Biomedical subjects

F Merlo

Publications and source records attributed to F Merlo.

At least 37 records · Page 2Linked to original sources

PubMed1997

Teicoplanin concentrations in serum, pericardium, pericardial fluid and thoracic wall fat in patients undergoing cardio-pulmonary bypass surgery.

The concentrations of teicoplanin in serum, pericardium, pericardial fluid and thoracic wall fat were measured in patients undergoing cardio-pulmonary bypass (CPB) after the administration of a single i.v. 12 mg/kg dose. Five minutes after the start of CPB, teicoplanin serum concentrations decreased by, on average, 35% (95% confidence interval (CI): 28-42%) and remained significantly lower than the expected values over the subsequent 60 min period. After aortic unclamping drug concentrations rebounded but remained significantly lower than the expected values in the next 60 min. Immediately before CPB, penetration of teicoplanin in pericardium and thoracic wall fat was 0.44 (95% CI: 0.23-0.65) and 0.05 (95% CI: 0.03-0.7), respectively, and increased at the end of CPB to 0.90 (95% CI: 0.55-1.25) and 0.17 (95% CI: 0.05-0.29), respectively. MICs for most staphylococcal strains were attained during CPB procedure in pericardium but not in thoracic wall fat. However, since staphylococcal infections involve the interstitial space it is likely that penetration into fat cells is not important for antimicrobial prophylaxis. In this respect, it is worth noting that drug concentration in pericardial fluid, which should reflect the interstitial concentration, was higher than the MIC for most staphylococcal strains. Although no infective complications were observed in our limited series of patients, larger clinical trials are needed to assess whether the dose regimen employed is effective in preventing post-CPB surgery infections.

Adipose Tissue↗

PubMed1997

Airborne levels of polycyclic aromatic hydrocarbons: 32P-postlabeling DNA adducts and micronuclei in white blood cells from traffic police workers and urban residents.

An epidemiologic study on 94 traffic police officers exposed to airborne polycyclic aromatic hydrocarbons (PAH) and 52 age-matched urban residents working in confined spaces considered as referent subjects without occupational exposure to PAH was conducted to characterize individual exposure to benzo(a)pyrene (BaP), benzo(b)-, and benzo(k)fluoranthene (BbF and BkF) and the occurrence of DNA adducts and micronuclei in white blood cells (WBC). The study's findings indicated that mean concentrations of PAH in the city air were 10 to 30 times higher among the traffic police officers compared with referent subjects (4.55 +/- 3.44 ng/m3 and 0.15 +/- 0.30 ng/m3 of BaP among police officers and referents, respectively). 32P-postlabeling DNA adducts in WBC obtained from police officers (1.48 +/- 1.35 RAL/10(8)) were significantly higher than in referent subjects (1.01 +/- 0.63 RAL/10(8), P = 0.007), suggesting a possible role of exposure to airborne PAH in the DNA damage. The frequency of micronuclei was significantly increased (P = 0.02) in referent subjects (4.49 +/- 2.0% cells) compared with police officers (3.75 +/- 1.65% cells) due to the large proportion of females in the former group. Comparison of the mean micronuclei frequencies among 82 male police officers (3.73 +/- 1.6% cells) and referents (4.03 +/- 1.61% cells) failed to reveal a statistically significant difference (P = 0.38). Our findings support the evidence of a noxious effect of the exposure to airborne PAH found in large cities on the occurrence of DNA adducts in WBC, whereas there seems to be no effect on the cytogenetic risk assessed as micronuclei frequency.

Adult↗

PubMed1997

Cytogenetic biomonitoring in traffic police workers: micronucleus test in peripheral blood lymphocytes.

