Increased diagnosis of primary aldosteronism, including surgically correctable forms, in centers from five continents

Primary aldosteronism (PA) is a common form of endocrine hypertension previously believed to account for less than 1% of hypertensive patients. Hypokalemia was considered a prerequisite for pursuing diagnostic tests for PA. Recent studies applying the plasma aldosterone/plasma renin activity ratio (ARR) as a screening test have reported a higher prevalence. This study is a retrospective evaluation of the diagnosis of PA from clinical centers in five continents before and after the widespread use of the ARR as a screening test. The application of this strategy to a greater number of hypertensives led to a 5- to 15-fold increase in the identification of patients affected by PA. Only a small proportion of patients ( between 9 and 37%) were hypokalemic. The annual detection rate of aldosterone-producing adenoma (APA) increased in all centers ( by 1.3-6.3 times) after the wide application of ARR. Aldosterone-producing adenomas constituted a much higher proportion of patients with PA in the four centers that employed adrenal venous sampling ( 28 - 50%) than in the center that did not (9%). In conclusion, the wide use of the ARR as a screening test in hypertensive patients led to a marked increase in the detection rate of PA. Copyright © 2004 by The Endocrine Society

Either interleukin-12 or interferon-gamma can correct the dendritic cell defect induced by transforming growth factor beta(1) in patients with myeloma

The poor response to immunotherapy in patients with multiple myeloma (MM) indicates that a better understanding of any defects in the immune response in these patients is required before effective therapeutic strategies can be developed. Recently we reported that high potency (CMRF44(+)) dendritic cells (DC) in the peripheral blood of patients with MM failed to significantly up-regulate the expression of the B7 co-stimulatory molecules, CD80 and CD86, in response to an appropriate signal from soluble trimeric human CD40 ligand. This defect was caused by transforming growth factor beta(1) (TGFbeta(1)) and interleukin (IL)-10, produced by malignant plasma cells, and the defect was neutralized in vitro with anti-TGFbeta(1). As this defect could impact on immunotherapeutic strategies and may be a major cause of the failure of recent trials, it was important to identify a more clinically useful agent that could correct the defect in vivo. In this study of 59 MM patients, the relative and absolute numbers of blood DC were only significantly decreased in patients with stage III disease and CD80 up-regulation was reduced in both stage I and stage III. It was demonstrated that both IL-12 and interferon-gamma neutralized the failure to stimulate CD80 up-regulation by huCD40LT in vitro. IL-12 did not cause a change in the distribution of DC subsets that were predominantly myeloid (CD11c+ and CDw123-) suggesting that there would be a predominantly T-helper cell type response. The addition of IL-12 or interferon-gamma to future immunotherapy trials involving these patients should be considered.

Iron-rich intermetallic phases and their role in casting defect formation in hypoeutectic Al-Si alloys

Iron is the most common and detrimental impurity in aluminum casting alloys and has long been associated with an increase in casting defects. While the negative effects of iron are clear, the mechanism involved is not fully understood. It is generally believed to be associated with the formation of Fe-rich intermetallic phases. Many factors, including alloy composition, melt superheating, Sr modification, cooling, rate, and oxide bifilms, could play a role. In the present investigation, the interactions between iron and each individual element commonly present in aluminum casting alloys, were investigated using a combination of thermal analysis and interrupted quenching tests. The Fe-rich intermetallic phases were characterized using optical microscope, scanning electron microscope, and electron probe microanalysis (EPMA), and the results were compared with the predictions by Thermocalc. It was found that increasing the iron content changes the precipitation sequence of the beta phase, leading to the precipitation of coarse binary beta platelets at a higher temperature. In contrast, manganese, silicon, and strontium appear to suppress the coarse binary beta platelets, and Mn further promotes the formation of a more compact and less harmful a phase. They are therefore expected to reduce the negative effects of the phase. While reported in the literature, no effect of P on the amount of beta platelets was observed. Finally, attempts are made to correlate the Fe-rich intermetallic phases to the formation of casting defects. The role of the beta phase as a nucleation site for eutectic Si and the role of the oxide bifilms and AIP as a heterogeneous substrate of Fe intermetallics are also discussed.

Identifying health centers in Honduras infested with Rhodnius prolixus using the seroprevalence of Chagas disease in children younger than 13 years

The objective of this study is to determine if a Chagas disease protocol starting with a serological survey is as reliable at identifying insect-infested areas as one using the gold standard entomological survey. The study found that health center areas infested with Rhodnius prolixus were identified using a threshold seroprevalence of 0.1%. The serological survey took half the time and was 30% less expensive than the entomological survey. Developing countries with limited resources may find this strategy useful in combating Chagas disease. This strategy also identifies seropositive children, which facilitates their treatment.