Guillain-Barré syndrome in a local area in Japan, 2006-2015: an epidemiological and clinical study of 108 patients.

BACKGROUND AND PURPOSE: Many epidemiological studies of Guillain-Barré syndrome (GBS) and Fisher syndrome (FS) have been conducted in Europe and America. In contrast, epidemiological studies are rare in Asia where the GBS subtypes differ from those in Western countries. This study was undertaken to clarify the incidence of GBS and FS in a local area in Japan as well as their seasonal trends. METHOD: Seventy-one GBS and 37 FS patients were recorded from 2006 to 2015 in an area of approximately 1.5 million inhabitants in Japan. The incidence, seasonal trends and clinical features of GBS and FS were examined. RESULTS: The incidence rate of GBS was 0.42 cases per 100 000 person-years and that of FS was 0.22 cases per 100 000 person-years. The incidence of GBS increased with age and FS affected predominantly patients aged from 45 to 64 years old. There was some seasonal clustering of acute motor axonal neuropathy (AMAN) and FS in spring and summer, but it was not significant. AMAN and FS patients had a high frequency of preceding infection (AMAN, 68% gastrointestinal infection; FS, 65% upper respiratory infection). Antecedent respiratory infection was significantly associated with FS as an outcome. Serum antibodies to ganglioside GM1 were detected in 71% of AMAN patients and antibodies to GQ1b were detected in 81% of FS patients. CONCLUSIONS: Our study offers evidence of a lower incidence of GBS and a higher incidence of FS in a local area in Japan than in Western countries.

Effect of ultra-low-dose estradiol and dydrogesterone on arterial stiffness in postmenopausal women.

Abstract Background Ultra-low-dose estradiol is known to improve menopausal symptoms and increase bone mineral density. However, the effect of ultra-low-dose estradiol on vascular function has not been clarified. Objectives We examined the effects of ultra-low-dose estradiol on brachial-ankle pulse wave velocity (baPWV) and circulating markers of cardiovascular risk. Patients and methods Twenty-eight postmenopausal women were enrolled in this study. Fourteen women received oral estradiol (0.5 mg) and dydrogesterone (5 mg) every day for 12 months (ultra-low-dose group) as hormone replacement therapy (HRT) and 14 women as a control group did not receive HRT. The baPWV, lipid profiles, homeostasis model assessment of insulin resistance (HOMA-IR) and vascular inflammatory markers were measured. Results The baPWV level significantly decreased in the ultra-low-dose group (p = 0.037), while the baPWV level did not significantly change in the control group. HOMA-IR tended to decrease in the ultra-low-dose group (p = 0.076). Systolic blood pressure and diastolic blood pressure did not change significantly in either group. Conclusion An HRT regimen using oral ultra-low-dose estradiol and dydrogesterone has an effect on arterial stiffness and insulin resistance.

Abundant daily non-sedentary activity is associated with reduced prevalence of metabolic syndrome and insulin resistance.

BACKGROUND: Non-exercise activity thermogenesis has recently drawn attention because of its potential to prevent weight gain. AIM: This study evaluated the relationships between the duration of daily non-sedentary activities and the prevalence of metabolic syndrome and insulin resistance (IR) in the Japanese population. MATERIAL/SUBJECTS AND METHODS: A total of 518 eligible subjects (380 men and 138 women) who attended the Tokushima Prefectural General Health Checkup Center and participated in the baseline survey of a cohort study conducted in Tokushima Prefecture, Japan were analyzed. Information about lifestyle characteristics including leisure-time exercise and daily non-exercise activities was obtained from a questionnaire. Logistic and multiple linear regression analyses were performed to evaluate the associations between the duration of daily non-exercise non-sedentary activities (beyond sitting) and prevalence of metabolic syndrome (and its components) and IR. RESULTS: Subjects with longer duration of daily non-sedentary activities had significantly lower adjusted odds ratios for metabolic syndrome (p for trend =0.024), abdominal obesity (p for trend =0.023), and low HDLcholesterol levels (p for trend =0.002), after adjustment for sex, age, and other probable covariates including leisure-time exercise. Longer duration of daily non-sedentary activities was further associated with lower homeostasis model of assessment- IR (HOMA-IR) values (p for trend =0.009). CONCLUSIONS: Our results suggest that abundant daily non-sedentary activity might be associated with a lower prevalence of metabolic syndrome, especially for the components of central obesity and low HDL-cholesterol levels, and with a lower prevalence of IR, independent of leisure-time exercise.