Atmospheric pollution represents a relevant environmental hazard which has been associated with considerable excess mortality, morbidity, and increased rates of respiratory diseases in humans. To date, more than 3,000 environmental chemical compounds have been identified in the ambient atmosphere, including a variety of mutagenic and/or carcinogenic agents, such as polycyclic aromatic hydrocarbons (PAHs), aromatic amines, and heterocyclic compounds. Positive associations between cytogenetic markers and airborne levels of PAHs have been reported by experimental and human studies. Traffic has been implicated as the major determinant for the concentration of PAHs and, therefore, for the genotoxic activity of urban air. A biomonitoring study has been conducted in 82 italian traffic police workers exposed to air pollutants and 34 control subjects (matched by age, gender, and smoking habits) not exposed to traffic pollutants. The aim of this study was to assess the cytogenetic effects, such as micronucleus frequency in peripheral blood lymphocytes, and to estimate the association with individual exposure to PAH. Statistical analysis of the frequency of micronuclei in binucleated cells showed higher mean levels in referent subjects (4.03%) than in traffic police officers (3.73%). Smoking showed no effect on the frequency of micronuclei. The study failed to detect any association between micronucleus frequency and individual level of benzo(a)pyrene, considered a marker of exposure to PAHs. These findings indicate that exposure to urban air pollutants does not result in increased levels of micronuclei in peripheral white blood cells.

Adult↗

PubMed1996

Effect of the antiarrhythmic drug procainamide on the toxicity and antitumor activity of cis-diamminedichloroplatinum(II).

The class I antiarrhythmic drug procainamide (Pd) was tested on BDF1 mice for its chemoprotective activity against cis-diamminedichloroplatinum(II) (DDP) toxicity. Pd at the dose of 50 mg/kg protected mice against otherwise lethal doses of DDP (survivors at Day 14 after 25 mg/kg DDP or 25 mg/kg DDP-Pd treatment: 0% vs 100%) and greatly reduced the weight loss induced by DDP. Moreover, the increased plasma urea nitrogen levels caused by a single ip administration of DDP in water (8 or 16 mg/kg) as well as the tubular degenerative changes detected by light microscopy were prevented by Pd. Pd had no effect on the sensitivity of P388 leukemic cells to DDP in vitro, but the administration of DDP (16 mg/kg) and Pd (50 mg/kg) to BDF1 mice bearing P388 leukemic cells produced a significant increase in survivals compared to mice receiving ip DDP alone diluted in 0.9% NaCl solution. The increased efficacy of this combination therapy in P388 leukemic mice compared to a single DDP treatment at the same dose was observed both when the drugs were administered ip simultaneously (p = 0.042) and when DDP and Pd were given ip and iv, respectively (p = 0.018). Since procaine, which differs from Pd merely in the replacement of the amide by the ester linkage, has also been reported to significantly enhance DDP efficacy (M. Esposito et al., 1990, J. Natl. Cancer Inst. 82, 677-684.), a comparison of their effects in tumored mice exposed to DDP has been made. Although both drug combinations were superior to that of DDP alone, in terms of both survival time and numbers of cures, Pd treatment seems to offer better protection against DDP-induced lethality than did procaine.

Animals↗

PubMed1996

Cisplatin combined with the new cisplatin-procaine complex DPR: in vitro and in vivo studies.

The administration of combinations of platinum compounds is considered as a useful alternative therapeutic strategy to avoid the complications of toxic events during cancer chemotherapy in order to obtain a therapeutic advantage. On the basis of previous in vitro and in vivo findings, suggesting an antitumour activity of the new cisplatin-derived compound cis-diamminechloro-[2-(diethylamino)ethyl 4-amino-benzoate, N4]-chlorideplatinum(II) monohydrochloride monohydrate (DPR), we investigated the effectiveness of the combination of cisplatin (DDP) and DPR in vitro on murine leukaemic cells, which were either sensitive (P388) or resistant (L1210/DDP) to DDP, and on the murine M5076 reticulum cell sarcoma, and in vivo in BDF1 female mice transplanted with P388 leukaemic cells or cisplatin-resistant L1210/DDP leukaemic cells. The contemporaneous exposure in vitro to both platinum compounds gave a significantly higher cell growth inhibition than that expected on the basis of dose-response curves for single agents in all tumour models tested. In vivo, the combinations of DDP plus DPR elicited significant enhancement over the activity of the drugs alone both in the ascitic and solid P388 models. The combined treatment of 10 mg/kg DDP and 14 mg/kg DPR yielded 62.5% tumour-free mice compared with 6.2% with 10 mg/kg DDP alone, the best single agent. It is noteworthy that the combined application of DDP and DPR was also very effective in the solid cisplatin-resistant L1210/DDP model, inducing a significant reduction in the volume of tumour. A therapeutic advantage was achieved with combination treatments that had no effect on platinum-mediated body weight loss and were generally well tolerated by the mice. At equitoxic concentrations of DPR and carboplatin, the treatment with DDP plus DPR proved to have a higher efficacy against this tumour model compared to that observed after the combined treatment with DDP and carboplatin. In summary, the combination of DDP and DPR showed a therapeutic advantage over single drug treatment and has demonstrated promise at the preclinical level in its ability to circumvent acquired resistance to DDP both in vitro and in vivo.

