Search PubMed⌕ Search

Biomedical subjects

F Pagano

Publications and source records attributed to F Pagano.

At least 73 records · Page 4Linked to original sources

Bladder function in the aged rat: a functional and morphological study.

This study was designed to characterize urinary bladder function in the aged rat (27 months of age). For comparative purposes, two different control groups were included into the experimental protocol: normal 6-month old and hyperdiuretic 6-month old rats. Increased threshold volume for micturition and increased bladder mass were found in both aged and hyperdiuretic rats. No difference in the amplitude of micturition contractions was detected between groups. In the aged rat, but not in the hyperdiuretic one, augmented threshold volume and bladder mass were associated with increased intravesical pressure at micturition and structural changes of intramural bladder innervation. When activated, the vesicovesical reflex did not show any change in terms of rate of isovolumetric contractions. In the aged rat, altered sensory information on the state of maximum fullness seems to play an important role in determining abnormal cystometric findings.

Age Factors↗

Improving the efficacy of BCG immunotherapy by dose reduction.

Several clinical trials have shown intravesical bacillus Calmette-Guérin (BCG) to be effective in the prophylaxis of papillary tumour recurrences and in the therapy of bladder carcinoma in situ (CIS), as well as in delaying progression to muscle invasion. Nevertheless, the optimal regimen of BCG therapy for superficial bladder cancer has still to be defined. In a previous phase II trial, a low-dose regimen (BCG Pasteur strain, 75 mg) was able to achieve clinically significant response rates with a decrease in side-effects compared with other reported studies using standard-dose BCG. However, a phase III randomized trial--low dose versus standard dose (BCG Pasteur strain, 75 vs. 150 mg)--was considered necessary to clarify definitively the relationships between dose, efficacy and toxicity. The results of the interim analysis of 183 patients (performed in 1993) have shown response rates to be better in patients submitted to a low-dose BCG regimen (p = 0.0009) and a significant decrease in most of the common side-effects (cystitis, fever, haematuria; p < 0.05). Breaking down the results by stage, no differences in response rates were found in patients with stage TaM (70 vs. 62% in low-dose and standard-dose regimens, respectively, p = 0.5). In T1M and CIS stages, 82 and 0 (p = 0.07), and 64 and 0% (p = 0.0003) of patients were free of tumour following low-dose and standard-dose therapy, respectively. An additional 6-week course in patients who failed the induction course retrieved additional responses in both groups. No differences in progression rates were observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Intravesical↗

A simplified in vitro preparation of the corpus cavernosum as a tool for investigating erectile pharmacology in the rat.

This work describes a simple technique for the assessment of corpus cavernosum function in a species, the rat, representing a convenient model for basic research. We obtained measurable and reproducible responses to different pharmacological agents as well as to electrical field stimulation. In view of the present results we conclude that isolation of the erectile tissue together with the septum may constitute a valuable experimental tool for investigating both local erectile mechanisms and the action of drugs, in the rat corpus cavernosum. Data obtained in the presence of N-nitro-L-arginine and methylene blue further reinforce the concept that nitric oxide may be involved in the process of erection in the rats as well as in other animal species.

Animals↗

Technical options in complex ureteral lesions: 'ureter-sparing' surgery.

From January 1979 to December 1992, 74 patients with ureteral lesions due to ureteral or renal instrumentations, failed gynecological or reconstructive surgery were addressed to our department for a reconstructive program. Fifty-two of them were managed by standard ureteropyeloanastomosis or psoas bladder hitch and ureteral reimplants. Twenty-two patients (12 females, 10 males, age range 28-68 years) suffered from extensive ureteral lesions (5-7 cm) and were managed by major ureteral reconstructive surgery intended to restore urothelial continuity. Three patients had a solitary kidney, and 6 cases suffered from bilateral ureteral injuries. The procedures employed were: psoas kidney hitch with ureteropelvic anastomosis (4 cases), kidney psoas bladder hitch (5 cases), 'extended' psoas bladder hitch (5 cases), transureterouretero-anastomosis+psoas bladder hitch (5 cases), psoas kidney-bladder hitch and transureterouretero-anastomosis (1 case), renal autotransplantation (2 cases). Only 5 minor postoperative complications were observed and all patients but one had satisfactory results with a follow-up ranging from 6 to 84 months. The authors believe that the restoration of urothelial continuity is the best option compared to other technical solutions such as ileal replacement, or diversion and nephrectomy. Autotransplantation should be reserved for rare selected cases.

