The temporal profile of interactions between sensory information from both hands in the secondary somatosensory cortex.

OBJECTIVE: To elucidate the temporal profile of interactions between sensory information from both hands in the somatosensory cortex. METHODS: Somatosensory evoked fields (SEFs), generated by stimulation applied to the right index finger after a preceding stimulation to the left index finger, were recorded using a whole head-type magnetoencephalography (MEG). The paired electrical stimuli were applied with a stimulation onset asynchrony (SOA) of 50, 100, 200, 300, or 400 ms. RESULTS: The mean SEF intensities in the primary somatosensory area (SI) of five subjects, which were evoked approximately 40 ms after the latter of the paired stimuli, were not significantly smaller than that evoked in the control condition when only the right finger was stimulated. In contrast, SEFs in the secondary somatosensory area (SII), generated approximately 100 ms after the stimuli, were suppressed when the paired stimuli were applied at an SOA of 100 ms (P<0.05, t test). In addition, SEFs at approximately 150 ms after the stimuli were significantly suppressed at SOAs of 50, 100 (P<0.05), 200, and 300 ms (P<0.1). CONCLUSION: Within a time window of approximately 300 ms, sensory information from the left finger significantly affected the SEFs generated by sensory inputs from the right finger. This time window may be required for the integration of sensory input.     

Long-term results of arterial switch operation

Surgical results and late outcome in 202 patients who had undergone arterial switch operation from 1984 to 1997 were investigated. Actuarial survival was 90.6% at 10 years and 90.0% at 20 years. Fifty-two patients (25.7%) underwent reoperation for pulmonary stenosis and 7 patients (3.5%) had aortic valve replacement. Freedom from re-intervention was 71.9% at 10 years and 60.4% at 20 years. Using xeno-pericardial patch for pulmonary reconstruction was strong predictor for postoperative pulmonary stenosis. Coronary ischemic event was rare but some patients showed electorocardiogram (ECG) change on exercise and hypoplastic left coronary artery. Cardiopulmonary function was almost normal in long term survivors.     

Histopathological studies of microtubule disassembling agent-induced myocardial lesions in rats

Microtubule disassembling agents (MDAs) such as colchicine (COL) and vincristine sulfate (VCR) are known to be cardiotoxic. However, few attempts have been made to histopathologically examine cardiac lesions induced by MDAs. In this study, we endeavored to induce myocardial injury in rats by administering MDAs and to clarify the morphological features of these myocardial lesions. Male rats were intravenously administered COL (1.00 or 1.25 mg/kg for 2 days at single daily doses) or VCR (0.50 or 0.75 mg/kg for 2 days at single daily doses). The day after administration, hearts were excised and examined histopathologically, immunohistochemically and electron microscopically. Degeneration and necrosis of myocardial cells with vacuolation were observed in rats administered COL at 1.25 mg/kg or VCR at 0.75 mg/kg. Electron microscopic examination revealed vacuoles in swollen mitochondria. Moreover, there were cells showing pyknosis and karyorrhexis in the interstitium. TUNEL and immunohistochemical staining for endothelial cells and electron microscopic examination identified the apoptotic cells in the interstitium to be vascular endothelial cells. These vascular endothelial lesions were induced by lower doses of MDAs than were myocardial lesions. Furthermore, common sites of cardiac lesions induced by MDAs had almost the same distribution as areas positive for pimonidazole, a marker of hypoxia. These findings indicate that MDAs occasionally damage mitochondria in myocardial cells, and suggest that these changes involve microcirculatory dysfunction induced by endothelial cell injury.     

Saturated and Unsaturated Bone Marrow Lipids Have Distinct Effects on Bone Density and Fracture Risk in Older Adults

Greater bone marrow adiposity (BMAT) is associated with lower bone mineral density (BMD) and vertebral fractures; less is known about BMAT composition and bone. We studied BMAT composition and bone outcomes in 465 participants from the Age Gene/Environment Susceptibility (AGES)-Reykjavik study. BMAT saturation and unsaturation, measured with magnetic resonance spectroscopy, were defined as the ratio of saturated (1.3 ppm peak) or unsaturated (5.3 ppm peak) lipid to total marrow contents, respectively. At baseline and follow-up visits, spine and hip BMD were assessed with quantitative computed tomography (QCT) and dual-energy X-ray absorptiometry (DXA) and vertebral fractures were identified with DXA. Incident clinical fractures were identified through medical records for up to 8.8 years of follow-up. Associations between BMAT composition and BMD, bone loss, and fractures were evaluated in adjusted regression models. At baseline, mean ± standard deviation (SD) participant age was 81.7 ± 4.3 years, mean BMAT unsaturation was 3.5% ± 1.0%, and mean saturation was 46.3% ± 7.2% in the full cohort (47.7% women). Each SD increase in BMAT saturation was associated with lower trabecular BMD: −23.6% (spine) and −13.0% (total hip) (all p < 0.0001). Conversely, BMAT unsaturation (per SD increase) was associated with higher trabecular BMD: +17.5% (spine) and +11.5% (total hip) (all p < 0.001). BMAT saturation (per SD increase) was associated with greater risk for prevalent (odds ratio [OR] 1.46; 95% confidence interval [CI], 1.11–1.92) and incident (OR 1.55; 95% CI, 1.03–2.34) vertebral fracture. BMAT unsaturation (per SD increase) was associated with lower risk for incident vertebral fracture (OR 0.58; 95% CI, 0.38–0.89). In gender stratified analyses, BMAT saturation and unsaturation had opposite associations with incident clinical fracture among men. In general, saturated marrow lipids were associated with worse skeletal outcomes, whereas unsaturated lipids were associated with better outcomes. We recommend that future studies of marrow fat and skeletal health report measurements of saturated and unsaturated marrow lipids, rather than total marrow fat content alone. © 2022 American Society for Bone and Mineral Research (ASBMR).     

