Maternal abdominal subcutaneous fat thickness as a predictor for adverse pregnancy outcome: a longitudinal cohort study.

OBJECTIVE: To assess maternal abdominal subcutaneous fat thickness (SFT) measured by ultrasound as an independent predictor of adverse pregnancy outcomes. DESIGN: A prospective longitudinal cohort study performed on pregnancies delivered between 2012 and 2014. SETTING: Sydney, Australia. POPULATION: About 1510 pregnant women attending routine obstetric ultrasounds. METHODS: Maternal SFT was measured on routine ultrasounds at 11-14 weeks' gestation (SFT1) and 18-22 weeks' gestation (SFT2). SFT measurements were assessed for estimating risks for obesity-related pregnancy outcomes using logistic regression modelling adjusted for maternal age, parity, smoking status and body mass index (BMI). MAIN OUTCOME MEASURES: Hypertensive disease, gestational diabetes, caesarean section, low birthweight, preterm delivery, neonatal respiratory distress, Apgar scores, and admission to a neonatal intensive care unit. RESULTS: SFT1 and SFT2 were measured on 1461 and 1363 women, respectively. Mean thickness (range) were 21.2 mm (6.9-73.9) for SFT1 and 20.3 mm (7.5-68.0) for SFT2. Complete outcome data were available for 1385 pregnancies. In all, 54% of the women were overweight/obese. The SFT measures decreased from early to mid-pregnancy in overweight/obese women. There was moderate correlation between BMI and SFT1 (R(2) = 0.56) and BMI and SFT2 (R(2) = 0.55). In a multivariate model, SFT1 and SFT2 were better predictors for adverse pregnancy outcomes than BMI. CONCLUSION: Maternal SFT is a significant independent predictor of adverse pregnancy outcomes. Incorporation of SFT into future models for adverse pregnancy outcome may prove valuable.

Peri-operative management of the obese surgical patient 2015: Association of Anaesthetists of Great Britain and Ireland Society for Obesity and Bariatric Anaesthesia.

Guidelines are presented for the organisational and clinical peri-operative management of anaesthesia and surgery for patients who are obese, along with a summary of the problems that obesity may cause peri-operatively. The advice presented is based on previously published advice, clinical studies and expert opinion.

Prevalence of difficult intubation in a bariatric population, using the beach chair position.

SUMMARY: We retrospectively reviewed the anaesthetic charts of patients who had undergone bariatric surgery in our regional centre since the start of the service. We identified Cormack and Lehane grade of laryngoscopy, any difficulties associated with tracheal intubation, and the impact of age, gender and body mass index on laryngoscopy grade. The patients were anaesthetised in the in the 'beach chair' position prior to laryngoscopy. One hundred and ninety-two patients' notes were available for review out of a total of 198. Mean age was 43.3 years (SD 10.3) and mean BMI 50.8 (SD 8.0). Grade of laryngoscopy was unrecorded in 20 patients. Of the 192 patients, 162 (84%) had a Cormack and Lehane grade of 1 or 2. Nine (4.7%) patients were graded as 3 and only one patient had a grade 4 laryngoscopy. There were two cases (1%) of difficulty in intubation. A bougie was used 16 times (8%). Logistic regression showed that age was a significant factor for increasing laryngoscopy grade (p = 0.0102) but that BMI was not (p = 0.6271).

Multiple system atrophy as a cause of upper airway obstruction.

A patient presented to the ear, nose and throat department with inspiratory stridor, dysphagia and a sore throat. Clinical and radiological examination was normal. During induction of anaesthesia for a planned microlaryngoscopy, the patient developed complete upper airway obstruction that was overcome by applying positive pressure via a facepiece until awake. He subsequently developed respiratory failure, requiring mechanical ventilatory support. An elective tracheostomy was inserted for his symptoms. Neurological opinion confirmed the diagnosis of multiple system atrophy with akinetic rigid syndrome. We review this obscure condition and how it may occasionally present to anaesthetists.

Serious consequences of a sore throat.

