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To evaluate the 72-month clinical results of trabectome surgery (TOM) in patients with primary open-angle glaucoma (POAG), secondary OAG and childhood glaucoma. A total of 305 eyes from 249 glaucoma patients were analyzed in the current retrospective single-center study. Kaplan-Meier analysis was performed using three criteria: criterion A (postoperative intraocular pressure [IOP] ≤ 21 mmHg and ≥ 20% reduction from baseline IOP); criterion B (postoperative IOP ≤ 18 mmHg and ≥ 20% reduction from baseline IOP); and criterion C (postoperative IOP ≤ 16 mmHg and ≥ 20% reduction from baseline IOP). The changes in IOP, medication score, success probability, results of the multivariate analysis for success and failure risk factors, and complications were analyzed. The baseline IOP in all glaucoma patients decreased from 29.2 ± 9.8 mmHg with a 5.3 ± 1.7 medication score to 16.4 ± 5.8 mmHg (− 43.8%) with a 4.2 ± 1.5 medication score at 72 months (p

To analyze the rate and time of occurrence of intraocular pressure (IOP) elevation early after trabectome surgery (TOM) and the characteristics of glaucoma patients recovering from IOP elevation. Four hundred sixty eyes of 460 glaucoma (191 primary and 269 secondary open-angle glaucoma) patients who underwent TOM were evaluated. IOP elevation early after TOM was diagnosed when IOP increased by more than 5 mmHg over baseline within 1 week to 3 months. If the IOP decreased with the administration of anti-glaucoma eye drops alone, patients were classified as recovered. If the IOP did not decrease despite additional anti-glaucoma eye drop use, patients were classified as non-recovered. The rate and time of occurrence of IOP elevation early after TOM were investigated. Demographic and ocular variables related to recovery and non-recovery were identified by multivariate logistic regression analysis. Of the 460 patients, IOP elevation early after TOM occurred in 102 (22.2%). IOP elevation occurred most frequently at postoperative week 1. Of the 102 patients with IOP elevation, 55 (53.9%) recovered and 47 (46.1%) did not. A large hyphema size the day after surgery was associated with increased likelihood of recovery from IOP elevation (odds ratio [OR], 6.6). A history of past selective laser trabeculoplasty (SLT; OR, 0.10) and high baseline IOP (OR, 0.86) were associated with reduced likelihood of recovery from IOP elevation. IOP elevation early after TOM occurred most frequently at postoperative week 1. Patients with a large hyphema size, no history of SLT, and a lower baseline IOP recovered from IOP elevation early after TOM. A large hyphema the day after surgery suggested an increased likelihood of recovery from IOP elevation.

To determine the differences in scleral shape between the superonasal and superotemporal quadrants, the sites of scleral flap creation in trabeculectomy, using anterior segment optical coherence tomography (OCT). Thirty-four right eyes of 34 enrolled subjects without ocular disease, with the exception of cataract or ametropia, were studied. Mean patient age was 63.2 ± 15.9 (standard deviation) years (range 28–84 years). The same examiner captured all images using anterior segment swept source OCT. The mean measurements were calculated from three images captured for each eye, 60° from the horizontal line passing through the pupillary center in the superonasal and superotemporal sclera. The radius of the scleral surface curvature and the area of the convex part of the sclera between the superonasal and the superotemporal quadrants were determined using image analysis software and the paired t test. The radius of the scleral curvature was significantly different in the superonasal quadrant and superotemporal quadrant (34.3 ± 12.6 vs. 18.3 ± 3.6 mm, respectively; P

To describe a modified glaucoma staging system (Modified GSS) based on the visual field index (VFI) and evaluate the performance of the Modified GSS compared with the Bascom Palmer GSS and Enhanced GSS.A total of 549 eyes of 549 patients were studied retrospectively. The Modified GSS was used to classify the glaucomatous visual field defects into stage 0 to 5 based on the VFI. The cutoff values for each stage were derived from VFI that were equivalent to mean deviations of -6, -12, -20, and -25 dB by receiver operating characteristic analysis. The staging performances, based on each of three GSSs, were compared with both the Advanced Glaucoma Intervention Study (AGIS) and Collaborative Initial Glaucoma Treatment Study (CIGTS) scores.The VFI cutoff values calculated for each stage were 81.5, 62.5, 42.5, and 22.5%, respectively. The correlation coefficient of Modified GSS was greater than that of Bascom Palmer GSS (p0.001), and correlation coefficients of Modified GSS and Enhanced GSS were equivalent. However, Enhanced GSS tended to classify moderate to severe AGIS and CIGTS scores into higher stages (p0.001).The Modified GSS is easy to use and accurate, and the staging performance is either equal or superior to existing GSSs.

