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Biomedical subjects

G Strada

Publications and source records attributed to G Strada.

18 recordsLinked to original sources

[Orthotopic ileal neobladders in men and women: techniques and comparison].

PURPOSE: evaluation of results and complications of ileal orthotopic neobladders in men and women with transitional cell carcinoma. MATERIALS AND METHODS: between 12-89 and 12-95 we performed 146 radical cystectomy for bladder neoplasm, in 32 patients we can perform ileal orthotopic neobladder, 29 were male and 3 were female. Oncologic indications to this kind of operation were: clinical stage T2, T3a, T3b, T1G3 multicentric and or recurrence, absence of metastasis absence of nodal metastasis, negativity of urethral biopsy. General contraindications were urethral stenosis and incontinence. Oncological contraindications, in woman, were bladder neck neoplasm or urethral neoplasm. In 4 patients we use Camey II technique, in 19 pts we performed the paduan ileal neobladder, in 9 pts we use Hautmann technique. 7 patients performed neoadjuvant chemotherapy with 4 circles of MVAC, 4 pts underwent adjuvant chemotherapy, and 2 pts salvage chemotherapy. In woman we take care during cystectomy to dissect cardinal ligament very close to cervix uteri, to resect the uterosacral ligament far to the sacrum. We did not dissect under the ureter and we cut the urethra 0.5-1 cm far from the bladder neck. RESULTS: follow up was between 6 and 66 months. 24 patients are now alive and disease free, 2 patients are alive with disease progression, 1 have a pelvic recurrence and 1 have pulmonary recurrence. 4 pts died for disease progression and 2 for non oncological cause, quality of life was considered as regard to continence and sexual activity. 1 pts was completely incontinent and 1 pts has nocturnal incontinence with a daily micturation every 1 hour. We can evaluate only 18 patients for sexual activity and 4 reported normal erection. COMPLICATIONS: in three cases we had to reoperate for early complications due to mechanical bowel obstruction, ileocutaneous fistula and wound dehiscence. In three cases we had the formation of stones, in two patients ureteroileal stenosis, in two cases urethro-ileal stenosis and 1 reflux from the neobladder. Orthotopic ileal neobladder allows a very good quality of life and is the first choice derivation after radical cystectomy.

Antineoplastic Combined Chemotherapy Protocols↗

[Lymphocyte levels before treatment with subcutaneous interleukin-2 and during maintenance treatment in relation to the clinical efficacy in metastatic renal carcinoma].

AIMS AND BACKGROUND: the antitumor activity of IL-2 is mediated by an increase in lymphocyte number. Moreover, our previous studies have shown that therapy for 1 week/month with low-dose subcutaneous IL-2 is sufficient to maintain high levels of lymphocytes in cancer patients who have had tumor regression or stable disease (SD) in response to IL-2 immunotherapeutic cycles. This study was performed to establish whether tumor progression in cancer patients chronically treated with IL-2 may be associated with lymphocyte number decline. METHODS: the study included 60 metastatic renal cell patients, who were treated with 2 induction cycles of IL-2 subcutaneous immunotherapy (6 million IU/day for 5 days/week for 6 weeks, corresponding to one cycle). Tumor regression occurred in 17/60 patients, 23 patients a SD, and the remaining 20 cases progressed. Non-progressed patients (n = 40) underwent a maintenance therapy consisting of one week of therapy every month. After a median follow-up of 18 months, 29/40 patients with response or SD had progressed. The immune investigation consisted of lymphocyte, T lymphocytes, NK cell number determination and sCD25 level detection. RESULTS: the mean number of lymphocytes, T lymphocytes and NK cells observed on IL-2 maintenance therapy was significantly higher than that seen before beginning the immunotherapy. Moreover, mean number of lymphocytes and mean levels of sCD25 observed at the time of tumor progression were respectively lower and higher than those seen on maintenance therapy in the same patients, without, however, significant differences. CONCLUSION: despite the importance of lymphocytes in mediating the antitumor activity of IL-2, this study shows that tumor progression in cancer patients chronically treated with low-dose IL-2 after response or SD during IL-2 induction cycles is not associated with a significant decline in lymphocyte, T lymphocyte or NK cell numbers. Further studies, carried out to analyze the functional status of immune cells at the time of tumor progression, will be necessary to define the role of immunity in cancer patients progressing under IL-2 chronic therapy.

