Physical activity attenuates the effect of increased left ventricular mass on the risk of ischemic stroke: The Northern Manhattan Stroke Study

OBJECTIVES: The goal of this study was to determine whether the risk of ischemic stroke associated with increased left ventricular mass (LVM) is modified by physical activity (PA). BACKGROUND: Increased LVM is associated with an increased risk for stroke. Physical activity can decrease the risk of stroke and may have variable effects on LVM. METHODS: We used a case-control study design in a multiethnic population in northern Manhattan, New York, to study 394 case subjects who had a first ischemic stroke and 413 stroke-free control subjects. All subjects were interviewed and two-dimensional echocardiograms obtained to determine LVM. RESULTS: A sharp increase in risk of ischemic stroke was seen in the highest quartile of LVM (odds ratio [OR]: 6.14 [95% confidence interval [CI]: 3.04 to 12.38]). Thus, increased LVM was defined by the highest quartile of LVM. In multivariate analysis, the effect of increased LVM on the risk of stroke was significantly decreased by the presence of any level of PA versus no PA (OR: 1.59 [95% CI: 0.99 to 2.57] p < 0.07 vs. 3.53 [95% CI: 1.94 to 6.42] p < 0.0001). Although PA decreased the risk of stroke in all patients, the effect was stronger in subjects with increased LVM than among those without increased LVM (p = 0.033). CONCLUSIONS: Increased LVM is associated with an increased risk of stroke, especially among sedentary patients. Physical activity decreases the risk of stroke among patients with increased LVM to a level comparable to that of patients without increased LVM. Recommending PA may be a nonpharmacologic tool to reduce the stroke risk, especially among patients with increased LVM.     

Intraductal papillary adenoma: Usefulness of magnetic resonance cholangiopancreatography in the diagnosis of cystic branch-duct dilatation of the pancreas

A 70-year-old woman with gastric cancer was referred to our hospital for further evaluation of a cystic mass in the head of the pancreas. Endoscopic ultrasonography (EUS) showed a mural nodule in the cystic mass. Endoscopic retrograde cholangio pancreatography (ERCP) revealed a cystic lesion with a filling defect caused by obstruction with mucus. Magnetic resonance cholangiopancreatography (MRCP) allowed visualization of the entire configuration of the cystic lesion despite the presence of mucus. Pancreatic juice was positive for K-ras point mutation. Pancreatoduodenectomy was performed, with a diagnosis of intraductal papillary adenoma or adenocarcinoma with gastric cancer. Pancreatography of the resected specimen showed a cystic lesion in the uncinate process, consistent with the MRCP findings. Histological examination revealed an intraductal papillary adenoma. MRCP is very useful for demonstrating the total configuration of cystic lesions and is not impeded by impacted mucin. Nevertheless, because of its lower spatial resolution, this noninvasive modality is of limited value in detecting mural nodules. At present, therefore, surgical indications for cystic lesion of the pancreas should be determined by comprehensively analyzing: size and sequential changes in size of the cyst; presence of mural nodules, cytologic examination for presence of malignant cells, and/or K-ras point mutation in pure pancreatic juice.     

Activated leukocytes and endothelial cells enhance retention of ultrasound contrast microspheres containing perfluoropropane in inflamed venules

PURPOSE: To characterize the flow dynamics of albumin ultrasound contrast microspheres containing perfluoropropane (PFP) in normal and inflamed microvasculature. MATERIALS AND METHODS: Mesenteric microvessels of rats were examined after an intravenous injection of fluorocein-labeled erythrocytes or PFP microspheres by fluorescence intravital microscopy with and without local application of 10(-8) M platelet activating factor (PAF) as an experimental form of inflammation. RESULTS: All the microspheres passed freely through arterioles and capillaries. Mean velocities of the microspheres in each vessel were closely correlated with those of erythrocytes. Only a minor fraction of the microspheres was retained in the venules (> or =0.1 s stoppage) by attachment to endothelial cells. The frequency of microsphere retention in venules was significantly enhanced by PAF (2.6+/-2.1%, P<0.01 vs. control), especially in regions with leukocyte adhesion. Treatment with a monoclonal antibody to intercellular adhesion molecule-1, P-selectin or the common leukocyte antigen inhibited PAF-induced microsphere retention in venules (P<0.05). In the inflamed microcirculation, a small subgroup of microspheres becomes attached to venular endothelial cells in regions with leukocyte adhesion via interaction among microspheres, activated leukocytes and endothelial cells via adhesion molecules. CONCLUSION: In inflamed microcirculation, a small subgroup of microspheres becomes attached to venular endothelial cells in regions with leukocyte adhesion via interaction among microspheres, activated leukocytes and endothelial cells via adhesion molecules. These results suggest that ultrasonography with microspheres has the potential to evaluate inflammatory site distribution as well as tissue perfusion.     

