Case Report: A Pediatric Case of Familial Mediterranean Fever Concurrent With Autoimmune Hepatitis.

Familial Mediterranean fever (FMF) is a hereditary, autoinflammatory disease that causes recurrent fever, arthritis, and serositis. The diagnosis of FMF is based on the presentation of typical clinical symptoms and the Mediterranean fever gene (MEFV) test. However, the challenge lies in diagnosing atypical cases. In this report, we have described a pediatric patient with complex FMF whose diagnosis required trio-whole exome sequencing (WES) and functional validation of a rare MEFV variant. A 3-year-old boy presented with recurrent episodes of elevated liver enzymes and arthralgia. He was diagnosed with autoimmune hepatitis (AIH), and his liver enzymes improved rapidly with steroid treatment. However, he exhibited recurrent arthralgia and severe abdominal attacks. Trio-WES identified compound heterozygous mutations in MEFV (V726A and I692del). Ex vivo functional assays of the patient's monocytes and macrophages, which had been pre-treated with Clostridium difficile toxin A (TcdA) and colchicine, were comparable to those of typical FMF patients, thereby confirming the diagnosis of FMF. Although he was intolerant to colchicine because of liver toxicity, subsequent administration of canakinumab successfully ameliorated his abdominal attacks. However, it was ineffective against liver injury, which recurred after steroid tapering. Therefore, in this case, the pathogenesis of AIH was probably interleukin-1ß (IL-1ß)-independent. In fact, AIH might have been a concurrent disease with FMF, rather than being one of its complications. Nevertheless, further studies are necessary to determine whether FMF-induced inflammasome activation contributes to AIH development. Moreover, we must consider the possibility of mixed phenotypes in such atypical patients who present distinct pathologies simultaneously.

Anesthesia Experience for Tonsillectomy in a Patient With Hypofibrinogenemia: A Case Report.

A 26-year-old male patient with hypofibrinogenemia was scheduled to undergo tonsillectomy. Hypofibrinogenemia, defined as low plasma fibrinogen (Fbg) concentration, is a type of congenital Fbg deficiency and is a rare coagulopathy. Perioperative replenishment of Fbg is performed during minor surgeries, aimed at maintaining plasma Fbg concentrations of 50 mg/dL. In this case, failure to replenish Fbg during the postoperative period may have caused the postoperative hemorrhage. Considering the half-life of Fbg (3-4 days), the plasma Fbg concentration should be monitored for ≥6 postoperative days, aiming at a target level of 50 mg/dL during the postoperative period.

[Diagnosis and treatment of acute appendicitis in children].

In this review article, we discussed the pathogenesis, pathophysiology, diagnosis and treatment of acute appendicitis in children. Indications for early surgery, the operative methods of laparoscopic appendectomy and the treatment outcome are also presented.

[Remifentanil for awake craniotomy].

We report two cases of awake craniotomy successfully managed using remifentanil. During the intraoperative awake period lasting 2 to 2.5 hours, the infusion of low doses of remifentanil (0.02-0.05 microg x kg(-1) min(-1)) with or without propofol kept the patients comfortable and sufficiently awake to conduct various tasks but did not produce excessive respiratory depression. Because remifentanil can be titrated rapidly due to its extremely short duration of action, it may be useful for awake craniotomy for which both analgesia and sedation have to be tuned carefully according to the patient's need.

[Utility of QuantiFERON TB-2G for tuberculosis contact investigations in public health services].

OBJECTIVE: The objective of the present study was to examine the utility of QuantiFERON TB-2G (QFT) in tuberculosis contact investigations performed by a public health center. METHODS: Adachi City Public Health Center, Tokyo, started using QFT in its laboratory service in June, 2005. The results of QFT, as well as tuberculin skin tests (TSTs) performed in tuberculosis contact investigations in the 10 month period since then were here analyzed. QFT was carried out for 67 contacts two months after their last contact with the index case. TST was given simultaneously. RESULTS: Of the total of 67 contacts investigated during the period, 9 were positive for QFT, 5 were doubtful positive, and the remaining 53 were negative. Among 48 subjects tested with TST, 22 had strong reactions with erythema > or = 30 mm, out of which 4 were positive for QFT. In addition, there were 5 QFT-positives among the remaining 26 with weak tuberculin reactions. These 9 subjects with positive QFT were indicated for chemoprophylaxis. CONCLUSIONS: Adachi City Public Health Center is pioneering the application of new technology for detection of latent tuberculosis infection in contact investigations of the inhabitants. As expected from trial findings, QFT was shown to be a useful tool in a practical setting for the purpose of detecting TB infection, with greater accuracy than with TST, independent of the history of BCG vaccination. This approach can help avoid both over-diagnosis and under-diagnosis.

Central effects of fexofenadine and cetirizine: measurement of psychomotor performance, subjective sleepiness, and brain histamine H1-receptor occupancy using 11C-doxepin positron emission tomography.

Histamine H1-receptor (H1R) antagonists, or antihistamines, often induce sedative side effects when used for the treatment of allergic disorders. This study compared the sedative profiles of the second-generation antihistamines, fexofenadine and cetirizine, using 3 different criteria: subjective sleepiness evaluated by the Stanford Sleepiness Scale, objective psychomotor tests (simple and choice reaction time tests and visual discrimination tests at 4 different exposure durations), and measurement of histamine H1-receptor occupancy (H1RO) in the brain. Subjective sleepiness and psychomotor performance were measured in 20 healthy Japanese volunteers at baseline and 90 min after administration of fexofenadine 120 mg or cetirizine 20 mg in a double-blind, placebo-controlled crossover study. Hydroxyzine 30 mg was included as a positive control. H1RO was measured using positron emission tomography (PET) with (11)C-doxepin in 12 of the 20 subjects, and a further 11 volunteers were recruited to act as controls. In psychomotor tests, fexofenadine was not significantly different from placebo and significantly less impairing than cetirizine on some tasks, as well as significantly less impairing than hydroxyzine on all tasks. For subjective sleepiness, fexofenadine was not significantly different from placebo, whereas cetirizine showed a trend toward increased sleepiness compared with fexofenadine and placebo. H1RO was negligible with fexofenadine (-0.1%) but moderately high with cetirizine (26.0%). In conclusion, fexofenadine 120 mg is distinguishable from cetirizine 20 mg, as assessed by H1RO and psychomotor testing.