Rescue therapy for refractory status asthmaticus with updosed omalizumab adjusted for IgE level, body weight and effect.

Status asthmaticus is a life-threatening condition with a high mortality rate of up to 10.3% [1].Milger et al. recently described a rapid clinical improvement and a reduction in serum IgE levels in a patient with status asthmaticus who received salvage therapy with omalizumab [2]. This treatment is not approved for status asthmaticus. Therefore, the authors based their dose finding on the recommendations approved by the by the European Medicines Agency for the treatment of severe persistent allergic asthma. For this indication the maximum dose generally does not include an option for patients with a higher body weight and high IgE levels [2].A significant number of patients with persistent severe allergic asthma cannot be treated because there are insufficient data to support the administration of omalizumab above the recommended maximum dose of 600mg every 2 weeks [3]. In contrast, there is a lot of evidence in the existing literature for a very good safety profile for omalizumab [4,5]. OBJECTIVE: Here we report for the first time the successful treatment of a patient with refractory status asthmaticus by salvage therapy with updosed omalizumab adjusted for actual baseline IgE level, body weight and effect.

A Prospective Randomized Clinical Trial of Single vs. Double Layer Closure of Hysterotomy at the Time of Cesarean Delivery: The Effect on Uterine Scar Thickness.

PURPOSE: We undertook a randomized clinical trial to examine the outcome of a single vs. a double layer uterine closure using ultrasound to assess uterine scar thickness. MATERIALS AND METHODS: Participating women were allocated to one of three uterotomy suture techniques: continuous single layer unlocked suturing, continuous locked single layer suturing, or double layer suturing. Transvaginal ultrasound of uterine scar thickness was performed 6 weeks and 6 - 24 months after Cesarean delivery. Sonographers were blinded to the closure technique. RESULTS: An "intent-to-treat" and "as treated" ANOVA analysis included 435 patients (n = 149 single layer unlocked suturing, n = 157 single layer locked suturing, and n = 129 double layer suturing). 6 weeks postpartum, the median scar thickness did not differ among the three groups: 10.0 (8.5 - 12.3 mm) single layer unlocked vs. 10.1 (8.2 - 12.7 mm) single layer locked vs. 10.8 (8.1 - 12.8 mm) double layer; (p = 0.84). At the time of the second follow-up, the uterine scar was not significantly (p = 0.06) thicker if the uterus had been closed with a double layer closure 7.3 (5.7 - 9.1 mm), compared to single layer unlocked 6.4 (5.0 - 8.8 mm) or locked suturing techniques 6.8 (5.2 - 8.7 mm). Women who underwent primary or elective Cesarean delivery showed a significantly (p = 0.03, p = 0.02, "as treated") increased median scar thickness after double layer closure vs. single layer unlocked suture. CONCLUSION: A double layer closure of the hysterotomy is associated with a thicker myometrium scar only in primary or elective Cesarean delivery patients.

Synthesis of antibacterial 1,3-diyne-linked peptoids from an Ugi-4CR/Glaser coupling approach.

A library of ten 1,3-diyne-linked peptoids has been synthesized through an Ugi four-component reaction (U-4CR) followed by a copper-catalysed alkyne homocoupling (Glaser reaction). The short and chemoselective reaction sequence allows generating diverse (pseudo) dimeric peptoids. A combinatorial version allows the one-pot preparation of, e.g., six-compound-libraries of homo- and heterodimers verified by ESI-MS and HPLC. In a preliminary evaluation, some compounds display moderate activity against the Gram-positive bacterium Bacillus subtilis.

Radiofrequency ablation as a minimally invasive procedure in the treatment of twin reversed arterial perfusion sequence in twin pregnancy.

Twin reversed arterial perfusion sequence is a rare anomaly of monochorionic multiple pregnancies affecting 1 of 35,000 pregnancies and 1% of monochorionic twin pregnancies. In this condition the affected twin has lethal malformations including poor or absent heart development and is reversely perfused by a structurally normal co-twin. We report a case of a 21-year-old woman with a monochorionic twin pregnancy affected by twin reversed arterial perfusion sequence. This case highlights the therapeutic options and the management by radiofrequency ablation, which has been shown to be an easy and reliable technique with a high success rate compared with technically demanding fetoscopic procedures.

