Methamphetamine effects on rat circadian clock depend on actograph

Methamphetamine effects on the rest-activity rhythm were examined in 12 blinded rats using two different actographs, an Animex and a running-wheel. D-Methamphetamine was administered chronically by dissolving it in drinking water. During methamphetamine treatment, the rest-activity rhythm measured by an Animex showed a clear sign of relative coordination in addition to the general enhancement of activity level. Analyses of pre- and posttreatment activity rhythms revealed that neither the phase nor the period was affected by methamphetamine treatment. On the other hand, the circadian period was lengthened by methamphetamine treatment when locomotor activity was measured by a running-wheel. These results confirmed our previous findings that the chronic treatment of methamphetamine modified the expression of the circadian rhythms but did not affect the underlying oscillation when measured by an Animex, and further indicated that methamphetamine could affect the underlying oscillation when rats had free access to a running-wheel. It is concluded that the effects of methamphetamine on the circadian clock depend on actograph.     

A case of sarcoidosis manifesting as acute febrile polyarthritis following bronchoalveolar lavage]

A 32-year-old man was incidentally found to have abnormal shadows on a chest X-ray film and was admitted on May 2004. His chest images showed mediastinal and bilateral hilar lymphadenopathy. The serum level of angiotensin-converting enzyme was elevated. We also found non-caseating epithelioid cell granulomas in transbronchial lung biopsy specimens, and confirmed the diagnosis of sarcoidosis. We carried out bronchoalveolar lavage (BAL) for evaluation of disease activity of sarcoidosis. After BAL, he suffered high fever and polyarthralgia. Both ankles were extremely inflamed. We suspected infectious arthropathy caused by atypical pathogens and thus administered antibiotics, but they had no effect at all. Also, no findings suggesting collagen-vascular disorders, including rheumatoid arthritis, were detected. His symptoms improved after three-weeks of treatment with non-steroidal anti-inflammatory drugs. Thus, this case was diagnosed as having acute sarcoid polyarthritis. BAL may have influenced the onset of febrile arthritis in this patient This case indicates that sarcoidosis should be considered as a possible cause of acute febrile polyarthritis.     

Report of the Japan Atherosclerosis Society (JAS) Guideline for Diagnosis and Treatment of Hyperlipidemia in Japanese adults

This paper described the Guideline for Diagnosis and Management of Hyperlipidemias for Prevention of Atherosclerosis proposed by The Japan Atherosclerosis Society (JAS) Guideline Investigating Committee (1,995-2,000) under the auspices of the JAS Board of Directors. 1) The guideline defines the diagnostic criteria for serum total cholesterol (Table 1), LDL-cholesterol (Table 1), triglycerides (Table 4) and HDL-cholesterol (Table 7). It also indicates the desirable range (Table 1), the initiation levels of management (Table 2) and the target levels of treatment (Table 2) for total and LDL-cholesterol. 2) Though both total and LDL-cholesterol are shown as atherogenic parameter in the guideline, the use of LDL-cholesterol, rather than total cholesterol, is encouraged in daily medical practice and lipid-related studies, because LDL-cholesterol is more closely related to atherosclerosis. 3) Elevated triglycerides and low HDL-cholesterol are included in the risk factors, since no sufficient data have been accumulated to formulate the guideline for these two lipid disorders. 4) Emphasis is laid on evaluation of risk factors of each subject before starting any kind of treatment (Table 2). 5) This guideline is applied solely for adults (age 20-64). Lipid abnormalities in children or the youth under age 19, and the elderly with an age over 65 have to be evaluated by their own standard. 6) This part of the guideline gives only the diagnostic aspects of hyperlipidemias. The part of management and treatment will follow in the second section of the guideline that will be published in future.     

Maternal phase setting of fetal circadian oscillation underlying the plasma corticosterone rhythm in rats

We examined the entraining effect of the maternal circadian system on the fetal circadian oscillation during pregnancy. The circadian rhythm of locomotor activity and plasma corticosterone of pregnant rats was abolished by bilateral ablation of the suprachiasmatic nuclei at day 10 of gestation. At term, pups were removed by Cesarean section and were blinded immediately. To avoid possible rhythmic influences of a nursing mother on the pups' circadian rhythms, alternating nursing was imposed on blinded infants. Thus, pups were exchanged every 12 h between two foster mothers, one entrained to a light-dark cycle and the other to dark-light, so that one group of pups were always nursed in the light period and the other in the dark. Both groups of pups showed free-running circadian hormone rhythms with similar phase angles. However, the circadian rhythm of these pups was always phase delayed by about 8 h to that of blinded control pups which were born to unoperated mothers. Furthermore, blinded pups born to and nursed by a suprachiasmatic nuclei lesioned mother developed a circadian hormone rhythm which was phase delayed by 4 h to that of the control. It is concluded that the circadian oscillation underlying the rhythm of corticosterone release in rats has entrained to the maternal circadian system during fetal life. It is further suggested that the entrainment starts before day 10 of gestation.     

