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Biomedical subjects

M Sisti

Publications and source records attributed to M Sisti.

At least 19 recordsLinked to original sources

Measurement of the p to s wave branching ratio of 187Re beta decay from beta environmental fine structure.

The mixed occurrence of s-wave and p-wave contributions in a first forbidden unique Gamow-Teller beta decay has been investigated for the first time by measuring the beta environmental fine structure (BEFS) in a 187Re crystalline compound. The experiment has been carried out with an array of eight AgReO4 thermal detectors operating at a temperature of approximately 100 mK. A fit of the observed BEFS spectrum indicates the p-wave electron emission as the dominant channel. The complete understanding of the BEFS distortion of the 187Re beta decay spectrum is crucial for future experiments aiming at the precise calorimetric measurement of the antineutrino mass.

Journal Article↗

New limit on the neutrinoless betabeta decay of 130Te.

We report the present results of CUORICINO, a search for neutrinoless double-beta (0nu betabeta) decay of 130Te. The detector is an array of 62 TeO2 bolometers with a total active mass of 40.7 kg. The array is cooled by a dilution refrigerator shielded from environmental radioactivity and energetic neutrons, operated at approximately 8 mK in the Gran Sasso Underground Laboratory. No evidence for (0nu betabeta) decay was found and a new lower limit, T(1/2)(0nu) > or = 1.8 x 10(24) yr (90% C.L.) is set, corresponding to [m(nu)] < or = 0.2 to 1.1 eV, depending on the theoretical nuclear matrix elements used in the analysis.

Journal Article↗

Bolometric bounds on the antineutrino mass.

High statistics calorimetric measurements of the beta spectrum of 187Re are being performed with arrays of silver perrhenate crystals operated at low temperature. After a substantial modification of the experimental setup, a new measurement with ten silver perrhenate microbolometers has been running since July 2002. The crystals have masses around 300 microg and their average FWHM energy resolution is of 28.3 eV at the beta end point. The Kurie plot collected during 4485 h x mg effective running time has an end-point energy of 2466.1+/-0.8(stat)+/-1.5(syst) eV, while the half lifetime of the decay is found to be 43.2+/-0.2(stat)+/-0.1(syst) Gy. These values are the most precise obtained so far for 187Re. The best fit value for m(2)(nu(e)) is 147+/-237(stat)+/-90(syst) eV(2), which corresponds to an upper limit for the electron antineutrino mass m(nu(e))< or =21.7 eV at 90% C.L.

Journal Article↗

Antifungal activity of Brassica oleracea var. botrytis fresh aqueous juice.

The antifungal activity of fresh, aqueous Brassica oleracea var. botrytis juice against Candida albicans and other pathogenic fungi was investigated. The juice was found to be effective both in inhibiting the growth of blastoconidia and reducing the appearance of C. albicans germ tubes. Furthermore, the juice inhibited the growth of some pathogenic, filamentous fungi.

Antifungal Agents↗

Azomethine ylide cycloaddition/reductive heterocyclization approach to oxindole alkaloids: asymmetric synthesis of (-)-horsfiline.

The intermolecular [3 + 2] annulation of azomethine ylides with 2(2-nitrophenyl)acrylate dienophiles followed by reductive heterocyclization affords the spiro(indole-pyrrolidine) ring system. Hence, this enable us to accomplish a concise and highly enantioselective synthesis of (-)-horsfiline 1, based on chiral auxiliary-directed pi-face discrimination in the 1,3-dipolar cycloaddition of (1S,2R)-2-phenyl-1-cyclohexyl ester 4f with N-methylazomethine ylide.

Alkaloids↗

Efficacy of macrolides used in combination with ethambutol, with or without other drugs, against Mycobacterium avium within human macrophages.

The activities of clarithromycin or roxithromicin used in combination with other antimicrobial drugs were tested in human macrophages experimentally infected with 23 strains of Mycobacterium avium. Overall, clarithromycin-ethambutol-rifampicin was the most active combination tested. The reduction in intracellular viable bacilli was found to be more than 1 log(10) for 95% and more than 2 logs(10) for 65% of the strains. The second most active combination was roxithromycin-ethambutol-rifampicin, which was found to be bactericidal for about 80% and highly bactericidal for 20% of the strains. Others combinations were only bacteriostatic or weakly bactericidal for many of the strains. The addition of a third drug did not necessarily promote enhanced bacterial killing inside the macrophage.

