Sonographic findings of immunoglobulin G4-related sclerosing sialadenitis

Purpose

We evaluated the sonographic findings of immunoglobulin G4-related sclerosing sialadenitis (IgG4-SS).

Methods

Nineteen patients with IgG4-SS and 12 healthy volunteers (controls) were enrolled. The following sonographic features were evaluated: (1) enlargement of the submandibular gland by measurement of the longitudinal diameter and thickness; (2) the contour texture of the submandibular gland (smooth or rough); (3) the internal echo texture, categorized into three sonographic patterns (homogeneous, multiple hypoechoic nodule, and diffuse hypoechoic); and (4) quantitative color Doppler signaling.

Results

The longitudinal diameter and the thickness (mean ± SD) of the submandibular gland were significantly greater in patients than in controls (p = 0.005 and p < 0.001, respectively). Contour roughness was seen in 62.9 and 8.3 % of patients and controls (p < 0.001), respectively. Homogeneous echo textures alone were seen in controls, whereas multiple hypoechoic nodule patterns were seen in 60 % of the patients, and diffuse hypoechoic patterns were seen in 40 %. Color Doppler signaling (mean ± SD) was significantly higher in patients as compared with controls (p < 0.001).

Conclusion

Patients could be distinguished from healthy volunteers using four distinctive sonographic findings, suggesting that ultrasonography would be a useful diagnostic tool for IgG4-SS.

     

Synaptic vesicle dynamics in the mossy fiber-CA3 presynaptic terminals of mouse hippocampus

The mossy fiber (MF)-CA3 synapse in the hippocampus is unique in the CNS because of its wide dynamic range of transmitter release during short- and long-term plasticity. The presynaptic mechanisms underlying the fidelity of transmission were investigated for the MF-CA3 synapses. The relative size of readily releasable pool (RRP) of vesicles was estimated by counting the number of docked vesicles at an active zone (AZ) on the transmission electron microscopy (TEM) image. The size of the releasable pool and the exo-endocytosis kinetics were directly measured from individual large MF boutons in hippocampal slices of transgenic mice that selectively express synaptopHluorin (SpH), a pH-sensitive GFP fused to the lumenal aspect of one of the vesicular membrane proteins, VAMP-2, in these boutons. Here we found (1) there are distinct two vesicle pools, the resting pool which is resistant to exocytosis, and the releasable pool, (2) the initially docked vesicles are easily depleted and the RRP is maintained by refilling from the reserve subpopulation of releasable pool ("reserve" releasable pool), and (3) the contribution of rapid reuse of recycled vesicles is relatively small. Therefore, the fidelity of transmission is suggested to be ensured by the rapid refilling rate of RRP.     

Extramural cancer deposits without nodal structure in colorectal cancer: optimal categorization for prognostic staging

To establish an optimal categorization of cancer deposits without lymph node structure (extranodal cancer deposits [EX]) in a prognostic staging system, we analyzed 1,027 cases in which patients underwent potentially curative surgery for advanced colorectal adenocarcinoma. EX was classified as vascular invasion-type (VAS) or non-VAS.A total of 512 foci of EX were identified in 205 patients (20.0%), with VAS and non-VAS found in 68 and 182 patients, respectively. The hazard ratio for patients with nodal involvement was 3.6 and for patients with VAS and non-VAS, 2.5 and 4.7, respectively. Based on multivariate analysis of these 3 parameters, only nodal involvement and non-VAS were significant prognosticators. By using the Akaike information criterion, N staging was capable of predicting survival outcome with the highest accuracy when both nodal involvement and non-VAS were treated together as an N factor and VAS was treated as a T factor ("new categorization"). The clinical significance of the TNM grading system for colorectal cancer would be enhanced if we treat EX as a new categorization.     

Human plasma metabolic profiles of benzydamine,a flavin-containing monooxygenase probe substrate,simulated with pharmacokinetic data from control and humanized-liver mice

1.?Benzydamine is used clinically as a nonsteroidal anti-inflammatory drug in oral rinses and is employed in preclinical research as a flavin-containing monooxygenase (FMO) probe substrate. In this study, plasma concentrations of benzydamine and its primary N-oxide and N-demethylated metabolites were investigated in control TK-NOG mice, in humanized-liver mice, and in mice whose liver cells had been ablated with ganciclovir.

