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Biomedical subjects

F Marchetti

Publications and source records attributed to F Marchetti.

At least 37 records · Page 2Linked to original sources

Pretreatment with intravenous ketamine reduces propofol injection pain.

BACKGROUND: Paediatric procedural sedation using propofol has been shown to be safe and effective and is widely used. Pain at the injection site is a frequent complaint and can be particularly distressing for children, especially for those undergoing repeated procedures. Ketamine has analgesic properties and can diminish the incidence of propofol infusion pain in adults. The aim of the study was to investigate whether pretreatment with ketamine would reduce infusion line pain in propofol sedation in children. METHODS: We performed a prospective, randomized, double-blind trial in a paediatric sedation unit of a tertiary referral teaching hospital. A total of 122 children admitted for gastroscopy were randomly allocated into two groups. Group 1 received atropine and ketamine before propofol infusion. Group 2 received atropine, normal saline solution, and a mixture of propofol with lidocaine. The main outcome measure evaluated was pain associated with the infusion and secondary outcome measures were mean medium arterial pressure decrease and desaturation. RESULTS: The incidence of pain of the infusion was significantly lower in patients pretreated with ketamine (8% vs 37%, P = 0.0001). CONCLUSIONS: Pretreatment with ketamine (0.5 mg.kg-1) is very effective in preventing propofol infusion pain.

Adolescent↗

Minimally invasive surgical management of primary venous ulcers vs. compression treatment: a randomized clinical trial.

OBJECTIVES: to compare minimally invasive surgical haemodynamic correction of reflux (CHIVA) with compression in the treatment of venous ulceration. DESIGN: prospective randomised study. MATERIALS AND METHODS: from a cohort of 80 patients with 87 venous leg ulcers, 47 were randomised to either surgery or compression. RESULTS: at a mean follow-up of 3 years, healing was 100% (31 days) in the surgical and 96% (63 days), in the compression group (p<0.02). The recurrence rate was 9% in the surgical and 38% in the compression group (p<0.05). In the surgical group, all plethysmographic parameters except ejection fraction, had improved significantly at 6 months in the surgical group, and at 3 years residual volume fraction remained in the normal range. Finally, quality of life significantly improved in the operated group. CONCLUSIONS: this study supports the effectiveness of surgical therapy for leg ulceration secondary to superficial venous reflux.

Aged↗

Prevalence, diagnosis and treatment of prostatitis in Italy: a prospective urology outpatient practice study.

OBJECTIVE: To report a prospective, multicentre descriptive study designed to determine the prevalence of the diagnosis of prostatitis in male outpatients examined by urologists in Italy, and to further examine the diagnostic evaluation and treatment of patients identified with a clinical diagnosis of prostatitis. PATIENTS AND METHODS: Between July 2001 and October 2001, 70 urologists, representing a cross-section of urological centres in Italy, counted and recorded the overall total of men reported in the clinic and that of patients diagnosed with prostatitis over a 5-week period. Data on demographics, previous diagnoses, symptoms, physical examination, laboratory data and therapy instituted were collected. Patients with a diagnosis of prostatitis completed questionnaires on symptom frequency and severity, and quality of life. RESULTS: In all, 8503 patients were included in the primary outcome analysis; 1148 were identified with prostatitis (12.8%; mean age 47.1 years, range 16-83) with all age ranges equally represented, and 68% had had their first symptom within the last year. The most common presenting symptoms were severe, bothersome urinary frequency, obstructive voiding symptoms, perineal, suprapubic and penile pain or discomfort. The self-administered questionnaire confirmed that the most frequently reported and most severe symptoms at the time of evaluation were irritative voiding symptoms, perineal and suprapubic pain and discomfort. Over three-quarters of the patients were dissatisfied with their quality of life. While 98% of the patients had a digital rectal examination and expressed prostatic secretion was successfully recovered in 44%, < 3% of the patients had the traditional Meares-Stamey four-glass test. The most common treatment prescribed was drug therapy (not antibiotic). CONCLUSION: The prevalence of a clinical diagnosis of prostatitis in urology outpatient practice in Italy was 12.8%. The prevalence, diagnosis, evaluation and treatment of prostatitis reported in this prospective study was very similar to that reported in other retrospective series from other countries.

