Salivary Alpha-Amylase Activity and Mild Cognitive Impairment among Japanese Older Adults: The Toon Health Study.

BACKGROUND: There is growing interest in examining objective markers for early identification and behavioral intervention to prevent dementia and mild cognitive impairment in clinical and community settings. OBJECTIVE: To investigate the association between salivary alpha-amylase as an objective measure of psychological stress response and mild cognitive impairment for the implication of psychological stress in the development of mild cognitive impairment. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study involved 865 participants aged ≥ 65 years. A saliva sample was collected in the morning, and the levels of salivary alpha-amylase were assayed. Mild cognitive impairment was evaluated using the Japanese version of the Montreal Cognitive Assessment; a score < 26 was indicative of mild cognitive impairment. A multivariable logistic regression model was used to examine the association of salivary alpha-amylase and mild cognitive impairment after adjusting for age, sex, current drinking status, current smoking status, body mass index, hypertension, diabetes mellitus, physical activity, education, social support, social network, and heart rate variability. RESULTS: Salivary alpha-amylase was associated with mild cognitive impairment (the multivariable-adjusted odds ratio [95% confidence interval] for the 1-standard deviation increment of log-transformed salivary alpha-amylase was 1.24 [1.07-1.44]). This significant association persisted after adjusting for various confounding factors. CONCLUSION: Elevation of salivary alpha-amylase was associated with mild cognitive impairment among Japanese community-dwelling older adults. This suggests that salivary alpha-amylase is a useful objective marker of psychological stress responses associated with mild cognitive impairment.

Identification of the rate-determining process in the hepatic clearance of atorvastatin in a clinical cassette microdosing study.

Clearance of atorvastatin occurs through hepatic uptake by organic anion transporting polypeptides (OATPs) and subsequent metabolism by cytochrome P450 (CYP) 3A4. To demonstrate the relative importance of OATPs and CYP3A4 in the hepatic elimination of atorvastatin in vivo, a clinical cassette microdose study was performed. A cocktail consisting of a microdose of atorvastatin along with probe substrates for OATPs (pravastatin) and CYP3A4 (midazolam) was orally administered to eight healthy volunteers. The pharmacokinetics of this cocktail was observed at baseline, after an oral dose of 600 mg rifampicin (an inhibitor of OATPs), and after an intravenous dose of 200 mg itraconazole (a CYP3A4 inhibitor). Rifampicin increased the pravastatin dose-normalized area under the plasma concentration-time curve (AUC) (4.6-fold), and itraconazole significantly increased the midazolam dose-normalized AUC (1.7-fold). The atorvastatin dose-normalized AUC increased 12-fold when coadministered with rifampicin but did not change when coadministered with itraconazole. These results indicate that hepatic uptake via OATPs makes the dominant contribution to the hepatic elimination of atorvastatin at a subtherapeutic microdose.

Pyoderma gangrenosum of the eyelid: report of two cases and review of the literature.

Pyoderma gangrenosum (PG) of the eyelid is extremely rare, and its proper management is essential for the preservation of visual function. Here, we report 2 cases of PG of the eyelid with intraorbital involvement. In both cases, the skin and intraorbital lesions improved after systemic immunosuppressive therapies; however, corneal perforation occurred in 1 case. In order to assess the clinical features of PG of the eyelid and to obtain clues for optimal treatment, we reviewed 15 well-documented cases in the literature, including the present cases. Corneal perforation occurred in 4 cases and defective ocular motility in 1 case. Three patients eventually underwent enucleation of the affected eye. Our cases and the literature review clearly indicate that MRI is a powerful tool for evaluating the extent of extracutaneous PG lesions around the eye and that early diagnosis and immediate immunosuppressive therapy are crucial for the preservation of visual acuity.

Microdose study of a P-glycoprotein substrate, fexofenadine, using a non-radioisotope-labelled drug and LC/MS/MS.

