Surface defect healing in annealing from nanoporous carbons to nanoporous graphenes.

Nanoporous graphene (NPG) materials have the pronounced electrochemical stability of the seamless graphene structures developed over the 3D space. We revisited the Raman spectra of nanoporous carbons (NPCs) synthesized using θ-/γ-Al2O3 templates and NPGs converted from NPCs by annealing at 1800 °C to identify the type and density of defects. We found that both the NPCs and NPGs mostly consist of single-layered graphene with a few single vacancies and Stone-Wales defects. The density of vacancy defect per hexagon in the graphene sheet is estimated to be 10-2 for NPCs, while the annealing reduced the value to 10-3-10-4 for NPGs. This supports the outstanding chemical and electrochemical stability of the novel porous carbon materials.

Modified Cut-Off Value of the Urine Protein-To-Creatinine Ratio Is Helpful for Identifying Patients at High Risk for Chronic Kidney Disease: Validation of the Revised Japanese Guideline.

Chronic kidney disease (CKD) is a global public health issue, and strategies for its early detection and intervention are imperative. The latest Japanese CKD guideline recommends that patients without diabetes should be classified using the urine protein-to-creatinine ratio (PCR) instead of the urine albumin-to-creatinine ratio (ACR); however, no validation studies are available. This study aimed to validate the PCR-based CKD risk classification compared with the ACR-based classification and to explore more accurate classification methods. We analyzed two previously reported datasets that included diabetic and/or cardiovascular patients who were classified into early CKD stages. In total, 860 patients (131 diabetic patients and 729 cardiovascular patients, including 193 diabetic patients) were enrolled. We assessed the CKD risk classification of each patient according to the estimated glomerular filtration rate and the ACR-based or PCR-based classification. The use of the cut-off value recommended in the current guideline (PCR 0.15 g/g creatinine) resulted in risk misclassification rates of 26.0% and 16.6% for the two datasets. The misclassification was primarily caused by underestimation. Moderate to substantial agreement between each classification was achieved: Cohen's kappa, 0.56 (95% confidence interval, 0.45-0.69) and 0.72 (0.67-0.76) in each dataset, respectively. To improve the accuracy, we tested various candidate PCR cut-off values, showing that a PCR cut-off value of 0.08-0.10 g/g creatinine resulted in improvement in the misclassification rates and kappa values. Modification of the PCR cut-off value would improve its efficacy to identify high-risk populations who will benefit from early intervention.

Efficacy and tolerability of levetiracetam as adjunctive therapy in Japanese patients with uncontrolled partial-onset seizures.

AIMS: The aim of this study was to confirm the efficacy and safety of adjunctive levetiracetam in adult Japanese patients with uncontrolled partial-onset seizures. METHODS: In a double-blind, placebo-controlled, confirmatory trial, eligible patients were randomized to receive levetiracetam 500, 1000, 2000, or 3000 mg/day or placebo for 16 weeks. The primary end-point was percentage reduction from baseline in seizure frequency/week over a 12-week evaluation period. Tolerability assessments were also conducted. Findings of this and a previous randomized, double-blind trial were compared. RESULTS: Of 401 patients screened, 352 were randomized and 316 completed the study. Median percentage reduction in seizure frequency/week from baseline was 12.92%, 18.00%, 11.11% and 31.67% in the levetiracetam 500, 1000, 2000 and 3000-mg groups, respectively, compared with 12.50% in the placebo group. Unlike the previous trial, the primary efficacy analysis between the levetiracetam 1000 and 3000-mg and placebo groups did not reach statistical significance (P = 0.067). Exploratory analyses demonstrated that the difference in seizure reduction versus placebo was 14.93% (95% confidence interval, 1.98-27.64; P = 0.025) for the levetiracetam 3000-mg group. All levetiracetam doses were well tolerated. The main difference between the two trials was a high placebo response in the present trial. CONCLUSIONS: The primary efficacy analysis did not reach statistical significance, a finding that could be attributed to an unexpectedly high placebo response. Nonetheless, exploratory analysis suggests that levetiracetam at 3000 mg/day may, at least marginally, be beneficial for patients with uncontrolled partial-onset seizures.

Validity of salt intake assessment system based on a 24-h dietary recall method using a touch panel computer.

