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Biomedical subjects

A Tortora

Publications and source records attributed to A Tortora.

At least 19 recordsLinked to original sources

Phase I and pharmacokinetic study of BMS-184476, a taxane with greater potency and solubility than paclitaxel.

PURPOSE: To assess the feasibility, toxicity, pharmacokinetics, and preliminary activity of BMS-184476 administered as a 1-hour intravenous (IV) infusion every 3 weeks. PATIENTS AND METHODS: Patients with advanced solid malignancies were treated with escalating doses of BMS-184476 as a 1-hour IV infusion every 3 weeks without premedication to prevent hypersensitivity reactions (HSR). Plasma sampling and urine collections were performed to characterize the pharmacokinetics and pharmacodynamics of BMS-184474. RESULTS: Thirty-four patients were treated with 78 courses of BMS-184476 at five dose levels ranging from 20 to 80 mg/m2. Dose-limiting toxicity (DLT), consisting of severe neutropenia with fever, severe diarrhea, and/or severe mucositis, was experienced during course 1 by six of nine minimally pretreated patients treated at the 70 and 80 mg/m2 dose level. In contrast, of 15 assessable patients treated at the 60 mg/m2 dose level, which is the maximum-tolerated dose (MTD) of BMS-184476 on this administration schedule, only one heavily pretreated patient developed DLT (grade 4 neutropenia with fever and grade 3 diarrhea). One patient developed a grade 2 HSR during a second course of BMS-184476 at the 40 mg/m2 dose level. A previously untreated patient with an advanced cholangiocarcinoma experienced a partial response, and a patient with an untreated carcinoma of the gastroesophageal junction had a minor response. The pharmacokinetics of BMS-184476 seemed linear in the dose range studied. Mean +/- SD values for clearance, volume of distribution at steady-state, and terminal half-life were 220 +/- 89 mL/min/m2, 402 +/- 231 L/m2, and 40.8 +/- 21.8 hours, respectively. CONCLUSION: The MTD and recommended dose for phase II evaluations of BMS-184476 is 60 mg/m2 as a 1-hour IV infusion every 3 weeks. The results of this study suggest that BMS-184476 may have several advantages compared with paclitaxel in terms of toxicity, pharmacokinetics, pharmaceutics, and administration and warrants further clinical development.

Adult↗

Antimicrobial activity and postantibiotic effect of flurithromycin against Helicobacter pylori strains.

The minimal inhibitory concentrations (MIC) of flurithromycin on 49 clinical isolates of Helicobacter pylori was investigated. The MICs were determined using an agar dilution technique. Flurithromycin inhibited the growth of H. pylori strains with MIC(50) and MIC(90) values of 0.156 and 0.625 mg/l, respectively. The postantibiotic effects (PAE) were studied on ten strains, by exposure of the bacteria to flurithromycin at five and ten times MIC for 1 or 2 h. Regrowth was determined by measuring the viable counts after drug removal by a 10(3) dilution procedure. All PAEs increased as a function of concentration and time of exposure. The mean duration of PAEs varied between 1.5 and 6 h. These data are encouraging since macrolides play a key role in the clinical treatment of H. pylori infections, and the strong PAE caused by flurithromycin may contribute to the in vivo efficacy of this drug.

Anti-Bacterial Agents↗

Gastro-intestinal permeability is increased in patients with limited systemic sclerosis.

OBJECTIVE: to evaluate gastro-intestinal (GI) permeability in patients with limited systemic sclerosis (LSS) at baseline and after oral acetylsalicylic acid (ASA). METHODS: 13 patients with LSS and 10 controls were studied. Baseline GI permeability was assessed with orally administered sucrose, mannitol, and lactulose. Gastric lesions and Helicobacter status were investigated by endoscopy. In 5 patients and 6 controls (with normal baseline permeability) the GI permeability response was assessed after oral ASA. RESULTS: compared with controls, gastric (p<0.05) and intestinal (p<0.02) permeability was higher in LSS patients, at baseline. After oral ASA gastric permeability (sucrose) increased in both groups (controls: 186%, LSS: 265%), whereas the lactulose/mannitol ratio raised significantly only in LSS (+31% and +148%; p<0.05 vs controls). CONCLUSIONS: baseline permeability is altered in LSS; the exaggerated response of the small intestine to ASA may represent a genetically determined or a disease-related dysfunction of the mucosal barrier.