OBJECTIVE: Fexofenadine is a P-glycoprotein substrate of low bioavailability. It is primarily excreted into faeces as a parent drug via biliary excretion. The predictability from microdose data for the drug absorbed via transporters such as P-glycoprotein is not known. Therefore, this study assessed the predictability of therapeutic-dose pharmacokinetics of fexofenadine from microdosing data using non-radioisotope-labelled drug and liquid chromatography/electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS). METHOD: In a single dose, randomized, two-way crossover study, eight subjects received a microdose (100 microg) or a therapeutic dose (60 mg) of fexofenadine. Blood samples were collected until 12 h after dosing, and assayed using LC/MS/MS. RESULTS: Plasma concentration-time curves of fexofenadine between microdose and therapeutic dose were similar. The mean +/- SD of C(max) normalized to 60 mg dose after microdose and therapeutic dose were 379 +/- 147 and 275 +/- 145 ng/mL respectively. The mean AUC(last) normalized to 60 mg dose after microdose and therapeutic dose were 1914 +/- 738 and 1431 +/- 432 ng/h/mL respectively. The mean dose-adjusted C(max) and AUC(last) after microdose were higher compared with those after therapeutic dose. Individual plots of C(max) and AUC(last) normalized to 60 mg dose, were similar for microdose and therapeutic dose. None of the pharmacokinetic parameters were statistically different using anova. Overall, the microdose pharmacokinetics profile was similar to, and hence predictive of, that of the therapeutic dose. CONCLUSION: For the P-glycoprotein substrate fexofenadine, the predictability of therapeutic-dose pharmacokinetics from microdose data was good. A microdose study using a non-radioisotope-labelled drug and LC/MS/MS is convenient, and has the potential to aid the early selection of drug candidates.

Primary cutaneous CD30+ anaplastic large-cell lymphoma with generalized skin involvement and involvement of one peripheral lymph node, successfully treated with low-dose oral etoposide.

Primary cutaneous CD30+ anaplastic large-cell lymphoma (PCALCL) in adults is rare, and the prognosis is generally excellent. Multifocal PCALCL tends to relapse after multiagent chemotherapy and is generally considered more prone to progress to extracutaneous involvement than is the localized disease. We report a 43-year-old woman with PCALCL who had generalized skin involvement accompanied by involvement of one peripheral draining lymph-node region. Although the disease relapsed after multiagent chemotherapy regimens, the disease was successfully treated with low-dose etoposide. We reviewed the previously reported cases of PCALCL treated with low-dose etoposide. We suggest that oral etoposide might be a useful effective treatment for treatment of relapsed multifocal PCALCL.

Changes in higher-order aberrations after scleral buckling surgery for rhegmatogenous retinal detachment.

PURPOSE: To evaluate changes in higher-order aberrations (HOAs) after scleral buckling surgery for the treatment of rhegmatogenous retinal detachment (RD). DESIGN: Prospective observational comparative case series. PARTICIPANTS: The study included 67 eyes of 67 rhegmatogenous RD patients undergoing scleral buckling surgery, and the fellow normal eyes comprised the control group. Twenty-seven eyes were treated with the segmental buckling procedure and 40 eyes received the encircling buckling procedure alone. METHODS: Hartmann-Shack wavefront analysis was performed at 2 weeks, 1 month, and 3 months postoperatively. MAIN OUTCOME MEASURE: Time course of changes in HOAs. RESULTS: Scleral buckling surgery significantly increased HOAs at 2 weeks (P<0.0001), 1 month (P<0.0005), and 3 months (P<0.05) postoperatively as compared with the control group. At 3 months postoperatively, the HOAs were significantly lower in the encircling group than in the segmental buckling group (P<0.05). The vertical coma (Zernike Z(3)(-1)) became negative (significantly lower than zero, P<0.01) in patients who received segmental buckling in the upper quadrant. The ocular HOAs and logarithm of the minimum angle of resolution best-corrected visual acuity significantly correlated at 3 months postoperatively (third-order root mean square [RMS]: r = 0.445, P<0.0005; fourth-order RMS: r = 0.489, P<0.0001). CONCLUSIONS: Scleral buckling surgery significantly increased HOAs. The segmental buckling procedure increased the HOAs to a greater extent and for a longer duration than the encircling procedure. The direction of coma aberration corresponded to the location of the segmental buckle. The increase in HOAs can be one of the factors responsible for visual disturbances after scleral buckling surgery.

