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Biomedical subjects

L Viganò

Publications and source records attributed to L Viganò.

At least 37 records · Page 2Linked to original sources

Recurrences and progression of superficial bladder cancer following long-term intravesical prophylactic therapy with mitomycin C: 48-month follow-up.

A total of 208 patients with superficial transitional-cell carcinoma of the bladder (STCC) after transurethral resection were treated with 30 mg intravesical instillations of mitomycin C (MMC) weekly for 8 weeks, followed by monthly maintenance doses for 12 months. All patients were controlled with a urinary cytological examination every 2 months and with cystoscopy every 3 months. Mean follow-up was 47.8 and 49.3 months in the prophylaxis and control groups, respectively. The incidence of tumor recurrences at the 12th and 48th months was 29 and 44%, respectively, in the MMC group and 45 and 58%, respectively, in the control group. Progression evaluated by grade and stage was significantly higher in the control group. These data indicate that MMC appears to be effective in the prophylaxis of STCC, but the possibility of long-term relapse suggests maintenance of a longer therapy.

Administration, Intravesical↗

Bioconcentration of trace metals in rainbow trout: a field study.

Caged rainbow trout were exposed for a month at two sites in the river Po, one upstream and the other downstream of the river Lambro inlet. Gills, spleen, kidney, muscle, and vertebral bone were examined for metal content after 7, 15, and 30 days of exposure. Cd accumulated mostly in spleen and muscle; Hg in muscle and kidney; Pb in bone, spleen, and kidney; Cr in spleen, muscle, and gills; and Cu in kidney. The highest Zn levels were measured in gills, but no consistent variations were observed. Trends of accumulation, target organs, and estimated whole body contents are discussed. Although the metal content of most organs was low and variations in concentrations were relatively contained, differences between the two stations were observed for Cd, Hg, Pb, and Cr.

Animals↗

Densitometric and biochemical alterations in bony tissue induced by ureterosigmoidostomy.

The mineral content of bone was measured in 134 male patients who underwent ureterosigmoidostomy within the past 18 years. Moreover, the principal humoral indices of bone metabolism, together with hematic pH and alkaline reserve (BE) values were evaluated. This study showed that after approximately 6 years from a ureterosigmoidostomy there was significant bone demineralization. These data, supported by a parallel increase of serum osteocalcin, show that ureterosigmoidostomy represents a risk factor for osteoporosis especially in those patients who already have below normal values of bone mineral density prior to surgery.

Alkaline Phosphatase↗

[Laser and ultrasonic therapy in simultaneous emission for the treatment of plastic penile induration].

Induratio penis plastica (IPP) or Peyronie's Disease is characterized by the presence of one or more fibrous patches in the tunica albuginea or intercavernous septum. IPP is a slowly evolving disease which may cause a bending of the penis as well as pain during erection. As an alternative to the numerous pharmacological therapies already existing, or in association with them, some kinds of physical treatments, such as ionophoresis, ultrasound therapy and laser therapy, have recently been used. In this study we have evaluated the effectiveness of physical therapy combined with laser and Ultrasounds in the treatment of IPP. Sixty-eight patients were randomly divided into three groups: the first group was treated with orgotein infiltrations, the second with laser and Ultrasounds and the third with an association of both treatments. On the basis of this study, we can affirm that the effectiveness of laser therapy associated with ultrasounds in treating painful symptomatology of IPP at its initial phase overlaps that of orgotein infiltrations. No measurable modifications were documented neither in patch dimensions nor in their echostructures and in no case remarkable modifications of the penile bending were evidenced. Therefore laser therapy associated with ultrasounds represents at the moment an efficacious alternative to medical treatment of IPP at the initial phase, as it does not present any kind of contraindications and it is surely better tolerated than any treatment with penile infiltrations.

Adult↗

Bioconcentration of polychlorinated biphenyls (PCBs) in rainbow trout caged in the River Po.

Two groups of rainbow trout were caged in the River Po upstream and downstream of the confluence with the River Lambro, a relatively small tributary which drains the most industrialized and urbanized area of the entire basin. Fish were analyzed for PCB concentration at the start of the experiment and after 7, 15, and 30 days of exposure. The results demonstrate that the emission of the River Lambro represents an important point source of PCBs to the River Po and that part of the transported load is readily bioavailable, since caging virtually excluded trophic transfers. On the basis of PCB levels measured in downstream trout, the steady-state concentration and the congener pattern were predicted by means of a computer program. These projections were compared with published data obtained with native fish caught downstream from the River Lambro.

Animals↗

Treatment of bladder carcinoma in situ with mitomycin C: long-term follow-up.

