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Biomedical subjects

T Colombo

Publications and source records attributed to T Colombo.

At least 37 records · Page 2Linked to original sources
PubMed1998

Taxoids in combination with anthracyclines and other agents: pharmacokinetic considerations.

The combination in clinical trials of taxoids with doxorubicin has focused attention on possible drug interactions. One specific finding requiring explanation is the relative lack of cardiotoxicity of the docetaxel (Taxotere; Rhône-Poulenc Rorer, Antony, France)/doxorubicin combination compared with that of the paclitaxel/doxorubicin combination. Data in mice demonstrate that epirubicin concentrations in cardiac tissue 24 hours after treatment are approximately doubled by the coadministration of paclitaxel. This effect appears to be less marked with docetaxel administered in its normal polysorbate vehicle or when the drug is given in Cremophor EL (Sigma, St Louis, MO). Both Cremophor EL or polysorbate appear to cause an increase in epirubicin tissue levels, although the levels were less than those seen with paclitaxel. Pharmacokinetic data from women being treated with combination therapy for advanced breast cancer demonstrate that the administration of docetaxel following doxorubicin does not alter doxorubicin's area under the plasma concentration-time, curve, maximum plasma concentration, or time until maximum plasma concentration is reached. However, the area under the curve of docetaxel is significantly increased by the prior administration of doxorubicin. These findings may explain both the low cardiotoxicity and the high clinical efficacy of the docetaxel/doxorubicin combination. Phase I clinical trials of combinations in which docetaxel was used together with vinorelbine, ifosfamide, or 5-fluorouracil have shown no evidence of relevant pharmacokinetic interactions.

Animals↗
PubMed1997

Combined heart and kidney transplantation: an effective therapeutic option--report of six cases.

Six cases of combined heart and kidney transplantation with organs from the same donor are reported. All six patients suffered from primary end-stage kidney disease, two chronic glomerulonephritis, two glomerulosclerosis, one chronic pyelonephritis and one with unknown etiology. Four patients were undergoing hemodialysis. Three patients had the diagnosis of ischemic heart disease, one dilated cardiomyopathy secondary to congenital heart disease, two idiopathic dilated cardiomyopathy. Five were males and one female. Ages ranged from 38 to 54 years. On-site or short-distance young donors with normal renal function and good cardiac function necessitating low inotropic support were selected. ABO compatibility was used exclusively. Orthotopic heart transplantation was performed first. During cardiopulmonary bypass, hemofiltration was used in four cases. Kidney transplantation was performed immediately after the closure of the chest. Diuresis was immediate in all cases. No cardiac rejection was documented at EMB. Renal function normalized within few days with no signs of kidney rejection. All six patients are alive and well with normal cardiac and renal function at a mean follow-up of 43 months. Patients and donors selection associated with a proper surgical strategy and prompt immunosuppressive therapy administration make the combined heart and kidney transplantation an effective therapeutic option.

ABO Blood-Group System↗
PubMed1997

The use of polydimethylsiloxane in the treatment of incontinence after radical prostatectomy.

OBJECTIVE: To report the results of transurethral submucosal injection therapy of polydimethylsiloxane (PDS) to treat incontinence after radical prostatectomy (RP). PATIENTS AND METHODS: Since 1993, about 80 retropubic RPs have been carried out at our institution each year. Severe post-operative incontinence occurred in six patients, with a mean duration of incontinence after RP of 28 months. The pre-operative evaluation consisted of cysto-urethroscopy and urodynamics. Because we have no experience with artificial sphincter implantation, transurethral injection therapy was used to treat the post-operative incontinence, using PDS (vulcanized silicone rubber particles). This material has a mean particle size of 188 microns, providing stability of the material at the injection site. The six patients with severe post-operative incontinence were treated using injection therapy with PDS. RESULTS: After a mean follow up of 15.5 months, five patients, who suffered from day and night incontinence and required at least five pads per day, were dry after injection therapy. One patient improved significantly but still required two pads during the day, but was continent during the night; three patients required a second injection. A mean of 7.5 mL of PDS was used per patient and the side-effects of therapy (dysuria and urinary retention) were minimal. CONCLUSION: Because PDS has excellent biocompatibility, few side-effects or complications, transurethral injection therapy using silicone particles is a justifiable procedure for treating incontinence after RP.

