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Biomedical subjects

R Leone

Publications and source records attributed to R Leone.

At least 37 records · Page 2Linked to original sources
PubMed1999

Extended vertical transseptal approach versus conventional left atriotomy for mitral valve surgery.

BACKGROUND AND AIM OF THE STUDY: Mitral valve surgery requires optimal exposure of the valvular apparatus, particularly when a conservative procedure is used. Retrospectively, we compared surgical results in patients who underwent mitral valve surgery using the vertical transseptal approach (which has been adopted routinely in our institute) with those in patients undergoing conventional left atriotomy. METHODS: A total of 172 consecutive patients operated on for mitral procedures were allocated to either group A (those operated on through a longitudinal left atriotomy; n = 62), or group B (mitral valve exposure achieved through an extensive vertical transseptal approach; n = 110). RESULTS: In group A, there were 24 valvular reconstructions and 38 valvular replacements. Mean (+/- SD) cardiopulmonary bypass (CPB) time was 65.9 +/- 17 min and mean ischemia time 37.4 +/- 13 min. Total postoperative bleeding was 277 +/- 171 ml. There was no surgical re-exploration for bleeding. One patient in this group died (mortality rate 2%). Among 40 patients in atrial fibrillation preoperatively, four had one episode of temporary junctional rhythm, six had temporary sinus rhythm and two had stable sinus rhythm. Among patients with preoperative sinus rhythm, six (27%) had episodes of atrial fibrillation and two (9%) temporary atrioventricular block. In group B, 46 mitral reconstructions and 64 mitral replacements were performed. Mean CPB time was 67.9 +/- 20 min and mean ischemia time 48.1 +/- 17 min. Total postoperative bleeding was 400 +/- 189 ml. Three patients in this group died (mortality rate 2.7%). Among 60 patients with preoperative atrial fibrillation, six (10%) had one episode of temporary junctional rhythm, 14 (24%) had temporary sinus rhythm and two (3%) had conversion to stable sinus rhythm. Among those in sinus rhythm preoperatively, 16 (32%) had episodes of temporary junctional rhythm, two (4%) had temporary atrial fibrillations, and four (8%) had stable atrial fibrillation. In group B patients, the incidences of ischemia time and total postoperative bleeding (p = 0.004), and postoperative junctional arrhythmia in those with preoperative sinus rhythm (p < 0.001), were greater than in group A patients. CONCLUSIONS: No technique-related deaths occurred; neither were causes of re-exploration for bleeding related to technique, and there was no evidence of residual interatrial shunt. In conclusion, transseptal extended atriotomy provides excellent exposure for mitral valve surgery. Disadvantages of minimally increased ischemia time and surgical bleeding are minor compared with the superior and more complete surgical reconstruction achieved. The advantages of the technique are undermined by the higher incidence of junctional arrhythmia which, even if temporary, requires strict postoperative monitoring.

Cardiopulmonary Bypass↗
PubMed1999

Emergency surgical management of acute aortic dissection: role of transesophageal echocardiography.

