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T Colombo

Publications and source records attributed to T Colombo.

At least 73 records · Page 4Linked to original sources
PubMed1990

[Renal cell carcinoma with venous invasion: therapy--prognosis].

Between 1966 and 1988 a total of 406 patients with renal cell carcinoma (RCC) was treated at our department. Among these 51 patients were found to have gross renal vein involvement, in 21 cases with extension into V. cava. In one case the tumor-thrombus has been reaching the level of the hepatic veins, in two cases the right atrium. MR and sonography, especially echocardiography, seems to be the best choice of diagnostics. Because of the advanced stage of disease only 21 patients were selected for operative treatment, in two cases under extracorporal circulation. Prognosis seems to be very poor, 11 patients (more than 50%) died within 2 years after diagnosis. But still the high risk and the great expense of tumor nephrectomy and thrombectomy in such cases, even with substitution of extracorporal circulation, seems to be justified by the actuarial 5-year survival rate of 20%.

Carcinoma, Renal Cell↗
PubMed1990

[Neonatal screening and follow-up of congenital hip luxation using echography. Review of the literature and personal contribution on 1421 newborns].

US screening for hip dysplasia was performed on 1421 full-term newborns. The study was aimed at: 1) evaluating US feasibility in an unselected maternity ward population; 2) determining the frequency of the different types of hips, and correlating ours with literature data; 3) evaluating the efficacy of both an early prevention and treatment. All US examinations were performed within the first week of life and the 2842 hips classified according to Graf. At birth, normal hips (Ia, Ib) were 2064 (72.6%) (group I); physiologically immature hips (IIa) were 721 (25.4%) (group II); pathological hips (group III) were: 43 (1.5%) IIc, 8 (0.3%) IId, 6 (0.2%) III. Hips in group B were checked at 3 months: 502 were normal, 51 were type IIb, and 1 was type IId: the latter 52 hips were treated and normalized in the following months. Hips in group C (types IIc, IId, and III = 57 hips) were treated and checked every seventh week until normalization. Our experience confirms US value in the evaluation of hip dysplasia in the newborn. In our opinion, the use of this method should be encouraged, although US screening of all newborns remains controversial on a cost-benefit ratio. Multicentric studies will better define US sensitivity, specificity and reliability. The correlation of our results with literature data was difficult, because study populations are not always homogeneous. As for therapy, we found the plastic splint very effective and easy to use. In 2 cases, Milgram devices were used for a few months.

Female↗
PubMed1989

Lymphokine-activated killer (LAK) and monocyte-mediated cytotoxicity on tumor cell lines resistant to antitumor agents.

In this study we have examined the susceptibility of tumor cell lines exhibiting different patterns of resistance to chemotherapeutic agents, to the cytotoxic action of lymphokine-activated killer (LAK) cells and activated monocytes. The susceptibility of tumor cells with pleiotropic drug resistance to these cytotoxic mechanisms was not different from that of their parental, chemo-sensitive cell lines. Tumor lines used in this study included three human cell lines (LOVO N and LOVO/Dx, I-407 and I-407/Dx, MCF7 and MCF7a) selected for being resistant to doxorubicin and showing a pleiotropic pattern of resistance, and the murine ovarian reticulum cell sarcoma M5076 and its variants resistant to individual antitumor agents (cisplatin, cyclophosphamide and 5-aza-2'-deoxycytidine). These results demonstrate that drug-resistant tumor cell lines, irrespective of the pattern of resistance, were susceptible to the in vitro cytotoxicity mediated by LAK cells and activated monocytes with levels of lysis similar to those of parental chemosensitive lines. Moreover, freshly isolated tumor cells from ovarian cancer patients unresponsive to different chemotherapeutic treatments (operationally drug-resistant) were significantly killed in vitro by LAK cells. These findings support the concept that activated effector cells have the potential to complement conventional chemotherapy by eliminating drug-resistant tumor variants.

Animals↗
PubMed1989

Metabolism and pharmacokinetics of p-(3,3-dimethyl-1-triazeno) benzoic acid in M5076 sarcoma-bearing mice.

The pharmacokinetics of the anticancer agent p-(3,3-dimethyl-1-triazeno) benzoic acid (pCOOH-DMT), a drug now in phase I clinical trial in Europe, was investigated in C57Bl female mice with M5076 reticulum-cell sarcoma that were treated i.v. with 200 mg/kg pCOOH-DMT. The drug disappeared from plasma with a terminal half-life of about 2.5 h. Plasma clearance was approximately 6 ml/min per kg. Distribution studies showed some differences in drug levels in different tissues. The highest levels were found in the tumor, liver, kidney and lung; lower levels were found in the spleen and gut, and the lowest, in the brain. The N-desmethyl derivative of pCOOH-DMT was not detectable in plasma or tissues of mice treated with the drug. Therefore, the previous evidence of low N-demethylation of pCOOH-DMT was confirmed. pCOOH-DMT glucuronide was identified by mass spectrometry and quantified by high-performance liquid chromatography (HPLC) in plasma, tissues and urine samples. pCOOH-DMT glucuronide appears to be the major urinary metabolite of pCOOH-DMT in mice. Another metabolite identified by mass spectrometry and quantified by HPLC in some tissues and urine was pCOOH-DMT glycinate.