Dimethylpolysiloxanes↗
PubMed1997

Restrictive criteria for heart transplantation candidacy maximize survival of patients with advanced heart failure.

BACKGROUND: The shortage of organ donors and the amelioration of medical management of advanced heart failure mandate strict selection of heart transplant candidates on the basis of the need and probability of success of transplantation, with the aim of maximizing survival of patients with advanced heart failure, both with and without transplantation. This study analyzes the impact of restricting the criteria for heart transplantation candidacy on the outcome of patients with advanced heart failure referred for transplantation. METHODS: Survival and freedom from major cardiac events (death, resuscitated cardiac arrest, transplantation while supported with inotropes or mechanical devices) were compared between patients listed during 1990 to 1991, when standard criteria were applied (group 1, n = 118), and patients listed during 1993 to 1994, when only patients requiring continuous/recurrent intravenous inotrope therapy in spite of optimized oral medications and outpatients showing actual progression of the disease were admitted to the waiting list (group 2, n = 88). Survival and freedom from cardiac events (defined as above plus listing in urgent status) were also calculated in stable outpatients evaluated in 1993 to 1994, who were potential heart transplant candidates according to standard criteria but were not listed because of restrictive criteria (group 3, n = 52, New York Heart Association functional class > or = III, mean echocardiographic ejection fraction 0.22 +/- 0.05, mean peak oxygen consumption 12.3 +/- 1.5 ml/kg/min, mean follow-up 19 +/- 10 months). RESULTS: Thirty-one percent, 40%, and 50% of group 1 patients versus 58%, 65%, and 77% of group 2 patients underwent transplantation within 3, 6, and 12 months after listing (p < 0.0007). The 1- and 2-year survival rates after listing were 80% and 71% in group 1 versus 85% and 84% in group 2 (p < 0.0001). Freedom from death/urgent transplantation was lower in group 2 than in group 1 (55% and 48% versus 72% and 59% at 6 and 12 months, respectively; p < 0.0001). In patients undergoing transplantation, the postoperative survival rate was similar (87% and 91% at 2 years in group 1 and group 2, respectively). Two years after heart transplantation candidacy was denied, 86% of group 3 patients were alive, and 74% were event-free. CONCLUSIONS: Restricting the admissions to the waiting list to patients with refractory/progressive heart failure improved survival rates after listing by increasing the probability to undergo transplantation in a short time. Selection of most severely ill candidates did not affect postoperative survival. Survival and freedom from cardiac events were good in patients with advanced but stable heart failure, in spite of their severe functional limitation. Thus restrictive criteria for heart transplantation candidacy allows maximal survival benefit from both medical therapy and transplantation.

Adolescent↗
PubMed1997

Multidrug resistance-reversing agents increase vinblastine distribution in normal tissues expressing the P-glycoprotein but do not enhance drug penetration in brain and testis.

