The Impact of Tofogliflozin on Physiological and Hormonal Function, Serum Electrolytes, and Cardiac Diastolic Function in Elderly Japanese Patients with Type 2 Diabetes Mellitus.

The sodium glucose transporter 2 (SGLT2) inhibitor tofogliflozin is a glucose-lowering drug that causes the excretion of surplus glucose by inhibiting SGLT2. Because of tofogliflozin's osmotic diuresis mechanism, patients' serum electrolytes, body fluid levels, and cardiac function must be monitored. We retrospectively analyzed the cases of 64 elderly Japanese patients with type 2 diabetes mellitus (T2DM) who received tofogliflozin for 3 months. Their HbA1c, serum electrolytes (sodium, potassium, chloride), hematocrit, brain natriuretic peptide (cardiac volume load marker) and renin and aldosterone (RAA; an index of regulatory hormones involved in body fluid retention) were continuously monitored during the investigation period. Renal function and cardiac function (by echocardiography) were assessed throughout the period. HbA1c significantly decreased (ß1=-0.341, p<0.0001, linear regression analysis [LRA]). Most of the hormonal, electrolyte, and physiological parameters were maintained throughout the study period. In these circumstances, E/e' tended to decrease (ß1=-0.382, p=0.13, LRA). Compared to the baseline, E/e' was significantly decreased at 1 and 3 months (p<0.01, p<0.05). In the higher E/e' group (E/e'≥10, n=34), E/e' decreased significantly (ß1=-0.63, p<0.05, LRA). ΔE/e' was correlated with body-weight change during treatment (r=0.64, p<0.01). The 3-month tofogliflozin treatment improved glycemic control and diastolic function represented by E/e' in T2DM patients, without affecting serum electrolytes, renal function, or RAA. No negative impacts on the patients were observed. Three-month tofogliflozin treatment lowered glucose and improved cardiac diastolic function.

Postoperative Urinary Retention in Japanese Elderly Males with a Femoral Neck or Trochanteric Fracture.

We assessed risk factors for postoperative urinary retention (UR) in elderly males with femoral bone fractures: 169 Japanese males (mean age 81.95 ± 1.19 years) who had undergone hip surgery at a municipal hospital (Toyama, Japan). A multiple logistic regression analysis was used to test possible risk factors for UR: age, body mass index, serum albumin, cognitive impairment, activities of daily living (ADL), and history of diabetes mellitus (DM). UR occurred in 24 (14.2%) of the 169 patients. A multivariate logistic regression analysis with age adjustment showed that ADL (odds ratio [OR] 3.88; 95% confidence interval [CI]: 1.2-12.5, p=0.023) was significantly associated with the development of UR, and a history of DM showed marginal significance for UR occurrence (OR 0.36, 95%CI: 0.11-10, p=0.064). These results suggests that ADL is a risk factor for UR development in elderly males who have undergone surgery for femoral neck or trochanter fractures.

Orthogeriatric co-management at a regional core hospital as a new multidisciplinary approach in Japanese hip fracture operation.

BACKGROUND: This study aimed to evaluate the effects of orthogeriatric co-management of hip fractures at a regional core hospital. METHODS: This study included patients with proximal hip fracture. Patients were divided into two groups, conventional multidisciplinary group I including patients attending the hospital between April 2015 and March 2016 and orthogeriatric group II including patients attending the hospital between April 2016 and March 2017, which were compared etrospectively. In the control group, the conventional multidisciplinary team treated patients as whole-body controls. In the intervention group, the newly recruited geriatricians performed physical examinations, laboratory tests, radioactive imaging, and physiological tests. Furthermore, they consulted ward pharmacists, rigorously conducted positive polypharmacy interventions , and evaluated the type and number of mediated drugs on admission. RESULTS: The number of medicated drugs significantly decreased from 6.03 ± 4.3 on admission to 5.50 ± 3.59 on discharge in group II, whereas group I did not show a significant decrease. Despite the more number of hospitalized patients in group II (166 patients) than in group I (126 patients), the recovery rate from postoperative urinary retention increased significantly from 57.8% (19/30) in group I to 84.3% (32/59) in group II (p = 0.049), while the incidence of aspiration pneumonia decreased from 7.1% (9/126) in group I to 2.49% (4/166) in group II (p = 0.08). The patients received six or more prescribed drugs on admission, and the number remained constant. However, the number of medicated drugs on discharge showed a marginally significant decrease from 6.03 ± 4.3 in group I to 5.50 ± 3.59 in group II (p < 0.05). CONCLUSIONS: Compared to the conventional multidisciplinary group, the orthogeriatric team contributed to reducing the number of multi-effect drugs and perioperative complications without negatively affecting mortality despite the increased number of patients. The in-hospital mortality rate did not change between the groups. The orthogeriatric program succeeded in preventing and treating perioperative complications.