Changing in the work environment in recent years, an occupational physician needs to make a countermeasure to mental health disorders. When the occupational physician works with employees who have, or are suspected of having, high-functioning developmental disorders, it is necessary to consider the following: Whether, in the course of addressing problems faced by employees, occupational health staff members are able to consider the possibility of developmental disorders. An additional issue is whether the occupational physician, when working with the treating psychiatrist, is able to appropriately provide precise information. Furthermore, when an employee is diagnosed with a developmental disorder, there are questions of whether a smooth internal company approach is possible in the context of appropriate workplace support, and whether it is possible to obtain the understanding of colleagues prior to implementing appropriate workplace assignments and accommodations. Additionally, it is necessary to consider the career paths of employees with high-functioning developmental disorders that are discovered subsequent to being hired. In this paper, introducing some cases, It was summarized the challenges of developmental disabilities in the workplace and discussed correspondence in the workplace.

To evaluate the short-term results of Trabectome surgery performed on Japanese patients.Retrospective observational study. Trabectome surgery was performed on 117 eyes from 101 patients at Kitasato University Hospital from December 2010 to June 2013, involving 48 eyes with primary open-angle glaucoma (POAG), 62 eyes with secondary open-angle glaucoma (SOAG), and 7 eyes with developmental glaucoma. Trabectome surgery alone was performed on 34 phakic eyes (the phakic group) and 35 pseudophakic eyes (the pseudophakic group), and Trabectome surgery combined with phacoemulsification (the combined surgery group) was performed on 48 eyes. The main outcomes assessed were intraocular pressure (IOP), number of IOP-lowering medications, and success probabilities using Kaplan-Meier life-table analyses. Failure risk factors were identified using the Cox proportional hazards ratio.In all cases, after a mean follow-up of 18.5 ± 13.5 months, IOP was reduced from 31.6 ± 9.9 (SD) mmHg using 5.0 ± 1.7 medications to 16.4 ± 5.4 mmHg using 3.8 ± 1.8 medications. One year after surgery, IOP was reduced from 29.4 ± 7.8 to 16.1 ± 3.8 mmHg in POAG, from 33.6 ± 11.1 to 14.7 ± 2.9 mmHg in SOAG, from 33.0 ± 10.2 to 15.7 ± 3.3 mmHg in the phakic group, from 32.6 ± 9.3 to 15.3 ± 3.0 mmHg in the pseudophakic group, and from 29.9 ± 10.0 to 15.2 ± 3.0 mmHg in the combined surgery group. There were no statistically significant differences in IOP at each measurement point, either between POAG and SOAG or among the three procedure subtypes. The POAG and SOAG success rates at 12 months using postoperative IOP ≤ 21 mmHg and ≥20 % reduction in baseline as criteria were 53.9 and 77.2 %, respectively (p = 0.024, log-rank test). Twenty-one eyes (17.9 %) needed additional trabeculectomy. None of the univariate and multivariate risk factors for failure were detected.Trabectome surgery is safe and effective for Japanese patients whose target IOP is 18 mmHg or above. However, it is necessary to carefully consider Trabectome surgery for advanced POAG cases.

Summary OBJECTIVE We previously reported the clinical characteristics of Graves' disease with undetectable TSH binding inhibitor immunoglobulins (TBII) at first visit, but a study of the prognosis of untreated TBII negative patients with anti-thyroid drug medication has never been undertaken. The aim of this paper is to study the difference between negative and positive TBll Graves' disease in relation to the effect of anti-thyroid drug treatment. PATIENTS From January 1986 to April 1991,1545 patients with untreated Graves' disease were referred to Kuma Hospital, Kobe, Japan. Of these, 94 TRAb negative patients were identified. Another 83 TRAb positive patients were randomly selected from the other Graves' disease patients and served as a comparison group. Fifty-six of the 94 patients in the TBII negative group and 52 of the 83 patients in the TBII positive group completed treatment with methimazole only. MEASUREMENTS The trial was conducted as a retrospective study with a maximum treatment period of 36 months and a follow-up period of a further 12 months. From the original pool of patients, we classified 56 TBII negative patients into two groups according to the clinical course taken; Group A in whom TBII remained undetectable throughout methimazole treatment (9 men and 34 women, age 37.2 ± 2.2 years), and Group B who became TBII positive (4 men and 9 women, 31.2 ± 44 years). Fifty-two TBII positive patients served as the comparison Group C (8 men and 44 women, age 38.1 ± 2.0 years). RESULTS Serum free T4 and free T3 levels in groups A and B were significantly lower before treatment than those of Group C (P < 0.001). The thyroid volumes of Group A and B patients were significantly smaller than those of Group C (P < 0.01). The level of TBII in Groups A and B was significantly lower than that in Group C (8.3 ± 0.7 and 8.8·1.1 vs 57.0 ± 28%, respectively, P < 0.001). The level of thyroid stimulating antibody (TSAb) in Groups A and B was significantly lower than that in Group C (478 ± 71.0 and 761 ± 140.3 vs 2143 ± 280%, respectively, P < 0.01), and there were no significant differences in TSAb activities between Groups A and B. The remission rates in Groups A, B and C were 77.4, 36.4 and 36.5%, respectively. These data Indicate that Group A has a good prognosis, but Group B has the same prognosis as Group C. CONCLUSION We conclude that patients In whom TSH binding inhibitor Immunoglobulins remained negative have a much better prognosis than TSH binding inhibitor immunoglobulins positive patients or those who become TSH binding inhibitor immunoglobulins positive, having been initially negative.