The aim of this study was to assess whether P-glycoprotein (Pgp) inhibitors altered the blood-brain barrier and enhanced vinblastine (VBL) distribution in brain, testis and other Pgp-expressing tissues. Trifluoperazine, cyclosporin A, amiodarone, quinidine, the nifedipine analog Bay K8644 and verapamil were selected among Pgp inhibitors and were administered intraperitoneally 1 hr before an intravenous dose of 10 mg/kg VBL. Trifluoperazine and cyclosporin A were also administered intraperitoneally for 7 days before VBL. VBL and its metabolite O4-deacetylvinblastine were measured in tissues by high-performance liquid chromatography assay. None of the reversing agents (RA) appreciably raised VBL concentrations in brain and testis, whereas all except quinidine significantly enhanced VBL distribution in liver and kidney; the most effective were trifluoroperazine and cyclosporin A. In mice treated with RA and VBL combined, O4-deacetylvinblastine levels in liver and kidney reached either the same or higher levels than in mice treated with VBL alone, indicating that the increase in VBL levels is not due to inhibition of its metabolism. The main conclusions are that (1) inhibitors of Pgp, even at high doses, do not increase the permeability of the blood-brain barrier in mice, suggesting caution in the clinical use of RA combined with antitumor agents for brain tumors; and (2) several RA achieve high enough concentrations to enhance the distribution of VBL in other normal tissues expressing Pgp, thus potentially increasing VBL toxicity.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

[Heart transplantation 1985-1995: 10 years experience at the "Angelo De Gasperis" center. Improvement of results by progress in operative criteria].

BACKGROUND: At 10-years from beginning of transplant experience in our Center we analyzed the overall results in an attempt to identify risk factors for early (3 months) and late (over 3 months) mortality after heart transplantation (HTx). METHODS: The data of 313 patients transplanted from November 1985 to June 1995 were studied and analyzed with a multivariate logistic regression and Cox's proportional hazard model. Seventy pre, intra and postoperative variables were considered: demographics, clinical status, hemodynamic parameters, donor characteristics, donor-recipient mismatch, complications, immunosuppressive protocols. In this paper we compared results in patients operated on from 1985 to 1990 (Group I) and from 1991 to 1995 (Group II) in order to assess improvements due to changes in HTx indication and in perioperative treatments. RESULTS: Overall mortality in the entire group was 19.8% (62/313): 30-days, 3 months and late mortality rates were 8.0%, 10.2%, 10.7% respectively. In Group II mortality rates were 7.1%, 8.6% and 2.8% respectively despite significant increase in Status I patients (21.5% in Group I vs 40.1% in Group II, p = 0.0008). Main causes of early death were: graft failure (46.9%), infection (28.1%), acute- rejection (12.5%). Main causes of late death were: cardiac allograft vasculopathy (40.0%) and neoplasm (23.3%). The mean follow-up of the 281 survivors more than 3 months is 45.6 +/- 30.0 months (range 3 to 120 months). Actuarial survival is 86.9 +/- 1.9%, 78.4 +/- 2.7% and 70.7 +/- 3.9% at 1, 5 and 10 years respectively. The difference in the 5-years actuarial survival between Group I and Group II patients is statistically significant (70.7 +/- 4.2% vs 84.5 +/- 4.5%, p = 0.005). TPG (OR 1.19), RAP (OR 1.13) and MD-HD inotropic support of donor (OR 3.81) were identified as independent risk factors for early mortality. Number of moderate rejection at biopsy (OR 1.56) and early postTx infection (OR 3.37) were identified as independent risk factors for late mortality. CONCLUSIONS: The overall results of our ten-year experience are very satisfying in relation to early and late mortality, with a significant favourable trend between patients transplanted in the early era (1985-1990) and those transplanted in the recent era (1991-1995). The study confirm that morbidity and mortality have the highest incidence during the early post-transplantation phase. Pulmonary hypertension and elevated preoperative right filling pressure appear to indicate a significantly increased risk of early death and only marginally influence late survival that is principally related to the severe postoperative complications. Differently from other observations, among the donor-related and recipient-donor matching variables, this analysis evidenced as significant only the need for MD-HD catecolamines during donor-management.

Actuarial Analysis↗
PubMed1997

Mt. Cimone Observatory: baseline station for the measurement of gaseous substances and radioactive tracers in the atmosphere.

An extensive research program to record atmospheric physicochemical parameters and to track climatological trends was established at a remote Alpine station at Mt. Cimone Observatory in Italy. The main features of the study are outlined briefly and the results thus far collected, including surface ozone, carbon dioxide, stratospheric NO2 and O3, and airborne radioactivity are provided.

