CT colonography: contrast enhancement of benign and malignant colorectal lesions versus fecal residuals.

We retrospectively reviewed the computed tomographic colonographic datasets of 22 patients. Mean attenuation values of benign polyps before and after contrast administration were 30 +/- 15 HU and 90 +/- 18 HU, respectively. Mean attenuation values of colorectal cancer before and after contrast administration were 43 +/- 15 HU and 124 +/- 18 HU, respectively. The mean attenuation value of solid fecal residuals was 43 +/- 15 HU. The difference in attenuation value between precontrast and postcontrast studies of polyps was statistically significant (mean 60 HU, p < 0.01); the same was true for colorectal cancer (mean 81 HU, p < 0.01). The difference between postcontrast density of polyps and cancer with respect to density of solid fecal residuals was statistically significant (p < 0.01). The use of contrast medium could be of help in computed tomographic colonography for discriminating polypoid benign lesions and colorectal cancer from fecal residuals.

An exploratory study on pharmacogenetics of inosine-monophosphate dehydrogenase II in peripheral mononuclear cells from liver-transplant recipients.

Mycophenolate mofetil (MMF) is an immunosuppressant used for the prophylaxis of rejection in renal, pancreas, and liver transplantation. It inhibits the inducible isoform of the enzyme inosine-monophosphate dehydrogenase (IMPDH II) via its active metabolite mycophenolic acid (MPA). IMPDH II is necessary for de novo purine synthesis in activated lymphocytes. The aims of the present study were to evaluate the feasibility of a real-time polymerase chain reaction (PCR) quantitative assessment of IMPDH II gene expression in liver transplant recipients as well as to provide a preliminary evaluation of possible correlations with drug tolerability. RNA was extracted from peripheral blood mononuclear cells of liver recipients after at least 6 months of MMF administration. IMPDH II gene expression was assessed using quantitative, real-time PCR and normalized using glyceraldheyde-3-phosphate dehydrogenase (GAPDH). Finally, adverse events associated with MMF administration were recorded. Real-time PCR quantitation of IMPDH II gene expression was reliable, sensitive, and specific. The intrapatient variability for both IMPDH II and GAPDH assays was lower than 0.6% in all patients. The results demonstrated a wide interpatient variability, with the mean value +/- standard deviation of 0.949 +/- 0.525 (95% confidence interval, 0.669-1.229) and a median value of 0.797. Patients with treatment-related toxicities displayed a trend to a higher level of IMPDH II expression than those without toxicity (mean, 1.126 vs 0.771). In conclusion, pharmacogenetic analysis of IMPDH II may represent a novel approach to MMF therapeutic monitoring.

Relationship between 5-fluorouracil disposition, toxicity and dihydropyrimidine dehydrogenase activity in cancer patients.

BACKGROUND: Previous work demonstrated that 5-fluorouracil (5-FU) metabolism is a critical factor for treatment tolerability. In order to study the predictivity of pharmacokinetics with respect to the occurrence of 5-FU toxicity, this study investigates the relationship between the pharmacokinetics of 5-FU and its metabolite 5-fluoro-5,6-dihydrouracil (5-FDHU), dihydropyrimidine dehydrogenase (DPD) activity in peripheral blood mononuclear cells (PBMNC) and treatment tolerability. PATIENTS AND METHODS: Pharmacokinetics and metabolism of 5-FU and activity of DPD in PBMNC were examined in 110 colorectal cancer patients given adjuvant 5-FU 370 mg/m2 plus L-folinic acid 100 mg/m2 for five days every four weeks. Drug levels were examined by HPLC. while toxicities were graded according to WHO criteria. RESULTS: DPD activity in patients with mild toxicities (WHO grade < or = 1) was 197.22 < or = 11.34 pmol of 5-FDHU/min/ mg of protein, while in five patients with grade 3-4 gastrointestinal toxicity, DPD ranged from low to normal values (range 31.12-182.37 pmol/min/mg of protein). In these patients. 5-FU clearance (CL) was lower (range 14.12-25.17 l/h/m2), and the area under the curve (AUC) was higher (range 14.70-26.20 h x microg/ml) than those observed in 84 patients with mild toxicities (CL, 56.30 +/- 3.60 l/h/M2; AUC, 7.91 +/- 0.44 h x microg/ml). The severity of adverse events was associated with increased 5-FU/5-FDHU AUC ratio and reduced 5-FU CL, while 5-FU and 5-FDHU pharmacokinetics were not related to DPD activity. CONCLUSION: This study shows that DPD activity in PBMNC is unrelated to 5-FU/5-FDHU disposition and patients with severe toxicity display marked pharmacokinetic alterations while a reduction of DPD activity may not occur.