To evaluate the reproducibility and interexaminer consistency in analyzing the optic disc parameters using a newly fundus stereoscopic camera, and their correlation with parameters of the Heidelberg Retina Tomograph II (HRT II) was also examined.This study examined 53 eyes of 53 healthy volunteers (mean age, 21.8 y). Fifty-five eyes of 55 glaucoma patients (mean age, 59.3 y) were also involved. A Nonmyd WX retinal camera was used for stereoscopic fundus imaging. The diagnostic parameters for the optic nerve head analyses were examined under the following conditions: (1) the intraexaminer reproducibility was determined by a certified orthoptist (CO) with 1 year's experience, with the appropriate coefficient of variation in 8 healthy eyes; and (2) the interexaminer consistency of the diagnostic parameters by both glaucoma specialist and CO was examined in 45 healthy eyes and 55 glaucomatous eyes. By subgroup analysis, the healthy eyes were classified into 2 groups based on the degree of myopia, the optic disc of glaucomatous eye was classified into 4 types: focal ischemic, generalized enlargement, myopic, and senile sclerotic, and also classified into 3 stages (early, moderate, and severe) by Hodapp-Anderson-Parrish scale. (3) The correlation of parameters common to Nonmyd WX and HRT II was examined in 18 eyes of randomly selected patients.The results were as follows: (1) Mean coefficient of variation of 2.6% to 17.6%, with volume parameters considerably lower than the other parameters. (2) In both groups, a high or moderate degree of consistency was obtained (r=0.40 to 0.99; P=0.032 to0.0001), except only the upper rim width in healthy subjects (r=0.28; P=0.137). In particular, good consistency was obtained in healthy eye with-3 D of myopia, in glaucoma patients with the generalized type of optic disc and severe glaucomatous stage. (3) A strong correlation with HRT II was obtained only in the cup area and the disc area by both specialist and CO (r=0.75 to 0.90; P=0.0003 to0.0001).Our studies indicated that most of the parameters were highly reproducible and consistent, and less difference was found between the results obtained by an experienced glaucoma specialist and a non-expert CO in patients with deep cupping and severe eye, but the examiner needs a clear understanding of the criteria for the rim and the cup.

Zoledronic acid(ZA)dosage should be adjusted according to the risk it poses for renal impairment. The recommended dosage for patients with creatinine clearance(Ccr)of less than 60mL/min was established on the basis of an area under the curve analysis, but is doubted because it was calculated without performing a clinical trial. Creatinine secretion from the renal tubule affects Ccr; therefore, using Ccr as the basis for dosage adjustment may be inappropriate since this can cause an overestimation of the glomerular filtration rate(GFR). The Japanese Society of Nephrology recommends using the estimated GFR(eGFR)for evaluating renal function. Therefore, this study investigated the relationship between renal function before and adverse events(AEs)after ZA administration. The dosage of only 3 of the 47 patients with Ccr less than 60mL/min could be adjusted on the basis of Ccr. During ZA therapy(3 courses), the blood urea nitrogen level and occurrence of hypokalemia were higher in the non-adjusted group than in the adjusted group, but the total number of AEs was equivalent for both groups. For all the patients, Ccr and eGFR were used as parameters for investigating AEs; the total number of AEs was equivalent for patients with differing levels of renal function. Therefore, we suggest that AEs observed during ZA therapy did not depend on the renal function level before ZA administration.

To determine the histological characteristics of hyperthyroid Graves' disease with undetectable TSH receptor antibodies (TRAb), we examined the thyroid histological findings of patients with hyperthyroidism who were referred for subtotal thyroidectomy and who lacked circulatory TRAb. Four patients had undetectable TRAb (6.4 +/- 4.2%) before treatment (group A). Their pathological and clinical findings were compared with those of four patients who had hyperthyroid Graves' disease with detectable TRAb (83.8 +/- 8.3%) before treatment (group B). The groups were matched for sex, age, duration of antithyroidal drug therapy, anti-Tg antibody, and antimicrosomal antibody levels. All patients were in a euthyroid state just before operation. Papillate hyperplastic epithelia in group A were significantly less severe than in group B. Enlarged colloids were not observed in two of the four patients in group A but were observed in all four patients in group B. Moderate or marked lymphocytic infiltrations were observed in all patients in group A but were virtually absent in group B. Based on these results, it is probable that hyperthyroid Graves' disease with undetectable TRAb titers represents an early stage or subtype of usual hyperthyroid Graves' disease in which there is marked or moderate lymphocytic infiltration.

