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E Breda

Publications and source records attributed to E Breda.

At least 19 recordsLinked to original sources

Phase II study of liposomal doxorubicin and gemcitabine in the salvage treatment of ovarian cancer.

In total, 70 patients were enrolled into this phase II study, to evaluate the activity of the pegylated liposomal doxorubicin (PLD) and gemcitabine (GEM) combination in recurrent ovarian cancer patients. PLD, 30 mg m(-2), was administered on day 1 by 60' i.v. infusion, followed by GEM, 1000 mg m(-2), given by 30' i.v. on days 1 and 8; cycles were repeated every 21 days. In all, 67 patients are so far evaluable for response. Seven complete responses (10.4%, 95% CI: 3.1-17.7), 16 partial responses (23.9%, 95% CI: 13.7-34.1), 26 disease stabilisations (38.8%, 95% CI: 27.1-50.5) and 18 progressions (26.9%, 95% CI: 16.3-37.5) have been registered. Within the resistant population (n=36), the response rate was 25% (95% CI: 10.9-39.1). Within the group of platinum-sensitive patients (n=31), the response rate was 45.2% (95% CI: 27.7-62.7). A total of 443 courses are evaluable for toxicity. Grade 3-4 hematological toxicity was registered in 30 patients (42.8%), mainly represented by neutropenia (35.6%); palmar-plantar erythrodysesthesia affected 24 patients (34.2%), but it was of grade 3 in only seven of them (10%).

Adult↗

Insulin secretory responses to rising and falling glucose concentrations are delayed in subjects with impaired glucose tolerance.

AIMS/HYPOTHESIS: We hypothesized that beta-cell responses to changes in glucose would not be normal in subjects with impaired glucose tolerance (IGT). METHODS: Three groups of 6 subjects were studied: normal weight with normal glucose tolerance (control subjects); obese with normal glucose tolerance (Obese-NGT); and obese with IGT (Obese-IGT). All subjects had a graded glucose infusion protocol to increase (step-up) and then decrease (step-down) plasma glucose. We obtained average insulin-secretion rates (ISR) over the glucose range common to all three groups during step-up and step-down phases, minimal model indices of beta-cell function (f(b), f(d), f(s), T(up), T(down) ), and insulin sensitivity (Si). RESULTS: ISR differed significantly between step-up and -down phases only in Obese-IGT individuals. Basal (f(b)) and stimulated (f(d), f(s)) beta-cell sensitivity to glucose were similar in the three groups. Delays between glucose stimulus and beta-cell response during both step-up (T(up)) and -down (T(down)) phases were higher in Obese-IGT compared to Controls and Obese-NGT individuals. The product ISR x Si (10(-5.)min(-2) x l) was lower in Obese-IGT compared to Controls, both during step-up (919 +/- 851 vs 3192 +/- 1185, p < 0.05) and step-down (1455 +/- 1203 vs 3625 +/- 691, p < 0.05) phases. Consistently, the product f(s) x Si (10(-14.)min(-2). pmol(-1) x l) was lower in Obese-IGT than in control subjects (27.6 +/- 25.4 vs 103.1 +/- 20.2, p < 0.05). CONCLUSION/INTERPRETATION: Subjects with IGT are not able to secrete insulin to compensate adequately for insulin resistance. They also show delays in the timing of the beta-cell response to glucose when glucose levels are either rising or falling.

Adult↗

Insulin secretion rate during glucose stimuli: alternative analyses of C-peptide data.

The ability to evaluate the pancreatic insulin secretion rate (ISR) is essential for a quantitative understanding of the glucose regulation system in man. Various approaches have been developed for evaluation of the ISR in vivo. The aim of this study was to compare input/output and compartmental models of C-peptide to reconstruct the ISR in response to both physiological and nonphysiological glucose stimuli in healthy humans. In particular we applied the nonparametric stochastic deconvolution and the C-peptide minimal model approaches to the graded up&down glucose infusion protocol, where glucose was infused at progressively increasing and then decreasing rates, and to the intravenous glucose tolerance test (IVGTT), where an impulse dose of glucose was administered. Our results show that the two models give virtually identical results when glucose and C-peptide (and thus ISR) profiles are smooth and regular, but when vigorous nonstationarities are present, like during the first 4 min of the IVGTT, the two ISR profiles are different (but not their areas under the curve). The C-peptide minimal model, albeit requiring, at variance with deconvolution, the knowledge of glucose data, has the advantage of providing quantitative indices of the beta-cell function, which is important in the parametric definition of different physiopathological states.