Carcinoma, Renal Cell↗

[Prognostic predictive factors of the clinical response to immunotherapy with subcutaneous interleukin-2, in patients with metastatic renal carcinoma: analysis of 60 cases].

The intravenous immunotherapy with high-dose interleukin-2 (IL-2) would constitute one of the most effective treatments of metastatic renal cell carcinoma (RCC). More recently, IL-2 subcutaneous therapy has also appeared active, either alone or in association with interferon, with results comparable to those found with the intravenous route of injection, but with a lower toxicity. On this basis, we have designed a protocol of treatment with low-dose IL-2 alone given subcutaneously as a first or a second line therapy in metastatic RCC. The study included 60 consecutive patients (pts) (M/F: 39/21, median age 56 years, range 26/74). IL-2 was given at a dose of 3 millions IU twice/day for 5 days/week, for 6 weeks, corresponding to one cycle. In non progressed pts a second cycle was repeated after a 28-day rest period. Dominant metastasis sites were, as follows: soft tissues: 8; bone: 11; lung: 29; liver: 3; liver plus lung: 7; adrenal: 2. The minimum follow-up was 18 months and the median follow-up was 34 months (range 18-48). A complete response (CR) was achieved in 2/60 (3%) pts. A partial response (PR) was obtained in 15/60 (25%). Therefore, tumor objective rate (CR + PR) was 17/60 (28%). The median duration of response was 13 months (4-33).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

CYP2D6-related oxidation polymorphism in Italy.

The distribution of the oxidation polymorphism related to cytochrome CYP2D6 (debrisoquine type) was determined in 246 healthy Italian volunteers. Phenotyping was based on HPLC determination of the dextrometorphan/dextrorphan concentration ratio (metabolic ratio) in urine samples collected over an 8 h interval following a single oral 30 mg dose of dextromethorphan hydrobromide. Urinary excretion of dextromethorphan showed a wide interindividual variability, ranging from < or = 0.04 to 3.9% and from 0.5 to 79.6% of the dose, respectively. Metabolic ratios ranged from < or = 0.001 to 6.6. Eleven of the 246 subjects showed a metabolic ratio greater than 0.30, indicating that 4.5% of the population could be ascribed to the poor metabolizer status. The frequency of the poor metabolizer phenotype in this population is within the range described for other Caucasian ethnic groups.

Cytochrome P-450 CYP2D6↗

[Andrological complications after pancystoprostatovesiculectomy surgery: utility of the bulbocavernosus reflex].

The technique for radical cystoprostatectomy was modified to avoid injury to the branches of pelvic plexus that innervate the corpora cavernosa (monolateral neurovascular bundle preservation or "Nerve sparing technique"). The studies of Walsh and coll. demonstrated that the branches of pelvic plexus that innervate the corpora cavernosa are situated between the rectum and urethra and penetrate the urogenital diaphragm near to the muscular wall of the urethra. Injuries to the pelvic plexus can occur during 1) division of posterior pedicle of bladder (the seminal vesicle can be used as a landmark intraoperatively to avoid injury to pelvic plexus), 2) during apical dissection of prostate with transection of the urethra. The return of sexual function postoperatively is related to preservation of autonomic innervation; the excision of the neurovascular bundle on one side may prevent impotence in 68% patients. Our study was undertaken to identify the cause of impotence in men undergoing radical cystoprostatectomy with "Nerve sparing technique" using bulbo cavernous reflex. Our results suggest that bulbo cavernosus reflex may not be a sensitive clinical tool to establish a diagnosis of neurogenic erectile dysfunction after pelvic surgery. The Authors examine the recent neuro-uro-physiological diagnostic methods for the study of neurogenic erectile dysfunction.

Aged↗

Characterization of alpha 1-adrenoceptor subtypes in prostate and prostatic urethra of rat, rabbit, dog and man.

