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Biomedical subjects

G Gatti

Publications and source records attributed to G Gatti.

At least 19 recordsLinked to original sources
PubMed2006

Early detection of cancer: ideas for a debate.

Even if the overall number of cancer is increasing, the mortality has started to decrease in the Western World. The role of early detection in this decrease is a matter of debate. To assess its impact on mortality it is important to distinguish between diagnosis of cancer in symptomatic patients, and early detection in asymptomatic individuals who may self-refer or who may be offered ad hoc or systematic screening. The policies for early detection and screening vary greatly between European countries, despite many similarities in their cancer burden, and this partly reflects the uncertainties surrounding asymptomatic testing for cancer. A Task Force of European expert, held in Azzate (VA), Italy, established to address these issues, acknowledged the need for more research in the field of individual risk assessment since general statistics are more and more perceived as inadequate to design personal early detection plans. The group also recognised that combinations of early detection and screening will enforce the effectiveness of new treatments in curbing mortality curves, although policies will vary with different cancers.

Breast Neoplasms↗
PubMed2006

Penetration of didanosine in semen of HIV-1-infected men.

OBJECTIVES: The disposition of antiretroviral agents into genital tissue and fluids is one of the factors implicated in the control of viral replication within the male genital tract and should be an objective of highly active antiretroviral therapy. We have investigated didanosine penetration in seminal plasma of 16 HIV-infected patients. PATIENTS AND METHODS: A total of 16 patients on didanosine (200 mg every 12 h or 400 mg once daily) participated in the pharmacokinetic study. After the didanosine morning dose, peripheral blood plasma and semen plasma were collected within the intervals 0-4, 4-8 and 8-12 h in the twice-daily regimen and 0-4, 4-12 and 12-24 h in the once-daily regimen. RESULTS: Within each sampling time interval didanosine concentrations in seminal plasma were higher than in blood. The interquartile range of concentrations in seminal plasma was 292-1217 ng/mL, compared with 50-150 ng/mL in blood plasma. Didanosine could be detected in 14 of the 16 semen samples analysed and in 8 of the 16 blood samples. CONCLUSIONS: We have demonstrated that didanosine penetrates into the seminal plasma in higher concentrations than in blood plasma.

Adult↗
PubMed2006

Breast conservative treatment in association with implant augmentation and intraoperative radiotherapy.

After conservative treatment for small breast cancer the use of breast implants is controversial due to the negative effects of external conventional radiotherapy on soft tissues and the risk of capsular contracture. The literature reports several cases of unsuccessful breast augmentation due to implant displacement, a high percentage of capsular contracture and postoperative complications. We report the case of a 47-year-old woman with a small tumour between the inner quadrants of the left breast. She underwent quadrantectomy and sentinel node biopsy and intraoperative radiotherapy (IORT) of the target zone. Simultaneously, she received a bilateral augmentation mammaplasty. One year later we observed no evidence of local recurrence, no local fibrosis and radiodistrophy. Cosmetic results are excellent and the patient is very satisfied. The surgical technique and the possible advantage of such a procedure are also discussed.

Breast Implants↗
PubMed2006

Rapamycin induces a caspase-independent cell death in human monocytes.

The immunosuppressive activity of rapamycin (RAPA) and its efficacy as an anti-rejection agent in organ transplantation have been ascribed principally to its anti-proliferative effects on T cells, while the activity on monocytes is partially unknown. In vitro, RAPA reduced monocyte survival by inducing a caspase-independent cell death. RAPA-induced monocyte cell death (RAPA-CD) was impeded by activation of granulocyte macrophage-colony stimulating factor family receptors or toll-like receptor 4, and by exposure to inflammatory cytokines. In vivo, in patients who received RAPA monotherapy as part of pre-conditioning for islet transplantation, RAPA affected survival of myeloid lineage cells. In the peripheral blood, CD33(+) and CD14(+) cells decreased, whereas lymphocytes appeared unaffected. In the bone marrow, myeloid precursors such as CD15(+) and CD15(+)/CD16(+) were selectively and significantly decreased, but no major cytotoxic effects were observed. The RAPA-CD suggests a dependence of monocytes on mammalian target of RAPA pathways for nutrient usage, and this feature implies that RAPA could be selectively useful as a treatment to reduce monocytes or myeloid cells in conditions where these cells negatively affect patient, suggesting a potential anti-inflammatory action of this drug.