Glutathione peroxidase-2 and selenium decreased inflammation and tumors in a mouse model of inflammation-associated carcinogenesis whereas sulforaphane effects differed with selenium supply.

Chronic inflammation and selenium deficiency are considered as risk factors for colon cancer. The protective effect of selenium might be mediated by specific selenoproteins, such as glutathione peroxidases (GPx). GPx-1 and -2 double knockout, but not single knockout mice, spontaneously develop ileocolitis and intestinal cancer. Since GPx2 is induced by the chemopreventive sulforaphane (SFN) via the nuclear factor E2-related factor 2 (Nrf2)/Keap1 system, the susceptibility of GPx2-KO and wild-type (WT) mice to azoxymethane and dextran sulfate sodium (AOM/DSS)-induced colon carcinogenesis was tested under different selenium states and SFN applications. WT and GPx2-KO mice were grown on a selenium-poor, -adequate or -supranutritional diet. SFN application started either 1 week before (SFN4) or along with (SFN3) a single AOM application followed by DSS treatment for 1 week. Mice were assessed 3 weeks after AOM for colitis and Nrf2 target gene expression and after 12 weeks for tumorigenesis. NAD(P)H:quinone oxidoreductases, thioredoxin reductases and glutathione-S-transferases were upregulated in the ileum and/or colon by SFN, as was GPx2 in WT mice. Inflammation scores were more severe in GPx2-KO mice and highest in selenium-poor groups. Inflammation was enhanced by SFN4 in both genotypes under selenium restriction but decreased in selenium adequacy. Total tumor numbers were higher in GPx2-KO mice but diminished by increasing selenium in both genotypes. SFN3 reduced inflammation and tumor multiplicity in both Se-adequate genotypes. Tumor size was smaller in Se-poor GPx2-KO mice. It is concluded that GPx2, although supporting tumor growth, inhibits inflammation-mediated tumorigenesis, but the protective effect of selenium does not strictly depend on GPx2 expression. Similarly, SFN requires selenium but not GPx2 for being protective.

Severe H1N1-infection during pregnancy.

H1N1 is known to induce fulminant courses in youths and young adults. We report the case of a 24-year gravida 4 para 2 with singleton pregnancy admitted to obstetrical unit for fever up to 38°C during the 20th week of a so far uncomplicated pregnancy. Ultrasound examination and urine test was inconspicuous. Throat complaints were initially relieved during antibiotic therapy, but the patient developed dyspnea with progressing signs of cyanosis. Intubation was necessary on the fifth day because of decreasing oxygen saturation. Coincidentally, progressive pancytopenia and increased inflammatory activity was recorded. Echocardiography, blood cultures, and bronchial lavage brought no pathological findings, but CT revealed acute respiratory distress syndrome and hepatomegaly. Recent human immunodeficiency virus, cytomegalic virus, herpes simplex virus, classical influenza and parainfluenza infections were excluded. An H1N1-infection was confirmed by PCR on the sixth day. The antiviral therapy was changed from zanamivir to oseltamivir. Extracorporeal membrane oxygenation was necessary due to insufficient oxygen saturation by mechanical ventilation. Until this time, pregnancy seemed to be unimpaired, but a sudden spontaneous expulsion of the fetus occurred on the seventh day (weight 460 g, no anomalies detectable). Curettage post abortem was not necessary. As a result of the antiviral therapy, H1N1-DNA was not detectable at day 16. Despite all endeavors, the respiratory situation could not be improved significantly; the patient additionally developed multiorgan failure during the time course and died on the 28th day of treatment. The recent case illustrates a very dangerous and imposing course of an H1N1-infection during pregnancy.

Prenatal two- and three-dimensional imaging in two cases of severe penoscrotal hypospadias.

