Amniotic air insufflation during minimally invasive fetoscopic fetal cardiac interventions is safe for the fetal brain in sheep

BACKGROUND: Amniotic air insufflation during experimental fetoscopic fetal cardiac interventions greatly improves the visualization of intra-amniotic contents. The purpose of this study was to assess any histologically discernible effects from this approach on the fetal brain after short-term studies and long-term survival in sheep. METHODS: Thirty pregnant ewes between 80 and 110 days of gestation underwent amniotic air insufflation during various fetoscopic fetal cardiac interventions. After 18 short-term and 12 long-term studies, the brains of the operated fetuses and-if available-their unoperated siblings were examined for hemorrhage, embolism, infarctions, inflammatory changes, and abnormal cortical maturation. RESULTS: Amniotic air insufflation during minimally invasive fetoscopic fetal cardiac interventions did not result in any histologically discernible damage to the brain in short-term and long-term studies in any but 2 sibling sheep. In the 2 affected siblings, a small area of chronic cortical frontal lobe infarction was observed after long-term survival. CONCLUSIONS: Amniotic air insufflation during minimally invasive percutaneous fetoscopic fetal cardiac interventions is safe for the fetal brain and does not compromise maternal hemodynamics in sheep. These findings encourage further investigation of the role this technique might play during fetoscopic fetal cardiac interventions in humans.     

Characterization of plasminogen variants in healthy subjects and plasminogen mutants in patients with inherited plasminogen deficiency by isoelectric focusing gel electrophoresis

Plasmin(ogen) plays an important role in fibrinolysis and wound healing. Severe hypoplasminogenemia has recently been linked to ligneous conjunctivitis. Plasminogen (plg) is known as a polymorphic protein and most of these variants have been identified using isoelectric focusing (IEF) gel electrophoresis. Here, we studied common plg variants from healthy subjects and plg mutants from three patients with hypoplasminogenemia and three subjects with dysplasminogenemia by molecular genetic analysis and IEF. Analysis of 24 healthy subjects showed that subjects with the most common IEF plg phenotype A (n=12) were homozygous for aspartate at position 453 (453D), while both subjects with IEF plg phenotype B were homozygous for asparagine at this position (453N). Subjects with IEF plg phenotype AB (n=10) were compound-heterozygous for 453D/453N. Three patients with severe hypoplasminogenemia and different plg gene mutations exhibited characteristic "abnormal" IEF band patterns when compared with IEF plg phenotypes A and B. In all heterozygous family members the observed IEF plg phenotype was derived from the wild type plg molecule only, probably due to low concentration of the mutant plg molecule in plasma. In contrast, in three unrelated subjects with heterozygous dysplasminogenemia an equal "mixture" of wild type and mutant plg was found by IEF analysis. In conclusion, plg phenotyping by IEF in combination with molecular analysis of the plg gene seems to be a useful method for characterization of plg variants and mutants.     

Effects of acute psychological stress on adhesion molecules,interleukins and sex hormones: implications for coronary heart disease

Abstract Rationale. Subjects with high levels of daily stress suffer from an increased risk of coronary heart disease. Increased concentrations of the intercellular adhesion molecule-1 (ICAM-1) contribute to atherosclerosis. Cell adhesion molecules may be activated by psychological stress exposure, depending on their interaction with the interleukin network, sex hormones and cortisol secretion. Objectives. To assess effects of acute psychological stress on the interaction between cell adhesion molecules, interleukins, sex hormones and cortisol in healthy male subjects. Methods. Cell adhesion molecules, interleukin-1 beta (IL-1β), IL-2, IL-6, sex hormones and cortisol levels of 18 healthy male physicians were measured before and after an academic oral presentation and on a control day. Results. The oral presentation was perceived as a stressful event and was accompanied by a significant increase in cortisol secretion in all volunteers. Soluble ICAM-1 and IL-1β also increased in all subjects after psychological stress exposure. The stress-associated increase in IL-2 concentrations approached statistical significance and correlated negatively with luteinizing hormone plasma levels. Estradiol concentrations correlated positively with IL-6 levels. Conclusions. Subjective ratings and the increase in cortisol plasma concentrations support the validity of the chosen stress model. Acute stress exposure was followed by an increase in IL-1β, IL-2 and soluble ICAM-1 plasma concentrations, which can contribute to coronary heart disease and immunological disorders. Electronic Publication     

Tartrolone C: a novel insecticidal macrodiolide produced by Streptomyces sp. CP1130

A new member of the tartrolone series of macrodiolides, tartrolone C (1), was isolated from a Streptomyces species on the basis of its insecticidal activity. Metacycloprodigiosin (2) and undecylprodigiosin (3) were also isolated on the same basis. The structure of all compounds was established by spectroscopic data (NMR, MS, and UV).     

Resection of residual disease in patients with metastatic gastrointestinal stromal tumors responding to treatment with imatinib

Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the gastrointestinal tract. Long-term survival of patients with metastatic disease has only been observed in patients with completely resected disease. Recently, the tyrosine kinase inhibitor imatinib has been found to yield responses in the majority of patients with metastatic GIST suggesting improved resectability in responding patients. Combined treatment approaches including resective surgery after imatinib treatment in patients with advanced metastatic disease have rarely been explored. We report a series of 90 patients with metastatic GIST in whom treatment with imatinib enabled 12 patients with mostly recurrent and extensive disease to be considered for resection of residual disease. In 11 of these patients, complete resection could be achieved. Viable tumor cells were found in all but one resected specimens suggesting that despite favorable radiological or clinical responses, imatinib is unlikely to induce pathological complete responses. Until more mature data from prospective trials are available, these data suggest that an early aggressive surgical approach should be considered for all patients with metastatic GIST. Further trials investigating a combined surgical and pre/postoperative treatment with imatinib in patients with advanced metastatic GIST are warranted.