Biological constants in migrants

Until now, clinical chemists, clinicians, physicians dealing with the problem of migrant biology dispose only reference limits established for an autochtone population. But can these really be applied? We compared 28 blood constituents of a migrant population with those of the french population. We defined five geographic areas: Italy, the Iberian Peninsula, Northern Africa, Northern and Central Europe and the Near and Middle East.     

Air trapping: The major factor limiting diaphragm mobility in chronic obstructive pulmonary disease patients

Background and objective:   Patients with COPD can have impaired diaphragm mechanics. A new method of assessing the mobility of the diaphragm, using ultrasound, has recently been validated. This study evaluated the relationship between pulmonary function and diaphragm mobility, as well as that between respiratory muscle strength and diaphragm mobility, in COPD patients.
Methods:   COPD patients with pulmonary hyperinflation ( n  = 54) and healthy subjects ( n  = 20) were studied. Patients were tested for pulmonary function, maximal respiratory pressures and diaphragm mobility using ultrasound to measure the craniocaudal displacement of the left branch of the portal vein.
Results:   COPD patients had less diaphragm mobility than did healthy individuals (36.5 ± 10.9 mm vs 46.3 ± 9.5 mm, P  = 0.001). In COPD patients, diaphragm mobility correlated strongly with pulmonary function parameters that quantify air trapping (RV: r  = −0.60, P  < 0.001; RV/TLC: r  = −0.76, P  < 0.001), moderately with airway obstruction (FEV₁: r  = 0.55, P  < 0.001; airway resistance: r  = −0.32, P  = 0.02) and weakly with pulmonary hyperinflation (TLC: r  = −0.28, P  = 0.04). No relationship was observed between diaphragm mobility and respiratory muscle strength (maximal inspiratory pressure: r  = −0.11, P  = 0.43; maximal expiratory pressure: r  = 0.03, P  = 0.80).
Conclusion:   The results of this study suggest that the reduction in diaphragm mobility in COPD patients is mainly due to air trapping and is not influenced by respiratory muscle strength or pulmonary hyperinflation.     

Endothelial cells are activated by cytokine treatment to kill an intravascular parasite, Schistosoma mansoni, through the production of nitric oxide.

Like many pathogens that undergo an intravascular stage of development, larvae of the helminth parasite Schistosoma mansoni migrate through the blood vessels, where they are in close contact with endothelial cells. In vitro exposure of murine endothelial cells to various cytokines (interferon gamma, tumor necrosis factor alpha, and interleukin 1 alpha or 1 beta) resulted in their activation to kill schistosomula through an arginine-dependent mechanism involving production of nitric oxide (NO). Cytokine-treated endothelial cells showed increased expression of mRNA for the inducible form of the NO synthase, and both NO production and larval killing were suppressed by treatment with competitive inhibitors. The effector function of cytokine-treated endothelial cells was similar to that of activated inflammatory tissue macrophages, although activation appeared to be differentially regulated in these two cell types. Activated endothelial cells killed older (18-day) forms of the parasite, such as those currently thought to be a primary target of immune elimination in the lungs of mice previously vaccinated with radiation-attenuated cercariae, as well as newly transformed larvae. In C57BL/6 mice, which become resistant to S. mansoni infection as a result of vaccination with irradiated cercariae, endothelial cell morphology characteristic of activation was observed in the lung by 1-2 weeks after challenge infection. Similar endothelial cell changes were absent in P-strain mice, which do not become resistant as a result of vaccination. Together, these observations indicate that endothelial cells, not traditionally considered to be part of the immune system, may play an important role in immunity to S. mansoni and, by means of NO-dependent killing, could serve as effectors of resistance to other intravascular pathogens.     