We present the prenatal two- and three-dimensional (3D) ultrasound (US) findings in two cases of severe penoscrotal hypospadias. 3D sonography was used for better definition of ambiguous genitalia. The images were compared with postnatal clinical features. Despite hypospadias being the most common urogenital anomaly of male neonates, the diagnosis is often missed before birth. Performing prenatal ultrasound should include the study of genitals, not only determining the sex.

Breakdown products of neoglucobrassicin inhibit activation of Nrf2 target genes mediated by myrosinase-derived glucoraphanin hydrolysis products.

Glucosinolates (GLSs) present in Brassica vegetables serve as precursors for biologically active metabolites, which are released by myrosinase and induce phase 2 enzymes via the activation of Nrf2. Thus, GLSs are generally considered beneficial. The pattern of GLSs in plants is various, and contents of individual GLSs change with growth phase and culture conditions. Whereas some GLSs, for example, glucoraphanin (GRA), the precursor of sulforaphane (SFN), are intensively studied, functions of others such as the indole GLS neoglucobrassicin (nGBS) are rather unknown as are functions of combinations thereof. We therefore investigated myrosinase-treated GRA, nGBS and synthetic SFN for their ability to induce NAD(P)H:quinone oxidoreductase 1 (NQO1) as typical phase 2 enzyme, and glutathione peroxidase 2 (GPx2) as novel Nrf2 target in HepG2 cells. Breakdown products of nGBS potently inhibit both GRA-mediated stimulation of NQO1 enzyme and Gpx2 promoter activity. Inhibition of promoter activity depends on the presence of an intact xenobiotic responsive element (XRE) and is also observed with benzo[a]pyrene, a typical ligand of the aryl hydrocarbon receptor (AhR), suggesting that suppressive effects of nGBS are mediated via AhR/XRE pathway. Thus, the AhR/XRE pathway can negatively interfere with the Nrf2/ARE pathway which has consequences for dietary recommendations and, therefore, needs further investigation.

Mirror syndrome: a systematic review of fetal associated conditions, maternal presentation and perinatal outcome.

INTRODUCTION: Mirror syndrome, also referred to as Ballantyne's syndrome, is normally defined as the development of maternal edema in association with fetal hydrops. The incidence of mirror syndrome is low and few cases have been published. We describe a case report in association with fetal Ebstein anomaly and provide a systematic review on the fetal associated conditions, maternal presentation and perinatal outcome reported for mirror syndrome. DATA SOURCES: A PubMed database search was done until December 2008 (English, French or German) without any restriction of publication date or journal, using the following key words: Ballantyne syndrome, Mirror syndrome, Triple edema, Pseudotoxemia, Maternal hydrops syndrome, Pregnancy toxemia, Acute second trimester gestosis, and Early onset preeclampsia. Reported cases were considered eligible when fetal associated conditions, maternal symptoms and fetal outcome were clearly described. RESULTS: Among 151 publications a total of 56 reported cases satisfying all inclusion criteria were identified. Mirror syndrome was associated with rhesus isoimmunization (29%), twin-twin transfusion syndrome (18%), viral infection (16%) and fetal malformations, fetal or placental tumors (37.5%). Gestational age at diagnosis ranged from 22.5 to 27.8 weeks of gestation. Maternal key signs were edema (80-100%), hypertension (57-78%) and proteinuria (20-56%). The overall rate of intrauterine death was 56%. Severe maternal complications including pulmonary edema occurred in 21.4%. Maternal symptoms disappeared 4.8-13.5 days after delivery. DISCUSSION: Mirror syndrome is associated with a substantial increase in fetal mortality and maternal morbidity.

Does the time of onset of severe sepsis in a surgical intensive care unit influence mortality rates: a single-center retrospective analysis.

