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Biomedical subjects

L Leone

Publications and source records attributed to L Leone.

At least 37 records · Page 2Linked to original sources
PubMed1998

Determination of meropenem in serum by high-performance liquid chromatography with column switching.

A rapid, accurate and sensitive liquid chromatographic assay with on-line solid-phase extraction for determination of meropenem in serum is described. Sample was directly injected onto the extraction column for sample clean-up and extraction. Thereafter, using an on-line column-switching system the drug was quantitatively transferred and separated on a C18 analytical column. Ultraviolet absorption at 298 nm was used for detection. The assay was linear from 1 to 100 micrograms/ml. Recovery was 98.5%. Based on a 20-microliters sample volume (serum- water, 1:1, v/v), detection limit was 0.1 microgram/ml. An application of the method to study the pharmacokinetics of meropenem is given.

Chromatography, High Pressure Liquid↗
PubMed1998

Quality of life after proctocolectomy and ileo-anal anastomosis for severe ulcerative colitis.

OBJECTIVE: Impaired quality of life (QOL) in patients with ulcerative colitis (UC) may be a prominent feature of the disease, and in some cases, may become an indication for surgical treatment. The objective of this study was to assess QOL in patients who underwent proctocolectomy with ileo-anal anastomosis with a J pouch for severe UC and to compare it with patients with UC of different severity who were under medical treatment. METHODS: We used a validated, disease-specific research instrument (a 29 item, self-administered questionnaire) that examines the following four functions: intestinal (score 0-24) and systemic symptoms (0-21), and emotional (0-27) and Social Function (0-15). High scores indicate an impairment of the function examined and the sum of the four scores (maximal total score = 87) reflects the patient's QOL. We studied 29 operated patients (22 men, mean age 35 yr, mean time after intervention 3.8 yr) and compared their scores with those of 57 UC patients (39 men, mean age 36 yr) with different degrees of disease activity, and with those of 72 healthy controls (38 men, mean age 31 yr). RESULTS: In UC, scores were significantly higher than in controls, increasing with the severity of the disease. Even patients in remission had higher scores than controls in the "systemic" (4.6 vs. 2.0) and emotional (5.6 vs. 2.5) functions. Patients who underwent surgical treatment had much better scores than patients with severe disease (total score 20.1 vs. 38.2), with values comparable to those of patients in remission or with mild disease activity. There was no significant gender difference, either for UC and ileo-anal anastomosis patients, or in healthy controls. CONCLUSION: In patients with UC, even in remission, there is a measurable impairment of QOL, which increases with the severity of disease. Operated patients have a QOL that is comparable to that of patients in remission or with mild disease, and proctocolectomy with ileo-anal anastomosis may restore an acceptable QOL in patients with moderate/severe UC.

Adult↗
PubMed1998

Pharmacokinetics of ifosfamide administered according to three different schedules in metastatic soft tissue and bone sarcomas.

Ifosfamide is a leading drug in soft tissue sarcoma therapy. Recently high dose therapy (>9 g/m2) has been introduced in different schemes to obtain a higher response rate. All these higher doses can be administered following two different schedules: continuous infusion 24 hours a day for 4-5 days or bolus administration for 5 consecutive days. In this study we compare the differences in the pharmacokinetic profile between the two schedules. In both schemes we saw a very important autoinduction phenomenon, with a corresponding half-life decrease and total body clearance increase during the days of therapy. The clearances were not directly correlated with the administered dose. We can conclude that ifosfamide continuous infusion therapy is equivalent to fractionated administration, at least from a pharmacokinetic point of view. Short-term infusion is subjectively better tolerated and is therefore preferred.

Adult↗
PubMed1998

Phase I trial of weekly paclitaxel in advanced lung cancer.