Insulin-like growth factor-I receptors in nonfunctioning thyroid nodules

We have recently demonstrated the production of insulin-like growth factor-I (IGF-I) as well as the presence of type I IGF receptors in human thyroid cells in primary culture. The role of IGF-I in the control of thyroid cell growth has been well established. In order to investigate the involvement of IGF-I in abnormal thyroid growth, the density of IGF-I receptors in solitary, cold, micro- and macro-follicular thyroid adenomas, and in extranodular histological normal tissue was studied. Forty-three euthyroid patients with isolated cold nodules were selected for the study. In 30 patients the presence of IGF-I receptors was evaluated by using quantitative immunohistochemistry; in 10 patients by using radioligand binding studies, and in 3 patients by using affinity labeling. Cross-linking and binding studies clearly demonstrated the presence of a homogeneous class of binding sites for type I IGF receptors. Furthermore, radioligand studies did not show any significant differences in receptor density between the 2 types of thyroidal tissues. Conversely, the computerized analysis of 900 fields of nodular and normal thyroid tissues immunostained with the monoclonal antibody alpha-IR3, strongly indicated that higher concentrations of IGF-I receptors were present in the epithelial cells of non-functioning thyroid nodules than in the adjacent extranodular thyroid tissues. These studies strongly suggest that the same type I IGF receptor is present in thyroid follicular adenomas as in histological normal thyroid tissue removed from the same patient. The higher concentration of IGF-I receptors as documented by immunostaining in the adenomas suggests that IGF-I may contribute to the abnormal growth of the neoplasms.     

Intracoronary thallium-201 scintigraphy after thrombolytic therapy for acute myocardial infarction compared with 10 and 100 day intravenous thallium-201 scintigraphy

Thallium-201 imaging has been utilized to estimate myocardial salvage after thrombolytic therapy for acute myocardial infarction. However, results from recent animal studies have suggested that as a result of reactive hyperemia and delayed necrosis, thallium-201 imaging may overestimate myocardial salvage. To determine whether early overestimation of salvage occurs in humans, intracoronary thallium-201 scans 1 hour after thrombolytic therapy were compared with intravenous thallium-201 scans obtained approximately 10 and 100 days after myocardial infarction in 29 patients. In 10 patients with angiographic evidence of coronary reperfusion, immediate improvement in thallium defects and no interim clinical events, there was no change in imaging in the follow-up studies. Of nine patients with coronary reperfusion but no initial improvement of perfusion defects, none showed worsening of defects in the follow-up images. Six of these patients demonstrated subsequent improvement at either 10 or 100 days after infarction. Seven of 10 patients with neither early evidence of reperfusion nor improvement in perfusion defects had improvement of infarct-related perfusion defects, and none showed worsening. In conclusion, serial scanning at 10 and 100 days after infarction in patients with no subsequent clinical events showed no worsening of the perfusion image compared with images obtained in acute studies. Therefore, there is no evidence that thallium-201 imaging performed early in patients with acute myocardial infarction overestimates improvement.     

Evaluation of gene expression profiles in thyroid nodule biopsy material to diagnose thyroid cancer

CONTEXT: Detection of thyroid cancer among benign nodules on fine-needle aspiration biopsies (FNAB), which presently relies on cytological examination, is expected to be improved by new diagnostic tests set up from genomic data. OBJECTIVE: The aim of the study was to use a set of genes discriminating benign from malignant tumors, on the basis of their expression levels, to build tumor classifiers and evaluate their capacity to predict malignancy on FNAB. DESIGN: We analyzed the level of expression of 200 potentially informative genes in 56 thyroid tissue samples (benign or malignant tumors and paired normal tissue) using nylon macroarrays. Gene expression data were subjected to a weighted voting algorithm to generate tumor classifiers. The performances of the classifiers were evaluated on a series of 26 sham FNAB, i.e. FNAB carried out on thyroid nodules after surgical resection. RESULTS: A series of 19 genes with a similar expression in follicular adenomas and normal tissue and discriminating follicular adenomas+normal tissue from the following: 1) follicular thyroid carcinomas (FTCs), 2) papillary thyroid carcinomas (PTCs), or 3) both FTCs and PTCs. These were used to generate four classifiers, the FTCs, PTCs, common (FTC+PTCs), and global classifiers. In 23 of the 26 sham FNAB, the four classifiers yielded a diagnosis in agreement with the diagnosis of the pathologist used as reference; in the three other cases, the correct diagnosis was given by three of four classifiers. CONCLUSIONS: We developed a procedure of molecular diagnosis of benign vs. malignant tumors applicable to the material collected by FNAB. The molecular test complied with a preclinical validation stage; it must be now evaluated on ultrasound-guided FNAB in a large-scale prospective study.     