Hyperkyphotic posture and poor physical functional ability in older community-dwelling men and women: the Rancho Bernardo study

BACKGROUND: Physical functional decline is often the determining factor that leads to loss of independence in older persons. Identifying risk factors for physical disability may lead to interventions that may prevent or delay the onset of functional decline. Our study objective was to determine the association between hyperkyphotic posture and physical functional limitations. METHODS: Participants were 1578 older men and women from the Rancho Bernardo Study who had kyphotic posture measured as the distance from the occiput to table (units = 1.7-cm blocks, placed under the participant's head when lying supine on a radiology table). Self-reported difficulty in bending, walking, and climbing was assessed by standard questionnaires. Physical performance was assessed by measuring grip strength and ability to rise from a chair without the use of the arms. RESULTS: Men were more likely to be hyperkyphotic than were women (p <.0001). In multiply adjusted comparisons, there was a graded stepwise increase in difficulty in bending, walking and climbing, measured grip strength, and ability to rise from a chair. For example, the odds ratio (OR) of having to use the arms to stand up from a chair increased from 1.6 (95% confidence interval [CI]: 0.9-3.0) for individuals defined as hyperkyphotic by 1 block to 2.9 (95% CI: 1.7-5.1) for individuals defined as hyperkyphotic by 2 blocks to 3.7 (95% CI: 2.1-6.3) for individuals defined as hyperkyphotic by > or = 3 blocks compared to those who were not hyperkyphotic (p for trend < .0001). CONCLUSIONS: Older persons with hyperkyphotic posture are more likely to have physical functional difficulties.     

Iron chelator deferasirox rescued mice from Fas‐induced fulminant hepatitis

Aim: Fulminant hepatitis is a disease characterized by development of hepatic failure due to severe liver cell injury. Orthotopic liver transplantation is the therapy proven to improve patient survival; however, less burdensome and safer strategies are required. In a previous study, we showed that iron was intimately involved in hepatocyte apoptosis by demonstrating that spontaneous development of fulminant hepatitis in Long–Evans cinnamon rats was prevented by feeding an iron‐deficient diet. Recently, a new iron chelator, deferasirox, has become widely available for the treatment of transfusional hemosiderosis. Deferasirox demonstrated good efficacy and improved compliance due to convenient, once‐daily p.o. administration. Our aim was to investigate the efficacy of deferasirox as a therapeutic drug against fulminant hepatitis. Methods: Human primary hepatocytes undergoing Fas‐stimulated apoptosis were challenged with deferoxamine (DFO) in vitro. In further in vivo experiments, we tested DFO in a mice model of fulminant hepatitis induced by Fas‐stimulation. Results: The apoptosis‐inducing activity of anti‐Fas antibody on human primary hepatocytes was inhibited by the chelation of iron with DFO. DFO suppressed the Fas‐induced production of reactive oxygen species (ROS) and the activation of caspase‐3, both of which were also suppressed by antioxidant, N‐acetyl‐L‐cystein. In the in vivo experiments, deferasirox effectively reduced hepatic iron concentrations and rescued mice from Fas‐induced fulminant hepatitis. Conclusion: These findings indicated that the iron chelation exerted a hepatoprotective effect by scavenging ROS upstream of caspase‐3 and that iron chelation with deferasirox is a potential treatment for patients with fulminant hepatitis.     

Thyroid-stimulating antibody in a patient with euthyroid Graves' disease

We report an 11-year-old girl with euthyroid Graves' disease. She was referred to our clinic because of left exophthalmos without other symptoms suggestive of hyperthyroidism. Her serum concentration of free thyroxine (FT4) and free triiodothyronine (FT3) were normal, but thyroid-stimulating hormone (TSH) was below normal and impaired TSH response to TSH releasing hormone (TRH) was found. Although the sera were positive for anti-TSH receptor antibody (TRAb) and thyroid-stimulating antibody (TSAb), both titers were not as high as usually observed in Graves' disease. Three months later, she developed hyperthyroidism and was treated with propylthiouracil. Within 2 weeks of the initiation of therapy, all symptoms except exophthalmos disappeared, and after 2 months of treatment TRAb was negative though TSAb remained positive. TSAb is therefore a good indicator to use in the diagnosis and follow-up of euthyroid Graves' disease and should be measured in patients with exophthalmos of unknown origin, even in children.     

