Diffuse, micronodular lung disease. The high-resolution CT approach. A pictorial essay

Careful HRCT evaluation of the preferential distribution of micronodular lesions within the secondary lobule provides a fundamental contribution in the correct interpretation of the different associated patterns. This paper suggests a modern diagnostic algorithm that, together with clinical-anamnestic data and additional imaging features, is able to provide a definitive diagnosis or to reduce the possible differential diagnoses.     

Factors affecting the decision regarding amniocentesis in women at genetic risk because of age 35 years or older

OBJECTIVE: To evaluate the effects of anamnestic factors and sonographic findings on the patient's decision regarding amniocentesis in a cohort of women at genetic risk because of advanced age. METHODS: All women 35 years of age or older registered for prenatal care between January 1990 and December 1998 were asked about their attitude towards genetic amniocentesis during the course of individual genetic counseling and once again after ultrasound examination inclusive of markers of aneuploidies (nuchal fold thickness greater than 6 mm, renal pyelectasis, choroid plexus cysts, and hyperechogenic bowel). Their attitudes towards genetic amniocentesis before and after ultrasound examination were compared using chi-square, Fisher's exact test, Mann-Whitney U-test, and logistic regression analysis, with a two-tailed p < 0.05 or an odds ratio (OR) with 95% confidence interval (CI) not inclusive of the unity considered significant. RESULTS: Among the 1486 women in the cohort, 1368 (97%) expressed an opinion towards genetic testing at the time of counseling: 501 (37%) were in favor and 867 (63%) were against having the procedure. After ultrasonographic examination, 33% (446/1368) of women opted for amniocentesis, 36% (146/402) after abnormal findings and 31% (300/966) after normal ultrasound findings. Significantly more women with abnormal than normal ultrasound findings opted for diagnostic testing in both groups. Overall, only 8% (115/1368) of women changed their attitude towards diagnostic testing after ultrasonographic examination. Normal sonographic findings were three times more likely to change the attitude of women initially interested in amniocentesis than abnormal sonographic findings did in women a priori not interested in the procedure (20% versus 7%, p < 0.001, OR = 3.2, 95% CI 1.8; 5.8). CONCLUSIONS: In a cohort of women at genetic risk because of advanced age, the key determinant of the choice regarding genetic amniocentesis is the a priori opinion of the woman towards the procedure, which was expressed by 93% of women. Ultrasonography plays a secondary role in changing or confirming women's attitude towards invasive diagnostic testing. Normal sonographic findings affect women's decisions more powerfully than abnormal sonographic findings, suggesting that ultrasonography has an important reassuring function for the woman.     

Diffusion-weighted MR imaging of pyogenic ventriculitis

OBJECTIVE: The purpose of this study was to describe the features of pyogenic ventriculitis (ventricular empyema, pyocephalus) on diffusion-weighted MR imaging. CONCLUSION: Markedly increased signal intensity of dependent intraventricular fluid on diffusion-weighted MR imaging and an apparent diffusion coefficient that is less than that of normal cerebral white matter indicate restricted water diffusion in purulent fluid and suggest the diagnosis of pyogenic ventriculitis.     

Glucose-6-phosphate dehydrogenase expression associated with NADPH-dependent reactions in cerebellar neurons

This review describes the variation of glucose-6-phosphate dehydrogenase (G6PD) activity in the main neurons of the molecular and granular layers as well as in the deep nuclei of the cerebellum as observed so far by optical and electron microscopy studies. Light microscopy and semiquantitative microphotometry of histochemical staining showed that the highest G6PD activity was expressed by Purkinje cells and neurons of the deep cerebellar nuclei; the elements of the molecular layer showed a diffuse G6PD staining, while the granular layer displayed only scattered G6PD activity. Electron microscopy analysis showed that the basket and stellate cells, as well as the Golgi cells, have a remarkable G6PD activity, while in the granule cells the enzyme was barely detectable. The results show that cerebellar G6PD activity changes with different neuron types as a function of its role in sustaining NADPH dependent pathways in these cells.     

Expansion of tumor-specific CD8+ T cell clones in patients with relapsed myeloma after donor lymphocyte infusion

Donor lymphocyte infusions (DLI) provide effective therapy for patients with multiple myeloma who have relapsed after allogeneic bone marrow transplantation. However, the immunological mechanisms of the graft-versus-myeloma (GVM) effect have not been defined, and the target antigens of this response have not been identified. Molecular analysis of CDR3 Vbeta repertoire after CD4+ DLI demonstrated previously that the development of GVM and graft-versus-host-disease (GVHD) were associated with the clonal expansion of distinct T-cell populations in patient peripheral blood. In the current study, we undertook a molecular and functional characterization of GVM- and GVHD-associated T-cell clones. T-cell clones associated with GVM were detectable by clone-specific PCR at a low level in peripheral blood before DLI and expanded approximately 10-fold after DLI. In contrast, T-cell clones associated with GVHD were not detectable before DLI or before the development of clinical GVHD. Two T-cell clones associated with GVM were isolated and expanded in vitro, allowing their phenotypic and functional characterization. Both GVM clones were derived from donor cells and had a CD3+CD8+CD4- phenotype. One GVM clone specifically recognized patient myeloma cells in an HLA class I-restricted manner, but was not reactive with patient normal bone marrow cells or patient EBV transformed B cells. Taken together, these findings suggest that the GVM response is mediated by donor-derived CD8+ T-cell clones with antimyeloma specificity that may be present before DLI. In contrast, T-cell clones associated with GVHD are expanded de novo after DLI.     