Low Prevalence Rate of Indeterminate Serological Human Immunodeficiency Virus Results among Pregnant Women from Burkina Faso,West Africa

Rapid human immunodeficiency virus (HIV) antibody tests have been adopted into national guidelines for HIV testing in many countries in sub-Saharan Africa. One goal of HIV rapid testing is to minimize the occurrence of indeterminate results. From January 2005 to December 2007, plasma (or serum) samples from pregnant women in Bobo-Dioulasso (Burkina Faso, West Africa) were screened for HIV by using two rapid tests (the Determine HIV1/2 test [Abbott] and Genie II HIV-1/HIV-2 [Bio-Rad]) through a sequential algorithm prior to enrollment of HIV-1-infected women in a prevention of mother-to-child transmission (PMTCT) trial (WHO/ANRS 1289 Kesho Bora trial). Samples exhibiting indeterminate results (Determine positive and Genie II negative) were further tested with a fourth-generation HIV enzyme immunoassay (EIA) (Murex HIV Ag/Ab combination in 2005 and 2006 and Vironostika HIV Uni-Form II Ag/Ab in 2007). If positive, they were finally assessed for HIV-1 RNA (Generic HIV-1 RNA viral load assay; Biocentric). From a total of 44,653 samples tested, 597 (1.3%) showed indeterminate results. Of these, 367 could be analyzed by EIA. Only 15 (15/367, 4.1%) samples were found EIA reactive. Of these, 11 could be tested for HIV-1 RNA. All were HIV-1 RNA negative. In our clinical practice, pregnant women with such indeterminate results are now reassured during posttest counseling that they are very unlikely to be infected with HIV-1. As a consequence, such women with indeterminate results can reliably be considered negative when urgent clinical decisions (such as providing PMTCT prophylaxis) need to be taken.In sub-Saharan Africa, rapid testing for human immunodeficiency virus (HIV) is the most efficient and sometimes the only feasible way to quickly provide information about HIV status among adults and children ≥18 months of age (6, 29). In contrast to enzyme immunoassays (EIAs) and Western blot assays (WBs), HIV rapid tests are relatively cheap, easy to use, and fast to perform. Most of them do not require refrigeration, sophisticated laboratory equipment, skilled technicians, and an electricity supply. Results from serum, plasma, whole-blood, urine, or saliva samples are obtained by visual reading after a few minutes. Some of the rapid tests can distinguish HIV type 1 (HIV-1) from HIV type 2 (HIV-2). They are also accurate and reliable as a result of applying a quality system approach recommended by the World Health Organization (WHO) (36). Due to their low cost and technical advantages, they have been adopted into national HIV voluntary counseling and testing (VCT) guidelines in many African countries. Their sensitivity and specificity have been studied in Kenya (12), Tanzania (22), Uganda (15), Zambia (30), South Africa (25), Cameroon (1), Central African Republic (24), Democratic Republic of Congo (19), Ghana (2), Ivory Coast (32), and Burkina Faso (23, 28).One objective for rapid HIV testing is to minimize the occurrence of indeterminate results (i.e., discordant results when using at least two different rapid tests). It is often quite difficult for HIV counselors and health care providers to disclose such indeterminate results. In the context of interventions for prevention of mother-to-child transmission (PMTCT) of HIV-1 (which can require immediate decisions, notably during labor), medical staff need to know rapidly the HIV status of the woman from the laboratory in order to provide her, or not, antiretroviral (ARV) prophylaxis (5, 26, 27). The prolonged delay in the decision (by performing additional tests or by retesting women 14 days later) can be inappropriate in the clinical routine since women may deliver before obtaining definitive results.The aims of this study conducted among pregnant women from Burkina Faso (West Africa) with a low risk of early HIV-1 seroconversion were (i) to determine the prevalence rates of indeterminate results by using two rapid tests in a sequential algorithm, as recommended in Burkina Faso, and (ii) to assess, using additional tests, the biological significance of indeterminate results in order to define a more rational strategy at the individual and public health levels.(This work was presented in part at the 15th Conference on AIDS and STDs in Africa, Dakar, Senegal, 3 to 7 December 2008 [17].)