[The relationship between death from renal insufficiency and diuretic therapy among older adults at two nursing homes catering atomic bomb survivors].

AIM: In Geriatrics Gerontology International we previously reported the efficacy of reducing diuretics to prevent falls and fractures in older adults. We have since noticed another important problem, regarding the diuretic therapy for older adults with decreased muscle and water volumes. We performed a study on renal insufficiency and diuretic therapy in an attempt to confirm the need for case control study between standard diuretic therapy administered, according to guidelines and "NY-mode" diuretic therapy, which involves the administration of the mineral-corticoid receptor inhibitor spironolactone at 12.5 mg orally every other day. METHODS: We reviewed the causes of death among 1,855 residents living at 2 atomic bomb survivors nursing homes, with a focus on the death certification and diuretic therapy status of 48 older adults who died due to renal insufficiency. We also evaluated the relationship between the estimated glomerular filtration rate of 407 residents using serum creatinine data and the level of independence in daily life of disabled older adults. RESULTS: We found that deaths due to chronic renal insufficiency were concentrated within certain period in two nursing homes examined and in patients receiving standard diuretic therapy (continuous daily loop diuretics or combination of loop diuretics with mineral-corticoid receptor inhibitor). Older adults with a relatively low level of independence in daily life showed a relatively higher estimated glomerular filtration rate, depending on their muscle volume. CONCLUSION: These results suggest the need for a case control study of standard diuretic therapy and "NY-mode" therapy among older adults with decreased muscle and water volumes to not only prevent falls and fall-related fractures but also protect the kidney from damage.

Reduction of diuretics and analysis of water and muscle volumes to prevent falls and fall-related fractures in older adults.

AIM: In an attempt to decrease the incidence of falls and fall-related fractures at a special geriatric nursing home, we endeavored to reduce diuretic doses, and examined the relationship between the effectiveness of this approach with the body compositions and activities of daily living of the study cohort. METHODS: We enrolled 93 participants living in the community, 60 residents of an intermediate geriatric nursing home and 50 residents of the 100-bed Kandayama Yasuragien special geriatric nursing home. We recorded body composition using a multifrequency bioelectrical impedance analyzer. Daily loop diuretic and other diuretic regimens of those in the special geriatric nursing home were reduced or replaced with "NY-mode" diuretic therapy, namely, spironolactone 12.5 mg orally once on alternate days. RESULTS: The incidence of falls fell from 53 in 2011 to 29 in 2012, and there were no fall-related proximal femoral fractures for 3 years after the introduction of NY-mode diuretic therapy. We also found statistically significant differences in muscle and intracellular water volumes in our elderly participants: those with higher care requirements or lower levels of independence had lower muscle or water volumes. CONCLUSIONS: We found that reducing or replacing daily diuretics with NY-mode therapy appeared to reduce the incidence of falls and fall-related proximal femoral fracture, likely by preserving intracellular and extracellular body water volumes. Low-dose spironolactone (12.5 mg on alternate days) appears to be an effective means of treating elderly individuals with chronic heart failure or other edematous states, while preventing falls and fall-related fractures. Geriatr Gerontol Int 2017; 17: 262-269.

The experience of dissolving polypharmacy by reducing the prescription of anti-ulcer drugs in residents of a special geriatric nursing home.

AIM: As part of a broader study on polypharmacy among elderly nursing home residents, we examined the impact of reducing or discontinuing the prescription of proton pump inhibitors and other anti-ulcer drugs. METHODS: We employed a strategy of reducing and discontinuing the prescription of drugs to 160 elderly residents of the Hiroshima Atomic Bomb survivors nursing home, Kandayama Yasuragien. The residents had entered the home between April 2012 and November 2015. As part of this study into anti-ulcer drugs, we also measured the concentrations of Helicobacter pylori antigen in stool specimens, and the serum concentrations of H pylori antibodies and pepsinogen I and II. RESULTS: The proportions of residents who were taking more than six drugs on April 2012, August 2014 and November 2015 were 55.2%, 49.0% and 43.0%, respectively. At the same times, the proportions of residents who were taking anti-ulcer drugs were 50.0%, 49.0% and 6.0%, respectively. The presence of H pylori antigen and antibodies, and serum pepsinogen concentrations, did not influence the decisions to continue or discontinue anti-ulcer drugs. CONCLUSIONS: We have already reported that reduction of diuretics reduces the incidence of falls and fall-related fractures in our residents, and have demonstrated the benefits of discontinuing folic acid and drugs that are given to control hyperkalemia. In the present study, we found that many anti-ulcer drugs were also of low necessity to elderly care home residents. It is essential to examine the clinical benefits of addressing polypharmacy in elderly individuals. In the future, we intend to focus on reducing hypnotics, laxatives and other drugs.