The accuracy of transesophageal echocardiography in the diagnosis and surgical management of acute aortic dissection was determined in 54 patients who underwent surgery for acute aortic dissection. Results of the investigations were compared to the surgical assessment. From April 1993 to November 1997, we operated 54 patients (44 male and 10 female) for acute aortic dissection. Mean age was 60 +/- 9 years. At surgery, a De Bakey type I aortic dissection was diagnosed in 30 patients, type II in 23 and type III retrograde in 1. Operating procedures were: replacement of ascending aorta (24 cases), replacement of ascending aorta and aortic arch (17 cases), replacement of ascending aorta and aortic valve replacement (2 cases), Bentall procedure (6 cases) and end-to-end anastomosis of the ascending aorta (4 cases). Initial diagnosis, performed in emergency wards, was done on a clinical basis in 6 patients, on CT scan in 19, on transthoracic echocardiography in 14, and on TEE basis in 12. Three patients underwent angiography before our evaluation. As per our protocol, all patients underwent confirmation of the diagnosis by TEE. Seven patients needed additional instrumental investigations, 2 with CT scan and 5 with angiography. TEE confirmed the diagnosis of aortic dissection in all cases but one. Moreover, it described the site of the intimal tear, the extension of the dissecting process and accessory findings, such as pericardial effusion, aortic incompetence and left ventricular function. The interval between patient presentation and skin incision was a maximum of 70 minutes. At surgery, diagnosis of De Bakey classification was confirmed in 98% of cases; in 90.7% of cases exact location of the entry site was confirmed. In one case, an entry site in the arch diagnosed by TEE but not recognized at surgery, was observed at necropsy. Intraoperatively, we routinely used TEE to monitor retrograde systemic perfusion and correct implant of the vascular prosthesis. One case of malperfusion of the thoracic aorta through the false lumen was observed and managed. In one case we diagnosed acute obstruction of the prosthesis by bleeding in the wrapped aorta, which required reoperation. Assessment of ventricular function was obtained in all patients: in two cases, observation of low right ventricular function led us to perform aortocoronary by-pass to the right coronary artery. In conclusion, the high level of correspondence between TEE diagnosis and surgical anatomy prompted us to perform transesophageal echocardiography as the primary and often sole diagnostic procedure in acute aortic dissection. TEE, in experienced hands, has proven to be a highly reliable, safe and low-cost diagnostic tool. It can be performed at the patient's bedside within just a few minutes of the suspected diagnosis, thereby lowering the mortality rate of the natural history. Again, it can also be used in the operating theatre as an "on-line examination" as well as for assessment of correct surgical repair. Other diagnostic procedures do not yield more information and can cause dangerous delays in intervention.

Adult↗
PubMed1998

Decreased drug accumulation and increased tolerance to DNA damage in tumor cells with a low level of cisplatin resistance.

In an attempt to examine the cellular changes associated with cisplatin resistance, we selected a cisplatin-resistant (A43 1/Pt) human cervix squamous cell carcinoma cell line following continuous in vitro drug exposure. The resistant subline was characterized by a 2.5-fold degree of resistance. In particular, we investigated the expression of cellular defence systems and other cellular factors probably involved in dealing with cisplatin-induced DNA damage. Resistant cells exhibited decreased platinum accumulation and reduced levels of DNA-bound platinum and interstrand cross-link frequency after short-term drug exposure. Analysis of the effect of cisplatin on cell cycle progression revealed a cisplatin-induced G2M arrest in sensitive and resistant cells. Interestingly, a slowdown in S-phase transit was found in A431/Pt cells. A comparison of the ability of sensitive and resistant cells to repair drug-induced DNA damage suggested that resistant cells were able to tolerate higher levels of cisplatin-induced DNA damage than their parental counterparts. Analysis of the expression of proteins involved in DNA mismatch repair showed a decreased level of MSH2 in resistant cells. Since MSH2 seems to be involved in recognition of drug-induced DNA damage, this change may account for the increased tolerance to DNA damage observed in the resistant subline. In conclusion, the involvement of accumulation defects and the increased tolerance to cisplatin-induced DNA damage in these cisplatin-resistant cells support the notion that multiple changes contribute to confer a low level of cisplatin resistance.

Antineoplastic Agents↗
PubMed1998

Comparison of phospholipase production in Cryptococcus neoformans isolates from AIDS patients and bird droppings.

Secreted phospholipase has been recently proposed as a virulence determinant in Cryptococcus neoformans as well as Candida albicans. This issue of cryptococcal phospholipase requires screening of phospholipase production in a larger number of isolates from clinical and environmental sources. In this study we examined phospholipase production in a total of 67 C. neoformans isolates from AIDS patients and bird droppings by using the egg-yolk plate method. Phenoloxidase activity, capsule size and growth at 37 degrees C were also measured in these strains in order to observe a possible relationship between phospholipase production of different C. neoformans strains and its virulence. Four of the 21 AIDS strains at 28 degrees C and 1 at 37 degrees C did not produce phospholipase, respectively. In contrast, 38 and 34 of the 46 bird dropping strains were negative for phospholipase production at 28, and 37 degrees C, respectively. Statistical analysis revealed a significant difference in phospholipase production, capsule size and growth ability at 37 degrees C, but not phenoloxidase activity, between the AIDS and the bird dropping strains. The highly prevalent distribution of phospholipase activity in the AIDS strains suggests a role of the enzyme in invading the host.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Ovarian cancer cisplatin-resistant cell lines: multiple changes including collateral sensitivity to Taxol.