Anti-Bacterial Agents↗

[GdPCP2A(H(2)O)(2)](-): a paramagnetic contrast agent designed for improved applications in magnetic resonance imaging.

A novel ligand based on a pyridine-containing macrocycle bearing two acetic and one methylenephosphonic arms (PCP2A) has been synthesized. An efficient synthesis of PCP2A is based on the macrocyclization reaction between 2,6-bis(chloromethyl)pyridine and a 1,4, 7-triazaheptane derivative bearing a methylenephosphonate group on N-4. The Gd(III) complex of PCP2A displays characteristic properties which make it a very promising contrast agent for improved applications in magnetic resonance imaging. In fact it shows (i) a very high stability constant (log K(GdPCP2A) = 23.4) which should guarantee against the in vivo release of toxic free Gd(III) ions and free ligand molecules and (ii) a relaxivity that is about 2 times higher than the values reported for contrast agents currently used in the clinical practice. Its high relaxivity is the result of the presence of two water molecules in the inner coordination sphere and a significant contribution from water molecule(s) hydrogen bonded to the phosphonate group. Moreover, the inner sphere water molecules are involved in an exchange with the bulk water which is relatively fast. This property is important for the attainment of an even higher relaxivity once the molecular reorientation rate of the [GdPCP2A(H(2)O)(2)](-) moiety is lengthened by means of conjugation to a macromolecular substrate.

Bridged Bicyclo Compounds, Heterocyclic↗

Non-covalent conjugates between cationic polyamino acids and GdIII chelates: a route for seeking accumulation of MRI-contrast agents at tumor targeting sites.

Three novel Gd chelates containing on their external surface pendant phosphonate and carboxylate groups, which promote the interaction with the positively charged groups of polyornithine and polyarginine, have been synthesized. Their solution structures have been assessed on the basis of 1H- and 31P-NMR spectra of the Eu and Yb analogues. A thorough investigation of the relaxometric (1H and 17O) properties of the Gd chelates has been carried out and the observed relaxivities have been accounted for the sum of three contributions arising from water molecules in the first, second, and outer coordination layers, respectively. It has been found that the occurrence of a tight second coordination coating renders the dissociation of the water molecule directly coordinated to the Gd ion more difficult. The binding interactions between the negatively charged Gd chelates and the positively charged groups of polyornithine (ca. 140 residues) and polyarginine (ca. 204 residues) have been evaluated by means of the proton relaxation enhancement (PRE) method. Although the binding interaction decreases markedly in the presence of competitive anions in the solution medium, the affinity is strong enough that in blood serum it is possible to meet the conditions where most of the chelate is bound to the polyamino acid substrate. On this basis one may envisage a novel route for a MRI location of tumors as it is known that positively charged polyamino acids selectively bind to tumors having a greater negative charge than non-tumor cells.

Chelating Agents↗

Ternary Gd(III)L-HSA adducts: evidence for the replacement of inner-sphere water molecules by coordinating groups of the protein. Implications for the design of contrast agents for MRI.

Two novel gadolinium(III) chelates based on the structure of the heptadentate macrocyclic 1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid (DO3A) ligand have been synthesized and their relaxometric and luminescent properties thoroughly investigated. They contain two water molecules in the inner coordination sphere in fast exchange with the bulk solvent and bear either a p-bromobenzyl or a p-phosphonatomethylbenzanilido substituent for promoting further interaction with macromolecular substrates. Upon interaction with human serum albumin the expected relaxation enhancement is not observed owing to displacement of the two inner-sphere water molecules of the complexes by a donor atom (likely from a carboxylate group) on the protein and possibly the phosphate anion of the buffered solution, respectively. We modeled the observed behavior by measuring the decrease of the relaxation rate of the water protons upon addition of malonate anion to aqueous solutions of the complexes. Conversely, no change in the hydratation state of the Gd(III) center for both complexes has been observed when the substrate for the formation of the macromolecular adduct is represented by poly-beta-cyclodextrin.