PURPOSE: The purpose of this study was to investigate possible differences in characteristics and mortality rates between early- and late-onset severe sepsis in surgical intensive care unit (ICU) patients. MATERIALS AND METHODS: Prospectively collected data from all adult patients (>18 years) admitted to our 50-bed surgical ICU between 1st March 2004 and 30th July 2006 were analyzed retrospectively. RESULTS: Of 5925 patients admitted during the study period, 234 patients (3.9%) had severe sepsis: 74 (31.6%) early onset and 160 (68.4%) late onset. Respiratory infections (48.1 versus 27.0%, P = .002) and infections of unknown origin (21.9 versus 12.2%, P = .005) were recorded more frequently in patients with late-onset than in those with early-onset severe sepsis; abdominal infections were more frequent in early-onset than in late-onset severe sepsis (20.3% versus 7.5%, P = .005). Gram-positive infections were more frequent in late-onset than in early-onset severe sepsis (63.1 versus 51.4%, P = .036). The time of onset of severe sepsis was not independently associated with an increased risk of ICU (early versus late: odds ratio, 1.1; confidence interval, 0.78-0.59; P = .786) or in-hospital (early versus late: odds ratio, 0.68; 95% confidence interval, 0.36-1.29; P = .689) death. CONCLUSIONS: Patterns of infection are different in patients with early-onset and those with late-onset severe sepsis. The time of onset of severe sepsis in surgical ICU patients has no impact on mortality. These data may be important in risk stratification and may be useful in resource allocation in the ICU.

Low Apgar score without acidosis may indicate neuromuscular disorder.

OBJECTIVE: We hypothesized that in term infants low Apgar score with normal umbilical artery pH (UApH) indicates prenatal damage to the neuromuscular system. STUDY DESIGN: Retrospective database search of 42,117 liveborn infants born 1993-2005. Medical record analysis of 3104 term infants with cardiorespiratory maladaptation referred for special neonatal care. Focus on infants with UApH >7.00 and 5-min Apgar <6 (group A, n=74), UApH <7.00 and 5-min Apgar >5 (group B, n=49), and UApH <7.00 and 5-min Apgar <6 (group C, n=14). RESULTS: Incidence of 5-min Apgar score <6 was 0.50% in term infants. Mean (SD) UApH was 7.262 (0.075, P=0.075); incidence of UApH <7.00 was 0.30% in term infants. Nucleated red blood cells were elevated without differences in all three groups. Parental consanguinity was present in 39 of the 137 maladapted infants. In groups A/B/C, 10/18/2 infants were small for gestational age (P=0.002 for A vs B) and in 16/1/0 neuromuscular anomalies were identified (P=0.004 for A vs B). Eight of the 17 anomalies had been suspected prenatally. Logistic regression proved neuromuscular disorder the only independent variable discriminating between groups A and B. CONCLUSIONS: Neuromuscular problems are the cause rather than the result of maladaptation. For unexplained low Apgar score, especially without acidosis, meticulous examination of the infant including brain imaging and EEG is justified.

The value of rotation thromboelastometry to monitor disturbed perioperative haemostasis and bleeding risk in patients with cardiopulmonary bypass.

Rotation thromboelastometry (ROTEM) performed on whole-blood samples provides information on the contribution of fibrinogen and platelets to clot formation. Such measurements are believed superior to classical plasma coagulation measurements as a means of monitoring disturbed haemostasis. On-pump cardiac surgery is associated with high bleeding risk. The study objective was to obtain information on the frequency of abnormal values of ROTEM variables and to assess their value in estimating bleeding risk in such patients. We studied 150 patients undergoing elective on-pump cardiac surgery. We found a significant surgery-induced decrease in haemostatic potential, with more abnormal ROTEM values in intrinsically activated coagulation (up to 50%) than in extrinsically activated coagulation (up to 27%) or the maximum clot firmness in FIBTEM (10%), a test measuring the contribution of fibrinogen. All ROTEM variables tend to normalize within 14-18 h postoperatively. Best positive predictive values and specificity for a postoperative blood loss above 600 ml were found for the clot formation time in extrinsically activated coagulation (71%/94%) and the maximum clot firmness in FIBTEM (73%/95%); these values were superior to the activated partial thromboplastin time or prothrombin time (56%/72% and 43%/5%, respectively). There was no relation between preoperative or early postoperative ROTEM values and intraoperative bleeding. ROTEM recorded a benefit of administration of platelet concentrates or fresh-frozen plasma, particularly when given postoperatively, on haemostasis. In contrast, intraoperative administration of red blood cells impaired haemostasis. ROTEM can provide a more detailed diagnostic basis enabling a focused therapy to cardiac surgery patients with high bleeding risk.