BACKGROUND: Alteration in apoptosis pathways (in particular mutations of p53 gene) may result in resistance of ovarian carcinoma to cisplatin. However, cisplatin resistance is likely to be multifactorial. An understanding of the molecular alterations associated with the development of resistance may be of considerable relevance in an attempt to optimize the therapeutic approach. STUDY DESIGN: Two cisplatin-resistant sublines (IGROV-1/Pt0.5 and IGROV-1/Pt1), both characterized by mutant p53 (Cancer Res 1996; 56: 556-62), but with different degree of resistance were studied in terms of pattern of cross-resistance, susceptibility to drug-induced apoptosis, expression of gluthathione-dependent system, cellular pharmacokinetics, drug-induced DNA damage. The resistance index (ratio between the IC50 of resistant and sensitive cells) after a 96-hour drug exposure was 10 for IGROV-1/Pt0.5 and 14 for IGROV-1/Pt1 cells. RESULTS: Resistant cells were cross-resistant to DNA-damaging agents and, interestingly, they had a collateral sensitivity to Taxol. The cellular response to Taxol paralleled the drug ability to induce apoptosis. The intracellular glutathione level was significantly increased in IGROV-1/Pt cells compared to the sensitive counterpart. In contrast, glutathione S-transferase level was consistently reduced in both sublines. gamma-Glutamyl transpeptidase activity, which was lower in resistant than in sensitive cells, was not directly correlated with glutathione level, thus suggesting a complex regulation of cellular glutathione content. In the resistant cells with the highest glutathione content, a reduced level of cisplatin-induced cross-link was found. Analysis of DNA platination revealed a slight decrease of DNA-bound platinum only in IGROV-1/Pt1 cells. Again, this reduction is consistent with a protective role for glutathione. The expression of metallothionein IIa was increased in both resistant variants. CONCLUSIONS: Multiple changes are involved in acquired resistance of ovarian carcinoma cells including reduced susceptibility to apoptosis as consequence of inactivation of p53 and expression of defence mechanisms. The relative contribution is related to the degree of drug resistance. In particular, the glutathione-dependent system could have a role only in the development of a high degree of resistance. Finally, the finding that Taxol was very effective in inducing apoptosis in resistant sublines with p53 mutation supports the expression of an intact p53-independent pathway of apoptosis and suggests the pharmacological interest of Taxol in the treatment of p53-mutated tumors.

Adenocarcinoma↗
PubMed1998

bcl-2 but not p53 expression is associated with resistance to chemotherapy in advanced breast cancer.

Programmed cell death is an important determinant of the response to chemotherapy. Among the factors controlling this process, a significant role is played by bcl-2 and p53, the expression of which, together with estrogen receptor content and tumor proliferative activity, was investigated by means of immunohistochemistry in 55 advanced breast cancer patients (median age, 60 years; range, 25-71 years). Analysis of bcl-2 expression identified two groups of patients with a significant difference in response rate. A total of 17 patients (31%) responded to chemotherapy (5 had a complete response and 12 had a partial response): 14 of 32 (44%) bcl-2-negative patients (< 40% stained cells) and only 3 of 23 (13%) bcl-2-positive patients (> or = 40% of stained cells; P = 0.019 by Fisher's exact test). The two groups were well balanced in terms of age, performance status, disease-free survival, menopausal status, and type of chemotherapy. bcl-2-negative tumors showed a tendency toward a higher p53 expression and proliferation rate, whereas an excess of bone as the dominant disease site was evident among the bcl-2-positive ones. However, the only variable to result significantly different between the two groups was estrogen receptor expression (P = 0.004). A multivariate logistic regression model showed that bcl-2 maintained its power of discriminating two groups with a different probability of responding to chemotherapy, although the greatest contribution was given by dominant disease site and type of chemotherapy. In conclusion, the results of this study suggest a possible role for bcl-2 in predicting resistance to chemotherapy.

Adult↗
PubMed1997

Aetiology and therapy of community-acquired pneumonia: a hospital study in northern Italy. Veneto Pneumonia Research Group.