Animals↗

PubMed1996

Treatment of stage IIIB non-small-cell lung cancer with surgery followed by infusion of tumor infiltrating lymphocytes and recombinant interleukin-2: a pilot study.

Stage IIIb non-small-cell lung cancer (NSCLC) has a poor prognosis. The median survival is approximately 6 months, and only 30% of patients are alive 1 year after diagnosis. The need for effective treatment is evident. The aim of this study was to evaluate whether the infusion of tumor-infiltrating lymphocytes (TILs), isolated from resected tumor, expanded in vitro and injected together with recombinant Interleukin-2, is feasible and may at least partially modify the poor prognosis in these patients. The infusion of TILs, derived from surgically resected NSCLC and expanded in vitro, together with subcutaneous (s.c.) injections of recombinant interleukin-2 (rIL-2) was attempted in a group of 11 patients. Treated patients were infused i.v. with in vitro expanded TILs (from 4 to 70 x 10(9) cells), and rIL-2 was injected s.c. at doses varying from 61 to 378 x 10(6) IU. Toxic side effects (fever and, in some cases, hypotension) were observed and limited the dose of rIL-2 infused. Follow-up was continued for 40 months. The mean survival time was 13.8 months. Three of five TIL-treated patients with residual disease have no evident disease after 1 year, and two of them are still alive and have no evidence of disease after 40 months. This pilot study suggests that the infusion of in vitro expanded TILs, derived from surgical samples, is feasible and seems to prolong overall survival and to control the residual disease in patients with advanced NSCLC.

Aged↗

PubMed1996

(32)P-postlabeling detection of DNA adducts in peripheral white blood cells of greenhouse floriculturists from western Liguria, Italy.

Pesticides are widely used in agriculture to enhance crop yields and to control disease vectors. Floriculturists work frequently in greenhouses and may be exposed to high levels of pesticides, which may result in adverse health effects. To evaluate the relationship between exposure to pesticides and DNA adduct formation in peripheral WBCs of Italian floriculturists, the nuclease P1 modification of a (32)P-postlabeling assay was used to analyze WBC DNA from floriculturists (n = 26) and matched controls (n = 22). DNA adduct-positive samples were more frequent in floriculturists (11/26; 42%) than in matched controls (2/22; 9%) (P < 0.01). Slightly higher frequencies of DNA adduct-positive samples were observed in floriculturists > or = 44 years of age (53%) and in female floriculturists (57%). Floricultural practice was found to be associated with a significantly higher DNA adduct-positive rate in WBCs (rate ratio, 5.12; 95% confidence interval, 1.1-23.7) after allowing for the effects of age and gender. These two latter covariates were not significantly associated with DNA adduct-positive rates. The quantitative levels of DNA adducts were significantly higher in floriculturists than in matched controls according to the Mann-Whitney nonparametric statistic (P = 0.0052). The median adduct level for positive samples among floriculturists was 1.5/10(8) bases. A specific, well-visible spot, named alpha adduct, was detected in 7 out of the 11 DNA adduct-positive samples from floriculturists but in none of the (22 + 20) referent samples (P = 0.0004). The presence of pesticide-related DNA adducts was confirmed clearly using the butanol extraction procedure. Six of 8 floriculturists and 0 of 10 referents were found positive with this method. The median adduct level for positive samples was 6.0/10(8) bases. Two strong spots close to the origin could be identified in all six positive floriculturists, using the butanol extraction procedure. No association between DNA adducts and use of specific pesticides was observed.