Adult↗

Cytoskeletal and cytocontractile protein composition of smooth muscle cells in developing and obstructed rabbit bladder.

The differentiation patterns of smooth muscle cells (SMC) in rabbit bladder during development and in the hypertrophic response to partial outflow obstruction induced in adult animals were evaluated by biochemical and immunochemical techniques and by using a panel of monoclonal antibodies specific for desmin, vimentin, alpha-actin of smooth muscle (SM) type, SM myosin, and nonmuscle (NM) myosin isoforms. Desmin and SM alpha-actin were homogeneously distributed in SMC of developing, adult, and obstructed bladders. Conversely, marked changes in the ratio and antigenicity of SM myosin isoforms were observed by SDS electrophoresis and Western blotting, respectively. In particular, the 205 K (SM1) isoform was down-regulated with development whereas the 200 K (SM2) isoform was up-regulated around 7 days after birth and down-regulated in the obstructed bladder. Vimentin was expressed in SMC of the fetal bladder and declined markedly during postnatal, physiological hypertrophy of SMC, which occurs concomitantly with diminution of DNA synthesis. This polypeptide became detectable, however, in SMC of obstructed bladders. The 196 K (NM) myosin isoform recognized by NM-A9 antibody, present only in endothelium of blood vessels and in mucosa of normal fetal and adult bladders, became expressed in detrusor muscle, when SMC underwent a process of pathological hypertrophy. The reexpression of vimentin and the de novo appearance of NM myosin isoform in hypertrophic bladders can be reversed when the tissue mass is reduced, such as in bladders after 1-month recovery from partial obstruction. Thus, a specific NM myosin isoform can be used as a marker of SMC hypertrophy in obstructed bladder. In addition, the combined use of anti-vimentin and NM-A9 antibodies can distinguish between SMC which are in the physiological or in the pathological condition of adaptive bladder hypertrophy.

Animals↗

Electrical stimulation of the dorsal nerve of the penis evokes reflex tonic erections of the penile body and reflex ejaculatory responses in the spinal rat.

An animal model using the spinal rat was characterized. Electrical stimulation of the dorsal nerve of the penis elicited reflex tonic erections of the penile body and reflex bulbospongiosus muscle activity, flips and ejaculations. The tonic erections of the penile body are independent from contractions of the bulbospongiosus muscle and appear to be the result of a neurovascular process. Our observations suggest that reflex bulbospongiosus muscle activity, flips and ejaculations are a single complex reflex response, which we define as reflex ejaculatory response. Two parameters predicted the occurrence and type of reflex response. The visualization of bulbospongiosus muscle activity during surgical isolation of the dorsal nerve of the penis was sufficient to anticipate the elicitability of reflex ejaculatory responses. The latter, together with a systemic systolic pressure > or = 73 mmHg., warranted the elicitability of reflex tonic erections. The similarities found in the physiology of rat tonic penile body erections and of human erections make this model promising for further elucidation of sexual function. Moreover, the present model may prove useful for the investigation of neurogenic erectile dysfunction, and of neurogenic ejaculatory disorders.

Animals↗

Photosensitization of cystine stones to induce laser lithotripsy.

We report the preliminary results of laser lithotripsy of cystine stones accomplished in 2 patients with the use of a new method of photosensitization. Transurethral rigid ureterorenoscopy was performed with an 8.5F instrument to reach 0.8 and 1.8 cm. stones located in the right and left lumbar ureters, respectively. A 320 mu. fiber was then inserted and pushed into contact with the stone. Then, 400 preliminary impulses were released from a pulsed dye laser (504 nm) with energy output at 140 mJ. and at a rate of 5 Hz. without any visible modification of the stone structure. The saline solution used as irrigation fluid was then substituted with a 2% solution of rifamycin. Totals of 95 and 152 impulses released at the same energy output previously used were then sufficient to produce a satisfactory fragmentation of the stone in both cases. Sonography and excretory urography showed no alterations of the treated urinary tract in either case. The use of rifamycin in the irrigation fluid is suggested for laser treatment of hard or nonabsorbent stones, since this substance favors optical coupling and lowers the threshold of plasma formation on the surface of the stone.

Adolescent↗

Five years experience in experimental laser lithotripsy.