Adolescent↗

Comparative bactericidal activity of fluoroquinolones against clinical isolates resistant to fluoroquinolones.

The bactericidal activity of levofloxacin, ciprofloxacin, moxifloxacin and norfloxacin against clinical isolates conventionally classified as resistant to fluoroquinolones were compared at their maximum concentrations in serum, urine (except moxifloxacin) and bronchial mucosa (except norfloxacin). Time killing curves against Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, Staphylococcus epidermidis, and Streptococcus pneumoniae were performed. Serum concentrations of the tested drugs were not able to produce a bactericidal effect on fluoroquinolone-resistant strains. In the urine series, levofloxacin was always bactericidal (decrease > or = 3 logs CFU/ml), while norfloxacin and ciprofloxacin were bactericidal on E. coli (both), P. mirabilis (norfloxacin) and P. aeruginosa (ciprofloxacin). In the bronchial mucosa series, S. pneumoniae was rapidly killed by levofloxacin and moxifloxacin, and K. pneumoniae by levofloxacin after 12 hours. In conclusion, the maximum levofloxacin concentrations achievable at certain body sites allowed killing even of strains defined as resistant by conventional breakpoints.

Anti-Infective Agents↗

Current and future perspectives for levofloxacin in severe Pseudomonas aeruginosa infections.

The question of whether levofloxacin includes Pseudomonas aeruginosa in its spectrum of clinical activity is discussed by reviewing the major findings on this issue, mainly those published in Italy. The in vitro activity of levofloxacin against P. aeruginosa is now documented on thousands of strains worldwide. The pharmacodynamic properties of levofloxacin allow for the treatment of pseudomonal infections. The levofloxacin clinical results extrapolated from published studies document the efficacy of levofloxacin in the treatment of infections sustained by P. aeruginosa.

Anti-Bacterial Agents↗

Etoposide induces heritable chromosomal aberrations and aneuploidy during male meiosis in the mouse.

Etoposide, a topoisomerase II inhibitor widely used in cancer therapy, is suspected of inducing secondary tumors and affecting the genetic constitution of germ cells. A better understanding of the potential heritable risk of etoposide is needed to provide sound genetic counseling to cancer patients treated with this drug in their reproductive years. We used a mouse model to investigate the effects of clinical doses of etoposide on the induction of chromosomal abnormalities in spermatocytes and their transmission to zygotes by using a combination of chromosome painting and 4',6-diamidino-2-phenylindole staining. High frequencies of chromosomal aberrations were detected in spermatocytes within 64 h after treatment when over 30% of the metaphases analyzed had structural aberrations (P < 0.01). Significant increases in the percentages of zygotic metaphases with structural aberrations were found only for matings that sampled treated pachytene (28-fold, P < 0.0001) and preleptotene spermatocytes (13-fold, P < 0.001). Etoposide induced mostly acentric fragments and deletions, types of aberrations expected to result in embryonic lethality, because they represent loss of genetic material. Chromosomal exchanges were rare. Etoposide treatment of pachytene cells induced aneuploidy in both spermatocytes (18-fold, P < 0.01) and zygotes (8-fold, P < 0.05). We know of no other report of an agent for which paternal exposure leads to an increased incidence of aneuploidy in the offspring. Thus, we found that therapeutic doses of etoposide affect primarily meiotic germ cells, producing unstable structural aberrations and aneuploidy, effects that are transmitted to the progeny. This finding suggests that individuals who undergo chemotherapy with etoposide may be at a higher risk for abnormal reproductive outcomes especially within the 2 months after chemotherapy.

Aneuploidy↗

Reflux elimination without any ablation or disconnection of the saphenous vein. A haemodynamic model for venous surgery.

