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Biomedical subjects

F Marchetti

Publications and source records attributed to F Marchetti.

At least 19 recordsLinked to original sources

The effects of male age on sperm DNA damage in healthy non-smokers.

BACKGROUND: The trend for men to have children at older age raises concerns that advancing age may increase the production of genetically defective sperm, increasing the risks of transmitting germ-line mutations. METHODS: We investigated the associations between male age and sperm DNA damage and the influence of several lifestyle factors in a healthy non-clinical group of 80 non-smokers (mean age: 46.4 years, range: 22-80 years) with no known fertility problems using the sperm Comet analyses. RESULTS: The average percentage of DNA that migrated out of the sperm nucleus under alkaline electrophoresis increased with age (0.18% per year, P = 0.006), but there was no age association for damage measured under neutral conditions (P = 0.7). Men who consumed >3 cups coffee per day had approximately 20% higher percentage tail DNA under neutral but not alkaline conditions compared with men who consumed no caffeine (P = 0.005). CONCLUSIONS: Our findings indicate that (i) older men have increased sperm DNA damage associated with alkali-labile sites or single-strand DNA breaks and (ii) independent of age, men with substantial daily caffeine consumption have increased sperm DNA damage associated with double-strand DNA breaks. DNA damage in sperm can be converted to chromosomal aberrations and gene mutations after fertilization, increasing the risks of developmental defects and genetic diseases among offspring.

Adult↗

Efficacy of the combination of levofloxacin plus ceftazidime in the treatment of hospital-acquired pneumonia in the intensive care unit.

To investigate the efficacy and tolerability of treatment with a combination of levofloxacin and ceftazidime in Gram-negative hospital-acquired pneumonia (HAP) in the Intensive Care Unit (ICU), we performed a prospective, open-label, non-comparative, 1-year study in an Italian ICU. Patients received levofloxacin 500 mg twice a day intravenously plus ceftazidime 2 g three times a day intravenously for 7-14 days. Primary efficacy variables were clinical and microbiological responses at test-of-cure visit. Twenty-one patients were enrolled. Pseudomonas aeruginosa and Klebsiella pneumoniae were the most frequently identified pathogens. Clinical success was achieved in 17/21 clinically evaluable patients (81%) and in 12/15 microbiologically evaluable patients (80%). Regarding only the group with ventilator-associated pneumonia, cure was achieved in 10/14 clinically evaluable patients (71%) and in 11/14 microbiologically evaluable patients (79%). Therapy was well tolerated. We conclude that this combination regimen is safe and clinically and microbiologically efficacious in the treatment of Gram-negative HAP.

Aged↗

Quantitative effects of male age on sperm motion.

BACKGROUND: Semen quality is associated with fertility status, but there is little quantitative information on risk factors that affect semen quality, especially in non-clinical populations. Advancing male age has been associated with a decline in semen quality, with the largest effect being on sperm motility. However, there is little quantitative data on the specific components of sperm motion that are affected by male age. METHODS: We performed linear regression analyses of 14 aspects of semen quality measured by computer-assisted semen analysis (CASA) in a non-clinical cohort of 90 non-smoking men, aged 22-80 years, who had no history of infertility or reproductive problems. RESULTS: We found age-associated declines in CASA-determined motility (% motile, 0.8% per year; % progressively motile, 0.9% per year; % rapidly motile, 0.4% per year, P <or= 0.001) and three quantitative aspects of sperm motion [linearity (LIN), 0.2% per year; straight line velocity (VSL), 0.2% per year, and average path velocity (VAP), 0.3% per year, P < 0.05], with no evidence for age thresholds and no significant association with abstinence duration. Age was not significantly associated with amplitude of lateral head (ALH) displacement, beat cross frequency (BCF) and nuclear elongation or size. CONCLUSIONS: Quantitative analysis of sperm motion indicates that as men age, they produce fewer motile sperm, which are able to travel less along a linear path, thus covering less forward distance per unit time. These findings may have fertility implications for men who choose to delay fatherhood.

Adult↗

Substrate reduction therapy in the infantile form of Tay-Sachs disease.

Substrate reduction therapy (SRT) with miglustat has been proposed for treatment of some lysosomal storage disorders. Based on the positive experience in Gaucher disease and experimental data in Tay-Sachs (TSD) and Sandhoff animal models, the authors investigated the clinical efficacy of SRT in two patients with infantile TSD. SRT could not arrest the patients' neurologic deterioration. However, a significant drug concentration in CSF as well as macrocephaly prevention were observed.

1-Deoxynojirimycin↗

Incidence of surgical site infections in general surgery in Italy.

