Seasonal Patterns of Buruli Ulcer Incidence,Central Africa, 2002–2012

To determine when risk for Buruli ulcer is highest, we examined seasonal patterns in a highly disease-endemic area of Cameroon during 2002–2012. Cases peaked in March, suggesting that risk is highest during the high rainy season. During and after this season, populations should increase protective behaviors, and case detection efforts should be intensified.     

The role of growth hormone in the glucose intolerance of uremia

Summary The fasting plasma growth hormone (GH) concentration and the plasma growth hormone response to sustained hyperglycemia was examined in 8 chronically uremic subjects before and after hemodialysis employing the hyperglycemic clamp technique. The plasma glucose concentration was actuely raised and maintained at +125 mg/100 ml above basal levels. Since the glucose concentration was held constant, the glucose infusion rate is an index of glucose metabolism (M) and M divided by the plasma insulin response (I) is a measure of tissue sensitivity to insulin. Predialysis, the fasting GH concentration, 4.0±1.0 ng/ml, was significantly greater than controls, 0.3±0.1 ng/ml (p<0.01), and failed to suppress normally following sustained hyperglycemia. Both M, 4.23±0.36 mg/kg·min, and M/I, 5.05±0.79 mg/kg·min per μU/ml, were significantly reduced compared to controls (p<0.001). There was no correlation between either the fasting GH concentration or the GH response to sustained hyperglycemia and either M or M/I. Following dialysis both M, 6.30±0.64 mg/kg·min, and M/I, 8.39±1.06 mg/kg·min per μU/ml, increased (p<0.01) without significant change in either the fasting GH level, 4.0 ± 1.2 ng/ml, or the plasma GH response to hyperglycemia. It is concluded that while deranged GH physiology is a common accompaniment of the uremic state, it is not responsible for the glucose intolerance and tissue insensitivity to insulin observed in uremia. The middle of the weight range for subjects of medium frame from the 1959 Metropolitan Life Insurance Company table for desirable weight was used.     

Lung injury mediated by antibodies to endothelium. III. Effect of chlorpromazine in rabbits

In rabbits intravenous administration of antibodies to lung angiotensin converting enzyme (ACE) results in a rapid redistribution of ACE on the plasma membrane of pulmonary endothelium with fixation of complement and development of fatal pulmonary edema. In survivors given daily injections of antibodies, ACE disappears from the lung ("antigenic modulation") and the rabbits become resistant to further immune injury. To test the hypothesis that these events depend on a functionally intact mechanism of cell activation, rabbits received, in addition to anti-ACE antibodies, chlorpromazine, a drug that inhibits calmodulin and protein kinase C and decreases plasma membrane fluidity. Initially, chlorpromazine inhibited antigen redistribution, fixation of complement, and development of pulmonary edema. In rabbits maintained on chlorpromazine and receiving daily anti-ACE antibodies this effect became attenuated and the rabbits eventually developed ACE redistribution, complement fixation, and pulmonary edema. We conclude that chlorpromazine temporarily inhibits antigenic modulation in vivo, presumably through its action on calcium-mediated antibody-cell surface antigen interaction.     

Predictors and consequences of aggressive behavior by community-based dementia patients

The frequency, nature, context, and caregivers' reactions to aggressive behavior in 213 dementia patients residing in the community was studied. Aggression was reported in 57.2% of the patients and in 10.6% of the caregivers. Predictors of patient aggression were greater frequency of behavior and memory problems, premorbid aggression, and a more troubled premorbid social relationship between patient and caregiver. Patient aggression predicted the decision to discontinue home care.     

