Myeloperoxidase-dependent generation of hypochlorite-modified proteins in human placental tissues during normal pregnancy

Myeloperoxidase (MPO), which is released from cytoplasmic granules of activated phagocytes by a degranulation process, reacts with H(2)O(2) (generated during the oxidative burst) and chloride ions to generate hypochlorous acid/hypochlorite (HOCl/OCl(-)). HOCl, a strong oxidant, in turn reacts with proteins to form HOCl-modified proteins. The presence of these cytotoxic chloramines during inflammatory conditions, eg, atherosclerosis and glomerular and tubulointerstitial injury, suggested that chloramines are powerful oxidants that can have profound biologic effects. In the present study, immunoreactive MPO was identified in fetal membranes and the basal plate and in maternal and fetal blood cells of human placental tissues. Monocytes/macrophages represent the major cell source for MPO in human placental tissues. Immunohistochemical findings revealed that HOCl-modified proteins are present in normal human term placenta but not during the first trimester of pregnancy (Weeks 7 to 12). HOCl-modified proteins were localized in areas formed by fetally derived cells as well as maternal decidual tissues, ie, areas where fetal extravillous trophoblast cells invade the maternal tissue and stimulate the maternal immune system. HOCl-modified proteins, products of the MPO-H(2)O(2)-chloride system in vivo, were not present intracellularly, but immunoreactivity for HOCl-modified proteins was cell-associated and/or present in the extracellular matrix. Extravillous trophoblast cells, which may also exert phagocytic activities, showed no intracellular immunoreactivity for MPO or HOCl-modified proteins. The present findings indicate that the generation of HOCl-modified proteins during normal pregnancy is a physiologic rather than a pathophysiologic process.     

Quantitative reflection spectroscopy at the human ocular fundus

A new model of the reflection of the human ocular fundus on the basis of the adding-doubling method, an approximate solution of the radiative transport equation, is described. This model enables the calculation of the concentrations of xanthophyll in the retina, of melanin in the retinal pigment epithelium and the choroid, and of haemoglobin in the choroid from fundus reflection spectra. The concentration values found in 12 healthy subjects are in excellent agreement with published data. In individual cases of pathologic fundus alterations, possible benefits to the ophthalmologic diagnostics are demonstrated.     

In vivo efficacy of bone-marrow-coated polycaprolactone scaffolds for the reconstruction of orbital defects in the pig

Alloplastic materials offer a number of advantages over bone autografts in the reconstruction of craniofacial defects. These include: lack of donor site morbidity, unlimited quantities of available material, and the possibility to conform exactly to the defect. An ideal bioresorbable material would degrade slowly, and have osteoconductive properties to allow replacement and remodeling by osseous tissue. This is seldom observed, the materials instead being replaced by fibrous tissue. Polycaprolactone (PCL), an FDA-approved bioresorbable polymer, has several properties that might make it suitable for reconstruction of craniofacial defects. The technique of fused deposition modeling (FDM) allows for the fabrication of highly reproducible bioresorbable 3D scaffolds. The nature of the fully interconnected pore network might enhance vascular ingrowth and osteoconductive properties. It was hypothesized that coating the scaffolds in bone marrow might enhance bone formation due to the osteoinductive nature of the bone-marrow mesenchymal cells. This study aimed to test these hypotheses in the pig model. Defects measuring 2 x 2 cm were surgically created in each orbit of eight Yorkshire pigs. The orbits were divided into three groups: Group 1 (n=4), no reconstruction (control); Group 2 (n=6), reconstruction with no coated PCL scaffolds; and Group 3 (n=6) reconstruction with bone-marrow-coated PCL scaffolds. The results were evaluated at 3 months by histological and histomorphometric analyses. The defects in Group 1 were covered with fibrous scar tissue. The shape of the reconstructed area was insufficient. The defects in Groups 2 and 3 were reconstructed correctly. In Group 2 the noncoated scaffolds showed 4.5% of new bone formation compared with 14.1% in Group 3, which is statistically significant (p<0.05). The entirely interconnected 3D polycaprolactone scaffold seems to be a promising material. It induces the bone ingrowth required for reconstructing craniofacial and orbital defects. Further long-term evaluations of these PCL scaffolds must be made in order to confirm these conclusions.     

Stabilities of free and complexed human immunodeficiency virus p24 antigens during short- and long-term storage.

By the standard p24 assay there was a 25 to 27% decrease in free p24 antigen in serum after storage at 4 degrees C over 14 days but no loss at -70 degrees C. There was no loss at either temperature by the immune complex dissociation (ICD) procedure. Furthermore, there was no significant loss of detectable p24 in serum by either the ICD or the standard p24 assay after 700 days of storage at -70 degrees C.     