Adult↗

Quantitative indexes of beta-cell function during graded up&down glucose infusion from C-peptide minimal models.

Availability of quantitative indexes of insulin secretion is important for definition of the alterations in beta-cell responsivity to glucose associated with different physiopathological states. This is presently possible by using the intravenous glucose tolerance test (IVGTT) in conjunction with the C-peptide minimal model. However, the secretory response to a more physiological slowly increasing/decreasing glucose stimulus may uncover novel features of beta-cell function. Therefore, plasma C-peptide and glucose data from a graded glucose infusion protocol (seven 40-min periods of 0, 4, 8, 16, 8, 4, and 0 mg. kg(-1). min(-1)) in eight normal subjects were analyzed by use of a new model of insulin secretion and kinetics. The model assumes a two-compartment description of C-peptide kinetics and describes the stimulatory effect on insulin secretion of both glucose concentration and the rate at which glucose increases. It provides in each individual the insulin secretion profile and three indexes of pancreatic sensitivity to glucose: Phi(s), Phi(d), and Phi(b), related, respectively, to the control of insulin secretion by the glucose level (static control), the rate at which glucose increases (dynamic control), and basal glucose. Indexes (means +/- SE) were Phi(s) = 18.8 +/- 1.8 (10(9) min(-1)), Phi(d) = 222 +/- 30 (10(9)), and Phi(b) = 5.2 +/- 0.4 (10(9) min(-1)). The model also allows one to quantify the beta-cell times of response to increasing and decreasing glucose stimulus, equal to 5.7 +/- 2.2 (min) and 17.8 +/- 2.0 (min), respectively. In conclusion, the graded glucose infusion protocol, interpreted with a minimal model of C-peptide secretion and kinetics, provides a quantitative assessment of pancreatic function in an individual. Its application to various physiopathological states should provide novel insights into the role of insulin secretion in the development of glucose intolerance.

Adult↗

Oral glucose tolerance test minimal model indexes of beta-cell function and insulin sensitivity.

The simultaneous assessment of quantitative indexes of insulin secretion and action in a single individual is important when quantifying their relative role in the evolution of glucose tolerance in different physiopathological states. Available methods quantify these indexes in relatively nonphysiological conditions, e.g., during glucose clamps or intravenous glucose tolerance tests. Here, we present a method based on a physiological test applicable to large-scale genetic and epidemiologic studies-the oral glucose tolerance test (OGTT). Plasma C-peptide, insulin, and glucose data from a frequently sampled OGTT with 22 samples throughout 300 min (FSOGTT300-22) were analyzed in 11 subjects with various degrees of glucose tolerance. In each individual, two indexes of pancreatic sensitivity to glucose (phis [10(9) min(-1)] and phid [10(9)]) and the insulin sensitivity index (SI) (10(5) dl/kg per min per pmol/l) were estimated by using the minimal model of C-peptide secretion and kinetics originally proposed for intravenous graded glucose infusion and the minimal model approach recently proposed for meal/OGTTs. The indexes obtained from FSOGTT300-22 were used as a reference for internal validation of OGTT protocols with reduced sampling schedules. Our results show that 11 samples in a 300-min period (OGTT300-11) is the test of choice because the indexes it provides (phis = 36 +/- 3 [means +/- SE]; phid = 710 +/- 111; SI = 10.2 +/- 2.4) show excellent correlation and are not statistically different from those of FSOGTT300-22 (phis = 33 +/- 3; phid = 715 +/- 120; SI = 10.1 +/- 2.3). In conclusion, OGTT300-11, interpreted with C-peptide and glucose minimal models, provides a quantitative description of beta-cell function and insulin sensitivity in a single individual while preserving the important clinical classification of glucose tolerance provided by the standard 120-min OGTT.

Adult↗

Drug-induced modulation of carcinoembryonic antigen (CEA) expression in neoplastic cells from a patient with rectal cancer.