BACKGROUND: An electronic system for salt intake assessment using a 24-h dietary recall method has been developed in Japan. We evaluated the validity of this salt intake system for assessing salt intake. METHODS: We prospectively obtained data on estimated salt intake using 24-hour urinary sodium excretion (24-hUNaCl) and salt intake by the salt intake assessment system from 203 consecutive outpatients with essential hypertension (age: 67.8 ± 10.7 years; 53.7% men). RESULTS: Mean values were 9.7 ± 2.9 g/day for 24-hUNaCl and 9.1 ± 2.9 g/day for the salt intake assessment system before corrections. The salt intake estimated by the present system was significantly correlated with 24-hUNaCl (r = 0.66, p < 0.0001). After corrections for habitual use of discretionary seasonings, habitual intake of salty foods, and physical activity, correlation coefficients between salt intake and 24-hUNaCl increased from 0.60 to 0.66 in men <65 years, from 0.80 to 0.81 in men ≥ 65 years, from 0.64 to 0.75 in women <65 years, and from 0.52 to 0.59 in women ≥ 65 years. After further correction for regional differences in average salt intake, the correlation coefficient reached 0.72 in all patients. CONCLUSION: After correction for dietary habits, lifestyle factors, and differences in average salt intake by region, this system may be a useful tool in Japan to encourage salt restriction in the clinical treatment of hypertension and improve public health in terms of salt restriction overall.

Effects of green tea polyphenols on iodide-induced autoimmune thyroiditis in nonobese diabetic mice.

Because green tea polyphenols (GTPs) possess anti-inflammatory properties and are effective in inhibiting autoimmune diseases in experimental settings, we examined whether GTPs prevented the development of autoimmune thyroiditis in iodide-treated nonobese diabetic (NOD) mice, an animal model of Hashimoto's thyroiditis (HT). Mice were given 0.05% iodide water or iodide water supplemented with 0.2% GTPs for 8 weeks. GTPs administration led to an enhanced production of interleukin-10 by concanavalin A-stimulated splenocytes but did not interfere with thyroiditis development. Serum thyroxine levels were not influenced by GTPs. Our data suggest that administration of GTPs may not be an effective strategy for the prevention of HT.

Effects of synthetic retinoid Am80 on iodide-induced autoimmune thyroiditis in nonobese diabetic mice.

We examined whether a synthetic retinoid Am80 prevented the development of autoimmune thyroiditis in iodide-treated nonobese diabetic mice, an animal model of Hashimoto's thyroiditis (HT). Am80 (0, 0.1 or 1 mg/kg/day) was orally administered in feed during the 8-week iodide treatment. While iodide ingestion effectively induced thyroiditis, Am80 administration failed to interfere with thyroiditis development and serum anti-thyroglobulin antibody levels regardless of the dose of the retinoid. Splenic T cell numbers, splenocyte proliferation and interferon-γ production were decreased in the Am80-treated mice. Our data suggest that Am80 is not a candidate for use in the prevention of HT.

Erythrocyte zinc concentration as an indicator to distinguish painless thyroiditis-associated transient hypothyroidism from permanent hypothyroidism.

Red blood cell (RBC) zinc (Zn) concentration reflects a patient's mean thyroid hormone level over the preceding several months. The aim of this study was to examine whether RBC Zn level can be used as an indicator to distinguish painless thyroiditis-associated transient hypothyroidism (TH) from permanent hypothyroidism (PH). RBC Zn level was measured in 30 untreated PH patients with Hashimoto's thyroiditis and 7 untreated TH patients with painless thyroiditis in whom preceding transient thyrotoxicosis had been confirmed. RBC Zn concentration was significantly lower in TH patients than that in PH patients. There was a positive correlation between RBC Zn and serum TSH, and the latter was clearly lower in TH patients than that in PH patients. However, RBC Zn level was again significantly lower in TH patients than PH patients despite of the comparable serum TSH levels in both groups when RBC Zn was evaluated in patients with serum TSH levels of less than 50 mU/L. Thus TH patients could be identified with RBC Zn measurement, allowing us avoidance of unnecessarily prolonged T4 administration to them.

A novel EEG index for evaluating the sleep quality in patients with obstructive sleep apnea-hypopnea syndrome.

