[Evaluation of Intervention by an Antimicrobial Stewardship Team for Patients with Bacteremia].

In this study, antimicrobial stewardship team (AST) intervention was evaluated by comparing patient outcomes and consumption of broad-spectrum antibiotics [carbapenem antibiotics and tazobactam/piperacillin (TAZ/PIPC)] before and after the intervention. There was no fluctuation in the consumption rate of carbapenem, TAZ/PIPC and other antibiotics, but there was a decreased annual consumption of antibiotics after AST intervention compared to before intervention. For the carbapenems, antimicrobial use density (AUD) of meropenem (MEPM) was highest in both periods, at 20.1 and 20.4 before and after AST intervention, respectively, with no significant change after AST intervention. However, the days of therapy (DOT) for MEPM were 27.4 and 24.8 d, respectively, with a decreasing trend after AST intervention. AUD and DOT for TAZ/PIPC after AST intervention were 6.5 and 8.1 d, respectively, which were lower than the pre-intervention values. Rapid identification of the causative strain enables early de-escalation and may improve the economics of antibiotic use, but there was no difference from before to after AST intervention. Compared with before and after strain identification, the carbapenem administration rate after AST intervention was significantly lower than the pre-intervention rate (p<0.01). There was no difference in 28-day mortality and treatment period before and after AST intervention, and there were no differences in outcomes such as resolution of bacteremia, mortality, exacerbation and no change from before to after AST intervention. Based on these results, we suggest that AST intervention can reduce consumption of antibiotics without altering patient outcomes.

Biomineral/Agarose Composite Gels Enhance Proliferation of Mesenchymal Stem Cells with Osteogenic Capability.

Hydroxyapatite (HA) or calcium carbonate (CaCO3) formed on an organic polymer of agarose gel is a biomaterial that can be used for bone tissue regeneration. However, in critical bone defects, the regeneration capability of these materials is limited. Mesenchymal stem cells (MSCs) are multipotent cells that can differentiate into bone forming osteoblasts. In this study, we loaded MSCs on HA- or CaCO3-formed agarose gel and cultured them with dexamethasone, which triggers the osteogenic differentiation of MSCs. High alkaline phosphatase activity was detected on both the HA- and CaCO3-formed agarose gels; however, basal activity was only detected on bare agarose gel. Bone-specific osteocalcin content was detected on CaCO3-formed agarose gel on Day 14 of culture, and levels subsequently increased over time. Similar osteocalcin content was detected on HA-formed agarose on Day 21 and levels increased on Day 28. In contrast, only small amounts of osteocalcin were found on bare agarose gel. Consequently, osteogenic capability of MSCs was enhanced on CaCO3-formed agarose at an early stage, and both HA- and CaCO3-formed agarose gels well supported the capability at a later stage. Therefore, MSCs loaded on either HA- or CaCO3-formed agarose could potentially be employed for the repair of critical bone defects.

The expression of both peroxisome proliferator-activated receptor delta and cyclooxygenase-2 in tissues is associated with poor prognosis in colorectal cancer patients.

BACKGROUND: The role of peroxisome proliferator-activated receptor delta (PPAR δ) in the development and progression of colorectal cancer (CRC) remains controversial. AIMS: We investigated the impact of PPAR δ expression in tissues on liver metastasis of CRC. METHODS: We analyzed samples of primary CRC and matched normal adjacent tissues from 52 patients for the expression of PPAR δ, cyclooxygenase (COX)-2, vascular endothelial growth factor (VEGF)-A, and CXC chemokine receptor 4 (CXCR4). Correlations of the molecules expressions with clinical characteristics and prognosis of patients were studied. RESULTS: The number of patients positive for PPAR δ, COX-2, CXCR4, and VEGF-A was 25, 33, 18, and 19, respectively. Among the PPAR δ (+)/COX-2 (+), PPAR δ (-)/COX-2 (+), PPAR δ (+)/COX-2 (-), and PPAR δ (-)/COX-2 (-) patient groups, PPAR δ (+)/COX-2 (+) patients had the highest incidence of liver metastasis (p<0.01). PPAR δ (+)/COX-2 (+) expression was a significant independent prognostic factor (HR=7.108, 95% CI 1.231-41.029, p=0.0283) by Cox proportional analysis. PPAR δ (+)/COX-2 (+) patients had the highest positivity for CXCR4 or VEGF-A in tissues (p<0.01). Among the patients in the CXCR4 (+)/VEGF-A (+), CXCR4 (+)/VEGF-A (-), CXCR4 (-)/VEGF-A (+), and CXCR4 (-)/VEGF-A (-) groups, CXCR4 (+)/VEGF-A (+) patients had the highest incidence of liver metastasis (p<0.01). CONCLUSIONS: The expression of both PPAR δ and COX-2 in tissues may lead to liver metastasis and consequent poor prognosis in CRC patients.