Lemierre's syndrome, caused by Fusobacterium necrophorum, is a potentially fatal sequelae of a sore throat characterised by septicaemia, internal jugular vein thrombophlebitis and metastatic abscesses. The Chief Medical Officer reported in February 2001 that the incidence is increasing. Two cases seen in one year, with different presentations, are reported. The first patient presented with sepsis, jaundice, hepatic abscesses and portal vein/superior mesenteric vein thrombosis, whilst the second presented with sepsis, sore throat and internal jugular vein thrombophlebitis. Both patients were treated with antibiotics and anticoagulants with a favourable outcome.

Liver damage by infiltrating CD8+ T cells is Fas dependent.

Ag stimulation of CD8+ lymphocytes in vivo results in their migration to various tissues as well as the activation of a cytolytic program involving perforin, TNF-alpha, and Fas ligand. The liver is one of the main sites for infiltration by activated CD8+ T cells, and this is followed by the death of hepatocytes. The contribution of the various cytolytic components to this process is unclear. Hepatocyte damage by CD8+ T cells was studied using the MHC class I-restricted OVA-specific TCR transgenic mouse (OT-1) to examine the contribution of Fas to hepatocyte death. Activated CD8+ T cells from both OT-1 and Fas-deficient OT-1lpr mice migrated to the liver in similar numbers after OVA administration, but only in OT-1 mice was there evidence of significant hepatocyte damage histologically and by elevation of serum aspartate transaminase. These differences were not the result of inefficient induction of cytolytic activity in OT-1lpr liver T cells, since they were as cytolytic in vitro as OT-1 liver T cells. This was supported by findings of similar high levels of message for perforin, TNF-alpha, and Fas ligand in liver lymphocytes from both mice. These findings demonstrate that following Ag activation, infiltrating liver CD8+ T lymphocytes induce hepatocyte damage in a Fas-dependent manner.

Requirement of the JIP1 scaffold protein for stress-induced JNK activation.

The c-Jun N-terminal kinase (JNK) signal transduction pathway is activated in response to the exposure of cells to environmental stress. Components of the JNK signaling pathway interact with the JIP1 scaffold protein. JIP1 is located in the neurites of primary hippocampal neurons. However, in response to stress, JIP1 accumulates in the soma together with activated JNK and phosphorylated c-Jun. Disruption of the Jip1 gene in mice by homologous recombination prevented JNK activation caused by exposure to excitotoxic stress and anoxic stress in vivo and in vitro. These data show that the JIP1 scaffold protein is a critical component of a MAP-kinase signal transduction pathway.

Fasciola: kinetics and quality of humoral responses to fatty acid binding protein and cathepsin l following delivery as DNA vaccines in mice.

The humoral response to DNA vaccination of mice with two important Fasciola antigens has been investigated. Both F. gigantica fatty acid binding protein (FABP) and F. hepatica cathepsin L5 (FhCatL5) were shown to be expressed in COS 7 cells and induced a humoral response when delivered as secretory constructs in mice. FABP induced an IgGl dominant response, with significant IgE, IgG2a, and IgG2b responses also present, indicating a mixed Th1/Th2 response. The total Ig response peaked at 1:24,500 and antibody titers were sustained for at least 32 weeks. In contrast, the delivery of FABP as a nonsecreted construct did not result in the induction of a measurable humoral response. FhCatL5 was delivered as a secretory construct, with secretion mediated by the native F. hepatica signal sequence, which was shown to operate in COS 7 cells. The humoral response peaked at 1:2000 at week 8 and was sustained for at least 20 weeks. Antibody isotype analysis demonstrated a Th2-like response, which was qualitatively different from that obtained for FABP with an IgE dominant response, and lower titers to IgG1 and IgG3. The results demonstrate that Fasciola antigens can be delivered as DNA vaccines, but that the quality of the response varies between antigens and is influenced by the method of vaccine delivery.

Caspase activation is required for T cell proliferation.

