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.

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.

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.

Trivalent cold recombinant influenza live vaccine in institutionalized children with bronchial asthma and patients with psychomotor retardation.

Twenty asthmatic children and 48 patients with severe psychomotor retardation were inoculated intranasally with trivalent cold-adapted recombinant (CR) influenza vaccine containing CR-125 (H1N1), CR-159 (H3N2) and CRB-117 (B). The vaccinees were mostly seropositive. Severe adverse reactions or asthmatic attacks were not observed, but 7 (15%) of 48 vaccinees with severe psychomotor retardation developed mild to moderate fever. Significant antibody responses in hemagglutination-inhibition tests were demonstrated in 33 (49%) vaccinees to CR-125, 20 (29%) to CR-159 and 8 (12%) to CRB-117. Two nosocomial outbreaks of influenza were observed in the subsequent winter. During an outbreak with H3N2 in one ward of severe psychomotor retardation patients, 2 (11%) of 18 vaccinees became infected compared with 10 (48%) of 21 placebo controls in the same ward (P < 0.05). In the other outbreak, with influenza B virus, 2 (14%) of 14 vaccinees and 13 (52%) of 25 controls in the ward for asthmatic children were infected (P < 0.05). The results indicate that trivalent CR vaccine is safe and effective against nosocomial outbreaks of influenza.

Imprint cytology of cat scratch disease. A report of eight cases.

The cytologic features of cat scratch disease (CSD) from eight cases in imprint smears are presented. All patients were clinicopathologically diagnosed with CSD as follows: 1) a history of animal exposure was recorded 2 to 4 weeks before lymphadenopathy; 2) the disease occurred in the autumn and winter months; 3) a characteristic histopathology in the biopsied lymph node specimens was observed; and 4) Warthin-Starry silver stain-positive bacteria were detected in four of the seven cases examined. The characteristic cytologic finding was the presence of confluent epithelioid cells with nearby and central scattering of neutrophils against a background of polymorphic inflammatory cells. Furthermore, a varying number of medium-sized to large lymphoid cells with an appearance suggestive of monocytoid B lymphocytes (MBLs) were noted to be associated with the epithelioid cells. These cytologic findings closely paralleled the histologic patterns of epithelioid cell granulomas, with and without MBLs, which we have previously reported are probably associated with the disease.

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.

Correlative interpretation of staphylococcal resistance to penicillinase-resistant penicillins by ceftizoxime disk susceptibility test using Showa disks.

The Showa disk susceptibility test (Showa Yakuhin Kako Company, Japan) was evaluated to discriminate between the strains of Staphylococcus aureus resistant to penicillinase-resistant penicillins (PRPs) and those susceptible. When we tested 129 PRP-resistant and 112 susceptible strains, many PRP-resistant strains were interpreted to be false susceptible to methicillin and oxacillin, especially when incubated at 37 degrees C. Growth at 30 degrees C and when NaCl was added to the medium improved the test reliability for detection of PRP resistance. Ceftizoxime disk (30 micrograms) susceptibility test results highly correlated with reference PRP resistance when incubated at 35 degrees C. All the PRP-resistant strains produced no zone of inhibition, whereas all of the PRP-susceptible strains were categorized as susceptible to ceftizoxime (greater than or equal to 22 mm, less than or equal to 3.13 micrograms/ml), for example, 100% correlation. It was concluded that the Showa ceftizoxime disk, in replacement of PRPs, will provide a reliable, alternative method to predict PRP resistance in S. aureus pending reevaluation of the Show PRP disk tests.

In vitro activity of 43 antimicrobial agents tested against ampicillin-resistant enterococci and gram-positive species resistant to vancomycin.

A total of 57 strains of ampicillin-resistant and -susceptible enterococci representing 10 species and 23 strains of vancomycin-resistant Gram-positive bacteria (Leuconostoc and Pediococcus) were tested to determine their susceptibility to 43 antimicrobial agents by the reference broth microdilution method. The drug MICs for the ampicillin-resistant enterococci were generally similar to those of ampicillin-susceptible strains, that is, highly resistant to cephalosporins, moderately susceptible or resistant to quinolones, and susceptible to "glycopeptides." Some investigational quinolones (PD127391, sparfloxacin, WIN57273), minocycline, and rifampin were highly active. Vancomycin-resistant strains were usually resistant to other "glycopeptides," for which correlation coefficients of MICs ranged from 0.881 to 0.978, except ramoplanin (MICs, 0.008-0.5 micrograms/ml). Most isolates resistant to vancomycin were susceptible to the newer quinolones, penicillins, aminoglycosides, clindamycin, and erythromycin, but highly resistant to cephalosporins. Discrepancies between the MICs and MBCs for glycopeptides were noted (greater than or equal to 8-fold, MBC50/MIC50), but not for ramoplanin. The vancomycin disk test was in 96.1% absolute agreement by identifying resistant strains without contributing false-susceptible, very major error.