Changes in corneal topography after 25-gauge transconjunctival sutureless vitrectomy versus after 20-gauge standard vitrectomy.

PURPOSE: To evaluate the changes in regular and irregular corneal astigmatism after 25-gauge transconjunctival sutureless vitrectomy and 20-gauge standard vitrectomy. DESIGN: Prospective observational comparative case series. PARTICIPANTS: Thirty-two eyes of 32 patients undergoing 25-gauge transconjunctival sutureless vitrectomy and 25 eyes of 24 patients undergoing 20-gauge standard vitrectomy. METHODS: Corneal topography was obtained preoperatively and at 2 weeks and 1 month postoperatively. MAIN OUTCOME MEASURES: The dioptric data of the central 3-mm zone of the cornea were decomposed using Fourier harmonic analysis into spherical power, regular astigmatism, asymmetry, and higher-order irregularity. RESULTS: None of the 4 Fourier indices changed throughout the observation period in the 25-gauge group. In the 20-gauge group, regular astigmatism, asymmetry, and higher-order irregularity were increased significantly at 2 weeks after vitrectomy (P<0.05, Wilcoxon signed-ranks test) and returned to preoperative levels by 1 month. The spherical power in the 20-gauge group did not change after surgery. For regular astigmatism, asymmetry, and higher-order irregularity, the 20-gauge group showed significantly greater surgically induced changes than the 25-gauge group (P<0.05, Mann-Whitney U test). CONCLUSIONS: Twenty-five-gauge transconjunctival sutureless vitrectomy does not induce significant changes in corneal topography and exerts little influence on the optical quality of the cornea.

A case of Bockenheimer's syndrome (genuine diffuse phlebectasia): venous involvement inside muscles was detected by magnetic resonance imaging.

We report a 13-year-old girl with an extensive bluish phlebectasia of the upper right arm and right side of the chest, which had been present since birth. There was no difference in length between the right (affected) and left (healthy) limbs, but the involved limb was thicker than the noninvolved limb. Magnetic resonance imaging showed distended veins with slow blood flow under the skin of the right limb. The veins inside the muscles of forearm were also involved. Histological examination of the bluish lesions revealed large phlebectasia showing distended veins without any proliferation of endothelial cells. The amount of elastin in the walls of these veins was decreased. The patient was diagnosed with Bockenheimer's syndrome. The characteristics of this rare syndrome are indicated and discussed.

Radiotherapy for extramammary Paget's disease: histopathological findings after radiotherapy.

Several reports have suggested the efficacy of radiotherapy for treating extramammary Paget's disease (EMPD); however, these reports comprised only clinical observations, without in-depth histopathological observations. We report our experience of genital EMPD treated by radiotherapy in two elderly women, and the marked efficacy of radiotherapy, confirmed both by clinical observation and by detailed histopathological investigations. Our cases agree with the notion that radiotherapy is useful as an alternative therapy for EMPD, and should be considered particularly in elderly patients who may not tolerate surgery well.

Bullous pemphigoid associated with dermatomyositis and colon carcinoma.

It has been suggested that both bullous pemphigoid (BP) and dermatomyositis are associated with internal malignancies. However, there are no reports of the coexistence of these three conditions in one patient. We report the first case, to our knowledge. of coexistent BP, dermatomyositis and colon carcinoma. An 81-year-old Japanese woman was diagnosed with dermatomyositis based on muscular weakness and tenderness of the extremities, increased levels of circulating muscle enzymes and histological inflammatory changes in skeletal muscle and skin. Carcinoma of the sigmoid colon was detected during screening for internal malignancy; she was therefore surgically treated. Ten days after the operation, several large bullous eruptions appeared on her extremities. From the histopathological, immunofluorescence microscopy and BP180 ELISA study findings, we diagnosed the bullous eruptions as BP. Coexistence of BP with dermatomyositis or colon carcinoma is rare. Although the reason why our case exhibited these three disorders is not understood, it is suggested that these conditions may be associated with epitope spreading.

Detection of legionella species in clinical samples: Comparison of polymerase chain reaction and urinary antigen detection kits.