Gene silencing of complement C5a receptor using siRNA for preventing ischemia/reperfusion injury.

Ischemia/reperfusion (I/R) injury in organ transplantation significantly contributes to graft failure and is untreatable using current approaches. I/R injury is associated with activation of the complement system, leading to the release of anaphylatoxins, such as C5a, and the formation of the membrane attack complex. Here, we report a novel therapy for kidney I/R injury through silencing of the C5a receptor (C5aR) gene using siRNA. Mice were injected with 50 microg of C5aR siRNA 2 days before induction of ischemia. Renal ischemia was then induced through clamping of the renal vein and artery of the left kidney for 25 minutes. The therapeutic effects of siRNA on I/R were evaluated by assessment of renal function, histopathology, and inflammatory cytokines. siRNA targeting C5aR efficiently inhibited C5aR gene expression both in vitro and in vivo. Administering C5aR siRNA to mice preserved renal function from I/R injury, as evidenced by reduced levels of serum creatinine and blood urea nitrogen in the treated groups. Inhibition of C5aR also diminished in vivo production of the pro-inflammatory cytokine tumor necrosis factor-alpha and chemokines MIP-2 and KC, resulting in the reduction of neutrophils influx and cell necrosis in renal tissues. This study demonstrates that siRNA administration represents a novel approach to preventing renal I/R injury and may be used in a variety of clinical settings, including transplantation and acute tubular necrosis.

Association factors for atopic dermatitis in nursery school children in Ishigaki islands - Kyushu University Ishigaki Atopic Dermatitis Study (KIDS).

Atopic dermatitis (AD) is a multifactorial disease that usually decreases the quality of life of affected patients. The purpose of this study was to evaluate the associated factors for atopic dermatitis, asthma, rhinitis, and food allergy by physical examination of the skin and a questionnaire in nursery school children in Ishigaki Island, Okinawa, Japan. Enrolled in this study were 460 children from 0 to 6 years of age. Physical examination of skin symptoms and blood tests were performed. Information on past history and family history of atopic dermatitis, asthma, rhinitis, and food allergy were collected by questionnaire. The prevalence of atopic dermatitis was 12.2% (56/460). The cumulative prevalence of asthma, rhinitis, and food allergy was 19.9% (91/458), 3.3% (15/457), and 5.5% (25/456), respectively. In multivariate analysis, maternal history of rhinitis, atopic dermatitis siblings, past history of asthma and food allergy, and elevation of total IgE were significantly related to atopic dermatitis. A high total IgE level was a strong risk factor specific for atopic dermatitis in this population.

Antigen-specific therapy of rheumatoid arthritis.

BACKGROUND: Immunotherapy offers the promise of antigen-specific suppression of pathological immune responses in conditions such as autoimmunity and organ transplantation. Substantial advances have been made in recent years in terms of understanding basic immunological mechanisms of autoreactivity, as well as clinically implementing immune-based therapies that are antigen nonspecific. OBJECTIVE: To provide an integrated overview of the current state of the art in terms of antigen-specific tolerance induction, as well as to predict future directions for the field. METHODS: Examples of successes and failures of antigen-specific immunotherapy were sought. Particular attention was paid to the well-established collagen II-induced model of arthritis. RESULTS/CONCLUSIONS: Previous failures of antigen-specific immunotherapy were associated with lack of identification of clinically relevant antigens, as well as inappropriate tolerogenic methodologies. The advances in proteomics combined with novel gene-specific immune modulatory techniques place today's translational researchers in a unique position to tackle the problem of antigen-specific immunotherapeutic protocols.

