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Telemedicine has changed from a way to treat patients with limited access to hospitals to a necessary method of treatment for non-urgent conditions during the coronavirus disease 2019 pandemic. There are two styles of telemedicine, namely "hybrid medical care" and "gateway medical care," which take advantage of the characteristics of online medical care and might become important in the near future. During hybrid medical care, a patient and their primary care physician have face-to-face medical care while simultaneously being examined by a specialist physician through telemedicine, leading to an overall improvement in the level of local medical care and expansion in the number of treatable diseases. Gateway medical practice is a form of telemedicine used for patients who would otherwise refuse or not receive in-person medical care to engage in consultation with a physician. Telemedicine allows physicians to determine disease severity and triage patients, while reducing unnecessary home visits, emergency hospitalizations and the spread of infection. Telemedicine is less intense than in-person medical care, and allows for easier collaboration with other healthcare providers. However, telemedicine is not optimal for conditions requiring a definitive diagnosis and a comprehensive understanding of the patient's medical history. It is limited by the patient's ability to use telemedicine devices, and the risk of accidental treatments and fraud. The use of telemedicine might result in the development of new, online comprehensive geriatric assessment tools and technologies. Geriatr Gerontol Int 2022; 22: 913-916.

OBJECTIVE To investigate the predictive factors associated with physical impairment among older patients with type 2 diabetes mellitus (T2DM) in Japan and to examine the potential impact of physical impairment on patient-reported health outcomes in this population. METHODS A cross-sectional analysis was conducted using patient-reported data from the 2012-2014 Japan National Health and Wellness Survey. Physical impairment was measured using the Physical Component Summary (PCS) score of the Short-Form 36-Item Health Survey (SF-36) three-component model (using Japanese norms). Older T2DM patients (≥65 years old; n = 1511) were dichotomized into physically impaired (PCS ≤ 25th percentile; n = 378) and non-physically impaired (PCS > 25th percentile; n = 1133). Work productivity (absenteeism, presenteeism and overall work impairment), activity impairment and healthcare resource utilization were compared between these groups. RESULTS Age, female sex, low and high body mass index (BMI), diabetes-related complications, cardiovascular events, unawareness of having hypoglycemic events in the past 3 months, and lack of regular exercise were significant factors associated with physical impairment in multivariable analysis. The physically impaired group reported significantly more regular outpatient visits (13.48 vs. 10.16, respectively, p

A 70-year-old man with a 28-year history of type 2 diabetes mellitus was admitted due to persistent vomiting and neurological abnormalities in Nov 2012. He had developed gait disturbance and diplopia for six months during antiplatelet therapy, which was initiated following the diagnosis of a cerebellar infarction in June 2012. He had nystagmus, truncal ataxia and an ocular motility disorder, and the MRI study showed increased FLAIR and DWI signals in the peri-third ventricle and periaqueductal region, in addition to the cerebellar vermis. Wernicke encephalopathy was suspected according to his symptoms, and thiamine administration dramatically improved his condition. He did not have a history of alcohol abuse or poor eating habits; however, various coexisting factors, including diabetes mellitus, pyloric stenosis and the use of antiulcer drugs and insulin, were considered to be responsible for Wernicke encephalopathy. This case demonstrates the importance of distinguishing Wernicke encephalopathy from cerebrovascular disease in elderly patients.

A 74-year-old man with diabetes mellitus since 64 years of age had been treated with glimepiride, metformin and alogliptin; however, his glycemic control remained poor, i.e., a casual blood glucose level of 318 mg/dl, HbA1c level of 10.6% and glycated albumin level of 24.9%. Although his blood glucose level improved with intensive insulin therapy, he exhibited dementia with an MMSE score of 9/30 and was unable to continue insulin injections by himself, thus rejecting his family's help. The extended-release form of the GLP-1 agonist exenatide (Bydureon(®)) was recently introduced in Japan. This new anti-diabetic agent enables the administration of once-weekly type 2 diabetes treatment that delivers a continuous dose of exenatide in a single weekly injection. We employed weekly exenatide therapy in combination with oral hypoglycemic agents in this case. The patient visited our outpatient clinic for injections every week, showing a remarkable improvement in his HbA1c level, from 10.7% to 7.1% in five months. Subcutaneous induration was the only side effect of weekly exenatide injection. Weekly exenatide therapy can be easily managed by other caregivers and is expected to be a useful treatment approach in elderly diabetic patients with dementia.

An 81-year-old woman had been visiting 2 hospitals for hypertension and dementia, prior to admission to our emergency room for nausea, hypertension, severe hypokalemia (K 1.29 mEq/l) and abnormal electrocardiography findings. She had been taking a Chinese herbal remedy (Yokukansan, 7.5 g/day) for the behavioral and psychological symptoms of dementia (BPSD) for 6 months before admission. On admission, she presented with metabolic alkalosis with hypokalemia, a high urinary excretion of potassium, low plasma rennin activity and hypoaldosteronism. We diagnosed pseudoaldosteronism caused by the Chinese herbal remedy Yokukansan (which includes licorice). Discontinuation of Yokukansan and the administration of potassium supplements normalized her serum potassium level within 2 weeks. However, we could not successfully control her BPSD by drugs such as tiapride hydrochloride or risperidone. BPSD is a serious problem in an aging society, with the ever-increasing incidence of dementia. The use of Yokukansan has recently been receiving attention as a new treatment modality for BPSD. Because this agent has relatively few adverse effects compared with typical antipsychotic agents, the use of Yokukansan is continuing to increase sharply. Pseudoaldosteronism, if caused by Yokukansan, may cause death by severe hypokalemia, but the early identification of hypokalemia is sometimes difficult because drug-induced hypokalemia is not dose-dependent. We think it is important to create awareness of the possible adverse effects of Yokukansan, such as hypertension and electrolyte abnormalities to make the most of this commonly used drug for the treatment of BPSD among dementia patients.