PURPOSE: We conducted a phase I study in chemotherapy-naive patients with advanced non-small-cell lung cancer (NSCLC) to determine the maximum-tolerated dose (MTD) of paclitaxel using an extended weekly schedule. PATIENTS AND METHODS: Patients with stage IIIB/IV NSCLC were treated with paclitaxel administered weekly over 3 hours for 6 weeks of an 8-week cycle. Doses were modified for granulocyte counts less than 1,800/microL or neurotoxicity greater than grade I. Groups of three patients were entered at each dose level. The dose was escalated to the next level if less than 50% of patients developed unacceptable toxicity and received more than 80% of the intended first-cycle dose. RESULTS: Twenty-six patients were entered through six dose levels (100, 125, 135, 150, 175, and 200 mg/m2/wk). Four of six patients at the 175-mg/m2 dose level and only one of six patients at the 200-mg/m2 level received all scheduled doses of paclitaxel during cycle 1. Neutropenia was dose-limiting. Fourteen patients were treated with subsequent cycles of paclitaxel. Grade II to III neuropathy developed in five of 24 patients. It occurred more commonly with greater duration of therapy, but improved following dose reduction. Nine of 26 (35% +/- 10%) patients demonstrated an objective response. CONCLUSION: The MTD of paclitaxel using a weekly schedule is 175 mg/m2/wk for 6 of 8 weeks. Neutropenia limits dosing acutely, but neuropathy is limiting with sustained therapy. This schedule of paclitaxel results in a twofold to threefold increase in dose-intensity with less toxicity than anticipated from conventional dosing. Further evaluation of this schedule is warranted to assess efficacy and toxicity of prolonged administration.

Adult↗
PubMed1998

Phase I study to determine the maximum-tolerated dose of radiation in standard daily and hyperfractionated-accelerated twice-daily radiation schedules with concurrent chemotherapy for limited-stage small-cell lung cancer.

PURPOSE: An improvement in radiation dose schedule is necessary to increase local tumor control and survival in limited-stage small-cell lung cancer. The goal of this study was to determine the maximum-tolerated dose (MTD) of radiation (RT) in both standard daily and hyperfractionated-accelerated (HA) twice-daily RT schedules in concurrent chemoradiation. METHODS: The study design consisted of a sequential dose escalation in both daily and HA twice-daily RT regimens. RT dose to the initial volume was kept at 40 to 40.5 Gy, while it was gradually increased to the boost volume by adding a 7% to 11 % increment of total dose to subsequent cohorts. The MTD was defined as the radiation dose level at one cohort below that which resulted in more than 33% of patients experiencing grade > or = 4 acute esophagitis and/or grade > or = 3 pulmonary toxicity. The study plan included nine cohorts, five on HA twice-daily and four on daily regimens for the dose escalation. Chemotherapy consisted of three cycles of cisplatin 33 mg/m2/d on days 1 to 3 over 30 minutes, cyclophosphamide 500 mg/m2 on day 1 intravenously (IV) over 1 hour, and etoposide 80 mg/m2/d on days 1 to 3 over 1 hour every 3 weeks (PCE) and two cycles of PE. RT was started at the initiation of the fourth cycle of chemotherapy. RESULTS: Fifty patients were enrolled onto the study. The median age was 60 years (range, 38-79), sex ratio 2.3:1 for male to female, weight loss less than 5% in 73%, and performance score 0 to 1 in 94% and 2 in 6% of patients. In HA twice-daily RT, grade > or = 4 acute esophagitis was noted in two of five (40%), two of seven (29%), four of six (67%), and five of six patients (86%) at 50 (1.25 Gy twice daily), 45, 50, and 55.5 Gy in 1.5 Gy twice daily, 5 d/wk, respectively. Grade > or = 3 pulmonary toxicity was not seen in any of these 24 patients. Therefore, the MTD for HA twice-daily RT was judged to be 45 Gy in 30 fractions over 3 weeks. In daily RT, grade > or = 4 acute esophagitis was noted in zero of four, zero of four, one of five (20%), and two of six patients (33%) at 56, 60, 66, and 70 Gy on a schedule of 2 Gy per fraction per day, five fractions per week. Grade > or = 3 pneumonitis was not observed in any of the 19 patients. Thus, the MTD for daily RT was judged to be at least 70 Gy in 35 fractions over 7 weeks. Grade 4 granulocytopenia and thrombocytopenia were observed in 53% and 6% of patients, respectively, during the first three cycles of PCE. During chemotherapy cycles 4 to 5, grade 4 granulocytopenia and thrombocytopenia were noted in 43% and 29% of patients at 45 Gy in 30 fractions over 3 weeks (MTD) by HA twice-daily RT and 50% and 17% at 70 Gy in 35 fractions over 7 weeks (MTD) by daily RT, respectively. The overall tumor response consisted of complete remission (CR) in 51% (24 of 47), partial remission (PR) in 38% (1 8 of 47), and stable disease in 2% (one of 47). The median survival time of all patients was 24.4 months and 2- and 3-year survival rates were 53% and 28%, respectively. With regard to the different radiation schedules, 2- and 3-year survival rates were 52% and 25% for the HA twice-daily and 54% and 35% for the daily RT cohorts. CONCLUSION: The MTD of HA twice-daily RT was determined to be 45 Gy in 30 fractions over 3 weeks, while it was judged to be at least 70 Gy in 35 fractions over 7 weeks for daily RT. A phase III randomized trial to compare standard daily RT with HA twice-daily RT at their MTD for local tumor control and survival would be a sensible research in searching for a more effective RT dose-schedule than those that are being used currently.