Obstructive sleep apnea-hypopnea syndrome (OSAHS) is a highly prevalent sleep disorder characterized by recurrent episodes of oxygen desaturation during sleep, decreased sleep quality, and excessive daytime sleepiness. A basic method of evaluating sleep quality is polysomnography (PSG) where sleep stages are identified from the electroencephalogram (EEG), electrooculogram and chin electromyogram. The implementation of PSG is limited to sleep laboratories because this test is rather complicated to perform and quite time-consuming to analysis, requiring skilled technicians. Development of simple alternative methods to PSG could enable sleep tests to be performed at home. Our study aimed to identify simple measures for evaluating the sleep quality. We focused on a simple index, entropy, which is derived from power spectrum of EEG signals throughout the night, and reflects the dynamics of EEG signals, and examined whether the entropy of EEG reflects the sleep quality of OSAHS. The EEG signals for the analysis of EEG entropy were recorded from the temple area. The EEG entropy was compared with the sleep quality by traditional approaches of EEG from PSG in 58 OSAHS patients and 8 healthy volunteers. The EEG entropy in each subject showed the negative values and fluctuated during sleep. There was a significant correlation between the EEG entropy and the sleep quality (r = 0.626, p < 0.001); namely, the amplitude of the fluctuation was increased with the increase in the sleep quality. We therefore propose that the EEG entropy could be useful for evaluating the sleep quality of OSAHS.

Establishment of a method to detect microalbuminuria by measuring the total urinary protein-to-creatinine ratio in diabetic patients.

Diabetes and chronic kidney disease (CKD) which are risk facters of cardiovascular disease, are increasing global public health problems. Microalbuminuria is an early sign of progressive cardiovascular and renal disease in individuals with or without diabetes. Screening for microalbuminuria and early treatment are recommended for patients with increased cardiovascular and renal risk factors. However, the procedure used to measure urinary albumin is expensive. Alternatively, the measurement of total urinary protein is simple and inexpensive. Thus, we aimed to establish a method that could predict the presence of microalbuminuria by measuring the total protein-to-creatinine ratio. Spot urine samples were obtained from 150 patients with diabetes mellitus, and the total protein-to-creatinine ratio and the albumin-to-creatinine ratio (ACR) were measured. There was a significant positive correlation between the protein-to-creatinine ratio and the ACR (r = 0.95). The presence of albuminuria (both micro- and macroalbuminuria) could be predicted from the value of the protein-to-creatinine ratio in more than 90% of patients. A receiver-operating characteristic curve analysis revealed that the protein-to-creatinine ratio had a sensitivity and a specificity of 90.8% and 91.9%, respectively, for the detection of albuminuria and a cutoff value of 0.091 g/g creatinine. These results suggest that screening for microalbuminuria can be replaced by the detection of the protein-to-creatinine ratio, which may be cost-effective for patients with cardiovascular risks as well as for the general population.

Does the Japanese Society for Hygiene need its own Code of Conduct? A comparison of the responses of councilors and junior members based on a questionnaire survey.

OBJECTIVE: The purpose of this study was to compare current awareness of the "On a Code of Conduct for Scientists" (OCCS) among members of the Japanese Society for Hygiene (JSH). METHOD: An anonymous self-administered questionnaire was mailed to JSH members, including 439 councilors and 376 junior members (who were under 50 years of age with a membership of 3 years or longer, excluding councilors). Councilors were surveyed from November to December 2007, while junior members were surveyed from November to December 2008. RESULTS: The overall response rate was 40.6% (n = 331/815), with responses from 46.7% of the councilors (n = 205/439) and 33.5% of the junior members (n = 126/376). Among the respondents, 36.0% of councilors (n = 68) and 59.8% of junior members (n = 73) did not know the contents of "On the Code of Conduct for Scientists" (P < 0.01), while 76.3% of councilors (n = 145) and 61.4% of junior members (n = 75) had not heard of it (P < 0.05). However, a majority of the respondents reported interest in the Code [70.0% of councilors (n = 133), 68.6% of junior members (n = 83)] (P < 0.05) and a favorable attitude towards research ethics education [69.3% of councilors (n = 133), 68.9% of junior members (n = 84)] (P < 0.54). In addition, 24.3% of the responding councilors (n = 46) and 15.7% of the responding junior members (n = 19) believe it necessary for JSH to formulate its own code of conduct for scientists (P < 0.01). CONCLUSION: We clarified the current state of awareness of the OCCS among JSH members as well as the opinion of members for the JSH to have its own Code of Conduct for Scientists. This result provides important information that should be considered during the formulation of an individual code of conduct for scientists in the JSH.

