Five‐year efficacy of finasteride in 801 Japanese men with androgenetic alopecia

Finasteride is standard medical treatment for androgenetic alopecia; however, no large studies with 5 years or more of follow up have been performed in Japan. The authors followed Japanese men with androgenetic alopecia treated with finasteride for 5 years to evaluate long‐term treatment efficacy. Of 903 men treated with finasteride (1 mg/day), 801 patients were evaluated over 5 years by modified global photographic assessment. Although the proportion of improvement was high (99.4%), modified global photographic assessment scores after 5 years of treatment were lower in patients with more advanced disease as measured by the modified Norwood–Hamilton scale. After separating patients into “sufficient” and “insufficient” efficacy groups according to the modified global photographic assessment score after 5 years (scores ≥6 and <6, respectively), multivariate analysis showed that independent risk factors of insufficient efficacy were age at start of treatment of 40 years or more (P = 0.021) and classification on the modified Norwood–Hamilton scale (P < 0.001), whereas presence of stress at start of treatment was a negative predictor (P = 0.025). In conclusion, continuous finasteride treatment for 5 years improved androgenetic alopecia with sustained effect among Japanese. Younger age and less advanced disease at start of treatment were the key predictors of higher finasteride efficacy.     

Outcomes After Aortic Valve Replacement for Asymptomatic Severe Aortic Regurgitation and Normal Ejection Fraction

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Infective Endocarditis Due to Treponema pallidum: A Case Diagnosed Using Polymerase Chain Reaction Analysis of Aortic Valve

Syphilis is a sexually transmitted disease caused by Treponema pallidum. Syphilitic aortitis might coexist in a dysfunctional aortic valve, but the etiology remains unclear, because microbiological diagnosis is difficult. A 62-year-old man with low-grade fever was diagnosed with aortitis and infective endocarditis, due to Treponema pallidum infection, using polymerase chain reaction analysis. This case suggests that syphilis might cause infective endocarditis.     

Population Pharmacokinetic and Exposure-Response Analyses of Baloxavir Marboxil in Adults and Adolescents Including Patients With Influenza

Baloxavir marboxil, a prodrug that is metabolized to baloxavir acid, suppresses viral replication by inhibiting cap-dependent endonuclease. Our aim is to characterize its pharmacokinetics and exposure-response relationships. Population pharmacokinetic analysis of the baloxavir acid was performed using 8310 plasma concentration data points from 1109 subjects. Exposure-response analyses were performed regarding the time to alleviation of symptoms and the reduction in the influenza virus titer. A 2-compartment model with first-order absorption and lag time well described the plasma concentration data for baloxavir acid, and body weight and race were found to be the most important factors influencing the clearance and distribution volume. A dose regimen based on the body weight (40 mg for patients weighing <80 kg and 80 mg for patients weighing ≥80 kg) could provide sufficient exposures for expecting efficacy irrespective of body weight or race; however, the exposures were dependent on the body weight and race. Exposure-response analyses suggested that the reduction in the influenza virus titer was greater in any exposure-based groups in baloxavir marboxil treatment than in the oseltamivir phosphate treatment and placebo groups. In conclusion, the population pharmacokinetic model and exposure-response relationships would be useful for understanding the pharmacokinetic and pharmacodynamic characteristics of baloxavir acid.     

Influence of SNPs in cytokine-related genes on the severity of food allergy and atopic eczema in children

Although many single nucleotide polymorphism (SNP) studies have reported an association of atopy, allergic diseases and total serum immunoglobulin E (IgE) levels, almost all of these studies sought risk factors for the onset of these allergic diseases. Furthermore, many studies have analyzed a single gene and hardly any have analyzed environmental factors. In these analyses, the results could be masked and the effects of other genes and environmental factors may be decreased. Here, we described the correlation between four genes [interleukin (IL)-4 (C-590T), IL-4 receptor (A1652G), FCER1B (G6842A) and STAT6 (G2964A)] in connection with IgE production; the role of IL-10 (C-627A) as a regulatory cytokine of allergy; and the severity of food allergy (FA) and atopic eczema (AE) in 220 Japanese allergic children. In addition to these SNPs, environmental factors, i.e., patient's attitude, indoor environment, and so on, were also investigated in this study. Our study was retrospective, and the correlation was analyzed by our defined clinical scores divided into three terms: worst symptoms, recent symptoms and general amelioration at the most recent examination during the disease course. Our results indicated that IL-10 AA, the genotype with lower IL-10 production, is associated with higher IgE levels in the serum (p < 0.0001, estimate; 0.912). Marginal liver abnormalities were observed in the subject group with both FA and AE (p < 0.1191, estimate; 0.1490). Our defined clinical scores enabled evaluation of various aspects of disease severity. Based on the scores, while no single SNP selected in this study determined severity, the combination of the SNP with laboratory data and environmental factors appeared to determine severity.     