Antigens, CD↗
PubMed2005

Modulation of vitellogenin synthesis through estrogen receptor beta-1 in goldfish (Carassius auratus) juveniles exposed to 17-beta estradiol and nonylphenol.

Many synthetic chemicals, termed xenoestrogens, have been shown to interact as agonists with the estrogen receptor (ER) to elicit biological responses similar to those of natural hormones. To date, the regulation of vitellogenesis in oviparous vertebrates has been widely used for evaluation of estrogenic effects. Therefore, Carassius auratus juveniles were chosen as a fish model for studying the effects of estradiol-17beta and different concentrations (10(-6) and 10(-7) M) of 4-nonylphenol (4-NP) on the expression of liver ERbeta-1 subtype; plasma vitellogenin and sex steroids (androgens and estradiol-17beta) were also evaluated together with the bioaccumulation process, through mass-spectrometry. C. auratus is a species widespread in the aquatic environment and, on the toxicological point of view, can be considered a good "sentinel" species. Juveniles of goldfish were maintained in tanks with only tap water or water with different concentrations (10(-6) and 10(-7) M) of 4-nonylphenol (4-NP), or 10(-7) M of estradiol-17beta. After 3 weeks of treatment, animals were anesthetized within 5 min after capture, and blood was immediately collected into heparinized syringes by cardiac puncture and stored at -70 degrees C; the gonads were fixed, then frozen and stored at -70 degrees C; the whole fish, liver, and muscle tissues were harvested and immediately stored at -70 degrees C for molecular biology experiments and bioaccumulation measurements. The estrogenic effects of 4-NP were evidenced by the presence of plasma vitellogenin in juveniles exposed both to estradiol-17beta and the two doses of 4-NP; moreover, exposure to 4-NP also increased aromatization of androgens, as suggested by decreasing androgens and increasing estradiol-17beta plasma levels. The changes of these parameters were in agreement with the increasing transcriptional rate of ERbeta-1 mRNA in the liver, demonstrating that both estradiol-17beta and 4-NP modulate the vitellogenin rate through interaction with the ERbeta-1 subtype. The present study also suggests that 4-NP at the concentration of 10(-6) M bioaccumulates in the liver.

Androgens↗
PubMed2005

Intraoperative electron beam radiotherapy (ELIOT) to the breast: a need for a quality assurance programme.

Intraoperative radiotherapy (IORT) is a technique in which a high, single-fraction radiation dose is delivered directly to the tumour bed during a surgical intervention, after the removal of a neoplastic mass. IORT has been recently used in early stage cancer as an exclusive radiation modality, rather than as a boost, especially for breast tumours, in particular at the European Institute of Oncology in Milan, where the technique has been called electron intraoperative therapy (ELIOT). Our studies on more than 1000 patients have demonstrated the feasibility of the technique and it is expected that its application will become more widespread in the immediate future. It is important to emphasise that ELIOT relies not only on new technological developments, but also on a multidisciplinary team with clear roles and responsibilities, the establishment of a programme of quality assurance with appropriate guidelines and a comprehensive staff development programme.

Breast Neoplasms↗
PubMed2005

Avoiding axillary dissection in breast cancer surgery: a randomized trial to assess the role of axillary radiotherapy.

BACKGROUND: The need to dissect axillary nodes in patients with early breast cancer and clinically negative axilla remains controversial. The aim of the study was to assess the role of axillary radiotherapy (RT) in reducing axillary metastases in patients with early breast cancer who did not receive axillary dissection. PATIENTS AND METHODS: From 1995 to 1998, 435 patients over 45 years old with breast cancer up to 1.2 cm and no palpable axillary nodes were randomized 214 to breast conservation without axillary treatment and 221 to breast conservation plus axillary RT. RESULTS: After a median follow-up of 63 months, overt axillary metastases were fewer than expected: three cases in the no axillary treatment group (1.5%) and one in the RT group (0.5%). Expected cases were 43 in the no axillary treatment group and 10 in the RT group. Rates of distant metastases and local failures were low, and 5-year disease free survival was 96.0% (95% confidence interval, 94.1%-97.9%) without significant differences between the two arms. CONCLUSIONS: This study suggests that occult axillary metastases might never become clinically overt and axillary dissection might be avoided in patients with small carcinomas and a clinically negative axilla. Axillary RT seems to protect the patients from axillary recurrence almost completely.