BACKGROUND: Epidemiological study to determine surgical site infection (SSI) rates in surgical patients in Italy using the National Nosocomial Infections Surveillance system (NNIS), to monitor current surgical antimicrobial prophylaxis, and to identify possible modifiable risk factors for SSI. MATERIALS AND METHODS: Thirty-two general surgeries participated in the study. Main criteria for site inclusion were: > 20 operations per week and amoxycillin/clavulanate among prophylactic options. Each patient operated from April 1st to May 30th 2002 was surveyed until 30 days after the operation. SSI cumulative incidence rates and 95% confidence intervals (95%CI) were calculated. RESULTS: During the study period, 3,066 surgical procedures were performed in 2,972 patients. A total of 158 SSI were diagnosed in 154 patients: 96 (62.3%) were at superficial incision, 23 (14.9%) were at deep incision and 35 (22.7%) were at organ-space site. Incidence of SSI every 100 operations was 5.2% (95% CI 4.4-6.0). Of the 2,437 operated patients with clean or elective clean/contaminated or contaminated surgical procedure, 2,105 (86.4%) received antimicrobial prophylaxis, mainly amoxicillin/clavulanate (28.3%) and ceftizoxime (11.4%). Pre-operative hospital stay > or = 48 h, diabetes, obesity, and HIV/AIDS infection were statistically significantly associated with increased risk of SSI. CONCLUSIONS: The SSI rates found are comparable with European studies and can be a benchmark for national incidence data and for inter- and intra-hospital SSI rate comparisons.

Adolescent↗

Transrectal colour Doppler contrast sonography in the diagnosis of local recurrence after radical prostatectomy--comparison with MRI.

OBJECTIVE: To assess the usefulness of colour power-Doppler transrectal sonography before/after contrast agent in the detection of local recurrence in patients with rising prostate-specific antigen values after radical prostatectomy and to compare with magnetic resonance imaging . MATERIALS AND METHODS: 18 patients with rising prostate-specific antigen values after prostatectomy underwent digital rectal examination, bone scintigraphy, magnetic resonance imaging, transrectal colour power-Doppler sonography before/after contrast agent, and transrectal sonography-guided biopsy. Sensitivity, specificity, accuracy, positive and negative predictive values were calculated. Results were correlated using McNemar binomial 2-tailed P-test. RESULTS: Baseline and contrast-enhanced transrectal colour power-Doppler sonography and contrast-enhanced magnetic resonance imaging identified recurrent disease in 6, 10 and 10 patients, respectively. Biopsy confirmed recurrence in 10 patients, but was positive also in 2 additional patients who were negative at contrast-enhanced transrectal colour power-Doppler sonography and contrast-enhanced magnetic resonance imaging. The remaining 6 patients were negative also at diagnostic imaging and biopsy after 30 days. Grey-scale transrectal sonography values were: sensitivity 91.7 %, specificity 66 %, PPV 91.6 %, NPV 40 %. Baseline colour power-Doppler transrectal sonography values were: sensitivity 38.5 %, specificity 85 %, diagnostic accuracy 50 %, PPV 83.3 %, NPV 33.3 %. Contrast enhanced colour power-Doppler transrectal sonography and magnetic resonance imaging values were: sensitivity 76.9 %, specificity 100 %, diagnostic accuracy 83.3 %, PPV 100 %, NPV 62.5 %. CONCLUSION: Contrast-enhanced transrectal colour power-Doppler sonography increases specificity in the detection of local recurrence after prostatectomy. Magnetic resonance imaging yields equivalent accuracy. Biopsy remains the diagnostic gold standard, but the use of imaging methods may reduce the number of biopsies.

Aged↗

A pilot study on prevention of catheter-related urinary tract infections with fluoroquinolones.

The objective of this multicenter, randomized, controlled, parallel group trial was to evaluate the efficacy of levofloxacin 250 mg oral, once daily (LVFX), placebo one tablet oral once daily (Placebo [P] group) and ciprofloxacin (CPFX) 500 mg oral, twice daily (single blind), prophylaxis in preventing bacteriuria (> or = 10(3) CFU/ml) in post-surgical catheterized patients. In the modified intention-to-treat (M-ITT) population of the 82 enrolled patients, negative bacteriuria was observed in 92% of LVFX group, in 80% of P group and in 100% of CPFX group while in the per-protocol (PP) population figures were: 100%, 86.4% and 100% respectively. Only one symptomatic urinary tract infection and one surgical wound infection were observed in the P group. Both drugs were well tolerated, showing a safety profile comparable to placebo. The high frequency of negative bacteriuria in the placebo group sounds encouraging as it underlines that the adoption of closed urinary drainage system catheters in hospital setting may reduce the frequency of hospital-acquired infections.

Administration, Oral↗

Mechanisms and chemical induction of aneuploidy in rodent germ cells.

