A role for interleukin-6 in host defense against murine Chlamydia trachomatis infection

Interleukin-6-deficient (IL-6(-/-)) knockout mice had significantly increased Chlamydia trachomatis levels in lung tissue and increased mortality compared to B6129F2/J controls early after intranasal infection. Gamma interferon production and chlamydia-specific antibody levels were consistent with a decreased but reversible Th1-like response in IL-6(-/-) mice. IL-6 is needed for an optimal early host response to this infection.     

Pollutant transport during a regional O3-episode in the mid-Atlantic states

Ozone (O3) concentrations in the Baltimore-Washington (B-W) metropolitan area frequently exceed the National Ambient Air Quality Standard (NAAQS) in the summer months. The most extreme O3 events occur in multi-day high O3 episodes. These events can be regional in scale, with O3 concentrations exceeding the NAAQS at numerous locations along the eastern U.S. seaboard, and are typically associated with slow-moving or stagnant high pressure systems. In the B-W region, the most extreme events typically occur with surface high pressure overhead or just west of the region and an upper air high-pressure area (ridge) to the west or northwest. Besides providing conditions conductive to local O3 production (subsidence and strong low-level inversions, weak horizontal winds, little cloud cover), this weather pattern may also result in transport of O3 and its precursors from heavily industrialized areas west and north of the B-W region. In this paper, observations and back trajectories made during the severe regional O3 event of July 12-15, 1995, are used to confirm the hypothesis that significant regional-scale transport of O3 and its precursors occur during extreme O3 events of the standard type in the B-W area.     

Frame slippage verification in stereotactic radiosurgery

PURPOSE: To develop a method for detecting frame slippage in stereotactic radiosurgery by interactively matching in three dimensions Digitally Reconstructed Radiographs (DRRs) to portal images. METHODS AND MATERIALS: DRRs are superimposed over orthogonal edge-detected portal image pairs obtained prior to treatment. By interactively manipulating the CT data in three dimensions (rotations and translations) new DRRs are generated and overlaid with the orthogonal portal images. This method of matching is able to account for ambiguities due to rotations and translations outside of the imaging plane. The matching procedure is performed with anatomical structures, and is used in tandem with a fiducial marker array attached to the stereotactic frame. The method is evaluated using portal images simulated from patient CT data and then tested using a radiographic head phantom. RESULTS: For simulation tests a mean radial alignment error of 0.82 mm was obtained with the 3D matching method compared to a mean error of 3.52 mm when using conventional matching techniques. For the head phantom tests the mean alignment displacement error for each of the stereotactic coordinates was found to be delta(x) = 0.95 mm, delta(y) = 1.06 mm, delta(z) = 0.99 mm, with a mean error radial of 1.94 mm (SD = 0.61 mm). CONCLUSION: Results indicate that the accuracy of the system is appropriate for stereotactic radiosurgery, and is therefore an effective tool for verification of frame slippage.     

Elevated platelet factor 4 and beta-thromboglobulin plasma levels in depressed patients with ischemic heart disease

Clinical depression has recently been recognized as an independent risk factor for cardiac mortality in patients after myocardial infarction. The underlying mechanisms of this increased mortality remain unclear. This study investigated the hypothesis that patients suffering from ischemic heart disease (IHD) and depression concurrently may have abnormal platelet activation resulting in an increased risk of thrombosis. Platelet factor 4 (PF4) and beta-thromboglobulin (beta-TG) were measured in young healthy control subjects, in nondepressed patients with IHD, and in depressed patients with IHD. Mean PF4 and beta-TG plasma levels in the IHD group with depression were found to be significantly higher than those of the control and IHD groups. This increase was not related to age, gender, racial difference, aspirin use, or severity of cardiac disease. This finding suggests that in depressed patients with IHD there is greater platelet activation, and may indicate an increased risk of thrombotic complications.     

Electrophysiological indices of information processing in methylphenidate responders

Event-related potential (ERP) studies report that the positive deflection following stimulus evaluation at 300 msec (P3) in hyperactive children is augmented by methylphenidate (MP). This study investigates P3 and preceding ERP components using an auditory oddball task in attention-deficit hyperactivity disorder (ADHD). Mismatch negativity, negativity at 100 and 200 msec, and positivity at 200 msec and 300 msec (P3) were obtained from 14 control and hyperkinetic children. ADHD children who responded to MP were tested on two separate days while receiving either MP or placebo. Controls were tested once. No differences were found between groups for ERP components preceding P3. P3 amplitude was significantly larger under MP than under placebo, but did not differ from controls. Under MP, differences in P3 amplitude unexpectedly occurred when no response was required. A P3 amplitude increase under MP and the unexpected P3 suggest that MP affects attention regulation.     