Pharmacological profile of the novel anti-inflammatory corticosteroid NS-126, a therapeutic agent for allergic rhinitis.

NS-126 (9-fluoro-11beta,17,21-trihydroxy-16alpha-methylpregna-1,4-diene-3,20-dione 21-cyclohexanecarboxylate 17-cyclopropanecarboxylate) is a novel, highly lipophilic anti-inflammatory corticosteroid. We compared NS-126 and the widely used intranasal corticosteroid fluticasone propionate (FP) in a guinea-pig model of allergic rhinitis and a rat model of airway eosinophilia. In the allergic rhinitis model, NS-126 and FP reduced sneezing and nasal obstruction to similar extents. In the airway eosinophilia model, both compounds inhibited the infiltration of eosinophils into the bronchoalveolar lavage fluid, but the effect of NS-126 was longer-lasting than that of FP. In vitro, NS-126 showed lower affinity than FP for the glucocorticoid receptor and was a weaker inhibitor of Th(2) cytokine and chemokine production and mast-cell secretory responses. We also investigated DX-17-CPC, a metabolite of NS-126 generated in nasal tissue by carboxylesterase-catalyzed hydrolysis at the 17-position. DX-17-CPC showed greater affinity than NS-126 for the glucocorticoid receptor and was a stronger inhibitor of Th(2) cytokine and chemokine production and mast-cell secretory responses. The long duration of the anti-allergic effects of NS-126 may be explained by its high lipophilicity, while the strength of its anti-allergic effects may be explained by the generation of the active metabolite DX-17-CPC. NS-126 is a long-acting intranasal corticosteroid and a promising therapeutic agent for allergic rhinitis.

Sunitinib-induced thyrotoxicosis followed by persistent hypothyroidism with shrinkage of thyroid volume.

Sunitinib, a tyrosine kinase inhibitor, has been approved for the treatment of cancers, such as advanced renal cell carcinoma (RCC). On the other hand, sunitinib treatment is known to induce thyroid dysfunction in a substantial proportion of patients treated for advanced RCC; in fact, hypothyroidism is a frequent complication. However, little is known about sunitinib-induced thyrotoxicosis and destructive thyroiditis. Here, we report a patient with RCC who developed transient overt thyrotoxicosis followed by hypothyroidism due to sunitinib treatment. A 58-year-old woman, who had been treated with chronic thyroiditis, was diagnosed as having left RCC with bone metastasis to the rib. The patient underwent resection of the left kidney and the bone metastasis lesion. However, 3 months later, bone metastasis to the rib recurred, and sunitinib treatment was started. At 6 weeks of sunitinib therapy, the patient developed transient thyrotoxicosis, followed by persistent hypothyroidism. In the thyrotoxic phase, the patient was diagnosed as having destructive thyroiditis based on an increased thyroglobulin level, a low radioactive iodine uptake, increased free thyroxine level, and suppressed thyroid-stimulating hormone level. The thyroid volume in the hypothyroid phase was 68% of that in the thyrotoxic phase. In conclusion, the present report suggests that sunitinib-induced persistent hypothyroidism may be a consequence of preceding destructive thyroiditis with transient thyrotoxicosis. The decreased volume of the thyroid during the hypothyroid phase indicates irreversible organ damage in the present patient, thereby resulting in persistent hypothyroidism. Thus, periodic surveillance of thyroid function is mandatory during sunitinib therapy.

[Attitudes towards the code of conduct for scientists among council members of the Japanese Society for Hygiene].