We studied the viability of high-performance liquid chromatography and mass spectrometry (LC/MS) as a selective and sensitive analytical method for measuring blood concentrations of the local anesthetic ropivacaine. Ropivacaine was effectively separated using a reverse-phase column and monitored at 275 m/z ion. The LC/MS method allowed measurement of concentrations of ropivacaine of lower than 75 ng/mL. The standard curve was linear and in the range of

A functional polymorphism in methylenetetrahydrofolate reductase (MTHFR) has been identified at codon 677 (C677T). The T-allele variant (valine type) has lower enzyme activity than the wild type (C-allele or alanine type), resulting in a slightly elevated homocysteine level, which has been recently recognized as a risk factor for fracture. However, whether subjects bearing the T allele have higher susceptibility to fractures is still controversial. We have investigated the effects of MTHFR polymorphism on fracture susceptibility in Japanese postmenopausal women. A total of 502 postmenopausal ambulatory Japanese women were followed up for 5.1 +/- 3.4 (mean +/- SD) years, and a total of 155 patients with incident fractures (121 patients with vertebral fractures and 34 cases with fractures at other sites) were recorded. When compared with the patients without any fractures, the patients with incident fractures were older, had more prevalent fractures, had higher urinary levels of bone turnover markers as well as plasma homocysteine level, but were shorter in body height and had lower bone mineral density. The prevalence of the TT genotype of MTHFR was significantly higher in the patients with incident fractures compared to the other genotypes. The subjects with the TT genotype had a higher incidence rate of fracture and higher plasma level of homocysteine than the subjects bearing the non-TT genotype. This relationship was observed in both osteoporotic and nonosteoporotic groups. The hazard ratio for TT genotype without osteoporosis, non-TT genotype with osteoporosis, and TT genotype with osteoporosis was 1.49 (0.91-2.45), 3.64 (2.50-5.29), and 7.21 (4.34-11.97), respectively, compared to the non-TT genotype without osteoporosis. A higher hazard ratio for the TT genotype with osteoporosis was still apparent after adjustment for age, body size, and number of prevalent vertebral fractures. These results indicate that the TT genotype of MTHFR may be a risk factor for future fracture in addition to the traditional risk factors.

Objectives Primary graft dysfunction (PGD) is a major cause of early morbidity and mortality after cadaveric lung transplantation (CLT). This study examined the incidence, time course and predictive value of PGD after living-donor lobar lung transplantation (LDLLT). Methods We retrospectively investigated 75 patients (42 with LDLLT and 33 with CLT) who underwent lung transplantation from January 2008 to December 2013. Patients were assigned PGD grades at six time points, as defined by the International Society for Heart and Lung Transplantation: immediately after final reperfusion, upon arrival at the intensive care unit (ICU), and 12, 24, 48 and 72 h after ICU admission. Results The incidence of severe (Grade 3) PGD at 48 or 72 h after ICU admission was similar for LDLLT and CLT patients (16.7 vs 12.1%; P = 0.581). The majority of the LDLLT patients having severe PGD first developed PGD immediately after reperfusion, whereas more than half of the CLT patients first developed severe PGD upon ICU arrival or later. In LDLLT patients, severe PGD immediately after reperfusion was significantly associated with fewer ventilator-free days during the first 28 postoperative days [median (interquartile range) of 0 (0-10) vs 21 (13-25) days, P = 0.001], prolonged postoperative ICU stay [median (interquartile range) of 20 (16-27) vs 12 (8-14) days, P = 0.005] and increased hospital mortality (27.3 vs 3.2%, P = 0.02). Severe PGD immediately after reperfusion was not associated with ventilator-free days during the first 28 postoperative days, time to discharge from ICU or hospital, or hospital mortality in CLT patients. Conclusions Postoperative incidence of severe PGD was not significantly different between LDLLT and CLT patients. In LDLLT patients, the onset of severe PGD tended to be earlier than that in CLT patients. Severe PGD immediately after reperfusion was a significant predictor of postoperative morbidity and mortality in LDLLT patients but not in CLT patients.

An 83-year-old Japanese man had a 29-year history of well-controlled diabetes mellitus. His HbA1c level was approximately 6.0%, with no microalbuminuria and a serum creatinine level seven days before admission of 0.8 mg/dl (eGFR: 69.67 ml/min/1.73 m(2)). Five days before admission, he visited an ophthalmologist with inflammation of the right palpebra and conjunctiva and began taking valacyclovir at a dose of 3,000 mg for the treatment of herpes zoster. Two days before admission, he was prescribed loxoprofen at a dose of 180 mg for a headache. One day prior to admission, he developed dysarthria, wandering and loss of appetite. He was subsequently admitted to our hospital with progressive deterioration of consciousness (Japan Coma Scale: II-20). On admission, he exhibited renal dysfunction, with a serum creatinine level of 5.11 mg/dl (eGFR: 9.16 ml/min/1.73 m(2)). Based on his diverse symptoms and current treatment with valacyclovir, the patient was diagnosed with acyclovir-induced neurotoxicity and his symptoms rapidly improved after hemodialysis. The serum acyclovir level on admission was found to be 9.25 μg/ml. Although acyclovir-induced neurotoxicity is commonly seen in elderly patients with renal dysfunction, there are also reports of this condition in patients with a normal renal function. Valacyclovir is frequently prescribed to the elderly to treat diseases such as herpes zoster. As valacyclovir induces renal dysfunction, which raises the serum acyclovir level to the toxic range, special attention must be paid when administering this drug in elderly subjects.