Increasing incidence of elderly onset patients with myasthenia gravis in a local area of Japan.

OBJECTIVE: As the number of elderly patients with myasthenia gravis (MG) has recently increased in Europe and the USA, a retrospective survey of Japanese MG patients was conducted in a single neurological centre over several decades. METHODS: The study consisted of 112 consecutive MG patients with onset of the disease from 1971 to 2006 from an area of approximately 0.8 million inhabitants in Japan. Patients were classified into three subgroups according to age at onset: young onset (39 years old), middle aged onset (40-59 years old) and elderly onset (60 years old). The trends in incidence rate and clinical features were examined: disease severity, seropositivity for antiacetylcholine receptor antibody, occurrence of other autoimmune diseases, occurrence of thymoma and therapeutic response. RESULTS: The onset adjusted age specific average annual incidence per 100,000 of the elderly onset MG patients increased 20-fold from 1981-1990 (0.06; 95% CI 0.00 to 0.36) to 2001-2006 (1.30; 95% CI 0.77 to 2.05). Clinical features of the elderly onset MG patients included low antiacetylcholine receptor antibody titres (mean 24.6 nmol/l), less frequent autoimmune overlaps (8.0%) and nearly no complete stable remission with or without thymectomy. CONCLUSION: The increasing incidence of elderly onset MG in Japanese patients similar to that reported in Caucasians has been confirmed. The clinical features suggest different immunological backgrounds between young onset and elderly onset MG patients, irrespective of the ethnic background.

A genome-wide association study of coping behaviors suggests FBXO45 is associated with emotional expression.

Individuals use coping behaviors to deal with unpleasant daily events. Such behaviors can moderate or mediate the pathway between psychosocial stress and health-related outcomes. However, few studies have examined the associations between coping behaviors and genetic variants. We conducted a genome-wide association study (GWAS) on coping behaviors in 14088 participants aged 35 to 69 years as part of the Japan Multi-Institutional Collaborative Cohort Study. Five coping behaviors (emotional expression, emotional support seeking, positive reappraisal, problem solving and disengagement) were measured and analyzed. A GWAS analysis was performed using a mixed linear model adjusted for study area, age and sex. Variants with suggestive significance in the discovery phase (N = 6403) were further examined in the replication phase (N = 7685). We then combined variant-level association evidence into gene-level evidence using a gene-based analysis. The results showed a significant genetic contribution to emotional expression and disengagement, with an estimation that the 19.5% and 6.6% variance in the liability-scale was explained by common variants. In the discovery phase, 12 variants met suggestive significance (P < 1 × 10-6 ) for association with the coping behaviors and perceived stress. However, none of these associations were confirmed in the replication stage. In gene-based analysis, FBXO45, a gene with regulatory roles in synapse maturation, was significantly associated with emotional expression after multiple corrections (P < 3.1 × 10-6 ). In conclusion, our results showed the existence of up to 20% genetic contribution to coping behaviors. Moreover, our gene-based analysis using GWAS data suggests that genetic variations in FBXO45 are associated with emotional expression.

Circulating profiles of osteoprotegerin and soluble receptor activator of nuclear factor kappaB ligand in post-menopausal women.

OBJECTIVE: The aim of this study was to elucidate the detail profiles of circulating osteoprotegerin (OPG) and soluble receptor activator of nuclear factor kappaB ligand (sRANKL) in post-menopausal women. METHODS: Eighty Japanese post-menopausal women were enrolled in this cross-sectional study. Circulating OPG and free fraction of sRANKL (free sRANKL), PTH, calcium and phosphorus, age, years since menopause, body mass index, bone mineral density of the vertebral bodies (LBMD) and bone turnover markers were determined in each subject. RESULTS: In rank order correlation analysis, serum OPG concentrations had a significant positive correlation with age (r=0.291, p=0.024) and a marginal significant negative correlation with LBMD (r=-0.247, p=0.062). However they did not have correlations with LBMD or other parameters after adjustment for age. Serum free sRANKL concentrations had a significant positive correlation with age (r=0.332, p=0.010) and a significant negative correlation with LBMD (r=-0.608, p<0.001). This correlation with LBMD persisted after adjustment for age. In a multiple regression analysis with a stepwise model, the main determinants of LBMD were age and serum free sRANKL (p=0.015 and p=0.006, respectively). CONCLUSIONS: We found the increase in circulating OPG and sRANKL with age and a robust negative correlation between circulating free sRANKL and LBMD after adjustment for age. The increase in circulating free sRANKL may reflect directly or indirectly the conditions coexistent with bone loss in post-menopausal women.

