Biomedical subjects

T Colombo

Publications and source records attributed to T Colombo.

At least 19 recordsLinked to original sources

PubMed1992

Human plasma lipid peroxide levels show a strong transient increase after successful revascularization operations.

This study was performed to evaluate the hypothesis that oxygen radicals/lipid peroxidation are involved in reperfusion injury in humans. The study included 37 patients, who underwent surgical revascularization operations for kidney transplantation (9 subjects) or limb salvage (28 subjects). Peripheral venous blood samples were taken 30 min before starting reperfusion (baseline) and 1, 2, 3, 4, and occasionally 6 to 18 h after revascularization. The amount of plasma malonaldehyde formed in the reaction with thiobarbituric acid (MDA-TBA) was determined by high-performance liquid chromatography (HPLC). The baseline MDA-TBA values of the patients were very close to the value determined for 20 age-matched healthy subjects (i.e. mean +/- SD 0.689 +/- 0.294 nmol/mL plasma [range 0.2 to 1.37] vs. 0.700 +/- 0.209 nmol/mL plasma [range 0.385 to 1.29]). All patients responded to successful revascularization with significant increase of the plasma MDA-TBA within about 1 h after onset of reperfusion. Thereafter the values decreased nearly to the preoperative state. The mean increase of MDA-TBA was 107% in kidney transplantation and 54% in limb revascularization. In a few patients with severe arteriosclerosis, revascularization was not optimal and no increase in the MDA-TBA value occurred. The results of this study indicate that therapeutic intervention to prevent lipid-peroxidation-mediated reperfusion injury is confined to a rather narrow time window and must be undertaken either prior to or immediately after revascularization.

Aged↗

PubMed1992

Evaluation and treatment of secondary tricuspid insufficiency.

To define the role of functional tricuspid insufficiency and right ventricular (RV) failure in patients with mitral disease, the data of 121 patients with secondary tricuspid insufficiency that underwent mitral valve replacement (MVR) from January 1982 to December 1987 were analyzed. The mitral hemodynamic lesion was: stenosis in 41 patients (33.9%); insufficiency in 11 (9.1%) and mixed stenosis and insufficiency in 69 (57.0%). NYHA functional class was: II in 4 patients (3.3%), III in 78 (64.5%) and IV in 39 (32.2%). In 100 cases (group 1) with tricuspid insufficiency defined as moderate or severe, a De Vega annuloplasty was performed while in 21 (group 2) with mild tricuspid insufficiency, no tricuspid surgical procedure was performed. Hospital deaths occurred in 17 of 121 patients [14% (CL 10.8-17.0)]. There was no significant difference in hospital mortality between group 1 and group 2 (15% vs 9.5%; P = 0.75). Incremental risk factors for hospital mortality as determined by multivariate analysis, include: cardiothoracic ratio (P = 0.0016), total aortic cross-clamp time (P = 0.006), associated cardiac disease (P = 0.0209) and emergency operations (P = 0.0318). Mean follow-up of surviving patients was 50.1 +/- 28.1 months. Late deaths occurred in 16 patients [15.4% (CL 11.7-18.7)]. The actuarial survival rate was 85.6% and 73.8% at 5 and 9 years, respectively. Nine patients [8.6% (CL 5.9-11.3)] required reoperation. There was no significant difference between group 1 and group 2 in the rate of late cardiac related deaths (5.9% vs 5.3%, P = 0.66) and of tricuspid reoperations (4.7% vs 5.3%, P = 0.62).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1992

In situ extracorporeal shock wave lithotripsy of ureteral calculi with the MPL-9000X lithotriptor.

