Novel computed tomographic chest metrics to detect pulmonary hypertension

Background  

Early diagnosis of pulmonary hypertension (PH) can potentially improve survival and quality of life. Detecting PH using echocardiography is often insensitive in subjects with lung fibrosis or hyperinflation. Right heart catheterization (RHC) for the diagnosis of PH adds risk and expense due to its invasive nature. Pre-defined measurements utilizing computed tomography (CT) of the chest may be an alternative non-invasive method of detecting PH.     

The scavenger receptor MARCO mediates cytoskeleton rearrangements in dendritic cells and microglia

Macrophage receptor with collagenous structure (MARCO) is a scavenger receptor expressed in peritoneal macrophages and in a subpopulation of macrophages in the marginal zone of the spleen and in the medullary cord of lymph nodes. By global gene expression analysis, it has been found that the MARCO mRNA was one of the most up-regulated in splenic dendritic cells (DCs) following lipopolysaccharide or bacterial activation and in granulocyte-macrophage colony-stimulating factor (GM-CSF)-treated microglial cells. Here we show that MARCO is expressed on splenic DCs at late time points after activation and that its expression correlates with profound changes in actin cytoskeleton organization in DCs and microglia. During maturation, DCs undergo profound rearrangements of actin cytoskeleton. Immature DCs are adherent with visible actin cables, while fully mature, MARCO-expressing, splenic DCs are nonadherent, round in shape, and have an actin cytoskeleton with a punctate distribution. The simple expression of MARCO was sufficient to induce these cytoskeleton modifications in DCs. MARCO-transfected immature DCs acquired a typical morphology of mature DCs and did not rearrange the actin cytoskeleton following activation. Moreover, DCs in which MARCO was knocked down did not reach the mature phenotype and maintained the typical morphology of transitional DCs. MARCO expression in DCs and microglial cells was also associated with a decrease of antigen internalization capacity. Thus, the MARCO receptor is important for actin cytoskeleton rearrangements and the down-regulation of antigen uptake function during DC and microglial cell maturation.     

Chagas disease in rural areas of Chaco Province, Argentina: epidemiologic survey in humans, reservoirs, and vectors

We studied the seroprevalence of antibodies against Trypanosoma cruzi in the human population along with domiciliary infestation by triatomine bugs in an area endemic for Chagas disease in the Chaco Province of Argentina. In addition, we carried out parasitologic surveys in patients, dogs, wild mammals, and vectors. The mean seroprevalence in humans was 27.81% (109 of 392) and 24.14% (63 of 261) in 1-15-year-old children. The minimum domiciliary infestation rate was 13.33%, with certain areas reaching 53.85%. The prevalence was 15.09% (16 of 106) in dogs and 35.71% (10 of 28) in opossums. Infection with T. cruzi was detected in 30.10% (59 of 196) of the Triatoma infestans tested. Compared with nationwide studies, our data suggest that 1) there are zones requiring immediate sanitary action, and 2) nationwide estimates are based on very heterogeneous epidemiologic situations. This heterogeneity emphasizes the importance of in-depth studies of restricted areas to provide additional information for a better understanding of the present status of Chagas disease in Argentina.     

Induction and treatment of anergy in murine leprosy

Leprosy is a disease consisting of a spectrum of clinical, bacteriological, histopathological and immunological manifestations. Tuberculoid leprosy is frequently recognized as the benign polar form of the disease, while lepromatous leprosy is regarded as the malignant form. The different forms of leprosy depend on the genetic and immunological characteristics of the patient and on the characteristics of the leprosy bacillus. The malignant manifestations of lepromatous leprosy result from the mycobacterial‐specific anergy that develops in this form of the disease. Using murine leprosy as a model of anergy in this study, we first induced the development of anergy to Mycobacterium lepraemurium (MLM) in mice and then attempted to reverse it by the administration of dialysable leucocyte extracts (DLE) prepared from healthy (HLT), BCG‐inoculated and MLM‐inoculated mice. Mice inoculated with either MLM or BCG developed a robust cell‐mediated immune response (CMI) that was temporary in the MLM‐inoculated group and long‐lasting in the BCG‐inoculated group. DLE were prepared from the spleens of MLM‐ and BCG‐inoculated mice at the peak of CMI. Independent MLM intradermally‐inoculated groups were treated every other day with HLT‐DLE, BCG‐DLE or MLM‐DLE, and the effect was documented for 98 days. DLE administered at a dose of 1.0 U (1 × 10⁶ splenocytes) did not affect the evolution of leprosy, while DLE given at a dose of 0.1 U showed beneficial effects regardless of the DLE source. The dose but not the specificity of DLE was the determining factor for reversing anergy.     