OBJECTIVES: The aim of this study was to clarify the attitudes towards the code of conduct for scientists among council members of the Japanese Society for Hygiene (JSH). We also aimed to collect information to be used as baseline data for future studies. METHODS: From November to December 2007, 439 Council members of the Japanese Society for Hygiene completed a self-administered questionnaire. RESULTS: The valid response rate was 43.7% (n=192/439). The mean ages of the subjects were 56.2 years for males (n=171), and 53.0 years for females (n=19). Many council members were unfamiliar with the "Code of Conduct for Scientists" established by the Science Council of Japan, suggesting that most of the regular members were also unfamiliar with these guidelines. However, the high level of interest in the "Code of Conduct for Scientists" established by the Science Council of Japan indicated a positive attitude towards learning about research ethics. Moreover, one-half of the subjects responded that JSH should establish a code of conduct for scientists. Below are some of the reasons for requiring JSH to establish a code of conduct: 1. Private information is prevalent in the field of hygiene. 2. The overall stance as an academic society would be established and would encourage individuality in academic societies. 3. Members have various backgrounds within the field of hygiene, and they should have a code of conduct different from that of their institution of affiliation. CONCLUSION: We clarified attitudes towards the Code of Conduct for Scientists among council members of the Japanese Society for Hygiene.

[Education in the medical technology course, Tohoku University School of Health Sciences].

The purpose of education in the Course of Medical Technology, Tohoku University School of Health Sciences, is to educate students to become medical technologists in hospital laboratories, or scientific staff of medical companies. Many papers have been published in this journal about proper education in the Course of Medical Technology; therefore, in the present paper, I describe my thoughts on how to teach students, and my personal opinion on the national examination for medical technologists.

[Evaluation of a simplified index (spectral entropy) about sleep state of electrocardiogram recorded by a simplified polygraph, MemCalc-Makin2].

BACKGROUND: Polysomnography (PSG) is the gold standard for the diagnosis of sleep apnea hypopnea syndrome (SAHS), but it takes time to analyze the PSG and PSG cannot be performed repeatedly because of efforts and costs. Therefore, simplified sleep respiratory disorder indices in which are reflected the PSG results are needed. The Memcalc method, which is a combination of the maximum entropy method for spectral analysis and the non-linear least squares method for fitting analysis (Makin2, Suwa Trust, Tokyo, Japan) has recently been developed. Spectral entropy which is derived by the Memcalc method might be useful to expressing the trend of time-series behavior. AIM: Spectral entropy of ECG which is calculated with the Memcalc method was evaluated by comparing to the PSG results. SUBJECTS: Obstructive SAS patients (n = 79) and control volanteer (n = 7) METHODS: ECG was recorded using MemCalc-Makin2 (GMS) with PSG recording using Alice IV (Respironics) from 20:00 to 6:00. Spectral entropy of ECG, which was calculated every 2 seconds using the Memcalc method, was compared to sleep stages which were analyzed manually from PSG recordings. RESULTS: Spectral entropy value (-0.473 vs. -0.418, p < 0.05) were significantly increased in the OSAHS compared to the control. For the entropy cutoff level of -0.423, sensitivity and specificity for OSAHS were 86.1% and 71.4%, respectively, resulting in a receiver operating characteristic with an area under the curve of 0.837. The absolute value of entropy had inverse correlation with stage 3. CONCLUSIONS: Spectral entropy, which was calculated with Memcalc method, might be a possible index evaluating the quality of sleep.

[Effect of age on electrocardiogram entropy value of parameters by sleep respiratory disturbance].

BACKGROUND: Spectral entropy of electrocardiogram (ECG), which was calculated using the MemCalc method with a portable bio-signal measurement instrument (PBSM), might be a possible parameter for evaluating the quality of sleep. AIM: This study assessed the effects of ECG spectral entropy on obstructive sleep apnea/hypopnea syndrome (OSAHS) depending on age. STUDY DESIGN: ECG was recorded using a PBSM, and the maximum entropy of ECG every 9 RR intervals was calculated. These entropies were compared with the age and sleeping indices obtained with a conventional polysomnography (PSG) system. SETTING AND PARTICIPANTS: Seventy-six patients suspected of OSAHS were recorded from 20:00 to 06:00 using a conventional PSG system (Alice III) and a PBSM (MemCalc-Makin2) simultaneously. RESULTS: ECG entropy showed correlations to high frequency (HF, 0.15-0.40 Hz) heart rate variability in the cardiac parasympathetic activity index, as did the ECG entropy value, and a negative correlation was found with the age (r = 0.538, p < 0.0001), and positive correlation with the HF value (r = 0.810, p < 0.0001). The ECG entropy value in subjects aged > or = 40 with no different sleep respiratory disturbance index by PSG data (AHI, Arousal Index, DSI, and sleep efficiency, etc.) to 60 years old was compared with those aged > or = 60. The ECG entropy value and HF value decreased at > or = 60 years old with statistically significant. CONCLUSION: The value of ECG entropy corresponds to cardiac parasympathetic function, and it decreases according to age (increase by the absolute value).

