The apparition macrophage and Döderlein bacillus is negatively correlated in class I Papanicolaou smear: A morphological examination.

BACKGROUND: Nonspecific vaginitis, also known as Bacterial vaginosis, unlike genital candidiasis and trichomoniasis, is caused by microbiome breakdown. Döderlein's bacillus are gram-positive bacillus that form a microbiome, reproduce in the female vagina after gaining sexual maturity, secrete lactic acid, and prevent the growth of other vaginitis-causing bacteria. Clue cell are squamous epithelial cells with Gardnerella sp. attached to their cell surface. The presence of clue cell is one of the diagnostic criteria for nonspecific vaginitis. Additionally, although macrophages are reported to protect against candidal vaginitis, there are no reports of studies examining the association between macrophages and clue cell. MATERIALS AND METHODS: After re-staining 300 class I specimens by cervical cancer screening with Papanicolaou staining, the appearance of Döderlein's bacillus, macrophages, and clue cell was observed. RESULT: Age group and appearance of Döderlein's bacillus were negatively correlated. The rate of appearance of macrophages was positively correlated with the age group. In people aged 50 years or more, the appearance rate of clue cells was significantly lower in the macrophage appearance group than that in the non-appearance group. CONCLUSION: This study suggested that macrophages, and not Döderlein's bacillus, may play an important role in defense against nonspecific vaginitis.

Effect of Oral Alfacalcidol on Clinical Outcomes in Patients Without Secondary Hyperparathyroidism Receiving Maintenance Hemodialysis: The J-DAVID Randomized Clinical Trial.

Importance: Patients with chronic kidney disease have impaired vitamin D activation and elevated cardiovascular risk. Observational studies in patients treated with hemodialysis showed that the use of active vitamin D sterols was associated with lower risk of all-cause mortality, regardless of parathyroid hormone levels. Objective: To determine whether vitamin D receptor activators reduce cardiovascular events and mortality in patients without secondary hyperparathyroidism undergoing hemodialysis. Design, Setting, and Participants: Randomized, open-label, blinded end point multicenter study of 1289 patients in 207 dialysis centers in Japan. The study included 976 patients receiving maintenance hemodialysis with serum intact parathyroid hormone levels less than or equal to 180 pg/mL. The first and last participants were enrolled on August 18, 2008, and January 26, 2011, respectively. The final date of follow-up was April 4, 2015. Interventions: Treatment with 0.5 µg of oral alfacalcidol per day (intervention group; n = 495) vs treatment without vitamin D receptor activators (control group; n = 481). Main Outcomes and Measures: The primary outcome was a composite measure of fatal and nonfatal cardiovascular events, including myocardial infarctions, hospitalizations for congestive heart failure, stroke, aortic dissection/rupture, amputation of lower limb due to ischemia, and cardiac sudden death; coronary revascularization; and leg artery revascularization during 48 months of follow-up. The secondary outcome was all-cause death. Results: Among 976 patients who were randomized from 108 dialysis centers, 964 patients were included in the intention-to-treat analysis (median age, 65 years; 386 women [40.0%]), and 944 (97.9%) completed the trial. During follow-up (median, 4.0 years), the primary composite outcome of cardiovascular events occurred in 103 of 488 patients (21.1%) in the intervention group and 85 of 476 patients (17.9%) in the control group (absolute difference, 3.25% [95% CI, -1.75% to 8.24%]; hazard ratio, 1.25 [95% CI, 0.94-1.67]; P = .13). There was no significant difference in the secondary outcome of all-cause mortality between the groups (18.2% vs 16.8%, respectively; hazard ratio, 1.12 [95% CI, 0.83-1.52]; P = .46). Of the 488 participants in the intervention group, 199 (40.8%) experienced serious adverse events that were classified as cardiovascular, 64 (13.1%) experienced adverse events classified as infection, and 22 (4.5%) experienced malignancy-related serious adverse events. Of 476 participants in the control group, 191 (40.1%) experienced cardiovascular-related serious adverse events, 63 (13.2%) experienced infection-related serious adverse events, and 21 (4.4%) experienced malignancy-related adverse events. Conclusions and Relevance: Among patients without secondary hyperparathyroidism undergoing maintenance hemodialysis, oral alfacalcidol compared with usual care did not reduce the risk of a composite measure of select cardiovascular events. These findings do not support the use of vitamin D receptor activators for patients such as these. Trial Registration: UMIN-CTR Identifier: UMIN000001194.