A 93-year-old male was urgently admitted to our hospital with dyspnea and disturbance of consciousness. The patient had been visiting a general physician regularly for ten years, for treatment of type 2 diabetes. He had been treated with glibenclamide and voglibose, until voglibose was replaced with buformin 3 months before admission. During pre-admission treatment, his HbA1c was 10-12% and serum Cr level was around 2mg/dL, but insulin therapy had never been considered because of "being too old". The patient had started taking furosemide one year before admission, because of edema of the lower legs, and also spironolactone two months before admission. Anorexia had continued for one month before admission on May 29, 2003. On admission, his laboratory data were; blood glucose 87mg/dL, HbA1c 12.5%, BUN 75mg/dL, Cr 3.9mg/dL, lactate 253.1 mg/dL, and blood gas analysis; pH 6.97, anion gap 45.3mmol/L breathing room air, suggesting marked lactic acidosis with renal failure. Intensive care with bicarbonate and fluid therapy was successful, and his glycemic control improved markedly with insulin. On the other hand, his activity of daily living (ADL) severely deteriorated while in hospital Home follow-up was therefore not indicated, and he had to change a hospital for further follow-up. This case report gives rise to the question of how we should manage diabetes in the oldest elderly, including the use of insulin and biguanides. In addition, complications of biguanides in the elderly are reviewed.

Increasing evidence indicates a significant role for vitamin K in bone metabolism and osteoporosis. In this study, we found a large geographic difference in serum vitamin K2 (menaquinone-7; MK-7) levels in postmenopausal women. Serum MK-7 concentrations were 5.26 +/- 6.13 ng/mL (mean +/- SD) in Japanese women in Tokyo, 1.22 +/- 1.85 in Japanese women in Hiroshima, and 0.37 +/- 0.20 in British women. We investigated the effect of Japanese fermented soybean food, natto, on serum vitamin K levels. Natto contains a large amount of MK-7 and is eaten frequently in eastern (Tokyo) but seldom in western (Hiroshima) Japan. Serum concentrations of MK-7 were significantly higher in frequent natto eaters, and natto intake resulted in a marked, sustained increase in serum MK-7 concentration. We analyzed the relation between the regional difference in natto intake and fracture incidence. A statistically significant inverse correlation was found between incidence of hip fractures in women and natto consumption in each prefecture throughout Japan. These findings indicate that the large geographic difference in MK-7 levels may be ascribed, at least in part, to natto intake and suggest the possibility that higher MK-7 level resulting from natto consumption may contribute to the relatively lower fracture risk in Japanese women.

Calcitonin (CT), a calcium-regulating hormone, lowers the calcium level in serum by inhibiting bone resorption. Because CT may play a role in the pathogenesis of osteoporosis, genetic variations in or adjacent to the CT gene may be associated with variations in bone mineral density (BMD). The present study examined the correlation between a dinucleotide (cytosine-adenine; CA) repeat polymorphism at the CT locus and BMD in 311 Japanese postmenopausal women (mean age, 64.1 years). Seven alleles were present in this population; each allele contained 10, 11, 16, 17, 18, 19, or 20 CA repeats. Thus, we designated the respective genotypes A10, A11, A16, A17, A18, A19, and A20. The A10 and A17 alleles were the predominant alleles in the population studied. Z scores (a parameter representing deviation from the age-specific weight-adjusted average BMD) were compared between individuals that possessed one or two alleles of each genotype and those that did not possess the allele. Subjects who possessed one or two A10 alleles had lower BMD Z scores than those who did not (lumbar 2-4 BMD Z score; -0.148 +/- 1.23 vs 0.182 +/- 1.54; P = 0.04). No significant relationships were observed between allelic status and background data or biochemical parameters. The significant association observed between BMD and genetic variations at the CT locus implies that polymorphism at this locus may be a useful marker for the genetic study of osteoporosis.

A novel variation of the estrogen receptor-alpha (ERalpha) gene was identified by polymerase chain reaction-single-strand conformational polymorphism (PCR-SSCP). It is one base substitution in codon 325 (CCC [allele M] to CCG [allele m]) in exon 4 of the human ERalpha gene. This substitution did not cause an amino acid change. We categorized 306 unrelated Japanese postmenopausal women into three genotypes: MM, Mm, and mm; the frequency of each genotype was 26.5%, 43.1%, and 30.4%, respectively. Then, the association of this polymorphism with bone mineral density (BMD) of lumbar spine and bone-calcium metabolic markers was studied. There was no significant difference in BMD of the lumbar spine or most of the bone metabolic markers. However, the urinary calcium (Ca) excretion ratio (u-Ca/Cre) corrected by creatinine was significantly lower in the genotype mm group compared with the genotype MM group (MM vs mm, 0.247 +/-0.158 vs 0.200 +/- 0.105; P0.05). We examined the relationship of restriction fragment length polymorphisms (RFLPs) (PvuII, XbaI) in intron 1 and the polymorphism in exon 4. The frequency of genotype MM was higher in the genotype PPxx, which was reported to be associated with lower BMD in the same population of Japanese postmenopausal women. The ER polymorphism identified in this study might be related to some biological mechanisms that regulate calcium metabolism.