OBJECTIVES: to investigate the possibility of the haemodynamic suppression of reflux in the greater saphenous vein (GSV) without any high ligation and/or stripping procedure. DESIGN: prospective study; single group of patients. MATERIALS: forty patients affected by primary chronic venous insufficiency of all clinical classes, with demonstrated duplex incompetence both of the sapheno-femoral junction (SFJ) and the GSV trunk, with the re-entry perforator located on a GSV tributary. The re-entry point was defined as the perforator, whose finger compression of the superficial vein above its opening eliminates reflux in the GSV. METHODS: air-plethysmographic parameters as well as duplex scanning were performed both preoperatively, and 1 and 6 months later, respectively. Operation consisted in flush ligation and division from the GSV of the tributary containing the re-entry perforating vein. RESULTS: duplex investigation demonstrated both a forward flow and reflux disappearance in the GSV in 100% and 85% of the cases after 1 and 6 months, respectively. All air-plethysmographic parameters, with the exception of Ejection Fraction, improved significantly: Venous Volume changed from 150+/-9 ml to 114+/-7 ml (p <0.0001), Venous Filling Index from 4.9+/-0.5 ml/s to 2.3+/-0.2 ml/s ( p <0.0001), and Residual Volume Fraction from 42+/-3 ml to 30+/-2 ml ( p <0.0001). CONCLUSIONS: this study demonstrates that reflux in the GSV system is supported by a gradient of pressure between the anatomical point of reflux and the point of re-entry in the deep veins. Disconnection of the flow to the re-entry perforator without high ligation of the sapheno-femoral junction suppresses GSV reflux.

Analysis of Variance↗

Differential inhibition of human liver and duodenum sulphotransferase activities by quercetin, a flavonoid present in vegetables, fruit and wine.

1. Quercetin is a natural flavonoid present in vegetables, fruit and wine, and is known to inhibit sulphotransferase. Drugs are often taken orally and the intestinal mucosa is an early site of drug metabolism. The aims of this investigation were to study the inhibition of dopamine, (-)-salbutamol, minoxidil and paracetamol sulphation by quercetin in the duodenal mucosa and liver and to compare the IC50 in these tissues. 2. The rates (pmol min(-1) mg(-1)) of sulphation of 4-nitrophenol were 343+/-92 (liver) and 164+/-22 (duodenum; p = 0.031), of dopamine were 15+/-11 (liver) and 656+/-516 (duodenum; p = 0.049), of (-)-salbutamol 153+/-31 (liver) and 654+/-277 (duodenum; p = 0.018), of minoxidil were 156+/-47 (liver) and 105+/-7 (duodenum; n.s.), and of paracetamol were 229+/-86 (liver) and 328+/-187 (duodenum; n.s.). 3. The IC50 of quercetin for 4-nitrophenol was 48+/-11 nM (liver) and 56+/-1 nM (duodenum, n.s.), for dopamine was 5.7+/-0.7 microM (liver) and 170+/-12 microM (duodenum, p < 0.0001), for (-)-salbutamol was 54+/-4 nM (liver) and 16+/-8 microM (duodenum; p = 0.025), for minoxidil was 134+/-22 nM (liver) and 3+/-0.3 microM (duodenum, p = 0.013), and for paracetamol was 57+/-7 nM (liver) and 35+/-1 microM (duodenum; p = 0.0002). 4. Quercetin inhibited the sulphation of 4-nitrophenol, dopamine, (-)-salbutamol, minoxidil and paracetamol both in liver and duodenum. With dopamine, (-)-salbutamol, minoxidil and paracetamol as substrates, quercetin was a more potent inhibitor in the liver than the duodenum. Such a difference may reflect the different composition of sulphotransferase forms in the liver and duodenum.

Acetaminophen↗

Evaluation of inter-scorer and inter-laboratory reliability of the mouse epididymal sperm aneuploidy (m-ESA) assay.

