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Biomedical subjects

A Colombo

Publications and source records attributed to A Colombo.

At least 253 records · Page 14Linked to original sources

Interaction of ionizing radiation with topotecan in two human tumor cell lines.

The effect of topotecan, a topoisomerase I inhibitor, on ionizing radiation-induced cytotoxicity was studied in 2 human tumor cell lines characterized by a different expression of the target enzyme. The cytotoxicity of topotecan alone or in combination with radiation was assessed in exponentially growing non-small-cell lung cancer (H460) and glioblastoma (GBM) cells using the colony-forming assay. An isobologram method was used to evaluate the treatment interaction. An apparent supra-additive effect in cell killing following drug-radiation-combined treatment was observed only in GBM cells exposed to topotecan for 24 hr. In the case of H460 cells, interaction varied from a strong infra-additive effect at low radiation doses to a slight supra-additive effect when cells were exposed to radiation doses greater than 3 Gy. Northern blot analysis indicated that topoisomerase I expression in H460 cells was 8-fold higher than that of GBM cells. Although the H460 cell line exhibited an increased sensitivity to topotecan, only in the GBM cell line (which expressed a lower level of topoisomerase I) did the drug potentiate the radiation cytotoxicity. The observation that the radiosensitization by topotecan was related to topoisomerase I level is consistent with a putative role of the enzyme in processes involved in the repair of radiation damage. It is conceivable that the modulation of enzyme function results in an effective reduction of cellular capability for repair of radiation damage only if the enzyme is not over-expressed. Although a precise role of topoisomerase I in the cellular response to ionizing radiations (in particular, in DNA repair) remains to be documented, such results suggest the potential interest of topoisomerase I inhibitors in combination with radiation therapy for tumors expressing low topoisomerase I levels.

Antineoplastic Agents↗

Heparin-coated Palmaz-Schatz stents in human coronary arteries. Early outcome of the Benestent-II Pilot Study.

BACKGROUND: The purpose of the Benestent-II Pilot Study was to evaluate the safety of delaying and eliminating anticoagulant therapy in patients receiving a heparin-coated stent in conjunction with antiplatelet drugs. METHODS AND RESULTS: The study consisted of three initial phases (I, II, III) during which resumption of heparin therapy after sheath removal was progressively deferred by 6, 12, and 36 hours. In phase IV, coumadin and heparin were replaced by 250 mg ticlopidine and 100 mg aspirin. Of the 207 patients with stable angina pectoris and a de novo lesion in whom heparin-coated stent implantation was attempted, implantation was successful in 202 patients (98%). Stent thrombosis did not occur during all four phases, and the overall clinical success rate at discharge was 99%. Bleeding complications requiring blood transfusion or surgery fell from 7.9% in phase I to 5.9%, 4%, and 0% in the three following phases. Hospital stay was 7.4, 6.1, 7.2, and 3.1 days for the consecutive phases. The restenosis rate for the combined four phases was 13% (15% in phase I, 20% in phase II, 11% in phase III, and 6% in phase IV). The overall rate of reintervention for the four phases was 8.9%. At 6 months, 84%, 75%, 94%, and 92% of the patients of phases I to IV, respectively, were event free. For the four phases, the event-free rate was 86%, which compares favorably with the rate observed in the Benestent-I study (80%; relative risk, 0.68 [0.45 to 1.04]). CONCLUSIONS: The implantation of stents coated with polyamine and end-point-attached heparin in stable patients with one significant de novo coronary lesion is well tolerated, is associated with no (sub)acute stent thrombosis, and results in a favorable event-free survival after 6 months.

Aspirin↗

A randomized comparison of combined ticlopidine and aspirin therapy versus aspirin therapy alone after successful intravascular ultrasound-guided stent implantation.

BACKGROUND: Previous studies have shown that it is feasible to withhold anticoagulation after a successful intracoronary stent procedure with a low incidence of stent thrombosis. The importance of specific antiplatelet agents when stenting is performed without anticoagulation is unknown. METHODS AND RESULTS: After successful intravascular ultrasound-guided stenting, 226 patients were randomly assigned to receive either aspirin therapy alone (n = 103) or a combination of ticlopidine and short-term aspirin therapy (n = 123). Primary angiographic and clinical end points were stent thrombosis, death, myocardial infarction, the need for postprocedure coronary artery bypass surgery or repeated angioplasty, and significant medication side effects requiring termination of the medication within the first month of a successful procedure. At 1 month, the rate of stent thrombosis was 2.9% in the aspirin only group and 0.8% in the ticlopidine-aspirin group (P = .2). Cumulative major clinical events after successful stenting occurred in 3.9% of the patients in the aspirin group and in 0.8% in the ticlopidine-aspirin group (P = .1). There were no medication side effects in the aspirin group; in the combined ticlopidine-aspirin group, medication side effects occurred in 3 patients (P = .2). CONCLUSIONS: At 1 month, there was no difference in the incidence of stent thrombosis or other clinical end points between the two poststent antiplatelet regimens. However, the relatively small size of the study and the low incidence of thrombosis events may have contributed to the failure to detect differences in angiographic and clinical end points between the two groups.