Evaluation of percutaneous transluminal angioplasty screening using color Doppler ultrasonography.

PURPOSE: Well-functioning vascular access is important in hemodialysis patients. The aim of this study was to assess stenosis using color Doppler ultrasonography as well as to investigate a possible association between the need for percutaneous transluminal angioplasty and hemodynamic parameters. METHODS: A prospective study of the medical records of color Doppler ultrasonography routine examinations of 372 patients was conducted at a dialysis satellite clinic in Japan. Data were analyzed using logistic regression analysis and the receiver operating characteristic curve. The cutoff point for hemodynamic parameters was determined to explore the predictors of percutaneous transluminal angioplasty. RESULTS: Logistic regression analysis showed that brachial artery flow volume, brachial artery resistance index and puncture point flow volume divided by the quantity of dialysis blood flow rate were independently associated with percutaneous transluminal angioplasty.Brachial artery resistance index over 0.61, brachial artery blood flow volume under 665 mL/min and puncture point flow volume divided by dialysis blood flow rates under 1.25 were predictive values of the need for percutaneous transluminal angioplasty. CONCLUSIONS: These parameters could be used as markers for assessing percutaneous transluminal angioplasty risk in hemodialysis patients.

Questionnaire survey and serum phosphorus levels in maintenance hemodialysis patients switching lanthanum carbonate formulation from chewable tablets to granules.

We conducted a questionnaire survey of 79 maintenance hemodialysis patients switching lanthanum carbonate (LC) formulation from chewable tablets to granules, to investigate the compliance and patient preferences of these two formulations. For the number of times chewed when taking chewable tablets, the ratio of patients who responded 10 times or more was 54.4%, who responded four to nine times was 24.1% and who responded three times or less was 8.9%. Thirty-seven patients (46.8%) responded "Granules are easier to take", 22 patients (27.8%) responded "Chewable tablets are easier to take", and 20 patients (25.3%) responded "No difference between formulations." Changes in serum phosphorus (P) levels were also measured for 4 weeks after switching formulation, but no significant differences were observed before and after switching. We think that these questionnaire survey results show the compliance status and the patient needs for LC in the clinical practices.

Hepatitis C virus infection in 2,744 hemodialysis patients followed regularly at nine centers in Hiroshima during November 1999 through February 2003.

Patients on maintenance hemodialysis (HD) are at increased risk of infection with hepatitis C virus (HCV). A prospective follow-up study on HCV infection from November 1999 to February 2003 was conducted in nine hemodialysis (HD) units in Hiroshima. A total of 2,744 HD patients were surveyed regularly for HCV RNA in serum. The prevalence of HCV RNA decreased from 15.7% (262/1,664) on the first survey to 12.9% (242/1,882) in the last one (P<0.05). This decrease may be attributed to the inclusion of patients with a lower prevalence of HCV RNA compared to patients leaving dialysis centers (111/1,080 [10.3%] vs. 132/862 [15.3%], P<0.01). During the 40 months of this study, 16 de novo HCV infections were documented in the nine HD units corresponding to an incidence of 0.33% per year. These cases included eight new HCV infections, three re-infections, and five infections that presumably occured in the window period when tested during the first survey. Our study shows that the annual incidence of de novo HCV infection during HD was 0.33%, and emphasizes the need for frequent serum HCV RNA testing and for stringent disinfection procedures in order to prevent the transmission of HCV in these settings.

Early dynamics of hepatitis C virus in the circulation of chimpanzees with experimental infection.

