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Biomedical subjects

R Colombo

Publications and source records attributed to R Colombo.

At least 127 records · Page 7Linked to original sources

Combined intravesical chemotherapy with mitomycin C and local bladder microwave-induced hyperthermia as a preoperative therapy for superficial bladder tumors. A preliminary clinical study.

Twelve patients suffering from superficial transitional cell carcinoma of the bladder underwent treatment combining simultaneous mitomycin C topical instillation and local endocavitary hyperthermia as a preoperative adjunct to transurethral resection in a preliminary clinical study. A specifically designed system to deliver and monitor local bladder hyperthermia was used. The feasibility, the subjective tolerance and the side effects of the combined treatment were the main target of our investigation. Endoscopic and histologic features, assessed before, during and after this combined approach, showed selective damage to neoplastic areas with minimal changes in the normal urothelium. Local intravesical concurrent chemotherapy and hyperthermia administration is found to be a safe and well-tolerated approach for superficial bladder tumor treatment. The preliminary results encourage further studies to define the limits and prospects of this regimen, in both superficial bladder tumor ablation and prophylaxis of recurrences.

Administration, Intravesical↗

Long term experience with the prostatic spiral for urinary retention due to benign prostatic hyperplasia.

Twenty high risk patients with benign prostatic hyperplasia and urinary retention were treated by insertion of an intraprostatic spiral. The device was positioned under fluoroscopic guidance using a technique developed by us. The procedure required only local anaesthesia and successfully relieved the obstruction in all patients. At the six-month follow-up full continence had been achieved in 15 patients (75%). Three patients (15%) complained of mild stress incontinence but this was not severe enough to require removal and repositioning of the spiral. A 92-year-old patient reported severe incontinence despite correct positioning of the spiral. Removal of the spiral was necessary in one of the continent patients who was receiving anti-coagulant drugs because of sudden, severe macrohaematuria with subsequent acute urinary retention. The spiral became displaced and required repositioning in one patient. Median residual urine volume was constantly lower than 50 ml and the median maximal flow rate at six-month follow-up was 13.2 ml/s. Our long term follow-up study shows the effectiveness and safety of the prostatic spiral as an alternative treatment for selected patients with urinary retention caused by benign prostatic hyperplasia.

Aged↗

In-vitro susceptibility of Haemophilus influenzae to loracarbef (LY 163892) and other oral antibiotics. Collaborative Study Group on Pediatric Infectious Disease in Lombardy.

Data on susceptibility of Haemophilus influenzae are scanty in Italy. We compared the activity of loracarbef (Ly 163892), a new carbacephem, with that of 4 other agents against 265 strains of H. influenzae (46 type b, 219 nontypable) isolated from adults and children at Istituti Clinici di Perfezionamento of Milano, between 1/1/84 and 1/1/89, and also from 7 children at pediatric departments in Lombardy during 1988. In adults 72 strains were all isolated from sputum of patients with pneumonia or chronic bronchitis; in children 199 strains were isolated from conjunctiva (53% of the patients had also a concomitant respiratory infection), 24 from middle ear, 18 from sputum and 32 from blood or cerebrospinal fluid. Minimal inhibiting concentrations (MIC) were determined by the broth microdilution technique. The incidence of resistance of H. influenzae to ampicillin was 3.8%; the lowest percentage of resistance was found for loracarbef (0%) and the highest for erythromycin (94% for strains isolated from children and 97% for strains isolated from adults).

Adult↗

Renal lithium clearance in the different stages of hypertension.

