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.

Familial Dysalbuminemic Hyperthyroxinemia in a Japanese Man Caused by a Point Albumin Gene Mutation (R218P).

Familial dysalbuminemic hyperthyroxinemia (FDH) is a familial autosomal dominant disease caused by mutation in the albumin gene that produces a condition of euthyroid hyperthyroxinemia. In patients with FDH, serum-free thyroxine (FT4) and free triiodothyronine (FT3) concentrations as measured by several commercial methods are often falsely increased with normal thyrotropin (TSH). Therefore, several diagnostic steps are needed to differentiate TSH-secreting tumor or generalized resistance to thyroid hormone from FDH. We herein report a case of a Japanese man born in Aomori prefecture, with FDH caused by a mutant albumin gene (R218P). We found that a large number of FDH patients reported in Japan to date might have been born in Aomori prefecture and have shown the R218P mutation. In conclusion, FDH needs to be considered among the differential diagnoses in Japanese patients born in Aomori prefecture and showing normal TSH levels and elevated FT4 levels.

[Effects of Long-Term Treatment with Levetiracetam as an Adjunctive Therapy in Japanese Children with Uncontrolled Partial-Onset Seizures: A Multicenter, Open-Label Study].

Following the first period of the multicenter, open-label, single-armed N01223 trial, the second period of the N01223 trial was conducted to evaluate long-term safety, along with the efficacy of adjunctive levetiracetam treatment (individualized dose range, 20-60 mg/kg/day or 1,000-3,000 mg/day) in Japanese pediatric patients with uncontrolled partial-onset seizures (POS). Of the 62 children who completed the first period, 55 children [age: 10.4 ± 3.4 years (mean ± standard deviation)] were elected to enter the second period for a maximum of 39 months. Twenty children were withdrawn during this second period. Frequencies of treatment-emergent adverse events (TEAEs) and adverse drug reactions (ADRs) were 98.2% (54/55 cases) and 27.3% (15/55 cases), respectively. The most common TEAEs were nasopharyngitis (76.4%), influenza (36.4%) and pyrexia (25.5%). The only frequent ADR (>2%) was somnolence (3.6%). Although serious TEAEs and death were reported in 8 cases and 1 case (drowning), respectively, a serious ADR was only reported in 1 case (vomiting). The median percentage reduction and 50% response rate for POS were 43.32% and 41.8%, respectively. One child showed a maximum seizure-free period of 163 days. In conclusion, levetiracetam demonstrated long-term safety and good tolerance with beneficial efficacy as an adjunctive therapy in Japanese children with uncontrolled POS. (Received June 30, 2015; Accepted July 14, 2015: Published November 1, 2015).

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.

How Should a Globalized CTD Be Created? An Introduction to the Japanese 3-Layer Approach.

This article is based on the consensus of a task force of the Data Science Expert Committee, Japan Pharmaceutical Manufacturers Association. Common Technical Documents (CTDs) need to be harmonized in all of the ICH regions to enhance the scientific value and efficiency of these documents. Region-specific CTDs often require modifications for submission in different countries-an urgent issue not only for Japan but also for the countries where participation in the ICH framework will expand. CTDs themselves should be globalized, which means they should use not only a common format but also common contents, by incorporation of a 3-layer approach. In layer 1 of this approach, efficacy and safety of a study drug are evaluated through the overall study results; layer 2 entails evaluation of whether there is inconsistency in efficacy and/or safety of the study drug for a specific subgroup with overall results; and in layer 3, the results of layers 1 and 2 are used to evaluate benefits and risks in each applying country. The 3-layer approach can be used to create a globally common model using data collected in all countries in the study. This global evaluation allows benefits and risks to be evaluated in all countries and should allow globalized CTDs to be developed. Alignment between research and development sites by pharmaceutical companies and success of regulatory conventions can reduce the total amount of review time. Ultimately, these changes would lead to faster approval of new drugs.

Pharmacokinetics of the antiepileptic drug levetiracetam in healthy Japanese and Caucasian volunteers following intravenous administration.