The alpha 1-adrenoceptor subtypes present in the smooth muscle of urethra and prostate of different animal species, including man, were characterized by using receptor binding techniques. In prostatic urethra and prostate membranes, [3H]prazosin labelled a single population of alpha 1-adrenoceptors (Hill coefficient not different from unity) with a high affinity in the range 0.21-0.51 nM. The number of specific [3H]prazosin binding sites was partially affected by chloroethylclonidine only in human and rat prostate membranes, whereas this agent proved practically devoid of activity in rabbit and dog prostate membranes as well as in the prostatic urethra membranes of all the animal species examined. These findings indicate that in prostatic and urethral membranes the alpha 1-adrenoceptors mainly belong to the alpha 1A subtype. The binding results were confirmed by in vitro functional studies on noradrenaline-induced contractions of rabbit and dog urethral preparations. The agonist-induced contractions were practically unaffected by preincubation of both tissues with chloroethylclonidine, but were sensitive to nifedipine. We found, moreover, a good correlation between the potency of different selective and non-selective alpha 1-adrenoceptor antagonists (WB-4101, 5-methylurapidil, phentolamine, spiperone, prazosin and urapidil) tested against the noradrenaline-induced contractions of rabbit urethra and their affinity for the alpha 1A-adrenoceptor subtype, no correlation with the affinity for the alpha 1B subtype, and a lower correlation with the affinity for the alpha 1C-adrenoceptor subtype.

Adrenergic alpha-Antagonists↗

Large bowel perforations in war surgery: one-stage treatment in a field hospital.

Over a period of 14 months between 1990 and 1992, 73 Afghan war wounded with penetrating colon injuries were admitted and treated by a single surgical team in a field hospital of the International Committee of the Red Cross (ICRC). There were 67 males and 6 females, with a mean age of 23 years (range 6 to 80 years). Fifty six (77%) patients had multiple associated injuries; admission was delayed longer than 12 hours in 39 (44%); hypotension or deep shock was present at admission in 34 (47%) and 12 (16%) respectively. At laparotomy faecal contamination was limited to one quadrant in 58 (79.5%) cases and major in 15 (20.5%). Fifty-two (71.2%) patients underwent resection and primary anastomosis and 21 (28.8%) primary repair. Exteriorisation or diverting colostomy were never used. Four (5.5%) patients died and 11 (15%) had postoperative complications. Overall failure rate was 2.7%, including one faecal fistula conservatively treated and one colostomy raised as a precaution in a patient undergoing relaparotomy for intra-abdominal abscess. No primary repair leaked Deaths were significantly related to delay in admission and age, but not to surgical treatment. One stage primary treatment of large bowel injuries from penetrating abdominal wounds has low mortality, failure and colostomy rates suggesting its wider use regardless of risk factors.

Adult↗

The pharmacokinetics of oxcarbazepine and its active metabolite 10-hydroxy-carbazepine in healthy subjects and in epileptic patients treated with phenobarbitone or valproic acid.

The kinetics of oxcarbazepine (OXC) and its active metabolite 10-hydroxy-carbazepine (10-OH-CZ) after a single oral OXC dose (600 mg) were compared in healthy control subjects and in epileptic patients treated with phenobarbitone or sodium valproate (n = 8 in each group). In all groups, serum 10-OH-CZ concentrations were much higher than those of the parent drug. In patients on valproate, the kinetics of OXC and 10-OH-CZ did not differ significantly from those observed in controls. In patients on phenobarbitone, AUC values of both OXC and 10-OH-CZ were lower than in controls (2.9 +/- 0.4 vs 5.1 +/- 0.7 microg ml(-1) h and 89 +/- 7 vs 119 +/- 10 microg ml(-1) h respectively, means +/- s.e. mean, P < 0.05), whereas 10-OH-CZ half-lives were only marginally shorter (17 +/- 1 h vs 20 +/- 2 h, NS). These data indicate that the biotransformation of OXC and 10-OH-CZ may be accelerated by concomitant treatment with phenobarbitone but that the magnitude of this effect is unlikely to be of great clinical significance.

Administration, Oral↗

Treatment of bowel injuries in war surgery.

Provided that the surgeon is familiar with small and large bowel surgery, primary resection and anastomosis of the bowel, as well as primary suture of the perforations, are safe and advantageous procedures in treating war related intestinal perforations, whereas the use of colostomosis should be restricted to selected cases.

Adolescent↗

[Neoadjuvant chemotherapy using cisplatin (CDDP) and methotrexate (MTX) in carcinoma of the bladder].