This study investigated whether fractional lithium excretion (FELi), used as a marker of proximal fluid delivery, changes during different phases of essential hypertension. Forty-eight subjects were studied: 12 essential hypertensives (EH); 12 borderline hypertensives (BL); 12 normotensives with a positive family history of essential hypertension (NH) and 12 normotensives without a family history of essential hypertension (NN). Measurements were performed in the recumbent position, both in basal conditions and after a saline load (2% body weight in 1 h; 0.333 ml/min per kg body weight). In basal conditions, a moderate extracellular volume expansion was already present in the subjects. In these conditions, FELi of EH was significantly higher than that of all the other groups (P less than 0.01). After the saline load, fractional sodium excretion increased in all the groups (P less than 0.01), but to a significantly greater extent in EH (P less than 0.01). FELi rose significantly only in BL (P less than 0.05). The change in FELi of BL correlated positively (P less than 0.02) with the change in blood pressure in 10 of these subjects 3 years after this study. Moderate extracellular volume expansion may be able to either reveal or stimulate an increase of FELi in subjects with established hypertension. When a greater degree of extracellular volume expansion is induced, this increases FELi in BL and this effect may be related to the subsequent development of hypertension.

Adolescent↗

[Comparison of rectal examination, transrectal echography, CAT and MRI in the local staging of prostatic carcinoma].

From January 1978 to June 1990, 120 prostate cancer patients were submitted to radical retropubic prostatectomy. Local pathological staging evidenced 70 patients (58%) in stage B of disease (intraprostatic disease) and 50 patients (42%) in stage C of disease (extraprostatic disease). Sensitivity of rectal examination, transrectal ultrasonography, CT or NMR for stage B was 61%, 75%, 54% respectively and for stage C 61%, 70%, 50%. This study underscores the effectiveness of transrectal ultrasonography in the diagnosis of prostate cancer non evidenced at rectal examination. CT and NMR are not valuable for local staging and are now used only in patients at risk for extraprostatic or systemic disease.

Evaluation Studies as Topic↗

[Local prostatic hyperthermia in the therapy of urinary obstruction caused by prostatic adenoma. Experimental, clinico histologic and structural findings].

A specifically designed system of selective prostate heating was used to treat 197 patients with prostatic diseases: 164 benign prostatic hypertrophy cases, 14 prostatic adenocarcinoma cases, 19 chronic abacterial prostatitis cases. Ninety-one benign prostatic hypertrophy patients could be evaluated at the three month follow-up date. Sixty-eight patients complained of severe obstructive symptoms and 23 had an indwelling catheter. Prostates were heated up to 42 +/- 0.5 degrees C during 60 minute long sessions, once or twice a week for five weeks. Local prostatic hyperthermia determined a marked amelioration of the clinical picture in 67% of patients who presented without an indwelling catheter. Sixteen patients (70%) were weaned off the catheter. Major complications were not encountered.

Aged↗

Morphodynamic and biochemical assessment of seminal plasma in patients who underwent local prostatic hyperthermia.

Fourteen young and sexually active patients with chronic abacterial prostatitis who failed to respond to conventional medical therapy underwent four 60 minute sessions of local prostatic hyperthermia. Calculated prostatic temperature was 42 +/- 0.5 degrees C. Analysis of seminal plasma was performed pre- and postoperatively and included: number, motility, and morphology of spermatozoa; zinc, citric acid, D-fructose, and free testosterone content. Preoperative semen analysis was normal in five patients and abnormal in nine. Morphodynamic and biochemical patterns of seminal plasma were not significantly altered by thermotherapy. Local prostatic hyperthermia can be safely used in patients with chronic abacterial prostatis not responding to conventional medical therapy and desiring to preserve their reproductive potential.

Adult↗

Regulation of tonoplast k channels by voltage in the range of physiological electric potentials.

The presence of tonoplast ion channels regulated by voltage in the physiological range of transtonoplast electric potential was studied in isolated vacuoles from Acer pseudoplatanus cultured cells. In symmetrical KCl or K-gluconate depolarizing pulses induced instantaneously developing, decaying outward currents, while in symmetrical tetramethylammonium chloride these currents were absent. The outward currents were reduced if the depolarizations were applied from a holding potential of +30 millivolts and increased upon depolarizations from a holding potential of -30 millivolts and even more from a holding potential of -50 millivolts. These results indicate that the outward currents are due to K(+) movement through channels which are open around 0 millivolt and close at positive potentials. These K(+) channels, regulated in the range of the physiological electric potentials reported for the vacuoles in situ, are likely the same K(+) channels activated by hyperpolarizations which we have previously described (R Colombo, R Cerana, P Lado, A Peres [1988] J Membr Biol 103: 227-236).

