The Effects of the Antirheumatic Agents N-(2-Carboxyphenyl)-4-Chloroanthranilic Acid Disodium (Cca) and D-Penicillamine on the NK and ADCC Activities and Interferon Production of Lymphocytes

CCA and D-penicillamine enhanced the NK activity of human lymphocytes in vitro incubation. ADCC activity of the lymphocytes was increased slightly by D-penicillamine but not by CCA. CCA enhanced interferon production from lymphocytes but D-penicillamine did not.     

Analysis of weight-bearing kinematics of posterior-stabilized total knee arthroplasty with novel helical post-cam design

We developed a new posterior-stabilized total knee arthroplasty (TKA) with a unique post-cam design that induces and accommodates internal tibial rotation with deep knee flexion. To validate the design concept of this system, we conducted an image analysis study employing a computer-aided diagnosis system for 24 TKA-implanted knees. In the analysis, the tibiofemoral relationship in the following 3 postures was evaluated: standing at extension, forward lunge, and kneeling with maximum knee flexion. The results of the image analysis showed achievement of consistent internal rotation of the tibia in deep flexion with a broad contact area at the post-cam interface as intended by the original design concept of this TKA system.     

Worse long-term surgical outcomes in elderly patients undergoing SPARC retropubic midurethral sling placement

Study Type – Diagnostic (case series) Level of Evidence 4

OBJECTIVE

? The purpose of our study was to evaluate long‐term clinical outcomes following placement of a retropubic mid‐urethral sling in patients aged 70 and over and to compare outcomes with those of a younger cohort of patients.

MATERIALS AND METHODS

? Patients with stress urinary incontinence undergoing retropubic polypropylene sling (SPARC^TM) placement were entered into a prospective, institutional review board‐approved database. ? Patients with at least 12 months follow‐up were sent postoperative questionnaires assessing outcomes. Results of these questionnaires were compared for patients aged 70 or older and those younger than 70 years.

RESULTS

? A total of 337 patients who underwent SPARC sling placement in an 8‐year period were identified. Of these, 290 patients had a minimum of 12 months follow‐up, and among these patients, 235 (81%) answered postoperative mailed questionnaires. Average follow‐up was 45.2 months. ? Thirty‐seven patients were 70 or older, and 198 were younger than 70. The older group had significantly lower success (53.1% vs 83.6%) and dry (6.1% vs 35.3%) rates than the younger cohort. ? Assessment of preoperative variables determined that the older cohort had significantly more vaginal deliveries and a higher percentage of patients who had undergone either hysterectomy, previous prolapse and/or incontinence surgery. ? There was no significant difference in Valsalva leak‐point pressure, percentage of patients with intrinsic sphincteric deficiency or type 0 stress urinary incontinence between the two groups.

CONCLUSIONS

? Experience at our Institution shows that there are clearly lower success rates in older patients undergoing a SPARC sling as compared with a younger cohort of patients. ? Parity, hysterectomy and previous pelvic organ prolapse/anti‐incontinence surgery may also play a role in the difference in outcomes.     

Early detection and quantification of lamivudine-resistant hepatitis B virus mutants by fluorescent biprobe hybridization assay in lamivudine-treated patients

Background Long-term lamivudine treatment induces the emergence of lamivudine-resistant hepatitis B virus (HBV). The objective of this study was to develop a fluorescent biprobe hybridization (FBH) assay for the detection and quantification of HBV mutants in the clinical course of lamivudine-treated patients and to evaluate its clinical usefulness. Methods We developed an FBH assay to detect mutations in the HBV DNA polymerase gene. The assay's detection sensitivity was determined using a dilution series of wild-type/mutant plasmid DNA. Blood samples obtained from 27 lamivudine-treated patients were analyzed. Results Mutant DNA levels as low as 10% of total HBV DNA were detected (sensitivity = 100%, specificity = 80%). HBV mutants were detected in five of the 27 patients during an average follow-up of 20 months after lamivudine administration. In one of the five patients, the YIDD mutant was detected at the initiation of lamivudine treatment, while the remaining four patients were identified as having YIDD mutants within 3 months after beginning lamivudine administration. Of the five patients with an HBV mutant, four developed breakthrough hepatitis more than 10 months after the detection of HBV mutants, following the reappearance or a re-increase of HBV DNA, characterized by a predominance of the mutant. The YIDD mutant was detected in one patient, even when the titer of the serum HBV DNA was below the detection limit of commercially available quantitative polymerase chain reaction. Conclusions The FBH assay is an efficient method for detecting and quantifying HBV mutants, as early as 3 months after lamivudine administration.     