In the first part of our experience approximately 300 stones of different composition have been treated in vitro with three different laser sources: Nd-YAG laser (1,064 nm), dye laser (504 nm) and alexandrite laser (755 nm). Calcium oxalate monohydrate and brushite stones appeared to be the most resistant to lithotripsy. Highest fragmentation rates were obtained for calcium oxalate dihydrate stones followed by struvite, uric acid and hydroxyapatite stones. The Nd-YAG laser did not appear to be ideal for lithotripsy since early damage to the fiber tip was observed when this source was used. Both the dye and the alexandrite lasers were almost always effective in fragmenting the various types of stones. We subsequently treated some cystine stones while immersed in water or in solutions of carmine indigo (2%), methylene blue (5%), rifamycin (0.6 and 6%) and rifampicin (0.8 and 0.3%) with the dye or the alexandrite laser. The spectra of these solutions, previously analyzed with the spectrophotometer, showed that rifamycin and rifampicin absorbed large amounts of light radiation at the wave length of the dye laser (504 nm). Successful fragmentation occurred only when the dye laser was used to treat stones immersed in the more concentrated solutions of these two substances. The quantity of fragmented material after treating a 10-cm3 cystine stone previously immersed in the more concentrated solutions of rifamycin and rifampicin (30 and 10 mm3, respectively) confirmed previous results.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗

Effects of bacillus of Calmette-Guerin, Candida albicans and human recombinant interferon-gamma on RNA metabolism and on in vitro release of tumor necrosis factor-alpha by human monocytes/macrophages.

Bacillus of Calmette-Guerin (BCG) was found to be effective in the therapy of superficial bladder cancer, although the mechanisms by which this occurs have not yet been clarified. One hypothesis is related to the ability of monocytes/macrophages (MN/M phi) to release tumor necrosis factor-alpha (TNF-alpha), a monokine with cytotoxic and cytostatic effects against certain tumor cell lines. The present study demonstrates that BCG and C. albicans are both very efficient inducers of TNF-alpha, while they inhibit uridine uptake and incorporation into human MN/M phi RNA. However, unlike C. albicans, BCG is cytotoxic for MN/M phi, as determined by release of labelled leucine from target cells.

Animals↗

Ultrastructural analysis of the cavernous and dorsal penile nerves in experimental diabetes.

The present study was designed to investigate whether experimental diabetes determines structural changes in peripheral nerves involved in reflexogenic erection, namely the cavernous and the dorsal nerve of the penis. Myelinated axons were examined in the dorsal nerve of the penis from rats with streptozotocin-induced diabetes (3- and 6-month duration). Morphometric analysis disclosed a significant decrease of myelinated fibre size most likely due to a progressive axonal atrophy. In addition, morphological analysis revealed diffuse accumulation of glycogen within axons, lipid droplets in Schwann cells and pronounced sequestration of axoplasm by adaxonal Schwann cell processes. These signs were particularly prominent in 6-month-diabetic rats. Myelinated and unmyelinated axons of the cavernous nerve were analysed in 6-month-diabetic animals. No substantial ultrastructural abnormalities were found in the cavernous nerves. These results suggest that in experimental diabetes regionally specific structural changes occur in neuronal pathways subserving erectile function.

Animals↗

Myofibroblast-derived smooth muscle cells during remodelling of rabbit urinary bladder wall induced by partial outflow obstruction.

BACKGROUND: Fibrosis of serosa, along with smooth muscle (SM) cell hypertrophy, has been shown to occur in the rabbit bladder after partial outflow obstruction. Identification of cells involved in the serosal thickening can be of primary interest to elucidate the functional changes that this organ undergoes. EXPERIMENTAL DESIGN: Cytoskeletal protein composition of cells present in the thickened serosa at different times from the onset of obstruction (7, 15, 30 and 60 days) was evaluated. This was accomplished by means of a panel of monoclonal antibodies specific for a number of differentiation markers of mesenchymal cells (vimentin, desmin, alpha-actin of SM type, nonmuscle (NM) and SM myosins), and by immunocytochemical and immunochemical techniques. RESULTS: The immunocytochemical study revealed that cells in serosal thickening follow a two-step maturation process from pre-existing vimentin-positive cells. In the first time period (7 to 15 days of obstruction), these cells predominantly achieved an immunophenotype corresponding to that of a specific myofibroblast subtype (i.e., containing vimentin, NM myosin, and SM alpha-actin). After 30 days from the onset of obstruction, the cytoskeletal protein content of serosal cells, as also revealed by Western blotting experiments, shifted towards that of fetal-type SM cells (i.e., presence of vimentin, NM myosin, SM alpha-actin, and SM myosin isoforms). Distribution of vimentin, desmin, SM alpha-actin, and SM myosin in tissue culture as well as the ultrastructure in vivo very closely resembled that of SM cells. Bromodeoxyuridine incorporation studies indicated that cells accumulated in the serosa of obstructed bladders did not derive, at least initially, from SM cells of the detrusor muscle. CONCLUSIONS: These findings are consistent with the existence of a differentiation process in which resident mesenchymal cells of bladder serosa may transform to myofibroblasts and, subsequently, in fetal-type SM cells during experimental outflow obstruction.