Predictive variables for malignant transformation in 452 patients with asymptomatic IgM monoclonal gammopathy

The natural history of asymptomatic IgM monoclonal gammopathies (MG) and variables predicting evolution to symptomatic lymphoproliferative disorders were investigated in 452 patients diagnosed from 1975 to 2001. Univariate and multivariate Cox models were used to identify possible predictors of disease progression. At a median follow-up of 49 months (range, 12 to 233), 41 cases (9.1%) evolved to symptomatic Waldenstrom's macroglobulinemia (n = 36), non-Hodgkin's lymphoma (n = 2), B-cell chronic lymphocytic leukemia (n = 1), IgM multiple myeloma (n = 1), and primary amyloidosis (n = 1); the median interval from diagnosis was 53 months (range, 12 to 154). The cumulative probabilities of transformation into a symptomatic lymphoproliferative disease at 5 and 10 years were 8% (95% confidence interval [CI], 6% to 12%) and 21% (95% CI, 16% to 29%), respectively. At univariate analysis, monoclonal component size and hemoglobin level as continuous parameters, lymphocytosis (>4 x 10(9)/L), bone marrow lymphoplasmacytoid infiltration (>10%), erythrocyte sedimentation rate (>40 mm/h), and detectable Bence Jones proteinuria were significantly related with evolution probability. At multivariate analysis, paraprotein level (P <.0001), hemoglobin level (P <.05), and lymphocytosis (P <.0001) independently predicted malignant evolution (P <.0001). In conclusion, patients with asymptomatic IgM-MG showing hematological features predictive of progression should be carefully monitored in view of an early treatment of the disease.     

Effects of cannabinoids on non-adrenergic non-cholinergic-mediated relaxation in guinea-pig trachea

The effects of cannabinoid receptor agonists on the non-adrenergic non-cholinergic (NANC) inhibitory responses to electrical field stimulation in guinea-pig trachea were assessed. R-(+)-[2,3-dihydro-5-methyl-3-[(morpholilinyl) methyl]pyrrolo [1,2,3-de]-1,4-benzoxazin-6-yl]-(1-naphthalenyl)methanone mesylate (WIN 55,212-2; 10(-5) M) significantly enhanced the frequency-dependent response to electrical stimulation. The same concentration of R-(N)-(2-hydroxy-1-methylethyl)-5Z,8Z,11Z,14Z-eicosatetraenamide (R(+)methanandamide) and 1-propyl-2-methyl-3-(1-naphthoyl)indole (JWH-015) did not affect significantly the electrically induced inhibitory NANC responses. The effect of WIN 55,212-2 was not modified by the cannabinoid CB1 and CB2 receptor-selective antagonists, N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide hydrochloride (SR141716A; 10(-5) M) and N-(1S)-endo-1,3,3-trimethyl bicyclo [2.2.1] heptan-2-yl]-5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)-pyrazole-3-carboxamide (SR 144528; 10(-5) M), respectively. Moreover, the nitric oxide synthase inhibitor, L-NG-nitro-arginine methyl ester (L-NAME; 10(-4) M), but not the peptidase, alpha-chymotrypsin (2 U/ml), blocked the effect of WIN 55,212-2. Postsynaptically, WIN 55,212-2 did not produce any change of tracheal smooth muscle tone, either basal or histamine-induced, and did not interfere with the relaxant activity of the nitric oxide donor, sodium nitroprusside (10(-8)-10(-4) M). In conclusion, our results suggest that (a) cannabinoid CB1 and CB2 receptor stimulation does not alter the inhibitory NANC transmission in guinea-pig trachea, and (b) WIN 55,212-2 potentiates the NO-mediated component of the NANC relaxant response to electrical stimulation through a cannabinoid receptor-independent mechanism.     

Synthesis and pharmacological evaluation of new N-methyl-arylpyrrolidinols with analgesic activity

In the present paper, we report on the synthesis and antinociceptive activity of a new series of N-methyl-arylpyrrolidinols that we designed for a rational structure-activity relationship (SAR) study. The antinociceptive properties were investigated in vivo by the hot plate and formalin tests in mice and control on the locomotory activity was also monitored by the rota rod test. With this aim, the evaluation of the lipophilicity of all compounds was performed by the Daylight computational method in order to better understand the SAR. Interesting properties were proven for the compounds of the entire series.     

The xanthones gentiacaulein and gentiakochianin are responsible for the vasodilator action of the roots of Gentiana kochiana

Gentiana kochiana Perr. et Song. (Gentianaceae), a plant used in the traditional medicine of Tuscany (Italy) as antihypertensive remedy, exerts a vasodilator action on in vitro aortic rings that is probably linked to the blocking of the ryanodine-sensitive Ca++ channels. In the present study, three known xanthones were isolated from the crude methanolic extract of the roots: gentiacaulein, gentiakochianin, and swertiaperennin. The first two showed a vasorelaxing activity in rat aortic preparations, pre-contracted by 3 microM norepinephrine (pIC50 = 5.00 +/- 0.032 for gentiacaulein, pIC50 = 4.95 +/- 0.068 for gentiakochianin), 20 mM KCl (pIC50 = 4.90 +/- 0.15 for gentiacaulein; 4.59 +/- 0.069 for gentiakochianin), or 5 mM caffeine; on the contrary, in the same conditions, swertiaperennin did not show any vasodilator effect. In conclusion, gentiacaulein and gentiakochianin seem to be the compounds responsible for the vasorelaxing properties of the crude extract of Gentiana kochiana roots.