Contrast Media↗

Evaluation of the environmental impact of microbial aerosols generated by wastewater treatment plants utilizing different aeration systems.

Using three sampler devices (SAS, Andersen Six-Stages and All Glass Impinger), the environmental impact of bacterial and fungal aerosols generated by municipal wastewater treatment plants operating with different methods of sludge oxygenation were evaluated. The highest microbial concentrations were recovered above the tanks (2247 cfu m-3) and in downwind positions (1425 cfu m-3), where a linear correlation (P < 0.05) was found between the quantity of sewage treated and the entities of microbial aerosol dispersion. Moreover, an exponential increase (P < 0.05) in the bacteria recovered from the air occurred at increasing times of treatment. However, after long-term plant operation, high bacterial and fungal concentrations were found in almost all of the sites around the plant. Coliforms, enterococci, Escherichia coli and staphylococci were almost always recovered in downwind positions. Considerable fractions (20-40%) of sampled bacteria were able to penetrate the final stages of the Andersen apparatus and thus, are likely to be able to penetrate the lungs. The plant operating with a fine bubble diffused air system instead was found to generate rather low concentrations of bacteria and fungi; moreover, staphylococci and indicator micro-organisms were almost absent. Finally, salmonellae, Shigella, Pseudomonas aeruginosa and Aeromonas spp. were not detected in either of the plants. The results indicate a remarkable dispersion of airborne bacteria and fungi from tanks in which oxygen is supplied via a mechanical agitation of sludge, and suggest the need to convert them to diffused aeration systems which pose a lesser hazard for human health.

Air Microbiology↗

Cranioplasty in acoustic neuroma surgery.

OBJECTIVES: To measure the incidence of postoperative headaches after retrosigmoid resections of acoustic neuromas and to evaluate the impact of cranioplasty on the prevention and management of these headaches. STUDY DESIGN: A prospective evaluation was performed on 30 consecutive patients who underwent a cranioplasty after retrosigmoid excision of their acoustic neuroma. The results were compared with 30 historical control patients who underwent the same procedure but did not have reconstruction with a cranioplasty. The patients were evaluated by review of office records and via telephone questionnaire. METHODS: One group of patients (30 patients) had no cranioplasty, and the other group of 30 patients had primary reconstruction with a titanium mesh-acrylic cranioplasty. All 60 patients were asked to report on the duration and severity of their headaches by means of a standard questionnaire, grading their symptoms on a scale of 1 to 4. The data were subjected to chi2 and Student t test statistical analyses. RESULTS: New-onset, postoperative headaches occurred in 27% of patients, 23% in the cranioplasty group compared with 30% in the group without cranioplasty (a difference that was not statistically significant [P = .158]). However, there was a statistically significant difference in the severity of the headaches (P<.03). The headaches in the cranioplasty group were less severe and were not disabling. There were no complications, infections, or extrusions related to the cranioplasty. CONCLUSIONS: Cranioplasty has not been able to eliminate postoperative headaches. However, the use of cranioplasty has significantly decreased the severity of postoperative headaches after retrosigmoid excision of acoustic neuromas.

Adult↗

A phase I study of high-dose BCNU, etoposide and escalating-dose thiotepa (BTE) with hematopoietic progenitor cell support in adults with recurrent and high-risk brain tumors.