Aged↗

Implantation of the peripheral Wallstent for diffuse lesions in coronary arteries and vein grafts.

The Wallstent (Schneider, Bulach, Switzerland) is available in different lengths without much compromise in flexibility and radial support compared to some other stents. We treated 24 patients (26 vessels) with diffuse coronary lesions or vein graft lesions with intravascular ultrasound-guided peripheral Wallstent implantation. Average balloon pressure during stent optimization was 16.4 +/- 2.7 atm. The stents could be successfully implanted in 24 vessels. Minimal lumen diameter and percent diameter stenosis after stenting were 3.60 +/- 0.62 mm and -8 +/- 13%, respectively. Average stent length was 63.7 +/- 22.7 mm. There was one procedure-related complication. After stenting, all patients were treated only with antiplatelet agents. During 1-month follow-up, there was one subacute stent thrombosis due to incomplete coverage of a distal dissection. These preliminary results show the feasibility of this novel approach in selected lesions.

Adult↗

Acute recoil of Palmaz-Schatz stent: a rare cause of suboptimal stent implantation--report of two cases with intravascular ultrasound findings.

It is generally believed that the Palmaz-Schatz stent maintains a strong radial force, preventing stent recoil. However, the capacity to prevent recoil is largely governed by the hardness or resistance of the lesion. We report two cases of "acute Palmaz-Schatz stent recoil," documented by intravascular ultrasound, and suggest a novel treatment of this unusual problem.

Angioplasty, Balloon, Coronary↗

Concurrent preoperative chemotherapy with 5-fluorouracil and mitomycin C and radiotherapy (FUMIR) followed by limited surgery in locally advanced and recurrent vulvar carcinoma.

To prospectively evaluate the feasibility and efficacy of neoadjuvant chemoradiotherapy locally advanced or recurrent vulvar carcinoma, 58 patients referring for primary (41) or recurrent (17) disease received preoperative external radiotherapy to a dose of 54 Gy, divided into two courses with an interval of 2 weeks. 5-Fluorouracil (750 mg/m2 daily for 5 days) and mitomycin-C (15 mg/m2 single bolus) were given at the start of each cycle. Wide local excision and inguinal lymphadenectomy were planned after treatment. Eighty-nine percent of patients completed the chemoradiotherapeutic treatment, whereas 72% underwent surgery. Objective responses were observed in 80% of vulvar diseases and in 79% of groin metastases. Pathologic complete response of both the vulvar and inguinal disease was confirmed in 13 patients (31%). Early severe toxicity was recorded in 3 patients and severe worsening of performance status in 3. Three deaths occurred shortly after treatment and at least one is directly related to toxic effects. This treatment allows good control of locally advanced and recurrent vulvar cancer with acceptable side effects. Further follow-up is required to determine the long-term outcome and the effectiveness of the surgical procedure.

Antibiotics, Antineoplastic↗

Results of coronary stenting for restenosis.

OBJECTIVES: This study attempted to analyze immediate and long-term angiographic and clinical results of coronary stent implantation for restenosis in a consecutive group of patients. BACKGROUND: The rate of stent utilization in patients with coronary artery disease has increased exponentially in recent years. There are many unanswered questions about the use of stenting in patients with restenosis, particularly with respect to late clinical and angiographic results. METHODS: A total of 159 stents were implanted in 128 consecutive patients with 139 lesions (mean 1.3 stents/patient). A technique of optimal stent expansion was used in all patients, and intravascular ultrasound guidance with no subsequent anticoagulation was performed in 41 patients. RESULTS: Stent implantation was successful in 126 patients (98%). Four patients (3.1%) had complications (in two after successful stenting): death in one, emergency bypass surgery operation in two and subacute stent thrombosis in one. Stents were implanted with a final balloon size (mean +/- SD) of 3.5 +/- 0.5 mm and a mean maximal pressure of 11 +/- 4 atm (range 8 to 20). Angiographic restenosis occurred in 27 patients (25%). Regression analysis on clinical and angiographic variables for prediction of restenosis showed no statistical significance for any variable. Late events occurred in 23 patients (19%). The actuarial survival rate was 98% at 1 year and at 3 years, and the event-free survival rate including freedom from repeat angioplasty for restenosis was 95% and 76%, respectively. CONCLUSIONS: The late angiographic outcome, restenosis rate and total clinical events are favorable for selected patients undergoing stent implantation for the indication of restenosis.