Adult↗

Haemophilus influenzae porin contributes to signaling of the inflammatory cascade in rat brain.

In the present study we observed that the Haemophilus influenzae type b (Hib) porin, among the different surface bacterial components, is involved in the pathophysiology of bacterial meningitis. This study demonstrates that inoculation of Hib porin into the fourth cerebral ventricle causes the simultaneous expression of interleukin-1alpha (IL-1alpha), tumor necrosis factor alpha (TNF-alpha), and macrophage inflammatory protein 2 (MIP-2) at 6 h after inoculation. At 24 h, the expression of MIP-2 decreases while the expression of IL-1alpha and TNF-alpha increases. The mRNA expression of IL-1alpha, TNF-alpha, and MIP-2 is correlated with injury to the blood-brain barrier as demonstrated by the appearance of serum proteins and leukocytes in cerebrospinal fluid and by the increase in brain water content.

Animals↗

[Optimization of dosage and exam technique in the use of oral contrast media in magnetic resonance].

PURPOSE: Aim of our study was to optimize the dose, scan delay and sequences for use in MR studies with an oral contrast agent (FerriSeltz, Bracco, Milan, Italy) to obtain positive or negative contrast enhancement in the bowel lumen. MATERIAL AND METHODS: In vitro: 10 mL vials with increasing concentrations (10-100 mg/mL) of the agent, containing 200 mg ferric ammonium citrate/g, were studied with a 1.5 T magnet (Philips NT, The Netherlands), by acquiring T2-weighted STIR and TSE and T1-weighted TFE sequences. Signal intensity was compared by using a ROI. In vivo: 16 volunteers were examined with the same sequences at 20 minutes and 2 hours after the oral administration of 6-27 g of the product diluted in 600 mL water. Images were analyzed by two radiologists and scored on a 4-point scale based on signal intensity; results were compared with Student's "t"-test. RESULTS: In vitro: MR signal was always hyperintense on T1-weighted images, as well as on T2-weighted TSE and SPIR images at concentrations lower than 45 mg/mL. Hypointense signal was seen on T2-weighted TSE and SPIR images at higher concentrations and on STIR sequences at 10-20 mg/mL concentrations. In vivo: the bowel exhibited positive enhancement on T1-weighted TFE and T2-weighted TSE and SPIR images 20 minutes after contrast agent administration at concentrations lower than 45 mg/mL. At 2 hours, bowel loops were hypointense on T2-weighted TSE and SPIR images at 15-20 mg/mL concentrations. STIR images showed hypointense bowel loops at both 20 minutes and 2 hours after 10-20 mg/mL contrast agent administration. Quantitative analysis showed a statistically significant superiority (p < .05) of T2-weighted STIR images in providing negative opacification of the bowel lumen. CONCLUSIONS: Ferric ammonium citrate, being a positive or negative contrast agent according to its dilution, permits to tailor the dose to optimize bowel lumen opacification.

Administration, Oral↗

[Computerized tomography, magnetic resonance, and nuclear medicine in the non-invasive diagnosis of focal nodular hyperplasia of the liver].