Incidence of atopic dermatitis in nursery school children - a follow-up study from 2001 to 2004, Kyushu University Ishigaki Atopic Dermatitis Study (KIDS).

Atopic dermatitis (AD) is a multifactorial disease that usually decreases the quality of life of affected patients. We monitored the incidence of AD and serum total IgE levels annually among nursery school children in Ishigaki Island, Okinawa, Japan, from 2001 to 2004. A total of 1731 children were enrolled. The prevalence of AD ranged from 3.7 to 11% in each year, with no significant difference between boys and girls. 869 children were examined at least twice. 71.6% (53/74) of AD patients regressed spontaneously, whereas 5.5% (44/795) of non-AD individuals developed AD during the 3-year follow-up. Increases in total IgE levels were greater and more rapid in children with long-term AD than in those who had spontaneously regressed, had newly-developed AD or did not have AD. The regression rate of AD was > 70% while new-onset AD occurred at a rate of 3.67%/person year in nursery school children of Ishigaki Island.

[Pseudomembranous colitis after Helicobacter pylori eradication therapy].

A 69-year-old woman with gastritis was prescribed a 1-week triple regimen therapy of Amoxicillin, Clarithromycin, and Lansoprazole to eradicate Helicobacter pylori (H. pylori) starting on March 7, 2005. H. pylori was detected on the gastric mucosa by the urease test. Twenty days after eradication therapy, she began to suffer from profuse watery diarrhea. Colonoscopy on April 12 showed multiple pseudomembranes in the cecum and the transverse colon, leading to a diagnosis of pseudomembranous colitis. Because she had not taken Vancomycin (VCM) (500 mg/day) as directed, she had a relapse of watery diarrhea and was admitted on April 30. A stool test for Clostridium difficile (CD) toxin was positive, although colonoscopy showed only a few aphthoid erosions in the cecum and the transverse colon on May 6. She was treated with oral VCM (2000 mg/day) from May 6, and diarrhea disappeared by May 11. The stool test for CD toxin was negative, so VCM was discontinued. Care must thus be taken in H. pylori eradication to ensure that the triple regimen therapy does not lead to pseudomembranous colitis.

Strenuous physical labor is important as a cause of elevated alanine aminotransferase levels in Japanese patients with chronic hepatitis C viremia.

To clarify the influence of lifestyle habits on the elevated alanine aminotransferase (ALT) levels deterioration of Japanese patients with chronic hepatitis C virus (HCV) viremia, we investigated the effects of smoking, drinking, and physical labor on the disease course of the residents living in a rural area of Kyushu, Japan. The data of patients with chronic HCV viremia and control subjects without HCV infection were analyzed retrospectively from 1986 to 1992 and prospectively from 1993 to 2000. In 2000, a questionnaire was given to 268 HCV-infected patients and 275 control subjects to survey for the lifestyle habits. The data of serial ALT level testing during the observation period was used as a measure of liver damage: 183 HCV patients (68.3%) and 10 control subjects (3.6%) had abnormal ALT levels greater than 35 IU/1 for more than half of their observation period. The percentage of HCV patients with elevated ALT levels significantly increased with the daily consumption of alcohol (p < 0.0001), the length of time spent in strenuous physical labor per day (p = 0.0056), and the number of cigarettes smoked per day (p = 0.0003). A stepwise logistic regression analysis showed male sex (p = 0.003), platelet counts (p < 0.001), strenuous physical labor (p = 0.002), and drinking history (p = 0.007) to be significantly associated with the elevated ALT levels of HCV patients. When strenuous physical labor was done for over 2 h, the probability of elevated ALT levels was increased compared with patients engaging in strenuous physical labor under 2 h (estimated odds ratio = 1.82 [under 2 h], 20.60 [over 2 h]). Interestingly, strenuous physical labor was extracted before alcohol consumption as a significant factor in the elevated ALT levels. Among the control subjects, only the amount of alcohol consumed per day (p = 0.0001) was significantly associated with the elevated levels. These data suggests that strenuous physical labor over a long period of time might be related to elevated ALT levels in patients with chronic HCV viremia as well as drinking.