Neuroinflammation, Oxidative Stress, and Neurogenesis in a Mouse Model of Chronic Fatigue Syndrome, and the Treatment with Kampo Medicine.

The diagnosis of chronic fatigue syndrome (CFS) is mainly symptom-based, and the etiology is still unclear. Here, we evaluated the pathological changes in the brain of a mouse model of CFS and studied the effects of Kampo medicine. A mouse model of CFS was established through six repeated injections of Brucella abortus (BA) every two weeks for a period of 12 weeks. Neuroinflammation was measured by estimating interleukin (IL)-1ß, IL-6, and interferon-gamma (IFN-γ), and oxidative stress by nitrotyrosine (3-NT) and 4-hydroxynonenal (4-HNE) 6 weeks after the last injection. Hippocampal neurogenesis was evaluated through Ki-67, doublecortin (DCX), and 5-bromodeoxyuridine (BrdU) assays. The effects of Kampo medicines (Hochuekkito (TJ-41) and Hachimijiogan (TJ-7)) on neuroinflammation during CFS were studied. The wheel-running activity of mice was decreased by about 50% compared to baseline at 6 weeks after the last BA injection. The levels of IL-1ß, IL-6, 3-NT, and 4-HNE were increased in both the cortex and the hippocampus of CFS mice at 6 weeks after the last BA injection. Hippocampal neurogenesis was unchanged in CFS mice. Treatment with TJ-41 and TJ-7 reduced the expressions of IL-1ß, IL-6, and IFN-γ in the hippocampus but not in the cortex. The results of the present study indicate that neuroinflammation and oxidative stress play important roles in the pathogenesis of CFS. The data further suggest that treatment with TJ-41 and TJ-7 could help reduce the inflammation associated with CFS in the hippocampus, but failed to improve the symptoms in CFS mice.

Case study of early detection and intervention of infectious disease outbreaks in an institution using Nursery School Absenteeism Surveillance Systems (NSASSy) of the Public Health Center.

Objectives Detecting outbreaks early and then activating countermeasures based on such information is extremely important for infection control at childcare facilities. The Sumida ward began operating the Nursery School Absenteeism Surveillance System (NSASSy) in August 2013, and has since conducted real-time monitoring at nursery schools. The Public Health Center can detect outbreaks early and support appropriate intervention. This paper describes the experiences of Sumida Public Health Center related to early detection and intervention since the initiation of the system.Methods In this study, we investigated infectious disease outbreaks detected at 62 nursery schools in the Sumida ward, which were equipped with NSASSy from early November 2013 through late March 2015. We classified the information sources of the detected outbreak and responses of the public health center. The sources were (1) direct contact from some nursery schools, (2) messages from public officers with jurisdiction over nursery schools, (3) automatic detection by NSASSy, and (4) manual detection by public health center officers using NSASSy. The responses made by the health center were described and classified into 11 categories including verification of outbreak and advice for caregivers.Results The number of outbreaks detected by the aforementioned four information sources was zero, 25, 15, and 7 events, respectively, during the first 5 months after beginning NSASSy. These numbers became 5, 7, 53, and 25 events, respectively, during the subsequent 12 months. The number of outbreaks detected increased by 47% during the first 5 months, and by 87% in the following 12 months. The responses were primarily confirming the situation and offering advice to caregivers.Conclusion The Sumida Public Health Center ward could achieve early detection with automatic or manual detection of NSASSy. This system recently has become an important detection resource, and has contributed greatly to early detection. Because the Public Health Center can use it to achieve real-time monitoring, they can recognize emergent situations and intervene earlier, and thereby give feedback to the nursery schools. The system can contribute to providing effective countermeasures in these settings.

Effects of 6-month administration of tofogliflozin on cardiac function in elderly patients with heart failure with preserved ejection fraction: A retrospective study of a patient cohort.