From June 1986 to November 1989, 7 patients (pts.) with transitional bladder cancer were treated with CDDP 70 mg/m2 i.v. on day 1 and MTX 40 mg/m2 i.v. on days 8 and 15. The initial stage was T2 N0 M0 (2), T2 N0 M0 (8), T4 N0 M0 (4) and T3-4 N+ M0 (3). The median age was 56 years. After a median number of two cycles (1-5) of CDDP-MTX, 3/17 pts. (17.6%) had a complete remission (CM), 9/17 pts. (53%) a partial response (PR) greater than 50%, 4/17 pts. (23.4%) a PR less than 50%, 1/17 pts. (6%) a stable disease. Nausea and vomiting occurred in almost all pts., 20% of pts. had grade 3 stomatitis, 35% of pts. had diarrhoea, 20% of pts. had conjunctivitis, 7% of pts. had a bone marrow depression and hair loss. One patient had severe renal and liver toxicity and grade 4 bone marrow suppression with sepsis, completely controlled after intensive care. The treatment after neoadjuvant chemotherapy was: radical cystectomy (11)- in one following radiotherapy -; partial resection + lymphoadenectomy (2); TUR (4) in 1 pt. with lymphoadenectomy. After a median follow-up of 28 months (6-36), 12/17, equivalent to 71% of pts. are disease free, 3/17 (17%) are alive with disease, 2/17 (12%) died. In conclusion the association of neoadjuvant CDDP-MTX can induce a high percentage of response, and can preserve bladder function in some patients. Further controlled trials and a longer follow-up are needed to better define the exact role of this combination in terms of disease free survival, total survival and quality of life.

Aged↗

[Complications and limitations of endoscopic therapy for urethral stenosis].

Endoscopic treatment of urethral stenosis is not an alternative to surgical therapy but is an ideal therapeutical partner. The limits of endoscopic resection lie in the lack of anatomopathologican and clinical knowledge regarding the long-term maintenance of stability of the urethral lumen that in every case the internal urethrotomy manages to create. In fact internal urethrotomy is capable of almost totally eliminating the urethral stenosis but with a higher incidence of relapse, even in the short-term. The complications of endoscopic therapy of urethral stenosis are the usual local complications and of mild seriousness. Among the most frequently noted are the swelling and/or peno-scrotal suffusion by incorrect routes, and post-operative urethraemorrhagia. More rarely, but with serious effects, are purulent urethritis or sepsis. In our case list major complications such as priapism, cavernositis or septic shock were not noted. In conclusion endoscopic therapy of urethral stenosis is a simple technique, repeatable with low morbidity and is the best technique in the congenital 'ring'.

Endoscopy↗

[Prognostic parameters in extracorporeal lithotripsy].

Extracorporeal lithotripsy consists of applying shock waves (electrohydraulic and piezoelectric) from outside the human body, which pass through the body tissues without damaging them breaking down the urinary calculi into particles which can then be automatically expulsed through the excretory tract. The object of this study is to analysis some of the important parameters which affect the success of the extracorporeal lithotripsy. These factors are as follows: 1) type of shock wave: electrohydraulic or piezoelectric, their action mechanism, methods of fragmenting the urolites; 2) the chemical composition of the calculi and its consequential resistance to the fragmented shock waves; 3) Patency, tone and peristalsis of the intra and extrarenal excretory tract for expulsing the urolite particles; 4) general conditions of the urinary apparatus. From the interaction of these 4 variables arise different clinical situations which must be evaluated before operating in order to develop the proper therapeutic subscription for a renal-urethral lithiasis. The current therapeutic procedures for renal-urethral lithiasis are as follows: electrohydraulic and piezoelectric extracorporeal lithotripsy; electrohydraulic waves or ultrasound percutaneous litholapaxy; operative urethroscope; traditional surgery; chemolysis.

Humans↗

[Results of calcitonin therapy of the painful symptoms caused by osteolytic metastases of prostatic carcinoma].

Albeit within the limits imposed on us by the restricted number of cases, we can state that--in the present state of research--calcitonin constitutes a useful complement in treatment of osteolytic metastasis induced by carcinoma of the prostate. Is utilisation is justified by the effects observed: on the one hand, osteogenesis as a factor protecting against the aggressivity of the tumoural cells, and on the other the considerable antalgic strength allied with improvement in the calcium, phosphorus and phosphatase values. For some time we have replaced pig calcitonin with salmon calcitonin: the comparative results with this second product will be the subject of a subsequent paper.

