be provided by manufacturers. Clinical studies with adequate follow-up are needed as well, to verify the risk of autoinjector-induced extracorporal drug delivery, and the occurrence of intracavernosal nodules or penile curvature, compared to manual self-injection.

Adult↗
PubMed1996

Bellini duct carcinoma. A clinical and in vitro study.

OBJECTIVE: Bellini duct carcinoma (BDC) is a rare and highly aggressive renal tumor whose histogenesis is still a matter of debate although a putative origin from collecting ducts has been proposed. METHODS: A primary tumor cell culture was obtained from a BDC of a 57-year-old man who presented with a mass of the right kidney. The patient died from disease progression 18 months after diagnosis. The light and ultrastructural features were consistent with previous reports on BDC. The expression of low (Ker 18) and high (Ker 5, Ker 8, Ker 10) molecular weight keratins was studied. RESULTS: The BDC tumor cells displayed strong positivity for keratins, 5, 8 and 18 but did not react with the anti-keratin 10 antibody. Northern blot analysis of total mRNA revealed expression of the c-erbB-1 oncogene unlike two conventional clear cell carcinomas of the kidney used as control. Cytogenetic analysis revealed an aneuploid karyotype: 53,XY,del(1)(p34),+iso(1q),+iso(5p),+4,+7,+8,-14,del(16)(q22). No submicroscopic deletion on p14-21 and p26 regions of the short arm of chromosome 3 was detected on Southern blot analysis. CONCLUSIONS: The absence of structural changes in the short arm of chromosome 3 (usually present in hereditary and sporadic renal cell carcinomas) in the presence of chromosomal abnormalities observed in malignant lesions of urothelial origin confers to BDC a unique genetic profile among papillary tumors of the kidney.

Carcinoma, Papillary↗
PubMed1995

Solid-phase binding of clinical isolates of Escherichia coli expressing different piliation phenotypes. Effect of glycosaminoglycans.

Pili (or fimbriae) are frequently present on most Escherichia coli strains and they mediate binding to specific receptors. In the present work we used type 1 and P-fimbriated E. coli strains isolated from patients with urinary tract infections to study the antiadhesive effect of some synthetic commercial glucosaminoglycans (GAGs). Quantitative determinations of tritiated bacteria associated with specific receptor-activated resins indicated that displacement by GAGs was more effective in the presence of nonspecific binding. Glucuronilglucosaminoglycan sulfate (Glu-g) and esosaminoglycan sulfate (Eso-g) at a concentration of 10 mg/ml were the most active substances against P-fimbriated E. coli, while galactosaminoglucuronglycan sulfate (Gal-g) behaved as an anti-adhesive agent on type 1 fimbriated E. coli also at a lower concentration. The possible use of GAGs for the prophylaxis or treatment of chronic urinary tract infections implies a previous characterization of the piliation phenotype of the clinical isolates.

Bacterial Adhesion↗
PubMed1995

Effects of prostaglandin E1, and papaverine on non-neurogenic and neurogenic contraction of the isolated rabbit erectile tissue.

Experiments were performed to get further insights into the erectogenic mechanism of prostaglandin E1 (PGE1), which was compared to that of papaverine (PAP). PGE1 and PAP were effective in abolishing the contraction induced by N-ethylmaleimide (NEM), an adenylate cyclase blocker. However, preincubation with PGE1 but not with PAP markedly attenuated the amplitude of adrenergic nerve mediated contraction following prolonged electrical field stimulation. Preincubation with PGE1 was ineffective in counteracting the increase in tension due to exogenous norepinephrine. These data together with previous studies corroborate the hypothesis that in the presence of PGE1 a dual erectogenic mechanism takes place in modulating the cyclic-adenosine-monophosphate metabolism of the cavernous smooth muscle cell as well as the release of norepinephrine from the sympathetic terminal.

Alprostadil↗
PubMed1995

Transurethral laser surgery with a conventional modified resectoscope.

A new 1,800-microns side fiber made of pure silica with laser beam deviation of 82 degrees and divergence of 18 degrees was inserted into a modified transurethral resectoscope and used to treat in vitro some prostates removed during radical prostatectomy. Sterilization of prostatic tissue with a depth of penetration of 12 mm was observed after treatment with 20 W for 2 min. Irradiation with 60 W for 1 min produced vaporization and explosion of the tissue and a depth of penetration of 15 mm. The laser resectoscope was then successfully employed for the treatment of 6 cases of benign prostatic hyperplasia (BPH) as well as in high risk patients with bulky bleeding bladder tumors (4 cases) and with transitional carcinoma of the prostate invading the parenchyma (2 cases). 3 patients with small size BPH underwent only laser irradiation. All others were submitted to traditional transurethral resection followed by laser treatment with Nd: YAG using the same instrument. Our laser resectoscope lowers costs since the side fiber is reusable for 4-5 treatments and brings laser treatment nearer to traditional endoscopic treatment, thereby making its application more comfortable for the urologist.

Cystoscopy↗