The incidence of leukemia, lymphoma and multiple myeloma among atomic bomb survivors: 1950-2001.

A marked increase in leukemia risks was the first and most striking late effect of radiation exposure seen among the Hiroshima and Nagasaki atomic bomb survivors. This article presents analyses of radiation effects on leukemia, lymphoma and multiple myeloma incidence in the Life Span Study cohort of atomic bomb survivors updated 14 years since the last comprehensive report on these malignancies. These analyses make use of tumor- and leukemia-registry based incidence data on 113,011 cohort members with 3.6 million person-years of follow-up from late 1950 through the end of 2001. In addition to a detailed analysis of the excess risk for all leukemias other than chronic lymphocytic leukemia or adult T-cell leukemia (neither of which appear to be radiation-related), we present results for the major hematopoietic malignancy types: acute lymphoblastic leukemia, chronic lymphocytic leukemia, acute myeloid leukemia, chronic myeloid leukemia, adult T-cell leukemia, Hodgkin and non-Hodgkin lymphoma and multiple myeloma. Poisson regression methods were used to characterize the shape of the radiation dose-response relationship and, to the extent the data allowed, to investigate variation in the excess risks with gender, attained age, exposure age and time since exposure. In contrast to the previous report that focused on describing excess absolute rates, we considered both excess absolute rate (EAR) and excess relative risk (ERR) models and found that ERR models can often provide equivalent and sometimes more parsimonious descriptions of the excess risk than EAR models. The leukemia results indicated that there was a nonlinear dose response for leukemias other than chronic lymphocytic leukemia or adult T-cell leukemia, which varied markedly with time and age at exposure, with much of the evidence for this nonlinearity arising from the acute myeloid leukemia risks. Although the leukemia excess risks generally declined with attained age or time since exposure, there was evidence that the radiation-associated excess leukemia risks, especially for acute myeloid leukemia, had persisted throughout the follow-up period out to 55 years after the bombings. As in earlier analyses, there was a weak suggestion of a radiation dose response for non-Hodgkin lymphoma among men, with no indication of such an effect among women. There was no evidence of radiation-associated excess risks for either Hodgkin lymphoma or multiple myeloma.

Radiation doses among residents living 37 km northwest of the Fukushima Dai-ichi Nuclear Power Plant.

External and internal radiation doses were estimated for 15 residents who lived approximately 37 km northwest of the Fukushima Dai-ichi Nuclear Power Plant, which released radioactive plumes on March 11, 2011 as the result of the Tohoku earthquake and subsequent tsunami damage. Residents were interviewed on where they stayed and what they ate after the incident. To estimate external dose, the air dose rate around each person's home was measured, and cumulative effective doses up to 54 d after the deposition were calculated. To estimate committed effective dose, urinary bioassays were performed using a low-background Ge spectrometer on 54 d and 78-85 d after the deposition. The average cumulative effective dose was 8.4 mSv for adults and 5.1 mSv for children. The average committed effective dose from (134)Cs and (137)Cs was 0.055 mSv for adults and 0.029 mSv for children. Iodine-131 was observed from urinary samples of five residents, the equivalent doses for thyroid gland were 27-66 mSv at maximum. We discuss the necessity of reducing the risk of further exposure.

Characterization of late-arising chromosome aberrations in human B-cell lines established from alpha-ray- or gamma-ray-irradiated lymphocytes.