Mitomycin C (MMC) was given intravesically to 14 patients with transitional-cell carcinoma in situ of the bladder (CIS) between 1985 and 1989. Of the 10 patients with complete response two presented progression during the follow-up: one of them in T2 at the 32nd month, and one had a relapse of CIS with diffusion to the prostatic urethra at the 34th month: both patients underwent cystectomy. One patient died of an unrelated cause. At the 48th month 5 out of 7 patients were free from neoplasm. Neoplastic recurrence occurred in 3 patients: one responded to a second endoscopic resection and instillation of MMC, two presented further recurrences. Two patients underwent cystectomy: one for neoplastic progression and one for involvement of the prostatic urethra. MMC seems to be effective in the treatment of CIS of the urinary bladder and the unresponsiveness to chemotherapy must be considered as an adverse prognostic factor for the progression of the neoplasm.

Administration, Intravesical↗

Cellular expression of lymphocyte function-associated antigen-1 and intercellular adhesion molecule-1 in normal kidney structures and in renal cancer. Possible significance in immune response and in the clinicopathological correlation.

In this study we investigated the presence of lymphocyte function-associated antigen-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1) on renal cell cancer in 16 patients who underwent nephrectomy. In all cases, normal renal tissues presented ICAM-1 on the parietal epithelial cells lining Bowman's capsule while neither the visceral epithelium nor the glomerular endothelium were stained. The epithelial proximal and distal tubular cells were stained poorly (5 +/- 3 positive tubular cross sections/mm2). No renal cells were stained by the monoclonal antibody for LFA-1. In contrast, in renal cancer tissue we found 6 cases, negative for ICAM-1 and the others positive with a mean number of positive tubular cross sections of 52 +/- 37/mm2. In 10 cases staining with LFA-1 antibody was negative, while for the other cases the mean number of positive tubular cross sections was 11 +/- 8/mm2. Our results suggest that the expression of ICAM-1 and LFA-1 on the surface of malignant cells may explain the unusual clinical aspects of renal cell carcinoma, its association with the immune system, and clarify certain aspects of immunotherapy.

Carcinoma, Renal Cell↗

[Role of color-Doppler in the assessment of erectile impotence: personal experience].

We present our experience with colour duplex sonography in the assessment of 38 impotent men, whose ten underwent radical prostatectomy, following intracavernous pharmacological stimulation with PGE1. All patients with a clinical good response following PGE1 injection had peak cavernosal artery velocities > 30 cm/sec. The remaining suboptimal responders who presented an elevated end-diastolic velocity (> 5 cm/sec) showed a venous leakage demonstrated with cavernosography. Colour duplex sonography is a valuable and non-invasive tool in the assessment of impotence and can provide valuable information in the diagnosis of vasculogenic erectile dysfunction.

Aged↗

Intravesical mitomycin C for the treatment of carcinoma in situ of the bladder: 36 months follow-up.

Mitomycin C (MMC) was given intravesically over a period of 36 months to 14 patients with transitional-cell carcinoma in situ of the bladder (CIS). Initial complete response was obtained in 10 patients. Of these patients, 5 presented recurrences; one in T2 at the 32nd month, one had a relapse of CIS with diffusion to the prostatic urethra at the 34th month: both patients underwent cystectomy. The remaining three patients presented Ta or T1 relapses and underwent endoscopic resection and a new instillation of MMC. The 4 patients who did not respond were treated with a new instillation of MMC:3 were unsuccessful and underwent cystectomy (one at the 9th month, one at the 12th month for progression to T2 and one at the 14th month for involvement of the prostatic urethra); the 4th patient responded to the treatment but at the 14th month had a relapse of CIS and he underwent cobalt-therapy. At the 36th month, 7 out of 13 patients were free from neoplasm. A neoplastic progression occurred in 3 patients: one out of the 9 patients who responded to the treatment and two out of the 4 who did not respond. Diffusion to the prostatic urethra was observed in 2 of the 13 patients; one patient responded to MMC and the other did not. Five patients underwent cystectomy: 3 for neoplastic progression and 2 for involvement of the prostatic urethra. MMC seems to be effective for the treatment of CIS of the urinary bladder and the absence of a response to chemotherapy must be considered an adverse prognostic factor for the neoplastic progression.

Administration, Intravesical↗

Multiple genotoxicity biomarkers in fish exposed in situ to polluted river water.