[Examination of spirometry techniques on instruction by medical technologists for screening purposes].

BACKGROUND: The burden of chronic obstructive pulmonary disease (COPD) remains very high. Current consensus guidelines emphasize the importance of the early detection of COPD, but its underdiagnosis is common in general practice. Spirometry is the "gold standard" in the diagnosis of COPD. However, it remains underused in general practice because the application of spirometry is viewed as difficult to obtain accurate results. AIMS: To clarify the accuracy of spirometry techniques for screening purposes. METHOD: Subjects (n = 142) were told about the spirometry procedure using pre-determined descriptions, followed by the first spirometry test. Special medical technologists gave instructions on the detailed spirometry procedure on reference to the first test of results, and the second spirometry test was performed. The second spirometric indices, SVC, FVC, FEV1, FEV1%, and PEF, were compared with the first ones. RESULTS: The instruction by special medical technologists significantly improved all spirometric indices except for FEV1%. For a diagnosis of restrictive disorder (VC<80%), the impact of intervention by the special medical technologists was highly significant (p<0.001). In contrast, for the diagnosis of obstructive disorder (FEV1%<70%), the impact was small. CONCLUSION: To detect obstructive disorder, the high-level accuracy of special spirometry techniques is not always necessary.

Forsterite exposure causes less oxidative DNA damage and lung injury than chrysotile exposure in rats.

Chrysotile (CH) is a pathogenic waste building material that can potentially be rendered innocuous via conversion to forsterite (FO) by heating at high temperatures. We compared the ability of FO and CH to cause oxidative DNA damage and lung injury. A single 1-mg intratracheal dose of CH or FO was administered to rats. Significant changes were observed 3 to 7 days after CH injection in alveolar macrophages, neutrophils, eosinophils, lymphocytes, total protein, and lactate dehydrogenase. High concentrations of 8-hydroxy-29-deoxyguanosine (8-OHdG) were also observed in the macrophages, other infiltrating inflammatory cells, granulomas, and in bronchiolar and alveolar epithelial cells. The overexpression of 8-OHdG was limited to airway epithelial and inflammatory cells surrounding the fibrotic foci 540 days after injection, indicating that the inflammatory effects of CH were persistent yet decreased with time. Compared to the CH group, acute lung inflammation observed in the FO group was less apparent and exhibited no progressive fibrosing lesions. The expression of 8-OHdG was transient and weak in the bronchiolar epithelial cells as well as in the inflammatory cells, consistent with low concentrations of 8-OHdG observed in the lungs. These findings confirm that FO causes significantly less inflammation and oxidative DNA damage in the lungs than CH.

A comparison of urinary albumin-total protein ratio to phase-contrast microscopic examination of urine sediment for differentiating glomerular and nonglomerular bleeding.