Patients with type 2 diabetes mellitus are frequently hospitalized for heart failure. The ratio of early diastolic mitral inflow velocity to early diastolic mitral annulus velocity (E/e'), measured by echocardiography, is a simple and convenient indicator of diastolic dysfunction. Various large clinical trials have reported that sodium glucose transporter-2 inhibitor therapy reduced cardiovascular events and hospitalizations in heart failure patients. We examined the effect of tofogliflozin on various physiological and cardiac function. A retrospective analysis was performed on elderly patients aged 65 years or older with type 2 diabetes mellitus attending Himi Municipal Hospital who were taking oral tofogliflozin 20 mg/day. Measurement of physiological and hormonal variables, blood sampling, and echocardiographic evaluations at 0, 1, 3, and 6 months were performed on those with ejection fraction (EF) of 40% or greater at the time of treatment. Statistical analysis was performed using t-tests and mixed-effects models, with brain natriuretic peptide less than or not less than 100 pg/mL, estimated glomerular filtration rate (eGFR) less than or not less than 50 mL/min/1.73 m2, and diuretics administered or not. Hypoglycemic effects were observed at 0, 1, 3, and 6 months. At each time point, EF was retained and E/e' was significantly reduced. On the other hand, most physiological parameters and laboratory results showed no clinical abnormalities. Mixed-effects models showed time-dependent reduction of E/e' in high/low brain natriuretic peptide, high/low eGFR, with or without diuretics between baseline and at 6 months. The interaction with time was significant in high/low eGFR. Tofogliflozin was shown to improve E/e', a measure of diastolic function, while maintaining EF, with hypoglycemic effects and no clinical side effects.

Procalcitonin, brain natriuretic peptide and albumin as markers to predict prognosis in hospitalized older Japanese patients with a risk of infection.

AIM: Whether serum concentration of procalcitonin (PCT), brain natriuretic peptide (BNP) and albumin (Alb) have an association with the outcome of hospitalized older patients is unclear. We investigated clinical outcomes and any predictive factors in hospitalized Japanese older patients with a risk of infection. METHODS: In the retrospective study, 820 Japanese patients were followed up for 30 days or until death. During the observation period, 656 patients survived and 164 patients died. The predictive factors of death were analyzed according to demographic and clinical variables. RESULTS: The survival rate was decreased as the serum PCT increased from <0.5 to ≥10 ng/mL, as was also the case with BNP from <300 to ≥300 pg./mL, whereas low Alb (<2.5 g/dL) showed a lower survival rate than high Alb (≥2.5 g/dL; P < 0.01). Using the Cox regression model, the multivariable-adjusted hazard ratios (95% confidence interval) were as follows: PCT 0.5-2 versus <0.5 ng/mL: 1.61(1.04-2.49), PCT 2-10 versus <0.5 ng/mL: 1.91(1.15-3.16), PCT ≥10 versus <0.5 ng/mL: 2.90(1.84-4.59), high BNP 1.26 (0.89-1.76) and low Alb 0.68 (0.52-0.87). The mortality rate increased as the number of scores (PCT + BNP + Alb) increased. CONCLUSIONS: Concentration-dependent high PCT, high BNP and low Alb were positive risk factors associated with poor prognosis in hospitalized older patients with a risk of infection. Geriatr Gerontol Int 2024; 24: 571-576.

Women Physicians in Academic Medicine of Japan.

Japan is a well-qualified country in promoting scientific advancement, but female scientists are too few in academic medicine positions. The government of Japan announced that the share of women in leadership positions accounted to at least 30% by 2020 in all fields in society. The number of female students also increased, but it was not much higher than other Organisation for Economic Co-operation and Development (OECD) countries. Women students always have higher passing frequencies in national examination for medical practitioners in Japan. The potential gap between physician gender and academic advancement is mentioned in any medical fields. Women physicians in academic medicine position are still few. For women physicians, medical and familial situations are inversely affected by the coronavirus disease 2019. We propose the recommendations to support women physicians' right in academic medicine, accordingly to patients' benefit. Women may be stepping up and leading efforts without titles or positions in ways that are significant and meaningful for their group or organization.

A new predictive tool consolidating CURB-65 with procalcitonin and albumin to assess short-term mortality in hospitalized elderly patients with infectious disease: A retrospective study of a patient cohort.