A comparison of postoperative respiratory complications associated with the use of desflurane and sevoflurane: a single-centre cohort study

Sevoflurane and desflurane are the most commonly used volatile anaesthetics for maintenance of anaesthesia. In this study, we aimed to evaluate the relationship between choice of volatile anaesthetic and early postoperative respiratory complications, and to address a critical knowledge gap in safety outcomes between these two commonly used agents. We performed a retrospective analysis of adult (non-cardiac surgery) patients who received sevoflurane or desflurane for the maintenance of general anaesthesia at our institution between 2005 and 2018. We evaluated the association between desflurane exposure (when compared with sevoflurane) and the primary outcome of postoperative respiratory complications, defined by early post-extubation desaturation (S_pO₂ < 90%) or re-intubation within 7 days postoperatively. Multivariable regression analyses were performed and adjusted for confounding factors, including patient, anaesthetic and surgical factors. Propensity matched, interaction and sub-group analyses were performed to assess outcomes in high-risk groups: morbidly obese (BMI > 35 kg.m⁻²); elderly (age > 65 years); and high risk of respiratory complications as well as the primary outcome at 24 h. Desflurane was used for 23,830 patients and sevoflurane for 84,608 patients. Patients exposed to desflurane did not demonstrate a reduced risk of postoperative respiratory complications when compared with sevoflurane (adjusted odds ratio 0.99, 95%CI 0.94–1.04, p = 0.598). These findings were consistent across all sub-groups of high-risk patients and in the propensity score matched cohort. In summary, desflurane use was not associated with reduced postoperative respiratory complications when compared with sevoflurane. In the context of environmental and cost concerns with volatile anaesthetic agents, our study provides important data to support organisational decisions regarding the use of desflurane.     

Organ-preference of metastasis

Summary The initial, site-specific colonization of secondary organs by blood-borne cancer cells appears to be mediated by endothelial cell adhesion molecules. These molecules are part of the organ-specific microvascular phenotype and are regulated through complex interactions of the endothelium with the extracellular matrix (e.g., distinct matrix macromolecules and growth factors). They are inducedin vitro by growing unspecific (large vessel) endothelial cells on extracts of organ-specific biomatrices. In many respects, these molecules are similar to the various classes of chemically different adhesion molecules that regulate lymphocyte traffic, but are believed to be distinct from the inducible adhesion molecules that govern leukocyte adhesion during acute episodes of inflammation. Biochemical and biophysical data indicate that preference of tumor cell adhesion to organ-specific microvascular endothelium may not require qualitative differences of such homing receptors between endothelia, but may be explained on the basis of quantitative receptor differences as well as differences of receptor avidity. Following adhesion, the metastatic cascade proceeds by the establishment of metabolic conduits between the endothelium and adherent tumor cells. This heterotypic coupling represents an early step in the extravasation of cancer cells from the microvasculature, initiating endothelial cell retraction from its basement membrane and recanalization around the arrested tumor cell. These events, together with local growth promoting effects exerted by the metastasized organ, are believed to provide the basis for Paget's seed and soil hypothesis of metastasis.     

Ends and means in public health policy in developing countries

International discussions of public health policy strategies in developing countries have been characterized by strong and conflicting positions. Differences regarding the means of health sector improvement can often be traced to differences about the ends, that is, the goals of the health sector. Three types of health sector goals are reviewed: health status improvement, equity and poverty alleviation, and individual welfare (utility) improvement. The paper argues that all three must be considered in developing health sector reform strategies in all countries. Highly normative policy positions often can be attributed a unidimensional affiliation with one health sector goal and denial of the relevance of the others. The current global interest in using cost-effectiveness analysis to set national health priorities is assessed in light of this eclectic approach. Examples are provided of how a health sector strategy based on cost-effectiveness would give sub-optimal solutions. These examples include situations where a private health care sector exists and provides some degree of substitution for publicly provided services; significantly high income elasticities exist for health care such that higher income beneficiaries may differentially capture public subsidies; and market failures exist in insurance. It is argued that these conditions are virtually universal in developing countries. Thus, rational policy development should explicitly consider multiple goals for the health sector.     

Impfentwicklungsland Deutschland? Ärzte- und Patientenbefragungen zum Thema Impfen gelangen zu widersprüchlichen Ergebnissen

Zusammenfassung Praktische ?rzte und Internisten empfinden die Impfsituation in Deutschland zum Gro?teil als unbefriedigend. Obwohl sie sich selbst die wichtigste Rolle beim Impfen zuschreiben, sehen sie die Ursachen für die niedrigen Impfzahlen vor allem in der Unwissenheit bei den Patienten, in der Angst vor der Spritze und in mangelhafter Compliance und Kontrolle. Um zu einem verbesserten Impfverhalten zu kommen, setzen die ?rzte vorwiegend auf positive Informationen in den Medien, aber auch auf die Kontrolle durch Beh?rden und Krankenkassen sowie die bessere Integration des Impfens in die Praxisorganisation. So lauten im Kern die Ergebnisse einer Untersuchung, die das Marktforschungsinstitut „Resultate” in Neu-Isenburg im Auftrag des Impfstoffherstellers Chiron Behring durchgeführt hat. Im Vergleich zu den Daten einer repr?sentativen Patientenumfrage von 1995 lassen sich übereinstimmungen finden: Tats?chlich sind die meisten Patienten schlecht informiert, insbesondere über die Notwendigkeit von Auffrischimpfungen. Ein Drittel der Befragten besitzt keinen Impfausweis, wodurch die Kontrolle erschwert wird. Im Gegensatz zu den Annahmen der ?rzte existiert jedoch eine hohe Impfbereitschaft, w?hrend Angst kaum ein Impfhindernis darstellt. Für die überwiegende Mehrheit der Patienten ist der Arzt der erste Ansprechpartner bei Impffragen.