The basic cancer pain management at our hospitalis based on WHO Cancer Pain Treatment Method-Opioid together with NSAIDs. We investigated 48 patients who were administered an opioid as management of cancer pain for three (3) months from May to July in 2008. Consequently, we found that 20 out of the 48 patients (41.7%) used an opioid together with NSAIDs. Meanwhile, we also investigated constipation and digestive impediment as side effects caused from opioid and NSAIDs, respectively. Of the 20 patients, 12 patients (60%) used laxative for constipation, and 18 patients (90%) used a digestive ulcer treatment drug for digestive impediment. Ten (20.8%) of the 48 patients used all 4 drugs-opioid, NSAIDs, laxative and digestive ulcer treatment drugs. As a result, we decided to further examine cancer pain management at our hospital.

To assess the effect of corneal astigmatism on intraocular pressure (IOP) measurements using an Ocular Response Analyzer (ORA) and a Goldmann applanation tonometer (GAT).We prospectively examined 59 normal eyes of 59 healthy volunteers (18 men, 41 women; age, mean +/- standard deviation, 40.5 +/- 14.2 years; age range, 19-68 years). We quantitatively assessed the values of corneal-compensated intraocular pressure (IOPcc) and Goldmann-correlated intraocular pressure (IOP(G)) using an ORA (Reichert Ophthalmic Instruments). We also measured the IOP using a GAT (GAT-IOP). The amount of corneal astigmatism was assessed with an autokeratometer. We carried out these measurements three times, and the mean value obtained was used for statistical analysis.The mean IOPcc, IOP(G), and GAT-IOP were 14.7 +/- 2.6, 14.0 +/- 2.8, and 14.2 +/- 1.7 mmHg respectively. The mean corneal astigmatism was 0.94 +/- 0.55 D. We found no significant correlation between IOPcc and corneal astigmatism (Pearson's correlation coefficient r = -0.04, p = 0.79), or between IOP(G) and corneal astigmatism (r = 0.09, p = 0.52). However, we found a weak, but significant, correlation between GAT-IOP and corneal astigmatism (Pearson's correlation coefficient r = 0.34, p = 0.009).Both IOPcc and IOP(G) measured with ORA were less affected by the amount of corneal astigmatism, and the GAT-IOP readings were significantly higher in eyes with greater corneal astigmatism, suggesting that IOPcc as well as IOP(G) may be helpful for accurate IOP measurements in eyes with some corneal astigmatism.

To investigate intraocular pressure (IOP) measurement values in normal tension glaucoma (NTG) eyes using two different types of tonometer that are supposed to be little affected by corneal biochemical properties.This study included 30 normal eyes of 16 healthy subjects and 30 eyes of 16 patients with NTG. IOP was measured with a Goldmann applanation tonometer (GAT), a Pascal dynamic contour tonometer (DCT), and a Reichert ocular response analyzer (ORA) three times each for normal and NTG eyes. The main measures were GAT-IOP, DCT-IOP, corneal-compensated IOP (IOPcc), Goldmann-correlated IOP (IOPg), and central corneal thickness (CCT).In normal eyes, GAT-IOP was 13.2 +/- 1.4 mmHg; DCT-IOP, 13.0 +/- 1.6 mmHg; IOPcc, 13.6 +/- 2.0 mmHg; and IOPg, 12.4 +/- 2.0 mmHg. Multivariate analysis revealed no significant differences between the four measurements (p = 0.08). CCT was 524.6 +/- 27.3 microns. In NTG eyes, GAT-IOP was 13.1 +/- 1.3 mmHg; DCT-IOP, 13.7 +/- 1.3 mmHg; IOPcc, 15.2 +/- 2.0 mmHg; and IOPg, 12.7 +/- 2.0 mmHg. Multivariate analysis showed significant differences between the four measurements (p0.01). Sheffé's test showed that IOPcc was significantly higher than GAT-IOP, DCT-IOP, and IOPg (GAT-IOP vs IOPcc: p0.0001; DCT-IOP vs IOPcc: p = 0.01; IOPcc vs IOPg: p0.0001). CCT was 515.4 +/- 32.9 microns, with no significant difference between normal and NTG eyes (p = 0.15).We investigated the values of IOP in NTG eyes as measured by the DCT and ORA. IOPcc was significantly greater than GAT-IOP, DCT-IOP and IOPg in NTG eyes, suggesting the possibility that IOP values may be underestimated.