Helper T cell cytokine response to ribavirin priming before combined treatment with interferon alpha and ribavirin for patients with chronic hepatitis C.

The viral genotype and serum viral level influence the response to interferon (IFN) treatment in patients with chronic hepatitis C virus (HCV) viremia. The aim of this study was to investigate a possible relationship between early virological response and helper T (Th) cell cytokine expansion by 4 weeks of ribavirin (RIB) alone followed by IFN and RIB combined in patients with genotype 1b and a high HCV RNA level, patients reported not to respond well to IFN treatment. Eighty-one patients with genotype 1b and a high HCV RNA level, over 100 international unit per milliliter (KIU/mL) (by Amplicor HCV Monitor), were assigned to two groups: Group A (N = 40) with a 4-week RIB administration followed by a 24-week combination treatment, and Group B (N = 41) with a 24-week combination treatment only. Blood was obtained from each patient on the following schedule: at Baseline (4 weeks before day 0), on day 0 (initiation day of the RIB and IFN combination treatment), weeks 4 (4 weeks after the start of the combination treatment), and at the end of the combination treatment. Flow cytometry was used to investigate sequential changes of IFN-gamma producing (Th1) and interleukin-4 producing (Th2) cells from whole blood samples after stimulation with PMA and ionomycin. Serum HCV RNA clearances were 32.5% at week 4, 43.2% at week 8, 85.7% at the end of the combination treatment, and 22.9% within the 24-week follow-up in Group A; and 17.1%, 27.0%, 66.7% and 19.4% in Group B, respectively. The mean Th1/Th2 ratio significantly increased from 15.9 at baseline to 17.6 at day 0 with a decrease of Th2 cells, and then significantly decreased from 17.6 at day 0 to 15.5 at week 4 in Group A, while there was no significant change in Group B between baseline and day 0. In Group A, 13 patients with HCV RNA clearance within 4 weeks had a significantly increased Th1/Th2 ratio, from 14.0 at baseline to 22.1 at day 0, and then a significantly decreased ratio, from 22.1 at day 0 to 15.0 at week 4, while the others had no significant change in the ratio. RIB administration preceding combined treatment of RIB with IFN was more effective in Th2 cell expansion than the usual combined treatment of IFN with RIB and led to a relatively early virological clearance in chronic hepatitis C patients with genotype 1b and a high HCV RNA level.

Confirmation of nosocomial hepatitis C virus infection in a hemodialysis unit.

OBJECTIVES: To investigate a hepatitis C virus (HCV) outbreak in a hemodialysis unit and determine the source of transmission. METHODS: We have prospectively investigated the epidemiology of hemodialysis-related HCV infection in a single unit since 1989. In September 2000, acute hepatitis C (AH-C) was diagnosed in 5 patients by alanine aminotransferase elevation and HCV genotype 1b viremia without antibody to HCV. We surveyed the epidemiologic situation and performed polymerase chain reaction sequence analysis of the HCV 5'-noncoding (5'NC) region in the patients for comparison with 9 patients with chronic HCV genotype 1b viremia. RESULTS: Sequence analysis of the 5'NC region showed the consistency in the 5 independent clones from each AH-C patient and those from each chronic HCV viremia patient and no quasispecies over time in the clones of any of 14 analyzed patients. All AH-C patients had the same sequencing of the 6 variations in the region with the only other patient. A saline ampoule, used for heparin solution during hemodialysis, had a recap function. It was difficult to determine whether the ampoule was new or had already been used. The source-patient often underwent hemodialysis before the AH-C patients and most of their hemodialysis-related medicine was prepared during the source-patient's treatment. These findings suggested a high possibility that the AH-C patients shared a single heparin-saline solution ampoule contaminated by HCV from the source-patient. CONCLUSION: Nosocomial HCV infection occurred as a result of poor infection control practice when a patient with chronic HCV viremia received treatment prior to other hemodialysis patients.

