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.     

Sentinel lymph node biopsy for 102 patients with primary cutaneous melanoma at a single Japanese institute

Sentinel lymph node biopsy (SLNB) is a widely accepted standard procedure for patients with clinically localized melanoma. Melanoma prevalence and Clark's subtype differ between Asians and Caucasians. Here, we evaluated our experience on SLNB for cutaneous melanoma in a Japanese population. SLNB was performed for patients with melanoma between July 2000 and June 2014. We retrospectively analyzed 102 patients regarding association of clinicopathological features with sentinel lymph node (SLN) status, melanoma‐specific survival (MSS) and disease‐free survival (DFS). A positive SLN was significantly associated with primary Breslow thickness. Compared with 43 patients with negative SLN, 59 patients with positive SLN had significantly shorter MSS (5‐year survival rate, 94.3% vs 63.2%; P = 0.0002) and DFS (5‐year survival rate, 92.7% vs 63.4%; P = 0.0004). According to our subgroup analyses, nine patients with positive non‐SLN had significantly shorter MSS compared with 32 patients with negative non‐SLN (5‐year survival rate, 32.4% vs 68.5%; P = 0.0273). The survival of 51 Japanese patients with acral lentiginous melanoma (ALM) was not inferior to the survival of patients with other Clark's subtype. Breslow thickness is an important factor for both MSS and DFS, and the status of SLN is the most predictive prognostic factor in Japanese patients with clinically localized melanomas, as in case of Caucasians. Features of ALM may be different between Asians and Caucasians.     

Association of kidney function with cancer incidence and its influence on cancer risk of smoking: The Japan Multi-Institutional Collaborative Cohort Study

The association between kidney function and cancer incidence is inconsistent among previous reports, and data on the Japanese population are lacking. It is unknown whether kidney function modifies the cancer risk of other factors. We aimed to evaluate the association of estimated glomerular filtration rate (eGFR) with cancer incidence and mortality in 55 242 participants (median age, 57 years; 55% women) from the Japan Multi-Institutional Collaborative Cohort Study. We also investigated differences in cancer risk factors between individuals with and without kidney dysfunction. During a median 9.3-year follow-up period, 4278 (7.7%) subjects developed cancer. Moderately low and high eGFRs were associated with higher cancer incidence; compared with eGFR of 60-74 ml/min/1.73 m², the adjusted hazard ratios (HRs) (95% confidence intervals [CIs]) for eGFRs of ≥90, 75-89, 45-59, 30-44 and 10-29 ml/min/1.73 m² were 1.18 (1.07-1.29), 1.09 (1.01-1.17), 0.93 (0.83-1.04), 1.36 (1.00-1.84) and 1.12 (0.55-2.26), respectively. High eGFR was associated with higher cancer mortality, while low eGFR was not; the adjusted subdistribution HRs (95% CIs) for eGFRs of ≥90 and 75-89 ml/min/1.73 m² were 1.58 (1.29-1.94) and 1.27 (1.08-1.50), respectively. Subgroup analyses of participants with eGFRs ≥60 and <60 ml/min/1.73 m² revealed elevated cancer risks of smoking and family history of cancer in those with eGFR <60 ml/min/1.73 m², with significant interactions. Our findings suggest that the relationship between eGFR and cancer incidence was U-shaped. Only high eGFR was associated with cancer mortality. Kidney dysfunction enhanced cancer risk from smoking.     

High-magnitude mechanical strain inhibits the differentiation of bone-forming rat calvarial progenitor cells

Purpose: Orthodontic tooth movement occurs during the bone remodeling induced by therapeutic mechanical strain. It is important to investigate the relation between the strength of mechanical stress and bone formation activity. The aim of this study was to determine the effect of high-magnitude mechanical strain on bone formation in detail.

Materials and methods: Osteoblast-like cells isolated from fetal rat calvariae were loaded with 18% cyclic tension force (TF) for 48?h. To phenotypically investigate the effect of TF, we measured the number and the size of bone nodules stained by von Kossa technique on day 21 after cell seeding and determined the calcium content of bone nodules on day 14. Furthermore, we examined the gene expression of BMP-2, Runx2 and Msx2, which are important factors for bone nodule formation, on days 1, 4 and 7 after TF loading.

Results: The maximum bone nodule size in the control group was 1620 and 719?μm in the TF group. Furthermore, the mean number of bone nodules sized over 360?μm in the TF group was significantly decreased compared to the control group. The calcium content was also significantly decreased to 42% by TF loading. The mRNA expression of BMP-2, Runx2 and Msx2 was decreased 1 and 4 days after TF loading.

Conclusion: The differentiation of bone forming progenitor cells into bone nodule forming cells was inhibited by TF due to the decreased expression of bone formation related factors such as BMP-2, Runx2 and Msx2.     

Validation of the Karolinska sleepiness scale against performance and EEG variables.