Within the wide armamentarium of urinary stone treatment modalities extracorporeal shock wave lithotripsy (ESWL) has been established as the first line procedure. With the Dornier MPL-9000X lithotriptor one has the choice of ultrasound or fluoroscopic localization of calculi throughout the entire urinary tract. Except for the kidney, ultrasound guidance is preferred for calculi in the distal ureter, while fluoroscopy is generally used on the proximal two-thirds of the ureter. Between January and December 1990, 123 ESWL treatments were performed on 83 patients suffering from ureteral calculi with an average stone size of 9.3 x 6 mm. Median treatment parameters were 1,597 shock waves at 19.3 kv. for 43 minutes. For stones in the upper two-thirds of the ureter sedation analgesia was given, while ESWL on the pelvic ureter did not create intolerable pain. Of the treatments 69% were done on an outpatient basis. In situ ESWL treatment of urinary calculi was successful in 72 patients (86.7%), and 20 patients (24.1%) were treated with multiple treatment sessions. ESWL therapy for 47 stones in the distal ureter showed better results than for 33 stones plus 2 steinstrasse in the proximal part (95.5% versus 80% stone-free rate). Of 4 patients with mid ureteral calculi 2 could be rendered stone-free by ESWL alone. Auxiliary procedures, such as percutaneous nephrostomy or ureteral splints, had to be performed in 15.7%. Final endoscopic stone extraction was done in 7 cases and open surgery in 4, constituting a 13.3% failure rate for ESWL therapy. The results prove that the MPL-9000X lithotriptor is effective for primary noninvasive stone treatment.

Combined Modality Therapy↗

PubMed1992

[Combined ultrasound-urodynamic study in paraplegic patients].

Over a period of 2 years (1989-1991), combined urodynamic and ultrasonic investigations of the lower urinary tract were performed in 80 patients with spinal cord injuries. The main advantage of this procedure proved to be the lack of irradiation to both patient and investigator. Besides the real-time image of the bladder, bladder neck, prostate, pelvic floor and urethra, functional conclusions were possible, especially when urodynamic pressure curves were also considered.

Adult↗

PubMed1992

[The effect of 6% HES 200/0.6-0.66 on plasma volume and blood coagulation].

The main goal of the recent study was to evaluate changes in plasma volume due to the application of 6% HES 200/0.6-0.66. 12 patients according to the ASA physical status classification (I, II) undergoing minor surgical interventions received 500 ml of this artificial plasma substitute within 30 min. In a control group (n = 12), 500 ml of lactated Ringer's solution was given within the same period. A further question of the present investigation was the possible influence of 6% HES on coagulation during the following period (1st-3rd postoperative days). 6% HES 200/0.6-0.66 led to an additional augmentation of plasma volume measured via the mechanical oscillator technique of 200 ml (40% of the volume given) immediately at the end of infusion. A second increase in plasma volume of 100 ml (20% of the volume infused) could be observed 1 h later. With exception of the activity of factor VIII, the coagulation parameters had not been altered by infusion of 6% HES. The activity of factor VIII decreased to about 50% of the control level but showed a tendency to normalization within the following observation period. 6% HES 200/0.6-0.66 has a marked volume-expanding effect and exerts no influence on coagulation except a temporary decrease of factor VIII activity.

Adult↗

PubMed1992

[Repeat myocardial revascularization].

Eighty-two consecutive patients undergoing reoperation for coronary revascularization from January 1980 to November 1990 were reviewed to determine early and late results and predictors of survival. Seventy patients were male and 12 female; age ranged from 36 to 75 years (mean 56.4 +/- 8.1). All were symptomatic for angina. The mean interval between first and second operation was 62.8 +/- 47.8 months (range 1 to 220 months). Angiographic indications for reoperation were: graft failure (34.1%), progression of atherosclerosis in the native coronary circulation (6.1%) and combination of the two (59.8%). Mean ejection fraction was 45.9 +/- 10.2 (range 11 to 67). Surgical indication was elective in 79.3%, urgent in 14.6% and emergent in 6.1%; 199 grafts were performed (2.4 +/- 1 grafts/patient). Hospital mortality was 6.1% (5 cases). Late mortality was 5.2% (4 cases). Actuarial survival rate (including hospital mortality) was 87.9% at 3, 5 and 10 years. Multivariate analysis identified left main stenosis (p = 0.00001), family history of coronary disease (p = 0.003), urgent/emergency operation (p = 0.015) as predictors of increased in-hospital mortality; postoperative myocardial infarction (p = 0.002) and preoperative heart failure (p = 0.01) as predictors of increased late mortality. Follow-up of in-hospital survivors (mean interval 42.7 +/- 25.8 months, range 3 to 120 months) documented 27 cardiac major events (other than death) in 24 patients (32.9%). Actuarial rates of freedom from major cardiac events were 70%, 52.9% and 48.1% at 3, 5 and 10 years respectively. Multivariate analysis identified preoperative ejection fraction (p = 0.01) as predictor of recurrence of angina and preoperative heart failure (p = 0.02) as predictor of occurrence of cardiac major events.