Local expression of immunoregulatory IL-12p40 gene prolonged syngeneic islet graft survival in diabetic NOD mice.

Local production of immunosuppressive cytokines will be one of the most suitable therapeutic strategies against organ-specific autoimmune diabetes. To establish such a new therapy, we constructed recombinant adenoviral vectors with inserted mIL-12p40 (Ad.IL-12p40) and mIL-10 (Ad.IL-10). Sufficient amounts of IL-12p40 and IL-10 were secreted by relevant adenovirus-transfected nonobese diabetic (NOD) islets. Shortly after transfection, 400 NOD islets transfected with Ad.IL-12p40 or Ad.IL-10 were transplanted under the renal capsule of a newly diabetic NOD mouse. NOD mice with IL-12p40-producing islet grafts kept normoglycemia in all of 14 grafted mice for over 4 wk after transplantation. In contrast, NOD mice with IL-10-producing islet grafts became diabetic in all of six grafted mice within 2 wk af-ter transplantation. Reverse transcription-PCR analysis revealed that local production of IL-12p40 led to the decrease of interferon-gamma and the augmentation of transforming growth factor-beta at the graft site. These results suggest that IL-12 plays an important role in the destruction of islet cells at the inflamed site of autoimmunity. Such a local blockade of IL-12 would be a useful gene therapy for human autoimmune diabetes.

Suppression and acceleration of autoimmune diabetes by neutralization of endogenous interleukin-12 in NOD mice.

A corpus of evidence suggests that T-helper type 1 (Th1)-dependent cellular immunity plays a pivotal role in the pathogenesis of autoimmune diabetes. This study was intended to find ways to prevent the development of NOD diabetes using a neutralizing anti-interleukin (IL)-12 antibody (C17.8) that inhibits Thl cell differentiation. When C17.8 was administered from 5 to 30 weeks of age, NOD mice exhibited suppression of both insulitis and diabetes. However, when C17.8 administration ceased at 15 weeks of age, 8 of 13 recipients showed diabetes at 30 weeks of age. These results suggest that IL-12 plays an important role not only in the development of effector cells but also in their activation. In contrast, when C17.8 was injected into 2-week-old female NOD mice for 6 consecutive days, all 16 recipients showed diabetes at 30 weeks of age, whereas 12 of 20 control mice became diabetic. This result suggests that depletion of endogenous IL-12 at a young age results in the enhancement of diabetes. Flow cytometric analysis indicated that activated memory T-cells were present in higher numbers after C17.8 treatment. Transfer of spleen cells from 15-week-old C17.8-treated NOD mice to NOD-scid mice resulted in an earlier onset and a higher incidence of diabetes. Furthermore, administration of C17.8 to 2-week-old NOD mice also resulted in a much earlier onset of diabetes. These results suggest that short-term treatment with anti-IL-12 antibody prohibits IL-2 production at a young age, which may influence the expansion and apoptosis of pathogenic T-cells, resulting in the acceleration of autoimmune diabetes.

Pre-operative serum levels of sialyl Tn antigen predict liver metastasis and poor prognosis in patients with gastric cancer.

AIMS: To clarify the prognostic value of preoperative serum levels of sialyl Tn antigen (STN) for survival of gastric cancer patients. METHODS: Pre-operative serum levels of STN, sialyl Lewis(a)antigen (CA19-9) and carcinoembryonic antigen (CEA) were examined in 180 patients who underwent resection of gastric cancer. Patients were divided into high and low antigen groups on the basis of a selected diagnostic-based cut-off value. Correlation between high antigen serum levels, established clinicopathologic factors and prognosis was examined by univariate and multivariate analysis. RESULTS: Twenty-eight patients (15.6%) were classified as high STN; 37 (20.6%) as high CA19-9; and 33 (18.3%) as high CEA. The survival time of the high STN, CA19-9 or CEA group was shorter than that of the respective low-antigen group (P<0.0001, P=0.0008 or P=0.0002, respectively). Patients with stage III/IV tumours with high STN had a shorter survival time that those with low STN (P=0.0004). Cox's regression with multiple covariates showed that high serum STN is an independent factor predicting a worse outcome in gastric cancer patients. Multiple logistic regression analysis revealed that high serum STN is an independent predictor for the development of liver metastasis. CONCLUSIONS: Pre-operative high serum levels of STN predict both liver metastasis and poor prognosis after resection for gastric cancer.

