Biomedical subjects

M Valenti

Publications and source records attributed to M Valenti.

At least 19 recordsLinked to original sources

PubMed2006

Hypoxic abdominal stop-flow perfusion in the treatment of advanced pancreatic cancer: a phase II evaluation/trial.

In the past decade, some authors have reported objective responses and prolonged median survival times using hypoxic abdominal perfusion (HAP) for the treatment of advanced pancreatic cancer. However, these promising results have not been confirmed by others, making it difficult to define the effectiveness of this loco-regional chemotherapy. The aim of this study, therefore, was to evaluate the response rate, time to disease progression and overall survival following HAP treatment of 22 consecutive patients with advanced pancreatic tumors. Within the period from 1999 to 2003, 22 patients with histological diagnosis of unresectable stage III/IV pancreatic cancer, not responsive to systemic chemotherapy, were treated with mitomycin C 30mg/m(2) and cisplatin 60mg/m(2) by HAP (stop flow technique). Immediately after perfusion, hemofiltration was performed to reduce systemic side toxic effects. Responses were assessed by CT-scan 30days from the end of treatment. Minor or partial responses were confirmed by a second CT-scan 4weeks later. Following 26 treatment cycles no death or technical complications were recorded; four patients (18.2%) achieved a partial response, 2 (9.1%) a minimal response and 13 (59.1%) stable disease. The remaining 3 patients (13.6%) showed progression of the disease. The median time to disease progression was 3 months (range 1-10). The median survival time from the start of regional chemotherapy was 6 months (range 1.9-16), with a 1-year survival rate of 9%. Our data show that HAP is a relatively effective second-line treatment for advanced stage pancreatic cancer with a low complication rate. We do not concur with the opinion of others that HAP is an inactive treatment approach. However, taking into account the invasiveness of this procedure, and associated morbidity and cost, HAP would not appear to be preferable to less invasive loco-regional chemotherapeutic alternatives.

Aged↗

PubMed2006

Neural contractions in colonic strips from patients with diverticular disease: role of endocannabinoids and substance P.

BACKGROUND AND AIMS: Diverticulosis is a common disease of not completely defined pathogenesis. Motor abnormalities of the intestinal wall have been frequently described but very little is known about their mechanisms. We investigated in vitro the neural response of colonic longitudinal muscle strips from patients undergoing surgery for complicated diverticular disease (diverticulitis). METHODS: The neural contractile response to electrical field stimulation of longitudinal muscle strips from the colon of patients undergoing surgery for colonic cancer or diverticulitis was challenged by different receptor agonists and antagonists. RESULTS: Contractions of colonic strips from healthy controls and diverticulitis specimens were abolished by atropine. The beta adrenergic agonist (-) isoprenaline and the tachykinin NK1 receptor antagonist SR140333 had similar potency in reducing the electrical twitch response in controls and diseased tissues, while the cannabinoid receptor agonist (+)WIN 55,212-2 was 100 times more potent in inhibiting contractions in controls (IC50 42 nmol/l) than in diverticulitis strips. SR141716, a selective antagonist of the cannabinoid CB1 receptor, had no intrinsic activity in control preparations but potentiated the neural twitch in diseased tissues by up to 196% in a concentration dependent manner. SR141716 inhibited (+)WIN 55,212-2 induced relaxation in control strips but had no efficacy on (+)WIN 55,212-2 responses in strips from diverticular disease patients. Colonic levels of the endogenous ligand of cannabinoid and vanilloid TRPV1 receptors anandamide were more than twice those of control tissues (54 v 27 pmol/g tissue). The axonal conduction blocker tetrodotoxin had opposite effects in the two preparations, completely inhibiting the contractions of control strips but potentiating those in diverticular preparations, an effect selectively inhibited by SR140333. CONCLUSIONS: Neural control of colon motility is profoundly altered in patients with diverticulitis. Their raised levels of anandamide, apparent desensitisation of the presynaptic neural cannabinoid CB1 receptor, and the SR141716 induced intrinsic response, suggest that endocannabinoids may be involved in the pathophysiology of complications of colonic diverticular disease.

Adrenergic beta-Agonists↗

PubMed2006

Obesity and related diseases: an epidemiologic study in eastern Sicily.