The etiology of subacute (de Quervain's) thyroiditis (SAT) is uncertain, although it probably represents a nonspecific inflammatory response by the thyroid to a variety of viruses. It has been suggested that nonimmune processes are involved in SAT patients who have negative autoantibody titers. The disease has a variable course; although it is self-limited in most cases, some patients develop transient hypothyroidism, and others do not during the recovery period. The present study was performed to evaluate the occurrence of TSH receptor antibody (TRAb), measured by RRA (TSH binding inhibitor), TRAb measured by stimulation assay (thyroid-stimulating antibody), and TRAb measured by blocking assay [TSH-blocking antibody (TSH-BAb)] activity in 68 patients with SAT who had negative autoantibody titers. The patients were divided into 2 groups: group I, 31 patients who developed hypothyroidism during the recovery period; and group II, 37 patients who remained euthyroid during recovery. Positive immunoglobulin activity occurred in about 20% of group I patients during follow-up, but in only 3% of group II patients. About 20% of group I patients developed positive TSH-BAb activity and were hypothyroid, requiring exogenous hormone therapy for 1.2-3.5 yr, whereas hypothyroidism was relatively transient in group I patients who had negative TSH-BAb activity (2-6 months). Although increased TSH-BAb activity may account for hypothyroidism in some patients with SAT, the precise mechanism for the development of transient hypothyroidism in SAT remains enigmatic.

It has been shown that hypothyroidism of some patients may be associated with increased activity of thyroid stimulating-blocking antibodies (TSBAb). The present study was undertaken to follow the course of thyroid blocking, stimulating immunoglobulins and TSH-binding inhibitor immunoglobulins (TBII) in six hypothyroid patients who had elevated TSBAb and were treated with T4. Four of the six had Graves' disease previously treated with antithyroidal drugs, one had Graves' disease treated with 131I and one had subacute thyroiditis and subsequently became hypothyroid. The patients were followed for 1-5 years. Blocking activity and TBII normalized in four of the six during T4 therapy, so T4 was discontinued and they remained euthyroid. These data indicate that it is important to monitor carefully thyroid function in hypothyroid patients treated with a fixed amount of T4 to avoid subclinical hyperthyroidism and its consequence, e.g. osteoporosis.

Background Small-scale enterprises (SSEs) usually share poorer resources for promoting occupational health. Aim To investigate inequality of health status among SSEs in Japan. Method A cross-sectional, multiple-centred study was carried out using the periodical health check-up data for the fiscal year 2000 to compare the age-adjusted proportions of workers with hypertension (HT), hyperlipidaemia, impaired glucose tolerance (IGT) and obesity and of current smokers by size of enterprise, i.e. ≤29, 30-49, 50-99, 100-299, 300-999 and 2:1000 employees in Japan. Results From five leading occupational health organizations, data were collected for 9833 enterprises with a total of 436 729 subjects, 302 383 males and 134 346 females. The proportions of workers in SSEs with ≤49 employees with HT, IGT and obesity were 8.5, 5.0 and 3.5%, respectively, higher than those in enterprises with ≥50 male employees. The prevalence of smokers in SSEs with ≤49 employees was 61%, 2-6% higher than in enterprises with≥50 male employees. These proportions showed a significantly increasing tendency with decreasing size of male workforce. Conclusion Despite the cross-sectional design and only adjusting age as a potential confounder, higher proportions of HT, IGT, obesity and smoking in male workers were found in SSEs compared to larger organizations.

A prospective study was conducted to evaluate the intraocular pressure (IOP) lowering effect of brinzolamide 1.0% ophthalmic suspension as an adjunctive therapy with latanoprost 0.005% ophthalmic solution in patients with open angle glaucoma or ocular hypertension.Fourteen patients with open angle glaucoma (OAG) or ocular hypertension (OH) who had been using latanoprost 0.005% for more than 6 months were initiated on adjunctive brinzolamide therapy. The IOP values at 1 month, 2 months, and 3 months were compared with those measured immediately before adding brinzolamide to the regimen (baseline). The incidence of adverse events such as conjunctival hyperemia and corneal epithelial defect were also examined.The baseline IOP was 21.1 +/- 4.8 mmHg (mean +/- standard deviation). After 1 month, 2 months, and 3 months of therapy IOP was 16.9 +/- 4.5 mmHg, 16.6 +/- 4.0 mmHg, and 15.9 +/- 3.1 mmHg, respectively, showing significant reductions in IOP at all the measuring time-points during the study compared with the baseline value (p0.01). Conjunctival hyperemia developed in one patient after 1 month and in another after 2 months; however, both were mild, and therapy was continued. Corneal epithelium defect was observed in 3 patients. One of them had mild defect before brinzolamide was added to the regimen. Increase of eye discharge was seen in one patient. No serious side effects were otherwise observed.The addition of brinzolamide to a latanoprost 0.005% regimen may further lower intraocular pressure in patients with open angle glaucoma or ocular hypertension.