Aged↗
PubMed2005

Development of axillary surgery in breast cancer.

Axillary surgery is a critical part of the treatment of breast carcinoma: its importance is related to the staging of disease, prescription of adjuvant therapy and prognosis. For years, complete axillary dissection has remained the standard approach to breast cancer lymphatic staging; its value is still high, but the development of sentinel-node biopsy has significantly changed the indication of the procedure. We discuss the evolution of axillary surgery in breast cancer.

Axilla↗
PubMed2004

Possible role of nitric oxide in the biology of breast carcinoma: review of the available literature.

Nitric oxide was studied to investigate its possible involvement in the promotion of breast carcinoma: both the development of the primary tumour and the process of metastasis seem to be influenced by the presence and the amount of nitric oxide. We review the available literature on this topic, which seems to suggest an influence of nitric oxide on the cancer cell biology in breast carcinoma, but the argument is still controversial. More studies are needed to clarify the sequence of events and the real impact of nitric oxide on the behaviour of the disease.

Breast Neoplasms↗
PubMed2004

Updated European recommendations for the clinical use of HIV drug resistance testing.

In most European countries, HIV drug resistance testing has become a routine clinical tool. However, its practical implementation in a clinical context is demanding. The European HIV Drug Resistance Panel was established to make recommendations to clinicians and virologists on this topic and to propose quality control measures. The panel recommends resistance testing for the following indications: i) drug-naive patients with acute or recent infection; ii) therapy failure, including suboptimal treatment response, when treatment change is considered; iii) pregnant HIV-1-infected women and paediatric patients with detectable viral load when treatment initiation or change is considered; and iv) genotype source patient when post-exposure prophylaxis is considered. In addition, for drug-naive patients with chronic infection in whom treatment is to be started, the panel suggests that resistance testing should be strongly considered and recommends testing the earliest sample for drug resistance if suspicion of resistance is high or prevalence of resistance in this population exceeds 10%. The panel does not favour genotyping over phenotype, however it is anticipated that genotyping will be used more often because of its greater accessibility, lower cost and faster turnaround time. For the interpretation of resistance data, clinically validated systems should be used to the greatest extent possible. It is mandatory that laboratories performing HIV resistance tests take regular part in quality assurance programs. Similarly, it is necessary that HIV clinicians and virologists take part in continuous education and meet regularly to discuss problematic clinical cases. Indeed, resistance test results should be used in the context of all other clinically relevant information for predicting therapy response. The panel also encourages the timely collection of epidemiological information to estimate the impact of transmission of resistant HIV and the prevalence of HIV-1 non-B subtypes in the different European countries.

Anti-HIV Agents↗
PubMed2003

Progressive multifocal leukoencephalopathy: diffusion-weighted imaging and pathological correlations.

We examined MRI of two patients with progressive multifocal leukoencephalopathy (PML), including diffusion-weighted imaging (DWI), with calculation of apparent diffusion coefficients (ADC). The pathology findings of one patient were compared with those of MRI. The lesions had different ADC and DWI appearances, depending on the stage of the disease. Newer lesions and the advancing edge of large lesions had normal-to-low ADC and gave high signal on DWI. Older lesions and the centre of large lesions had increased ADC and gave low signal. High signal on DWI and low ADC mark the regions of active infection and cell swelling, distinguishing them from areas of reparative gliosis.

Adult↗
PubMed2003

Pharmacokinetics and pharmacodynamics of nelfinavir administered twice or thrice daily to human immunodeficiency virus type 1-infected children.

