Circulating tuberculostearic acid in tuberculosis patients

Tuberculostearic acid (TBSA), a mycobacterial cell wall constituent, was measured in plasma samples using a highly sensitive high-performance liquid chromatography method. Plasma TBSA concentrations in patients with active tuberculosis (20 [0.5-347] nmol/l; n = 125) were higher than in patients with a variety of non-tuberculous pulmonary and extrapulmonary inflammatory conditions (0.1 [0-29] nmol/l; n = 116) and in healthy controls (0 [0-2] nmol/l; n = 102) (p = < 0.001). The calculated sensitivity, specificity, positive and negative predictive values for tuberculosis were 95.2%, 87.9%, 89.5% and 94.4%, respectively, indicating that assay of plasma TBSA might be a valuable complementary diagnostic tool.     

Inhibition of Desmoteplase-Induced Fibrinolytic Activity In Vitro

Introduction. Laboratory monitoring of the hemostatic system during thrombolytic therapy requires that the fibrinolytic activity generated in vivo be immediately inhibited at blood collection in order to prevent artificial results as a consequence of degradation of clotting proteins. For most thrombolytic drugs efficient inhibitors have been described, but not yet for the new thrombolytic agent, desmoteplase, which is vampire bat salivary plasminogen activator. Therefore, we investigated the effect of aprotinin and D-Phe-Pro-Arg-chloromethylketone (PPACK) on desmoteplase-induced fibrinolysis.Materials and methods. We added desmoteplase in pharmacological concentrations to blood samples supplemented with aprotinin, PPACK or both. Fibrinolytic activity was assessed by measuring degradation products of fibrin and fibrinogen, plasmin-antiplasmin complex, thrombin-antithrombin complex, fibrinogen and some overall clotting assays.Results. Desmoteplase caused in vitro activation of plasminogen with concomitant degradation of fibrin and fibrinogen. Aprotinin completely inhibited these effects, whereas PPACK gave only partial inhibition. Neither inhibitor prevented plasminogen activation and thus significant generation of plasmin-antiplasmin complex was observed.Conclusion. Blood collection for hemostatic analyses in clinical studies with desmoteplase requires addition of aprotinin (final concentration 250 KIU/mL) in order to prevent in vitro artifacts.     

Isolated femoral hypoplasia: an intrauterine differential diagnosis to campomelia

The isolated form of femoral bowing is an important differential diagnosis of campomelia. Therefore, knowledge of isolated anomalies is fundamental for prenatal diagnosis, especially for the differential diagnosis from severe syndromes. Four cases are presented to discuss the differential diagnosis of femoral bowing including a review of the literature. We report four newborn babies with unilateral bowing and shortening of the femur. Three had no further anomaly; one child had additional abnormalities due to coumarin embryopathy. The radiological findings were shortened femora with bowing and varus deformity and cortical thickening on the concave side. All other parts showed normal bone structure. The aetiology of femoral bowing is unknown. Early damage of the cartilaginous model followed by remodelling with thickening on the concave side of the bone similar to the healing of malaligned fractures is suspected. The isolated form of femoral bowing without any other anomalies has to be differentiated from complex and more often severe congenital syndromes such as campomelia. Postpartum radiological examination should be reduced to a single exposure of the affected limb and follow-up should be done by clinical examination.     

Mid- to late-Holocene El Nino-Southern Oscillation dynamics reflected in the subtropical terrestrial realm

High resolution pollen analysis of mid- to late-Holocene peat deposits from southwest Florida reveals a stepwise increase in wetland vegetation that points to an increased precipitation-driven fresh water flow during the past 5,000 years. The tight coupling between winter precipitation patterns in Florida and the strength of the El Ni?o-Southern Oscillation (ENSO) strongly suggests that the paleo-hydrology record reflects changes in ENSO intensity. A terrestrial subtropical record outside the Indo Pacific Warm Pool both documents ecosystem response to the known onset of modern-day ENSO periodicities, between approximately 7,000 and 5,000 years B.P., and subsequent ENSO intensification after 3,500 years B.P. The observed increases in "wetness" are sustained by a gradual rise in relative sea level that prevents a return to drier vegetation through natural succession.     

Virus-delivered small RNA silencing sustains strength in amyotrophic lateral sclerosis

Mutations in superoxide dismutase cause a subset of familial amyotrophic lateral sclerosis and provoke progressive paralysis when expressed in mice. After retrograde transport to the spinal cord following injection into muscles, an adeno-associated virus carrying a gene that encodes a small interfering RNA was shown to target superoxide dismutase messenger RNA for degradation. The corresponding decrease in mutant superoxide dismutase in spinal motor neurons preserved grip strength. This finding provides proof of principle for the selective reduction of any neuronal protein and supports intramuscular injections of a small interfering RNA-encoding virus as a viable therapy for this type of familial amyotrophic lateral sclerosis.     

Characterization of small nodules by automatic segmentation of X-ray computed tomography images

OBJECTIVE: To characterize the ability of an automatic lung nodule segmentation algorithm to measure small nodule dimensions and growth rates. METHODS: A phantom of 20 sets of 6 balls each (11 different nylon balls and 9 acrylic balls) of 1 to 9.5 mm in diameter, in foam, was imaged using x-ray computed tomography with slice thicknesses of 5, 2.5, and 1.25 mm, pitches of 3 and 6, and standard and lung resolution. Measurements consisted of volume and maximum in-plane cross-sectional areas and their derived maximum and effective diameters. Growth rates were simulated using pairs of groups of balls. RESULTS: Volume measurements overestimate volume, more so for thicker slices. For the largest balls, the error is 60% for 5-mm slices and 20% for 1.25-mm slices. Effective diameter calculated from volume better approximates actual diameter. For area measurements, errors are 0% to 5% for the largest balls, and the effective and actual diameters are closely matched. CONCLUSIONS: Below 5 mm in diameter, changes in volume should reach 100% for reliable indication of growth. Above 6 mm, the threshold for detecting change is on the order of 25% growth. Even under ideal conditions, results indicate the need for caution when making a diagnosis of malignancy on the basis of volume change.