Lung density for assessment of hydration status in hemodialysis patients using the computed tomographic densitometry technique

The density of the lung reflects the total mass of fluid, air, and dry lung tissue per unit volume of the lung. Lung density can be measured by evaluation of attenuation of an electron beam with computed tomography (CT). This technique has been shown to be sufficiently reliable and sensitive to distinguish normal from abnormal lung water. The aim of this study was to find out whether lung density properly reflects the hydration status in hemodialysis patients in comparison with other standard methods. Fourteen hemodialysis patients, with an ultrafiltration ranging from 0.3 to 4.5 liters per session, underwent CT measurements of lung density, ultrasonographic measurements of the diameter of the inferior vena cava after quiet expiration (IVCe) and quiet inspiration (IVCi), and measurements of the hematocrit and plasma levels of the biochemical hydration markers cyclic guanosine monophosphate (cGMP) and atrial natriuretic peptide (ANP). These measurements were performed before and 3.5 to 4 hours after termination of dialysis. Quantitative estimates of lung density were obtained within pixels with CT numbers ranging between -1000 and -100 Hounsfield Units (HU), and compared with normal data from 18 normal controls. In normal controls, the lung density ranged from -800 to -730 HU. In hemodialysis patients, lung density was significantly higher than normal before dialysis (-678 +/- 96 HU, P < 0.01) and significantly decreased after dialysis (-706 +/- 92 HU, P < 0.05), indicating a decrease in fluid content of the lung. The density was normalized in 5 patients. A significant correlation was found between lung density and IVCe both before and after dialysis (r = 0.8, P < 0.01 for both). Change in density was significantly correlated to amount of ultrafiltration (r = 0.67, P < 0.01) and percent change in blood volume (r = 0.63, P < 0.05), indicating that lung density is greatly affected by changes in the extracellular fluid volume, mainly the intravascular volume. In conclusion, lung water reflects the hydration status in hemodialysis patients and can be monitored by measuring the lung density by CT. Accordingly, normalization of lung density can help to achieve a proper dry weight in these patients.     

Chimeric analysis of fibroblast growth factor receptor-1 (Fgfr1) function: a role for FGFR1 in morphogenetic movement through the primitive streak

Fibroblast growth factor (FGF) signaling has been implicated in the patterning of mesoderm and neural lineages during early vertebrate development. In the mouse, FGF receptor-1 (FGFR1) is expressed in an appropriate spatial and temporal manner to be orchestrating these functions. Mouse embryos homozygous for a mutated Fgfr1 allele (fgfr1(delta tmk)) die early in development, show abnormal growth and aberrant mesodermal patterning. We have performed a chimeric analysis to further study FGFR1 function in the morphogenesis and patterning of the mesodermal germ layer at gastrulation. At E9.5, fgfr1(delta tmk)/fgfr1(delta tmk) cells showed a marked deficiency in their ability to contribute to the extra-embryonic, cephalic, heart, axial and paraxial mesoderm, and to the endoderm of chimeric embryos. Analysis at earlier stages of development revealed that fgfr1(delta tmk)/fgfr1(delta tmk) cells accumulated within the primitive streak of chimeric embryos, and consequently failed to populate the anterior mesoderm and endodermal lineages at their inception. We suggest that the primary defect associated with the fgfr1(delta tmk) mutation is a deficiency in the ability of epiblast cells to traverse the primitive streak. fgfr1(delta tmk)/fgfr1(delta tmk) cells that accumulated within the primitive streak of chimeric embryos tended to form secondary neural tubes. These secondary neural tubes were entirely fgfr1(delta tmk)/fgfr1(delta tmk) cell derived. The adoption of ectopic neural fate suggests that normal morphogenetic movement through the streak is essential not only for proper mesodermal patterning but also for correct determination of mesodermal/neurectodermal cell fates.     

A dose-dependent increase in mortality with vesnarinone among patients with severe heart failure. Vesnarinone Trial Investigators

BACKGROUND: Vesnarinone, an inotropic drug, was shown in a short-term placebo-controlled trial to improve survival markedly in patients with severe heart failure when given at a dose of 60 mg per day, but there was a trend toward an adverse effect on survival when the dose was 120 mg per day. In a longer-term study, we evaluated the effects of daily doses of 60 mg or 30 mg of vesnarinone, as compared with placebo, on mortality and morbidity. METHODS: We enrolled 3833 patients who had symptoms of New York Heart Association class III or IV heart failure and a left ventricular ejection fraction of 30 percent or less despite optimal treatment. The mean follow-up was 286 days. RESULTS: There were significantly fewer deaths in the placebo group (242 deaths, or 18.9 percent) than in the 60-mg vesnarinone group (292 deaths, or 22.9 percent) and longer survival (P=0.02). The increase in mortality with vesnarinone was attributed to an increase in sudden death, presumed to be due to arrhythmia. The quality of life had improved significantly more in the 60-mg vesnarinone group than in the placebo group at 8 weeks (P<0.001) and 16 weeks (P=0.003) after randomization. Trends in mortality and in measures of the quality of life in the 30-mg vesnarinone group were similar to those in the 60-mg group but not significantly different from those in the placebo group. Agranulocytosis occurred in 1.2 percent of the patients given 60 mg of vesnarinone per day and 0.2 percent of those given 30 mg of vesnarinone. CONCLUSIONS: Vesnarinone is associated with a dose-dependent increase in mortality among patients with severe heart failure, an increase that is probably related to an increase in deaths due to arrhythmia. A short-term benefit in terms of the quality of life raises issues about the appropriate therapeutic goal in treating heart failure.