The pathogenesis of osteoporosis is controlled by genetic and environmental factors. Considering the high prevalence of osteoporosis in homocystinuria, abnormal homocysteine metabolism would contribute to the pathogenesis of osteoporosis. It is known that the polymorphism of methylenetetrahydrofolate reductase (MTHFR), the enzyme catalyzing the reduction of 5, 10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, correlates with hyperhomocysteinemia. In this study, we examined the association of this polymorphism with bone mineral density (BMD). BMD was measured by dual-energy X-ray absorptiometry (DXA) in 307 postmenopausal women. MTHFR A/V polymorphism was analyzed using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). We compared BMD, clinical characteristics, and bone metabolic markers among MTHFR groups (AA, AV, VV). The groups did not differ in terms of baseline data. The values of lumbar spine BMD and total body BMD were as follows: lumbar spine: AA, 0.91 +/- 0.18, AV, 0.88 +/- 0.16, VV, 0.84 +/- 0.14 g/cm(2); total body: AA, 0.97 +/- 0.11, AV, 0.96 +/- 0.11, VV, 0.93 +/- 0.09 g/cm(2). In the VV genotype, lumbar spine BMD values were significantly lower than those of the women with the AA genotype (P = 0.016) and total body BMD was significantly lower than those of the women with AA genotype (P = 0.03) and AV genotype (P = 0.04). This is the first report that suggests that the VV genotype of MTHFR is one of the genetic risk factors for low BMD.

The contribution of genetic factors has been implicated in the determination of bone mass in twin and family studies. Some of the genes involved would regulate bone metabolism, bone formation, and resorption, all processes that determine bone mass. One candidate gene matrix Gla protein gene (MGP), has been implicated in the pathogenesis of bone loss through a repression of bone formation. To analyze the genetic background for osteoporosis in elderly women, we have investigated a possible association between the CA repeat polymorphism at the human MGP gene locus and bone mineral density (BMD) of radial bone in 460 elderly Japanese women. Genotypes were classified into six groups according to the number of CA repeats present, from 13 to 18 (alleles A1 through A6). BMD was expressed as the adjusted BMD (ADJBMD), which was the body mass index (BMI)- and age-adjusted average BMD. The 214 women who lacked an A2 allele (212 bp, containing 17 repeats of CA) had significantly lower adjusted BMD than the participants (n = 246) who possessed an allele of that size (mean +/- SD; 0.303 +/- 0.062 vs 0.315 +/- 0.062 g/cm2; P = 0.0382). This result suggests that genetic variation at the MGP locus is associated with some determinants for BMD in elderly women. Therefore, this locus should serve as one of the genetic markers for osteoporosis.

Twin studies have shown strong correlations between bone mass and genetic factors. Some of the genes involved could regulate bone metabolism and bone formation and resorption, all processes that determine bone mass. One candidate gene, interleukin 6 (IL-6), has been implicated in the pathogenesis of bone loss because it stimulates osteoclasts. We investigated a possible association between the CA repeat polymorphism at the IL-6 gene locus and the bone mineral density (BMD) of radial bone in 472 postmenopausal Japanese women. Genotypes were classified into six groups according to the number of CA repeats present, from 13 to 18. BMD was expressed as adjusted BMD, which was the body mass index (BMI)- and age-adjusted average BMD. The 73 women who possessed an A1 allele (134 bp, containing 18 repeats of CA) had significantly lower adjusted BMD than those participants (n = 399) who did not carry an allele of that size (mean +/- SD values, 0.294 +/- 0.064 vs 0.312 +/- 0.061 g/cm2; P = 0.0221). This result suggests that genetic variation at the IL-6 gene locus is associated with some determinants of BMD in postmenopausal women.

A 73-year-old woman was admitted to the geriatric ward of the University of Tokyo Hospital with anemia, osteepeina, and renal dysfunction. Although symptoms typical of multiple myeloma such as punched-out lesions and hyperproteinemia were not found, protein electrophoresis revealed that lambda type Bence-Jones protein was excreted in urine. Multiple myeloma was diagnosed. Furthermore, renal dysfunction was accompanied renal tubular acidosis type II (proximal type). Renal dysfunction in patient with multiple myeloma in usually caused by so-called myeloma casts in the distal tubules, but renal tubular acidosis type II is rarely observed. It is possible that injury of the proximal renal tubular eithelium by Bence-Jones protein resulted in renal tubular acidosis type II in this patient.

Lipoprotein(a) (Lp(a)) is an independent risk factor for cardiovascular diseases in non-diabetic people, but few studies have been done in diabetic patients. To investigate whether Lp(a) is a risk factor for cardiovascular disease in elderly people with diabetes, we examined the association of Lp(a) and serum lipid levels (total cholesterol: TC; triglycerides: TG; and high-density lipoprotein cholesterol: HDL-c) with the incidence of coronary artery disease and cerebrovascular disease. We studied 354 outpatients(131 men and 223 women, 60-97 years of age) with non-insulin-dependent diabetes mellitus. The mean concentration of Lp(a) was 21.1 +/- 19.6 mg/dl and the median was 14.0 mg/dl. The Lp(a) concentration did not correlate significantly with age or with sex, but it did correlate significantly with TC (r = 0.152, p0.05) and with the level of apoprotein B (r = 0.168, p0.05). The incidence of cerebrovascular disease was significantly higher in patients with high concentrations of Lp(a) (or = 30 mg/ dl) than in those with low concentrations (30 mg/ dl). Multivariate logistic regression analysis revealed that male sex, hypertension, a high level of HbA1c, a low level of HDL, and a high level of Lp(a) were independent risk factors for cerebrovascular disease. The incidence of coronary artery disease tended to the higher in those with high concentrations of Lp(a) (or = 30 mg/dl). However, multivariate logistic regression analysis revealed no significant correlation between Lp(a) concentration and the incidence of coronary artery disease. We conclude that a high concentration of Lp(a) is an independent risk factor for cerebrovascular disease in elderly patients with diabetes.