BACKGROUND: Recently, two excellent methods have been used for the diagnosis of Legionnaires' disease: urinary antigen detection and PCR. The purpose of the present study is to analyze and evaluate the sensitivity and specificity of three different urinary antigen detection kits as well as PCR. MATERIALS AND METHODS: A total of 148 samples were collected from 33 patients between 1993 and 2004. These consisted of 73 urine samples obtained from 33 patients, 57 serum samples provided by 29 patients, and 18 respiratory tract specimens from 13 patients. Three commercially available kits were used to detect urinary antigen. For the 5S PCR reaction, primers L5SL2 and L5SR84 were used. RESULTS: Positive results were shown in all patients' urine (representing 79.5% of total samples) using the Binax EIA kit, in 93.9% patients (representing 75.3% samples) using the Binax NOW immunochromatographic kit, and in 90.9% (representing 72.6% samples) using the Biotest EIA kit. Urine samples from 12.1% patients (representing 6.8% of total samples), serum samples from 41.4% patients (representing 35.1% of total samples), and respiratory samples from 84.6% patients (representing 88.9% of total samples) showed positive results with PCR. CONCLUSION: In testing urine of legionellosis patients, it was suggested that three kits were all valuable tools for diagnosis of legionellosis. Since over one-third of patients' serum samples and most respiratory specimens showed positive results with PCR, the addition of PCR for testing of these samples might be useful, particularly in cases of culture negative and serum antibody negative patients.

Determination of in vitro synergy when three antimicrobial agents are combined against Mycobacterium tuberculosis.

We determined the in vitro antimycobacterial activity of rifampicin, isoniazid and a third agent in combination using a three-dimensional chequerboard in Middlebrook 7H9 broth microdilutions. Of 28 agents screened, ethambutol, streptomycin, clarithromycin, minocycline, ciprofloxacin, levofloxacin, sparfloxacin, gatifloxacin and sitafloxacin were potentially synergistic. A further three-dimensional chequerboard assay quantitatively looked for synergy against ten clinical isolates of Mycobacterium tuberculosis, including seven multidrug-resistant isolates. Sitafloxacin, gatifloxacin and clarithromycin showed significant synergy, with fractional inhibitory concentration indices ranging from 0.41 to 0.79, 0.39 to 0.90 and 0.48 to 0.95, respectively. It is concluded that three-dimensional chequerboard assay can quantitatively determine antimycobacterial synergy, and that fluoroquinolones and antibacterial agents such as clarithromycin are effective against multidrug-resistant isolates of M. tuberculosis when combined with rifampicin and isoniazid.

Human herpesvirus 8 (HHV8) sequence variations in HHV8 related tumours in Okinawa, a subtropical island in southern Japan.

BACKGROUND: Although rare in mainland Japan, classic Kaposi's sarcoma (KS) is frequently reported in Okinawa, a subtropical island in southern Japan. Human herpesvirus 8 (HHV8) has been identified in the tumours and geographical differences occur. AIM: To sequence HHV8 in classic and AIDS associated KS in Okinawa. MATERIALS/METHODS: Eight classic KS cases, one AIDS associated KS, five granuloma pyogenicum cases, two inflammatory pseudotumours, two Castleman's disease cases, one angiosarcoma, and one primary effusion lymphoma (PEL) were studied. As a control, HHV8 positive cultured PEL cells (TY-1) were used. The presence of HHV8 sequences was evaluated by PCR and in situ hybridisation. PCR products were sequenced. RESULTS: There were no histological differences among KS resulting from the different virus genotypes. HHV8 was detected in all cases of KS, in one PEL, and one granuloma pyogenicum. Eight classic KS cases and one granuloma pyogenicum were infected with HHV8 genotype II/C (K1 region) or subtype C (ORF26 region), which had a five amino acid deletion at K1 VR2 region. An AIDS associated KS and a PEL were infected with type I/A virus. CONCLUSION: In Okinawa, classic KS cases and one granuloma pyogenicum case were infected with HHV8 genotype II/C, also classified as subtype C. AIDS associated KS and PEL were infected with a different HHV8 (genotype I/A), similar to that found in the USA. In Okinawa, HHV8 infection is more than four times higher than in mainland Japan, resulting in many cases of KS because of HHV8 genotype II/C infection.