Metabolic syndrome amplifies the age-associated increases in vascular thickness and stiffness

OBJECTIVES: We sought to evaluate whether the clustering of multiple components of the metabolic syndrome (MS) has a greater impact on these vascular parameters than individual components of MS. BACKGROUND: Intima-media thickness (IMT) and vascular stiffness have been shown to be independent predictors of adverse cardiovascular events. The MS is defined as the clustering of three or more of the cardiovascular risk factors of dysglycemia, hypertension, dyslipidemia, and obesity. METHODS: Carotid IMT and stiffness were derived via B-mode ultrasonography in 471 participants from the Baltimore Longitudinal Study on Aging, who were without clinical cardiovascular disease and not receiving antihypertensive therapy. RESULTS: The MS conferred a disproportionate increase in carotid IMT (+16%, p < 0.0001) and stiffness (+32%, p < 0.0001), compared with control subjects. Multiple regression models, which included age, gender, smoking, low-density lipoprotein, as well as each individual component of MS as continuous variables, showed that MS was an independent determinant of both IMT (p = 0.002) and stiffness (p = 0.012). The MS was associated with a greater prevalence of subjects whose values were in the highest quartiles of IMT, stiffness, or both. CONCLUSIONS: Even after taking into account each individual component of MS, the clustering of at least three of these components is independently associated with increased IMT and stiffness. This suggests that the components of MS interact to synergistically impact vascular thickness and stiffness. Future studies should examine whether the excess cardiovascular risk associated with MS is partly mediated through the amplified alterations in these vascular properties.     

Elevation of endothelial microparticles, platelets, and leukocyte activation in patients with venous thromboembolism

OBJECTIVES: The purpose of this research was to determine the levels of platelet, leukocyte, and endothelial activation and markers of cellular interactions in patients with venous thromboembolism (VTE). BACKGROUND: The details of interactions between endothelium, platelets, and leukocytes in VTE are not well understood. METHODS: We studied 25 patients with VTE and compared 25 healthy controls. We used flow cytometry to measure: 1) endothelial microparticles (EMP) identified by CD31+/CD42b- (EMP(31)) or E-selectin (EMP(62E)); 2) platelet microparticles (CD31+/CD42b+); 3) surface expression of P-selectin in platelets and CD11b in leukocytes; 4) EMP-monocyte conjugates (percentage of monocytes positive for E-selectin); and 5) platelet-leukocyte conjugates (PLC) expressed as percentage of leukocytes positive for CD41. RESULTS: Patients with VTE had marked elevations of EMP(31) (2,193 vs. 383 counts/microl; p = 0.003), EMP(62E) (368 vs. 223 counts/microl; p = 0.001), and EMP-monocyte conjugates (3.3% vs. 2.5%; p = 0.002), as well as increased activation of platelets (35.2 vs. 5.0 fluorescence intensity units for P-selectin; p < 0.0001) and leukocytes (13.9 vs. 7.7 U for CD11b; p = 0.004). Also elevated in VTE were PLC (61.7% vs. 39.6%; p = 0.01). Expression of CD11b in leukocytes strongly correlated with PLC (r = 0.74; p < 0.0001). CONCLUSIONS: Marked activation of endothelium, platelets, and leukocytes occurs in VTE, and VTE, or the accompanying inflammatory process, involves the release of EMP and formation of EMP-monocyte conjugates and PLC. These findings support prior studies suggesting that release of EMP and their binding to monocytes are key events in thrombogenesis. Our findings also support the concept that the formation of PLC regulates leukocyte activation and participates in linking thrombosis with inflammation.     

Bone tissue content of TGF-β2 changes with time in human heterotopic ossification after total hip arthroplasty

Transforming growth factor beta isoforms (TGF-β₁, TGF-β₂, and TGF-β₃) most likely play a role in bone physiology, but little is known about their relative importance in normal as well as in heterotopic bone. This study focused on possible differences in the localization and relative content of different TGF beta isoforms in heterotopic ossifications (HO) by comparing HOs, which have developed less than 17 months (immature HOs) with those developed 3–9 years (mature HOs). The HOs were harvested after total hip arthroplasty (THA) during revision surgery. The HO samples were decalcified, embedded in paraffin and sectioned. Azan staining was used to evaluate histological structure of the ossifications and immunohistochemical analysis was performed to estimate the localization of three TGF beta isoforms in the HOs. Comparison of different TGF beta isoforms in the immature and the mature ossifications showed that the content of TGF-β₂ was decreased by almost three times in the mature HO as compared to the immature HO (p = 0.0064). The proportions of other isoforms in HOs did not differ significantly. This study shows that the relative importance of TGF betas change with HO development.