Triggering of Fas (CD95) by its ligand (FasL) rapidly induces cell death via recruitment of the adaptor protein Fas-associated death domain (FADD), resulting in activation of a caspase cascade. It was thus surprising that T lymphocytes deficient in FADD were reported recently to be not only resistant to FasL-mediated apoptosis, but also defective in their proliferative capacity. This finding suggested potentially dual roles of cell growth and death for Fas and possibly other death receptors. We report here that CD3-induced proliferation and interleukin 2 production by human T cells are blocked by inhibitors of caspase activity. This is paralleled by rapid cleavage of caspase-8 after CD3 stimulation, but no detectable processing of caspase-3 during the same interval. The caspase contribution to T cell activation may occur via TCR-mediated upregulation of FasL, as Fas-Fc blocked T cell proliferation, whereas soluble FasL augmented CD3-induced proliferation. These findings extend the role of death receptors to the promotion of T cell growth in a caspase-dependent manner.

Phosphorylation of FADD/MORT1 and Fas by kinases that associate with the membrane-proximal cytoplasmic domain of Fas.

Fas (Apo-1, CD95), a member of the TNFR family, is expressed on a variety of cell types and transduces an apoptotic signal. Since Fas does not possess known enzymatic activities, proteins that interact with the cytoplasmic domain of Fas regulate the death signal. Several proteins have been identified, primarily using the yeast two-hybrid system, that associate with the death domain of Fas. One of these proteins, FADD/MORT1, can be phosphorylated, although the kinase that is responsible has not been identified. Furthermore, direct signaling connections between Fas and its known activation of sphingomyelinase or NF-kappaB have not been made, suggesting that other proteins may associate with Fas. In this study, a series of glutathione S-transferase fusion proteins was constructed that contained the cytoplasmic domain of murine Fas. These proteins were used to search for additional proteins that associate with Fas. Novel proteins, including kinases, were identified that associated specifically with the membrane-proximal, cytoplasmic tail of Fas but not with the death domain. One of these kinases phosphorylates FADD/MORT1. Moreover, the membrane-proximal region of Fas itself was phosphorylated by one of the associating kinases. These findings suggest that, similar to the Fas-related p55 TNFR, the membrane-proximal region of Fas likely participates in signaling.

Molecular cloning and characterization of two isoforms of Saccharomyces cerevisiae acyl-CoA:sterol acyltransferase.

Esterification of cholesterol by acyl-CoA:cholesterol acyltransferase (ACAT) is a key element in maintaining cholesterol homeostasis in cells of higher animals. In the budding yeast, Saccharomyces cerevisiae, accumulation of ergosteryl esters accompanies entry into stationary phase and sporulation. We have determined that two genes in yeast, SAT1 and SAT2, encode isozymes of acyl-CoA:sterol acyltransferase (ASAT) which are functionally related to ACAT. The SAT1 isozyme is the major catalytic isoform, accounting for at least 65-75% of total ASAT activity. Targeted deletions of one or both genes do not compromise mitotic cell growth or spore germination. However, diploids that are homozygous for a SAT1 null mutation exhibit significantly reduced sporulation efficiency. Furthermore, a larger fraction of the sporulating diploids arrest after the first meiotic division. Human ACAT expressed in sat1 sat2 mutant cells can catalyze esterification of cholesterol and, to a lesser extent, ergosterol in vitro, but restores ergosteryl oleate formation in vivo to only approximately 8% of that catalyzed by yeast ASAT in wild-type cells.

Drug use in the high intensity drug trafficking area of the US Southwest border.

This paper examines the prevalence of alcohol, tobacco and illicit drug use in the Southwest border region of the United States. Based on the seriousness of drug trafficking in the area, the Southwest border has been designated a "High Intensity Drug Trafficking Area." Yet there is little quantitative data on the nature and magnitude of drug use in the Southwest border region. This paper examines the prevalence of drug use in the area by extracting data from the National Household Survey on Drug Abuse. The data show that drug use rates in the Southwest border area are very similar to those found throughout the remainder of the United States. Hispanics, who constitute about 41% of the Southwest border population, have lower prevalence rates for most classes of drugs than non-Hispanics. The border Hispanics exhibit even lower prevalence rates than Hispanics in the remainder of the United States. However, many of these differences are attributable to the lower levels of drug use among women, and youth and older adults. As these demographic subgroups become increasingly acculturated, their drug use could come to more closely resemble that of their peers in the remainder of the United States.