From gender sensitive medicine aspect, sex hormones play most important roles in men and women's health. Both estrogen role in women and androgen role in men are well established recently. On the other hand, the effect of androgen on women's health has not been elucidated. Androgen is synthesized in the adrenal gland and the ovary. Androgen receptors (ARs) are found in many tissues. Androgen acts on numerous tissues, including bone (increased mineral density) , muscle (increased muscle mass) , adipose tissue (stimulation lipolysis) , bone marrows (stimulation of enzymatic metabolism) but not so well known. Testosterone provides dual action in breast tissues, stimulation with being converted into estrogen and suppressant effect as testosterone. In addition, women with hyperandrogenism have higher risk for cardiovascular disease and insulin resistance. Currently the testosterone replacement therapy for the woman is provided mainly on a sexual dysfunction, but the long-term safety with non-physiological concentrations is not confirmed without the standard direction for uses being established. The effects of androgens on well-being, quality of life, positive effects for body composition and cognitive function are currently the subject of increased attention. Much developmental work has to be done about testosterone for women's health.

Previous studies on the association between uric acid and bone mineral density yielded conflicting results. In this study, we demonstrated positive association between uric acid and lumbar spine bone mineral density in peri- and postmenopausal Japanese women. Further research is needed to elucidate the underlying mechanism. Oxidative stress has been implicated in the pathogenesis of osteoporosis. Uric acid, a potent antioxidant substance, has been associated with bone mineral density but previous studies have yielded conflicting results. The objective of the study was to examine the association between serum uric acid and lumbar spine bone mineral density (BMD). This was a retrospective analysis of medical records of 615 women, aged 45–75 years, who had lumbar spine BMD measurement by dual-energy X-ray absorptiometry as a part of health checkup from August 2011 to July 2012. Mean serum uric acid level was 4.7 mg/dL. Serum uric acid level was positively and significantly associated with lumbar spine BMD independent of age, body mass index, smoking, drinking, physical activity, years after menopause, diabetes mellitus, hypertension, serum calcium, estimated glomerular filtration rate, plasma C-reactive protein, and serum alkaline phosphatase (standardized beta = 0.078, p = 0.049). Uric acid rapidly increased until the age of 60 years, and then decelerated but continued to increase thereafter. The association between lumbar spine BMD and uric acid remained significantly positive after excluding women older than 60 years. The present study showed that higher uric acid levels were linearly associated with higher lumbar spine BMD in peri- and postmenopausal Japanese women. Further research is needed to elucidate the underlying mechanism of the association between uric acid and BMD.

61歳ではじめて異常ヘモグロビン血症 (HbJ Cape Town) と診断された男性例. 3年前より検診で食後高血糖を指摘されていたが放置. 平成6年3月全身倦怠感, 食欲不振が出現し, 近医にて尿糖, 尿蛋白陽性, 肝機能異常指摘され精査目的で入院. 入院時検査にて, 空腹時血糖116mg/dl, HbA1c 22.3%, GOT 24IU/l, GPT 17IU/l, Al-P 117IU/l, LAP 42IU/l, γGTP 104IU/l, ChE 199IU/l, 75gOGTT急峻型高血糖パターンを示した. 入院後の経過では, 急峻型高血糖は胃切除によるものであり, 糖尿病は否定された. HbA1c高値の原因を調べたところ, 等電点電気泳動法で異常ヘモグロビンを陽極側に検出し, CMクロマトグラフィーでのグロビン分画ではα鎖の前に異常ピークを認めた. このα鎖グロビンを逆相-HPLCで分析したところ正常鎖でα92位に存在するアルギニン (Arg) がグルタミン (Gln) に置換されていた. この異常ヘモグロビンは血色素構造解析によってHbJ-Cape Town であることが判明した. 異常ヘモグロビン血症は, 通常若年のうちに診断されるが, 60歳以上の高齢者において初めて診断されることも稀ではないと考えられた.

We measured lumbar bone mineral density (L2-4 MBMD) in the postmenopausal elderly diabetic women and made comparisons with age-matched controls in terms of the age, body mass index (BMI) and % BMD of age-matched. In addition we evaluated the correlation between BMD and menarche age, menopause age, HbA1c, serum calcium, serum phosphate, serum alkaline phosphatase (S-Alp) and the ratio of urine calcium to urine creatinine (UCa/Cr). Moreover we divided non-insulin dependent diabetic patients (NIDDM) into two groups; the high BMD group and the low BMD group. Serum Alp and the ratio of UCa/Cr were compared in these two groups. The relationships between regimen of therapy and BMD were also analyzed in female NIDDM. There were no significant differences of BMD and background factors between controls and NIDDM. The ratio of UCa/Cr in the high BMD group were significantly less than that in low BMD group (p < 0.05). BMD in NIDDM with retinopathy was lower, but not significantly, than that in NIDDM without retinopathy. The methods of therapy for NIDDM such as diet alone, an oral hypoglycemic agent and insulin did not influence BMD in elderly postmenopausal diabetics. These results indicated that BMD in elderly postmenopausal diabetics are dependent on UCa/Cr and retinopathy.

Although morning surge in blood pressure has been shown to be associated with the occurrence of myocardial ischemic events and stroke, few studies have been done regarding its pathogenesis, probably because of a lack of method for the quantitative assessment of awakening time. We conducted an echocardiographic study and ambulatory blood pressure monitoring in 23 elderly hypertensive patients to evaluate the relationship between the hypertensive cardiac change and morning surge in blood pressure. Of note was that the time of arising from bed was assessed quantitatively by an activetracer equipped with an internal acceleration sensor to monitor the physical activity. The change in systolic blood pressure after arising from bed was correlated significantly with the left ventricular mass index (r = 0.51, P < .02) and the A/E ratio, which represents the diastolic function (r = 0.70, P < .01). In contrast, the change in systolic blood pressure before rising from bed was not correlated with any echocardiographic parameters. We conclude that the magnitude of morning surge in blood pressure after arising from bed was related with the severity of hypertensive target organ damage.

