Characteristic findings of high-grade cervical intraepithelial neoplasia or more on magnifying endoscopy with narrow band imaging

Background

Colposcopy, which is a standard modality for diagnosing cervical intraepithelial neoplasia (CIN), can have limited accuracy owing to poor visibility. Flexible magnifying endoscopy with narrow band imaging (ME-NBI) has excellent diagnostic accuracy for early gastrointestinal neoplasms and is expected to be highly useful for CIN diagnosis. This study aimed to determine the characteristic findings and evaluate the diagnostic ability of ME-NBI for lesions ≥ CIN 3.

Methods

A well-designed prospective diagnostic case series conducted at multiple tertiary-care centers. A total of 24 patients who underwent cervical conization with a preoperative diagnosis of high-grade squamous cell intraepithelial lesions (HSILs) or lesions ≥ CIN 3 were enrolled. Prior to conization, still images and video of ME-NBI were captured to investigate the cervical lesions. The images were reviewed based on histological examination of the resected specimens.

Results

The NBI-ME images revealed the following abnormal findings: (1) light white epithelium (l-WE), (2) heavy white epithelium (h-WE), and (3) atypical intra-epithelial papillary capillary loop (IPCL). Pathological examination of the resected specimens confirmed cervical lesions ≥ CIN 3 in 21 patients. The ME-NBI findings were classified into four groups: l-WE, l-WE with atypical IPCL, h-WE, and h-WE with atypical IPCL, at rates of 0, 23.8, 9.5, and 66.7%, respectively. Additionally, all 3 patients with micro-invasive carcinoma showed a strong irregularity of IPCLs.

Conclusion

The lesions ≥ CIN 3 demonstrated characteristic ME-NBI findings of h-WE alone, or l-/h-WE with atypical micro-vessels. This study indicates that ME-NBI may have novel value for CIN diagnosis.

     

Drug binding and releasing characteristics of DNA/lipid/PLGA film

We evaluated the blended compound of DNA/lipid complexes and PLGA (poly(D,L-lactide-co-glycolide)) as a carrier material for drug delivery system (DDS). Transparent, self-standing DNA/lipid/PLGA films were prepared by casting from an organic solvent such as DMSO/chloroform. Daunorubicin hydrochloride (DH) could intercalate and groove bind into DNA in the films, whereby the amount of DH bound to the films was controlled by the latter's immersion period in DH aqueous solution. DH was released from DH films after immersion in PBS solution, whereby release rate was dependent on the chemical structure of lipids. Released DH caused reduction of cell viability during the cell culture of L929 mouse fibroblasts. These results suggested that DNA/lipid/PLGA film was a promising useful material for DDS.     

Differences in masticatory function of subjects with different closing path

PurposeThe purpose of this study was to clarify whether there was a difference in the masticatory function between two masticatory path patterns: a convex closing path and a concave closing path.MethodsFor 80 healthy subjects, the masticatory function (masticatory muscular activity, mandibular movement, and masticatory performance) when chewing a gummy jelly was recorded. Out of the 160 chewing cases (80 subjects chewing on either side), 65 cases (Group I) in which the incisal point opened in a linear or concave manner toward the working side and closed in a convex manner, and 15 cases (Group II) in which the opening path was the same as that in Group I, but the closing followed a concave path, were selected. For the masticatory function, the integral values per unit time of masseter and temporal muscular activities, the gape and masticatory width, the indicators representing the stability of movement path, and the glucose extraction from chewing gummy jelly were measured and compared between the two groups.ResultsThe integral values of muscular activities and the amount of glucose extraction were significantly greater in Group I. The gape and masticatory width were not significantly different between the groups. The values of the indicators representing the stability of path were smaller in Group I than in Group II.ConclusionFrom these results, it was suggested that there was a functional difference between Group I (with a convex closing path) and Group II (with a concave closing path), and that Group I had a superior masticatory function to Group II.     

Discovery, optimization, and pharmacological characterization of novel heteroaroylphenylureas antagonists of C-C chemokine ligand 2 function

Through the application of TRAP (target-related affinity profiling), we identified a novel class of heteroaroylphenylureas that inhibit human CCL2-induced chemotaxis of monocytes/macrophages both in vitro and in vivo. This inhibition was concentration-dependent and selective with regard to other chemokines. The compounds, however, did not antagonize the binding of (125)I-labeled CCL2 to the CCR2 receptor nor did they block CCR2-mediated signal transduction responses such as calcium mobilization. Optimization of early leads for potency and pharmacokinetic parameters resulted in the identification of 17, a potent inhibitor of chemotaxis (IC(50) = 80 nM) with excellent oral bioavailability in rats (F = 60%). Compound 17 reduced swelling and joint destruction in two rat models of rheumatoid arthritis and delayed disease onset and produced near complete resolution of symptoms in a mouse model of multiple sclerosis.     

Intermittent arm ischemia induces vasodilatation of the contralateral upper limb

Intermittent arm ischemia before percutaneous coronary intervention induces remote ischemic preconditioning (RIPC) and attenuates myocardial injury in patients with myocardial infarction. Several studies have shown that intermittent arm ischemia increases coronary flow and is related to autonomic nerve system. The aim of this study was to determine whether intermittent arm ischemia induces vasodilatation of other arteries and to assess changes in the autonomic nerve system during intermittent arm ischemia in humans. We measured change in the right brachial artery diameter during intermittent left arm ischemia through three cycles of 5-min inflation (200 mmHg) and 5-min deflation of a blood-pressure cuff using a 10-MHz linear array transducer probe in 20 healthy volunteers. We simultaneously performed power spectral analysis of heart rate. Ischemia-reperfusion of the left arm significantly dilated the right brachial artery time-dependently, resulting in a 3.2 ± 0.4% increase after the 3rd cycle. In the power spectral analysis of heart rate, the high-frequency domain (HF), which is a marker of parasympathetic activity, was significantly higher after the 3rd cycle of ischemia-reperfusion than baseline HF (P = 0.02). Intermittent arm ischemia was accompanied by vasodilatation of another artery and enhancement of parasympathetic activity. Those effects may play an important role in the mechanism of RIPC.     