2.?Following oral administration of benzydamine (10?mg/kg) in humanized-liver TK-NOG mice, plasma concentrations of benzydamine N-oxide were slightly higher than those of demethyl benzydamine. In contrast, in control and ganciclovir-treated TK-NOG mice, concentrations of demethyl benzydamine were slightly higher than those of benzydamine N-oxide.

3.?Simulations of human plasma concentrations of benzydamine and its N-oxide were achieved using simplified physiologically based pharmacokinetic models based on data from control TK-NOG mice and from reported benzydamine concentrations after low-dose administration in humans. Estimated clearance rates based on data from humanized-liver and ganciclovir-treated TK-NOG mice were two orders magnitude high.

4.?The pharmacokinetic profiles of benzydamine were different for control and humanized-liver TK-NOG mice. Humanized-liver mice are generally accepted human models; however, drug oxidation in mouse kidney might need to be considered when probe substrates undergo FMO-dependent drug oxidation in mouse liver and kidney.     

Dose rectification of an imbalance between DPP4 and GLP‐1 ameliorates chronic stress‐related vascular aging and atherosclerosis?

Exposure to psychosocial stress is a risk factor for cardiovascular disease, including vascular aging and regeneration. Dipeptidyl peptidase‐4 (DPP‐4) exerts many physiological and pharmacological functions by regulating its extremely abundant substrates [eg., glucagon‐like peptide‐1 (GLP‐1), stromal cell‐derived factor‐1α/C‐X‐C chemokine receptor type‐4, etc.]. Over the past decade, emerging data has revealed unexpected roles for DPP‐4 and GLP‐1 in intracellular signaling, oxidative stress production, lipid metabolism, cell apoptosis, immune activation, insulin resistance, and inflammation. This mini review focuses on recent findings in this field, highlighting an imbalance between DPP4 and GLP‐1 as a potential therapeutic target in the management of vascular aging and atherosclerosis in animals under experimental stress conditions.     

Surveillance of Infectious Disease Occurrences in the Community: An Analysis of Symptom Presentation in the Emergency Department

OBJECTIVES: To determine the effectiveness of a simulated emergency department (ED)-based surveillance system to detect infectious disease (ID) occurrences in the community. METHODS: Medical records of patients presenting to an urban ED between January 1, 1999, and December 31, 2000, were retrospectively reviewed for ICD-9 codes related to ID symptomatology. ICD-9 codes, categorized into viral, gastrointestinal, skin, fever, central nervous system (CNS), or pulmonary symptom clusters, were correlated with reportable infectious diseases identified by the local health department (HD). These reportable infectious diseases are designated class A diseases (CADs) by the Ohio Department of Health. Cross-correlation functions (CCFs) tested the temporal relationship between ED symptom presentation and HD identification of CADs. The 95% confidence interval for lack of trend correlation was 0.0 +/- 0.074; thus CCFs > 0.074 were considered significant for trend correlation. Further cross-correlation analysis was performed after chronic and non-community-acquirable infectious diseases were removed from the HD database as a model for bioterrorism surveillance. RESULTS: Fifteen thousand five hundred sixty-nine ED patients and 6,489 HD patients were identified. Six thousand two hundred eight occurrences of true CADs were identified. Only 87 (1.33%) HD cases were processed on weekends. During the study period, increased ED symptom presentation preceded increased HD identification of respective CADs by 24 hours for all symptom clusters combined (CCF = 0.112), gastrointestinal symptoms (CCF = 0.084), pulmonary symptoms (CCF = 0.110), and CNS symptoms (CCF = 0.125). The bioterrorism surveillance model revealed increased ED symptom presentation continued to precede increased HD identification of the respective CADs by 24 hours for all symptom clusters combined (CCF = 0.080), pulmonary symptoms (CCF = 0.100), and CNS symptoms (CCF = 0.120). CONCLUSIONS: Surveillance of ED symptom presentation has the potential to identify clinically important ID occurrences in the community 24 hours prior to HD identification. Lack of weekend HD data collection suggests that the ED is a more appropriate setting for real-time ID surveillance.