The effects of the bathing on short-term and ciracadian blood pressure (BP) in bedridden elderly patients were investigated in 10 bedridden patients (4 male: 6 female) living in a community home. The mean age of the subjects was 78.7 years old and causes of bedridden status were cerebrovascular disease in 9 and spinal damage in one. To study the short-term hemodynamic effect of bathing, BP and pulse rate were measured every 2 minutes from 10 minutes before bathing to 14 minutes after. Blood samples were collected before and after bathing for measurements of plasma catecholamine and plasma renin activity. To study the effect of warm bathing on circadian, BP, ambulatory BP was non-invasively monitored every 15 minutes for 24 hours on days with and without bathing. In the short-term phase, BP temporally elevated when washing the body outside the bathtub accompanied with a decline soaking in warm water (38 degrees C). Plasma catecholamine did not change after warm bathing. In the study of circadian change of BP, systolic BP on days of warm bathing remained at a lower level for 12 hours after bathing compared to days without bathing. In conclusion, hypotensive effects after bathing were prolonged in the bedridden elderly patients.

The salt intake of the Japanese is among the highest in the world, leading to a high prevalence of salt-sensitive hypertension. To prevent this, salt restriction, suppression of the rennin-angiotensin-aldosterone system, and natriuresis are important. Therefore, the use of a combination of an angiotensin II receptor blocker and thiazide diuretics is used for antihypertensive treatment. Some randomized controlled studies suggested that thiazide diuretics are useful not only to lower blood pressure, but also to prevent cardiovascular events and improve prognosis in the elderly, who are prone to being salt-sensitive. We encountered 2 elderly patients referred to our emergency room because of severe hyponatremia and consciousness disturbance, who had been treated with thiazide diuretics for 1 and 2 months, respectively. In both, hypernatriuria despite hyponatremia, slight dehydration, and refractory antidiuretic hormone (ADH) excess were observed, but activation of the rennin-angiotensin-aldosterone system was absent. Thyroid and adrenal functions were unremarkable. Theses phenomena have much in common with the condition called mineralcorticoid-responsive hyponatremia of the elderly (MRHE). Several weeks after discontinuation of diuretics, serum sodium values returned to normal levels, but transtubular potassium concentration gradient (TTKG) values were depleted despite slight hyperkalemia, and relative ADH excess was sustained, which suggested mineralocorticoid dysfunction and distal renal tubulointerstitial injury. Distal tubulointerstitial dysfunction is one of the most important causes of MRHE. On the basis of these 2 cases, we speculated whether distal tubulointerstitial injury may accelerate hyponatremia in the elderly. We need to check not only serum potassium, but also sodium levels, especially in elderly persons with suspected tubulointerstitial injury.

Aim: To assess the age-related change in plasma androgen levels in healthy middle-aged men and whether any clinical parameters are associated with the hormonal change. Methods: The study was comprised of male Japanese office-workers aged 40–64 years, who had undergone an annual health check-up in 2002 and 2007 (96 and 76 men, respectively). Body mass index and blood pressure were measured, and serum concentration of lipids, glucose and uric acid in addition to plasma total testosterone, free testosterone and dehydroepiandrosterone sulfate (DHEA-S) levels were determined in the morning after an overnight fast. The 5-year hormonal changes and their associations with clinical parameters were analyzed in 33 men who repeated the examination at both check-ups. The cross-sectional associations of hormonal levels with clinical parameters were also investigated. Results: Age was negatively associated with free testosterone (r = −0.399, P

A strong correlation between bone mass and genetic factors has been shown in twins and family studies. Some of the genes involved would regulate bone metabolism, bone formation, and resorption, all processes that determine bone mass. One candidate genes, calcium-sensing receptor (CASR) in the parathyroid gland, regulates calcium homeostasis by sensing decreases in extracellular calcium level and effecting an increase in secretion of parathyroid hormone (PTH) and calcium (Ca) reabsorption in the kidney. We have investigated a possible association between the CA-repeat polymorphism at the human CASR gene locus and the bone mineral density (BMD) of radial bone in 472 postmenopausal Japanese women. Genotypes were classified into nine groups according to the number of CA repeats present, from 20 to 12. BMD was expressed as the adjusted BMD, which was the body mass index (BMI), and age-adjusted average BMD. The 247 women who had an A3 allele (228 bp, containing 18 repeats of CA) had significantly lower adjusted BMD (mean +/- SD: 0.303 +/- 0.059 versus 0.316 +/- 0.063 g/cm(2); P = 0.0308) than the participants (n = 201) who did not carry an allele of that size. This result suggests that genetic variation at the CASR gene locus is associated with some determinants for BMD in postmenopausal women.

Pituitary apoplexy is a rare but potentially life-threatening clinical syndrome caused by the sudden enlargement of pituitary adenoma secondary to infarction and/or hemorrhage. It may be the first presentation of previously undiagnosed pituitary adenoma. Although various precipitating factors of pituitary apoplexy are indicated, the pathogenesis remains unknown. In this report, we describe for the first time a case of pituitary apoplexy developed explicitly during general anesthesia supplemented with interscalene brachial plexus block in beach chair or barbershop position for shoulder joint arthroplasty.