Bone Neoplasms↗

Possible involvement of prolactin in endocrine-resistant metastatic prostate cancer.

The hormone resistance of prostate cancer has been proved to depend at least in part on enhanced neuroendocrine activity and the resultant increase in blood concentrations of chromogranin A. Other experimental observations have suggested the involvement of prolactin (PRL), which appears to be a potential growth factor for prostate cancer. Abnormally high levels of PRL have been detected in metastatic prostate cancer, but the clinical significance of this finding has still to be clarified. In an attempt to explain the prognostic significance of serum PRL levels in prostate cancer, in this preliminary study we have analyzed the PRL levels in a group of metastatic prostate cancer patients with hormone-dependent or hormone-resistant cancer. The study included 50 patients with metastatic prostate cancer, 15 of whom had hormone-resistant tumors. The serum levels of PRL were measured by the RIA method. Abnormally high concentrations of PRL were found in 11/50 (22%) patients. Moreover, the percent of patients with cancer-related hyperprolactinemia was significantly higher in the hormone-resistant group than in the hormone-dependent group (8/15 vs 3/35, p < 0.01). This study confirms the possible existence of a hyperprolactinemic state in metastatic prostate cancer, as previously reported by other authors. Moreover, it appears to demonstrate that the occurrence of hyperprolactinemia is more frequent in hormone-resistant neoplasms, suggesting the possible involvement of PRL in hormone independence. Further studies concomitantly evaluating PRL and chromogranin A blood concentrations will be necessary to establish whether the hyperprolactinemia precedes and promotes the onset of hormone resistance in prostate cancer, or whether it is simply a consequence of the hormone independence.

Aged↗

A phase II study of tamoxifen in hormone-resistant metastatic prostate cancer: possible relation with prolactin secretion.

Recent experimental observations, showing the potential role of prolactin (PRL) as a tumor growth factor for prostate cancer and the unfavourable prognostic significance of enhanced chromogranin-A-secreting neuroendocrine cell proliferation, could contribute to a better understanding of the mechanisms responsible for the occurrence of hormone-resistance in the prostate cancer. Moreover, it has been shown that tamoxifen, which consistently exerts estrogenic activity in males, may inhibit prostate cancer cell proliferation in experimental studies. At present, there are no clinical data in humans. This preliminary phase II study was planned in an attempt to evaluate the therapeutic efficacy of tamoxifen in hormone-refractory metastatic prostate cancer. The study included 14 consecutive metastatic prostate cancer patients, who had progressed under the classical endocrine therapy with LHRH-analogs and/or anti-androgens. Patients received the same treatment plus tamoxifen at 20 mg/day orally. A decline greater than 50% in prostate-specific antigen (PSA) levels occurred in 4/14 (29%) patients within the first 2 months of therapy, with a median duration of 5 months. Mean pre-treatment levels of PRL were significantly higher in responder patients than in those who progressed. Moreover, abnormally high pre-treatment levels of PRL were found in 5/14 (36%) patients. The percent of clinical responses observed in patients with pre-treatment hyperprolactinemia was significantly higher than that found in patients with normal pre-treatment PRL concentrations. Finally, a significant decline in mean PRL levels upon tamoxifen therapy occurred only in the responder patients. This preliminary study seems to justify further clinical research to confirm the potential efficacy of tamoxifen in the treatment of hormone-refractory prostate cancer and to identify possible parameters, which may predict the response to treatment.

Aged↗

[Use of the Wiruthan prosthesis in uretero-cutaneostomy].

Ureterocutaneostomy (UCS) is a urinary diversion (UD) which is current little used, since, in addition to its very invalidating character, especially from a socio-psychological point of view, it is accompanied by complications such as ureteral stenosis, infections and parenchymal injury. Some of these complications may be partly related to the type of prosthesis used. From January 1987 prosthesis in Wiruthan polyurethane, an inert material with excellent biocompatibility features, were used in 20 patients who had to undergo UCS. The use of these long-lasting prosthesis was easy, well tolerated and enabled the patients to achieve a better quality of life. The prosthesis required moderate maintenance and reduced the complications which are often found in UCS. This positive experience prompts the Authors to recommend the use of these prosthesis in patients with UD.

Aged↗