Animals↗
PubMed1989

Doxorubicin toxicity and pharmacokinetics in old and young rats.

Doxorubicin (Dx) toxicity was compared in old (24 months) and young (6 weeks) Crl:CD(SD) BR male rats, and a clear age-related increase was found. The mortality of all animals receiving a single i.v. Dx dose was followed for 270 days. Old rats died after doses of 2.5 mg/kg, while young animals died after doses two times higher, 5 mg/kg. In old rats body weight loss started 10 to 15 days after Dx, compared to 50 to 80 days for young animals. In young and old rats pharmacokinetic and metabolic studies of Dx were conducted in vivo and in the liver perfusion model. Peak levels of Dx and areas under the time/concentration curves (AUC) in serum and in several tissues of old rats were 1.5 to 2 times higher than in young rats. Concentrations of Dx metabolites in serum and tissues (doxorubicinol, Dxol, and doxorubicinone, Dxone) in young and old rats were not noteworthy. However, higher percentages of Dxone than Dxol were found in both groups in vivo and in vitro. Old livers appeared to produce more Dxone as a percentage, particularly in the bile, which was higher. Urinary elimination of Dx markedly slowed with age; only small amounts of the metabolites were eliminated in urine. In vivo and in vitro availability of Dx and its metabolites is discussed in view of their possible role in the greater toxicity observed in 24-month-old rats.

Aging↗
PubMed1989

Problems in the design of anticancer agents.

Theoretically, two predominant paths for obtaining more selective anticancer agents may be envisaged. These are: (a) to make compounds which distribute only or preferentially in cancer cells; (b) to make compounds that are able selectively to kill or to differentiate cancer cells. Although in the last two decades research into new anticancer drugs has not produced satisfactory results, there is solid ground on which novel strategies can be developed, mainly based on a much greater biological knowledge of human tumours. This article does not review all the possible approaches that may be followed, but simply discusses some ideas and problems mainly taken from the current research of our laboratory.

Animals↗
PubMed1989

[Is the search for Meckel's diverticulum in appendectomy still a current problem in common surgical practice?].

During a ten year period from 1978 to 1988, 46 Meckel's diverticula (MD) were removed from patients with clinical symptoms of appendicitis. These were detected incidentally among 3230 appendectomies which were routinely followed by small bowel exploration. Only 45.6% had histopathologically inconspicuous diverticular mucosa. 17.4% of MD displayed pathological mucosal changes in the face of a normal appendix. In 10 patients both conditions co-existed. There were no postoperative deaths. Postoperative complications requiring operative revision occurred in one patient. The search for a MD should be routine, and not only consequence of finding a normal appendix. The rationale for the routine removal of a MD is not only its role as a potential risk factor and the lesser operative risk, but the fact that a macroscopically bland diverticulum reveals histopathological abnormalities considerably more often than commonly assumed.

Adult↗
PubMed1987

Effects of three new anthracyclines and doxorubicin on the rat isolated heart.

The acute cardiac toxicity of three second-generation anthracycline analogues and doxorubicin was compared in a model of the rat isolated Langendorff perfused heart. The drugs, doxorubicin (DX), 4-epi-doxorubicin (4'EDX), 4-demethoxy-daunorubicin (4DMDR) and 4'-deoxy-doxorubicin (4'dxDX) were infused for 40 min at a concentration of 26 microM into the isolated hearts. All four compounds significantly reduced cardiac work and its first derivative. The time to 50% decrease in work (TW50) was respectively 36, 23, 9 and 7 min for DX, 4'EDX, 4'dxDX and 4DMDR. The three anthracycline derivatives, but not DX, significantly increased coronary resistance. Heart rate was reduced by all compounds compared with baseline, but not compared with controls. Rhythm disturbances were seen with all five hearts perfused with 4DMDR, which stopped beating before 40 min; 2/5 hearts in the 4'EDX group and 1/5 hearts in the 4'dxDX group also stopped before the end of perfusion. All the compounds reached concentrations in the myocardium 8 to 50 times higher than in the perfusing medium. The more cardiotoxic the compound, the higher was its myocardial concentration; a significant correlation was found for all four agents. Noradrenaline was never measurable in the perfusate of control and DX hearts; perfusion with the three anthracycline derivatives caused some release, but the pattern was not clearcut and the maximum concentrations attained in the perfusate were relatively low (less than or equal to 1.6 X 10(-9) M). In conclusion, in the rat isolated perfused heart, the early cardiotoxicity induced by equimolar concentrations of the three anthracycline compounds was greater than that induced by DX and was directly related to drug accumulation in the myocardium. Catecholamines do not seem to have a major role in the development of toxicity in this model.