A 53-year-old man was hospitalized with general fatigue, headache, dizziness and polyuria. The laboratory findings revealed anterior hypopituitarism and central diabetes insipidus. He also showed eye movement disorder and facial sensory impairment. These symptoms were treated successfully with conservative medical treatment. Concurrently, abnormal pituitary MR imaging findings were revealed. Pituitary abscess was primarily suspected on MR imaging findings, although it was difficult to differentiate pituitary apoplexy by MR imaging findings, alone. In this report, we propose a new diagnostic approach of pituitary abscess, using a combination of CT, MR imaging and clinical manifestations, without either pituitary surgery or pituitary biopsy.

We investigated the meaning and the worth of lowering low-density lipoprotein cholesterol (LDL-C) to less than 100 mg/dL in Japanese type 2 diabetic patients using atorvastatin. As a multicenter open-labeled study, 84 type 2 diabetic Japanese patients with hypercholesterolemia were enrolled between September 2003 and April 2004. Subjects received 16 weeks of treatment with atorvastatin. High-sensitive C-reactive protein (hs-CRP), plasminogen activator inhibitor 1, monocyte chemotactic protein 1, interleukin 6, urine albumin-creatinine ratio, hemoglobin A(1c), total cholesterol, and LDL-C were measured at baseline and after 8 and 16 weeks of treatment. According to the Adult Treatment Panel III of the National Cholesterol Education Program, we divided the subjects into responders (final LDL-C100 mg/dL) and nonresponders (final LDL-Cor =100 mg/dL). After 16 weeks of atorvastatin treatment, as well as a reduction of total cholesterol and LDL-C, a significant reduction of hs-CRP was observed. Plasminogen activator inhibitor 1, monocyte chemotactic protein 1, and interleukin 6 were not changed. After stratification, hs-CRP declined only in responders. We concluded that atorvastatin not only improved hypercholesterolemia, but also reduced CRP even in Japanese diabetic patients. The results of this stratified study suggest that achievement of the Adult Treatment Panel III treatment goal of LDL-C might assure a reduction of inflammation, which is associated with cardiovascular events.

Although genetic factors determine the limits of peak bone mass, environmental factors can modify the outcome. Relation between lifestyle and osteoporosis is discussed, in terms of nutrition and habits. Significant link between calcium intake and bone mass has been reported. Although recommended daily allowance of calcium is 600 mg/day for adults, 850 mg/day or more shall be recommended later in life. Vitamin D insufficiency may lead to secondary hyperparathyroidism in the elderly, the condition that facilitates bone loss. Other nutrients that affect bone turnover include vitamin K, vitamin C, protein, potassium, salt, magnesium and phosphorus. Too much intake of caffeine or alcohol, as well as smoking is a risk factor of osteoporosis. Mechanical loading on the skeleton increases bone mass, therefore weight-bearing activity is recommended to gain or preserve bone mass.

Although white coat hypertension is common in clinical practice, 1–3 its pathogenesis and clinical prognosis remain unknown. In elderly patients with office hypertension, white coat hypertension should be differentiated from true hypertension, since the excessive reduction in blood pressure (BP) caused by antihypertensive medication may induce an ischemic event in a vital organ. The present study assesses the sensitivity and specificity of electrocardiography in detection of white coat hypertension and quantitatively measures left ventricular hypertrophy in such patients using echocardiography. Results are compared with those in normotensive control subjects and in patients with true persistent hypertension.

A 61-year-old female who had shown Raynaud's phenomenon and articular swelling for 10 years, was admitted to hospital because of fever of unknown origin (FUO) and dry cough. She was diagnosed by skin biopsy to have a collagen disease or overlap syndrome. Anemia developed rapidly and FUO persisted, but blood culture was negative. Although indomethacin and prednisolone were administered for the progression of clinical signs and symptoms, severe dyspnea developed, resulting in bradycardia, followed by recurrent episodes of ventricular tachycardia. In spite of extensive treatment for her arrhythmia she died on the 9th hospital day. An autopsy revealed generalized Wegener's granulomatosis with extensive cardiac involvement. Necrotizing angitis and severe granulomatous inflammatory foci affected characteristically the common bundle of His and right bundle branch in addition to the ordinary myocardium.

BACKGROUND—Enzymes that contribute to the local detoxification in alveoli and bronchioles have an important role in the defence mechanism against tobacco smoke. It has been suggested that genetic susceptibility to smoking injury may confer a risk for the development of chronic obstructive pulmonary disease (COPD). The polymorphisms in glutathione S-transferase P1 (GSTP1), a xenobiotic metabolising enzyme, were investigated in patients with COPD. METHODS—Polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) were performed to genotype GSTP1 polymorphisms in exon 5 (Ile105Val) and exon 6 (Ala114Val). Blood samples were taken from 53 patients with COPD and 50 control subjects at the Tokyo University Hospital, the Juntendo University Hospital, and the Tokyo Kenbikyoin Clinic for use in the study. RESULTS—The proportion of GSTP1/Ile105 homozygotes was significantly higher in the patients with COPD than in the control subjects (79% vs 52%). The odds ratio for GSTP1/Ile105 homozygotes versus all other genotypes was 3.5 (95% CI 2.7 to 4.6) for COPD. Polymorphism at residue 114 of GSTP1 was not found in either group. CONCLUSIONS—Genetic polymorphism of exon 5 of GSTP1 may be associated with COPD because the GSTP1/Ile105 genotype is predominantly found in COPD. It is suggested that the GSTP1/Ile105 genotype may be less protective against xenobiotics in tobacco smoke.