This phase I dose-escalation study was performed to determine the tolerability of three-drug combination high-dose BCNU (B) (450 mg/m2), escalating-dose thiotepa (500-800 mg/m2) and etoposide (1200 mg/m2) in divided doses over four days in 22 adults with malignant primary brain tumors. Patients received G-CSF and hematopoeitic support with peripheral blood progenitor cells (PBPC) (n = 18) or both PBPC and marrow (n = 4). The maximum tolerated dose of thiotepa with acceptable toxicity was determined as 800 mg/m2. The 100-day mortality rate was 9% (2/22). Grade III/IV toxicities included mucositis (71%), diarrhea (29%), nausea/vomiting (19%), and hepatic toxicity (14%). Neurological toxicities occurred in 24% and included seizures (two patients) and encephalopathy (three patients). Encephalopathy was transient in two patients and progressive in one patient. All patients had neutropenic fever. Median time to engraftment with absolute neutrophil count (ANC) >0.5 x 10(9)/l was 10 days (range 8-30 days). Platelet engraftment >20 x 10(9)/l occurred after 11 days (range 9-65 days). In the eighteen patients supported solely with PBPC, there was a significant inverse correlation between CD34+ dose and days to ANC (rho = -0.78, p = 0.001) and platelet engraftment (rho = -0.76, p = 0.002). Overall, 11% of evaluable patients (2/18) had a complete response to BTE. Median time to tumor progression (TTP) was 9 months, with an overall median survival of 17 months. BCNU (450 mg/m2), thiotepa (800 mg/m2) and etoposide (1200 mg/m2) in divided doses over four days is a tolerable combination HDC regimen, the efficacy of which warrants further investigation in adults with optimally resected chemoresponsive brain tumors.

Adult↗

Survival ability of cytotoxic strains of motile Aeromonas spp. in different types of water.

The ability of motile Aeromonas spp. to survive in drinking water (mineral and tap water) and in sea water was experimentally tested. Clinically isolated cytotoxic strains of A. hydrophila, A. caviae and A. sobria were selected for this study. After contamination of water samples, the survival of Aeromonas strains was studied for at least three months using viable counts. The results obtained show that the survival of the Aeromonas spp. varies considerably depending on species and water type. For all three species, the survival time was longest in mineral water, where viable bacteria of each strain were still detected after 100 d. Moreover, A hydrophila and A. caviae also re-grew on the first day. In tap water all strains showed marked survival, although to a lesser extent than in mineral water. Aeromonas cells showed a rapid decline in sea water (90% reduction in viable cells after about two d) and thus seem to be more sensitive to saline/marine stress than chlorination.

Aeromonas↗

Peak exercise oxygen consumption in chronic heart failure: toward efficient use in the individual patient.

OBJECTIVES: This study sought to 1) assess the short-, medium-and long-term prognostic power of peak oxygen consumption (VO2) in patients with heart failure; 2) verify the consistency of a nonmeasurable anaerobic threshold (AT) as a criterion of nonapplicability of peak VO2; 3) develop simple rules for the efficient use of peak VO2 in individualized prognostic stratification and clinical decision making. BACKGROUND: Peak VO2, when AT is identified, is among the indicators for heart transplant eligibility. However, in clinical practice the application of defined peak VO2 cutoff values to all patients could be inappropriate and misleading. METHODS: Six hundred fifty-three patients consecutively considered for eligibility for heart transplantation were followed up. Outcomes (cardiac death and urgent transplantation) were determined when all survivors had a minimum of 6 months of follow-up. RESULTS: Contraindication to the exercise test identified very high risk patients. The relatively small sample of women did not allow inferences to be drawn. In men, peak VO2 stratified into three levels (< or = 10, 10 to 18 and >18 ml/kg per min) identified groups at high, medium and low risk, respectively. The prognostic power of peak VO2 < or = 10 ml/kg per min was maintained even when the AT was not detected. In patients in New York Heart Association functional class III or IV, peak VO2 did not have prognostic power. In patients in functional class I or II, peak VO2 stratification was prognostically valuable, but less so at 6 than at 12 or 24 months. Age did not influence peak VO2 prognostic stratification. CONCLUSIONS: A contraindication to exercise testing should be considered a priority for listing patients for heart transplantation. Only in less symptomatic male patients does a peak VO2 < or = 10 ml/kg per min identify short-, medium- and long-term high risk groups. A peak VO2 >18 ml/kg per min implies good prognosis with medical therapy.

Anaerobic Threshold↗

High-dose thiotepa and etoposide-based regimens with autologous hematopoietic support for high-risk or recurrent CNS tumors in children and adults.