A Novel Approach to Improving Fat Delivery in Neonatal Enteral Feeding

Continuous infusion systems used for enteral nutrition support in the neonatal intensive care unit deliver as little as 60% of the fat in human milk to the neonate. This study determined the effect of mixing common feedings for preterm infants in the feeding bag and tubing on fat losses during enteral feeding. Laboratory models were developed to assess the contribution of various mixing techniques to delivered fat content. Fat content was measured periodically during feeding and compared to baseline measurements. A multistage approach incorporating a feeding bag inverter and a tubing circulation loop delivered >90% of milk fat when used in conjunction with a commercial continuous infusion system. With unfortified human milk, this approach delivered 91.9% ± 1.5% of fat content over a one hour feed, significantly greater (p < 0.01) than 77.5% ± 2.2% delivered by continuous infusion controls (Mean ± SEM). With fortified human milk, this approach delivered 92.1% ± 2.4% of fat content, significantly greater (p < 0.01) than 79.4% ± 1.0% delivered by a non-adapted infusion system (Mean ± SEM). Mixing human milk during continuous infusion improves fat delivery, which may improve nutrition and growth outcomes in low birth weight neonates.     

Relation of quantitative coronary lesion measurements to the development of exercise-induced ischemia assessed by exercise echocardiography

To assess the relation of quantitative measures of coronary stenoses to the development of exercise-induced regional wall motion abnormalities, 34 patients with isolated, single vessel coronary artery lesions and normal wall motion at rest underwent exercise echocardiography and quantitative angiography on the same day. Although all 11 patients with a visually estimated stenosis greater than or equal to 75% had an ischemic response and 10 (91%) of 11 patients with a less than or equal to 25% visually estimated stenosis had a normal response by exercise echocardiography, among 12 patients with a visually estimated stenosis of 50%, 6 (50%) had an ischemic response and 6 (50%) had a normal exercise echocardiogram. Quantitative measurements of stenosis severity distinguished patients with ischemic (group 1) from normal (group 2) exercise echocardiographic responses as follows: minimal luminal diameter (mm), group 1 1.0 +/- 0.4 versus group 2 1.7 +/- 0.4, p less than 0.0001; minimal cross-sectional area (mm2), group 1 0.9 +/- 0.6 versus group 2 2.5 +/- 1.1, p less than 0.0001; percent diameter stenosis, group 1 68.3 +/- 14.2 versus group 2 42.2 +/- 12.1, p less than 0.0001; and percent area stenosis, group 1 87.5 +/- 7.8 versus group 2 64.8 +/- 15.9, p less than 0.0001. These data validate the utility of exercise echocardiography by demonstrating that 1) coronary stenosis severity measured by quantitative angiography is closely related to wall motion abnormalities detected by exercise echocardiography, and 2) exercise echocardiography can be used as a noninvasive means to assess the physiologic significance of coronary artery lesions.     

Characterization of the antigen reactive with anti-Scl-70 antibodies and its application in an enzyme-linked immunosorbent assay

The characteristics of the Scl-70 antigen (topoisomerase I) have been analyzed by means of autoantibodies. This antigen is a DNA-binding protein, dissociable from DNA at 0.3M NaCl and bound to a fraction of DNA that is very sensitive to nucleases. The molecular weight of the antigen is 105,000 daltons, whether dissociation conditions are used or not. Using chicken erythrocytes, and taking advantage of the strong interaction of the antigen with hydroxyapatite, we have designed a simple and fast purification protocol that allows the determination of anti-topoisomerase I antibodies by enzyme-linked immunosorbent assay.     

The isolation and molecular characterization of Leishmania spp. from patients with American tegumentary leishmaniasis in northwest Argentina

American tegumentary leishmaniasis (ATL) is a group of zoonotic diseases caused by kinetoplastid flagellates of the genus Leishmania. A total of 66 patients diagnosed as positive ATL cases from northwest Argentina were included in this study. Leishmania stocks were isolated in vitro and analyzed over promastigote cultures sown on FTA through nested PCR and sequence of cytochrome b (cyt b). The molecular analysis resulted in the incrimination of L. (Viannia) braziliensis as the predominant species in the studied area, identifying two genotypes of L. (V.) braziliensis, 24 cases of Ab-1 cyt b and 41 cases of Ab-2 cyt b. One L. (V.) guyanensis strain was obtained from a traveler from the Brazilian Amazon. The prevalence of different genotypes was in agreement with previous studies, suggesting the necessity for new systems to study the genetic diversity in more detail. Most of the cases typified in this study were registered in the area of Zenta Valley (Orán, Hipólito Yrigoyen, and Pichanal cities), pointing a link between genotype and geographical origin of the sample. Sex and age distribution of the patients indicate that the transmission was predominantly associated with rural areas or rural activities, although the results might not exclude the possibility of peri-urban transmission. This work represents, so far, the largest isolation and molecular characterization of ATL cases in Argentina.