Primary Alloproliferative TH1 Response Induced by Immature Plasmacytoid Dendritic Cells in Collaboration with Myeloid DCs

The role played by dendritic cell (DC) subsets in the immune response to alloantigens is not well defined. In vitro experiments have extensively shown that freshly isolated myeloid (M)DCs induce a strong T lymphocyte proliferation whereas plasmacytoid (P)DCs do not, unless activated by CD40 ligation. The aim of these studies was to explore whether the interplay among PDCs, MDCs and T cells modulates alloresponse. Freshly isolated MDCs and PDCs were merged in different proportions and used as antigen presenting cells (APCs) in mixed lymphocyte cultures (MLC). As described, isolated PDCs only induced a mild alloresponse, while MDCs were potent inducers of alloproliferation. Unexpectedly, when PDCs were merged with even low numbers of MDCs (down to 100 cells) and used as APCs, a potent Th1 cell proliferation was detected. Survival and maturation of PDCs was increased in these MLC conditions, which could partially explain the magnitude of the T-cell response. Interestingly, the proportion of IFNgamma-producing cells generated in such cultures was higher compared to MDC-stimulated cultures. These data suggest that the interaction between both DC subsets is determinant to generate a potent Th1 response, at least in an allogeneic situation, and may be relevant to the outcome of allogeneic stem cell transplantation.     

Lactitol versus lactulose in the treatment of acute portal systemic encephalopathy (PSE): A controlled trial

Preliminary data suggest that lactitol (beta-galactoside-sorbitol), a new synthetic non-absorbable disaccharide, has beneficial effects on chronic portal systemic encephalopathy. To compare the efficacy of lactitol vs. lactulose in the treatment of acute portal systemic encephalopathy (PSE), 40 cirrhotic patients with an acute episode of PSE were randomly allocated to one of two groups: group A (20 patients) received lactulose (30 ml/6 h) and group B (20 patients) lactitol (12 g/6 h). These doses were adjusted daily to obtain two bowel movements per day. The duration of treatment was 5 days. Age, sex, hepatic and renal function, precipitating factors and level of PSE measured by clinical examination, EEG and number connection test were similar in the two groups. A complete clinical resolution of PSE occurred in 11 patients in each group. In 5 patients of the lactulose group and in 6 of the lactitol group there was a moderate improvement of PSE during the study. Finally, 4 patients in the lactulose group and 3 in the lactitol group did not respond to treatment. No side effects attributable to therapy were observed in either group. These results indicate that lactitol is as effective as lactulose in the management of patients with cirrhosis and acute PSE.     

Hyper-IgM syndrome with CHARGE association

A girl with coloboma of the iris, sensorineural deafness, growth delay, distinctive face, and cranial nerve dysfunction was diagnosed of CHARGE association in the first year of life. She presented with repeated otitis. At 3 yr of age, the patient suffered a septicemia ( Streptococcus pneumoniae , Corynebacterium sp.). The immunoglobulin G (IgG) and IgA serum levels were decreased, IgM increased and cellular immunity parameters were normal, supporting the diagnosis of hyper-IgM (HIM) syndrome. The sequence of CD40 ligand and cytidine deaminase genes were normal. From then on, she was receiving immunoglobulin intravenously with an excellent outcome . Here, we report the first case of CHARGE association and HIM syndrome in the same patient. Although the cause could not be identified, a non-random link is likely.     

Study of the localization of radiopacities similar to calcified carotid atheroma by means of panoramic radiography.

OBJECTIVE: To determine the location in soft tissues of the calcifications, similar to calcified carotid atheromas, that can be observed radiographically in the cervical region in panoramic radiographs. STUDY DESIGN: In each anatomic cadaver specimen preserved in formol, consisting of the head and neck, radiopaque spheres (made from gutta-percha) were positioned in anatomic structures of the cervical region that can be sites of calcification. For each anatomic structure marked in this way, panoramic radiography was performed, consisting of 17 radiographs. The images obtained were analyzed by 24 examiners who indicated which radiographs, in their opinion, presented the radiopaque reference projected in the region of bifurcation of the carotid artery. Analysis of 2 proportions from agreement and disagreement was used to determine radiopacities that could be confused in panoramic radiographs with calcified atheromas in the carotid artery. RESULTS: The results showed that 75% (18) of the examiners correctly indicated the reference in the bifurcation of the carotid artery and 79.2% (19) indicated a triticeous cartilage as calcified atheroma of the carotid artery. CONCLUSIONS: Calcified atheromas of the carotid artery are not the only features that can produce radiopaque images lateral to the panoramic radiograph; the presence of calcification in the triticeous cartilage also can induce an erroneous diagnosis of calcified carotid atheroma.     

Use of a violence risk assessment tool in an acute care hospital: effectiveness in identifying violent patients.

This study examined the use and effectiveness of the Alert assessment form. The form is part of the Alert system, used by one large acute care hospital to identify patients with a propensity for violence. All reported incidents of patient violence from August 1, 2003, through December 31, 2004, were included in patient charts. One hundred seventeen violent patient charts were reviewed and compared with 161 non-violent patient charts, randomly chosen from the same time period. Overall use of the Alert assessment form for violent and non-violent patients was 75.7% and 35.4%, respectively. The assessment form was found to have moderate sensitivity (71%) and high specificity (94%). It is reasonably effective in identifying potentially violent or aggressive patients when it is used according to protocol. Efforts to improve the tool are warranted, as is evaluation of its benefit in settings with low prevalence of violence. Also, greater effort must be taken to prevent violence once an aggressive patient has been identified.     

PIP2 hydrolysis underlies agonist-induced inhibition and regulates voltage gating of two-pore domain K+ channels

Two-pore (2-P) domain potassium channels are implicated in the control of the resting membrane potential, hormonal secretion, and the amplitude, frequency and duration of the action potential. These channels are strongly regulated by hormones and neurotransmitters. Little is known, however, about the mechanism underlying their regulation. Here we show that phosphatidylinositol 4,5-bisphosphate (PIP₂) gating underlies several aspects of 2-P channel regulation. Our results demonstrate that all four 2-P channels tested, TASK1, TASK3, TREK1 and TRAAK are activated by PIP₂. We show that mechanical stimulation may promote PIP₂ activation of TRAAK channels. For TREK1, TASK1 and TASK3 channels, PIP₂ hydrolysis underlies inhibition by several agonists. The kinetics of inhibition by the PIP₂ scavenger polylysine, and the inhibition by the phosphatidylinositol 4-kinase inhibitor wortmannin correlated with the level of agonist-induced inhibition. This finding suggests that the strength of channel PIP₂ interactions determines the extent of PLC-induced inhibition. Finally, we show that PIP₂ hydrolysis modulates voltage dependence of TREK1 channels and the unrelated voltage-dependent KCNQ1 channels. Our results suggest that PIP₂ is a common gating molecule for K⁺ channel families despite their distinct structures and physiological properties.