Atmosphere↗
PubMed1996

Distribution and activity of doxorubicin combined with SDZ PSC 833 in mice with P388 and P388/DOX leukaemia.

SDZ PSC 833 (PSC 833) is a non-immunosuppressive analogue of cyclosporin A and is a potent modifier of P-glycoprotein (P-gp)-mediated multidrug resistance. The present study was undertaken to evaluate whether doxorubicin (DOX) pharmacokinetic and anti-tumour activity on P388- and P388/DOX-resistant leukaemia was modified by PSC 833 pretreatment. P388- or P388/DOX-bearing mice were given PSC 833 intraperitoneally 30 min before an intravenous injection of DOX. The levels of DOX were determined by a high-performance liquid chromatography method in leukaemic cells and in normal tissues (heart, lung, liver, small intestine, kidney and spleen). In all tissues, DOX concentrations were significantly increased in mice pretreated with PSC 833. The difference was greatest in P-gp-overexpressing P388/DOX cells, the DOX area under the curve being approximately seven times greater after PSC 833 and DOX than after DOX alone. In P388 cells the difference was approximately 2.5 times, as in the majority of normal tissues. As expected DOX levels in P388 cells were higher than in P388/DOX cells in mice treated with DOX alone, whereas after PSC 833 and DOX the levels of DOX were similar in the two leukaemic lines. In spite of this PSC 833 was unable to reverse the resistance to DOX of P388/DOX leukaemia in vivo, suggesting that mechanisms other than P-gp expression are responsible for resistance.

ATP-Binding Cassette Transporters↗
PubMed1996

Paclitaxel induces significant changes in epidoxorubicin distribution in mice.

BACKGROUND: Inhibition of Pgp can affect the distribution and the pharmacokinetics of anthracyclines, causing marked changes in their toxicity. Since both paclitaxel and cremophor are substrates of Pgp, it was hypothesized that they could modify the pharmacokinetics of anthracyclines in a similar fashion. PURPOSE OF THE STUDY: To evaluate whether pretreatment of mice with cremophor or paclitaxel dissolved in cremophor could induce changes in the distribution of epidoxorubicin (EpiDx). MATERIALS AND METHODS: Male CDF1 mice were treated with ethanol or cremophor or paclitaxel and 30 min later with EpiDx (15 mg/kg i.v.). EpiDx serum and tissue levels were determined at several time points after EpiDx treatment by high pressure liquid chromotagraphy (HPLC) assay coupled with fluorimetric detection. RESULTS: Pretreatment with paclitaxel dissolved in cremophor induced a highly significant increase in EpiDx levels in all tissues examined including heart. At 8 h heart levels in mice treated with EpiDx alone, EpiDx and cremophor and EpiDx and paclitaxel were 8.3 micrograms/g, 10.9 micrograms/g and 16.7 micrograms/g (P < 0.01), respectively. Cremophor alone induced a similar increase in spleen EpiDx levels but had only a moderate effect on heart and lung EpiDx levels. Levels of doxorubicin (Dx) aglycone in kidney and liver of mice treated with paclitaxel and EpiDx were higher than those in mice treated with EpiDx alone. CONCLUSIONS: A pharmacokinetic interaction between paclitaxel and EpiDx was clearly demonstrated in mice. The much higher tissue levels of EpiDx after paclitaxel pretreatment may be the reason for the increased toxicity of EpiDx when administered soon after paclitaxel.

Animals↗
PubMed1996

Effect of extracorporeal shock wave lithotripsy on prostate specific antigen.