Adult↗

PubMed1992

[Surgical revascularization in acute myocardial infarct].

To determine the potential role of emergency surgical revascularization as treatment of acute myocardial infarction (AMI), results in 79 patients undergoing operation for myocardial revascularization during AMI from January 1986 to January 1991 were reviewed. Clinical characteristics for inclusion in the study were: 1) emergency operation; 2) persistent angina not controlled by medical therapy; 3) fixed ST segment elevation until surgical procedure, independently from magnitude of enzymatic levels. The 79 patients were divided in 2 groups: 27 with AMI or evolving AMI (Group 1); 52 with AMI due to complications during PTCA (Group 2). Twenty-eight patients had extremely severe clinical conditions. Mean interval between the beginning of AMI and operation was 4.2 +/- 6.7 hours, with a statistically significant difference between Group 1 (8.7 +/- 10.0) and Group 2 (1.9 +/- 1.0). One hundred ninety-two grafts were performed (2.4 +/- 1.1 grafts/patient). Overall hospital mortality was 10.1% (CL 6.7-13.3) (8 deaths) with a difference between Group 1 [18.5% (CL 10.7-25.3)] and Group 2 [5.8% (CL 4.7-6.6)] (p = 0.074). The incidence of perioperative myocardial infarction was 30.4% (CL 24.9-35.1) for that one in the area of ischemic muscle and 2.6% (CL 0.8-4.1) for infarction in remote muscle. Multivariate analysis for the entire series (79 patients) identified as independent predictors of increased in-hospital mortality: preoperative cardiogenic shock (p = 1.000E-4) and hyperlipidemia (p = 0.008). In Group 1 multivariate analysis identified as independent predictors of increased in-hospital mortality: the attempt of revascularization by PTCA and hyperlipidemia; in Group 2: preoperative need of mechanical ventilatory support.(ABSTRACT TRUNCATED AT 250 WORDS)

Chi-Square Distribution↗

PubMed1991

Ultrasonography of urinary tract and micturition as an alternative to radiologic investigations in the spinal-cord-injured patient.

Over a period of 1.5 years (July 1989-Jan. 1991), a total of 504 patients, 442 of them suffering from spinal cord injuries with subsequent voiding disorders, were investigated by ultrasonography of the genitourinary tract. Ultrasonography of the upper urinary tract as well as the bladder and prostate provided and accurate image of the pathomorphological changes which go along with this kind of malfunction of the lower urinary tract in this group of patients. The application of rectal ultrasonography using a linear array rectal transducer was able to provide equal or even better images of the micturition process than micturition cystourethrography (MCU). An adequate and accurate real time image of the bladderneck, the prostatic urethra and the external rhabdosphincter could be obtained in all instances. Combined micturition cytourethrosonography (MCUS) with urodynamic evaluation has also been performed, which made the observation and judgement of the bladder outlet as well as the position of the catheter possible throughout the procedure without the interference of X-rays.

Adult↗

PubMed1991

[Persistent bradycardia and apnea due to hypothyroidism in a very low-weight newborn infant].

Alterations in thyroid function are quite heterogeneous in VLBW preterm neonates. The case of a 1160-g newborn is reported, affected by severe RDS and persistent bradycardia during the first week of life, who later developed symptoms and signs of low-output cardiac failure. ECG showed low QRS. Echocardiography revealed small pericardial effusion. Therapy with L-thyroxine led to rapid improvement of clinical conditions and to normalization of ECG and echocardiographic pattern. Levels of thyroid hormones should be monitored in VLBW infants, since their deficiency may play a role in compromised clinical conditions.

Apnea↗

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↗

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↗