BACKGROUND: Hospitalized elderly patients are often at risk of life-threatening infectious diseases such as pneumonia and urinary tract infection, thus diagnostic tools for bacterial infections are demanded. We developed a new predictive tool consolidating modified CURB-65, procalcitonin (PCT) and albumin (Alb). METHOD: This is a retrospective study. Modified CURB-65 (mCURB-65) score, PCT, Alb, and various cardiovascular/respiratory/renal functions were measured. Survival analyses were conducted to assess 30-days mortality of elderly patients using mCURB-65 score, PCT and Alb. The consolidated scores were compared with the number of patients died. RESULTS: There were 445 elderly patients included. Kaplan-Meier survival curves showed significant differences between the high and low groups of mCURB-65, PCT and Alb (log-rank test, P < .001). Cox proportional regression showed that the hazard ratios (95% confidence intervals) for high mCURB-65, high Alb, and high PCT were all significant, 1.95 (1.24-3.05), 0.50 (0.32-0.77), and 2.09 (1.32-3.31), respectively. The consolidated scores showed tendency of increase with proportion of the number of patients died. CONCLUSIONS: The consolidated score consisted of mCURB-65, PCT and Alb can be a useful tool to predict short-term mortality of the hospitalized elderly patients with infectious disease.

Effects of tofogliflozin on adrenocorticotropic hormone, renin and aldosterone, and cortisol levels in elderly patients with diabetes mellitus: A retrospective study of a patient cohort.

ABSTRACT: Adrenocorticotropic hormone (ACTH) and cortisol reportedly play a role in glycemic control in patients with type 2 diabetes mellitus (T2DM); however, the underlying mechanism remains controversial. We retrospectively investigated the effect of tofogliflozin on serum ACTH and cortisol levels in elderly patients with T2DM.Patients received 20 mg tofogliflozin daily for 3 months. Serum ACTH and cortisol levels were measured at baseline, as well as after 1 month and 3 months of tofogliflozin therapy.Serum ACTH levels were significantly reduced 3 months after tofogliflozin treatment (P < .01). Additionally, serum cortisol levels were reduced 3 months after tofogliflozin treatment, demonstrating borderline significance (P = .05). The higher body mass index (BMI; ≥25 kg/m2) group showed higher ACTH and cortisol levels than the lower BMI (<25 kg/m2) group, with borderline significance (P = .05). Renin levels were significantly increased 1 month after treatment (P < .05), maintaining serum aldosterone levels in parallel with the extracellular fluid.Our findings suggested that tofogliflozin decreased both serum ACTH and cortisol levels, with higher levels observed in the high BMI group. Tofogliflozin increased serum renin levels while maintaining serum aldosterone and extracellular fluid levels. Collectively, tofogliflozin could affect the hypothalamic-pituitary-adrenal pathway in patients with T2DM, especially in the low BMI group.

Gender Differences in Cardiac Function Following Three-Month Administration of Tofogliflozin in Patients With Diabetes Mellitus.

BACKGROUND: Patients with type 2 diabetes mellitus (T2DM) are at increased risk for impairment in heart failure and diastolic relaxation while preserving ejection fraction (EF). Recently, several sodium glucose cotransporter-2 (SGLT2) inhibitors have demonstrated to decrease cardiovascular disease (CVD) events in elderly diabetic patients, although gender difference in the effect of SGLT2 inhibitors is unknown. The objective of the present study was to evaluate gender difference in the effect of tofogliflozin, one of the SGLT2 inhibitors, on CVD function in patients with diabetes mellitus. METHODS: This was a retrospective study. Patients received 20 mg of tofogliflozin daily for 3 months. EF, ratio of early filling to atrial filling (E/A), a change in mitral inflow E and mitral e' annular velocities (E/e'), left atrial dimension (LAD) and maximal diameter of inferior vena cava (IVCmax), including various physiological parameters were measured between baseline, 1 month and 3 months after administration of tofogliflozin. Interaction between gender and time after administration was evaluated using mixed effect model. RESULTS: The results showed significant decrease in E/e' (P < 0.01) and significant interaction between time and gender in E/A (P < 0.01), following administration of tofogliflozin for 3 months. EF was constantly higher significantly in women (P < 0.01). CONCLUSION: It is concluded that 3-month administration of tofogliflozin decreased E/e' with gender difference in EF and E/A.