Journal Article↗

Local bacillus Calmette-Guerin therapy for superficial bladder cancer: clinical, histological and ultrastructural patterns.

The effectiveness of intravesical administration of bacillus Calmette-Guerin as a prophylaxis of superficial bladder cancer has been definitely demonstrated. On the other hand, therapeutic regimens, duration effects, efficacy of either maintenance cycles or repeated courses of therapy in case of failures are still controversial. We report the results achieved in 15 cases of carcinoma in situ of the bladder and in 48 cases of superficial bladder cancer (Ta-T1 stage of disease) with bacillus Calmette-Guerin immunotherapy. Our patients underwent an initial six week cycle and a following maintenance cycle with monthly administrations for one year. Median follow-up was 19 months (range 18-21 months). Patients with carcinoma in situ are now free of disease; on the contrary, patients with Ta-T1 tumors experienced 18 recurrences (28%). There was a marked decrease of recurrence rate when compared to previous local chemotherapy. We report in detail the adverse effects encountered and both histologic and ultrastructural findings observed after immunotherapy. Bacillus Calmette-Guerin therapy can influence positively the natural history of the disease but possible adverse effects should always be considered before starting the treatment.

Administration, Intravesical↗

Predicting interindividual variations in antihypertensive therapy: the role of sodium transport systems and renin.

The efficacy of captopril at 75 mg/day, atenolol at 100 mg/day and canrenoate potassium at 200 mg/day was compared in 42 essential hypertensive patients in randomly assigned sequences. All the drugs lowered blood pressure significantly but variations were found in the individual response. Patients who were more responsive to captopril also seemed to be more responsive to atenolol and vice versa (r = 0.75; P less than 0.0001), while the relationship between mean blood pressure reached after canrenoate potassium and that reached after atenolol or captopril was much weaker. The patients who were responsive to atenolol and captopril were considered as one group (n = 22) and compared with the 12 patients more responsive to canrenoate potassium. Before treatment, the former group had higher plasma renin activity (PRA) and lower Na,K cotransport activity across the erythrocyte membrane than the latter. These two variables, considered together as a discriminant function, correctly classified 92% of cases in the canrenoate potassium responder group and 73% of cases in the atenolol-captopril responders. These results raise the problem of individual assessment to obtain the most effective antihypertensive therapy and suggest that PRA and Na,K cotransport may be useful in predicting the individual response to antihypertensive drugs.

Adolescent↗

Metal ions modulate the effect of doxorubicin on actin assembly.

Doxorubicin (DXR) exhibits a significant activity in many human malignant neoplasms but, unfortunately, produces many undesirable cellular troubles which mainly lead to a severe dose-dependent cardiomyopathy. Many Authors had suggested that doxorubicin interacts with actin and affects the intracellular ion composition; following this reasoning, we studied the effect of doxorubicin on actin polymerization in vitro induced by different metal ions. In this paper we show that the negative action of doxorubicin on actin polymerization (inhibition of filament growth, reduction of polymer amount and polymer size at steady-state) is strongly ion-dependent. With this finding, we suggest that the direct action of antibiotic on actin assembly, in the presence of the drug-related changes in cytoplasmic electrolyte pattern, could become predominant in vivo.

Actin Cytoskeleton↗

Pathogenetic mechanisms in essential hypertension. Analogies between a rat model and the human disease.

Essential hypertension is a genetic disease. Its phenotypic expression depends on the interaction between genetic and environmental factors. In prehypertensive rats of the Milan hypertensive strain (MHS) a genetically inherited increase of tubular reabsorption was found, which causes the increase of blood pressure. Studies of ion transport systems in these rats have shown that the Na-K cotransport activity is increased both in erythrocytes and in tubular cells of MHS rats compared with their normotensive controls (MNS) and that this alteration is genetically linked to the transmission of high blood pressure levels. Also, in young human normotensives prone to develop essential hypertension there is an abnormal pattern of renal function which could be in agreement with a primitive increase in tubular reabsorption. Studies of erythrocyte ion transport systems in these subjects suggest that at least in a subgroup of humans predisposed to develop essential hypertension a pathogenetic mechanism similar to the one proposed for the MHS rat can be at work.