BACKGROUND: Hematuria can be classified as either glomerular or nonglomerular, depending on the bleeding source. We recently reported that urinary albumin-total protein ratio is potentially useful for identifying the source of hematuria. STUDY DESIGN: Diagnostic test study. SETTING & PARTICIPANTS: 579 fresh urine specimens with microhematuria (> or =5 red blood cells/high-power field) collected from patients with the source of the hematuria confirmed on histopathologic and/or imaging studies and clinical criteria assessed. INDEX TEST: Each urine specimen was evaluated morphologically by using phase-contrast microscopy and biochemically by using urinary albumin-total protein ratio, albumin-creatinine ratio, and total protein-creatinine ratio. REFERENCE TEST: Each patient had a definitive clinical diagnosis established by means of biopsy (64.4%), imaging studies (21.2%), and routine optimal microscopic examination of urine sediment (14.3%). RESULTS: Of 579 specimens, 329 were obtained from patients with glomerular disease and 250 were obtained from patients with nonglomerular disease. Mean urinary albumin-total protein, albumin-creatinine, and total protein-creatinine ratios for those with glomerular versus nonglomerular diseases were 0.73 +/- 0.11 versus 0.41 +/- 0.14 mg/mg (P < 0.001), 1,110 +/- 1,850 versus 220 +/- 560 mg/g (P < 0.001), and 1,600 +/- 3,010 versus 480 +/- 1,160 mg/g (P < 0.001), respectively. The percentage of patients with greater than 3% glomerular red cells was 83.3% versus 24.8% (P < 0.001). Receiver operating characteristic curve analysis showed that areas under the curve for albumin-total protein ratio, albumin-creatinine ratio, and total protein-creatinine ratio were 0.992, 0.781, and 0.688, respectively (P < 0.001, albumin-total protein versus albumin-creatinine; P < 0.001, albumin-total protein versus total protein-creatinine). At cutoff values of 0.59 mg/mg, 71 mg/g, and 265 mg/g, albumin-total protein ratio, albumin-creatinine ratio, and total protein-creatinine ratio had sensitivities and specificities of 97.3% and 100%, 78.9% and 61.1%, and 68.8% and 62.0% for detecting glomerular disease, respectively. Phase-contrast microscopy had sensitivity of 83.3% and specificity of 75.2% for detecting glomerular disease. LIMITATIONS: Albumin-total protein ratio cannot be used in patients with urinary total protein less than 5 mg/dL (<0.05 g/L). Use of only 1 sample from 1 patient may not be sufficient to obtain definitive results. CONCLUSIONS: Urinary albumin-total protein ratio is much more useful than phase-contrast microscopy for differentiating between glomerular and nonglomerular disease in patients with microscopic hematuria.

Profile of serum testosterone levels after application of testosterone ointment (glowmin) and its clinical efficacy in late-onset hypogonadism patients.

INTRODUCTION: Testosterone replacement therapy has been applied to alleviate the various symptoms of late-onset hypogonadism (LOH) patients. Several routes are available for the administration of testosterone to LOH patients, and transdermal delivery is an attractive method above all. AIM: The aim of this article was to clarify the profile of serum total testosterone (TT) and free testosterone (FT) levels after application of testosterone ointment (Glowmin [GL], Daito Pharmaceutical Co. Ltd., Tokyo, Japan) and its clinical efficacy in LOH patients. METHODS: Serum TT and FT levels were examined in healthy male volunteers and LOH patients after application of 3 mg of GL. Then, 50 LOH patients received 3 mg of GL twice daily on scrotal skin (6 mg/day) for 12 weeks. Subsequently, TT and FT levels immediately prior to GL application were compared with those at 1 hour after GL treatment. Furthermore, the clinical effects of GL in the aforementioned 50 LOH patients were estimated after 12 weeks of GL treatment. MAIN OUTCOME MEASURES: Hormonal effects of GL were evaluated by serum TT and FT levels. Aging males symptoms (AMS), international index of erectile function (IIEF-5), and MOS 36-item short form Healthy Survey (SF-36) questionnaire were used to assess the clinical efficacy of GL for LOH patients. RESULTS: Maximum TT and FT values, which were detected 1-2 hours after application of a 2-cm line of GL (3 mg of testosterone) to scrotal skin, were not elevated beyond physiological levels; subsequently, these levels returned to circadian rhythm after 4 hours in four healthy male volunteers. The highest TT and FT levels were also obtained after 1-2 hours in four LOH patients involving identical administration methods; moreover, these levels were maintained within a normal range for 6 hours. After 12 weeks of GL treatment in 50 LOH patients, TT and FT levels demonstrated the same satisfactory response as that of the initial GL administration without GL accumulation effects. GL accumulation after 1 week in healthy men and after 12 weeks in LOH patients was not observed. Furthermore, AMS score decreased markedly; IIEF-5 and four domains of the SF-36 score were elevated significantly following GL application. Severe adverse reactions were not observed. CONCLUSIONS: Accordingly, GL, which is a short-acting testosterone ointment eliciting physiological elevation of TT and FT, appears to be suitable for LOH treatment.