The intravenous (iv) formulation of levetiracetam has been available in clinical practice worldwide for several years, but not in Japan. Two open-label studies were conducted: Study A evaluated the bioequivalence of iv and oral tablet formulations in healthy Japanese volunteers; and Study B subsequently compared the pharmacokinetics of iv levetiracetam in healthy Japanese and Caucasian volunteers. Study A had a randomised, two-way crossover design; a single 1,500 mg levetiracetam dose was administered as a 15-min iv infusion and as 3 × 500 mg oral tablets to Japanese volunteers. In Study B, 1,500 mg levetiracetam was administered as single and repeated 15-min iv infusions to Japanese and Caucasian volunteers. Overall, 26/27 volunteers completed Study A and 32/32 (16 Japanese; 16 Caucasian) completed Study B. In Study A, the point estimate and 90 % confidence interval (CI) for the geometric least squares mean (LSM) ratio (iv vs oral) were fully included within the acceptance range for bioequivalence (0.85-1.25) for the area under plasma concentration-time curve from 0 to last quantifiable observation (AUClast 0.97 [0.95, 0.99]), but not for the maximum plasma concentration (C max 1.64 [1.47, 1.83]). In Study B, after a single iv infusion, the point estimates (90 % CI) for the geometric LSM ratio (Japanese vs Caucasian) for body weight-normalised C max and AUClast were 1.21 (1.07, 1.36) and 0.97 (0.90, 1.04), respectively. Corresponding values after repeated iv infusions were C max,ss 1.01 (0.91, 1.12) and AUCτ,ss 0.89 (0.83, 0.96). Levetiracetam was well tolerated in both studies. Study A did not demonstrate the bioequivalence of single doses of levetiracetam 1,500 mg administered as an iv infusion and as oral tablets in healthy Japanese adults. Study B, however, showed that pharmacokinetic profiles were generally similar between Japanese and Caucasian adults after single and repeated iv infusions of levetiracetam 1,500 mg.

The total urine protein-to-creatinine ratio can predict the presence of microalbuminuria.

BACKGROUND: The Kidney Disease: Improving Global Outcomes chronic kidney disease (CKD) guidelines recommend that CKD be classified based on the etiology, glomerular filtration rate (GFR) and degree of albuminuria. The present study aimed to establish a method that predicts the presence of microalbuminuria by measuring the total urine protein-to-creatinine ratio (TPCR) in patients with cardiovascular disease (CVD) risk factors. METHODS AND RESULTS: We obtained urine samples from 1,033 patients who visited the cardiovascular clinic at St. Luke's International Hospital from February 2012 to August 2012. We measured the TPCR and the urine albumin-to-creatinine ratio (ACR) from random spot urine samples. We performed correlation, receiver operating characteristic (ROC) curve, sensitivity, and subgroup analyses. There was a strong positive correlation between the TPCR and ACR (R2 = 0.861, p<0.001). A ROC curve analysis for the TPCR revealed a sensitivity of 94.4%, a specificity of 86.1%, and an area under the curve of 0.903 for detecting microalbuminuria for a TPCR cut-off value of 84 mg/g of creatinine. The subgroup analysis indicated that the cut-off value could be used for patients with CVD risk factors. CONCLUSIONS: These results suggest that the TPCR with an appropriate cut-off value could be used to screen for the presence of microalbuminuria in patients with CVD risk factors. This simple, inexpensive measurement has broader applications, leading to earlier intervention and public benefit.

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.

[Efficacy and safety of levetiracetam as adjunctive therapy in Japanese children with uncontrolled partial-onset seizures: multicenter and open-label study (N01223), short term evaluation].

A multicenter, open-label, single-armed study (N01223) was conducted to evaluate efficacy and safety of levetiracetam (LEV) as an add-on therapy in Japanese pediatric patients with uncontrolled partial-onset seizures (POS). A total of 73 children aged 4-15 years (mean±SD=10.1±3.4 years) were enrolled in the study, which consisted of an 8-week baseline period and a 14-week treatment period, including a 4-week titration period. A historical placebo control from a pivotal overseas pediatric study in POS add-on therapy was used. A 16.3% median percent reduction from the baseline in POS was observed in this placebo control. Therefore, in the present study, this value (16.3%) was chosen as the predefined threshold for the lower limit of the 95% confident interval (95% CI) of the median percent reduction from the baseline for LEV. In the present study, the percentage reduction (95% CI) in POS during the treatment period was 43.21% (26.19-52.14%), indicating a beneficial impact of LEV. The incidences of treatment-emergent adverse events (TEAEs) and adverse drug reactions (ADRs) were 82.2% (60/73 cases) and 56.2% (41/73 cases), respectively. The most common TEAEs were somnolence, nasopharyngitis, upper respiratory tract infection, and pyrexia. Frequent ADRs (more than 3%) were somnolence and feeling jittery. No serious TEAE or death was reported during the study. Our results suggested that adjunctive therapy with LEV is clinically efficacious and well tolerated in Japanese children with uncontrolled POS.

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.

Assisting the diagnosis of overt hypothyroidism with pattern recognition methods, making use of a set of routine tests, and their multiple correlation with total T4.