Actins↗

Effect of streptozotocin-induced diabetes on electrically evoked erection in the rat.

This study was designed to investigate whether experimental diabetes in rats could functionally affect reflexogenic erection. Erection was elicited by means of electrical stimulation of the dorsal nerves of the penis and recorded as intracorporeal pressure. Rats were examined 1, 3 and 6 months after diabetes induction by streptozotocin. Three and 6 month diabetes caused a significant decrease of latency for erection and a slower phase of detumescence when compared to age-matched controls. In addition, a trend for a lower developed intracorporeal pressure was present in the 6 month diabetes group. Our results indicate that experimental diabetes is associated with alterations of reflexogenic erection.

Animals↗

Clinical value of pathologic changes after intravesical BCG therapy of superficial bladder cancer.

Bladder pathologic features related to intravesical bacillus Calmette-Guerin (BCG) therapy in superficial bladder cancer (Ta, T1, Tis) were evaluated and related to clinical outcome. A total of 105 patients were treated with 75 mg Pasteur BCG weekly for six consecutive weeks. When tumor was not demonstrated a maintenance course was given. An additional six-week course was given when tumor recurrence or persistence, without progression, was observed after the induction course. An inflammatory change in the bladder was the most common pathologic finding. Granuloma was the only specific BCG-related feature and did not appear to be a prognostic factor because of low incidence (24%) and lack of correlation with clinical course. Dysplasia occurred more frequently (57%) in nonresponder patients and (26%) in responder patients, often heralding recurrence of tumor. All patients showing concurrent squamous and/or glandular metaplasia were unresponsive to BCG therapy. Histology and cytology did not correlate perfectly: cytology was ineffective in low-grade tumors and improved diagnostic accuracy, particularly when dysplasia was histologically evident.

Administration, Intravesical↗

Mitomycin C in multiple superficial bladder tumors: short-term therapy, long-term results.

At the Institute of Urology, University of Padova, 125 patients with multifocal superficial bladder cancer underwent treatment with intravesical Mitomycin C (MMC; 1 weekly instillation of 40 mg for 8 consecutive weeks) between January 1982 and December 1988. Eighty-four patients had multifocal papillary tumors (stages Ta-T1) and 41 patients had carcinoma in situ of the bladder. At 6 and 36 months the tumor free percentage in the group with papillary tumors was 69 and 36%, respectively; for carcinoma in situ the complete response percentage at the same intervals was 80 and 36%. Thirty-one patients previously unsuccessfully treated with adriamycin did not show any difference compared to untreated ones. The authors emphasize the efficacy and low toxicity of intravesical MMC in multiple superficial bladder cancer. The possibility of long-term relapse suggests maintenance therapy.

Administration, Intravesical↗

Renal cell carcinoma with extension into the inferior vena cava: problems in diagnosis, staging and treatment.

Management of renal cell carcinoma with extension into the vena cava is one of the highest challenges in urology. The delineation of the upper level of the endocaval thrombus, its possible extension into the hepatic veins and possible involvement of the caval wall are crucial points and dictate the operative strategy. From 1978 to 1989, at the Department of Urology of the University of Padua, 29 patients with renal cell carcinoma and caval extension were submitted to surgery. Seventeen patients were staged V2 according to the UICC TNM Staging System 1983, 2 patients V3 and 10 V4. The median patient age was 57 years and the male:female ratio was 1.9:1. A complete thrombus removal was accomplished in all patients. In 2 patients, a caval resection was necessary. Five patients died during the perioperative period. The patient survival rate was comparable to that of T3N0M0-staged cases. Survival rates at 1 and 4 years were, respectively, 96.8 and 40% for V2 cases, 100 and 100% for V3, 85.7 and 40% for V4. It seems, therefore, that in patients with locoregional disease and satisfactory conditions, the presence of vascular invasion did not lead to a worst prognosis. By itself, the extent of the caval thrombus seems not to influence the prognosis.

Adult↗