Aged↗

Immunomodulation of LPS ability to induce the local Shwartzman reaction.

Immunologically, the septic shock is a natural model of immunomediated vascular pathology where the interaction between cytokines and the endothelium mediates the syndrome and lethality. Tumour necrosis factor (TNF), a non-species-specific cytokine, has outstanding pleiotropic activities as an important mediator of the septic shock syndrome. In rabbits, passive immunization with anti-lipopolysaccharide (LPS) polyclonal antibodies prior to the intravenous (i.v.) injection of LPS inhibits the haemorrhagic necrotic lesion characteristic of the local Shwartzman reaction (an excellent localized in vivo correlate of the septic shock). Paradoxically, tested in an ex vivo assay (short-term whole human blood culture, stimulated with LPS), these antibodies mediated an increase in TNF production by mononuclear phagocytes and, in the rabbit model, they induced an increase in body temperature, as compared with the pre-immune reagent. Although anchoring of immune complexes containing LPS to receptors (Fc or C4b-C3b) on circulating monocytes may facilitate the access of LPS to these cells, access to localized, LPS-sensitized macrophages may be impaired. Consequently inhibition of the local Shwartzman reaction and increased TNF production in the ex vivo system were observed. Concordantly, the higher temperature in the passively immunized animals may be a consequence of a higher, immune complex-induced, systemic TNF production. These experimental results suggest that the use of anti-LPS immunoglobulins, as a potential immunotherapy for septic shock syndrome in vertebrates, may lead to increased TNF production, with adverse effects such as the pyrogenic.

Animals↗

Epidemiological survey of amyotrophic lateral sclerosis in the province of Reggio Emilia, Italy: influence of environmental exposure to lead.

We carried out a retrospective incidence, prevalence and mortality survey of amyotrophic lateral sclerosis (ALS) in the province of Reggio Emilia, northern Italy. Based on 79 patients, the mean incidence per year for the period 1980 through 1992 was 1.5 cases per 100,000. On December 31st, 1992, the prevalence rate was 5.4 per 100,000. In the 10-year period of 1983-1992 the average mortality rate was 1.3 per 100,000 per year. The average age at onset was 61.3 +/- 10.2, the average survival period thereafter was 26.3 months +/- 17.7; 27.3 +/- 17.6 for classic ALS, 19.5 +/- 8.4 for progressive bulbar palsy and 36.3 +/- 41.4 for pseudopolyneuritic ALS. The incidence rate, recorded in public health district No.12, an area with documented lead pollution since the 1970s, was standardized to the sex and age of the population of the province. Its incidence and prevalence rate were comparable to the rates found in the remaining area of the province.

Adult↗

Relation between hemostatic variables and increase of common carotid intima-media thickness in patients with peripheral arterial disease.

BACKGROUND AND PURPOSE: Increases in common carotid intima-media thickness (CC-IMT), as measured by B-mode ultrasonography, have been widely used in both population studies and clinical trials in the search for risk factors for early atherosclerosis progression and have been found to correlate with age and with high concentrations of low-density lipoprotein cholesterol, leukocytes, and hemoglobin. We have now investigated the relation between several baseline hemostatic and conventional risk factors and CC-IMT changes over 16 months in 64 patients with peripheral arterial disease randomly selected from the prospective PLAT study series. METHODS: Samples from 24 patients (37.5%) who showed increases in CC-IMT during the follow-up period were compared with those from 40 (62.5%) in whom CC-IMT remained unchanged. RESULTS: Baseline conventional risk factors and coagulation variables were similar in the two groups except for higher plasma concentrations of von Willebrand factor (vWF) (178.3 +/- 53.6% versus 141.2 +/- 53.7%, P=.01) and factor VII (FVII) (133.9 +/- 36.4% versus 107.0 +/- 27.3%, P=.001) in the patients with increased CC-IMT. CC-IMT increase correlated positively with plasma levels of FVII (r=.31, P<.01) and vWF (r=.31, P<.01). Multiple stepwise regression analysis identified FVII as the only independent variable associated with an increase in CC-IMT (beta=.83, P=.01). CONCLUSIONS: High plasma concentration of FVII and vWF may be associated with the progression of early carotid atherosclerosis in patients with peripheral arterial disease.