Clinico-pathological comparative study between brainstem encephalitis of Iizuka type and neuro-Beh?et's disease

We experienced one necropsy case of brainstem encephalitis of Iizuka type (BSE) and one necropsy case of the brain-stem syndrome (BSS) of typical neuro-Beh?et's disease, and compared them clinically and neuropathologically. Clinically both of these cases showed chronic progressive mental disturbance, pseudobulbar paresis, spastic tetraparesis, cerebrospinal fluid pleocytosis, increased protein, and brainstem atrophy observed by X-CT. Neuropathologically, irregular, boundary-indistinct demyelinating lesions and obsolete softening lesions were sporadically found, associated with perivascular lymphocytic infiltration and gliosis centering on the brainstem. In this way, both cases were similar in many points except for the presence or absence of cutaneo-muco-ocular signs specific for Beh?et's disease. Also BSE and BSS reports in the literature showed that both diseases were similar not only in clinical findings consisting of mental disturbance and brainstem signs but also in neuropathological findings with similar topographical distribution of the same histopathological changes, including the variations and diversity of these characteristics. Especially of much interest is their similarity in characteristic mental disturbance. In discriminating BSE from multiple sclerosis and other diseases with exclusive involvement of the brainstem, it is important to understand their clinical characteristics. The characteristic mental disturbance includes damage to memory and sentiment, a change in personality, and lowering in spontaneity, but calculation ability and orientation are comparatively preserved. Of course the similarity in clinical and neuropathological findings does not necessarily mean the identical etiopathogenesis. However, it is possible to consider that neuro-Beh?et's disease (syndrome) may form a wide spectrum with BSE and typical neuro-Beh?et's disease at the both ends, regarding the time and spatial diversity of the appearance of cutaneo-muco-ocular signs.     

Quantitative and qualitative changes of apolipoprotein AI-containing lipoproteins in patients on continuous ambulatory peritoneal dialysis

Using immunoaffinity chromatography, two species of apo-AI containing lipoproteins (AILp); lipoprotein containing apo-AI and apo-AII (Lp-AI/AII), and lipoprotein containing apo-AI, but no apo-AII (Lp-AI) were isolated from 13 female patients on continuous ambulatory peritoneal dialysis (CAPD), then characterized. The results were compared with findings obtained in agematched normolipidemic (control I) and mild hypertriglyceridemic (control II) female subjects. In comparison with control I: In AILp, the levels of total cholesterol (TC), cholesteryl ester (CE) and phospholipid (PL), and the levels of apoE were significantly lower in the CAPD patients while the levels of triglyceride (TG) and apo-CIII were significantly higher in these patients. The levels of apo-AI and apo-AII did not differ between the CAPD and control subjects. In Lp-AI/AII, changes of TC, CE, PL, TG, and apolipoproteins were similar to those of AILp, except for the ratio of apo-AI/apo-AII and the level of apo-CII, which was higher in the CAPD patients. In Lp-AI, changes of TC, CE, PL, and TG were also similar to those of AILp and Lp-AI/AII, but the apo-AI level was significantly lower in the CAPD patients. In comparison with control II: In AILp, the levels of PL, apo-AI, apo-AII, and apo-E were significantly lower in CAPD patients, but the apo-CIII levels were significantly higher. In Lp-AI/AII, the levels of PL and apo-E were significantly lower in CAPD patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

In vivo kinetics and displacement study of a carbon-11-labeled hallucinogen,N,N-[11C]dimethyltryptamine

The endogenous hallucinogen, N,N-dimethyltryptamine (DMT), was labeled with carbon-11 and its regional distribution in rat brain studied. [¹¹C]DMT showed higher accumulation in the cerebral cortex, caudate putamen, and amygdaloid nuclei. Studies of the subcellular distribution of [¹¹C]DMT revealed the specific localization in the fractions enriched with serotonin receptors only when a very low dose was injected into rats. The proportions of the radioactivity in receptor-rich fractions were greatly enhanced by pretreatment with the monoamine oxidase inhibitor, pargyline. Specific binding of [¹¹C]DMT to serotonin receptors in dog brain was demonstrated by a positron emission tomographic study in which 5-methoxy-N,N-dimethyltryptamine caused approximately 20% displacement of the radioligand from the receptors.