Effects of basic fibroblast growth factor administration on vascular changes in wound healing of rat palates.

OBJECTIVE: The purpose of this study was to investigate the vascular changes induced by mucoperiosteal denudation of rat palate and to elucidate the effects of basic fibroblast growth factor (bFGF) administration on the palatal vascular network in wound healing. METHODS: A total of 117 male Wistar rats were used for the study on their 20th postnatal day. The animals were divided into three groups: a scar formation group, a basic fibroblast growth factor group, and a control group. The scar formation and basic fibroblast growth factor groups had lateral mucoperiosteum excised from the palate. In the basic fibroblast growth factor group, a solution of basic fibroblast growth factor was injected into the operated area 1 week after excision. At 6, 8, and 10 weeks postoperatively, palatal vascular changes were investigated by immunohistochemical staining and corrosion cast techniques. RESULTS: Throughout the experimental period, there were significantly fewer vessels in the scar formation group than in the control and basic fibroblast growth factor groups. In the basic fibroblast growth factor group, the elongation of new vessels and capillary proliferation proceeded, and after 10 weeks a highly organized vascular network was established. The scar formation group showed few Volkmann's canals that were shrunken or closed, whereas the basic fibroblast growth factor group evidenced Volkmann's canals with arterioles or venules, as seen in the control. CONCLUSIONS: The results suggested that injection of basic fibroblast growth factor into palatal wounds improves the vascular supply to the operated mucosa and underlying bone during and after palatal wound healing, which may contribute to tissue remodeling of the palate during growth.     

Efficacy and safety profile of imatinib mesylate (ST1571) in Japanese patients with advanced gastrointestinal stromal tumors: a phase II study (STI571B1202)

BACKGROUND: Imatinib mesylate, an inhibitor of KIT, ABL protein, and platelet-derived growth factor receptor alpha (PDGFRalpha) tyrosine kinase, has recently been found to have a dramatic antitumor effect on gastrointestinal stromal tumor (GIST). The aim of this study was to assess the efficacy and safety of imatinib mesylate in Japanese patients with advanced GIST. METHODS: Patients with measurable lesions were enrolled between April 1, 2002, and September 20, 2002, using a design based on previous phase II studies in the United States and the European Union. The diagnosis of GIST was proven histologically with positive immunostaining for KIT (CD117). Imatinib mesylate was administered at a dose of either 400 mg or 600 mg once a day. Pharmacokinetic parameters and mutation analysis of c-kit were also assessed in a subgroup of patients. RESULTS: A total of 74 patients (28 receiving imatinib mesylate at 400 mg/day; 46 receiving 600 mg/day); median age, 56.0 years, were enrolled. No patient had a complete response, 51 patients (69%) had a partial response, and 19 patients (26%) had stable disease. The median progression-free survival time was 96 weeks. The estimated 3-year overall survival (Kaplan-Meier) rate for all patients was 73.6%. The most frequent adverse effects related to the drug were nausea (78%), diarrhea (70%), dermatitis (62%), facial edema (61%), edema of the lower limbs (58%), vomiting (54%), and eyelid edema (51%). Most of the adverse effects were mild and manageable. CONCLUSION: Imatinib mesylate is generally safe and has significant activity in the treatment of advanced GIST in Japanese patients.     

Clinical evaluations of pituitary apoplexy in incidental nonfunctional pituitary adenomas

Pituitary apoplexy is an uncommon syndrome that often results in spontaneous hemorrhage or infarction of pituitary tumors or glands. We previously reported pituitary apoplexy occurred most frequently in nonfunctional pituitary adenomas among all types of pituitary incidentalomas. In the present study, we aimed to investigate the characteristics of pituitary apoplexy in patients with incidental nonfunctional pituitary adenomas. 65 patients with pituitary incidentaloma were enrolled. All patients underwent clinical/endocrinological/pathological investigations. As a result, 33 patients were diagnosed with nonfunctional pituitary adenomas. Of these, 12.1% of patients had pituitary apoplexy. There was no difference in tumor diameter, age, or sex between the apoplexy and the non-apoplexy groups. However, the liver enzymes aspartate transaminase and alanine aminotransferase were significantly higher, and plasma sodium and chloride levels were significantly lower in the apoplexy group than in the non-apoplexy group (each P < .05). In addition, low-density lipoprotein-cholesterol was significantly higher in the apoplexy group than in the non-apoplexy group (P < .05). Besides, thyroid-stimulating hormone, luteinizing hormone, follicle-stimulating hormone, and prolactin deficiencies were significantly more frequent in the apoplexy group than in the non-apoplexy group (each P < .05), and growth hormone and adrenocorticotropic hormone deficiencies were more frequent in the apoplexy group than in the non-apoplexy group (P = .09 and.08, respectively). Furthermore, tumor diameter was not associated with pituitary apoplexy, whereas thyroid-stimulating hormone, luteinizing hormone, and follicle-stimulating hormone deficiencies were significantly associated with the apoplexy group (each P < .05). Hence, the present study indicated that pituitary apoplexy could not be related to tumor diameter. Moreover, hormonal deficiencies, hepatic dysfunction, hyponatremia or hypochloremia, and dyslipidemia might be indicators of pituitary apoplexy. There could be the possibility the treatment for dyslipidemia prevents pituitary apoplexy.