Prognostic usefulness of serum uric acid after acute myocardial infarction (the Japanese Acute Coronary Syndrome Study)

Serum uric acid (UA) levels reflect circulating xanthine oxidase activity and oxidative stress production. Hyperuricemia has been identified in patients who have congestive heart failure and is a marker of poor prognosis in such patients. We investigated the relation between serum UA levels and Killip's classification suggestive of the severity of heart failure and whether hyperuricemia influences mortality of patients who have acute myocardial infarction (AMI). Using the Japanese Acute Coronary Syndrome Study database, we evaluated 1,124 consecutive patients who were hospitalized within 48 hours of onset of symptoms of AMI from January to December 2002. There was a close relation between serum UA concentration and Killip's classification. Patients who developed short-term adverse events had high UA concentrations. Serum UA levels, Killip's class, age, and peak creatine phosphokinase level were significant predictors of long-term mortality. The hazard ratio for patients in the highest quartile of UA was 3.7 compared with those in the lowest quartile for death after AMI after adjustment for independent factors that were related to mortality. The combination of the best UA cutoff (447 micromol/L) for predicting survival based on receiver-operating characteristics analysis and Killip's class significantly predicted the prognosis of acute and long-term AMI-related complications. In conclusion, our results suggest that hyperuricemia after AMI is associated with the development of heart failure. Serum UA level is a suitable marker for predicting AMI-related future adverse events, and the combination of Killip's class and serum UA level after AMI is a good predictor of mortality in patients who have AMI.     

Health-related quality of life of unrelated bone marrow donors in Japan

To promote bone marrow donation, both the safety and well-being of healthy unrelated volunteer donors must be protected. This prospective cohort study evaluated donors' health-related quality of life (HRQOL) and identified factors associated with it. Using the Medical Outcomes Study Short Form 36 Health Survey (SF-36) before bone marrow harvesting (BMH), and again 1 week and 3 months after the donors' discharge, we evaluated HRQOL of 565 donors (329 men, 236 women) registered with the Japan Marrow Donor Program (JMDP). We also examined the data routinely collected by the JMDP, such as BMH-related problems and other demographic and medical variables, to determine whether such data could be used to predict donors' HRQOL after discharge. Mean scores of all pre-BMH SF-36 subscales showed better functioning than the national norm. One week after discharge, mean scores on physical functioning (PF) and role-physical (RP) subscales, indicative of physical states, and bodily pain (BP) were approximately 1 SD lower than the national norm; however, mental health (MH) and general health perception (GH) remained above normal; the most frequent BMH-related problems were pain at the donation site and lower back pain, which were associated with lower PF, RP, and BP scores. Female gender and duration of procedure predicted lower PF, RP, and BP. Three months after discharge, mean scores of all SF-36 subscales had returned to baseline levels. These data show that the adverse effects of BMH on donors' HRQOL are transient and can be minimized by better management of pain.     

Quality of life improvements in dialysis patients receiving darbepoetin alfa

Short-acting hematopoietic agents can improve the quality of life (QOL) of hemodialysis patients, but questions remain regarding the domains of QOL affected, the relative importance of initial and final hemoglobin (Hb) concentrations, and the use of long-acting hematopoietic agents. We measured Hb concentrations and QOL in 487 hemodialysis patients who were switched from treatment with recombinant human erythropoietin to treatment with darbepoetin alfa. QOL was measured with the Japanese-language version of the SF-36, at the start of therapy with darbepoetin alfa and again 7-14 weeks later. We examined changes in QOL over time in the group as a whole, and in subgroups stratified by the change in Hb concentration. We also studied relationships between the final Hb concentration achieved and the magnitude of change in QOL. QOL scores increased significantly in all SF-36 domains except Social Functioning. The greatest increases were in vitality and in the two role-functioning domains. The magnitude of the increase in Hb concentration was related to the magnitude of the increase in QOL for only one subscale: Vitality. Patients with higher final Hb concentrations also had greater increases in Vitality scores. Hematopoiesis induced by darbepoetin alfa is associated with increased vitality and may also be associated with improved role functioning. Vitality increased significantly only in those patients with the greatest increases in Hb concentration and in those with higher final Hb concentrations.     

Association of des-γ-carboxy prothrombin production and Sonazoid-enhanced ultrasound findings in hepatocellular carcinomas of different histologic grades

Purpose

We previously reported that hepatocellular carcinoma (HCC) changes to a phenotype producing des-γ-carboxy prothrombin (DCP) during epithelial mesenchymal transition (EMT) in vitro. To confirm this change in vivo, we evaluated the association between DCP production and HCC hemodynamics in patients undergoing resection as EMT and hemodynamic changes are closely associated with each other.