The objective of this review is to suggest that the advances being made in our understanding of the molecular events surrounding chromosome segregation in non-mammalian and somatic cell models be considered when designing experiments for studying aneuploidy in mammalian germ cells. Accurate chromosome segregation requires the temporal control and unique interactions among a vast array of proteins and cellular organelles. Abnormal function and temporal disarray among these, and others to be identified, biochemical reactions and cellular organelles have the potential for predisposing cells to aneuploidy. Although numerous studies have demonstrated that certain chemicals (mainly those that alter microtubule function) can induce aneuploidy in mammalian germ cells, it seems relevant to point out that such data can be influenced by gender, meiotic stage, and time of cell-fixation post-treatment. Additionally, a consensus has not been reached regarding which of several germ cell aneuploidy assays most accurately reflects the human condition. More recent studies have shown that certain kinase, phosphatase, proteasome, and topoisomerase inhibitors can also induce aneuploidy in rodent germ cells. We suggest that molecular approaches be prudently incorporated into mammalian germ cell aneuploidy research in order to eventually understand the causes and mechanisms of human aneuploidy. Such an enormous undertaking would benefit from collaboration among scientists representing several disciplines.

Aneuploidy↗

In vitro and in vivo synergy of levofloxacin or amikacin both in combination with ceftazidime against clinical isolates of Pseudomonas aeruginosa.

The aim of the present study was to explore the antibacterial activity of the levofloxacin (LVX) and ceftazidime (CAZ) combination compared with the amikacin (AMK)/CAZ combination against Pseudomonas aeruginosa. Minimum inhibitory concentrations (MICs) were determined according to NCCLS. FIC indices (Fl) were calculated by the checkerboard technique. CAZ combined with LVX or AMK yielded Fls indicating synergism (Fl < or = 0.5) for 71/102 (69.6%) and 81/102 (79.4%) (p = 0.108), indifference (FI > 0.5-4) for 24/102 (23.5%) and 12/102 (11.7%) (p = 0.027), and antagonism (Fl > 4) for 7/102 (6.8%) and 9/102 (8.8%) (p = 0.602) strains, respectively. In vivo, CAZ/LVX was as bactericidal as CAZ/AMK combination. Our results support the potential role of LVX as an alternative to AMK in the combination therapy with CAZ in the treatment of P. aeruginosa severe infections. Anyway, further investigations and clinical trials are awaited until any definitive conclusions can be drawn.

Amikacin↗

Prevalence and clinical management of complicated urinary tract infections in Italy: a prospective multicenter epidemiological study in urological outpatients.

The objectives of the study were to evaluate the prevalence of complicated urinary tract infections among Italian patients attending the urologist's office, to describe the frequency of different complication factors, the encountered bacterial pathogens and the clinical attitude of urologists in management of complicated urinary tract infections (CUTIs). The study was a prospective, multicenter study which was undertaken by office urologists throughout Italy. During the May-June 2002 timeframe, the prevalence of each urologist's diagnosis of CUTIs was noted for a 4-week slot. The prevalence of CUTIs in over 13,000 patients observed was 10.8% (n = 1201), with a trend (not statistically significant) of higher figures in the South/Islands (12.2%) with respect to Center (11.4%) or North (8.7%) of Italy. We have confirmed the significant relevance of CUTI among the Italian patients attending the urologist office and the clinical data collected may contribute to improve the diagnosis and empiric therapy of complicated urinary tract infections.

Adult↗

Detection of structural and numerical chromosomal abnormalities by ACM-FISH analysis in sperm of oligozoospermic infertility patients.

BACKGROUND: Modern reproductive technologies are enabling the treatment of infertile men with severe disturbances of spermatogenesis. The possibility of elevated frequencies of genetically and chromosomally defective sperm has become an issue of concern with the increased usage of ICSI, which can enable men with severely impaired sperm production to father children. Several papers have been published reporting aneuploidy in oligozoospermic patients, but relatively little is known about chromosome structural aberrations in the sperm of these patients. METHODS: We examined sperm from infertile, oligozoospermic individuals for structural and numerical chromosomal abnormalities using a multicolour ACM fluorescence in situ hybridization (FISH) assay that utilizes DNA probes specific for three regions of chromosome 1 to detect human sperm that carry numerical chromosomal abnormalities plus two categories of structural aberrations: duplications and deletions of 1pter and 1cen, and chromosomal breaks within the 1cen-1q12 region. RESULTS: There was a significant increase in the average frequencies of sperm with duplications and deletions in the infertility patients compared with the healthy concurrent controls. There was also a significantly elevated level of breaks within the 1cen-1q12 region. There was no evidence for an increase in chromosome 1 disomy, or in diploidy. CONCLUSIONS: Our data reveal that oligozoospermia is associated with chromosomal structural abnormalities, suggesting that oligozoospermic men carry a higher burden of transmissible, chromosome damage. The findings raise the possibility of elevated levels of transmissible chromosomal defects following ICSI treatment.