Homocysteine levels and decline in physical function: MacArthur Studies of Successful Aging

PURPOSE: To test whether elevated homocysteine levels are associated with an increased risk of decline in physical function in older persons. METHODS: We performed a prospective cohort study of 499 highly functioning men and women aged 70 to 79 years who were enrolled in the MacArthur Studies of Successful Aging. We measured total homocysteine levels and performance-based physical function at baseline; physical function measures were repeated an average of 28 months later. A summary measure of physical performance from tests of balance, gait, lower body strength and coordination, and manual dexterity was developed, and a change score was calculated as the difference in scores from 1988 to 1991. RESULTS: The mean (+/-SD) homocysteine level was 11.6 +/- 4.3 micromol/L. With each SD increase in homocysteine, there was an increased risk of being in the worst quartile of decline in physical function (odds ratio = 1.5; 95% confidence interval: 1.2 to 1.9) in analyses that adjusted for age, sex, baseline physical performance, smoking status, vitamin B(12) levels, and incident stroke. Similar results were seen when change in physical performance was treated as a continuous variable. CONCLUSION: Older persons with elevated plasma homocysteine levels are at an increased risk of decline in physical function.     

An algorithm for identification of ST-elevation myocardial infarction patients by emergency medicine services

Objective

ST-elevation myocardial infarction (STEMI) identification by emergency medicine services (EMS) leading to pre-hospital catheterization laboratory (CL) activation shortens ischemic time and improves outcomes. We examined the incremental value of addition of a screening clinical tool (CT), containing clinical information and a Zoll electrocardiogram (ECG)-resident STEMI identification program (ZI) to ZI alone.

Methods

All EMS-performed and ZI-analyzed ECGs transmitted to a percutaneous coronary intervention hospital from October 2009 to January 2011 were reviewed for diagnostic accuracy. ZI performance was also compared to ECG interpretations by 2 experienced readers The CT was then retrospectively applied to determine the incremental benefit above the ZI alone.

Results

ST-elevation myocardial infarction was confirmed in 23 (7.5%) of 305 patients. ZI was positive in 37 (12.1%): sensitivity: 95.6% and specificity: 94.6%, positive predictive value (PPV), 59.5%, negative predictive value (NPV), 99.6%, and accuracy of 93.8%. Moderate agreement was observed among the readers and ZI. CT criteria for CL activation were met in 24 (7.8%): 20 (83.3%) were confirmed STEMIs: sensitivity: 86.9%, specificity: 98.5%, a PPV: 83.3%, and NPV: 98.6%, accuracy of 97.7%. CT + ZI increased PPV (P < 0.05) and specificity (P < 0.003) by reducing false positive STEMI identifications from 15 (4.9%) to 4 (1.3%).

Conclusions

In an urban cohort of all EMS transmitted ECGs, ZI has high sensitivity and specificity for STEMI identification. Whereas the PPV was low, reflecting both low STEMI prevalence and presence of STEMI-mimics, the NPV was very high. These findings suggest that a simplified CT combined with computer STEMI interpretation can identify patients for pre-hospital CL activation. Confirmation of these results could improve the design of STEMI care systems.     

Circulating levels of interleukin-6, its soluble receptor and interleukin-6/interleukin-6 receptor complexes in patients with type 2 diabetes mellitus

We evaluated the relationship between plasma fibrinogen concentration and the serum levels of interleukin-6 (IL-6), its soluble receptor, and their complex in patients with type 2 diabetes mellitus. The study comprised 57 patients with type 2 diabetes and 15 normal healthy controls. Serum levels of IL-6, soluble IL-6 receptor (IL-6R), and circulating IL-6/IL-6R complex were determined by enzyme-linked immunosorbent assays. Correlations between the different study parameters and serum IL-6, IL-6R, or IL-6/IL-6R complex levels were determined by multiple linear regression analysis. Any association between the different study parameters and the serum levels of IL-6, IL-6R, or IL-6/IL-6R complex were determined by stepwise linear regression analysis. The serum IL-6 level in diabetic subjects was significantly higher than in normal healthy controls (3.48 ± 3.29 pg/ml vs 0.784 ± 0.90 pg/ml, mean ± SD, respectively, P = 0.0001). The specific optical density of the serum IL-6/IL-6R complex in diabetic patients was also significantly higher than in normal healthy controls, although there was no significant difference in the serum IL-6R level between diabetic patients and controls. The serum IL-6 concentration was correlated significantly with the HbA_1C level (β = 0.58, P = 0.04) by multiple regression analysis. Stepwise regression analysis revealed that the levels of serum IL-6 (F = 8.251), HbA_1C (F = 1.08), and serum urea nitrogen (F = 5.603) were associated with the plasma fibrino gen concentration. These results suggest that hyperglycaemia and increased levels of serum IL-6 can increase the plasma fibrinogen concentration, one of the known risk factors for atherosclerosis in patients with type 2 diabetes mellitus. Received: 24 August 1998 / Accepted in revised form: 2 February 1999