Antigen-specific T-cell activations distinguished by in vivo anti-CD4 antibody treatment.

This study identifies activation characteristics of PPD-responsive T-cells that emerge after treatment with anti-CD4 monoclonal antibody (Mab). PPD-stimulated T-cell proliferations, OX40 phenotype and protein tyrosine phosphorylations involving p56lck (pp56lck) were compared to Con A stimulations using T-cells isolated from spleen and draining lymph node of CFA/PPD-immunized rats either untreated or treated in vivo with anti-CD4 Mab. Splenocytes stimulated by concanavalin A (Con A) showed correlated increases in proliferation, levels of pp56lck, and OX40 expression; these parameters were not correlated in splenocytes after PPD-stimulations. T-cells isolated from lymph nodes draining the site of CFA/PPD immunization proliferated in response to stimulation by either PPD or Con A, but only PPD-responsive cells showed correlation to the OX40 activation phenotype and increased levels of pp56lck. CD4+ T-cells isolated from either tissue compartment after anti-CD4 Mab treatments showed higher background and PPD-stimulated proliferations, and expressed lower levels of OX40. In contrast, anti-CD4 Mab treatments reduced (60%) and abolished Con A-stimulated proliferations of splenocytes and lymph node T-cells, respectively. The effects of anti-CD4 Mab treatment on pp56lck levels correlated only to the changes observed for Con A stimulations of splenocytes. These results demonstrate that PPD antigen-specific T-cell populations recovered from different tissue compartments were resistant to in vivo anti-CD4 Mab treatments and did not show the activation changes characteristics of CD4+ T-cells after Con A stimulation.

Transoesophageal echocardiographic examination of a patient with venacaval and pericardial tears after blunt chest trauma.

A 58-yr-old male was admitted with blunt thoracic and abdominal trauma. Transoesophageal echocardiography (TEE) was performed acutely to determine the cause of intrathoracic haemorrhage. We found atrial septal haematoma and tear, which have not been described previously, and which may be useful indicators of major intrathoracic venous tears which are always difficult to diagnose. Although the outcome was not altered in this case, we feel that TEE is a useful adjunct in the diagnosis of acute thoracic trauma.

Effects of anti-CD4 antibody: enhancement of lymph node PPD-memory T cell response.

In vitro incubations of CD4+ T cells with anti-CD4 monoclonal antibody (Mab) demonstrated saturation binding and inhibited both PPD-stimulated proliferation and delayed-type hypersensitivity (DTH) after passive transfer of these cells into naive rats. In comparison, in vivo administration of anti-CD4 Mab into rats, 2 weeks after CFA immunization (PPD priming), saturated CD4 molecules expressed on T lymphocytes and depleted significant percentages of CD4+ T cells from blood, spleen, and lymph nodes, yet failed to cause significant inhibition of PPD-stimulated DTH ear swelling. Only repeated in vivo administration of anti-CD4 Mabs during the CFA/PPD antigen priming caused significant decreases (36 +/- 5%) in PPD-stimulated DTH ear swelling. T cells isolated from the blood and spleen showed insignificant relative decreases in PPD-stimulated proliferation after anti-CD4 treatments. In contrast, PPD-stimulated proliferation of T cells isolated from the draining lymph nodes after anti-CD4 treatments showed dramatic increases in PPD reactivity. PPD stimulation of T cells isolated from the draining lymph nodes of anti-CD4 Mab-treated rats produced relative phenotypic changes in CD4 coexpressions with CD45RC (inverse memory), CD49d (inflammatory adhesion integrin VLA-4), and OX40 (CD4+ blast), representative of memory CD4+ T cell blasts with reduced capacity for endothelial infiltration. These data demonstrate that depletion of CD4+ T cells by anti-CD4 Mab injections, administered either during or after antigen priming, selectively enhanced memory responses in T lymphocytes in the draining lymph nodes.