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Abstract Background Lipoprotein-associated phospholipase A2 (Lp-PLA2)/platelet-activating factor acetylhydrolase (PAF-AH) has been implicated in the pathogenesis of cardiovascular disease. A therapeutic targeting of this enzyme was challenged by the concern that increased circulating platelet activating factor (PAF) may predispose to or increase the severity of the allergic airway response. The aim of this study was to investigate whether Lp-PLA2 gene deficiency increases the risk of PAF and IgE-mediated inflammatory responses in vitro and in vivo using mouse models. Methods Lp-PLA2-/- mice were generated and back crossed to the C57BL/6 background. PAF-AH activity was measured using a hydrolysis assay in serum and bronchoalveolar lavage (BAL) samples obtained from mice. Aspergillus fumigatus (Af)-specific serum was prepared for passive allergic sensitization of mice in vivo and mast cells in vitro. β- hexosaminidase release was studied in bone marrow derived mast cells sensitized with Af-specific serum or DNP-IgE and challenged with Af or DNP, respectively. Mice were treated with lipopolysaccharide (LPS) and PAF intratracheally and studied 24 hours later. Mice were sensitized either passively or actively against Af and were studied 48 hours after a single intranasal Af challenge. Airway responsiveness to methacholine, inflammatory cell influx in the lung tissue and BAL, immunoglobulin (ELISA) and cytokine (Luminex) profiles were compared between the wild type (WT) and Lp-PLA2-/- mice. Results PAF-AH activity was reduced but not completely abolished in Lp-PLA2-/- serum or by in vitro treatment of serum samples with a high saturating concentration of the selective Lp-PLA2 inhibitor, SB-435495. PAF inhalation significantly enhanced airway inflammation of LPS treated WT and Lp-PLA2-/- mice to a similar extent. Sensitized WT and Lp-PLA2-/- bone-marrow derived mast cells released β-hexosaminidase following stimulation by allergen or IgE crosslinking to equivalent levels. Wild type and Lp-PLA2-/- mice responded to passive or active allergic sensitization by significant IgE production, airway inflammation and hyperresponsiveness after Af challenge. BAL cell influx was not different between these strains while IL-4, IL-5, IL-6 and eotaxin release was attenuated in Lp-PLA2-/- mice. There were no differences in the amount of total IgE levels in the Af sensitized WT and Lp-PLA2-/- mice. Conclusions We conclude that Lp-PLA2 deficiency in C57BL/6 mice did not result in a heightened airway inflammation or hyperresponsiveness after PAF/LPS treatment or passive or active allergic sensitization and challenge.

Purpose: The authors review their experiences during multiple cleft surgical missions to rural Bangladesh from 2006 to 2008. A significant number of patients who underwent primary palatoplasty or cheiloplasty were of adult age or size. Adult primary cleft lip and palate repair is often more challenging than repair at the standard age of fewer than 2 years. This patient population is rarely seen in the United States, but may be treated more often by American surgeons during surgical missions to the developing world. This report discusses the experiences of the authors' treatment of cleft lips and palates in rural Bangladesh., Patients and Methods: One hundred forty-six cleft-lip and cleft-palate patients were treated during 3 missions to rural Bangladesh, from 2006 to 2008. Thirty-three (23%) patients were of adult size, and aged 13 to 35 years. One hundred thirteen (77%) patients were aged 12 years or younger. Unilateral cleft lips were repaired with a Millard advancement-rotation technique. Bilateral cleft lips were repaired via the 1-stage procedure advocated by Mulliken and Salyer. Cleft palates were repaired using a 2-finger flap method., Results: Overall, 8 of 146 patients (5.5%) had nonlife-threatening complications (infection or wound dehiscence) requiring subsequent revision surgery. The adult-sized patients had clefts of significantly increased size secondary to patient growth, as well as maxillary expansion transversely and anteriorly. Adult cleft-lip repair required significant soft-tissue dissection to close the cleft adequately, and ensure symmetry to the upper lip and alar bases. However, this procedure sometimes resulted in placement of the lip cicatrix in an anatomically disadvantageous position. In addition, with the increased transverse dimension of the adult cleft palate, tension-free 3-layer closure was difficult. Again, aggressive dissection of the soft tissue was required: the nasal and muscular layers were closed without much tension, but oral closure was often under tension, requiring the assistance of dermal biomaterials to bolster the repair., Conclusions: Patients in the developing world often have limited access to specialized health care, and may not realize that cleft lips and palates can be repaired. As a result, there is an increased incidence of unrepaired clefts in adult-sized individuals in this part of the globe. The American surgeon may encounter these patients during surgical missions. The surgeon should be prepared to repair adult patients with clefts that are significantly enlarged in all 3 dimensions. Closure will require significant soft-tissue dissection as well as the use of biomaterials as needed to repair wide cleft palates.

Hemorrhage after childbirth, whether the delivery is vaginal or operative, is a clinical situation where knowledge, communication, and the availability and utilization of resources all play prominent roles. In this article we describe the thought processes and decisions that should occur, and the actions that should be taken by the anesthesiologist in the face of suspected, expected, or unexpected hemorrhage in the labor and delivery suite.