Relationship of genotype rather than race to hepatitis B virus pathogenicity: a study of Japanese and Solomon Islanders.

The aim of this study was to determine the predominant hepatitis B virus (HBV) genotype in the Solomon Islands and determine if there is any racial correlation between genotype and hepatitis B e antigen (HBeAg) production in Japanese and Melanesian individuals. A total of 403 serum samples from 206 Melanesian HBV carriers in the Solomon Islands and 197 Japanese carriers from Fukuoka (n = 106) and Okinawa (n = 91) living in Japan in 2001 were tested. The HBV genotypes of 206 Melanesian subjects were 114 with genotype C (55.3%) and 92 with genotype D (44.7%). The HBV genotypes of 197 Japanese subjects were 74 with genotype B (37.6%) and 123 with genotype C (62.4%). The total HBeAg prevalence of subjects in Fukuoka (36.8%) was significantly higher than that of subjects in Okinawa (14.3%) (P < 0.0001) and subjects in the Solomon Islands (35.0%; P = 0.0014, by the Mantel-Haenszel test). The genotype C prevalences were significantly different, ranging from 24.2% in Okinawa, to 54.4% in the Solomon Islands, to 95.3% in Fukuoka (all P < 0.0001, by chi-square test). The prevalence of HBeAg positivity was significantly higher in Melanesian genotype C subjects (42.0%) than Melanesian genotype D subjects (26.6%) (P = 0.0310). Similarly, the prevalence of HBeAg positivity was significantly higher in Japanese genotype C subjects (36.6%) than Japanese genotype B subjects (9.5%) (P < 0.0001). These findings indicate that that HBV was of genotypes C and D in the Solomon Islands, and that the pathogenesis of HBV-infected patients is related to HBV genotype rather than race.

Double point mutation in the core promoter region of hepatitis B virus (HBV) genotype C may be related to liver deterioration in patients with chronic HBV infection.

BACKGROUND AND AIM: Hepatitis B virus (HBV) genotype C has a more severe pathogenesis than genotype B in Japan. We retrospectively investigated the relationship between HBV genotype and the core promoter (CP) (nt 1762 and 1764) and precore (PreC) (nt 1896) mutations of the HBV genome. METHODS: A total of 129 Japanese patients (42 genotype B and 87 genotype C) with chronic HBV infection, living in two different geographical areas in Japan, were evaluated (mean follow-up period 10.1 +/- 3.8 years). In 2000, CP and PreC HBV mutations were analyzed by direct sequencing from sera. Hepatitis B e antigen (HBeAg), HBV DNA and serial alanine aminotransferase (ALT) changes were followed and determined using serological methods. RESULTS: Genotype C patients had significantly higher rates of HBeAg (40.2%vs 2.4%), HBV DNA positivity (75.9%vs 7.1%) and ALT abnormality (71.3%vs 11.9%) than genotype B patients (all P < 0.05). Among genotype B patients, CP wild type (92.9%) was predominant and PreC mutation (88.1%) was predominant. However, among genotype C patients, CP mutation (75.9%) was predominant and PreC mutation (66.7%) was predominant. The CP mutation was found significantly more in genotype C than in genotype B (P < 0.05). Of the 67 patients with ALT abnormality, five (7.5%) genotype B and 62 (92.5%) genotype C patients (31 HBeAg positive and 31 negative) were found. Among the 31 genotype C patients who were HBeAg positive, the combination of CP mutation and PreC wild (54.8%) was predominant, while among the remaining 31 genotype C patients who were HBeAg negative, the combination of CP mutation and PreC mutant (71.0%) was predominant. CONCLUSION: Genotype C might be one of the worse prognostic markers in patients with chronic HBV infection, possibly because of mutation in the CP region.

A decrease in mother-to-child transmission of human T lymphotropic virus type I (HTLV-I) in Okinawa, Japan.