To clarify the characteristics of late-arising (delayed) chromosome aberrations after irradiation in human lymphocytes, 30 B-cell lines were established from the peripheral blood from a healthy adult donor, the lymphocytes of which were exposed to alpha-rays or gamma-rays and then used for experiments. Chromosome aberrations were serially observed at several passages by both conventional cytogenetics and fluorescence in situ hybridization analysis using subtelomere probes. These B-cell lines derived from lymphocytes with a history of radiation exposure had higher percentages of delayed chromosome aberrations, such as dicentrics, rings, endoreduplication, hyperdiploid, hyperploidy, and telomere association. Furthermore, alpha-ray exposure induced higher chromosome instability than gamma-ray exposure, indicating that delayed chromosome aberrations were related with radiation quality. Chromosome instabilities were also observed at the subtelomere. Cell lines showing high chromosome instability had high DNA-PK activity, low expressions of Ku70, p53, and TRF1 proteins after stimulation with radiation. These results indicate that mechanisms underlying delayed chromosome aberrations might be epigenetic, and multiple factors such as defects of DNA-PK, subtelomere, and telomere might be associated.

Differential impact of family history on age-associated increase in the prevalence of hypertension and diabetes in male Japanese workers.

Family history and aging are independent risk factors for the development of hypertension as well as for the development of diabetes. However, it is unclear how the family histories influence the rate of age-associated increase in these diseases. Moreover, despite the fact that hypertension and diabetes often occur concomitantly, it is not known whether family history of hypertension increases the risk of diabetes or vice versa. To gain an insight into these questions, we investigated the cross-sectional prevalence and family history of hypertension and diabetes in 1,123 male subjects (mean age, 42.1 +/- 12 years; range, 20-60 years) who participated in annual medical check-ups. The data were analyzed by 10-year age groups (20s, 30s, 40s and 50s). The prevalence of hypertension increased with age group either in the absence (12% in the 20s and 39% in the 50s) or in the presence (21% in the 20s and 59% in the 50s) of family history of hypertension, and thus the increasing rate of prevalence with age was not affected by family history. The prevalence of diabetes in the absence of family history of diabetes was low until the 40s (< 1.2%) but it jumped in the 50s (4.3%). On the other hand, in the presence of family history, the prevalence was 4% in the 20s and progressively increased to 20% in the 50s. The impact of family history on the risk of diabetes was strong and appeared to increase with age. Family history of hypertension did not increase the risk of diabetes, and family history of diabetes did not increase the risk of hypertension. These results suggest that family history of hypertension has an additive impact on the age-associated increase in the risk of hypertension, whereas family history of diabetes has an exponential impact on aging-associated increase in the risk of diabetes.

[The present state of atomic bomb survivors, with special reference to biological late-effects of radiation].

Atomic bombs were dropped on Hiroshima and Nagasaki in August 1945. Within a few months, the bomb blast, heat and radiation emitted by the atomic explosions led to approximately 114,000 fatalities in Hiroshima and about 70,000 in Nagasaki. The radiation in particular continued to exert effects on the human body over a long period of time, resulting in the development of tumors and functional abnormalities in various organs. This paper briefly outlines the diseases caused by radiation as well as the biological late-effects on the survivors without any specific diseases, and stresses the necessity of our enthusiastic opposition to the use of any kind of nuclear weapons.

Synovial sarcoma with a secondary chromosome change der(22)t(17;22)(q12;q12).

A consistent, pathognomonic translocation, most commonly a balanced reciprocal translocation, t(X;18) (p11.2;q11.2), is found in more than 90% of synovial sarcomas. We report here a secondary chromosome change, der(22)t(17;22)(q12;q12), in addition to the primary t(X;18)(p11.2;q11.2) in a biphasic synovial sarcoma that occurred in the thigh of a 34-year-old woman. Although the karyotype of the primary tumor exhibited 46,X,t(X;18)(p11.2;q11.2), the recurrent tumor showed 46,X,der(X)t(X;18)(p11.2;q11.2),der(22) t(17;22)(q12;q12). The SYT-SSX1 fusion transcript was demonstrated in the primary and recurrent tumors using a reverse transcriptase polymerase chain reaction (RT-PCR). Southern blot analysis also confirmed that the detected messages were derived from the SYT-SSX fusion gene. However, we could not detect the EWS-E1AF fusion gene that has been reported to be generated through a t(17;22)(q12;q12) by RT-PCR. Furthermore, fluorescence in situ hybridization (FISH) with cosmid probes corresponding to loci flanking the EWSR1 region demonstrated no split of chromosome 22 in all analyzed interphase nuclei. To our knowledge, this is the first reported case of synovial sarcoma in which an additional (secondary) chromosome change, der(22)t(17;22)(q12;q12), has been demonstrated.