PURPOSE: We evaluated the effects of extracorporeal shock wave lithotripsy (ESWL) of distal ureteral calculi on serum prostate specific antigen (PSA). MATERIALS AND METHODS: A total of 29 consecutive men with distal ureteral calculi at a maximum of 25 mm. from the ureteral orifice, and without any history of urinary tract infection, benign prostatio hyperplasia or prostate cancer underwent ESWL with the Dornier MPL 9000 X lithotriptor. The therapeutic focus size was 48 X 7 mm. PSA was measured exactly 5 minutes before ESWL, as well as 120 minutes, 24 hours and 7 days after termination of treatment. RESULTS: Fragmentation rate was 100% and all patients were stone-free within 1 week of therapy. There was no statistically significant difference between PSA values before and after treatment. Only 15 patients had a slight increase in PSA at 120 minutes after treatment (range 0.01 to 0.41 ng./ml., mean 0.07). CONCLUSIONS: ESWL can be performed in men at risk for prostate cancer without impairing the predictive value of PSA.

Adult↗
PubMed1995

Changes in doxorubicin distribution and toxicity in mice pretreated with the cyclosporin analogue SDZ PSC 833.

SDZ PSC 833 (PSC 833) is a cyclosporin A analogue that is under clinical investigation in combination with doxorubicin (Dx) or other anticancer agents as a type-1 multidrug resistance (MDR-1)-reversing agent. The present study was focused on the effects of PSC 833 on the distribution and toxicity of Dx in non-tumor-bearing CDF1 male mice. Mice were given PSC 833 i.p. at 30 min before i.v. Dx treatment. Dx levels were determined by a high-performance liquid chromatography (HPLC) assay at different times during a 72-h period following Dx treatment in the serum, heart, intestine, liver, kidney, and adrenals of mice. In all tissues, Dx area under the concentration-time curve (AUC) values were much greater in mice receiving 10 mg/kg Dx in combination with 12.5 or 25 mg/kg PSC 833 than in mice receiving Dx alone. The highest increase in Dx concentrations was found in the intestine, liver, kidney, and adrenals. Lower, albeit significant, differences were found in the heart. PSC 833 did not appear to influence either urinary or fecal Dx elimination or Dx metabolism to a great extent. Doses of PSC 833 devoid of any toxicity potentiated the acute and delayed toxicity of Dx dramatically. The mechanism responsible for this enhanced toxicity has not yet been elucidated but is likely to be related to an increased tissue retention of Dx due to inhibition of the P-glycoprotein (Pgp) pump by PSC 833, as has recently been proposed for cyclosporin A.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

Hospital morbidity and mortality after myocardial revascularisation surgery: current changes in risk factors.

To identify the operating risks for mortality and morbidity in patients undergoing aortocoronary bypass surgery, the data of 514 myocardial revascularisation procedures performed consecutively between January 1991 and December 1992 were analysed; 73.2% of the patients had associated diseases and 59.3% had suffered one or more previous myocardial infarctions. The mean ejection fraction of the population as a whole was 52.2 +/- 13. In 10.5% of the cases there was severe left ventricular (LV) function impairment with a mean ejection fraction (EF) of 30.2 +/- 4.4 (range 20-35). A major preoperative complication occurred in 8.2% of the entire population and 68.8% of the patients undergoing emergency surgery. Surgery was elective in 72.7% of the cases, urgent in 15.4% and emergency in 11.9%. Hospital mortality was 4.1% (CL 3.2-4.9). In the group of electively operated patients, mortality was 2.7% (CL 1.8-3.5), with no statistically significant difference (P = 0.943) from the mortality observed in the patients undergoing urgent surgery [2.5% (CL 0.8-4.1)]. The mortality in both groups was statistically different (P = 0.0001 and P = 0.008) from that of the patients undergoing emergency surgery [14.7% (CL 10.1-18.9)]. Perioperative acute myocardial infarction occurred in 5.4% of the patients (CL 4.4-6.4), in three cases resulting in death [10.7% (CL 4.8-15.8)]. Fourteen of the acute myocardial infarctions (AMI) occurred in the 42 patients undergoing emergency surgery for acute coronary occlusion (33.3%). A percentage of 18.7% of the 493 surviving patients suffered a postoperative complication.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗
PubMed1995

[Indications and results of ex-vivo surgery of the kidney].