The mouse epididymal sperm aneuploidy (mESA) assay using 3-chromosome fluorescence in situ hybridization (FISH) was recently developed for assessing the aneugenic potential of chemicals on male germ cells. This study was designed to identify the major technical factors that affect inter-scorer and inter-laboratory variability of the mESA assay. Two laboratories participated in this study (GSF and Lawrence Livermore National Laboratory, LLNL). Mice (102/ElxC3H/El) F(1) were exposed in one laboratory (GSF) to vinblastine (VBL; single intraperitoneal injection of 0, 0.5, 1.0 or 2.0 mg/kg), one of the 10 priority compounds of the Commission of the European Communities (CEC) Aneuploidy Program. Twenty-two days later the mESA assay was applied to analyze sperm aneuploidy. In the initial evaluation, small but statistically significant differences were found between the two laboratories in baseline frequencies and there was also disagreement in the determination of a VBL aneuploid effect. Therefore, experiments were conducted to identify the sources of the inter-laboratory differences and technical factors that affected assay reliability and the VBL study was repeated. A harmonization experiment was conducted by bringing the microscope scorers from both laboratories to the same site (LLNL) for a cross-training exercise. Following this exercise, a second group of VBL-treated and control mice were evaluated, and we concluded that VBL is not a sperm aneugen. Our research has identified scoring criteria as the major source of inter-laboratory variation and emphasizes the importance of strict technical controls for the mESA assay, including controlling slide preparations for treatment-induced reductions in sperm count, coding of slides and selection of statistical tests. These considerations are particularly important for the interpretation of small effects (< or =2-fold) on sperm aneuploidy. Our findings suggest that 2-fold differences in frequencies can result from differences among scorers, samples and treatment groups, and are readily within the normal variation for the mESA assay. Such small differences should be viewed with caution until independently confirmed.

Aneuploidy↗

Pharmacokinetic evaluation of oral levofloxacin in human immunodeficiency virus-infected subjects receiving concomitant antiretroviral therapy.

The purpose of this study was to evaluate the pharmacokinetics (PK) profile of oral levofloxacin in human immunodeficiency virus-positive patients in steady-state treatment with nelfinavir (NFV) or with efavirenz (EFV) and to determine the effects of levofloxacin on the PK parameters of these two antiretroviral agents. For levofloxacin, plasma samples were obtained at steady state during a 24-h dosing interval. Plasma NFV and EFV concentrations were evaluated before and after 4 days of levofloxacin treatment. Levofloxacin PK do not seem affected by NFV and EFV. There was no significant difference between NFV and EFV plasma levels obtained with and without levofloxacin.

Administration, Oral↗

Synthesis, structure, and antitumor activity of a novel tetranuclear titanium complex.

The coordination complex cyclo-tetrakis[bis(1-phenyl-3-methyl-4-benzoylpyrazolon-5-ato++ +)mu-o xotitanium(IV)] has been synthesized and characterized with IR and NMR spectroscopies and X-ray diffraction. The core of this species consists of an eight-membered Ti-mu-oxo ring with alternate short-long Ti-O bond lengths. Besides these two O ligands, each metal is bound octahedrally to four O atoms from two chelating 1-phenyl-3-methyl-4-benzoylpyrazolon-5-ato anions. Several sets of Ti-O bond lengths are present: the shortest are the two Ti-O(oxo) (which are cis to each other), the longest are the two Ti-O(acyl) (cis to each other), and the two Ti-O(pyrazolonato) (trans to each other) are intermediate. The beta-diketonate ligand asymmetry, a feature considered essential in other antitumor Ti compounds, induces the short-long Ti-O(oxo) sequence of bond lengths. The antitumor activity of this compound, encapsulated in a dipalmitoylphosphatidylcholine liposome, has been studied in vitro using TA-3 (mouse mammary adenocarcinoma), HEP-2 (human epithelial larynx carcinoma), and VERO (African green monkey kidney) cell lines and in vivo in CF-1 and AJ female mice ip inoculated with TA-3. In vitro cytotoxicity is greater for TA-3 than for HEP-2 and null for VERO cell lines. In vivo results show a marked increase in survival time (T/C = 293% for AJ and 208% for CF-1), whereas tumor weight decrease was observed for CF-1-treated mice. These results suggest the Ti complex-liposome system may be promising as an antitumor drug.