Adult↗

Role of human-tissue transglutaminase IgG and anti-gliadin IgG antibodies in the diagnosis of coeliac disease in patients with selective immunoglobulin A deficiency.

BACKGROUND: Selective IgA deficiency is associated with coeliac disease, and studies have shown an increased prevalence of coeliac disease in these patients ranging from 0.71 to 30.7%, depending on the test used for screening. AIMS: To determine the sensitivity of IgG anti-gliadin-antibodies and of IgG human-tissue-transglutaminase for diagnosing coeliac disease and assessing its prevalence in subjects with IgA deficiency. SUBJECTS: We tested serum samples from 126 IgA-deficient children (66 female, median age: 10.8 years). METHODS: All samples were analysed to measure IgG anti-gliadin-antibodies and IgG anti-human-tissue-transglutaminase. Patients testing positive to either test underwent intestinal biopsy. Subjects testing positive for IgG anti-human-tissue-transglutaminase underwent genetic testing for the human leucocyte antigen heterodimer. RESULTS: Twenty-seven of 126 subjects tested positive for IgG anti-gliadin-antibodies (five of whom tested positive also for IgG anti-human-tissue-transglutaminase) and 18 (including the aforementioned five) for IgG anti-human-tissue-transglutaminase. Intestinal biopsy was performed in 37 of the 40 patients who tested positive (three subjects refused). Eleven had positive intestinal biopsies all of whom tested positive for IgG anti-human-tissue-transglutaminase, but only five of these tested positive also for IgG anti-gliadin-antibodies. All 22 patients testing positive for anti-gliadin-antibody alone had normal intestinal mucosa. All the patients who tested positive for IgG anti-human-tissue-transglutaminase and underwent genetic screening (15/18) had the coeliac-related human leucocyte antigen. Overall, coeliac disease was diagnosed in 11 of the 126 subjects with IgA deficiency (8.7%). CONCLUSIONS: The prevalence of coeliac disease in subjects with total IgA deficiency was 8.7%. Assay of IgG anti-human-tissue-transglutaminase can be recommended for screening coeliac disease in IgA-deficient subjects.

Adolescent↗

Antimicrobial susceptibility profiles of Pseudomonas aeruginosa and Staphylococcus aureus isolated in Italy from patients with hospital-acquired infections.

Here we report the results of the Sentinel Project 2000 and give the susceptibility to selected antibiotics of 108 Pseudomonas aeruginosa and 108 Staphylococcus aureus strains isolated from patients with hospital-acquired lower respiratory tract infections. In P. aeruginosa, susceptibility to aztreonam and ciprofloxacin was lower than 50%. The resistance rate to beta-lactams was up to 25% and to amikacin 15.7%. Blood isolates showed 80-90% susceptibility to all antibiotics tested except for aztreonam and tobramycin. Overall, oxacillin resistance in S. aureus was 45%, reaching 64.3% among the bronchoalveolar lavage isolates, and 42.9% among the blood isolates. These worrying results confirm the need for continuous monitoring of bacterial resistance trends in the hospitals, mainly in ICUs.

Anti-Bacterial Agents↗

Proton pump inhibitors in children: a review.

Proton pump inhibitors are often used to treat disorders associated with gastric hypersecretion in children, despite the lack of pediatric formulations. They are highly effective in the treatment of ulcers, gastro-esophageal reflux disorders and hypersecretory diseases. They provide a high level of gastric acid inhibition with few adverse effects. The aim of this article is to review the available studies concerning the use of proton pump inhibitors in pediatric populations and to point out: indications for use in children, optimal dosage, risk of adverse effects and consequences of the mechanism of action, and drug interactions. We performed a Medline and Embase search of publications printed from January 1980 to December 2002 concerning the use of proton pump inhibitors in children. We consider the available randomised controlled trials and several other uncontrolled studies conducted in the pediatric population, including all available information concerning the pediatric use of proton pump inhibitors. In children as well as in adults, there are clinical conditions (i.e., severe esophagitis or eradication of Helicobacter pylori) in which proton pump inhibitors offer clear advantages over histamine-2 receptor antagonists. The relatively common use of acid inhibitors (proton pump inhibitors and histamine-2 receptor antagonists) in uncomplicated gastro-esophageal reflux disorders or in the prevention of non-steroidal anti-inflammatory drugs/steroid gastropathy is often unsubstantiated and should be limited to very specific situations. Multicentre randomised controlled studies are needed to better define the efficacy profile, the optimal dosage with respect to the different indications and the safety profile for chronic therapy of proton pump inhibitors in children.

2-Pyridinylmethylsulfinylbenzimidazoles↗