Adult↗
PubMed1997

Preoperative chemoradiation coupled with aggressive resection as needed ensures near total control in advanced head and neck cancer.

BACKGROUND: Preoperative chemotherapy or chemoradiation protocols are generally associated with high clinical response rates, but limited pathologic responses for large primary tumors. We have initiated a prospective phase II study of weekly paclitaxel 60 mg/M2, and carboplatin (AUC of 1) plus concurrent fractionated external beam radiation (45 Gy) followed by organ-preserving (or function restorative) surgery when applicable to maximize local-regional tumor control. PATIENTS AND METHODS: Operable patients staged by triple endoscopy received a percutaneous endoscopic gastrostomy and vigorous dental and nutritional support during therapy. Weekly paclitaxel 60 mg/M2, carboplatin (AUC of 1), and radiation 45 Gy were given with rebiopsy of the primary site at 5 weeks. Patients with positive biopsy had definitive surgery in 4 to 5 weeks. Patients with negative biopsy-results received 3 additional weeks of radiation, to a total dose of 72 Gy plus carboplatin and paclitaxel. RESULTS: The 35 patients were 29 men and 6 women, aged 40 to 71 years, with stage III (12) or stage IV (23) cancer. The site of the cancer was oral cavity, 10; base of tongue, 3; oropharynx, 3; hypopharynx, 4; larynx, 12 (glottic, 6; supraglottic, 6), unknown primary, 2; other, nasal cavity, 1. Of 34 evaluable patients, 16 (47%) had a complete clinical response (CR) and 18 (53%) had a partial response (PR); total clinical response rate was 100%. A pathologic CR at the primary site occurred in 23 of 34 patients (68%; 2 had an unknown primary) who went on to completion radiation at 67 to 72 Gy. After induction chemoradiation 21 patients with N1-3 nodes had neck dissection; 6 (31%) had positive nodes. Twelve patients had residual cancer at the primary site at time of rebiopsy: mandible, 4; maxilla, 1; base of tongue, 2; larynx, 4; floor of mouth, 1; and nasal cavity, 1. All were resected with function-preserving reconstruction. At median follow-up of >12 months, progression-free and overall survivals were 71% and 83%, respectively. CONCLUSION: Preoperative treatment with paclitaxel, carboplatin, and radiation is associated with high CR at the primary site and a high level of organ preservation or functional restoration if ablation is done.

Adult↗
PubMed1997

Coenzyme Q homologs and vitamin E in synaptic and non-synaptic occipital cerebral cortex mitochondria in the ageing rat.

The coenzyme Q8 (CoQ8) and alpha-tocopherol contents of different mitochondrial fractions were investigated from occipital cerebral cortices of different ages. The highest CoQ8 and vitamin E concentrations were found in non-synaptic free mitochondria (FM) fractions. In several cases heavy mitochondria (HM) fractions displayed the lowest values. Occipital cerebral cortex mitochondria contained higher CoQ9 and lower CoQ10 amounts than those typical for other brain regions.