INTRODUCTION: Focal nodular hyperplasia (FNH) is a benign liver lesion requiring a prompt diagnosis and a conservative management. Aim of our study was to prospectively integrate enhanced CT, MRI, nuclear medicine in the noninvasive diagnosis of FNH. MATERIAL AND METHODS: 20 FNH lesions (diameter ranging 1.5-13 cm) in 18 asymptomatic patients were investigated with MRI and nuclear medicine. MRI examinations were performed with a 1.5 T superconducting system (Philiphs NT) by acquiring T1-weighted, T2-weighted, T2-weighted fat-suppressed Turbo Spin-Echo and dynamic MRI sequences, with breath-hold T1-weighted Turbo Field Echo and Gd-DTPA. Nuclear medicine included in all cases 99mTc sulfur colloid or 99mTc iminodiacetic acid studies. Diagnostic sensitivity of MRI was compared with that of nuclear medicine, and the sensitivity of the two modalities combined. The definitive diagnosis was made by percutaneous core-needle biopsy (12 lesions), surgery (2 lesions) and longterm follow-up (6 lesions). RESULTS: In 13 lesions larger than 3.5 cm typical findings, such as the central scar and homogeneous pattern, were observed in 9 cases (75%) with enhanced CT, in 10 cases (83%) with unenhanced MRI and in 11 cases (91%) after gadolinium injection. Hepatobiliary scintigraphy showed increased tracer uptake in delayed scans in 10/12 cases (83%) while sulfur colloid studies were diagnostic in 2/12 cases only (16%), showing the same tracer uptake than the surrounding liver parenchyma. In 7 lesions smaller than 3.5 cm, only 1 case showed typical findings; dynamic MRI showed typical early hypervascularity in 5 of the 6 remaining lesions (71%) which persisted on late images. In lesions smaller than 3.5 cm, sulfur colloid studies were diagnostic in 1/7 lesions (14%) and hepatobiliary scintigraphy in 3/7 lesions (42%). Considering all 20 lesions, MRI-nuclear medicine integration performed better than MRI alone. CONCLUSIONS: Enhanced MRI and biliary scintigraphy are important tools to make the final diagnosis of FNH. In small lesions both examinations should performed, but in large lesions MRI may be sufficient to make an unquestionable diagnosis, limiting hepatobiliary scintigraphy to questionable cases.

Contrast Media↗

[Ultrasonography in the preoperative assessment of candidates for laparoscopic cholecystectomy: examination technique and results].

Laparoscopic cholecystectomy needs a more specific preoperative diagnostic approach than open cholecytsectomy. We investigated the role of US in the preoperative assessment of patients candidate to laparoscopic cholecystectomy. Two hundred patients were examined and then submitted to laparoscopic cholecystectomy regardless of US results: the surgical approach had to be changed from laparoscopy to laparotomy only in 10 of them. We focused our study on two major parameters to reduce the surgical risk: the anatomical study of the so-called "Calot's triangle" (the hepatic artery, common duct and cystic duct) and the study of the gallbladder bed and of pericystic structures. In the study of gallbladder walls and bed, US had high sensitivity (100%) and diagnosed no false negatives and 11 false positives of pericholecystitis (94.5% specificity), with a trend toward overstaging; in these 11 cases, gallbladder wall thickening was seen but the organ was not particularly difficult to remove at surgery. In cystic duct studies, we correctly diagnosed 6 abnormalities (3 cystic duct stones, 2 anatomical variants and 1 anatomical variant plus stone), with no false-positive and 2 false-negative diagnoses of abnormal insertion (75% sensitivity and 100% specificity). The common duct was shown along its whole course in 80% of cases; both sensitivity and specificity were 100% in dilatation detection, while the presence of stones was diagnosed with 70% sensitivity and 100% specificity.

Adult↗

Upper gastrointestinal endoscopy can be a reliable screening tool for celiac sprue in adults.