OBJECTIVES: The primary aim of this study was to determine whether the use of a therapeutic protocol in the treatment of community-acquired pneumonia (CAP) proved equally effective as the initial empirical anti-infective therapy usually employed. A secondary aim was to compare the cost of therapy and the incidence of the pathogens responsible for so-called "atypical" pneumonia in the study area. METHODS: A comparison was made between 11 hospital departments agreeing to abide by the study protocol and 12 hospital departments, well matched for size and type, implementing their usual therapy. The protocol provided different anti-infective therapy options for the patients regarded as being at risk and not at risk, and, secondarily, for infections likely to be of the "typical bacterial" or so-called "atypical" type. The main outcome measures were need to change the initial anti-infective therapy owing to inefficacy, final clinical and radiological outcome, mean cost of pharmacological therapy per patient and result of the serological investigations of the pathogens responsible for "atypical" pneumonia. RESULTS: A total of 345 patients with CAP were assessed. The initial therapy was changed in 8.6% of patients treated according to the protocol, and in 24.5% of patients treated with the usual anti-infective therapies. The cost of therapy for the protocol was almost half of that in the control group. Clinical and radiological outcome was similar in the two groups, with a very low mortality rate. The overall proportion of cases of "atypical" pneumonia amounted to 13%. CONCLUSIONS: The use of the therapeutic protocol gave an efficacy comparable to that achieved with routine therapy, but at a distinctly lower cost of antibiotic therapy. The use of microbiological investigations is very limited in day-to-day clinical practice, and the incidence of so-called "atypical" pneumonia was low in the study area, apart from specific outbreaks.

Anti-Infective Agents↗
PubMed1997

Metabolism of arsenic after acute occupational arsine intoxication.

Among the elements of toxicological relevance, inorganic arsenic (As) probably exhibits the most complex metabolism, and we deemed it interesting to identify and quantify the different As species excreted after an occupational acute intoxication with arsine. For this purpose total As and five As species were determined using an hybrid analytical method coupling liquid chromatography with inductively coupled plasma mass spectrometry. The highest urinary elimination of total As was observed in the first 5 d after admission. The As species mostly excreted were monomethylarsonate (MMA), dimethylarsinate (DMA), As3+, arsenobetaine (AsB), and to a lesser extent As5+. The amount of AsB excreted in urine by the subject does not appear to be completely justified by AsB intake through food. Arsenic is excreted mainly via the urine with a clearance of 7.8 ml/h/kg and follows a triphasic model with periods of 28 h, 59 h, and 9 d, respectively. The evidence that DMA excretion culminates after a few days, when the excretion of the inorganic form is substantially reduced (while that of MMA is still elevated), seems to confirm the existence of two successive methylating enzyme activities. Furthermore, the elimination rate of As from blood follows a three-phase model and the half-lives of different species vary from about 27 to 86 h with the following gradient As5+ < MMA < As3+ < DMA < AsB.

Adult↗
PubMed1996

Physical specifications of clinical proton beams from a synchrotron.

Tumor treatment with charged particle beams is a quickly developing field aimed to translate the potential advantages offered by the superior physical dose distribution and relative biological effectiveness of heavy charged particles into a real improvement of tumor therapy. To this purpose the new proton and light-ion radiation therapy facilities must be designed according to strict clinical specifications to provide a reliable and effective tool against cancer. This paper provides the performance specifications of the accelerator and of the beam transport and delivery systems of the Italian Hadrontherapy Centre, which should be satisfied to meet the clinical specifications. A discussion is given on the requirements on energy range, energy variability, beam intensity, lateral penumbra, distal dose falloff, source-to-surface distance, time structure of the extracted beam, raster scanning system specifications, and beam abort time. Though the physical specifications are given for a particular accelerator, they can be used as a general guideline for the design of future biomedical particle accelerator facilities.

Biophysical Phenomena↗
PubMed1996

One leaflet immobilization after mitral valve replacement with a bileaflet prosthesis.

We report four cases of one leaflet immobilization which occurred early after mitral valve replacement with a Carbomedics bileaflet valve. The first case was diagnosed incidentally six days after surgery and did not require reoperation because of the spontaneous normalization of the valve movements the day before the scheduled reoperation. Since then, we have been using intraoperative transesophageal echocardiography in mitral procedures routinely (both valve repair or replacement). We were able to detect malfunctions which required reorientation in three other prostheses. We emphasize the importance of performing intraoperative transesophageal echocardiography routinely in these procedures; its high sensitivity and low risk can help to avoid a late reoperation.

