Diagnosis of common bile duct stones by intravenous cholangiography:prediction by ultrasound and liver function tests compared with endoscopic retrograde cholangiography

Routine intravenous cholangiography using the safer contrast medium, meglumine iotroxate, may be a useful investigation prior to laparoscopic cholecystectomy for the detection of suspected common bile duct stones. We compared this with endoscopic cholangiography.

Affinity-Purified Respiratory Syncytial Virus Antibodies from Intravenous Immunoglobulin Exert Potent Antibody-Dependent Cellular Cytotoxicity

Mixed infections are one of the major therapeutic challenges, as the current strategies have had limited success. One of the most common and widespread conditions of mixed infection is respiratory syncytial virus-mediated pathology of the respiratory tract in children. There is a dire need for the development of novel therapeutic approaches during mixed infections. Therapeutic intravenous immunoglobulin preparations, obtained from plasma pools of healthy donors have been used in immune deficiencies. This study was thus designed to characterize the functional efficacy of RSV-specific antibodies in IVIg. To explore the functional ability of these affinity-purified RSV-specific antibodies, the antibody-dependent and complement dependent cytotoxicity was determined using peripheral cells of healthy donors. This study demonstrates the existence of highly potent RSV-specific antibodies in IVIg preparations and provides the basis for the use of IVIg as broad-spectrum protective shield to RSV-infected children during mixed infections

A study of patient attitudes towards fasting prior to intravenous sedation for dental treatment in a dental hospital department

INTRODUCTION: Intravenous sedation is the most commonly used method of sedation for the provision of adult dental care. However, disparity exists in pre-operative fasting times in use for patients throughout the United Kingdom.

AIMS: The aims of the study were to obtain information on the effects of existing extended pre-operative fasting regimens, to canvas patient opinions on the fasting process, and to record their positive and negative experiences associated with it.

METHODS: A prospective cross-sectional descriptive study using survey methodology was conducted of adult patients attending a dental hospital for operative treatment under intravenous sedation. Sixty-four questionnaires were distributed over a four-month period, beginning 2nd October 2007.

RESULTS: The surveyed patient pool consisted of 38 females and 14 males with a mean age of 32.4 years. The response rate achieved was 81.2%. Seventy-one per cent of patients indicated that normally they consumed something for breakfast, the most common items being tea and toast. Fifty-one per cent of patients indicated that they would wish to eat the same as normal prior to their appointment and 59% wished to drink as normal. Only 19% of respondents reported that they did not wish to eat anything, with 8% preferring not to drink anything at all. Seventy-nine per cent of the patients reported that they had experienced at least one adverse symptom after fasting and 42% had experienced two or more such symptoms. In general, those patients with more experience of sedation found fasting less unpleasant than those attending for the first time (P<0.05). In addition, one-quarter of all patients indicated that the fasting process had made them feel more nervous about their sedation appointment.

CONCLUSIONS: The extended fasting regimen prior to intravenous sedation appeared to affect patients' wellbeing, as the majority reported adverse symptoms.

Pre-operative fasting for intravenous conscious sedation used in dental treatment: are conclusions based on relative risk management or evidence?

Intravenous sedation is a widely used pharmacological method of patient management commonly used in dental surgery for the treatment of anxious patients. Variety exists in fasting regimes between different centres offering dental sedation, with some advocating starvation in line with general anaesthesia protocols and others not enforcing starvation at all. The currently available guidelines on fasting protocols are ambiguous and open to interpretation partly because they are based on expert opinion rather than evidence-based research. This article reviews the available evidence on the subject of pre-operative fasting and discusses current guidelines.

Effect of intravenous haloperidol on the duration of delirium and coma in critically ill patients (Hope-ICU):A randomised, double-blind, placebo-controlled trial

Background: Delirium is frequently diagnosed in critically ill patients and is associated with poor clinical outcomes. Haloperidol is the most commonly used drug for delirium despite little evidence of its effectiveness. The aim of this study was to establish whether early treatment with haloperidol would decrease the time that survivors of critical illness spent in delirium or coma. Methods: We did this double-blind, placebo-controlled randomised trial in a general adult intensive care unit (ICU). Critically ill patients (≥18 years) needing mechanical ventilation within 72 h of admission were enrolled. Patients were randomised (by an independent nurse, in 1:1 ratio, with permuted block size of four and six, using a centralised, secure web-based randomisation service) to receive haloperidol 2·5 mg or 0·9% saline placebo intravenously every 8 h, irrespective of coma or delirium status. Study drug was discontinued on ICU discharge, once delirium-free and coma-free for 2 consecutive days, or after a maximum of 14 days of treatment, whichever came first. Delirium was assessed using the confusion assessment method for the ICU (CAM-ICU). The primary outcome was delirium-free and coma-free days, defined as the number of days in the first 14 days after randomisation during which the patient was alive without delirium and not in coma from any cause. Patients who died within the 14 day study period were recorded as having 0 days free of delirium and coma. ICU clinical and research staff and patients were masked to treatment throughout the study. Analyses were by intention to treat. This trial is registered with the International Standard Randomised Controlled Trial Registry, number ISRCTN83567338. Findings: 142 patients were randomised, 141 were included in the final analysis (71 haloperidol, 70 placebo). Patients in the haloperidol group spent about the same number of days alive, without delirium, and without coma as did patients in the placebo group (median 5 days [IQR 0-10] vs 6 days [0-11] days; p=0·53). The most common adverse events were oversedation (11 patients in the haloperidol group vs six in the placebo group) and QTc prolongation (seven patients in the haloperidol group vs six in the placebo group). No patient had a serious adverse event related to the study drug. Interpretation: These results do not support the hypothesis that haloperidol modifies duration of delirium in critically ill patients. Although haloperidol can be used safely in this population of patients, pending the results of trials in progress, the use of intravenous haloperidol should be reserved for short-term management of acute agitation. Funding: National Institute for Health Research. © 2013 Elsevier Ltd.