Genetic factors associated with elevation of uric acid after treatment with thiazide-like diuretic in patients with essential hypertension.

We investigated changes in blood pressure (BP) and metabolic adverse effects, especially elevation of uric acid (UA), after treatment with a thiazide-like diuretic (TD) in patients with essential hypertension. Furthermore, the role of genetic factors in the elevation of UA by TD was assessed by a 500 K SNP DNA microarray. The subjects included 126 hypertensive patients (57 women and 69 men, mean age 59 ± 12 years) who registered for the GEANE (Gene Evaluation for ANtihypertensive Effects) study. After one month of the nontreatment period, TD, indapamide, angiotensin II receptor antagonist valsartan, and Ca channel blocker amlodipine were administered to all patients for 3 months each in a randomized crossover manner. BP, renal function, serum UA level, and electrolytes were measured at baseline and at the end of each treatment period. Single nucleotide polymorphisms (SNPs) associated with UA elevation after treatment with indapamide were investigated by a genome-wide association study (GWAS). Indapamide significantly decreased both office and home BP levels. Treatment with indapamide also significantly reduced the estimated glomerular filtration rate and serum potassium and increased serum UA. Patients whose UA level increased more than 1 mg/dl showed significantly higher baseline office SBP and plasma glucose and showed greater decline in renal function compared with those who showed less UA increase (<1 mg/dl). Some SNPs strongly associated with an increase in UA after treatment with indapamide were identified. This study is the first report on SNPs associated with UA elevation after TD treatment. This information may be useful for the prevention of adverse effects after treatment with TD.

Immobilization stress inhibits intimal fibromuscular proliferation in the process of arterial remodeling in rats.

We investigated role of beta-endorphin (END), which is released by immobilization stress, on intimal fibromuscular proliferation in a rat model of arterial remodeling after intimal injury. The endothelium of the abdominal aorta of Wistar-Kyoto rats was denuded, and the rats were subjected to immobilization stress (6 h/d), which raised the serum concentration of END, and intraperitoneal administration of either END (20 ng/kg/d) or naltrexone (NAL: 4 mg/kg/d). The proliferative activity (PA) of medial smooth muscle cells (SMCs) and the intima/media area ratio (R) were determined at 3 and 14 d after denudation, respectively. PA and R were significantly reduced by immobilization (PA: 64.8%, R: 34.6%), and NAL treatment completely reversed the decreases in PA and R. On the other hand, END reduced both PA and R (PA: 21.7% and R: 24.9%), and NAL also reversed the decreases in PA and R. END (20 pg/mL) inhibited both the proliferation (79% at 96 h) and migration (26%) of SMCs cultured with 5% fetal bovine serum in vitro, and NAL (100 microg/mL) reversed the inhibition of both activities. Our results suggest that immobilization stress stimulates the release of endogenous END, which then prevents both proliferation and migration of medial SMCs after intimal injury.

Comorbidity of chronic kidney disease, diabetes and lower glycated hemoglobin predicts support/care-need certification in community-dwelling older adults.

AIM: Chronic kidney disease (CKD), diabetes and lower glycated hemoglobin (HbA1c ) range in diabetes patients are associated with higher mortality. We investigated whether these conditions were associated with the risk of loss of independence in community-dwelling older adults. METHODS: We analyzed 1078 older adults with no history of support/care-need certification in Long-Term Care Insurance aged 65-94 years. Associations of baseline CKD, diabetes, and lower HbA1c range of <6.0% in the diabetes patients, at baseline health checkup with risk of later certification and/or death for 5 years were estimated using the Cox proportional hazards regression model. RESULTS: The prevalence of both CKD and diabetes in the total population increased with age, due to a net increase in the coexistence of CKD and diabetes. The prevalence of the lower HbA1c range also increased with age in participants with the coexistence. During 5 years, 135 certifications and 53 deaths occurred. After adjustment, patients with comorbidity of the triad of CKD, diabetes and the lower HbA1c range had significantly higher hazard ratios (HR) for certification (HR 3.52, 95% confidence interval [CI] 1.91-6.48, P < 0.001) and for death (HR 3.79, 95% CI 1.46-9.85, P = 0.006) compared with those without CKD and diabetes. The harmful impact of the lower HbA1c range on later certification compared with higher HbA1c range of ≥6.0% was maintained in diabetes patients with use of antidiabetic agents and CKD (HR 2.40, 95% CI 1.06-6.45, P = 0.036). CONCLUSIONS: Excessive HbA1c reduction might cause discontinuance of disability-free survival in community-dwelling older diabetes patients with CKD. Geriatr Gerontol Int 2018; 18: 521-529.