Echocardiography, Doppler↗
PubMed1996

Inductively coupled plasma mass spectroscopy quantitation of platinum-DNA adducts in peripheral blood leukocytes of patients receiving cisplatin- or carboplatin-based chemotherapy.

Platinum-DNA adducts can be assayed in peripheral blood leukocytes by means of atomic absorption spectroscopy and ELISA, and high adduct levels have been correlated previously with favorable clinical response to platinum-based chemotherapy. Our purpose was to study adduct formation in peripheral blood leukocytes by means of a new method, inductively coupled plasma mass spectroscopy (ICP-MS), and to correlate adduct formation with clinical response and toxicity. Platinum (Pt)-DNA adducts were measured by means of ICP-MS in leukocytes of 66 patients receiving a cisplatin- or carboplatin-based chemotherapy, collected either before the beginning of treatment and incubated in vitro with cisplatin or 1 and 24 h after the administration of drug to the patient. The Pt-DNA adduct level in leukocytes from patients exposed to drug in vitro was 14.33 +/- 14.71 fmol/microgram DNA (mean +/- SD), which was not significantly different from the value of 23.4 +/- 19.53 fmol/microgram DNA observed in leukocytes from nine healthy volunteers. In samples collected after the administration of chemotherapy, Pt-DNA adducts ranged from 1.91 +/- 3.59 fmol/microgram DNA (mean +/- SD) at the 1-h time point to 2.61 +/- 3.35 fmol/microgram DNA at 24 h (P > 0.05). Adduct levels in leukocytes exposed in vitro did not correlate with adduct levels from patients treated with cisplatin-based chemotherapy (r = 0.085 and 0.011 at 1 and 24 h, respectively). At 24 h, adduct levels in patients receiving cisplatin (3.15 +/- 3.64 fmol/microgram DNA, mean +/- SD) were significantly higher (P = 0.02) than those observed in patients treated with standard dose carboplatin (0.57 +/- 0.73 fmol/microgram DNA) and also higher than those in patients receiving high-dose carboplatin (1.18 +/- 1.06 fmol/microgram DNA), although the latter difference did not reach statistical significance (P = 0.071). No differences in adduct levels (mean +/- SD) were evident between patients responsive (3.23 +/- 3.51 fmol/microgram DNA) and nonresponsive (2.34 +/- 3.01 fmol/microgram DNA) to chemotherapy. In the homogeneous group of patients treated with combination of cisplatin and 5FU, received dose intensity, hemoglobin decrease, and posttreatment creatinine could not be linked with the extent of leukocyte adduct formation. The data presented here demonstrate that ICP-MS allows the detection of adducts in patients treated with cisplatin or carboplatin and suggest that adduct formation in leukocytes is not a major determinant of response or toxicity.

Adult↗
PubMed1995

Cisplatin pharmacokinetics using a five-day schedule during repeated courses of chemotherapy in germ cell tumors.

Total and ultrafilterable platinum (Pt) disposition was investigated during 49 courses of chemotherapy in 13 patients with germ cell tumor treated with cisplatin (DDP), 20 mg/m2/day on 5 consecutive days. The following pharmacokinetic parameters were analyzed: distribution (t1/2 alpha) and elimination (t1/2 beta) half-lives, total body clearance (ClT), renal clearance (ClR), and areas under the concentration versus time curve (AUCs). Blood samples were collected immediately before and after DDP infusion (Day 1 through Day 5); in addition, on Day 5, samples were collected at 0.25, 0.5, 1, 8, 24, and 48 h after DDP infusion. Urine was collected during each day of treatment and up to 48 h after the last DDP dose. During each chemotherapy cycle plasma levels of total and ultrafilterable Pt progressively increased from the first to the last day of treatment. At the first cycle, total Pt concentrations ranged from 0.67 to 1.46 micrograms/ml (mean increase, 118%), and those of ultrafilterable Pt from 0.117 to 0.205 micrograms/ml (mean increase, 75%). Mean +/- SD total Pt plasma levels immediately postinfusion increased from 0.67 +/- 0.20 microgram/ml at the first cycle (first day of therapy) to 1.13 +/- 0.21 microgram/ml at the same time point at the fourth cycle. Mean total Pt peak levels were reached at the end of infusion on the last day of each cycle, and increased from 1.46 +/- 0.29 microgram/ml (first cycle) to 1.89 +/- 0.40 microgram/ml (fourth cycle). Total Pt was detectable in plasma before the beginning of all cycles following the first. As a result, AUC significantly increased and ClR significantly decreased.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Antimicrobial drug utilisation in hospitals in Italy and other European countries.