1,2-Dipalmitoylphosphatidylcholine↗

Bactericidal activity of levofloxacin and ciprofloxacin on clinical isolates of different phenotypes of Pseudomonas aeruginosa.

Levofloxacin has been reported to have in vitro activity against both gram-positive and gram-negative bacteria. A recent survey carried out at our Institution showed clinical isolates of Pseudomonas aeruginosa to be more susceptible to levofloxacin than to ciprofloxacin. The in vitro activity of the two fluoroquinolones was evaluated further by looking at their bactericidal activity against two strains of each of the following antibio-phenotypes of P. aeruginosa: levofloxacin- and ciprofloxacin-susceptible, levofloxacin-susceptible/ciprofloxacin-resistant, levofloxacin-susceptible/ciprofloxacin-susceptible and ceftazidime-resistant, (National Committee for Clinical Laboratory Standards susceptibility breakpoints were used). MIC and MBC values were measured and time-kill experiments were carried out. Drugs were used at susceptibility or resistance breakpoint concentrations in the time-kill experiments and results were recorded over 12 h in an attempt to link in vitro results with the clinical situation The polypeptide profiles of outer membrane preparations of the six strains were examined by gel electrophoresis. Levofloxacin was shown to be more bactericidal than ciprofloxacin in the time-kill experiments. No differences were observed between the outer membrane proteins of the six strains. Levofloxacin showed greater bactericidal activity against P. aeruginosa clinical isolates than ciprofloxacin.

Anti-Infective Agents↗

Levofloxacin in vitro activity and time-kill evaluation of Stenotrophomonas maltophilia clinical isolates.

The in vitro activity of levofloxacin and eight other antimicrobial agents against 60 clinical isolates of Stenotrophomonas maltophilia was determined by an agar dilution method using 10(4) and 10(6) cfu/spot inocula. At the lower inoculum, 85.0% of the isolates were susceptible to levofloxacin but only 58.3% were susceptible to ofloxacin; at the higher inoculum, 78.3% were susceptible to levofloxacin and 36.7% to ofloxacin. In time-kill studies, levofloxacin exerted bactericidal activity within 4 h. With ofloxacin and ciprofloxacin bacterial regrowth was observed after 8 h. Levofloxacin may represent an alternative drug in the treatment of infections caused by S. maltophilia.

Anti-Infective Agents↗

In vitro activity of ketolides telithromycin and HMR 3004 against italian isolates of Streptococcus pyogenes and Streptococcus pneumoniae with different erythromycin susceptibility.

Two ketolides, telithromycin and HMR 3004, were evaluated for their in vitro activity against erythromycin-susceptible and -resistant strains of Streptococcus pyogenes and Streptococcus pneumoniae. On the basis of their resistance to macrolide, lincosamide and streptogramin (MLS) antibiotics, erythromycin-resistant test strains were assigned to the constitutive resistance (cMLS) phenotype, the inducible resistance (iMLS) phenotype or the M phenotype. iMLS S. pyogenes strains were further subdivided into the three recently described subtypes iMLS-A, -B and -C. Telithromycin and HMR 3004 were uniformly and highly active against pneumococci (regardless of their susceptibility or resistance to erythromycin and/or penicillin), erythromycin-susceptible S. pyogenes and erythromycin-resistant S. pyogenes strains of the M phenotype (in which resistance is mediated by an efflux system) or iMLS-B or -C phenotype (in which resistance is mediated by a methylase encoded by the ermTR gene). Both ketolides were less active against erythromycin-resistant S. pyogenes strains with the cMLS phenotype or the iMLS-A subtype (where resistance is mediated by a methylase encoded by the ermAM gene), these strains ranging in phenotype from the upper limits of susceptibility to low-level resistant.

Anti-Bacterial Agents↗

17beta-estradiol corrects hemostasis in uremic rats by limiting vascular expression of nitric oxide synthases.