The effects of short-term low intensity aerobic training on the physiological indexes and the Quality of Life were examined in 43 middle-aged White Collar Workers. Training was carried out for 205 +/- 117 minutes/week, at least 2-3 times/week for 2 months on a cycle ergometer or walking with intensity level set at the 50% VO2max. Following this training protocol, thirty-six men (exercise group) completed the 2-month training program and 7 men dropped out (the dropout group). In the exercise group, both the VO2max (l/min) and VO2max/wt increased significantly (VO2max (l/min): P < 0.05. VO2max/wt: P < 0.01), whereas the weight, body mass index, %fat, fat (kg) and the waist hip ratio (WHR) decreased significantly (WHR: P < 0.05, others: P < 0.01) after 2 months. In addition, the DBP and serum TC, LDL-c/HDL-c decreased significantly (LDL-c/HDL-c: P < 0.01, others: P < 0.05) whereas the HDL-c increased significantly (P < 0.05). A modified Croog questionnaire was used to assess the subject's Quality of Life. The questionnaire consisted of 59 questions and the overall assessment was based on eight components. Regarding the Quality of Life, physical symptoms, work performance and satisfaction, total Quality of Life all improved significantly (physical symptoms, P < 0.05; others: P < 0.01) and social participation also tended to improve (P < 0.08). There was a significantly negative correlation between the initial Quality of Life and the changes in the Quality of Life (6 of the 8 components). In the all subjects, there was a significantly positive correlation between the changes in physical symptoms and the changes in VO2max/wt (r = 0.36, P < 0.05). In the dropout group, the FBS increased significantly (P < 0.05) but no other variables regarding the Quality of Life significantly changed after 2 months. In conclusion the above results suggest that short-term low intensity aerobic training in the present study can help improve the physiological indexes, VO2max and Quality of Life in middle-aged White Collar Workers and the observed improvement in the Quality of Life was also found to be greater in the subjects with a low Quality of Life than in those with a high Quality of Life.

OBJECTIVE TSH-binding inhibitory immunoglobulin (TBII) is undetectable in about 10% of untreated Graves' disease patients, but the clinical characteristics and immunological significance of this finding are unknown. In this study we evaluated the clinical characteristics of TBII negative Graves' disease. PATIENTS We examined TBII in 1048 untreated patients at Kuma hospital from 1986 to 1990 and found 69 TBII undetectable patients (12 men and 57 women, mean age +/- SEM 35 +/- 2 years, group A). MEASUREMENTS We compared the clinical characteristics and immunological findings of group A with 57 untreated TBII detectable Graves' patients who were selected randomly (11 men and 46 women, mean age +/- SEM 40 +/- 2 years, group B). T4, TSH, FT4, FT3, 123I thyroid uptake, TBII, thyroid stimulating antibodies (TSAb) and the volume of the thyroid using ultrasonography were measured at the first visit. RESULTS Serum T4, FT4 and FT3 levels in group A were significantly lower than those in group B (P < 0.001). The values of TSAb in group A were significantly lower than those in group B (593 +/- 67 (mean +/- SE) vs 2143 +/- 280%, respectively, P < 0.001). The 123I thyroid uptake in group A was significantly lower than that in group B (53.1 +/- 1.1 vs 61.4 +/- 1.4%, respectively, P < 0.01). The thyroid volume in group A was significantly smaller than that in group B (39.1 +/- 3.0 vs 51.3 +/- 3.3 ml, respectively, P < 0.01). TSAb was undetectable in about 10% (6) of the TBII negative untreated Graves' patients at their first visit. CONCLUSION In the present study, untreated TBII negative patients with Graves' disease were characterized by mild elevation of thyroid hormones, mildly elevated 123I uptake, weak TSAb activities and small goitres. The finding of both TBII and TSAb negative titres in untreated Graves' disease patients was also confirmed.

Eighty-five patients with Graves' disease in clinical remission after treatment for over 1 year by methimazole therapy (36 patients, group A) or subtotal thyroidectomy (49 patients, group B) who became undetectable for serum thyrotropin levels (TSH less than 0.05 mU/l), were further followed for 1 year or more. Eight patients in group A (22%) and 7 patients in group B (14%) relapsed. Eleven patients in group A (30%) and 5 patients in group B (10%) had fluctuating patterns of free T4 in the upper normal to slightly supranormal range indicative of subclinical hyperthyroidism. The remaining patients continued to have undetectable TSH levels or restored normal TSH levels and normal thyroid hormone concentrations in sera. The results of the present study indicate that the occurrence of undetectable serum TSH concentrations in Graves' disease patients previously treated with methimazole or surgery are not necessarily predictive of clinical relapse because the eventual outcome is variable.