Aging↗
PubMed1997

A new fast-moving variant causing erythrocytosis and mild hemolysis: Hb Gàmbara [beta 82(EF6)Lys-->Glu].

Hb Gàmbara is a new hemoglobin variant with abnormal beta chains that has been found in three out of four members of a family of Lombardy origin (Gàmbara, Brescia, Northern Italy). The affected subjects led a normal life, but they had modest erythrocytosis and mild (compensated) hemolysis with slight splenomegaly. Their abnormal hemoglobin was about 52% of the total hemoglobin, and was shown to be stable by the isopropanol test. Whole blood P50 of the proband was 19.3 Torr, Bohr effect was decreased (-0.25), as well as the molar ratio between the 2,3-diphosphoglycerate level and total hemoglobin of erythrocytes (0.68). The purified abnormal hemoglobin was characterized by an altered oxygen affinity, low n-factor, chloride, and 2,3-diphosphoglycerate effects. The Bohr effect was about 40% of the normal control. The abnormal hemoglobin moved faster than Hb A at alkaline electrophoresis, and split into two fractions, probably due to the formation of hybrid tetramers (alpha 2 beta A beta X). The reversed phase high performance liquid chromatogram from the tryptic digest of the aminoethylated abnormal beta chain subunits indicated the presence of an extra peptide, beta T-9, 10, replacing the individual peptides beta T-9 and beta T-10. Finally, the proband's DNA, drawn from a suitable segment of the beta structural gene (exon 2), revealed a nucleotide sequence carrying the heterozygous mutation AAG-->GAG at codon 82. This led to a Lys-->Glu substitution at position 82(EF6) of the beta chain.

Electrophoresis↗
PubMed1997

[The surgical therapy of prostatic tumors].

In this paper the authors review the latest international literature regarding prostate tumour surgery, comparing surgery with the so-called "wait and see" approach. Together with hormone treatment, the latter method has been used by many researchers over the past few years given the low mortality caused by this tumour in spite of the increasing number of cases diagnosed. The wait-and-see approach is now rendered controversial by improved diagnostic methods and the widespread introduction of early diagnosis programmes. The authors report a number of studies on the use of "wait-and-see" in relation to radical prostatectomy and compare the results of the two techniques in terms of morbidity, mortality and survival. They go on to describe the various types of surgical technique used and their respective pros and cons as well as the complications typical of each technique. In conclusion, the authors discuss the indications for radical prostatectomy which, if performed in selected patients, appears to be a promising therapeutic approach in terms of disease-free survival and with a low operating mortality with complications that are not impossible to resolve using appropriate treatment.

Humans↗
PubMed1997

Concurrent paclitaxel, carboplatin, and radiotherapy in advanced head and neck cancers: a phase II study--preliminary results.

Radiotherapy or surgery alone for advanced head and neck cancer generally yields poor results. Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and carboplatin have both shown excellent radiosensitization through two discrete mechanisms, namely, blocking the cell cycle in the G2/M phase and inhibiting DNA repair. In an effort to improve locoregional control and survival, a prospective phase II study was initiated using paclitaxel 60 mg/ml and carboplatin (area under the concentration-time curve of 1), each given as a single dose weekly with concurrent conventional fractionated external beam radiotherapy. Patients were stratified into two groups: operable and inoperable/unresectable. The operable and inoperable groups received 5 weeks (45 Gy) and 8 weeks (72 Gy) of chemoradiotherapy, respectively. Patients in the operable group were evaluated with repeat biopsies from the primary site after 5 weeks. Those with a positive biopsy underwent surgery; those with a negative biopsy received 3 additional weeks of chemoradiotherapy. Thirty-four patients were entered in the operable group (28 men and six women; 40 to 71 years of age; 12 stage III and 22 stage IV). Of 26 evaluable patients, 19 (73%) had a complete clinical response (95% confidence interval [CI], 52% to 88%) and six (23%) had a partial response (95% CI, 9% to 44%), for a total clinical response rate of 96% (95% CI, 80% to 100%). A pathologic complete response at the primary site (two had an unknown primary site) occurred in 17 of 24 (71%) patients (95% CI, 49% to 87%). Of 20 patients with N1-3 nodes who underwent neck dissection, 17 (85%) had pathologically negative lymph nodes. Seven patients with residual tumor at the primary site were resected (oral cavity, three; maxilla, one; base of tongue, one; and larynx, two). Grades 3 and 4 mucositis were seen in 19 (73%) patients; mucositis was the most common and significant morbidity. Accrual for the inoperable group continues. Concomitant paclitaxel, carboplatin, and external beam radiotherapy yielded excellent clinical responses, but produced significant grade 3/4 toxicity. In the operable group, the majority of responders had a complete pathologic response. These preliminary findings will be assessed in terms of response duration, organ preservation, and long-term survival.