To investigate the chronologic change of mother-to-child transmission of human T lymphotropic virus type I (HTLV-I) in Okinawa, Japan, the presence of antibody to HTLV-I was tested in 4,187 healthy residents between, 4,528 nursery school children, and 3,837 pregnant women between 1968 and 2000. The chronologic change of the feeding method and the length of the breast-feeding period among 1,117 healthy mothers from 1937 to 1995 were also obtained by interview. Age-adjusted prevalence of HTLV-I among healthy residents decreased from 9.1% in 1968-1970 to 7.8% in 1981-1984 and to 6.3% in 1996-1998. The crude prevalence of antibody to HTLV-I among healthy residents less than 20 years old decreased significantly from 4.6% in 1968-1970 to 0.1% in 1996-1998 (P < 0.0001). The prevalence of antibody to HTLV-I among nursery school children decreased significantly over the study period, from a high of 1.8% in 1984 to a low of 0.2% in 1998 (P = 0.03). The prevalence among pregnant women decreased significantly from 5.6% in 1989-1992 to 3.7% in 1997-2000 (P = 0.0275). Prior to 1967, all healthy mothers breast-fed their children. After 1968, the use of bottled and mixed milk (breast milk and bottled milk) increased, with bottled milk becoming predominant after 1990 (89%). The percentage of healthy mothers breast-feeding for more than one year significantly decreased from 68.3% in 1937-1947 to 0.4% in 1990-1995 (P < 0.0001). Infection with HTLV-I in Okinawa has decreased mainly due to a reduction in the number of mothers breast-feeding and a shortening of the breast-feeding period. However, because the mother-to-child transmission rate among non-breast-feeders decreased from 12.8% in 1986-1991 to 3.2% in 1995-1999, there may be other factors involved in the decrease in mother-to-child transmission.

A prospective comparison of the effect of interferon-alpha and interferon-beta treatment in patients with chronic hepatitis C on the incidence of hepatocellular carcinoma development.

To investigate differences in the effect of interferon (IFN) -alpha and IFN-beta treatment for hepatitis C on hepatocellular carcinoma (HCC) development, we prospectively followed 351 consecutive patients (median age, 56.6 years; mean follow-up, 5.7 +/- 2.6 years) with chronic hepatitis C virus (HCV) viremia. Of 260 IFN-alpha and 91 IFN-beta treated patients, 17 (6.5%) and 4 (4.4%), respectively, developed HCC. Virological response (VR) was defined as persistent HCV RNA disappearance from serum, and biochemical response (BR) as persistent alanine aminotransferase (ALT) normalization after treatment. No significant between-group differences in HCC development were found between those with and without VR. Although the HCC development rate in patients without BR was significantly higher than that in patients with BR in the IFN-alpha group (11.4% and 0.8%; P << 0.05), no significant difference was found in the IFN-beta group (6.3% and 2.3%). Similar rates of HCC development were found in patients with chronic HCV viremia treated with either IFN-alpha or IFN-beta.

A patient in whom only hepatitis B virus (HBV) was thought to have been contracted, by kissing, from a same-sex partner coinfected with HBV and human immunodeficiency virus-1.

A 31-year-old homosexual man was admitted to our hospital in August 2001 with liver dysfunction. His diagnosis was acute hepatitis B. He had had a steady partner coinfected with hepatitis B virus (HBV) and human immunodeficiency virus-1 (HIV) from August 2000 to July 2001. Because he knew that the partner was infected with HIV, the sexual relationship had included only deep kissing, with no oral-genital or anal-genital sex. The serum HBV DNA level of the partner was relatively high compared with the serum HIV RNA level. Direct sequencing of the full HBV DNA genome from serum showed that the entire base sequences of the viruses from both patients were of genotype A and identical. HBV infectivity was shown to be stronger than that of HIV in our patient, in whom only HBV was transmitted from a partner coinfected with HBV and HIV. This case highlights the importance of HBV as a sexually transmitted disease.

[Evaluation of an immunochromatography test kit for rapid diagnosis of influenza].