Two chimpanzees were inoculated with hepatitis C virus (HCV) and followed on a daily basis for 12 days. HCV RNA became detectable in their sera on day 5 by polymerase chain reaction with the detection limit of 10(2) copies/ml. Based on an exponential growth observed until 8 or 9 days after inoculation in their sera, the doubling time of HCV in the circulation was estimated at 6.3-8.6 h and log time (time required to grow 10-fold) at 31.3- 42.9 h. The exact doubling time of HCV determined in them would help plan an efficient strategy for screening out blood donors in the window period of infection between the exposure and the development of antibody to HCV in serum.

Sex- and age-specific carriers of hepatitis B and C viruses in Japan estimated by the prevalence in the 3,485,648 first-time blood donors during 1995-2000.

OBJECTIVE: Carriers of hepatitis B virus (HBV) and hepatitis C virus (HCV) in Japan were estimated on a national basis. METHODS: Sera from the first-time blood donors aged 16-64 years in eight jurisdictions of the Japanese Red Cross Blood Center during 1995-2000 were tested for hepatitis B surface antigen (HBsAg) and antibody to HCV (anti-HCV). Viremia with HCV was estimated to be present in 70% of donors with anti-HCV. RESULTS: HBsAg was detected in 22,018 of 3,485,648 (0.63%) blood donors including 12,990 of 1,780,149 (0.73%) men and 9,028 of 1,705,499 (0.53%) women, and anti-HCV in 17,010 (0.49%) including 8,504 (0.48%) men and 8,506 (0.50%) women. Multiplying the carrier rate by the population registered in the Census 2000, the total HBV carriers aged 15-65 years were estimated at 967,753 (95% confidence interval 806,760-1,128,745), of whom 571,210 (479,267-663,152) were men and 396,543 (327,494-465,593) were women. Likewise, the total HCV carriers were estimated at 884,954 (95% confidence interval 725,082-1,044,826), of whom 464,363 (377,927-550,799) were men and 420,591 (347,156-494,027) were women. CONCLUSION: Estimated numbers of HBV and HCV carriers would help plan to prevent the development of hepatocellular carcinoma in Japan.

Titration of hepatitis C virus in chimpanzees for determining the copy number required for transmission.

OBJECTIVE: To determine the copy number of hepatitis C virus (HCV) RNA, determined by nucleic acid amplification test (NAT) for screening blood units in Japan, that can transmit infection to chimpanzees. METHODS: Fresh-frozen plasma with markers of HCV infection, as well as inocula pedigreed from 1 of them, were evaluated for the infectious activity in chimpanzees. RESULTS: One unit each (273-282 ml) of fresh-frozen plasma from 2 blood donors or a pool from 13 donors to make a unit, which contained high-titered antibody to HCV but without HCV RNA detectable by NAT, did not infect any of 3 chimpanzees. Two chimpanzees were infected, however, when they were inoculated with 1 ml of serum from a blood donor in the 'window period' of HCV infection and containing 7.0 x 10(6) copies/ml of HCV RNA. The preacute phase serum from 1 of them harvested 7 weeks after the inoculation was titrated in 2 chimpanzees, and an inoculum containing approximately 2 x 10(1) copies of HCV RNA could transmit infection to both of them. CONCLUSION: Approximately 20 copies of HCV can transmit infection to recipients, which needs to be taken into consideration in planning the screening of blood units for HCV RNA by NAT. Although the sensitivity of present NAT could be improved further, there would be a limit of it in detecting a low-level HCV RNA in the window period of donors with the infectious capacity in recipients.

Lack of epidemiological evidence for a role of resolved hepatitis B virus infection in hepatocarcinogenesis in patients infected with hepatitis C virus in Japan.