Expect the unexpected: malposition of a large-bore central venous catheter in the urinary bladder.

We report the case of a femoral vein cannulation in a critically ill trauma patient with the malposition of a large-bore central venous catheter in the urinary bladder. Recognition of the malposition was hampered by bloody tamponade of the bladder in the context of blunt thoraco-abdominal trauma with kidney and liver laceration. A high index of clinical suspicion and the institution of adequate therapy were the key to achieving a successful clinical outcome. We discuss the anatomy of femoral veins, including their close relation to a distended bladder. The application of ultrasound even in emergency situations is stressed.

Extrahepatic biliary atresia and caudal regression syndrome in an infant of a diabetic mother.

Although most cases of extrahepatic biliary atresia are thought to result from perinatal obliterating inflammation, some are associated with a faulty morphogenesis. The authors report on a baby girl of a mother with ill-managed insulin-dependent diabetes mellitus. The baby presented with sacro-coccygeal agenesis, clubfoot, and ano-urinary incontinence. In addition, there was polysplenia, no inferior vena cava, and the portal vein was grossly distorted. Progressive conjugated hyperbilirubinemia prompted liver biopsy at 4 weeks of age, showing intracanalicular cholestasis without fibrosis. The diagnosis of extrahepatic biliary atresia was confirmed during laparotomy performed for hepatoportojejunostomy. Some cases of extrahepatic biliary atresia might be part of a spectrum of malformations associated with maternal diabetes mellitus.

Determinants of fetal growth at different periods of pregnancies complicated by gestational diabetes mellitus or impaired glucose tolerance.

OBJECTIVE: To determine maternal parameters with the strongest influence on fetal growth in different periods of pregnancies complicated by an abnormal glucose tolerance test (GTT). RESEARCH DESIGN AND METHODS: Retrospective study of 368 women with gestational diabetes mellitus (GDM; > or = 2 abnormal GTT values, n = 280) and impaired glucose tolerance (IGT; one abnormal value, n = 88) with 869 ultrasound examinations at entry to and during diabetic care. Both groups were managed comparably. Abdominal circumference (AC) > or = 90th percentile defined fetal macrosomia. Maternal historical and clinical parameters, and diagnostic and glycemic values of glucose profiles divided into five categories of 4 weeks of gestational age (GA; <24 weeks, 24 weeks/0 days to 27 weeks/6 days, 28/0-31/6, 32/0-35/6, and 36/0-40/0 [referred to as <24 GA, 24 GA, 28 GA, 32 GA, and 36 GA categories, respectively]) were tested by univariate and multiple logistic regression analysis for their ability to predict an AC > or = 90th percentile at each GA group and large-for-gestational-age (LGA) newborn. Data obtained at entry were also analyzed separately irrespective of the GA. RESULTS: Maternal weight, glycemia after therapy, rates of fetal macrosomia, and LGA were not significantly different between GDM and IGT; thus, both groups were analyzed together. LGA in a previous pregnancy, (odds ratio [OR] 3.6; 95% CI 1.8-7.3) and prepregnancy obesity (BMI > or = 30 kg/m(2); 2.1; 1.2-3.7) independently predicted AC > or = 90th percentile at entry. When data for each GA category were analyzed, no predictors were found for <24 GA. Independent predictors for each subsequent GA category were as follows: at 24 GA, LGA history (OR 9.8); at 28 GA, LGA history (OR 4.2), and obesity (OR 3.3); at 32 GA, fasting glucose of 32 GA (OR 1.6 per 5-mg/dl increase); at 36 GA, fasting glucose of 32 GA (OR 1.6); and for LGA at birth, LGA history (OR 2.7), and obesity (OR 2.4). CONCLUSIONS: In the late second and early third trimester, maternal BMI and LGA in a previous pregnancy appear to have the strongest influence on fetal growth, while later in the third trimester coincident with the period of maximum growth described in diabetic pregnancies, maternal glycemia predominates.