Prevalence of enterococcal high-level aminoglycoside resistance in Japan. Comparative detection by three methods.

A total of 250 strains of enterococci isolated in Kumamoto University Hospital, Japan, during the period from January to March 1992 were tested for high-level aminoglycoside resistance. Brain-heart infusion (BHI) agar plates supplemented with 1000 micrograms/ml of gentamicin or 2000 micrograms/ml of streptomycin detected 164 (66%) isolates resistant to either gentamicin or streptomycin alone, or both, and consisted of 107 (43%) resistant to gentamicin and 96 (38%) resistant to streptomycin. The Vitek Gram-Positive Susceptibility card (GPS-TA) revealed high correlations with those by agar screens, the results indicating a sensitivity of 100% and 99% to gentamicin and streptomycin, respectively, and 100% specificity to both. Also, the microdilution tests of the National Committee for Clinical Laboratory Standards (NCCLS) showed 100% and 92% sensitivity to gentamicin and streptomycin, respectively, and no false resistance (100% specificity) when compared with the results by agar screens.

In vitro activity of three carbapenem antibiotics. Comparative studies with biapenem (L-627), imipenem, and meropenem against aerobic pathogens isolated worldwide.

The in vitro activity of biapenem (formerly L-627 or LJC10, 627), a new carbapenem, was compared with that of imipenem and meropenem against > 6000 clinically significant pathogens isolated in six countries worldwide. Biapenem was active against members of the family Enterobacteriaceae with a 90% minimum inhibitory concentration (MIC90) ranging from < or = 0.06 to 2 micrograms/ml. Only Serratia spp. and Providencia spp. were less susceptible (MIC90, 8 micrograms/ml). Pseudomonas aeruginosa and Xanthomonas maltophilia displayed an MIC90 of > or = 8 micrograms/ml biapenem/ml whereas Acinetobacter spp. were susceptible at < or = 1 micrograms/ml. Oxacillin-resistant staphylococci were resistant to biapenem at > 8 micrograms/ml whereas oxacillin-sensitive staphylococci were susceptible at < or = 1 micrograms/ml. Biapenem, imipenem, and meropenem displayed poor activity against Ent. faecium (MIC90, > or = 8 micrograms/ml), and only imipenem displayed slightly better activity against Ent. faecalis (MIC90, 4 micrograms/ml). The rank order of activity against groups of isolates was Enterobacteriaceae (meropenem > biapenem > or = imipenem), Ps. aeruginosa (biapenem = meropenem = imipenem), oxacillin-sensitive staphylococci (imipenem > or = biapenem = meropenem), oxacillin-resistant staphylococci (biapenem = meropenem = imipenem), and Enterococcus spp. (biapenem = meropenem = imipenem). These in vitro suggest that further developmental work on biapenem is warranted.

Antimicrobial activity of FK-037, a new broad-spectrum cephalosporin. International in vitro comparison with cefepime and ceftazidime.

The in vitro activity of FK-037, a new parenteral 7-aminothiazolyl-methoxyimino cephalosporin, was compared with cefepime and ceftazidime against 6094 aerobic isolates collected in six medical centers worldwide. FK-037 demonstrated potent activity against the Enterobacteriaceae family except for some Enterobacter spp., Providencia spp., and Serratia liquefaciens (MIC90s, > or = 16 micrograms/ml). Against nonenteric Gram-negative bacilli, all compounds tested showed similar, but more limited activity. The FK-037 MIC50s for Pseudomonas spp. and P. aeruginosa were 2 and 4 micrograms/ml, respectively. The least susceptible organisms were Xanthomonas maltophilia, enterococci, and Bacillus spp. (MIC50s, > 16 micrograms/ml), followed by Flavobacterium spp., other nonenterics, and oxacillin-resistant Staphylococcus aureus (MIC50s, 16 micrograms/ml). Good FK-037 activity was observed against oxacillin-susceptible staphylococci as well as against beta-hemolytic and viridans-group streptococci (MIC90 range, < or = 0.12 to 2 micrograms/ml). While FK-037 was slightly more active than cefepime against Gram-positive organisms, enteric bacilli were most susceptible to cefepime. Overall, the antibacterial spectrum of both FK-037 and cefepime was superior to ceftazidime.

Quantification of urinary glucose and protein with test-strips through reflectometric analysis.

Reflectometric measurement of urine test-strips, using the Urotron RL9, was employed to quantify urinary glucose and protein. Although the test-strips (Combur-9-Test) are designed for qualitative use, the reflectance intensities determined by the Urotron RL9 are applicable to quantitative analysis. Reflectance quantitation and conventional colorimetric methods were closely correlated for glucose (r = 0.953) and protein (r = 0.906). Intra-assay coefficients of variation of reflectance value were less than 5%. The negative influence of ascorbic acid on glucose determination was defined quantitatively. A significant positive interference from hemoglobin on protein determination was also demonstrated, but effectively eliminated after compensating for urine color.