Risk-directed treatment of infant acute lymphoblastic leukaemia based on early assessment of MLL gene status: results of the Japan Infant Leukaemia Study (MLL96).

We studied the effectiveness of risk-directed therapy for infants younger than 13 months of age with acute lymphoblastic leukaemia (ALL). Fifty-five infants were assigned to different treatment programs (from December 1995 to December 1998) on the basis of their MLL gene status at diagnosis. Forty-two cases (76.3%) had a rearranged MLL gene (MLL+) and were treated with remission induction therapy followed by sequential intensive chemotherapy, including multiple genotoxic agents (MLL9601 protocol). Haematopoietic stem cell transplantation (HSCT) was attempted if suitable donors were available. Thirteen infants (23.7%) were classified as MLL- and treated for 2.5 years with intensive chemotherapy for high-risk B-ALL (MLL9602 protocol). Complete remission was induced in 38 of the 42 infants (90.5%) with MLL+ ALL and in all 13 patients (100%) with MLL- disease. In the MLL+ subgroup, the estimated event-free survival (EFS) rate at 3 years post diagnosis was 34.0% +/- 7.5%, compared with 92.3% +/- 7.4% in the MLL- subgroup (overall comparison, P = 0.001 by log-rank analysis). Both age less than 6 months (hazard ratio = 6.87, 95% CI = 0.91-52.3; P = 0.013) and central nervous system (CNS) involvement at diagnosis (hazard ratio = 2.92 95% CI = 1.29-6.63; P = 0.015) were significant independent predictors of an inferior outcome. These findings indicate a strategic advantage in classifying infant ALL as either MLL+ or MLL- early in the clinical course and selecting therapy accordingly. Standard chemotherapy for high-risk B-lineage ALL appeared adequate for MLL- cases. Novel therapeutic initiatives are warranted for infants with MLL+ disease, particularly those with initial CNS leukaemic involvement or age less than 6 months, or both.

Resveratrol, a natural product derived from grapes, is a new inducer of differentiation in human myeloid leukemias.

A natural product, resveratrol (3,4,40-trihydroxy-trans-stilbene), a phytoalexin found in grapes and other food products, is known as a cancer chemopreventive agent. We studied the in vitro biological activity of this compound by examining its effect on proliferation and differentiation in myeloid leukemia cell lines (HL-60, NB4, U937,THP-1, ML-1, Kasumi-1) and fresh samples from 17 patients with acute myeloid leukemia. Resveratrol (20 microM, 4 days) alone inhibited the growth in liquid culture of each of the 6 cell lines. Resveratrol (10 microM) enhanced the expression of adhesion molecules (CD11a, CD11b, CD18, CD54) in each of the cell lines except for Kasumi-1. Moreover, resveratrol (25 microM, 4 days) induced 37% of U937 cells to produce superoxide as measured by the ability to reduce nitroblue tetrazolium (NBT). The combination of resveratrol (10 microM) and all-trans-retinoic acid (ATRA) (50 nM, 4 days) induced 95% of the NB4 cells to become NBT-positive, whereas <1% and 12% of the cells became positive for NBT after a similar exposure to either resveratrol or ATRA alone, respectively. In U937 cells exposed to resveratrol (25 microM, 3 days), the binding activity of nuclear factor-kappaB (NFkappaB) protein was suppressed. Eight of 19 samples of fresh acute leukemia cells reduced NBT after exposure to resveratrol (20 microM, 4 days). Taken together, these findings show that resveratrol inhibits proliferation and induces differentiation of myeloid leukemia cells.