AIM: The aim of this study was to investigate the prevalence of obesity in a non selected cohort of adult subjects living in eastern Sicily. METHODS: Out of 2 296 examined subjects, 834 (36.3%) were affected by obesity. Of these, only 160 (19.1%) were affected by obesity alone while 674 (80.9%) showed other associated pathologies. RESULTS: The prevalence of arterial hypertension, diabetes mellitus, hepatic steatosis, hyperdyslipidemia and renal failure was significantly higher (P = 0.000) than in a control group of non-obese subjects comparable for sex and age. CONCLUSIONS: In a large part of obese patients, the presence of insulin resistance was observed suggesting that this alteration can play a pivotal role in the development of some important metabolic and cardiovascular complications related to obesity.

Age Factors↗

PubMed2005

The endocannabinoid system in the brain of Carassius auratus and its possible role in the control of food intake.

Cannabinoid receptors and the endocannabinoids anandamide and 2-arachidonoylglycerol have been suggested to regulate food intake in several animal phyla. Orthologs of the mammalian cannabinoid CB(1) and CB(2) receptors have been identified in fish. We investigated the presence of this endocannabinoid system in the brain of the goldfish Carassius auratus and its role in food consumption. CB(1)-like immunoreactivity was distributed throughout the goldfish brain. The prosencephalon showed strong CB(1)-like immunoreactivity in the telencephalon and the inferior lobes of the posterior hypothalamus. Endocannabinoids were detected in all brain regions of C. auratus and an anandamide-hydrolysing enzymatic activity with features similar to those of mammalian fatty acid amide hydrolase was found. Food deprivation for 24 h was accompanied by a significant increase of anandamide, but not 2-arachidonoylglycerol, levels only in the telencephalon. Anandamide caused a dose-dependent effect on food intake within 2 h of intraperitoneal administration to satiated fish and significantly enhanced or reduced food intake at low (1 pg/g body weight) or intermediate (10 pg/g) doses, respectively, the highest dose tested (100 pg/g) being inactive. We suggest that endocannabinoids might variously contribute to adaptive responses to food shortage in fish.

Amidohydrolases↗

PubMed2005

Perioperative management of face-to-face craniopagus twins separation.

Craniopagus conjoining represents a complex and challenging issue for neurosurgeons as well as for anesthesiologists. A rare face-to-face case of conjoined twins underwent surgical separation and presented peculiar differences compared with those already reported in the literature. Even in cases lacking large cerebrovascular sinus connections, the impending risk of large blood loss and hemorrhagic shock in the infant requires a high level of surveillance and the institution of invasive monitoring.

Anesthesia, Inhalation↗

PubMed2005

Amyotrophic lateral sclerosis and sports: a case-control study.

An increased incidence of amyotrophic lateral sclerosis (ALS) amongst soccer players in Italy has recently been reported. A case-control study (300 cases and 300 matched controls) was conducted to explore the association between ALS and physical/sports activities, with specific reference to trauma-related risk. Neither the practice of competitive sports nor sports-related traumas were found to be associated with an increased risk of ALS. The practice of physical activities or sports is not per se a risk factor for ALS. Our results exclude sports-related microtraumas as etiopathogenic factors in the natural history of ALS.

Adult↗

PubMed2004

Craniopagus: the Thessaloniki-Rome experience.

OBJECT: A case of two female Greek twins conjoined at the left frontal and orbital regions is described. These conjoined twins were transferred to the Pediatric Neurosurgical Unit of the Gemelli Hospital, Catholic University Medical School, at the age of 4 months for possible surgical division. METHOD: Multiple diagnostic investigations, which included in particular advanced imaging techniques, demonstrated an independent cerebral vascularization of the two babies and excluded significant intracranial malformations. Such an accurate evaluation of the anatomy of the craniopagus at the level of the cranial junction allowed the feasibility of the surgical correction to be established. CONCLUSIONS: The operation was carried out by a multidisciplinary team in a single stage. The operating team included two distinct teams of neurosurgeons and anesthesiologists as well as a plastic surgeons' team. Both babies survived the operation. The postoperative course was uneventful. Both twins were discharged in good clinical and neurological condition after a 3-week period of hospitalization.

Brain↗

PubMed2004

Capillary gas chromatographic determination of spermidine in diet integrators.