[The triumph of China China] / Il trionfo della China china.

Malaria and its various remedies were frequently debated by Italian scientists in the 17th and 18th centuries. Physicians of the period discussed the probable origin of the disease, making use of the humoral theory, whilst upholding the efficacy of a new remedy, the bark of the cinchona tree. Knowledge of malaria, the various pathogenetic theories and some quite bizarre therapeutic attempts are amply documented in the medical literature of the age.

Strascino's compliant. Syphilis and the XVI Century Sienese theatre.

Niccolo Campani, known with the nickname "Strascino" (as shabby, beggarly), is among the most important poets in the XVI Century in Italian theatre. Famous for his sharp-witted humor and the perfect Tuscan rhyming, the Sienese poet left a work whose subject is syphilis, cooght by Campany from 1503 to 1511. In Strascino's Compliant, the poet describes in rhyme the course and recovery of the illness, giving a very personal testimony of being ill with the "la malaise francaise" and a broad overview of the sixteenth Century in Italy

The struggle against the variolous poison (Part 1).

Not available

[The struggle against the variolous poison (Part 2)] / La "questione dell'innesto de' vajuoli" ovvero la lotta contro il "veleno varioloso" (II parte).

Not available

A molecular model of artificial glycoprotein with predetermined multiple immunodeterminants for gram-positive and gram-negative encapsulated bacteria.

An artificial molecule was synthesized by covalently linking the oligosaccharide haptens derived frm Streptococcus pneumoniae type 6A and Neisseria meningitidis group C capsular polysaccharides to the non-toxic mutant protein CRM197, serologically related to diphtheria toxin. Immunochemical analysis using polyclonal and monoclonal antibodies showed in the glycoprotein the presence of specific immunodeterminants of the native polysaccharides and of the carrier protein. The immunological activity of this hybrid molecule tested in two animal models gave evidence for anamnestic induction of serum antibodies specifically directed to the three distinct native molecules. They neutralized the toxicity of diphtheria toxin, recognized the polysaccharide capsule of S. pneumoniae type 6A and 6B (group 6) strain and killed the N. meningitidis group C bacteria by complement-mediated bacterial lysis. These findings support the possibility of using in humans a multivalent antigen with immunogenic activity for several epidemiologically significant Gram-positive and Gram-negative encapsulated bacterial strains.

Specific antibodies to diphtheria toxin and type 6A pneumococcal capsular polysaccharide induced by a model of semi-synthetic glycoconjugate antigen.

A molecular model of a carbohydrate-protein conjugate is described, involving the non-toxic mutant protein CRM197, serologically related to the diphtheria toxin, covalently bound to a characterized oligosaccharide derived from the molecular structure of type 6A pneumococcal capsular polysaccharide. Physicochemical and immunochemical characteristics of this oligosaccharide-protein conjugate were consistent with a molecule showing a molar carbohydrate/protein ratio of 8, an av. mol. wt of 75,000, and retention of complete immunochemical identity when tested towards the homologous antisera. The immunological characteristics obtained after immunization of 2 animal models showed a high immunogenicity of the glycoconjugate specifically directed towards diphtheria toxin and the type 6A pneumococcal capsular polysaccharide.