Age Factors↗

[The evaluation of the acute recoil of the Palmaz-Schatz stent using echography. A case report].

Intravascular ultrasound, performed using a 0.018 in guide wire with a 30 MHz ultrasound transducer, allows to study the acute recoil of Palmaz-Schatz stent. This case showed that the acute recoil of the Palmaz-Schatz stent occurs immediately after stent implantation. The analysis of diameter and lumen cross-sectional area at the stent site was performed at different levels of dilatation. A 20% reduction of cross-sectional area was found immediately after stent expansion and balloon deflation.

Aged↗

[Respiratory failure caused by myopathy in severe sepsis].

OBJECTIVE: To describe a generalized myopathic disorder occurred in the convalescence phase of illness of a critically ill patient. SETTING: Neurological Intensive Care Unit. PATIENT: A 43-year-old man with acute leukoencephalopathy and severe sepsis complicated by sustained and prolonged cardiovascular, respiratory and renal failure. After 15 days of complete respiratory autonomy, the patient presented an acute ventilatory failure associated with generalized muscle weakness. Neither a relapse of sepsis nor neurological worsening were detected. MEASUREMENTS AND RESULTS: Electromyogram resulted in normal conduction velocity in both motor and sensitive nervous fibers. Muscular biopsy showed marked fiber size variability with several hypotrophic fibers type II fiber grouping, several areas of degeneration-necrosis with macrophage invasion, dishomogeneous oxidative enzymatic activity, no increase in glycogen or lipid content. CONCLUSIONS: These results excluded critical illness polyneuropathy and all the other known myopathies. Prolonged period of sepsis with multiple organ failure can result in a direct generalized myopathy. This possibility should be kept in mind while treating long term critically ill survivors.

Adult↗

[Histopathologic features in atherectomy samples obtained from patient with unstable angina, stable angina and restenosis. Directional Atherectomy Lombardi Group].

BACKGROUND: The present study was aimed at investigating the pathologic features of directional coronary atherectomy (DCA) samples obtained from 194 patients (14 females) with stable (n = 68) and unstable (n = 95) angina, and with restenosis (n = 27). METHODS: DCA samples were obtained from culprit lesions, using the Simpson technique. Unstable angina was classified according to E. Braunwald criteria. Stable angina was grouped according to the presence or absence of a prior myocardial infarction (MI). DCA samples were fixed, processed, serially cut and stained with hematoxilin-eosin and with Movat pentachrome stain. RESULTS: The major pathologic findings were thrombosis, inflammation of the superficial plaque layers, and neointimal hyperplasia which often coexisted within a same sample. Their frequencies, in that order, were distributed in the differing groups of patients as follows: 21% (n = 9), 29.2% (n = 12) and 51% (n = 21) of the 41 cases with stable angina without prior MI. 40.7% (n = 11), 40.7% (n = 11), and 51.8% (n = 14) of the 27 cases with stable angina with prior MI. 25% (n = 4), 56.2% (n = 9) and 68.7% (n = 11), of the 16 cases with BI unstable angina. 35.3% (n = 14), 55.8% (n = 19) and 44% (n = 15), of the 34 cases with BII unstable angina. 44.4% (n = 4), 33.3% (n = 3) and 33.3% (n = 3), of the 9 cases with BIII unstable angina. 48.2% (n = 14), 48.2% (n = 14) and 51.8% (n = 15), of the 29 cases with CII unstable angina at 35.8 days after MI. 60% (n = 3), 60% (n = 3) and 40% (n = 2), of the 5 cases with CIII unstable angina at 8.3 days after MI. 26% (n = 7), 48% (n = 13) and 85.1% (n = 23), of the 27 cases with restenosis. According to above observation, the frequency of coronary thrombosis increases with the increase of the severity of myocardial ischemia. However, thrombosis is not found in most unstable angina without prior MI (63% of BI-II-III unstable angina cases do not have thrombus). In addition, thrombus is not a specific finding of unstable angina, given its occurrence, although in a much lower percentage of cases, in stable angina and in restenosis. CONCLUSIONS: Present data show that different ischemic and plaque lesions. This observation questions on the pathogenetic role of thrombus in unstable angina and calls for further investigations on inflammation and neointimal hyperplasia, as well as on the the reciprocal relation between these findings which are often combined within a same lesion.

Adult↗