Adult↗

PubMed1995

Effects of cardiopulmonary bypass on teicoplanin serum disposition.

The time course of teicoplanin (T) serum concentrations was determined in 6 patients who had undergone cardiopulmonary bypass (CPB). The drug was given i.v. (12 mg/kg) 85-140 min before starting CPB. Serum concentrations of T were measured with an automated fluorescence polarization immunoassay, at appropriate times before, during and after CPB (total sampling interval: 12 h). Five min after initiating CPB, T serum concentrations decreased, on average, by 29% and remained less than the expected values (values extrapolated from the decay curve, measured excluding the CPB period) over the subsequent 60 min. When CPB was discontinued, the T serum concentrations rebounded to the expected values within 5 min. The mean area under the curve (AUC) during CPB was significantly lower than the mean extrapolated AUC. It was concluded that CPB reversibly reduced T serum concentrations, probably due to drug redistribution. Nevertheless, T serum levels were always above the mean inhibitory concentration (MIC) of the most common pathogenic organisms associated with CPB surgery infections.

Cardiopulmonary Bypass↗

PubMed1995

[Genotoxic damage in subjects exposed to automobile exhaust: preliminary results].

The associations between selected biomarkers of biologically effective dose (32P-post-labelling-DNA adducts), early biological effects (Micronuclei, MN) and sister chromatid exchanges (SCE) and individual measurements of exposure to benzo(a)pyrene (a surrogate index of exposure to polynuclear aromatic hydrocarbons, PAHs) are investigated in a study being conducted among traffic police workers and referent subjects in the City of Genova, Italy. Preliminary findings show B(a)P mean values of 1.33 ng/m3, SD = 1.35 ng/m3 and 0.06, SD = 0.17 in traffic police workers and referent subjects, respectively. Micronuclei mean levels in peripheral blood lymphocytes of 26 traffic police workers and 25 referents were 3.30, DS = 1.24 e 3.90, DS = 1.50 (per 1,000 binucleated cells). Eleven subjects (61%) out of 18 had detectable levels of DNA adducts (32P-post-labelling technique, range 1.8-9.0 Relative Adduct Level (RAL) per 10(9) nucleotides).

Adult↗

PubMed1995

Cancer, cardiovascular mortality, and diet in Italy and the Czech Republic.

A descriptive study aimed at comparing mortality and dietary patterns in Italy and the Czech Republic was conducted in the period 1970-1990. Mortality from all causes, all cancers, selected site specific cancers and cardiovascular diseases were found to be generally higher in the Czech Republic than in Italy. The North-South gradients observed within Italy have diminished in the course of the last twenty years, mostly due to a less contained decrease of the mortality from cardiovascular diseases and to a marked increase in cancer mortality for Southern regions compared to Central and Northern regions. The mediterranean diet with many health promoting, possibly protective components, mostly of vegetable origin, is consumed in most parts of Italy, particularly in the South. In contrast, a Central European diet abounding in animal products and lacking in fresh fruit and vegetables is generally followed in the Czech Republic. These differences in diet may play a role in the origin of the observed differences in mortality patterns. Some factors other than diet, such as smoking habits, alcohol consumption, endogenous factors, and occupation, that are not considered here, are known to be involved in the causation of some types of cancer. The results of this study are compatible with the hypothesis of a relevant role played by dietary and other life-style habits in the etiopathogenesis of neoplastic and cardiovascular diseases.

Cardiovascular Diseases↗

PubMed1995

Mortality among silicotics in Genoa, Italy, from 1961 to 1987.