The peroxisome proliferator-activated receptor gamma (PPARgamma) protein as well as its transcript was detected in primary osteoblasts derived from rat calvariae. To analyze the possible involvement of PPARgamma in the human bone metabolism, association between bone mineral density (BMD) and a polymorphism of PPARgamma gene was investigated in Japanese postmenopausal women. We examined a polymorphism corresponding to a silent C --T transition located in exon 6 of the PPARgamma gene, that was previously reported to be associated with plasma leptin levels in the obese. The frequencies of the C and T alleles in the population studied here were 0.851 and 0.149, respectively. When we separated the subjects into two groups, one bearing at least one T allele (CT + TT) and the other which did not (CC), the former subjects had lower BMD (Z score of total body; 0.056 +/- 1.00. L2-4; -0.25 +/- 1.26, mean +/- standard deviation). These data suggest that there is an association between the restriction fragment length polymorphism (RFLP) of PPARgamma gene and BMD and the possible involvement of this single nucleotide polymorphism (SNP) in the cause of postmenopausal osteoporosis in Japanese women.

Association of BST B1 restriction fragment length polymorphism (RFLP) of the parathyroid hormone (PTH) gene with bone mineral density (BMD) was examined in 383 healthy postmenopausal women in Japan who were unrelated. The RFLP was represented as B or b, the capital letter signifying the presence of and the small letter the absence of restriction site for BST B1. The frequency of each genotype-BB, Bb, and bb-was 82.5%, 16.7%, and 0.8%, respectively. When we statistically compared age, years after menopause, body height, and body weight between the BB genotype and the Bb genotype groups, there was no significant difference between the groups. However, the lumbar BMD and the score of BMD adjusted for age and body weight (Z score) were significantly lower in the group of genotype Bb than in the BB: 0.859 +/- 0.019 g/cm2 versus 0.925 +/- 0. 011 (mean +/- SE, P = 0.01) and -0.412 +/- 0.138 versus 0.067 +/- 0. 082 (mean +/- SE, P = 0.01). In addition, the Z score of total body BMD in the Bb genotype group was lower than that in the BB group. Comparison of serum and urinary biochemical bone metabolic markers suggested that the subjects with Bb genotype might be in a relatively higher state of bone turnover than those with BB genotype. These results suggest that the polymorphism in the PTH gene would be a useful genetic marker for lower BMD and the susceptibility for osteoporosis.

The polymorphism of insulin-like growth factor-I (IGF-I) gene was examined in Japanese postmenopausal women to analyze the genetic background for osteoporosis. In this study, the dinucleotide (cytosine-adenine; CA) repeat sequence lying upstream of the transcription initiation site of this gene was examined. We named the most frequent allele including (CA) 19 as J allele. There were 6 alleles (J-4 containing 17 CA repeats: (CA)17, [J-2 (CA)18, J (CA)19, J + 2 (CA)20, J + 4 (CA)21, J + 6 (CA)22]) in the Japanese population. The genotype distribution was different from that of Caucasians. There was no different in bone mineral density (BMD) between the group with one or two alleles of each genotype and that without that genotype. When we separate the subjects into three groups having two alleles, one allele, and no alleles, the three subjects who possess the allele 'J-2' in both strands had low BMD (Z score of L2-4; -1.24 +/- 0.56, total body; -0.943 +/- 0.59, mean +/- SE). On the other hand, sequence of IGF-I gene in this study was different from reported sequence of IGF-I gene; that was 2 base pair (bp) deletion following 3'end of CArepeat (-645adenine/-646guanine). The present study showed that there was no association between the microsatellite polymorphism of IGF-I gene and BMD in Japanese postmenopausal women, but some possibility remains that the microsatellite polymorphism of IGF-I gene is useful to detect a kind of particular osteoporosis.

Case 1. An 85-year-old woman had a papillary adenocarcinoma of the thyroid gland and a pleural effusion. The pleural effusion appeared to be a chylous exudate and it did not re-accumulate after thoracenthesis. Thoracic imaging indicated that the chylothorax was caused by direct invasion of the thoracic duct by the thyroid carcinoma. Case 2. A 53-year-old woman had a 20-year history of recurrent chylothorax. She died due to sepsis one year after the third admission for dyspnea and chylothorax. The autopsy findings included papillary adenocarcinoma of the thyroid gland with metastasis to the left supraclavicular lymph nodes. The thoracic duct was inflamed, fibrotic, and completely obstructed. Invasion by the carcinoma may have compressed and destroyed the thoracic duct, and caused chylothorax. Recurrent inflammatory granulation caused total obstruction of the thoracic duct. Reports of chylothorax associated with carcinoma of the thyroid gland are rare.

Morning rise in blood pressure (morning surge; MS) has been shown to be associated with the occurrence of myocardial ischemic events and stroke. This study aimed to elucidate the incidence and the mechanism of MS in hypertensive patients (HT). We monitored ambulatory blood pressure (BP) and physical activity in 68 untreated HTs using TM2421 (A & D Co. Ltd.) and ACTIVETRACER (GMS Ltd.) for detection of MS. MS was defined as a rise in BP > 50 mmHg (90% tile of 35 normotensives) during early morning (4:00 to 9:00 A.M.) compared with the lowest basal BP at night. MS was seen in 41 patients (52.6%) and was classified into two groups; MS1: BP rose steeply after waking up (27 patients) and MS2: BP started to rise gradually during sleep (14 patients). The mean age of MS1 was significantly higher than that of MS2 (72 vs. 62 years, p < 0.01). BP reached its basal value earlier in MS2 than in MS1 at night though the basal BP values were comparable between the two groups. Mean 24-hour BP and physical activity were similar between the two groups, though significantly higher incidence of cases with a correlation between SBP and activity was seen in MS1. In conclusion, there are two types of MS, the mechanisms of which may differ. MS occurring immediately after waking up was more common in older HTs, and possibly was related to augmented arousal response in BP, while MS beginning gradually during sleep was more common in younger HTs and was characterized by reaching basal BP earlier at night.