Prognostic value of carcinoembryonic antigen (CEA) in tumor tissue of patients with colorectal cancer.

To establish the prognostic value of carcinoembryonic antigen (CEA) concentration in tumor tissue (T-CEA), normal colonic mucosa (N-CEA) and pre-operative serum (S-CEA), we studied 79 patients who underwent resections for colorectal cancer. The patients were separated into groups reflecting laboratory values lower or higher than a diagnostic value (S-CEA) or the median value of the entire population (T-CEA, N-CEA). A high S-CEA predicted for more advanced stage (p = 0.028), whereas no association was noted between stage and CEA concentration for T-CEA and N-CEA groups. The high S-CEA and T-CEA groups had a worse clinical outcome (p=0.0036 and p=0.024, respectively), while survival of high versus low N-CEA groups did not differ. By Cox's regression analysis, high T-CEA concentration was an independent variable for poor outcome (Hazard ratio, 3.15), while S-CEA and N-CEA were not. In conclusion, a high T-CEA concentration was the only independent predictor of poor outcome after resection for colorectal cancer.

Reproducibility of urinary beta 2-microglobulin and cadmium excretion among residents in a cadmium-polluted area during a 3-year period.

To assess the measurement error by using single exposure measurement in epidemiologic studies, reproducibility of urinary beta 2-microglobulin and cadmium excretion was evaluated among persons exposed to environmental cadmium. We measured urinary beta 2-microglobulin concentrations in 47 subjects four times and urinary cadmium concentrations in 48 subjects twice, during a 3-year period. Between-person and within-person variance components of these variables were estimated using a random-effects one-way analysis of variance model. The intraclass correlation coefficient (ICC) for urinary beta 2-microglobulin concentration, when expressed as microg/g creatinine and microg/l, was 0.92 and 0.89, respectively. The ICC for standardized urinary cadmium concentration (expressed as microg/g creatinine) was 0.81, while it decreased to 0.33 without standardization. The findings suggest that single measurement of urinary beta 2-microglobulin and cadmium, when expressed as a function of creatinine, can reliably estimate average levels over at least a 3-year period. Standardization of concentration using urinary creatinine improved reproducibility especially for urinary cadmium excretion.

Significance of cadmium concentrations in blood and hair as an indicator of dose 15 years after the reduction of environmental exposure to cadmium.

To evaluate the significance of cadmium (Cd) concentrations in blood (B-Cd) and hair (H-Cd) as an indicator of dose, a cross-sectional study was performed on 40 residents in a Cd-polluted area, Nagasaki Prefecture, Japan, in 1996. In the study area, soil replacement of Cd-polluted rice fields ended in 1981. B-Cd and H-Cd were significantly higher in the study population than in the control subjects. B-Cd was positively correlated with urinary Cd (U-Cd) (Spearman r=0.50, P=0.06 for males and r=0.72, P=0.0001 for females), while H-Cd was weakly or moderately correlated with U-Cd. After adjustment for gender using logistic regression analysis, log(B-Cd) and log(U-Cd), but not log(H-Cd), were significantly associated with the prevalence of increased urinary beta2-microglobulin (P for trend <0.05). These findings suggest that B-Cd is a good indicator of cumulative dose many years after the reduction of environmental exposure to Cd. H-Cd may be weakly or moderately correlated with body burden.

The pathophysiology of glossal pain in patients with iron deficiency and anemia.