Biogenic polyamines, among which is spermidine (SPD, NH2-(CH2)4-NH-(CH2)3-NH2), are ubiquitous polycationic molecules that have a definitive role in many biological processes, such as nucleic acid metabolism, protein synthesis and cell growth. SPD is present in diet integrators because it seems to favour the hair growth. This work describes a capillary gas chromatographic (CGC) method for the quantitative determination of SPD in diet integrators using cadaverine internal standard (IS), a methyl siliconic capillary column and flame-ionization detector (FID). Diet tablets, containing SPD, are pulverized; an aliquot of powder is treated with an alkaline aqueous solution and added with IS. The suspension is extracted with diethyl ether containing ethyl chloroformate (ECF). The ether extracts, evaporated to dryness and reconstituted in ethyl acetate were analyzed in CGC/FID. Derivatives of polyamines with ECF were characterized in CGC/MS too. Validation has considered specificity, linearity, precision and accuracy of analytical method; this parameters are valid for the quantitative determination of SPD in diet integrators.

Chromatography, Gas↗

PubMed2004

Differential diurnal variations of anandamide and 2-arachidonoyl-glycerol levels in rat brain.

The endogenous ligands of cannabinoid receptors, also known as endocannabinoids, have been implicated in many physiological and pathological processes of the central nervous system. Here we show that the levels of the two major endocannabinoids, anandamide and 2-arachidonoyl-glycerol (2-AG), in four areas of the rat brain, change dramatically between the light and dark phases of the day. While anandamide levels in the nucleus accumbens, pre-frontal cortex, striatum and hippocampus were significantly higher in the dark phase, the opposite was observed with 2-AG, whose levels were significantly higher during the light phase in all four regions. We found that the activity of the fatty acid amide hydrolase, which catalyzes the metabolism of anandamide, was significantly lower during the dark phase, thus providing a possible explaination for the increase in anandamide levels. However, the activities of monoacylglycerol lipase and diacylglycerol lipase, two of the possible enzymes catalyzing the degradation and biosynthesis of 2-AG, respectively, changed significantly only in the striatum. These data suggest that the levels of the two major endocannabinoids might be under the control of endogenous factors known to undergo diurnal variations, and underscore the different roles, suggested by previous studies, of anandamide and 2-AG in neurophysiological processes.

Amidohydrolases↗

PubMed2004

Thoracic stop-flow perfusion in the treatment of refractory non small cell lung cancer.

This study was undertaken to determine the survival of patients with unresectable and refractory non small cell lung cancer (NSCLC) submitted to thoracic stop-flow perfusion (TSP). Forty-five patients with NSCLC confined to thoracic region entered the study. All 45 patients had been pretreated with some form of chemotherapy and had progression of disease. The cytostatic regimen was mitomycin 10 mg/m2, navelbine 25 mg/m2 and cisplatin 60 mg/m2. In 39/45 patients, immediately after TSP, hemofiltration was performed to reduce systemic side effects There were 16/45 responses to the first TSP (CR 0; PR 16): a response rate of 35.6%. Median time to progression was 4 months. Median survival was 7.5 months.1-year survival rate was 36.4%, 2-year survival rate was 14%, and 3-year survival rate was 5.7%.

Adult↗

PubMed2003

Clinical efficacy and cost-effectiveness evidence of spa therapy in osteoarthritis. The results of "Naiade" Italian Project.

AIM: The "Naiade" Project was carried out in execution of the Decree of December 1994 by the Italian Ministry of Health, with the objective of defining the therapeutic role of spa therapy in the various sectors of medicine. In this study the authors refer to the results obtained in osteoarthritis (OA). METHODS: The OA study included the observation of patients for 2 consecutive years, with the compilation of a series of clinical and socio-economic data. The initial sample was of 11437 patients suffering from primary and secondary OA, and in the 2(nd) year the total number of assessable patients was 6111 (53.4%). All patients underwent 1 annual cycle of balneotherapy and mud packs therapy for 2 consecutive years. The thermal treatments were carried out in 98 Italian spas with sulphurous water, sodium chloride-bromide-iodide water, sulphate water, and bicarbonate water. Analysis of the data collected confirmed the clinical efficacy of spa treatments for OA, particularly for localisations in the cervical and lumbar spine. The benefits of these treatments and the persistence of the therapeutic effects over time were clearly demonstrated by the collection of some socio-economic indicators relative to the year before each cycle of thermal therapy. RESULTS: In fact, the analysis of these indicators showed a significant reduction in recourse to additional treatments (hospital admissions, physical and pharmacological therapies) and absence from work. CONCLUSION: The obtained data was particularly interesting for the number of samples examined, the follow-up over a period of 2 years, and the collection of clinical and, especially, socio-economic parameters. The results of the Naiade Project confirmed the value of spa therapies in the treatment of OA.