SUMMARY Hashimoto's thyroiditis (HT) and lymphoma arc sometimes difficult to distinguish between. Moreover, lymphoma sometimes develops in a thyroid gland from pre-existing HT. Open- or large-needle biopsy usually distinguishes between them; the specimen may be examined histologically and subjected to immunohistochemistry. Another possible method of examination is fine-needle aspiration biopsy (FNAB). The cells obtained may be evaluated cytologically, and subjected to flow cytometry, using various antibodies. In this study, anti-kappa and anti-lambda antibodies are especially important, as a gross predominance of kappa or lambda B lymphocytes infiltrating the thyroid is evidence for a B cell monoclone. In this study, 15 patients were selected because of their rapidly growing goitres. They all underwent FNAB. Five had cytology typical of HT, and no evidence of monoclonality on flow cytometry. They were diagnosed as HT without further histopathology. The remaining 10 patients had cytology suspected of lymphoma, or evidence of monoclonality on flow cytometry, or both. These patients underwent open- or large-needle biopsy. Only three of them were diagnosed histopathologically as lymphoma; the other seven were diagnosed histopathologically as HT, making 12 cases of HT in all. Five of these 12 cases, and one of the three cases of lymphoma showed flow cytometrical evidence of monoclonality; thus evidence of monoclonality from FNAB, while interesting, does not necessarily serve to differentiate between HT and lymphoma. Furthermore, the immunohistochemical assessment of monoclonalily did not correlate with the flow cytometrical assessment. Follow-up evidence will be required to discover whether those patients with a B cell monoclone in their HT are the ones who develop a lymphoma.

To investigate genetic factors involved in the pathogenesis of Hashimoto's thyroiditis (HT; goitrous autoimmune thyroiditis), HLA class I and class II antigens were analyzed in both seropositive HT (99 patients) and seronegative HT (43 patients). The frequency of HLA-DRw53 antigen was increased significantly in both seropositive HT (antigen frequency, 0.83; relative risk, 33.3; P less than 0.0002; corrected P less than 0.001) and seronegative HT (antigen frequency, 0.81; relative risk, 3.02; P less than 0.01; corrected P less than 0.05). The etiological fraction values for HLA-DRw53 in seropositive HT and seronegative HT were 0.58 and 0.54, respectively. An increased frequency of HLA-DQw4 and a decreased frequency of HLA-DQw1 were observed in patients with seronegative HT. These data suggest that susceptibility to HT is primarily associated with HLA-DRw53 and that HLA-DQ alleles may control the production of autoantibodies to the thyroid gland. The mode of inheritance of disease susceptibility for HT (controlled by a major gene in linkage disequilibrium with HLA-DRw53) was investigated by the method of Thomson and Bodmer, and it was suggested that disease susceptibility was inherited in a dominant manner.

TSH binding inhibitor immunoglobulin (TBII) and thyroid-stimulating antibody (TSAb) activities were measured serially for 4-32 months in nine patients before and during development of hyperthyroidism due to Graves' disease. Initially, all were euthyroid, seven had thyroid enlargement, one had proptosis, and seven had high serum titers of antithyroid microsomal antibodies. The occurrence of hyperthyroidism was preceded by detection of both TBII and TSAb in four patients and detection of TSAb alone in four patients. One patient had neither TBII nor TSAb when euthyroid. The mean initial TBII and TSAb activities were 10.2 +/- 15.2% (+/- SD) and 2677 +/- 4620%, respectively, when these patients were euthyroid. When they became hyperthyroid, both TBII and TSAb activities increased in all patients. At that time, TBII was detected in all but one (eight of nine subjects; 88.9%), with a mean activity of 58.8 +/- 23.4% (+/- SD), and TSAb was detected in all nine patients, with a mean value of 4508 +/- 4429%. These findings not only indicate the crucial role of TSH receptor antibodies in the development of hyperthyroidism due to Graves' disease, but also suggest that a certain period of subclinical Graves' disease exists before the onset of overt hyperthyroidism in most patients, in the sense that they have TSH receptor antibodies, especially TSAb, in their serum even though they are euthyroid.

We studied the effect of therapy with 0.1 mg/day T4 for 3 months on goiter size in 49 patients with solitary thyroid nodules. The nodule volume in 18 patients (responders) decreased by more than 50%. In this group the mean serum thyroglobulin (Tg) levels decreased significantly (from 425 to 61 micrograms/L; P less than 0.01). In the nonresponders the mean serum Tg levels did not change significantly (145 vs. 250 micrograms/L). The mean serum T4, free T4, free T3, and rT3 concentrations increased significantly in both groups during T4 therapy, serum T3 levels did not change, and serum TSH decreased. These findings demonstrate that serum Tg levels decrease when T4 therapy is effective. Thus, serum Tg measurements may prove a useful indicator of the efficacy of T4 therapy in patients with solitary nodules.

We treated a 32-year-old man with "thyroidal prelymphoma", morphologically resembling Hashimoto's thyroiditis and associated with monoclonal gammopathy (IgG, lambda). Immunohistochemistry revealed intracytoplasmatic monoclonal immunoglobulin (IgG, lambda) containing lymphoid cells in the interstitium of the thyroid tissue. After total thyroidectomy had been performed, the monoclonal immunoglobulin disappeared. Three years have passed since the surgery and this writing, there has been no recurrence. The existence of thyroidal prelymphoma suggests that chronic antigenic stimulation might produce lymphocytes which are more susceptible to neoplastic change (Hashimoto's thyroiditis----thyroidal prelymphoma----malignant lymphoma of the thyroid).