BACKGROUND: It is well known that prolonged anemia causes atrophy of tongue papillae, glossal pain, and dysphagia, but it is uncertain whether iron (Fe) deficiency induces glossal pain without any objective manifestation. To resolve this matter, the relationship between Fe deficiency and glossal pain was examined. METHODS: Eighteen patients with Fe deficiency and 7 anemic patients manifesting spontaneous irritation or pain of the tongue without any objective abnormalities participated in this study. To ascertain the cause of glossal pain and the oral pathophysiology in Fe deficiency and anemia, peripheral blood was examined and the glossal pain threshold and salivary flow rates (SFRs) were estimated along with Candida albicans cell culture tests. RESULTS: Compared with patients with Fe deficiency, those with anemia had a longer history of tongue pain. In patients with anemia, painful areas of the tongue were more numerous than in patients with Fe deficiency. Pain thresholds were decreased in the painful portions, and both nonstimulated and stimulated SFRs were suppressed. Each patient was treated with oral Fe; within 2 months, most patients exhibited increased serum ferritin level (P< 0.02, paired t-test), pain threshold (P < 0.05) and salivation (P < 0.05) and glossal pain subsided. CONCLUSIONS: Fe deficiency causes glossal pain and the degree of glossal pain increases as Fe deficiency advances to anemia, manifesting hyposalivation and abnormalities of glossal papillae.

Treatment of xerostomia with the bile secretion-stimulating drug anethole trithione: a clinical trial.

BACKGROUND: Saliva protects the oral mucosa, inhibiting microbial overgrowth. Hyposalivation, therefore, induces multiple oral disorders, although treatment of hyposalivation is very difficult. METHODS: A cholagogue, anethole trithione (AT) was administered to patients with symptomatic hyposalivation (xerostomia) caused by senile hypofunction (4 men and 17 women; senile group), medications (6 men and 17 women; drug group), and oral cancer therapy (two men and three women; cancer group). For control groups, an artificial saliva was administered to 45 patients consisting of senile hypofunction (10 men and 16 women), drug-induced xerostomia (3 men and 10 women) and oral cancer therapy-induced xerostomia (four men and two women). RESULTS: Two weeks after administration of AT (6 tablets per day), both nonstimulated salivary flow rate (SFR) and stimulated SFR increased in a statistically significantly manner from 0.76 +/- 0.41 and 5.18 +/- 3.02 to 1.54 +/- 1.33 (P<0.05) and 9.07 +/- 4.10 mL/10 min (P<0.05), respectively. Of the three groups, the drug group showed the largest increases in both SFRs, from 0.90 +/- 0.54 and 6.29 +/- 4.12 to 1.69 +/- 1.65 and 12.09 +/- 5.10 mL/10 min (P<0.05 and P<0.02, respectively). Patients in the control group had almost constant SFRs. After AT administration, the salivary viscosity was, however, mildly decreased and concentrations of secretory-immunoglobulin A, lactoferrin, potassium, and chloride in nonstimulated saliva were almost constant. Corresponding with the increase of salivation, oral discomfort and inflammation were improved or resolved in 41 patients of the AT group within about 4 weeks, whereas improvement was observed in only nine patients of the control group. CONCLUSIONS: These results indicate that AT sufficiently stimulates salivation and improves xerostomia.

Expression of Lewis(a), sialyl Lewis(a), Lewis(x) and sialyl Lewis(x) antigens as prognostic factors in patients with colorectal cancer.

BACKGROUND: Altered expression of blood group-related carbohydrate antigens such as sialyl Lewis (Le)(x) antigen in tumours is associated with tumour progression behaviour and subsequent prognosis. However, the prognostic value of the expression of Le-related antigens in colorectal tumours remains unclear. PURPOSE: To clarify the prognostic value of Le(a), sialyl Le(a), Le(x) and sialyl Le(x) expression in colorectal carcinomas as prognostic factors after surgery. PATIENTS AND METHODS: Colorectal carcinoma samples from 101 patients with primary colorectal carcinoma who underwent surgical resection were subject to immunohistochemical analyses for Lea, sialyl Lea, Lex and sialyl Le(x) expression with the respective monoclonal antibodies. RESULTS: Le(a), sialyl Le(a), Le(x) and sialyl Le(x) were expressed in 69 (68.3%), 73 (72.3%), 66 (65.4%) and 76 (75.3%) carcinomas, respectively. The patients with sialyl Lex-expressing tumours had more advanced cancer than those with nonsialyl Lex-expressing tumours (P=0.0029). The survival time after surgery of patients with Le(x)- or sialyl Le(x)-expressing tumours was significantly shorter than the survival time of those with non-Le(x)- or nonsialyl Le(x)-expressing tumours, respectively (P=0.023 and P=0. 0001, respectively). Cox's regression analysis revealed that Le(x) and sialyl Le(x) expression, separate from stage and histological type, were prognostic variables for patient survival (hazard ratio [HR] for sialyl Le(x)-positive expression to sialyl L(x)-negative expression 2.90; HR for Le(x)-positive expression to Le(x)-negative expression 12.76 in stage I/IV, 0.63 in stage II and 1.69 in stage III). CONCLUSIONS: Le(x) expression and sialyl Le(x) expression in colorectal carcinomas are each associated with poor prognosis. These variables should be considered in the design of future trials.