Balneology↗

PubMed2002

Changes in the use of health resources by patients with chronic phlebopathies after thermal hydrotherapy. Report from the Naiade project, a nation-wide survey on thermal therapies in Italy.

BACKGROUND: Chronic venous disorders carry lifelong medical and social burdens. Within conservative approaches, spa hydrotherapy is popular among patients with venous disorders in Europe, but whether the practice is associated with health or social benefits remains controversial. METHODS: The present work is a substudy of the nation-wide Italian Naiade Project, a large multicenter observational exercise on spa treatments in different disease groups. The "Chronic Phlebopathies" substudy included 2504 patients with primary or secondary varicosis or non-varicose venous insufficiency. After a first visit and administration of a detailed questionnaire, patients underwent a "thermal cycle" of 15-20 days consisting of underwater active and passive physical therapy with mineral waters. The same procedures were repeated after 1 year on the 1352 patients (54%) who spontaneously returned to the same spa. Primary endpoints of the study were some indicators of the use of health resources related to the year after the first thermal cycle, compared with the same indicators recorded at first visit using appropriate statistical methods. RESULTS: The occurrence of acute venous episodes, working days missed, number and duration of hospital admissions, consumption of drugs and physical therapies were all significantly reduced in the year after thermal therapy, thus indicating lesser use of health resources. CONCLUSIONS: The study suggests that thermal hydrotherapy in patients with chronic venous disorders is associated with health and social benefits.

Data Collection↗

PubMed2001

Hypoxic pelvic perfusion with mitomycin C using a simplified balloon-occlusion technique in the treatment of patients with unresectable locally recurrent rectal cancer.

HYPOTHESIS: To evaluate the role of hypoxic pelvic perfusion in providing therapeutic options for palliation without relevant complications in a homogeneous group of patients with unresectable locally recurrent rectal cancer who are nonresponders or have disease progression after the standard treatments. DESIGN: Nonrandomized and noncontrolled phase II experimental study. SETTING: University hospital, L'Aquila, and the National Cancer Institute, Naples and Milan, Italy. PATIENTS: Eleven patients had symptomatic unresectable pelvic recurrent rectal cancer. The mean +/- SD product of the 2 maximum perpendicular diameters of the recurrent cancer was 24.2 +/- 11.0 cm(2) (range, 10-48 cm(2)). Tumor fixation to the pelvic side walls or proximal sacrum were the main criteria for unresectability. All patients were free from extrapelvic disease and had a life expectancy longer than 3 months. INTERVENTION: Patients were submitted to one course of pelvic perfusion with mitomycin C (MMC) (25 mg/m(2)) by means of a simplified balloon occlusion technique. A pharmacokinetic evaluation of the procedure was also performed. MAIN OUTCOME MEASURES: Response rate and time to disease progression were the primary endpoints; overall survival was the secondary endpoint. RESULTS: Mean +/- SD value of the ratios of pelvic MMC area under the plasma concentration curve (0 to 20 minutes) (AUC(0-20)) to systemic MMC AUC(0-20) was 13.30 +/- 6.52. During the procedures there were no technical, hemodynamic, or vascular complications, and no deaths occurred during surgery or in the postoperative period. The response rate was 36.3% (95% confidence interval [CI], 6.5%-66.1%). Pain response rate was 45.4% (95% CI, 16.6%-76.2%). Median survival was 12.2 months (range, 5.7-19.5 months). Median time to disease progression was 6 months (range, 3-8 months). Two-year overall survival was 9.1%. CONCLUSIONS: Hypoxic pelvic perfusion with MMC is a safe and good palliative treatment for patients with unresectable locally recurrent rectal cancer. Further studies are necessary to establish if a different sequence in the multimodular treatment of these patients could be more useful.