In our previous papers we proposed a novel screening method that assists the diagnosis of patients with overt Graves' hyperthyroidism by making use of routine test data and pattern recognition methods. This method can be applied by non-specialists during physical check-ups at low cost and is expected to lead to rapid referrals for examination and treatment by thyroid specialists, that is, to improve patients' QOL. In this report, we investigate whether a similar screening method is also applicable for overt hypothyroidism. Fifty-six subjects with 12 routine test data with a known diagnosis (30 patients with overt hypothyroidism and 52 healthy female volunteers, and 26 patients with overt hypothyroidism and 48 healthy male volunteers) were used as training data. Then, test samples of patients who had also undergone the same routine tests at the Tohoku university hospital were screened by our method for overt hypothyroidism. The present examination of the screening method showed its high screening ability with the set of four parameters used (lactate dehydrogenase [LDH], total cholesterol [TC], red blood cell [RBC] and serum creatinine [S-Cr]). It was found that there was a strong multiple correlation between the set of routine test parameters and serum total thyroxine (TT4) in the patients with overt hypothyroidism, which supports the usefulness of our screening method.

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.

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.

The sphingosine 1-phosphate receptor modulator FTY720 prevents iodide-induced autoimmune thyroiditis in non-obese diabetic mice.

FTY720 is an immunomodulator that alters migration and homing of lymphocytes via sphingosine 1-phosphate receptors. This compound has been shown to be effective in suppressing autoimmune diseases in experimental and clinical settings. In the present study, we tested whether FTY720 prevented autoimmune thyroiditis in iodide-treated non-obese diabetic (NOD) mice, a model of Hashimoto's thyroiditis (HT) in humans. Mice were given 0.05% iodide water for 8 weeks, and this treatment effectively induced thyroiditis. Iodide-treated mice were injected intraperitoneally with either saline or FTY720 during the iodide treatment. FTY720 clearly suppressed the development of thyroiditis and reduced serum anti-thyroglobulin antibody levels. The number of circulating lymphocytes and spleen cells including CD4(+) T cells, CD8(+) T cells, and CD4(+)Foxp3(+) T cells was decreased in FTY720-treated mice. Our results indicate that FTY720 has immunomodulatory effects on iodide-induced autoimmune thyroiditis in NOD mice and may be a potential candidate for use in the prevention of HT.

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.

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.

Experimental autoimmune thyroiditis in human parvovirus B19 transgenic mice.

Viral infection is implicated as a cause of autoimmune diseases. Whereas its role in Hashimoto's thyroiditis (HT) remains undefined, recent studies suggested a link between human parvovirus B19 (B19) infection and HT. We tested such possibility by using B19 nonstructural protein 1 (NS1) transgenic C57BL/6 mice, which harbor nonpermissive genetic background (H-2(b)). Mice were immunized with either thyroglobulin (Tg) or saline. No thyroiditis developed in saline-treated mice and Tg-immunized males regardless of the presence or absence of NS1. In contrast, thyroiditis was induced by Tg immunization in 25% of transgenic females, but not in wild-type females. However, the thyroiditis incidence in the former did not differ significantly from that of the latter. In addition, intrathyroidal T-cell receptor gene expression was not augmented in Tg-immunized transgenic females. Immunization with Tg led to a comparable increase in serum anti-Tg antibody levels in the wild-type and transgenic mice. Our results indicate that the introduction of B19 NS1 gene into C57BL/6 mice is insufficient to promote the development of autoimmune thyroiditis. Further studies are required, however, before concluding that B19 infection is not involved in HT induction.

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.

Assisting the diagnosis of Graves' hyperthyroidism with pattern recognition methods and a set of three routine tests parameters, and their correlations with free T4 levels: Extension to male patients.

In our previous paper, we proposed a novel screening method that aids the diagnosis of female patients with Graves' hyperthyroidism via two types of neural networks and the use of routine test data. This method can be applied by non-specialists during physical checkups at a low cost and is expected to lead to rapid referrals for examination and treatment by thyroid specialists; i.e., to improve patients' QOL. In this report, we investigate whether the screening method is also applicable to males since sex differences exist in routine test data. The values of 14 routine test parameters for 78 subjects with definite diagnoses (31 patients with Graves' hyperthyroidism and 48 healthy volunteers) were adopted as training data, and 133 individuals who had also undergone the same routine tests at Tohoku University Hospital were screened for Graves' hyperthyroidism using our method. The present examination of our screening method in males showed its high screening ability with the set of parameters used (low serum creatinine, elevated alkaline phosphatase, and low total cholesterol). It was also found that there is strong multiple correlation between a set of three parameters and serum free thyroxine (FT4) in male patients with Graves' hyperthyroidism. A formula for FT4 consisting of three parameters was obtained, and this can be utilized in place of the true FT4 value. This result also supports the usefulness of our screening method.