OBJECTIVE: The Karolinska sleepiness scale (KSS) is frequently used for evaluating subjective sleepiness. The main aim of the present study was to investigate the validity and reliability of the KSS with electroencephalographic, behavioral and other subjective indicators of sleepiness. METHODS: Participants were 16 healthy females aged 33-43 (38.1+/-2.68) years. The experiment involved 8 measurement sessions per day for 3 consecutive days. Each session contained the psychomotor vigilance task (PVT), the Karolinska drowsiness test (KDT-EEG alpha & theta power), the alpha attenuation test (AAT-alpha power ratio open/closed eyes) and the KSS. RESULTS: Median reaction time, number of lapses, alpha and theta power density and the alpha attenuation coefficients (AAC) showed highly significant increase with increasing KSS. The same variables were also significantly correlated with KSS, with a mean value for lapses (r=0.56). CONCLUSIONS: The KSS was closely related to EEG and behavioral variables, indicating a high validity in measuring sleepiness. SIGNIFICANCE: KSS ratings may be a useful proxy for EEG or behavioral indicators of sleepiness.     

Allergic Predisposition Among Infants with Bronchiolitis

Allergic predisposition among infants with bronchiolitis was examined. The number of infants with serum IgE exceeding mean +1 SD was 31/70 (44.3%). The rate of positive radioallergosorbent test (RAST) scores of 1 or more to mites, egg white, or milk was 31/71 (43.7%) and that of scores over 2 was 11/71 (15.5%). Eosinophils and/or mast cells were found in their nasal smears on several occasions. These results indicated that allergic predisposition may be observed among infants with bronchiolitis.     

GABAergic Interneurons at Supraspinal and Spinal Levels Differentially Modulate the Antinociceptive Effect of Nitrous Oxide in Fischer Rats

Background: The study hypothesizes that nitrous oxide (N2O) releases opioid peptide in the brain stem, which results in inhibition of [gamma]-aminobutyric acid-mediated (GABAergic) neurons that tonically inhibit the descending noradrenergic inhibitory neurons (DNIN), resulting in activation of DNIN. In the spinal cord, activation of DNIN leads to the release of norepinephrine, which inhibits nociceptive processing through direct activation of [alpha]2 adrenoceptor and indirect activation of GABAergic neurons through [alpha]1 adrenoceptor. Arising from this hypothesis, it follows that GABAergic neurons will modulate the antinociceptive effect of N2O in diametrically opposite directions at supraspinal and spinal levels. The authors have tested this tenet and further examined the effect of midazolam, a GABA-mimetic agent, on N2O-induced antinociceptive effect.

Methods: Adult male Fischer rats were administered muscimol (GABAA receptor agonist) intracerebroventricularly (icv), gabazine (GABAA receptor antagonist) intrathecally (intrathecal), or midazolam intraperitoneally (intraperitoneal). Fifteen minutes later, they were exposed to air or 75% N2O and were subjected to the plantar test after 30 min of gas exposure. In some animals administered with midazolam, gas exposure was continued for 90 min, and the brain and spinal cord were examined immunohistochemically.

Results: The N2O-induced antinociceptive effect, which was attenuated by icv muscimol, intrathecal gabazine, and intraperitoneal midazolam. Midazolam inhibited N2O-induced c-Fos expression (a marker of neuronal activation) in the pontine A7 and spinal cord.     

Independent determinants of second derivative of the finger photoplethysmogram among various cardiovascular risk factors in middle-aged men.

The second derivative of the finger photoplethysmogram (SDPTG) has been used as a non-invasive examination for arterial stiffness. The present study sought to elucidate independent determinants of the SDPTG among various cardiovascular risk factors in middle-aged Japanese men. The SDPTG was obtained from the cuticle of the left-hand forefinger in 973 male workers (mean age: 44+/-6 years) during a medical checkup at a company. The SDPTG indices (b/a and d/a) were calculated from the height of the wave components. Multiple logistic regression analyses revealed that the independent determinants of an increased b/a (highest quartile of the b/a) were age (odds ratio [OR]: 1.12 per 1-year increase, 95% confidence interval [CI]: 1.09-1.15), hypertension (OR: 1.65, 95% CI: 1.03-2.65), dyslipidemia (OR: 1.51, 95% CI: 1.09-2.09), impaired fasting glucose/diabetes mellitus (OR: 2.43, 95% CI: 1.16-5.07), and a lack of regular exercise (OR: 2.00, 95% CI: 1.29-3.08). Similarly, independent determinants of a decreased d/a (lowest quartile of the d/a) were age (OR: 1.11 per 1-year increase, 95% CI: 1.08-1.14), hypertension (OR: 3.44, 95% CI: 2.20-5.38), and alcohol intake 6 or 7 days per week (OR: 2.70, 95% CI: 1.80-4.06). No independent association was observed between the SDPTG indices and blood leukocyte count or serum C-reactive protein levels. In conclusion, the SDPTG indices reflect arterial properties affected by several cardiovascular risk factors in middle-aged Japanese men. The association between inflammation and the SDPTG should be evaluated in further studies.