Antibiotics, Antineoplastic↗

PubMed2001

High prevalence of HCV infection among the general population in a rural area of central Italy.

The hepatitis C virus infection (HCV) is the most frequent cause of hepatic infection in Europe. In Italy, anti-HCV positivity values are extremely variable, depending on the age and geographic location of the population being analysed. The aims of the study were: (1) evaluating positivity for anti-HCV antibodies in various age groups and determining the HBsAg in a mountainous and predominantly farming area in central Italy; (2) assessing some anamnestic and clinical variables through a questionnaire, submitted during the taking of blood samples, in order to determine HCV exposure and risk factors for the target population. 344 subjects selected by random sampling among 3308 people, older than 16, were considered as the target population. A prevalence study was carried out. The sources of data were: blood samples taken to carry out the HCV positivity test; a questionnaire including items about exposures at risk and case-historical and clinical patient data. The risk of infection was evaluated by a multiple logistic regression model. The inferred HCV+ prevalence rate is 22.4/100 (95% confidence interval (CI): 20.8-24.1). An increasing age trend is shown with a higher positive predominance among females (28.99/100 vs. 14.29/100 in males). The positive HBsAg prevalence in the examined survey is 1.2/100. Variables associated with the HCV occurrence are case history of pneumonopathy (OR: 4.9) and exposure to parenteral therapies with glass syringes (OR: 3.3). This study is consistent with literature about the hypothesis of a north-south geographic gradient in the hepatitis C occurrence in Italy. Data clearly show the effects of the inappropriate use of medical or surgery practices on the population, with particular reference to the use of glass syringes. No elements prove that the farming features of the area may be predictive of HCV infection risk. The extent of the recorded prevalence values calls for the implementation of programmes aimed at detecting clusters or population areas at risk.

Adult↗

PubMed2001

Spectral analysis of visual potentials evoked by pattern-reversal checkerboard in juvenile patients with headache.

Changes in visual evoked potentials, mainly affecting the amplitude of the major positive wave, are referred to by many authors and are related to the pathophysiological basis of primary headache. We performed both transient pattern-reversal visual evoked potentials and spectral analysis by means of fast Fourier transform of 8-Hz steady-state pattern-reversal visual evoked potentials in 34 children affected with migraine (14 with aura, 20 without aura), and compared them with 14 patients with tension-type headache and 10 healthy subjects. The amplitude of the response to the transient stimulation (P100) was higher and the latency shorter in the patients with headache compared with the controls, but the difference was not statistically significant. The absolute power of the first harmonic (1F) obtained by the spectral analysis of the steady-state stimulation was increased in all the patients with headache compared with the controls, and the increase was significant in patients with migraine. These data seem to confirm the hypothesis of abnormal processing of visual input in migraineurs and could be interpreted as neurophysiological support for the theory that different headache types are related conditions. Furthermore, the spectral analysis of steady-state pattern-reversal visual evoked potentials could be proposed as a test to diagnose migraine.

Child↗

PubMed2001

HPV16-E6 enhances mitoxantrone sensitivity in a human ovarian cancer line: an isolated instance or a trend?

A cellular isogenic system, in which wt-p53 expression level is challenged through human papilloma virus 16-E6 gene transfection, was previously developed in our laboratory. As an average trend, cancer lines bearing an inactivated p53 have a general tendency toward an increased resistance to chemotherapeutic agents. However, using the above isogenic system, the transfected line (A2780-N9) was found to be more sensitive to taxol than the parental one (A2780-WT). In a NCI meta-analysis study the average trend is that altered p53 status is related to cellular resistance to topoisomerase II inhibitors, while it is irrelevant in determining sensitivity/resistance to mitotic spindle poisons. We report that our E6 transfected line, previously shown to be hypersensitive to taxol, is also clearly hypersensitive to a topoisomerase II inhibitor (mitoxantrone). Differences in cytotoxicity are more evident after a shorter/more intense exposure, than after a milder/longer exposure, being A2780-WT 27-fold more resistant than the transfected clone in the former case. These differences seem to be related to the different activities ("cross-talks") of E6 protein, among which shortening of p53 half-life is only one aspect. After mitoxantrone treatment A2780-N9 cells display also an increased propensity to apoptosis. In addition, a literature survey of E6 effects in transfected cancer cell lines, seems to suggest that chemosensitization to different classes of antineoplastic agents is the rule rather than the exception in these E6-based isogenic systems.