Evaluation of sialyl Lewis(a), sialyl Lewis(x), and sialyl Tn antigens expression levels as predictors of recurrence after curative surgery in node-negative colorectal cancer patients.

This study aimed to determine whether sialyl Lewis(a) (Le(a)), sialyl Lewis(x )(Le(x)), or sialyl Tn antigen expression could identify a subset of node-negative colorectal cancer patients that are at high risk for recurrence after curative surgery. Tumor tissue samples from 90 patients with node-negative colorectal cancer, who had undergone surgical resection, were analyzed immunohistochemically for the expression of each antigen. Patients were classified as having low or high antigen expression depending on whether more or less than 40% of the field showed positive staining. The main outcome measure for each variable was disease-free interval. Sialyl Le(a), sialyl Le(x), and sialyl Tn antigens were expressed in 53 (58.9%), 41 (45.6%), and 34 (37.8%) carcinomas, respectively. The median follow-up was 83.5 months. Patients with high sialyl Le(x) expression had shorter disease-free intervals than those with low sialyl Le(x) expression (P = 0.0041); the expression of sialyl Le(a) or sialyl Tn antigens did not show a significant relationship with disease-free survival. Cox's regression analysis revealed that sialyl Le(x) expression was an independent predictor for disease-free survival, separate from T factor or tumor location. High sialyl Le(x) expression may be useful in identifying a subset of node-negative colorectal cancer patients who are at high risk for recurrence.

Increased serum level of sialyl Lewis(x) antigen in blood from the tumor drainage vein in patients with non-polypoid growth type of colorectal cancer.

Two types of colorectal cancer with distinct morphologies have been described in recent studies: polypoid growth type (PG-type) and non-polypoid growth type (NPG-type). We hypothesize that the morphologic differences may correspond to additional biological distinctions. Ratios of sialyl Lewisa (CA 19-9), sialyl Lewisx (SLX), or carcinoembryonic antigen (CEA) in the venous blood drainage from the tumor to that of the respective antigen in the peripheral venous blood (d/p ratio) was examined in order to ascertain whether or not the ratio is correlated with either the PG-type or NPG-type colorectal tumor growth pattern. Blood samples from 118 patients with colorectal cancer were obtained from a peripheral vein and from the tumor drainage vein during surgical excision of the tumor. Statistical tests were conducted by univariate and multivariate (logistic regression) analyses. Among the cancers examined there were 17 PG-type (14.4%) and 101 NPG-type (85.6%). NPG-type cancers had a higher frequency of moderately differentiated adenocarcinoma cells and T3/T4 tumors than PG-type cancers (P<0.0001 and P<0.0001, respectively). NPG-type cancers had a more advanced stage than PG-type cancers (P=0.0007). The d/p ratio of SLX in NPG-type cancers was significantly higher than that in PG-type cancers (P=0.028). Multivariate logistic regression analysis showed that three variables, namely histologic type, T factor, and d/p ratio of SLX, were independently related to tumor growth patterns. In conclusion, NPG-type cancers are characterized by a high SLX d/p ratio, which may be at least partly responsible for a different tumor progression pattern compared to other cancer types.

[Longitudinal studies on the health effects of exposure to environmental cadmium].