A historical cohort mortality study conducted among 515 silicotic subjects revealed higher than expected risks for all causes [standardized mortality ratio (SMR) 1.89], respiratory tract diseases (SMR 8.89), silicotuberculosis (SMR 27.00), respiratory tract cancers (SMR 3.14), and lung cancer (SMR 3.50). Mortality from cardiovascular diseases was lower than that expected (SMR 0.51). Lung cancer risk increased with duration of occupational exposure (SMR 2.80, 2.99, and 5.02 for 14, 15-29, and 30 years of employment, respectively). Lung cancer risk was higher for the silicotics without tuberculosis (SMR 3.72) than for those with tuberculosis (SMR 2.83). Indirect adjustment for smoking habits, including number of cigarettes smoked per day, showed that smoking would have been responsible for a maximum risk of 1.77. Thus smoking may have explained 50% of the observed excess mortality from lung cancer.

Adult↗

PubMed1994

Multiple regression analysis of cytogenetic human data.

Biomonitoring studies on cytogenetic outcomes in humans should be considered as epidemiological studies, rather than randomized trials. Under this light the emphasis given to the achievement of a significant p-value should be reduced, since this measure suffers from major limitations. The use of a point estimate (and its corresponding confidence interval) to measure the association between exposure and effect offers several advantages, including the adjustment for confounding, and the evaluation of possible interaction between factors. In most instances the use of multivariate statistical methods allows an efficient analysis of these studies, even in presence of a small sample size and several covariates. In this paper we re-analyzed four biomonitoring studies by using multivariate methods to estimate relative risks through statistical modeling. The use of multiple regression techniques allowed the computation of point estimates of association and their confidence intervals for each covariate evaluated by the studies considered; the estimate of the effect of confounding variables such as smoking habits, age and gender; and the presence of interaction between covariates. Measures of association estimated through univariate and multivariate statistical approaches are compared. The advantages of the latter technique are discussed.

Adult↗

PubMed1994

Tumour kinetics, response to chemotherapy and survival in primary ovarian cancer.

The analysis of thymidine labelling index (TLI) in relation to clinico-pathological variables and survival was carried out in 111 ovarian cancer patients. The significance of TLI in predicting response to aggressive first line chemotherapy regimens was examined. The overall median TLI value of 1.8% was used as a cut-off to discriminate slowly from highly proliferating cancers. 94 patients entered into two consecutive randomised trials, and were treated with six courses of cisplatin-based chemotherapy with or without doxorubicin. A significantly higher objective response of 60% was reported in the subset of patients with TLI > 1.8% as compared to 35% in patients with TLI < or = 1.8% (P = 0.03). In addition, patients achieving complete response had tumours with median TLI of 3.8% as compared to 2.4% for partial responders, 1.5% for patients with stable disease and 1.7% for those with progressive disease. A significant increase in tumour kinetics was observed in advanced cancers (P = 0.001), more undifferentiated tumours (P = 0.02) and postsurgical residual disease greater than 2 cm (P = 0.04). In univariate analysis, TLI failed to influence significantly clinical outcome: 26 versus 32 months median survival time for patients with high and low tumour TLI, respectively. In the Cox's regression model, the only independent prognostic variables were performance status and amount of residual disease after primary surgery (P = 0.000).

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1994

Effect of alkaline citrate therapy on clearance of residual renal stone fragments after extracorporeal shock wave lithotripsy in sterile calcium and infection nephrolithiasis patients.