Animals↗
PubMed1987

Results of heart valve replacement with the SORIN prosthesis.

From March 1977 to December 1981, 872 patients at our institution underwent valve replacement with a pyrolytic carbon tilting disc prosthesis manufactured in Italy by SORIN-Biomedica. To verify the performance characteristics of this prosthesis, we analyzed the intermediate-term results obtained over a cumulative total of 3,041 patient-years (pt-yr) of follow-up. Three hundred sixty-nine patients underwent mitral valve replacement (MVR), 309 had aortic valve replacement (AVR), and 194 had both mitral and aortic (double) valve replacement (DVR). Expressed in actuarial terms (% [+/- standard error of the mean] free of adverse events at 5 years) and in linearized terms (% pt-yr), respectively, valve-related complications occurred at the following rates: Thromboembolism, 89.9 +/- 1.9% and 2.1 +/- 0.4% pt-yr (MVR); 92.1 +/- 1.9% and 1.7 +/- 0.4% (AVR); 90.5 +/- 5.0% and 2.2 +/- 0.6% (DVR). Anticoagulant-related hemorrhage, 95.2 +/- 1.5% and 1.4 +/- 0.3% (MVR); 95.9 +/- 1.5% and 1.3 +/- 0.3% (AVR); 96.0 +/- 2.0% and 0.9 +/- 0.4% (DVR). Prosthetic valve endocarditis, 99.0 +/- 0.6% and 0.2 +/- 0.1% (MVR); 97.4 +/- 1.0% and 0.6 +/- 0.2% (AVR); 94.5 +/- 1.7% and 1.4 +/- 0.4% (DVR). Reoperation, 92.6 +/- 1.5% and 1.7 +/- 0.3% (MVR); 89.4 +/- 1.9% and 2.4 +/- 0.4% (AVR); 82.3 +/- 2.9% and 4.8 +/- 0.8% (DVR). The total valve-related morbidity and mortality was 79.6 +/- 2.6% and 4.9 +/- 0.6% (MVR); 79.7 +/- 2.6% and 5.1 +/- 0.6% (AVR); 70.5 +/- 4.0% and 7.7 +/- 1.1% (DVR). The 5-year actuarial survival rate without hospital mortality was 86.8 +/- 2.0% (MVR), 91.0 +/- 1.7% (AVR), and 78.8 +/- 3.7% (DVR). The intermediate-term survival and complication rates showed the performance of the SORIN prosthesis to be quite satisfactory.

Journal Article↗
PubMed1986

Antitumoral activity of the oxazaphosphorine derivative, mafosfamide-cyclohexylamine salt (ASTA 7557) on a murine ovarian reticular cell sarcoma and its subline resistant to cyclophosphamide.

The antitumor activity of mafosfamide (MFA), and its parent compound cyclophosphamide (CTX), was investigated against an ovarian reticular cell sarcoma growing i.m. in C57BI/6 mice (M5), which is very sensitive to CTX, and against a subline of this tumor (R16) resistant to CTX. MFA is the prototype of a class of oxazaphosphorines which do not require metabolic activation since under physiologic conditions they undergo rapid spontaneous hydrolyzation to the activated 4-hydroxyoxazaphosphorine and retain a spectrum of activity very similar to the parent compound. After a single dose (300 mg/kg X 1) or repeated low doses (100 mg/kg X 6) the antitumoral activity of MFA on the M5 tumor appeared comparable to or only slightly lower than CTX; the highest T/C value for median survival times was 167% in MFA-treated mice vs. 176% in the CTX group. MFA showed no activity against the R16 subline, thus indicating cross-resistance between the two drugs. Marked thickening of the glissonian capsule with compression of the lobular area of the liver, observed on i.p. administration of MFA, did not result in histopathologic abnormalities of the hepatic parenchyma. The therapeutic efficacy of MFA was similar with i.p. and the i.v. route. MFA may represent a good candidate to replace CTX in cases in which a compound acting per se, and not through metabolites, is preferred.

Animals↗
PubMed1986

Comparison between VP 16 and VM 26 in Lewis lung carcinoma of the mouse.