394 renal transplantations have been performed in our unit between 1974 and 1995. In all instances extra-corporal surgical procedures on the graft, its vessels and, in rare instances, on the collecting system were necessary. The surgical procedures, which took up to 90 minutes on the work-bench, ranged from repair of minor iatrogenic vascular injuries to major vascular reconstructions, in order to facilitate the subsequent implantation of the graft. During the same period work-bench surgical procedures with subsequent autotransplantation were performed in 8 patients. The indication for such a procedure was a renal cell carcinoma in 2 patients with a solitary kidney and bilateral renal cell carcinoma in 1 patient, as well as renovascular disease (renal artery stenosis, aneurysm of the renal artery) in the remaining 5 cases.

Adolescent↗
PubMed1995

[Prenatal diagnosis of abnormalities of the urinary tract].

During the period January 1983 to December 1993 malformations of the urinary tract were suspected in 166 cases prenatally and confirmed after birth. Boys dominated (72% of cases); in 66% of the cases the malformation was unilateral. The most frequent diagnosis was ureteropelvic obstruction in 74 infants (45%). 73 out of 166 infants (44%) required surgical intervention. Altogether 124 operations were performed (68% temporary diversions; 32% definitive corrections). The high number of required interventions already during the first month of life highlights the importance of prenatal screening for the early detection of urinary tract malformations, especially obstructive uropathy and multicystic-dysplastic kidney. On the other hand, vesicouretal reflux is usually detected only postnatally on investigation of a urinary tract infection.

Diagnostic Imaging↗
PubMed1995

[Nephrogenic adenoma after kidney transplantation].

We report five cases of nephrogenic adenoma that arose several years after cadaver kidney transplantation. Cystoscopy was performed in all patients because of gross haematuria and revealed multifocal tumorous lesions in all parts of the bladder. On admission to of hospital graft function was satisfactory in all patients. There were three female and two male patients. In all patients the therapeutic procedure consisted of transurethral resection. Only very small lesions were fulgurated. Postoperatively an indwelling catheter was left in place for 2-4 days, and after a check on kidney parameters and immunosuppressive therapy all patients were discharged. Postoperative management consisted in cystoscopy every 3 months in the first year and then every 6 months. Though the etiology of nephrogenic adenoma remains unclear, mechanical traumatization and recurrent urinary tract infection seem to be the most important factors in its development.

Adenoma↗
PubMed1994

Active infective endocarditis: surgical approach.

From January 1982 to December 1991, 65 interventions were performed in 61 patients with active infective endocarditis (IE): 32 on native valves (Group 1) and 33 on prosthetic valves (Group 2). In Group 1, 23 patients had a known previous valve disease; major preoperative clinical complications occurred in 16 patients (50%); 84% were in NYHA classes III and IV. In Group 2 major preoperative clinical complications occurred in 13 patients (44.8%); 86% were in NYHA classes III and IV. The mean time interval between the onset of hemodynamic impairment of varying degrees and surgery was 13 +/- 15 days for Group 1, and 8 +/- 11 days for Group 2. In all cases, the native valves or prostheses were replaced by mechanical valve prostheses. Particular procedures were performed in three patients in Group 1 and five patients in Group 2. In Group 1 there were 8 hospital deaths (25%) and 11 (34.4%) non-fatal complications. In Group 2 there were 9 deaths (31%) and 14 (48.3%) non-fatal complications. Risk factors for hospital death were "preoperative low cardiac output syndrome" and "time interval between the onset of cardiac failure and surgery" in Group 1, "cardiac failure+sepsis" in Group 2, "time interval between the onset of cardiac failure and surgery" and "particular procedures" in all 61 patients. Sepsis alone and the type of pathogenic agent does not significantly affect the risk of death. The recurrence of acute IE was 12.6% in Group 1, and 20% in Group 2. The incidence of reintervention was 12.6% in Group 1 and 35% in Group 2.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