Methods

We evaluated HCC hemodynamics by employing Sonazoid-enhanced ultrasound (SEUS) before surgical resection, and sought associations with histological grade and immunohistochemical staining of DCP in 19 areas from 11 patients.

Results

In 10 HCC areas showing early washout (3 min ≥) using SEUS, three areas corresponded to poorly differentiated HCC and the remaining seven areas corresponded to moderately differentiated HCC, and positive DCP staining was observed in only two of the seven moderately differentiated HCC areas, whereas no staining was observed in poorly differentiated HCC areas. Six HCC areas showing intermediate washout (3–10 min) using SEUS were moderately differentiated, of which five demonstrated positive DCP staining (83.3%, 5/6). However, all HCC areas without enhancement in the arterial phase were well-differentiated and did not show DCP staining.

Conclusion

Our preliminary findings suggest that HCC hemodynamics evaluated by SEUS are associated with histological grade and/or DCP production.

     

Cost-utility Analysis of Screening for Diabetic Retinopathy in Japan: A Probabilistic Markov Modeling Study

ABSTRACT

Purpose: To evaluate the cost-effectiveness for a screening interval longer than 1 year detecting diabetic retinopathy (DR) through the estimation of incremental costs per quality-adjusted life year (QALY) based on the best available clinical data in Japan.

Methods: A Markov model with a probabilistic cohort analysis was framed to calculate incremental costs per QALY gained by implementing a screening program detecting DR in Japan. A 1-year cycle length and population size of 50,000 with a 50-year time horizon (age 40–90 years) was used. Best available clinical data from publications and national surveillance data was used, and a model was designed including current diagnosis and management of DR with corresponding visual outcomes. One-way and probabilistic sensitivity analyses were performed considering uncertainties in the parameters.

Results: In the base-case analysis, the strategy with a screening program resulted in an incremental cost of 5,147 Japanese yen (¥; US$64.6) and incremental effectiveness of 0.0054 QALYs per person screened. The incremental cost-effectiveness ratio was ¥944,981 (US$11,857) per QALY. The simulation suggested that screening would result in a significant reduction in blindness in people aged 40 years or over (?16%). Sensitivity analyses suggested that in order to achieve both reductions in blindness and cost-effectiveness in Japan, the screening program should screen those aged 53–84 years, at intervals of 3 years or less.

Conclusions: An eye screening program in Japan would be cost-effective in detecting DR and preventing blindness from DR, even allowing for the uncertainties in estimates of costs, utility, and current management of DR.     

Pancreatic arteriovenous malformation with pancreatitis involving a pancreatico-venous fistula

An arteriovenous malformation of the pancreas is a very rare disease, but its presentation is distinct and unique. In this report, we describe a patient who presented with this malformation which was localized in the tail of pancreas and demonstrated by abnormal angiography findings. The patient was a 60-year-old male with severe left hypochondralgia. Angiography revealed an increased blood volume in the tail of the pancreas with arteriovenous shunting. Secondary pancreatitis caused by the arteriovenous malformation was suspected by abnormal laboratory data, and confirmed by histology from the resected tail of the pancreas. This is a very rare report in which pancreatic arteriovenous malformation involving a pancreaticovenous fistula was confirmed by endoscopic retrograde cholangiopancreatography (ERCP).     

Elderly-onset rheumatoid arthritis: ageing as an independent marker for better joint prognosis

To study the contribution of age to the outcome of rheumatoid arthritis (RA), 133 elderly-onset RA (ERA) patients (onset above 60-year-old) were selected out of 2164 out-patients with RA who (i) first visited the hospital within 2 years after onset of the disease, (ii) received no remission inducing drugs previously and (iii) who were treated in this hospital regularly without interruption for more than 2 years. The joint score of ERA patients between initial visit and final visit to the hospital was compared with that of matched 133 younger-onset RA (YRA) patients (onset below 60-year-old). Results indicated that, in ERA, the patients with no active joints requiring no remission inducing drugs were increased on final visit (P<0.001). Joint score at disease onset or on initial visit to the hospital was similar in the two groups, whereas joint score on final visit was significantly decreased in ERA (P=0.0001). In ERA, progression of the small joint disease and joint erosion was not accelerated, and the small joint disease was in fact decelerated as compared with YRA (P<0.0001) during initial visit and final visit. Discriminant function analysis of patients with or without no active joints on final visit reveals that joint erosion, in small joints on initial visit is a predictor of joint prognosis in ERA. The two groups were similar with regards to sex, disease duration, onset type and rheumatoid factor/antinuclear antibody positivity. Thus, older age is an independent marker of better joint prognosis of RA