We studied the pharmacokinetics and pharmacodynamics of nelfinavir administered 2 or 3 times per day to human immunodeficiency virus type 1 (HIV-1)-infected children receiving highly active antiretroviral therapy containing nelfinavir. The geometric mean trough concentrations of nelfinavir for the thrice- and twice-daily regimens were 1.55 mg/L and 1.11 mg/L, respectively (P=not significant). Nelfinavir concentrations did not correlate with total daily dose, dose per kilogram of weight, age, weight, previous protease inhibitor (PI) experience, or CD4(+) cell percentage. In the 25 PI-naive children, the virus load reductions at 24 weeks of treatment with the twice- and thrice-daily regimens were comparable. A significantly higher percentage of children in the twice-daily group had a trough concentration of nelfinavir of less than the inhibitory concentration of 95% (P=.042). The decrease in the virus load at 24 weeks of treatment was not correlated with the trough concentration of nelfinavir. The variability of trough concentrations was extremely high, particularly among recipients of the twice-daily regimen, resulting in a higher number of patients with subinhibitory concentrations of nelfinavir in this group.

Antiretroviral Therapy, Highly Active↗
PubMed2003

Paraneoplastic neurological disorders in breast cancer.

Paraneoplastic syndromes are the rarest neurological complications in patients with cancer. The neurological paraneoplastic syndromes that are mainly associated with breast cancer are subacute cerebellar degeneration, paraneoplastic retinopathy, opsoclonus-myoclonus syndrome, lower motor neuron diseases and Stiff-man syndrome. The aim of this paper is to briefly outline these paraneoplastic neurological syndromes and consider their relation to breast carcinoma.

Breast Neoplasms↗
PubMed2003

Intraoperative radiation therapy with electrons (ELIOT) in early-stage breast cancer.

Local recurrences after breast-conserving surgery occur mostly in the quadrant harbouring primary carcinoma. The main objective of postoperative radiotherapy should be the sterilisation of residual cancer cells in the operative area while irradiation of the whole breast may be avoided. We have developed a new technique of intraoperative radiotherapy of a breast quadrant after the removal of the primary carcinoma (ELIOT). A mobile linear accelerator with a robotic arm is utilised delivering electron beams able to produce energies from 3 to 9 MeV. Different dose levels were tested from 10 to 21 Gy without important side effects. A randomized trial is currently ongoing in order to compare conventional irradiation and ELIOT. More than 400 patients have been enrolled. In addition a new approach for nipple and areola complex conservation, including ELIOT, is under investigation.

Breast Neoplasms↗
PubMed2003

Upgrading of a small overloaded activated sludge plant using a MBBR system.

The aim of this research was the application of a biofilm system for the upgrading of a full-scale overloaded activated sludge MWWTP using the MBBR (Moving Bed Biofilm Reactor) technology. The choice of this fixed biomass system appeared appropriate because it offers several advantages including good potential in nitrification process, easiness of management and above all, the possibility to use the existing tank with very few modifications. MBBR system counts only few full-scale plants in Italy at the moment, thus a pilot-scale experimentation was preliminarily carried out. The acquired parameters were used for the fullscale MWWTP upgrading. The upgrading of the activated sludge reactor in the MBBR system has given (1) a relevant increase in the flowrate treated up to 60%; (2) a good efficiency in organic carbon removal and nitrification, equal to 88% and 90% respectively, with HRTs of 5.5-7 h; (3) the overcoming of the hydraulic overload of the secondary settler, applying a lamellar settler. It was observed a good correlation between the results obtained at pilot-scale and those observed in the full-scale plant.

Biofilms↗
PubMed2002

Synthesis of new C-6 alkyliden penicillin derivatives as beta-lactamase inhibitors.

New penicillin, penicillin sulfone and sulfoxide derivatives bearing a C-6-alkyliden substituent were prepared. Their chemical synthesis, in vitro antibacterial activity and inhibition properties against two selected enzymes representing Class A and C beta-lactamases are reported. Compounds 3a-c, 7a-c were able to inhibit either TEM-1 (a Class A enzyme, from Escherichia coli) or P-99 (a Class C enzyme, from E. cloacae), or both enzymes, when tested in competition experiments using nitrocefin as the reporter substrate. However, when tested in combination with amoxicillin, the same compounds did not show synergistic effects against E. coli and E. cloacae strains producing TEM-1 and P99 enzymes, respectively. This finding is most likely related to poor penetration through the bacterial cell wall, as shown by using a more permeable isogenic E. coli strain. Interestingly, a synergistic effect against a strain of S. aureus which produces PC1-enzyme (a Class A beta-lactamase) was observed for compound 3a when used in combination with amoxicillin.

Amoxicillin↗