Renal damage induced by cadmium (Cd) results in a proximal renal tubular dysfunction, characterized by low-molecular weight (LMW) proteinuria, renal glucosuria, generalized aminoaciduria and decreased renal tubular reabsorption of uric acid and phosphate. Since LMW proteinuria is thought to be one of the earliest adverse health effects caused by Cd, the prevention of the progress of LMW proteinuria is important to avoid further deteriorations in the health condition. Follow-up studies on residents in Cd-polluted areas and Cd-exposed workers have indicated that Cd-induced LMW proteinuria is generally irreversible and progressive even after the cessation or reduction of exposure. The intensity of exposure and the body burden of Cd before the reduction of exposure may influence the prognosis of Cd-induced LMW proteinuria. Several studies have reported a gradual decline in the glomerular filtration rate even after the reduction of Cd exposure. Cohort studies performed in Cd-polluted areas of Japan showed that renal tubular dysfunction and a decreased glomerular filtration rate were strongly associated with increased risk of mortality. However, the results also suggested that overall mortality rates in Cd-polluted areas were not necessarily increased, because of the low mortality among those with urinary beta 2-microglobulin concentrations < 1,000 micrograms/g creatinine. At present, incidence data are too limited to draw a conclusion regarding the cancer risk among residents in Cd-polluted areas.

[Potential exposure to inorganic mercury in people living near a sewage sludge dumping site: urinary excretion of mercury, subjective symptoms and renal function].

OBJECTIVE: The purpose of this study was to evaluate the presence of exposure to inorganic mercury and its health effects among people living near a sewage sludge dumping site in Nagasaki Prefecture, Japan. In this area, sewage sludge and industrial waste have been dumped since 1975, and total mercury levels exceeding the water quality standards (0.0006-0.0020 mg/l) have been detected in seeping water and river water since July 1997. METHODS: The population for the present study comprised 48 subjects (aged 11-91 years) living near a sewage sludge dumping site and 49 subjects (aged 10-82 years) living in a non-polluted area. In November and December 1998, subjective symptoms of inorganic mercury exposure, history of occupational exposure to inorganic mercury, frequency of fish intake, sources of drinking water and other health habits were inquired by a self-administered questionnaire. Total mercury and total protein levels and N-acetyl-beta-D-glucosaminidase (NAG) activity in morning urine specimens were also measured. RESULTS: Among males, the proportion of subjects who complained of tremor in the hands (P = 0.02) and increased irritability (P = 0.10) was higher in the polluted area than in the control area. In addition, the proportion of those who did not report being easily fatigued was lower in the polluted area than in the control area (P = 0.07). Among females there was no significant difference in the prevalence of self-reported symptoms related to the central nervous system disturbance between the two areas. After adjustment for gender and age using logistic regression analysis, the prevalence of increased irritability was significantly higher (P = 0.05) and the proportion of those who did not report being easily fatigued was significantly lower (P = 0.03) in the polluted area than in the control area. However, there was no significant difference in the geometric mean of urinary total mercury concentration (microgram/g creatinine) between the polluted area (0.66, 95% confidence interval [CI] 0.48-0.91 for men and 0.96, 95% CI 0.70-1.33 for women) and the control area (0.81, 95% CI 0.60-1.09 for men and 0.83, 95% CI 0.57-1.22 for women). There was no individual whose total mercury concentration in urine exceeded 30 micrograms/g creatinine, at which level of urinary total mercury toxic effects on the central nervous system have been reported in industrial workers. There was also no significant difference in the geometric means of urinary total protein level and NAG activity. CONCLUSION: There was no evidence of excessive exposure to inorganic mercury among residents in the polluted area. Thus, we concluded that the difference in the prevalence of subjective symptoms was not due to the direct effect of exposure to inorganic mercury. To prevent the contamination of water by taking measures against pollution sources, monitoring of the quality of drinking water, and finally to secure safe water supply by public waterworks are required.

[Hereditary spherocytosis associated with non-Hodgkin's lymphoma in the spleen].

A 60-year-old female was admitted complaining of anemia. We diagnosed her hereditary spherocytosis (HS) from spherocytosis and family history and found a tumor in her enlarged spleen. Splenectomy was performed and swollen paraaortic lymph nodes were found at laparotomy. The tumor in the spleen was diagnosed as Non-Hodgkin's lymphoma (follicular mixed type). After CHOP therapy she entered complete remission. Though the relationship between HS and malignant lymphoma was not clear, splenomegaly due to hemolysis inducing chronic stimulation might have resulted in malignant lymphoma.