The prognosis in patients with primary brain tumors treated with surgery, radiotherapy and conventional chemotherapy remains poor. To improve outcome, combination high-dose chemotherapy (HDC) has been explored in children, but rarely in adults. This study was performed to determine the tolerability of three-drug combination high-dose thiotepa (T) and etoposide (E)-based regimens in pediatric and adult patients with high-risk or recurrent primary brain tumors. Thirty-one patients (13 children and 18 adults) with brain tumors were treated with high-dose chemotherapy: 19 with BCNU (B) and TE (BTE regimen), and 12 with carboplatin (C) and TE (CTE regimen). Patients received growth factors and hematopoietic support with marrow (n = 15), peripheral blood progenitor cells (PBPC) (n = 11) or both (n = 5). The 100 day toxic mortality rate was 3% (1/31). Grade III/IV toxicities included mucositis (58%), hepatitis (39%) and diarrhea (42%). Five patients had seizures and two had transient encephalopathy (23%). All patients had neutropenic fever and all pediatric patients required hyperalimentation. Median time to engraftment with absolute neutrophil count (ANC) >0.5 x 10(9)/l was 11 days (range 8-37 days). Time to ANC engraftment was significantly longer (P = 0.0001) in patients receiving marrow (median 14 days, range 10-37) than for PBPC (median 9.5 days, range 8-10). Platelet engraftment >50 x 10(9)/l was 24 days (range 14-53 days) in children. In adults, platelet engraftment >20 x 10(9)/l was 12 days (range 9-65 days). In 11 patients supported with PBPC, there was a significant inverse correlation between CD34+ dose and days to ANC (rho = -0.87, P = 0.009) and platelet engraftment (rho = -0.85, P = 0.005), with CD34+ dose predicting time to engraftment following HDC. Overall, 30% of evaluable patients (7/24) had a complete response (CR) (n = 3) or partial response (PR) (n = 4). Median time to tumor progression (TTP) was 7 months, with an overall median survival of 12 months. These TE-based BCNU or carboplatin three-drug combination HDC regimens are safe and tolerable with promising response rates in both children and older adults.

Adolescent↗

Bactericidal effect of chlorine on motile Aeromonas spp. in drinking water supplies and influence of temperature on disinfection efficacy.

The susceptibility of toxigenic Aeromonas spp. to free chlorine in drinking water supplies, and the influence of environmental temperature on the bactericidal activity of the oxidant, were evaluated. The results showed inactivation curves characterized by an initial phase of rapid reduction of viable cells followed by a slow inactivation of bacteria. The effect of the chlorine compound was markedly influenced by water temperature. At a summer water temperature (20 degrees C), the efficacy of the chlorine concentrations tested was found to be two to three times lower compared to that found at a winter temperature (5 degrees C). Resistance was moderately, but significantly, greater in Aer. hydrophila vs Aer. caviae and Aer. sobria, but all Aeromonas spp. were more susceptible than Escherichia coli. Selective pressure with free chlorine did not produce Aeromonas cells with higher levels of chlorine resistance.

Aeromonas↗

[An analysis of the decision process in the pharmacological treatment of a patient with chronic heart failure by means of a therapy management information system: the experience of the Montescano Heart Failure Unit].

A computer-based system integrated into the hospital information system for the pharmacological management of the chronic heart-failure patients admitted to the heart-failure unit of Montescano is presented. The major aims of the system involved monitoring the patients' treatment history and the related therapeutic decision-making. The treatment history of the first 151 consecutive CHF patients admitted after the system implementation is examined. The prescribed drug doses at admission and at discharge are compared, as well as the differences in etiology and NYHA class between patients discharged with or without each drug. Several considerations can be drawn from this analysis. First of all, in heart failure patients the choice of drugs is limited and optimal treatment is a result of individualized dosages. Secondly, time and trials are necessary to obtain optimal treatment. Consequently, continuity of care and in- and out-hospital networks are advisable. Third, a computer-based system offers advantages not only for the pharmacological management itself, but also for improving the quality of care through continuous analysis of the decision-making process.

Cardiology Service, Hospital↗