In our study, we evaluated whether the combination of two endoscopic abnormalities in the duodenum (the "mosaic" appearance and loss of duodenal folds) is significantly associated with duodenal villous atrophy secondary to celiac sprue in adults. Fourteen patients referred for esophagogastroduodenoscopy for suspected celiac sprue and 146 for suspected peptic disease were enrolled in the study. At least one of the two endoscopic duodenal abnormalities was observed in all 10 untreated celiac patients but in only one of the dyspeptic patients. The sensitivity and specificity were 100 and 99.3%, with positive and negative predictive value of 90.9 and 100%, respectively. Such good results suggest that duodenal endoscopy can be a screening procedure for celiac sprue in patients who are undergoing endoscopy for other reasons.

Adolescent↗

Resection of liver gastrinoma leading to persistent eugastrinemia. Case report.

In a 30-year-old man with Zollinger-Ellison syndrome, the only detectable gastrinoma was in the right liver lobe. Removal of the lobe, without additional gastric surgery, was followed by normalization of the gastrin level. Long-term follow-up confirmed the good result. The usefulness of quick intraoperative gastrin assay is stressed.

Adult↗

[The prevention of postoperative deep venous thrombosis with heparan sulfate per os. A controlled clinical study vs. heparin calcium].

The paper reports the results of a randomised study carried out on a pool of 100 patients undergoing surgery in order to assess the efficacy and tolerability of orally administered heparan sulfate versus heparin calcium in the prevention of postoperative deep-vein thrombosis. Despite the limits of oral administration, heparan sulfate is indicated in the pharmacological prevention of postoperative deep-vein thrombosis.

Administration, Oral↗

Perineal colostomy and electrostimulated gracilis "neosphincter" after abdomino-perineal resection of the colon and anorectum: a surgical experience and follow-up study in 47 cases.

A series of 47 patients undergoing abdomino-perineal resection of the distal colon and anorectum and construction of a continent perineal colostomy using electrostimulated gracilis muscle is described. External and implanted pulse generators have both been used. An analysis of complications and oncological data are reported. There was no operative mortality. The incidence of complications, divided into three classes, mild (62%), moderate (27%) and severe (11%), has not significantly altered the functional results, with the exception of early ischaemia of the colonic stump in two cases. During the first 22 cases, no preoperative oncological staging was performed. In the last 23 patients endorectal ultrasonography and CT scanning were carried out. Functional results were evaluated by electromanometry, electromyostimulation and dynamic defaecography. Clinical data assessed postoperatively showed good function in 65% of cases, fair in 22.5% and poor in 12.5%. The quality of life in 15 patients with a perineal colostomy and electrostimulated gracilis was significantly better than in 15 patients having an abdomino-perineal resection without gracilis plastic reconstruction.

Adult↗

[Analgesic laser therapy in dentistry].

The authors, after an analysis of the laser structure and its main utilization, present some clinical reports in which the pain is resolved by soft-laser applications.

Dental Caries↗

[Endoscopy in non-neoplastic cholestasis].

The role of endoscopic treatment of cholestasis is well codified as an alternative or adjuvant therapy to surgery, particularly in those cases where non malignant cause has been identified. Non-neoplastic cholestasis therefore benefits very substantially from endoscopic treatment in a context where the traditional surgical approach presents limitations in terms of morbidity and mortality. It should be borne in mind, however, that the two approaches are strictly complementary for the correct management of these patients.

Cholestasis↗

[Benign esophageal stenosis: role of endoscopic therapy].

The authors report on their experience over a period of three years with the endoscopic treatment of benign oesophageal stenosis utilising the endoscopic balloon dilatation (EBD) technique or Savary-Gilliard cylindrical-conical dilators. They evaluate the results of the therapy with clinical and endoscopic follow-up at six-monthly intervals. The treatment proved effective, with total remission of dysphagia symptoms in approximately 95% of patients and with a low risk of complications.

Adolescent↗

[Emergency situations in ambulatory dentistry. 1. Local and systemic incidents].

After a preliminary classification, the authors describe their diagnostic process and the therapies to resolve the main emergency problems in dentistry. They suggest the basic equipment that every study needs and present future works in which they will analyze the most important aspects of this problem.

Anaphylaxis↗