Treatment with 5-fluorouracil (5-FU) or recombinant interferon-gamma (IFN), alone or in combination, was found to increase carcinoembryonic antigen (CEA) expression in several carcinoma cell lines. In this study we examined the in vitro effect of these agents on CEA expression of tumor cells, obtained from a patient operated for rectal cancer. The results showed that exposure of cancer cells to 5-FU or to IFN resulted in increased CEA levels in terms of percentage of CEA-positive cells and mean fluorescence values, as indicated by FACS analysis. However, drug combination did not induce CEA expression higher than that provided by single agents alone. Treatment with 5-FU or with IFN produced a reduction of the total number of viable cells. Moreover, Western blot analysis revealed that exposure of cancer cells to each drug was followed by a substantial increase of the total cellular CEA content. On the contrary, 5-FU in combination with IFN did not increase the expression of the antigen more than that obtained by single agents. Noteworthy, exposure of CEA-negative cells from adjacent normal rectal tissue to both agents alone or in combination, did not result in CEA induction. In conclusion, the present results suggest new approaches aimed at (a) increasing the sensitivity of diagnostic procedures based on detection of CEA-positive tumor cells; (b) facilitating the recognition of CEA-positive cancer cells by immune responses induced by anti-CEA peptide vaccines.

Adult↗

[Inguinal hernioplasty: current trends].

The Authors report their experience in the surgical management of 282 inguinal hernias classified according to Gilbert's classification. The different techniques used were compared analysing the results obtained in 104 patients operated with the Bassini hernioplasty, while in 120 cases the Lichteinstein tension-free repair and in 58 cases the Shouldice hernioplasty were performed. In the patients operated according to the Lichteinstein tension-free technique an Autosuture mesh was used. The Authors conclude that the Lichteinstein tension-free repair is preferable, not simply for the incidence, although low in this series, of recurrence observed with the Bassini hernioplasty, but particularly for the reduced postoperative pain, the fast return to full activities, the low cost, and the possibility to be performed in Day-Hospital.

Adolescent↗

[Subclavian steal syndrome. Clinical aspects and therapeutic problems].

Cerebrovascular disease is a leading cause of morbidity and mortality in Italy. Although atherosclerotic involvement of the carotid artery is more prevalent, some patients suffer from stenosis of the subclavian artery, usually proximal to the origin of the vertebral artery. Neurological symptoms result from reversed flow in the vertebral artery, so-called "subclavian-steal". This collateral pathway may rob the posterior circulation of perfusion to the degree of producing episodes of vertebrobasilar insufficiency. The authors have therefore reviewed their experience with this disease and present their findings, therapeutic procedures and short-term results. During 1990 four patients affected by "subclavian-steal syndrome" were observed at the Surgical Department of Montecchio Maggiore Hospital (VI). Two patients were operated on and axillo-axillary bypass operations were performed (with a 5 mm Gore-tex graft). The goal of surgical treatment is to alleviate cerebrovascular symptomatology by restoring flow to the subclavian artery distal to the occlusion. Axillo-axillary bypass offers distinct advantages over the alternative methods such as transthoracic procedures or carotid-subclavian bypass. Axillo-axillary bypass is a technically simple procedure with very good results and minimal complications. It avoids sternotomy, thoracotomy and clavicular resections: the carotid artery is not involved in the procedure. The authors conclude that axillo-axillary bypass is a cheap, safe and effective treatment for symptomatic subclavian artery insufficiency.

Aged↗

[Bioavailability of orally administered iron. Effects of alginate/antacid administration].

Sideropenia is often encountered in medical practice; the iron preparation that presents the highest bioavailability is unquestionably iron sulphate. This compound, however, frequently provokes numerous side-effects that induce the patient to suspend treatment. Here it is shown that the bioavailability of the drug is not changed after intake of alginic acid, while side-effects are considerably reduced.

Administration, Oral↗

[Role of surgery in the therapy of peptic ulcer after arrival of H2-blocking drugs].

This retrospective study was undertaken to determine if the advent of H2-blockers has altered the surgical treatment and the outcome of patients with peptic ulcer disease. The records of patients undergoing surgery for peptic ulcer disease at Montecchio Maggiore Hospital, Vicenza (Italy), from 1968 to 1977 (group A) and from 1979 to 1989 (group B) were reviewed. Data recorded included, ulcer location, surgical procedures (emergency or elective), indications for emergency surgery (perforation, bleeding). Statistical analysis was performed by means of the chi-square test. From 1968 to 1989, 15.810 surgical operations were performed: the indication was peptic ulcer disease in 398 cases (2.51%). The percentage of surgical operations performed for peptic ulcer was 3.54% in group A and 1.55% in group B. A marked decline in surgery for peptic ulcer was noted in group B, concerning both elective and emergency surgery; surgical interventions strongly decreased for both duodenal and gastric ulcer. This study demonstrates that H2-blockers have definitely altered the surgical treatment for peptic ulcer disease.

Duodenal Ulcer↗