This article demonstrates the broad range of considerations that affect the outcome of patients undergoing hepatectomy. The progressive improvements in survival, despite the increasing complexity of the surgery, area testament to advances in both surgery and anesthesia. The key elements include careful patient selection, appropriate monitoring, and mechanical and pharmacologic protection of the liver and other vital organs.

The effects of an anti-CD23 monoclonal antibody (B3B4) in CD23-deficient and CD23-overexpressing mice were compared in a murine model of allergic sensitization. After sensitization and challenge with OA, mice developed increased serum levels of OA-specific IgE and IgG(1) with airway eosinophilia and AHR when compared with nonsensitized animals. Anti-CD23 treatment was studied under two protocols: 10-d OA aerosol exposure and intraperitoneal sensitization followed by aerosol challenge. In both protocols anti-CD23 significantly reduced IgE and IgG(1) levels, abolished eosinophilia, and normalized AHR in BALB/c and wild-type CD23+/+ mice but not in CD23-/- mice. These changes were associated with increases in IFN-gamma and decreases in IL-4 production, suggesting that CD23 binding may affect not only IgE production but also the Th1/Th2 imbalance during the development of allergic AHR. Absence of CD23 in gene-deficient mice significantly enhanced OA-specific IgE and IgG(1) levels, airway eosinophilia, and AHR when compared with CD23+/+ wild-type littermates after sensitization and airway challenge. Sensitized and challenged CD23 transgenic mice also developed eosinophilic airway inflammation and methacholine hyperresponsiveness. However, the extent of AHR, BAL, and tissue eosinophilia in these animals showed a significant negative correlation with levels of CD23 expression on splenic T and B cells, demonstrating a limiting role of CD23 in the development of allergic AHR.

Allergic sensitization in asthma develops as a consequence of complex interactions between T cells and antigen-presenting cells. We have developed several in vivo models to study allergen-specific T cell and B cell function and their relevance to allergic airway hyperresponsiveness (AHR), focusing on the role of the costimulatory molecules CD80 and CD86. Treatment of mice with anti-CD86, but not anti-CD80, significantly inhibited increased serum levels of ovalbumin (OA)-specific IgE and IgG1, airway eosinophilia, and AHR both after 10 d of OA aerosol exposure (in the absence of adjuvant) and after intraperitoneal sensitization followed by repeated airway challenges. Inhibition of AHR was associated with decreased IL-4 and IL-5 levels in the BAL fluid of sensitized mice, suggesting impaired Th2 function in anti-CD86-treated animals. This effect was not seen when mice received treatment only before allergen challenge, indicating that anti-CD86 acts through inhibition of allergic sensitization and not simply by inhibiting the influx of inflammatory cells. These data suggest that the CD86 costimulatory ligand plays a major role in the development of allergic inflammation and AHR in allergen-challenged mice. Further, this study demonstrates that T-B cell interactions during allergic sensitization are amenable to therapeutic manipulation and that selective blockade of accessory signals can be an effective means for modulating distinct T cell functions.

We used isobolographic analysis to investigate the interaction of decamethonium with either hexamethonium or vecuronium in the rat phrenic nerve hemidiaphragm preparation. EC50 values of decamethonium, hexamethonium, and vecuronium were (mean +/- SEM) 47.36 +/- 9.58 microM, 4.27 +/- 0.53 mM, and 5.19 +/- 1.17 microM, respectively. Combinations of drugs in concentrations corresponding to the 1:2, 1:1, and 2:1 ratios of their EC50 values were used to determine three points of each isobole. Decamethonium and hexamethonium showed antagonism: significant deviations from the line of additivity were found at EC50 ratios of 2:1 and 1:1 (P < 0.01 and P < 0.05, respectively) indicating that hexamethonium is a potent antagonist of decamethonium. For decamethonium and vecuronium none of the three points on the isobole was significantly different from the corresponding point on the line of additivity. Hexamethonium is known to be a weak antagonist at the postsynaptic nicotinic acetylcholine receptor but a potent antagonist at the presynaptic nicotinic receptor. Vecuronium is a more potent antagonist at the postsynaptic nicotinic receptor but a much weaker antagonist at the presynaptic site. It was postulated that in the rat the primary site of action of decamethonium is at the presynaptic nerve terminal. Our findings suggest that presynaptic rather than postsynaptic potency of a nondepolarizing drug determines ability to antagonize the effect of a depolarizing drug in the rat.

We studied the effects of rocuronium and vecuronium as priming agents before both vecuronium and rocuronium neuromuscular blockade. Rocuronium is ineffective at priming rocuronium. Vecuronium is effective at priming rocuronium, producing an approximate 33% reduction in onset time. Rocuronium and vecuronium, when given as priming agents, both reduce the onset time of vecuronium block.

To predict postoperative infection after Caesarean section by bacteriological examination of amniotic fluid samples a prospective analysis was performed on amniotic fluid bacteriological results and infectious morbidity in 266 consecutive Caesarean sections. Culture and sensitivity results were analysed in relation to postoperative febrile complications and their antibiotic treatment. One hundred and twelve samples grew bacteria. There was a significantly higher frequency of postoperative pyrexial complications among those patients with a positive amniotic fluid culture (22.3% vs 14.2%). Eighty per cent of amniotic fluid samples with significant bacterial growth provided useful information when antibiotic treatment had been required. Routine amniotic fluid sampling for bacteriology at Caesarean section is of clinical value in the prediction and management of postoperative pyrexial complications.