Prostaglandin-Independent Stimulation of Interleukin-6 Production by Fibrinogen Degradation Product D in Perfused Murine Liver

Bacterial endotoxin (LPS) and fibrinogen degradation product D (FDP-D) are both potent stimulators of interleukin-6 (IL-6) production in liver, however, there are differences in their metabolic effects. The aim of the present study was to compare the role of prostaglandins in the enhancement of IL-6 production by LPS or FDP-D in perfused mouse livers. Indomethacin inhibited the effect of LPS significantly but was ineffective in the case of FDP-D. Accordingly, production of prostaglandins D₂ and E₂ was not elevated following the addition of FDP-D, while their formation was increased several fold by LPS. At the same time interleukin-1 (IL-1) production in perfused liver rose markedly upon the addition of FDP-D. It is suggested that prostaglandins are not involved in the effects of FDP-D on the liver. The stimulatory effect of FDP-P on IL-6 production might be the consequence of elevated IL-1 levels.     

Osteosarcomatosis

A review of the 690 cases of osteosarcoma in the radiographic file of the Armed Forces Institute of Pathology revealed 29 cases of "osteosarcomatosis" (multiple skeletal sites of osteosarcoma). Fifteen of these patients were 18 years old and under and manifested rapidly appearing, usually symmetric, sclerotic metaphyseal lesions. The remaining 14 patients were more than 18 years old and had fewer, asymmetric sclerotic lesions. In most patients (28 of 29), a radiographically dominant skeletal tumor was seen. Pulmonary metastases occurred in the majority of patients and were detected at the same time as the bone lesions. These 29 patients were studied with regard to demographic data and skeletal distribution and radiographic appearance of their lesions. As a result of the findings, a metastatic origin from a primary dominant osteosarcoma is favored over a multifocal origin as the basis for osteosarcomatosis. Osteosarcomatosis is more commonly encountered in the mature skeleton than has been previously recognized.     

Polyvinylchloride infusion lines expose infants to large amounts of toxic plasticizers

PURPOSE: The purpose of this study was to evaluate whether infusion lines are able to leach plasticizers in substantial amounts and thus be a candidate substance for hepatotoxic effects during long-term total parenteral nutrition (TPN). METHODS: TPN solutions, blood products, and selected drugs typical for preterm infants concerning amount, content, and infusion time were perfused through common polyvinylchloride (PVC) infusion lines. Concentration of diethylhexyl-phthalate (DEHP) before and after perfusion was determined by gas chromatography/mass spectrometry. RESULTS: Daily quantities of DEHP by 24-hour infusions were Lipid emulsion 20%: 10185.6 microg; aminoacid/glucose-solution: 116.2 microg; midazolaminfusion for sedation: 26.4 microg; fentanyl for sedation: 132.5 microg; propofol for sedation: 6561.0 microg. The amount of DEHP by single doses of blood products (20 mL) were packed red blood cells: 144-608 microg; platelet rich plasma: 928 microg; and fresh frozen plasma: 552-8108 microg. The dose of DEHP for a typical preterm neonate requiring TPN and additional therapy like sedation or blood products is at minimum 10 mg and can easily reach 20 mg/d. CONCLUSION: This large amount of DEHP is especially disturbing, because it effects the most vulnerable patients (neonates). Whether there is a relation to TPN-induced hepatobiliary dysfunction remains to be elucidated and is under investigation. With respect to recent literature, a biological effect of these doses must be assumed.     

Decreased elastic fibers and desmosine content in incompetent cervix

Incompetence of the uterine cervix is a syndrome of painless, progressive dilatation and effacement occurring between the sixteenth and twenty-fourth weeks of gestation that represents abnormal functioning. It may serve as a model to elucidate normal function. Because the incompetent cervix results in painless opening of this organ without uterine contraction before term gestation, it is considered one of the causes of midtrimester spontaneous abortion, habitual spontaneous abortion, and early preterm labor. Untreated, it leads to rapid expulsion and often death of the fetus. We used light microscopy to compare decreased elastic fibers in incompetent cervices with those of normal nonpregnant and pregnant cervices. Morphologic analysis of this difference was extended to biochemical quantification of elastin content in one patient with cervical incompetence. The decrease in elastin suggests that one function of cervical elastin may be to maintain a closed and undilated cervix throughout gestation. There may be a relationship between changes in cross-linked elastin and the incompetent cervix; further studies are therefore indicated.     

Leitlinie zur Betreuung von Neugeborenen diabetischer M��tter

All diabetic women are advised to give birth in a hospital with a pediatric service that allows for continuous intravenous glucose administration, precluding the need for out-of-house transfer of the infant. Women with pre-pregnancy diabetes or on insulin treatment during pregnancy should give birth in a hospital offering round-the-clock neonatal care. Early (breast) feeding is of paramount importance and should be started 30?min after birth, subsequently every 2?C3?h. A mandatory preprandial blood glucose measurement should be taken 2?C3?h after birth and again immediately before the infant is transferred out of the delivery room; subsequent preprandial measurements at 6, 12, and possibly 24?h of age. In the event of three consecutive values of >2.5?mmol/l (45?mg/dl), further controls may be dispensed with. Simultaneously, infants should be checked for symptoms of hypoglycemia by a midwife or nurse on the maternity unit. Clinical findings suspicious for hypoglycemia should prompt immediate blood glucose determinations. Blood glucose concentrations below 2?mmol/l (36?mg/dl; in infants without symptoms) or 2.5?mmol/l (45?mg/dl; in infants with hypoglycemia-related symptoms, prior hypoglycemia, or following asphyxia) require immediate intervention in the form of feeding (preferably breast milk, otherwise hydrolyzed formula, or hydrolyzed starch solution only temporarily), by gavage if necessary. Intravenous glucose administration if blood glucose falls below 1.7?mmol/l (30?mg/dl). Routine echocardiography or laboratory tests (Ca2+, Mg2+, hematocrit, bilirubin) are not necessary unless otherwise indicated. Breast feeding should be consistently encouraged before and after delivery.     

Die Anwendungsbreite der Paravertebralen Injektion

Ohne Zusammenfassung     

Mutational spectrum of ATRX aberrations in neuroblastoma and associated patient and tumor characteristics

Neuroblastoma is the most common extracranial solid tumor in children. The chromatin remodeler ATRX is frequently mutated in high‐risk patients with a poor prognosis. Although many studies have reported ATRX aberrations and the associated clinical characteristics in neuroblastoma, a comprehensive overview is currently lacking. In this study, we extensively characterize the mutational spectrum of ATRX aberrations in neuroblastoma tumors reported in previous studies and present an overview of patient and tumor characteristics. We collected the data of a total of 127 neuroblastoma patients and three cell lines with ATRX aberrations originating from 20 papers. We subdivide the ATRX aberrations into nonsense, missense, and multiexon deletions (MEDs) and show that 68% of them are MEDs. Of these MEDs, 75% are predicted to be in‐frame. Furthermore, we identify a missense mutational hotspot region in the helicase domain. We also confirm that all three ATRX mutation types are more often identified in patients diagnosed at an older age, but still approximately 40% of the patients are aged 5 years or younger at diagnosis. Surprisingly, we found that 11q deletions are enriched in neuroblastomas with ATRX deletions compared to a reference cohort, but not in neuroblastomas with ATRX point mutations. Taken together, our data emphasizes a distinct ATRX mutation spectrum in neuroblastoma, which should be considered when studying molecular phenotypes and therapeutic strategies.