Angiotensin I-converting enzyme inhibitor improves reactive hyperemia in elderly hypertensives with arteriosclerosis obliterans.

Endothelial function in elderly hypertensive patients with arteriosclerosis obliterans has not been evaluated. We examined whether antihypertensive drugs improve vasodilatory response to reactive hyperemia of the limbs in elderly hypertensive patients (83 +/- 8 [SD] years) without (n=46, 0.9 < or = ankle-brachial pressure index < or = 1.4) and with (n=24) arteriosclerosis obliterans (ankle-brachial pressure index < 0.2). Patients were randomized for treatment with monotherapy of either temocapril (14 with and 26 without arteriosclerosis obliterans) or amlodipine (10 with and 20 without arteriosclerosis obliterans) for 6 months. Blood flows of the forearms and legs were measured by strain-gauge plethysmography. The vasodilatory response to the release of compression of the forearms and thighs at 200 mmHg or 20 mmHg more than systolic blood pressure for 5 min and to sublingual administration of nitroglycerin (0.3 mg) was assessed. The maximum reactive hyperemic flow in 35 legs with arteriosclerosis obliterans was significantly (p < 0.001) decreased compared to the value in legs in the control hypertensive subjects. Moreover, maximum reactive hyperemic flow in the forearms of patients with arteriosclerosis obliterans was significantly (p = 0.002) decreased compared to that in the control subjects. Blood pressure was similarly decreased by treatment with temocapril or amlodipine. Response to nitroglycerin (0.3 mg) was not changed by either drug. Treatment with temocapril significantly improved maximum reactive hyperemic flow of not only the legs and forearms in control hypertensives but also the legs and forearms in patients with arteriosclerosis obliterans, and attenuated the worsening of activity of daily living in these patients, although treatment with amlodipine did not. These results suggest that the angiotensin-converting enzyme inhibitor temocapril has a beneficial effect on endothelial function in elderly patients with arteriosclerosis obliterans.

Tilting-induced decrease in systolic blood pressure in bedridden hypertensive elderly inpatients: effects of azelnidipine.

The object of this study was to examine blood pressure (BP) variability due to postural change in elderly hypertensive patients. The subjects studied were 154 elderly inpatients in a hospital for the elderly (48 male and 106 female; median age: 82 years), consisting of age- and sex-matched bedridden (n=39) and non-bedridden (n=39) normotensive controls and bedridden (n=38) and non-bedridden (n=38) hypertensive patients. BP and pulse rate (PR) were measured in the supine position, then again after a 2-min, 45 deg head-up tilt with the legs horizontal. The decrease in systolic BP (SBP) on tilting in the bedridden hypertensive group (median: -10 mmHg; range: -32 to 9 mmHg) was significantly (p<0.008) greater than those in the other three groups. Monotherapy with azeinidipine, a long-acting calcium channel blocker, for 3 months not only significantly reduced the basal BP and PR of hypertensive patients in the two groups, but also significantly (p<0.05) attenuated the tilt-induced decrease in the SBP to -3 mmHg (-19 to 25 mmHg) and enhanced the change in PR from -1 bpm (-10 to 7 bpm) to 1 bpm (-4 to 23 bpm) in the bedridden hypertensive group. Our findings indicate that tilt-induced decrease in SBP is a rather common phenomenon in bedridden elderly hypertensive patients, and that treatment with azelnidipine attenuates tilt-induced decrease in SBP, probably through an improvement of baroreceptor sensitivity.

[A ninety-eight-year-old woman with ruptured pancreatic anaplastic mucinous cystadenocarcinoma].