Clinical usefulness of the (1-->3)-beta-D-glucan measurement kit using the improved alkaline pretreatment method--comparison with conventional method

We had reported that the rate of non-specific reaction in measurement of (1-->3)-beta-D-glucan was decreased by improvement of the alkaline pretreatment reagent of Fungitec G-test MK (MK assay). To compare the clinical usefulness between conventional MK assay and new MK assay using improved alkaline pretreatment reagent, 121 plasma samples were tested. The sensitivity, specificity, positive predictive value (PPV), negative predictive values (NPV) in conventional MK assay were 91.7%, 85.3%, 44.0% and 98.8%, respectively. Those in new MK assay were 75.0%, 91.6%, 52.9% and 96.7%, respectively. On the other hand, area under the curve (AUC) of receiver operating characteristic (ROC) analysis in conventional and new MK assay was 0.9175 and 0.9123 without a significant difference. It has been recognized that the sensitivity in conventional MK assay is higher than those in other beta-glucan assays. Then, the specificity of new MK assay was improved by using improved alkaline pretreatment reagent, without decreasing the sensitivity. Thus, the present findings indicate that the new MK assay is clinically quite useful.     

Cloning, expression and purification of arylsulfate sulfotransferase from Eubacterium A-44

A gene (astA) encoding arylsulfate sulfotransferase (ASST), which transfers a sulfate group from phenolic sulfate esters to phenolic acceptors, was cloned from a Eubacterium A-44 genomic library. The probe (1.5 kb fragment) for the astA gene was prepared from the PCR product of the primers produced using two internal amino acid sequences of ASST, which had been purified from Eubacterium A-44. The astA gene was cloned into the pKF3 vector. Its sequence revealed a 1863 bp open reading frame (ORF) encoding a protein containing 620 amino acids with a secretary signal peptide, and showed 91% homology (identity) to Eubacterium rectale IIIH previously reported. The cloned astA gene was expressed under the T7 promoter of the expression vectors, pET-39b(+) and pET-26b(+), in Escherichia coli BL21 (DE3), and the expressed ASSTs were purified using His Bind column chromatography. The specific activities of the purified ASSTs were 25.6 micromol/min/mg and 37.1 micromol/min/mg, respectively.     

Clinical features of antinuclear antibodies-negative type 1 autoimmune hepatitis

Aim:  Antinuclear antibodies (ANA) are the main serologic markers of type 1 autoimmune hepatitis (AIH); however 20–30% of patients are negative for ANA. We assessed the clinical features of ANA-negative patients.
Methods:  A retrospective analysis was performed of 176 patients with type 1 AIH (153 females, median age 55 years). A diagnosis of AIH was made based on the revised scoring system proposed by the International Autoimmune Hepatitis Group. ANA titers were measured using a standard indirect immunofluorescence technique.
Results:  Thirty-eight patients (22%) had low titers of ANA (1:40 or 1:80), and 114 (65%) had high titers (≥ 1:160). Of 24 ANA-negative patients, 15 were positive for smooth muscle antibodies (SMA). Three of nine both ANA- and SMA-negative patients developed ANA during follow-up. The other six were diagnosed based on histological characteristics. Thirteen ANA-negative patients relapsed after the normalization of serum alanine aminotransferase (ALT) levels. ANA-negative patients more frequently showed acute presentation and, at presentation, had lower serum immunoglobulin G levels, higher serum levels of bilirubin and transaminase, and higher frequencies of histological acute hepatitis and zone 3 necrosis than those with high titers. However, the frequency of advanced stage of fibrosis was similar. The response to corticosteroids was not different among the three groups.
Conclusions:  ANA-negative type 1 AIH shows acute-onset more frequently but may include not only acute autoimmune hepatitis, but also acute exacerbation of inactive chronic disease. Regarding the diagnosis of ANA-negative AIH, the determination of ANA during follow-up and the response to immunosuppressive treatment may be helpful.