We have investigated the specific immune response to Epstein-Barr virus (EBV) of peripheral blood mononuclear cells (PBMC) from patients with malignant lymphoma of the thyroid. Coculture of PBMC and EBV resulted in EBV cell transformation and regression which was assayed by an EBV-induced B cell focus-regression assay technique. The EBV had been isolated from mouthwash samples. The specific immune response to EBV by outgrowth inhibition in PBMC from untreated EBV-seropositive patients with malignant lymphoma was significantly decreased when compared to PBMC from EBV-seropositive healthy subjects (p less than 0.05). This observation is at least consistent with the possibility that B-cell proliferation after continuous or recurrent EBV infection could be a causative factor or may potentiate malignant lymphoma of the thyroid.

Malignant lymphoma of the thyroid has been shown to be of B-cell origin. To clarify its genetic origin, we have investigated HLA-A, B, C, and DR antigens, and the immunoglobulin G (IgG) heavy-chain allotype, Gm, in such patients. There was no correlation between the occurrence of malignant lymphoma of the thyroid and the HLA antigens tested, but patients with this lymphoma had significantly lower frequency of the Gm1,21 haplotype than healthy persons. These results suggested a disorder of surveillance related to B-cells may be involved in the pathogenesis of malignant lymphoma of the thyroid.

Three hundred and fifty-three euthyroid relatives of Graves' disease patients were tested for TSH binding inhibitory immunoglobulins (TBII). Eighteen had elevated levels of TBII, and 232 who had negative TBII levels also agreed to be followed for a period of 6-30 months. TBII was chosen as the critical screening measurement for this study, rather than thyroid-stimulating antibodies (TSAb) and thyroid-stimulating blocking antibodies (TSBAb), because of the availability and ease of use of TBII RIA kits. Eleven of the 18 subjects with elevated TBII were T3 nonsuppressible (group I), and 10 of the 11 were TRH unresponsive. Nine of these 10 subjects showed TSH levels below 0.05 mU/L. The remaining 7 subjects were T3 suppressible and TRH responsive (group II). Alterations in thyroid status occurred in 8 of the 11 subjects in group I during follow-up. One developed hypothyroidism, and 7 became hyperthyroid. The hypothyroid subject had initial titers of TBII, TSAb, and TSBAb that were markedly elevated, and TSAb disappeared when she became hypothyroid. Six of the 7 subjects who developed hyperthyroidism had elevated TSAb and negative TSBAb titers while they were euthyroid. All 7 subjects in group II remained euthyroid during the follow-up period. Only 2 of the 232 relatives who initially had negative TBII titers became hyperthyroid during the follow-up period. The results indicate that euthyroid relatives with a family history of Graves' disease who have elevated TBII levels and suppressed basal serum TSH concentrations have a much higher potential to develop hyperthyroidism than those who have normal or negative TBII levels.

We reviewed the records of approximately 7000 Japanese patients whose hyperthyroidism was treated with methimazole (MMI) alone. Four patients (Group I) developed agranulocytosis during a second course of MMI therapy and eight patients (Group II) during an initial course. Six patients (three in each group) received less than 30 mg MMI daily. Agranulocytosis occurred after more than 2 months of therapy (12 weeks-1 year) in five patients. Seven patients were less than 40 years of age. One patient displayed a gradual protracted development of agranulocytosis. These results indicate that agranulocytosis after MMI may occur irrespective of dose, age, duration of treatment, and with a second exposure.

Silent (painless) thyroiditis has been recognized as a clinical entity for over a decade and is characterized by spontaneously resolving thyrotoxicosis. Its etiology is uncertain; however, a few reports have indicated the occurrence of TSH binding-inhibiting immunoglobulins (TBII) and thyroid-stimulating antibodies (TSAb) in some of the patients. The present study was undertaken to evaluate thyroid function and the occurrence of TBII and TSAb and thyroid autoantibodies (antithyroglobulin and antimicrosomal) in 53 patients with silent thyroiditis during the course of their disease. The patients were divided into 2 major groups: I) those who developed transient hypothyroidism and II) those who did not. All patients initially had significantly increased concentrations of serum T4, free T4, and free T3, suppressed TSH levels, and decreased thyroid radioiodine uptake. TBII and TSAb were initially positive in 8 (15.1%) and 10 patients (18.9%), respectively. Forty patients were available for follow-up. TBII was positive in 6 of 24 (25.0%), and TSAb was positive in 8 of 24 (33.3%) of the patients who developed transient hypothyroidism during the course of their disease. Among the patients who did not become hypothyroid at any time, TBII was positive in only 2 of 16 (12.5%), and none of the patients became TSAb positive. The findings indicate that increased TSAb and TBII activity may be detected in patients with silent thyroiditis and, when present, are associated with transient hypothyroidism during the course of the disease.