Specimens of rainbow trout (Oncorhynchus mykiss) were either kept in an aquarium under laboratory conditions or caged in the River Po (Northern Italy), upstream or downstream the confluence with the River Lambro, a small yet heavily polluted tributary. Genotoxicity biomarkers, evaluating the internal dose or early biological effects, were monitored after 7, 15 and 30 days of in situ exposure. With the exception of a slight increase of aminopyrine-N-demethylase and uridine-5'-diphospho-glucuronosyl-transferase, no significant effect was produced in fish kept upstream the River Lambro, as compared to control fish kept in the aquarium. In contrast, the responsibility of this tributary in carrying sublethal doses of both genotoxic agents and enzyme inducers into the main river was proved by the significant occurrence of early biological alterations in fish caged downstream. In fact, (a) bile extracts contained frameshift mutagens requiring metabolic activation, with a prevalence of liposoluble components after a short exposure, followed by a time-related increase of conjugated components, in minor part with glucuronic acid; (b) the monooxygenases aminopyrine-N-demethylase, uridine-5'-diphospho-glucuronosyl-transferase and, with sharp differences, arylhydrocarbon hydroxylase and 7-ethoxyresorufin-O-deethylase were enhanced in liver microsomal fractions; (c) the liver cytosolic fractions had an enhanced ability to convert 3-amino-1-methyl-5H-pyrido(4,3)indole into mutagenic metabolites in S. typhimurium; (d) cytogenetic damage was demonstrated by an increased frequency of micronuclei in peripheral blood erythrocytes.

Animals↗

Trigonoplasty by Gil Vernet in the treatment of vesicoureteral reflux in adult patients.

There are several surgical procedures for the correction of primary vesicoureteral reflux. Among them, the one of increasing success for its safety and effectiveness is that introduced by Gil Vernet at the beginning of the 1980s, primarily in the pediatric field. By the time of this study, its use had been extended to adult patients as well. We report the results obtained with this method in 17 adult patients with primary vesicoureteral reflux.

Adolescent↗

Self-retaining intraurethral device for treatment of prostatic obstruction.

We report our experience about insertion of 32 self-retaining intraurethral device (IUC) in patients with prostatic obstruction. Follow-up ranged between 2 and 38 weeks. Success rate of IUC insertion was 93.7% and 46.6% of patients have IUC in place without complications during follow-up. IUC is easy and quick to introduce, it allows spontaneous voiding, full continence, sexual activity and routine life-style. It represents a useful alternative to indwelling catheter in patients at high risk or refusing surgery and it might be used in patients who are waiting for surgery or need long term catheterization.

Aged↗

[Local hyperthermia in the treatment of benign prostatic diseases].

Local Prostatic Hyperthermia is a 8 year old procedure that has been used for treating benign prostatic hypertrophy, chronic non bacterial prostatitis and prostatic carcinoma. We treated 80 patients affected by benign prostatic diseases who referred to our Clinic from November 1990 to December 1991. 42 patients were affected by benign prostatic hypertrophy (7 of them with permanent bladder catheter) and 18 patients were affected by chronic non bacterial prostatitis. A 915 Mhz microwaves generator apparatus with endorectal probe and cooling circuit has been used. The criteria we used to include patients in treatment were the following: high operating risk, the refusing of the operation, a prostatic volume bigger than 180 cc and finally a rectum thick less than 10 mm. All patients underwent preliminary echographic, hematic , urodynamic and rectoscopic exams. A prostatic biopsy was taken at the beginning and at the end of the treatment. During every session, which lasted sixty minutes and was repeated twice a week, we applied a temperature of 42 C degrees in patients with benign prostatic hypertrophy, and a temperature of 41 C degree in those with chronic non bacterial prostatis. Patients were checked with the same echographic and urodynamic parameters three months, six months and 1 year after the treatment. Subjective and objective symptoms improved in 65% of cases, and we also noticed a 50% reduction of post-urination residue, with an increase of maximal urinary flux. We also noticed a decrease of the dysuria and nycturia.(ABSTRACT TRUNCATED AT 250 WORDS)

Chronic Disease↗

Pharmacology and clinical toxicity of 4'-iodo-4'-deoxydoxorubicin: an example of successful application of pharmacokinetics to dose escalation in phase I trials.