The natural history of post-extracorporeal shock wave lithotripsy residual stone fragments (clearance, growth and aggregation) is incompletely known, even though they are believed to constitute a risk in terms of new stone formation and persistent infection of the urinary tract. We addressed this issue and the hypothesis that alkaline citrate therapy improves residual stone fragment clearance in a 12-month followup study. There were 40 sterile calcium and 30 struvite stone patients with residual fragments after extracorporeal shock wave lithotripsy (diameter less than 5 mm.) consecutively enrolled and randomly assigned to a citrate therapy (6 to 8 gm. per day) or control (hygienic measures only) group. Infection stone patients also received adequate antibiotic therapy throughout the study. Among the patients in the untreated sterile group 21% and 32% were stone-free at 6 and 12 months, respectively. In the infection group these figures were 27% and 40%, respectively. Among the untreated sterile calcium stone patients in whom clearance was not achieved a high percentage experienced residual fragment growth or reaggregation. Citrate therapy significantly improved the stone clearance rate in the sterile (at 6 and 12 months 65% and 74% were stone-free, respectively) and infection (71% and 86%, respectively) stone patients, and prevented residual fragment growth or reaggregation in subjects in whom clearance was not achieved. The data show that growth and persistence are common in the natural history of residual stone fragments. Citrate ameliorated the outcome of these residual fragments by reducing the growth or agglomeration, and by increasing the clearance rate in calcium oxalate and in infection stone patients.

Adolescent↗

PubMed1994

Meniscal ossicles: two case reports and a review of the literature.

Intrameniscal ossicles of the knee are rare lesions. We present two cases. The first case occurred in a male soccer player who had knee trauma, with radiographic findings of a meniscal ossicle. Meniscal motions were normal, and symptoms resolved with conservative measures. The second case was found in a male athlete with acute medial compartment instability and complex meniscal tears. His medial meniscus, containing the ossicle, was removed. Initial conservative management is recommended for all cases of meniscal ossicle, and arthroscopic resection of the ossicle is recommended for symptomatic cases.

Adult↗

PubMed1994

Partial lateral meniscectomy in athletes.

Arthroscopic partial lateral meniscectomies performed for isolated meniscal tears, without associated ligamentous injury, in 41 athletes between August 1, 1988 and June 1, 1991 were reviewed for clinical and functional outcome. The study population was composed of 27 males and 14 females, with an average age of 26 years (range 17-40). Thirty-seven patients (90%) reported previous trauma to the knee. At an average follow-up of 3 years (range 2-5), 85% of the patients had excellent/good results, and 98% of the athletes returned to full sports activities after an average of 55 days. Patients' prognoses depended on (a) type of meniscal tear and (b) presence/absence of an articular cartilaginous lesion. Athletes who had isolated, longitudinal type tears of the lateral meniscus had the best outcome: 100% achieved excellent/good results and averaged 41 days to return to full sports activities. Athletes with complex meniscal tears and tears associated with articular cartilaginous lesions had the poorest results, achieving 79% and 64% excellent/good results, respectively, and averaging 64 and 78 days, respectively, for return to full sports activities.

Adolescent↗

PubMed1993

Biomonitoring of workers exposed to pesticides.

The potential clastogenic effects of pesticides was investigated in 71 floriculturists exposed to complex chemical mixtures. Exposed and referent subjects were selected from the same geographical area located in north western Italy. A significant association between micronuclei frequency and occupational exposure to pesticides was found (RR = 1.25). A positive dose-response gradient was observed with years of employment (used as an index of cumulative exposure) as a floriculturist. Individuals working exclusively in greenhouses (confined spaces) showed higher micronuclei levels than subjects working in open fields. The study supports the hypothesis that human exposure to pesticides causes a clastogenic damage.

Agriculture↗

PubMed1993

Heart rate variability and severe brain damage: preliminary data.

Severe brain damage may cause alterations of cardiovascular function: heart rate, particularly, require the integrity of the vagal, sympathetic and central nervous systems. We studied brain-heart functional relation and neurovegetative modulation by spectral analysis of heart rate variability (HRV). This technique allows separate evaluation of the sympathetic and vagal components of heart rate modulation. In order to correlate changes in HRV with brain damage, we performed 45 recordings in 6 patients (5/1 M/F) by means of autoregressive analysis (AAR). All patients were admitted to the ICU for severe brain damage (anoxic, traumatic or vascular). In 4 patients clinical outcome was brain death, in 2 permanent vegetative status. Two different patterns were found: one in patients with brain death, the other in patients with vegetative status. The small number of patients does not allow definitive conclusions from collected data, but that application of spectral analysis of HRV seems to be a useful monitoring of brain damage subjects.

Adolescent↗