We assessed the sensitivity and specificity of the Capilia Flu AB rapid diagnosis kit for influenza that utilizes the immunochromatography method. Tested were 114 influenza like illness patients in the 2001/2002 influenza season. We used Capilia Flu AB and Infu A . B Quick, a rapid diagnosis kit based on enzyme immunoassay. As laboratory confirmation tests, influenza virus isolation and polymerase chain reaction (PCR) were done. Those patients with positive results from virus isolation or PCR were regarded as influenza patients. The sensitivities of nasal swab, pharyngeal swab, and nasal wash specimens were 82.8%, 80.0%, and 75.0%, respectively. The specificities of nasal swab, pharyngeal swab, and nasal wash specimens were 95.3%, 93.9%, and 100%, respectively. A total of 20 patients displayed different results in comparison of their nasal and pharyngeal swabs: 15 patients were positive with the nasal swab but negative with the pharyngeal swab and 5 patients were negative with the nasal swab but positive with the pharyngeal swab. Nasal swab would seem to be preferable in terms of sensitivity. The sensitivity and specificity of Capilia Flu AB were a little higher than those of Influ A . B Quick, but with no significant difference. The one-step operation of Capilia Flu AB is easier than the four steps required by Influ A . B Quick, but the time required to make a diagnosis is the same. No significant age related difference in the effectiveness of the kits was found. The Capilia Flu AB rapid diagnosis kit is useful in clinical practice because it has good sensitivity (about 80%) and specificity (about 90%), and it is easy to use.

Clinical outcomes of hepatitis B virus (HBV) genotypes B and C in Japanese patients with chronic HBV infection.

The aims of this retrospective survey were to determine the epidemiologic distribution of hepatitis B virus (HBV) genotypes and analyze the genotype-related clinical differences among Japanese patients with chronic HBV infection. The 158 surveyed patients with chronic HBV infection lived in Fukuoka and Okinawa were serially tested for serum alanine aminotransferase (ALT) and hepatitis B e antigen (HBeAg). Follow-up was for a period of 10.8 +/- 6.4 years (mean +/- SD). The HBV genotypes were determined in sera by an enzyme-linked immunosorbent assay and detection of HBV DNA in serum was done by the transcription-mediated amplification-hybridization protection assay. Genotypes B and C were found in 58 (36.7%) and 100 (63.3%) of the patients, respectively. Genotype B was predominant in Okinawa (B = 86.9%, C = 13.1%), whereas genotype C was predominant in Fukuoka (B = 5.2%, C = 94.8%). The HBeAg positivity and ALT abnormality rates at the start of the observation period were significantly higher in patients with genotype C (66.0% and 84.0%) than in patients with genotype B (34.5% and 22.4%) (P < 0.05, respectively). The annual rate of spontaneous HBeAg disappearance in patients with genotype B was much higher than in patients with genotype C (8.38% versus 2.34%, respectively). Patients with genotype C who were continuously HBeAg negative from entry had a significantly higher ALT abnormality (58.8%) than those with genotype B (19.2%) (P < 0.05). Interestingly, patients with genotype C who became HBeAg negative after treatment with interferon had a high ALT abnormality (58.8%). All patients with an ALT abnormality were positive for HBV DNA in their serum. These findings indicate that patients with HBV genotype C have more severe liver deterioration because of the delay of HBeAg disappearance and continued HBV replication after HBeAg disappearance.

[A case of amyopathic dermatomyositis with systemic sclerosis sine scleroderma presenting abnormal vermiculation].

A 24-year-old Japanese woman was admitted to our hospital in January 2000 with daily diarrhea, abdominal distention, and abdominal pain. Raynaud's phenomenon with erythroderma desquamativum eruptions had been found in 1992. In 1999, small intestinal transillumination showed dilation of the second and third portion of the duodenum. She was diagnosed as amyopathic dermatomyositis because of Gottron's sign despite not having symptoms of myositis, normal serum CPK levels and no histological abnormality by muscle biopsy. In addition, the patient was diagnosed as systemic sclerosis sine scleroderma because Raynaud's phenomenon, leukoma and gastrointestinal dilation were present. Also, antinuclear antibody and anti centromere antibody were positive and anti Scl-70 antibody was dull-positive, despite the absence of scleroderma, extreme edema, and bone resorption. Careful, long term observation will be required because of the splanchnopathy in youth and the complications of systemic sclerosis.