A 98-year-old woman was admitted to our hospital complaining of anorexia, epigastralgia, and vomiting. An elastic hard tumor was palpable in her epigastric region. CT and US examination revealed a huge cystic lesion adjacent to the left lobe of the liver and the stomach. Her serum levels of CEA (13.6 ng/ml), CA19-9 (95 U/ml) and CA125 (99 U/ml) were high. She suffered from aspiration pneumonia on the 10th day of admission, which progressed to acute respiratory distress syndrome. On the 20th day of admission, the epigastric tumor suddenly disappeared. She passed away on the 31st day due to respiratory failure. Autopsy revealed that she had a ruptured pancreatic anaplastic mucinous cystadenocarcinoma. To the best of our knowledge, this is the oldest reported case of ruptured pancreatic cystadenocarcinoma in the world.

Reduction of pneumonia risk by an angiotensin I-converting enzyme inhibitor in elderly Japanese inpatients according to insertion/deletion polymorphism of the angiotensin I-converting enzyme gene.

BACKGROUND: We have reported that use of angiotensin I-converting enzyme (ACE) inhibitor, which is a class of antihypertensive agent that induces cough, is an independent factor in reducing risk of pneumonia among elderly inpatients. Insertion/deletion (I/D) polymorphism of the ACE gene (ACE) has been associated with the risk of pneumonia in elderly individuals. However, the ability of ACE inhibitors to reduce pneumonia-related morbidity in individuals with the ACE polymorphism is unclear. Therefore we determined the association of ACE inhibitor use and ACE genotypes with reduction of pneumonia risk in the Japanese elderly population. METHODS: We conducted a hospital-based, retrospective, case-control study to evaluate the effect of an ACE inhibitor and ACE polymorphism on incidence of pneumonia. Case subjects were pneumonia patients (N = 105) >or=65 years of age, during an 8-month period of a nonwinter season. Control subjects (n = 420) were elderly patients who were frequency matched to the case subjects by age (within +/- 2 years) and gender. Data were collected on medication with the ACE inhibitor temocapril and on known risk factors for pneumonia. The significances of differences for the risk factors were analyzed using univariate and multivariate comparisons of the case and control subjects. RESULTS: After adjustment for potential confounders by multiple logistic regression analysis, the odds ratio (OR) estimates for pneumonia were 0.458 (95% confidential interval [CI]: 0.230 to 0.909, P = .026) for ACE inhibitor use. Conditional logistic regression analysis according to ACE genotypes revealed significant reduction of pneumonia risk by use of temocapril compared with that in nonhypertensive individuals (ie, the reference group) in those with ACE ID + II (OR: 0. 416, 95% CI: 0.177 to 0.976, P = .044), but not in those with ACE DD (OR: 0.706, 95% CI: 0.198 to 2.518, P = .592). CONCLUSION: These results suggest that use of an ACE inhibitor is beneficial for reducing risk of pneumonia, particularly in individuals with the ACE genotypes ID + II.

Flow loading induces macrophage antioxidative gene expression in experimental aneurysms.

OBJECTIVE: Reactive oxygen species may act as proinflammatory mediators in abdominal aortic aneurysm (AAA) disease. Flow loading increases antioxidative enzyme expression and limits reactive oxygen species production in vascular smooth muscle cells in vitro, limits experimental AAA enlargement in rodent models, and is indirectly associated with reduced clinical AAA risk. We attempted to determine the mechanism or mechanisms by which flow loading limits AAA enlargement. METHODS AND RESULTS: Rodent AAAs were flow loaded via femoral arteriovenous fistula creation. Aortic wall shear stress and relative wall strain were significantly higher in flow-loaded rodents. Flow loading reduced AAA diameter by 26% despite evidence of flow-mediated aortic enlargement proximal to the aneurysmal segment. Messenger RNA from AAA tissue was harvested for cDNA labeling and hybridization to a 384-clone DNA microarray. Twenty-nine genes were differentially expressed (relative intensity/relative intensity of control ratio >1.5 and <0.67) in flow-loaded compared with normal flow AAA tissue, including heme oxygenase 1 (HO-1). Increased HO-1 expression was confirmed via reverse transcriptase-polymerase chain reaction. Immunohistochemistry localized HO-1 expression to infiltrative macrophages. alpha-Tocopherol was found to be as effective as flow loading in limiting AAA enlargement. Flow loading and alpha-tocopherol therapy reduced AAA reactive oxygen species production. CONCLUSIONS: Flow loading may attenuate AAA enlargement via wall shear or strain-related reductions in oxidative stress.