Animals↗

A possible primary role for the kidney in essential hypertension.

The role of the kidney in "essential" or "genetic" types of hypertension has been evaluated both in a rat model such as the Milan hypertensive strain (MHS) or in humans. In both species, abnormalities of renal function have been demonstrated before the development of hypertension. Moreover hypertension could be "transplanted" with the kidney when kidney cross-transplantation was carried out between MHS and the Milan normotensive strain (MNS). Also in humans, the familiality for hypertension of the donor affected the requirement of antihypertensive therapy of the recipient. Further studies furnished results that were consistent with the hypothesis that a primary increase in Na transport across the tubular cell could be responsible for the pressor effect of the kidney in MHS or in humans. Because many similarities were found between the function of the tubular cell and the red blood cell in MHS, red blood cells were used to gain information about the molecular genetic mechanisms underlying these cellular changes. The results so far obtained showed that red blood cell abnormalities in MHS were genetically determined within the stem cells and genetically associated with the development of hypertension in F2 hybrids obtained by crossing the F1 (MHS X MNS). Moreover, the abnormal Na transport across the cell membrane may be due to an abnormal function of the membrane skeleton proteins. Studies are in progress to evaluate a possible cause-effect relationship between: membrane skeleton protein-ion transport across the cell membrane and the development of hypertension.

Animals↗

Histological and ultrastructural evaluation of extracorporeal shock wave lithotripsy-induced acute renal lesions: preliminary report.

Biopsy material taken from kidneys of 14 patients with renal stones before performing extracorporeal shock wave lithotripsy (ESWL) and an average of 15 days after was examined histologically and ultrastructurally. In the post-ESWL specimens, light microscopy revealed edema and extravasation of urine and blood into the interstitial spaces, blocking of cortical tubules by hemorrhagic streaks and widespread dilatation of the veins, with signs of endothelial destruction and partial organization of thrombi. By using the electron microscope, abnormalities of the endothelium and glomerular epithelium, hemosiderin accumulations in the tubular cells and small linear patches of fibrosis at the corticomedullary junction and in the cortical interstitial spaces were seen. This preliminary report indicates that renal damage can be shown soon after ESWL on histological and ultrastructural studies and that the lesions observed can be either reversible or permanent.

Adult↗

How does doxorubicin interfere with actin polymerization?

It is well known that doxorubicin (adriamycin), an antibiotic with an antitumoral action, has some undesirable side effects. Among these, the most serious is, undoubtedly, damage to myocardial tissue (progressive cardiomyopathy). We have for some time focused our attention on the effect of this drug on cellular contractile systems and, more specifically, on the process of actin polymerization, which we consider to be an extremely delicate key point for the economy of most cellular motor manifestations. In the present study, using capillary viscometry, spectrofluorometry and electron microscopy, we have shown a negative action of doxorubicin on various important chemical events which contribute to the transformation of G-actin into F-actin. Specifically, we found that the drug mainly acts by reducing the polymer size. A possible action mechanism of the antibiotic is proposed and a plausible correlation among the events described in vitro and those observed in vivo is advanced.

Actins↗

Dose-dependence of doxorubicin effect on actin assembly in vitro.

Doxorubicin (Adriamycin), one of the most potent antibiotics used in tumor chemotherapy, shows many undesirable side effects. We studied the effect of different drug concentrations on the biochemistry of cell motility and, in particular, on potassium-induced actin polymerization. It is well known, in fact, that the actin aggregational status could dramatically influence many cell motility manifestations. Our results clearly show that stoichiometric and substoichiometric amounts of doxorubicin negatively influence actin polymerization by inhibiting both the filament growth and the polymer amount at steady-state; the balance between the two different effects seems to be in relation to the drug concentration. The obtained results could explain some of the doxorubicin effects previously observed in vivo.

Actins↗