Antineoplastic Agents↗

PubMed2001

Pharmacokinetic/pharmacodynamic study of ZD9331, a nonpolyglutamatable inhibitor of thymidylate synthase, in a murine model following two curative administration schedules.

ZD9331 is a nonpolyglutamatable antifolate inhibitor of thymidylate synthase currently in clinical development. This enzyme is crucial for DNA synthesis and catalyzes the reductive methylation of dUMP to form thymidylate, which is subsequently converted to dTTP. The pharmacokinetics of two curative antitumor doses of ZD9331 administered by either a single i.p. bolus injection (50 mg/kg) or by 24-h s.c. infusion (3 mg/kg) have been measured in a thymidine salvage-incompetent murine lymphoma model (L5178Y) using a sensitive and specific ELISA. To gain an understanding of the relationship between the pharmacokinetics of ZD9331 and antitumor activity perturbations in tumor, dTTP and dUMP concentrations were also determined. After bolus administration, ZD9331 was eliminated from plasma and tissues relatively rapidly, with terminal elimination (lambda(z) 0-24 h) of 4-6 h. Liver concentrations were 8-fold higher than those measured in the plasma. Kidney and lymphoma drug concentrations were similar to those of plasma, although there was evidence of a slower overall elimination of drug at later time points. Steady-state concentrations of ZD9331 were obtained 4-5 h after the start of the 24 h s.c. infusion. At the end of infusion, elimination rates were similar for plasma and tissues (approximately 3.5 h) but appeared to be slower in the tumor at later time points. Liver concentrations were approximately 4-fold higher, and kidney and tumor concentrations were similar to those in the circulation. Depletion of dTTP and elevation in dUMP in the tumor were consistent with inhibition of thymidylate synthase after both administration schedules, although the time for which dTTP was decreased was longer (approximately 24 h) for the infusional route than for the bolus injection (<16 h). The results suggest that antitumor activity is dependent on attaining adequate drug concentrations to affect dTTP pools as well as on the duration of effective drug levels.

Animals↗

PubMed2001

Preclinical antitumor activity and pharmacodynamic studies with the farnesyl protein transferase inhibitor R115777 in human breast cancer.

Antitumor and pharmacodynamic studies were performed in MCF-7 human breast cancer cells and companion xenografts with the farnesyl protein transferase inhibitor, R115777, presently undergoing Phase II clinical trials, including in breast cancer. R115777 inhibited growth of MCF-7 cells in vitro with an IC(50) of 0.31 +/- 0.25 microM. Exposure of MCF-7 cells to increasing concentrations of R115777 for 24 h resulted in the inhibition of protein farnesylation, as indicated by the appearance of prelamin A at concentrations >1 microM. After continuous exposure to 2 microM R115777, prelamin A levels peaked at 2 h post drug exposure and remained high for up to 72 h. R115777 administered p.o. twice daily for 10 consecutive days to mice bearing established s.c. MCF-7 xenografts induced tumor inhibition at a dose of 25 mg/kg [percentage of treated versus control (% T/C) = 63% at day 21]. Greater inhibition was observed at doses of 50 mg/kg (% T/C at day 21 = 38%) or 100 mg/kg (% T/C at day 21 = 43%). The antitumor effect appeared to be mainly cytostatic with little evidence of tumor shrinkage to less than the starting volume. Tumor response correlated with an increase in the appearance of prelamin A, but no changes in the prenylation of lamin B, heat shock protein 40, or N-Ras were detectable. In addition, significant increases in apoptotic index and p21(WAF1/CIP1) expression were observed, concomitant with a decrease in proliferation as measured by Ki-67 staining. An increase in prelamin A was also observed in peripheral blood lymphocytes in a breast cancer patient who responded to R115777. These data show that R115777 possesses preclinical antitumor activity against human breast cancer and that the appearance of prelamin A may provide a sensitive and convenient pharmacodynamic marker of inhibition of prenylation and/or response.

Alkyl and Aryl Transferases↗