Conjugated estrogens shorten the prolonged bleeding time in uremic patients and are similarly effective in a rat model of uremia. We have previously demonstrated that the shortening effect of a conjugated estrogen mixture or 17beta-estradiol on bleeding time was abolished by the nitric oxide (NO) precursor L-arginine, suggesting that the effect of these drugs on hemostasis in uremia might be mediated by changes in the NO synthetic pathway. The present study investigated the biochemical mechanism(s) by which conjugated estrogens limit the excessive formation of NO. 17beta-estradiol (0.6 mg/kg), given to rats made uremic by reduction of renal mass, significantly reduced bleeding time within 24 h and completely normalized plasma concentrations of the NO metabolites, nitrites and nitrates, and of NO synthase (NOS) catalytic activity, determined by NADPH-diaphorase staining in the thoracic aorta. Endothelial NOS (ecNOS) and inducible NOS (iNOS) immunoperoxidase staining in the endothelium of uremic aortas of untreated rats was significantly more intense than in control rats, while in uremic rats receiving 17beta-estradiol staining was comparable to controls. Thus 17beta-estradiol corrected the prolonged bleeding time of uremic rats and fully normalized the formation of NO by reducing the expression of ecNOS and iNOS in vascular endothelium. These results provide a possible biochemical explanation of the well-known effect of estrogens on primary hemostasis in uremia, in experimental animals and humans.

Animals↗

Absence of selection against aneuploid mouse sperm at fertilization.

Is there selection against aneuploid sperm during spermatogenesis and fertilization? To address this question, we used male mice doubly heterozygous for the Robertsonian (Rb) translocations Rb(6. 16)24Lub and Rb(16.17)7Bnr, which produce high levels of sperm aneuploid for chromosome 16, the mouse counterpart of human chromosome 21. The frequencies of aneuploid male gametes before and after fertilization were compared by analyzing approximately 500 meiosis II spermatocytes and approximately 500 first-cleavage zygotes using fluorescence in situ hybridization with a DNA painting probe mixture containing three biotin-labeled probes specific for chromosomes 8, 16, and 17 plus a digoxigenin-labeled probe specific for chromosome Y. Hyperhaploidy for chromosome 16 occurred in 20.0% of spermatocytes and in 21.8% of zygotes. Hypohaploidy for chromosome 16 occurred in 17.0% and 16.7% of spermatocytes and zygotes, respectively. In addition, there was no preferential association between chromosome 16 aneuploidy and either of the sex chromosomes, nor was there an elevation in aneuploidy for chromosomes not involved in the Rb translocations. These findings provide direct evidence that there is no selection against aneuploid sperm during spermiogenesis, fertilization, and the first cell cycle of zygotic development.

Aneuploidy↗

Comparative bacteriostatic and bactericidal activities of cefodizime against Borrelia burgdorferi sensu lato.

The MIC and MSC (minimum spirocheticidal concentration) and killing rate for Borrelia burgdorferi, the etiological agent of Lyme disease, were assessed for cefodizime in comparison with ceftriaxone, minocycline, azithromycin, roxithromycin, and ciprofloxacin. The range of cefodizime MICs was greater than those of azithromycin and roxithromycin but comparable to those of ceftriaxone and minocycline. The MSCs were 1 to 2 dilutions higher than the MICs of all of the tested compounds. The killing curves of cefodizime and ceftriaxone showed parallel courses. In conclusion, cefodizime exerted an activity comparable to that of ceftriaxone against B. burgdorferi.

Borrelia burgdorferi Group↗

Italian survey on comparative levofloxacin susceptibility in 334 clinical isolates of Pseudomonas aeruginosa.

A national survey on susceptibility patterns of 334 Pseudomonas aeruginosa isolates from intensive care units and hematology and oncology wards from 13 Italian hospitals compared the in vitro activity of levofloxacin, an injectable oral fluoroquinolone, to those of ciprofloxacin, ofloxacin, ceftazidime, imipenem, amikacin, and gentamicin. Amikacin and imipenem had the best susceptibility profiles. The activity of levofloxacin was superior to those of the other quinolones and was comparable to that of ceftazidime. The effect of levofloxacin in vitro on P. aeruginosa clinical isolates suggests that further clinical investigations are warranted.

Anti-Infective Agents↗