The antitumoral activity and pharmacokinetics of VP 16 and VM 26 were comparatively investigated in Lewis lung carcinoma (3LL)-bearing mice. When the two drugs were given at equitoxic doses, in single or repeated treatment, the superior antitumoral activity of VM 26 was clear. Compared to VP 16, VM 26 had a different pattern of distribution, with a larger volume of distribution, a longer elimination half-life time and a lower clearance. The tissue to plasma AUC ratios indicated that VM 26 concentrated more in tumor and heart while VP 16 gave highest concentrations in liver and intestine. Flow cytometry studies showed that VM 26 was more potent than VP 16 in causing cell cycle perturbation of 3LL cells growing in primary culture. VM 26 displayed cytotoxic activity at a concentration in the medium one-tenth that of VP 16. The uptake of VM 26 by 3LL cells was 15 times that of VP 16.

Animals↗
PubMed1985

Metabolic studies of a podophyllotoxin derivative (VP16) in the isolated perfused liver.

The metabolism of VP16 was studied in isolated perfused rat liver. The rate of elimination into the medium and excretion in bile were determined by h.p.l.c. with u.v. detection. With high VP16 concentrations (180 micrograms/ml medium), the elimination half-life of the compound was prolonged markedly (156 v. 45 min for lower doses), the percentage recovered in bile was more than halved and drug accumulation in the hepatic tissue was three times greater. These findings indicate saturation of metabolism and of biliary elimination during high-dose treatment. The presence of glucuronides in the bile of VP16 perfused livers indicates that VP16 undergoes conjugation with glucuronic acid. Formation of picro isomer of VP16 in the liver also occurs.

Animals↗
PubMed1985

Mycotic tuberculous aneurysm of the descending thoracic aorta.

Tuberculous aneurysm of the aorta is a rare and dangerous condition. Despite modern diagnostic and surgical techniques, it remains a challenge to recognize and treat. A successful resection of a false aneurysm of the descending aorta that ruptured into the lung of a 55-year-old woman is reported. A history of the patient and microscopic examination of the specimen indicated a diagnosis of tuberculosis. Antituberculosis chemotherapy was immediately implemented. The patient appears to be in good condition 8 months after operation; however, she remains under treatment for tuberculosis.

Journal Article↗
PubMed1985

Chronic traumatic aneurysms of the descending thoracic aorta.

Between 1970 and December 1984, 28 patients with post-traumatic chronic aneurysm of the descending thoracic aorta were consecutively operated on in our Division of Cardiac Surgery. Ages ranged from 16 to 66 years (mean 38 years); 25 were male and three were female. In all cases, a history of a major deceleration injury was documented. The interval between trauma and operation ranged from 2 to 50 years (mean 11.4 +/- 7.8). Twenty-three (82.1%) were asymptomatic. Only one operation was performed on an urgent basis for recurrent episodes of hemoptysis. All patients underwent resection with prosthetic tubulargraft (25 cases) and patch-graft (3 cases) replacements. In all patients but one, left heart bypass was employed. No hospital deaths, late deaths, paraplegia or graft-related complications occurred. Considering the risk of late rupture and the young age of most of the patients, surgery in chronic post-traumatic aneurysms of the descending thoracic aorta is always indicated. We consider left heart bypass a safe technique in preventing renal and medullar ischemic injuries.

Journal Article↗
PubMed1985

[Reinterventions on cardiac valve prosthesis].

From January 1978 to December 1984, 214 patients underwent a total of 243 reoperations for repair or replacement of a prosthetic heart valve. On the basis of the number of valve reoperations in the same anatomic position within the heart, the patients were divided into three groups. Overall hospital mortality was 23.4% (CL 20.3-26.7) in Group I (214 patients), 48% (CL 36.1-60.1) in Group II (25 patients), 25% (CL 3.3-62.6) in Group III (4 patients). Hospital mortality appeared to be related to urgency of reoperation (p less than 0.001 in Group I; p = 0.037 in Group II), primary indication for reoperation (p = 0.034 in Group I; p = 0.022 in Group II), association with other cardiac surgical procedures (p = 0.00253 in Group I). Hospital mortality in Group I was significantly higher (p = 0.0056) when reoperation was performed within one year after valve replacement. No significant differences in urgency and emergency rate were noted between reoperations on mechanical heart valves and bioprostheses. No significant differences in bleeding complications were noted between reoperations and initial valve replacement. Mean follow-up is 37.4 +/- 21.8 months (range 2 to 85 months). Actuarial survival rate is 82.8 +/- 3.1% at 1 year, 78.7 +/- 3.5% at 2 years and 71.5 +/- 5.1% at 5 years; 90.9% (CL 87.4-93.6) of the followed patients are in I or II NYHA class. The results appear to suggest that when significant (on clinical or instrumental criteria) prosthetic disfunction is diagnosed, reoperation should be undertaken early to minimize operative risk. The Authors point out that surgery in such patients also ensures satisfying long-term results.

Follow-Up Studies↗