Systemic immunization with streptococcal immunoglobulin-binding protein Sib 35 induces protective immunity against group: a Streptococcus challenge in mice

The streptococcal immunoglobulin (Ig)-binding protein Sib 35 binds to IgG, IgM and IgA in human, mouse and bovine. Since all group A Streptococcus pyogenes (GAS) strains examined express the sib 35 gene, we evaluated the Sib 35 as a vaccine candidate against GAS infections. We detected significantly higher anti-Sib 35 IgG antibody titers in sera from patients with GAS infections than from healthy volunteers. Immunization of mice with Sib 35 induced antigen-specific IgG antibodies in their sera, and rabbit Sib 35-specific antiserum showed opsonic activity. Immunization with Sib 35 enhanced survival rates in mice challenged with a GAS strain, while exhibiting no toxicity in hosts. We conclude that Sib 35 is a promising vaccine for prevention of GAS infections.     

Documentation of acute increase in ventricular capture threshold after direct current cardioversion with AutoCapture threshold record

This report describes acute and persistent increase in ventricular capture threshold after direct current cardioversion by using AutoCapture threshold record. Careful follow-up is required to be sure that the system continues to function according to its design specifications.     

Appendicectomy in children: a plea for the use of the transverse pararectal approach.

A retrospective study of 100 consecutive emergency appendicectomies in children is presented. All were performed through the transverse pararectal incision, the details of which are briefly outlined. A low rate of wound infection was present. It is suggested that this was mainly due to the approach, which combines atraumatic access with safety. The aim of the study is to dispel the reluctance of surgeons to adopt this incision in children.     

Methyl-CpG binding protein 2 gene (MECP2) variations in Japanese patients with Rett syndrome: pathological mutations and polymorphisms

A total of 45 different mutations of methyl-CpG-binding protein 2 gene (MECP2) were identified in 145 of 219 Japanese patients with typical or atypical Rett syndrome (RTT) (66.2%). A missense mutation, T158M was the most common mutation of MECP2, identified in 22 (19.1%) patients, followed by four nonsense mutations, R168X (14.8%), R270X (13.0%), R255X (9.6%), and R294X (6.1%) in 115 patients with classical RTT. Two missense mutations, R133C (33.3%) and R306C (23.3%), and a nonsense mutation, R294X (13.3%), were common in 30 patients with atypical RTT, including the preserved speech variant (PSV). Frameshift mutations due to nucleotide deletion or insertion were identified in 22 patients with MECP2 mutations, and one of them had a 3.6 kb deletion encompassing exons 3 and 4. Three patients with classical RTT had a splicing anomaly. The wide spectrum of phenotypic variability in patients with RTT has been considered to be correlated with the mutation type and location in MECP2, and X-inactivation. However, most patients showed a random X-inactivation pattern evaluated by an androgen receptor gene polymorphism in this study, suggesting that a skewed X-inactivation might not be a main modification factor on clinical phenotypes of RTT. In addition, three new missense mutations, P176R, A378V and T479M, were identified in patients with RTT, but also in healthy Japanese, indicating that these mutations are non-pathogenic in Japanese. Information about rare polymorphic variations is very important for the molecular diagnosis of RTT, although rare polymorphic variants might differ among ethnic groups.     

Differences in the contribution of HLA-DR and -DQ haplotypes to susceptibility to adult- and childhood-onset type 1 diabetes in Japanese patients

To clarify heterogeneity in Japanese adult-onset type 1 diabetes, we analyzed the HLA-DR and -DQ haplotypes, depending on the clinical phenotype, and compared them with those in childhood-onset type 1 diabetes (CO). The patients in a previously reported Ehime Study were divided into subgroups by the mode of onset of diabetes: 68 acute-onset type 1 diabetic patients (AO) and 28 slowly progressive type 1 diabetic patients (SO). HLA haplotypes were compared with those of 80 CO patients and 190 control subjects. Two major susceptible HLA haplotypes in the Japanese, DRB1*0405-DQB1*0401 (DR4) and DRB1*0901-DQB1*0303 (DR9), were significantly increased in the AO and CO groups, but only DR9 was increased in the SO group. AO subjects had a higher frequency of DR9 than CO subjects. Accordingly, the DR9:DR4 frequency increased with increasing age of onset. Another susceptible haplotype, DRB1*0802-DQB1*0302 (DR8), was involved only in the CO group. Analysis of haplotype combinations revealed that DR4 and DR9 had significant dosage effects on the AO and CO groups (P < 0.0001), but only DR9 had such an effect in the SO group (P < 0.03). These results suggest differences in the contribution of HLA class II haplotypes to susceptibility of type 1 diabetes depending on the clinical phenotype and also indicate that HLA class II haplotypes may be associated with the onset age of type 1 diabetes.     

Twenty-five years followup of patients who had valgus osteotomy for arthritic hips

We reviewed the long-term outcomes of intertrochanteric valgus femoral osteotomies in patients with arthritic hips to clarify any influencing factors. One hundred six patients (127 hips) were followed up during an average of 25 years. The average age of the patients at surgery was 42 years. The preoperative extent of degenerative change was classified radiologically into one of four grades according to the criteria of T?nnis. Radiographic measurements of acetabular coverage were made using AP radiographs obtained immediately after surgery. Thirty-eight patients (41 hips) had total hip arthroplasties; the 25-year survival rate was 69%. Radiologic evaluations of patients with mild preoperative degenerative changes (T?nnis Grade 1) improved and good clinical outcomes were obtained. In addition, radiologic evaluations of patients whose hips had better acetabular coverage (center-edge angle > 0 degrees, sharp angle < 50 degrees, or acetabular head index > 60%) also improved. However, radiographic measurements did not influence clinical scores. The mean score of patients younger than 50 years at surgery was higher than patients older than 50 years. The mean score of patients with unilateral hip involvement was higher than patients with bilateral involvement. Therefore, valgus osteotomies seem appropriate for younger patients with unilateral involvement.     

Characteristics of patients with chronic hepatitis C who develop hepatocellular carcinoma after a sustained response to interferon therapy

BACKGROUND: The objective of the current study was to determine the characteristic features of sustained responders who develop hepatocellular carcinoma after treatment with interferon for chronic hepatitis C. METHODS: This study included 3626 patients with chronic hepatitis C who had received interferon monotherapy. Cox proportional hazards analysis was used to compare sustained responders who did and did not develop hepatocellular carcinoma, and nonsustained responders who developed hepatocellular carcinoma in a multicenter, retrospective cohort study. RESULTS: Among 1197 sustained responders, 27 patients developed hepatocellular carcinoma (2.3%). Compared with sustained responders who did not develop hepatocellular carcinoma, patients who developed disease more often were male (P = 0.0212), were older (P = 0.0068), and had advanced-stage histologic disease before interferon therapy (P = 0.0345). Conversely, compared with patients with hepatocellular carcinoma who were not sustained responders, patients who were sustained responders tended to be older at the time of the initiation of interferon therapy (P = 0.0552) and at the time hepatocellular carcinoma was detected (P = 0.0593), and they also were predominantly male (P = 0.0507). The histologic staging and serum aminotransferase levels at the initiation of interferon therapy, the interval to the detection of tumor, and the tumor size showed no significant differences between the two groups. CONCLUSIONS: Sustained responders in the group at high risk for developing hepatocellular carcinoma after interferon therapy were older, more often were male, and had more advanced histologic disease stage. Such patients should be followed carefully periodically for > 10 years after they complete interferon therapy.