OBJECTIVE: The role of resolved hepatitis B virus (HBV) infection in promoting hepatocellular carcinoma (HCC) in patients infected with hepatitis C virus (HCV) in Japan was evaluated by epidemiological surveys. METHODS: Antibody to hepatitis B core (anti-HBc) was determined in age-matched blood donors, and the frequency was compared with that in patients with HCV-associated HCC in Japan. RESULTS: Anti-HBc was detected significantly more frequently in the blood donors with than without antibody to HCV (anti-HCV; 76/135 or 56.3% vs. 65/255 or 25.5%, p < 0.001). In the patients with HCV-associated HCC, anti-HBc was detected in 109 of 202 (54.0%), which was comparable to the frequency in anti-HCV-positive blood donors (56.3%). Among the blood donors with anti-HCV, the prevalence of anti-HBc was no different between those with and without HCV RNA in serum (40/77 or 51.9% vs. 36/58 or 62.1%). CONCLUSIONS: The individuals of an age with high cancer frequency (>or=40 years) in Japan would have been exposed to HBV frequently (>50%), whether or not they have developed HCV-associated HCC. Despite repeated assertions in the literature, no epidemiological evidence was obtained for a role of past HBV infection in hepatocarcinogenesis in patients infected with HCV in Japan.

Natural histories of hepatitis C virus infection in men and women simulated by the Markov model.

The Markov model was introduced to simulate natural histories of hepatitis C virus (HCV) infection in men and women. The data set was constructed on 942 HCV carriers who were examined at least once a year without receiving antiviral therapies. Based on 2,251 patient-year data, the probabilities of transition between any two of the four clinical states, i.e., asymptomatic carrier state, chronic hepatitis, liver cirrhosis and hepatocellular carcinoma in 1 year were calculated. Hepatocellular carcinoma was defined as the absorbing state from where no transitions occur. Probability matrices thus obtained on six each subsets of HCV infection (asymptomatic carrier state, chronic hepatitis and liver cirrhosis in men and women) in their forties, fifties, and sixties, were used to simulate long-term outcomes of HCV infection. Male asymptomatic carriers aged 40 years were expected to retain the asymptomatic carrier state in 2.6%, evolve into chronic hepatitis in 48.4%, liver cirrhosis in 14.6% and hepatocellular carcinoma in 34.4% after 30 years when they reached 70 years of age, in contrast to 1.9%, 45.3%, 32.8% and 20.0%, respectively, of female asymptomatic carriers. Likewise, male patients with chronic hepatitis aged 40 years were expected to remain with chronic hepatitis in 43.8%, evolve into liver cirrhosis in 15.0% and hepatocellular carcinoma in 41.1%, contrasting with 38.9%, 32.7% and 22.0%, respectively, of female patients during 30 years. The Markov model could simulate the outcomes of 153 HCV carriers identified among blood donors after 5 years. The Markov simulation would help in assessing the long-term outcome of HCV infection and making decisions in the management of HCV carriers toward prevention of hepatocellular carcinoma.

High incidence of extrahepatic manifestations in an HCV hyperendemic area.

We previously investigated the incidence of extrahepatic manifestations including oral precancerous disease among the inhabitants in a hepatitis C virus (HCV) hyperendemic area in Fukuoka in Japan. The present study design was based on a prospective cohort at the other HCV hyperendemic area. One oral surgeon examined the oral lesions of 59 adult inhabitants (21 men, 38 women; mean age of 70.7 years), of a hyperendemic area of HCV infection. Furthermore, all subjects were interviewed regarding the natural history of extrahepatic manifestations. All sera were examined for antibodies to HCV (anti-HCV), serum HCV RNA, HCV genotype, antinuclear antibody (ANA), rheumatoid factor (RF) activity, and anti-SS-A and-B antibodies. Anti-HCV or HCV RNA was detected in sera from 59 (100%) or 57 (96.7%) of all subjects. Oral lichen planus (OLP), leukoplakia with leukoedema, or only leukoedema was observed in 8 (8.5%), 1 (1.7%), or 2 (3.4%) subjects, respectively. The incidence of all subjects with one or more HCV-related extrahepatic manifestation was 66.1% (39/59). The subjects with dry mouth were 25.4% (15/59). There was no relation among these autoantibodies, symptoms of dry mouth, or prevalence of HCV-associated extrahepatic manifestations. These findings demonstrate that the inhabitants with HCV infection showed various extrahepatic manifestations, and was not always limited to specific HCV areas.