Invasive Fungal Sinusitis Involving the Orbital Apex in a Patient with Chronic Renal Failure

An 82-year-old man with chronic renal failure presented with invasive fungal sinusitis involving the right orbital apex. Intravenous liposomal amphotericin B was immediately administered with an intravenous sodium supplement. Subsequently, endoscopic sinus surgery was performed. Aspergillus fumigatus was detected in nasal discharge culture on day 12. Because the patient’s renal function had deteriorated by this time, therapy was changed to nasal inhalation of amphotericin B, which was discontinued after 1 month, and oral administration of voriconazole, which was discontinued after 2 months. During 6-month follow-up, the patient did not show recurrence of sinusitis or further decrease in renal function.     

Clostridioides difficile-related toxic megacolon after Cryptococcus neoformans cellulitis: A complex of two rare infections in an immunocompromised host

A 76-year-old Japanese woman was admitted due to uncontrolled cellulitis of the right lower leg. She had deep vein thrombosis on the right limb. Moreover, she had a long history of rheumatoid arthritis treated with corticosteroids. Skin biopsy and lumbar puncture were performed to diagnose disseminated cryptococcosis. She was administered antifungal agents (liposomal amphotericin B and 5-fluorocytosine). On treatment day 14, debridement was performed, and cryptococcosis was controlled. However, she developed toxic megacolon due to Clostridioides difficile infection (CDI). On day 32, she was transferred to the intensive care unit due to severe acidosis and acute kidney injury secondary to CDI-related toxic megacolon. Vancomycin, metronidazole, and tigecycline were administered for treatment of CDI.After several weeks of intensive care, toxic megacolon was improved, but renal replacement therapy was discontinued according to the patient's will. On day 73, she died of renal failure.We experienced a complex of rare diseases, Cryptococcus neoformans cellulitis and Clostridioides difficile-related toxic megacolon. Both diseases were presumed to be the result of corticosteroid and methotrexate use. Hence, careful monitoring is required when treating immunocompromised hosts to reduce the risk of developing complications.     

Efficacy and safety of fidaxomicin for the treatment of Clostridioides (Clostridium) difficile infection in a randomized,double-blind,comparative Phase III study in Japan

We assessed the efficacy and safety of fidaxomicin, a narrow-spectrum macrocyclic antibiotic, for treating inpatients with Clostridioides (Clostridium) difficile infection (CDI) in Japan. The objective was to demonstrate the non-inferior efficacy of fidaxomicin versus vancomycin.This Phase III, vancomycin-controlled, double-blind, parallel-group study enrolled adults with CDI. Patients were randomly assigned to receive fidaxomicin (200 mg twice daily, orally) or vancomycin (125 mg four-times daily, orally) for 10 days. The primary endpoint was global cure rate of CDI (proportion of patients cured at end of treatment with no recurrence during 28-day follow-up). Non-inferiority margin of 10% was pre-specified.Two-hundred and twelve patients were randomized and received treatment at 82 hospitals. Global cure rate was 67.3% (70/104) with fidaxomicin and 65.7% (71/108) with vancomycin: difference 1.2% [95% confidence interval (CI) ?11.3–13.7]. Non-inferiority was not demonstrated. Post-hoc analysis in full analysis set patients who received at least 3 days' treatment revealed a higher global cure rate for fidaxomicin [70/97 (72.2%)] than vancomycin [71/106 (67.0%)]: difference 4.6% (95% CI ?7.9–17.1). Recurrence rate in the full analysis set for recurrence was lower in fidaxomicin- [17/87 (19.5%)] than vancomycin-treated [24/95 (25.3%)] patients. Adverse event incidences and profiles were similar for both treatments.Though non-inferiority was not demonstrated for fidaxomicin versus vancomycin, global cure rate was numerically higher and recurrence rate lower for fidaxomicin than vancomycin. Fidaxomicin could be an option for the treatment of CDI in an era of reduced antibiotic susceptibility, and to reduce the incidence of recurrence in Japanese patients.