Adult↗
PubMed1997

[Endoscopic surgery of chronic venous insufficiency (CVI)].

The endoscopic technique in chronic venous insufficiency is simple and almost complication free. Our preliminary results due to a good postoperative course and to a quick return to social activity induce the Authors to indicate this type of procedure as the best treatment in chronic venous insufficiency.

Chronic Disease↗
PubMed1996

Reduction of bleeding after heart operations through the prophylactic use of epsilon-aminocaproic acid.

UNLABELLED: Excessive postoperative bleeding after heart operations continues to be a source of morbidity. This prospective double-blind study evaluated epsilon-aminocaproic acid as an agent to reduce postoperative bleeding and investigated its mode of action. One hundred three patients were randomly assigned to receive either 30 gm epsilon-aminocaproic acid (51 patients) or an equivalent volume of placebo (52 patients). In a subset of these patients (14 epsilon-aminocaproic acid, 12 placebo), tests of platelet function and fibrinolysis were performed. RESULTS: By multivariate analysis, three factors were associated with decreased blood loss in the first 24 hours after operation: epsilon-aminocaproic acid versus placebo (647 ml versus 839 ml, p = 0.004), surgeon 1 versus all other surgeons (582 ml versus 978 ml, p = 0.002), and no intraaortic balloon versus intraaortic balloon pump use (664 ml versus 1410 ml, p = 0.02). No significant differences in platelet function could be demonstrated between the two groups. Inhibited fibrinolysis, as reflected by less depression of the euglobulin clot lysis and no rise in D-dimer levels, was significant in the epsilon-aminocaproic acid group compared with the placebo group. CONCLUSION: The intraoperative use of epsilon-aminocaproic acid reduces postoperative cardiac surgical bleeding.

Aminocaproic Acid↗
PubMed1996

[Toxicity of high dose methotrexate repeated infusions in children treated for acute lymphoblastic leukemia and osteosarcoma].

We evaluated and compared hematologic, hepatic and renal cumulative toxicity of high dose methotrexate (HDMTX) repeated courses in two groups of pediatric patients: 22 patients affected by "non B" acute lymphoblastic leukemia (ALL) treated, in consolidation phase, with four courses of HDMTX 5 g/mq given intravenously over 24 hours infusion (for a total of 88 courses) according to the Italian Cooperative Protocols AIEOP LLA-88; 18 patients affected by non metastatic osteosarcoma of extremities (OST) treated, in preoperative and postoperative phases, with five courses of HDMTX 8 g/mq given intravenously over 6 hours infusion (for a total of 90 courses) according to CNR-NEO 2 protocol. Severe myelosuppression (neutropenia < 500/microliters and/or thrombocytopenia < 25000/microliters) was more frequently observed in ALL (7% of infusions) than in OST (3%). Hepatotoxicity (serum transaminase elevation > 350 IU/l) was significantly more frequent (p < 0.001) in OST (32% of courses) than ALL (6%). Nephrotoxicity was assimilable in the two groups and the elevation of serum creatinine was never higher than 1.9 mg/dl. We did not observe any increase of hematologic, hepatic and renal toxicity following the HDMTX courses repetition.

Antineoplastic Agents↗