Antibiotic prescribing patterns in hospitals are analysed in this review of three drug utilisation studies conducted in six European countries, with special emphasis to the third-generation cephalosporins. A great variability in the use of antimicrobial drugs is evident, both between countries and between hospitals in the same country. This variability is found also between patients with the same infectious disease. The possible reasons for these differences are discussed and a strategy to modify the hospital drugs prescribing is suggested.

Anti-Bacterial Agents↗
PubMed1994

Cisplatin pharmacokinetics in elderly patients.

The treatment of elderly patients with cancer may be difficult because of the narrow therapeutic index of antineoplastic drugs, the decline in the performance of organs and functions, and frequent comorbidity. In these patients, therapeutic drug monitoring may be useful in optimizing chemotherapy. Six patients older than 70 years with a variety of solid tumors received a total of 21 cycles of cisplatin (DDP)-based chemotherapy program (DDP dose, 50-65 mg/m2). Total and ultrafilterable platinum (Pt) were determined in plasma and urine during the first cycle of the therapy by means of atomic absorption spectroscopy. Pharmacokinetic parameters were analyzed with use of a two-compartment open model. The treatment was generally well tolerated. The most important side effects were a significant increase in serum creatinine level (from 0.98 to 1.23 mg/dl) and a decrease in creatinine clearance (from 44.4 to 38.9 ml/min) in comparison with pretreatment values. The mean decrease in hemoglobin levels was slight. The values of the main pharmacokinetic parameters of total Pt agreed well with the data obtained with other adult patients. Total and ultrafilterable Pt had a short distribution phase (t1/2 alpha = 0.35 and 0.54 h, respectively) followed by a prolonged elimination phase (t1/2 beta = 63.08 and 58.91 h, respectively). A reduced ability to clear ultrafilterable Pt (ClT = 123.52 ml h-1 kg-1) was evident and, as a result, the area under the curve increased (15.47 mg h L-1). The limited number of patients and the concomitant use of other agents prevent any firm conclusions.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1993

Antibiotic prescribing patterns in Italian hospital inpatients with pneumonia, chronic obstructive pulmonary disease, and urinary tract infections.

OBJECTIVE: The primary objective of this study was to describe the antibiotic prescribing patterns in hospital inpatients with pneumonia (PN), exacerbations of chronic obstructive pulmonary disease (COPD), and urinary tract infections (UTIs). A second objective was to verify if some selected variables (i.e., risk factors, patient age, size of hospitals) were affecting the therapeutic choice. DESIGN: Survey was performed on 1609 patients. The data were collected by physicians using a special form, covering a six-month period. SETTING: Twenty-six medical wards and 8 geriatric wards in 24 acute-care hospitals in the Veneto Region in Northern Italy. PATIENTS: A consecutive sample of PN, COPD, and UTI patients treated with antibiotics. MAIN OUTCOME MEASURES: The following information was collected: patient and hospital demographics, risk factors, diagnoses, and antibiotic regimens. RESULTS: Sixty-three antimicrobial agents used, with 2115 administrations, 1227 of which were single-drug therapy. The most frequently used drugs were third-generation cephalosporins (24.6 percent), fluoroquinolones (15.4 percent), aminopenicillins (15.0 percent), and ureidopenicillins (9.7 percent). There is great variability of therapeutic regimens in the various hospitals for the same disease. However, this variability is not explained by the different types of hospitals or by the patients' characteristics (e.g., age, risk factors). CONCLUSIONS: Our results show that the use of broad-spectrum antibiotics probably is excessive. Moreover, the treatment seems to be based more on the opinion of the treating physician and the local habits rather than objective criteria. These factors may have negative repercussions not only in economic terms, but also in terms of alteration of the bacterial ecology.

Adolescent↗