In a prospective phase I trial involving 35 patients with metastatic carcinoma, we tested a pharmacokinetic strategy for guiding dose escalation of the anthracycline 4'-iodo-4'-deoxydoxorubicin (I-DOX), a new analogue reported to be more potent and less toxic than doxorubicin. This strategy is potentially a safe and more rapid way of determining the maximum tolerated dose (MTD) of anticancer agents. Retrospective studies have shown that the total plasma drug exposure after a dose lethal to 10% of mice (LD10) is approximately equivalent to the total exposure produced in humans by the MTD. Thus, we intended to aim dose escalation in humans to achieve the area under the curve for I-DOX plasma concentration x time (AUC) equivalent to that produced in mice by an LD10. However, differences in I-DOX pharmacokinetics and metabolism in BDF1 mice and humans at the initial dose prevented immediate application of this strategy. Therefore, we escalated the dose by the modified Fibonacci scheme while investigating the pharmacology of I-DOX and its major plasma metabolite 4'-iodo-4'-deoxy-13-dihydrodoxorubicin (I-DOXOL). Plasma pharmacokinetics was characterized by rapid elimination and extensive metabolism of I-DOX to I-DOXOL. The ratio of I-DOXOL to I-DOX plasma AUC was 12.8 +/- 7.3 SD. The plasma pharmacokinetics of I-DOX and I-DOXOL were linear in the range of tested doses (2-90 mg/m2). The LD10 in mice was 6.8 mg/kg for I-DOXOL and 6 mg/kg for I-DOX, and the concentration of drug that inhibited by 50% (IC50) the growth of human granulocyte-macrophage colony-forming units (CFU-GM) was 80 nM for I-DOXOL and 50 nM for I-DOX. From these findings, we concluded that the toxic effects of I-DOX and I-DOXOL are equivalent and reset the pharmacokinetic target of escalation to the sum of I-DOX and I-DOXOL AUCs at I-DOX LD10. Then we safely applied pharmacokinetically guided escalation to determine the MTD (80 mg/m2). The plasma AUC of I-DOX and I-DOXOL at the human MTD is 71% of the AUC at mouse LD10. The only dose-limiting toxic effect was severe granulocytopenia.

Adult↗

Role of daunosamine and hydroxyacetyl side chain in reaction with iron and lipid peroxidation by anthracyclines.

Doxorubicin (Adr), daunorubicin (Dnr), and analogs of Adr modified in daunosamine (4'-epi-Adr and 3'-N-acetyl-Adr) were investigated with respect to their reaction with Fe(III) and analyzed for the ability of the corresponding iron complexes to sustain lipid peroxidation of isolated human platelet membranes. When the proportion of iron [25 microM Fe(III)] to Adr was 1:4, almost 50% of the metal was reduced following 1 hour of anaerobic reaction, while only approximately equal to 14% of the bound iron could be extracted as Fe(II) in the reactions of the Dnr complexes. The reaction of Adr was associated with formation of two main novel anthracyclines. One of the products had lost the C14 atom of the C9 chain and displayed chromatographic features and visible UV light spectra identical to those of authentic 9-dehydroxyacetyl-9-carboxyl-Adr. In complexes of iron and Dnr, no significant anthracycline degradation was observed. Reduction of anthracycline-bound Fe(III) by 4'-epi-Adr (38%) and 3'-N-acetyl-Adr (21.2%) was consistently less than that by Adr. Complexes of the anthracyclines investigated had different abilities to sustain lipid peroxidation, which was blocked (a) by the iron chelators deferoxamine and bathophenanthroline, indicating that Fe(III) and Fe(II) were needed for the reaction, and (b) by ICRF-198, the chelating product that forms intracellularly by hydrolysis of razoxane, which can prevent Adr cardiotoxicity. Peroxidation was not affected by scavengers of reduced oxygen radicals (superoxide dismutase, catalase, and mannitol). The isolated membranes contributed to the reduction of anthracycline-bound Fe(III) and probably represented the main determinant of lipid peroxidation by iron-Dnr. Lipid peroxidation was significantly less for complexes of iron with 4'-epi-Adr or 3'-N-acetyl-Adr than for complexes of iron with Adr. The observed differences may be relevant to the different biologic properties of Adr and its analogs, in particular their different degrees of cardiotoxicity.

Antibiotics, Antineoplastic↗

Approaches to modeling toxic responses of aquatic organisms to aromatic hydrocarbons.

Acute toxic effects on Salmo gairdneri, Poecilia reticulata, Daphnia magna, and the growth inhibition of Selenastrum capricornutum were measured for eight aromatic hydrocarbons. Toxicity measurements were carried out following the OECD standard guidelines modified as appropriate in order to prevent hydrocarbon loss by volatilization; the concentrations of the substrates in the test solutions were periodically measured by HPLC. The toxic responses were analyzed in terms of the n-octanol/water partition coefficients, by means of linear regression analysis, and in terms of five molecular properties simultaneously, by means of the partial least squares analysis in latent variables (PLS). The univariate and multivariate quantitative structure-activity relationship models obtained by the two approaches are compared and discussed.

Animals↗