Bactericidal/permeability-increasing protein attenuates systemic inflammation and acute lung injury in porcine lower limb ischemia-reperfusion injury.

OBJECTIVE: To investigate the role of recombinant bactericidal/permeability-increasing protein (rBPI21) in the attenuation of the sepsis syndrome and acute lung injury associated with lower limb ischemia-reperfusion (I/R) injury. SUMMARY BACKGROUND DATA: Gut-derived endotoxin has been implicated in the conversion of the sterile inflammatory response to a lethal sepsis syndrome after lower torso I/R injury. rBPI21 is a novel antiendotoxin therapy with proven benefit in sepsis. METHODS: Anesthetized ventilated swine underwent midline laparotomy and bilateral external iliac artery occlusion for 2 hours followed by 2.5 hours of reperfusion. Two groups (n = 6 per group) were randomized to receive, by intravenous infusion over 30 minutes, at the start of reperfusion, either thaumatin, a control-protein preparation, at 2 mg/kg body weight, or rBPI21 at 2 mg/kg body weight. A control group (n = 6) underwent laparotomy without further treatment and was administered thaumatin at 2 mg/kg body weight after 2 hours of anesthesia. Blood from a carotid artery cannula was taken every half-hour for arterial blood gas analysis. Plasma was separated and stored at -70 degrees C for later determination of plasma tumor necrosis factor (TNF)-alpha, interleukin (IL)-6 by bioassay, and IL-8 by enzyme-linked immunosorbent assay (ELISA), as a markers of systemic inflammation. Plasma endotoxin concentration was measured using ELISA. Lung tissue wet-to-dry weight ratio and myeloperoxidase concentration were used as markers of edema and neutrophil sequestration, respectively. Bronchoalveolar lavage protein concentration was measured by the bicinclinoic acid method as a measure of capillary-alveolar protein leak. The alveolar-arterial gradient was measured; a large gradient indicated impaired oxygen transport and hence lung injury. RESULTS: Bilateral hind limb I/R injury increased significantly intestinal mucosal acidosis, intestinal permeability, portal endotoxemia, plasma IL-6 concentrations, circulating phagocytic cell priming and pulmonary leukosequestration, edema, capillary-alveolar protein leak, and impaired gas exchange. Conversely, pigs treated with rBPI21 2 mg/kg at the onset of reperfusion had significantly reduced intestinal mucosal acidosis, portal endotoxin concentrations, and circulating phagocytic cell priming and had significantly less pulmonary edema, leukosequestration, and respiratory failure. CONCLUSIONS: Endotoxin transmigration across a hyperpermeable gut barrier, phagocytic cell priming, and cytokinemia are key events of I/R injury, sepsis, and pulmonary dysfunction. This study shows that rBPI21 ameliorates these adverse effects and may provide a novel therapeutic approach for prevention of I/R-associated sepsis syndrome.

A phase Ib trial of Docetaxel, Carboplatin and Erlotinib in ovarian, fallopian tube and primary peritoneal cancers.

The safety and maximum tolerated dose (MTD) of erlotinib with docetaxel/carboplatin were assessed in patients with ovarian cancer. Chemonaive patients received intravenous docetaxel (75 mg m(-2)) and carboplatin (area under the curve 5) on day 1 of a 3-week cycle, and oral erlotinib at 50 (cohort 1), 100 (cohort 2a) or 75 mg day(-1) (cohort 2b) for up to six cycles. Dose-limiting toxicities were determined in cycle 1. Forty-five patients (median age 59 years) received treatment. Dose-limiting toxicities occurred in 1/5/5 patients (cohorts 1/2a/2b). The MTD of erlotinib in this regimen was determined to be 75 mg day(-1) (cohort 2b; the erlotinib dose was escalated to 100 mg day(-1) in 11 out of 19 patients from cycle 2 onwards). Neutropaenia was the predominant grade 3/4 haematological toxicity (85/100/95% respectively). Common non-haematological toxicities were diarrhoea, fatigue, nausea and rash. There were five complete and seven partial responses in 23 evaluable patients (52% response rate). Docetaxel/carboplatin had no measurable effect on erlotinib pharmacokinetics. In subsequent single-agent maintenance, erlotinib was given at 100-150 mg day(-1), with manageable toxicity, until tumour progression. Further investigation of erlotinib in epithelial ovarian carcinoma may be warranted, particularly as maintenance therapy

The effect of treatment of cystic fibrosis pulmonary exacerbations on airways and systemic inflammation

Background: Chronic infection in cystic fibrosis (CF) and airway inflammation leads to progressive lung injury Neutrophils are considered to be responsible for the onset and promotion of the inflammatory response within the CF lung. The relationship between infection and inflammation is complex but circulating inflammatory markers may not truly reflect the local inflammatory response in the lung. The aims of this study were to investigate the change of inflammatory biomarkers and cells within sputum and blood before and after intravenous antibiotics for a pulmonary exacerbation of CF Methods: Assays included neutrophil elastase (NE) and complex, interleukin-8 (IL-8) and soluble intercellular adhesion molecule-1 (sICAM-1), fas ligand (FAS-L), and TNFr-1. Analysis of sputum cell differential and absolute cell counts and immunocytochemistry (CD11b and CD95) on sputum and isolated blood neutrophils were carried out. Results: There were no significant differences in absolute or differential sputum cell counts or sputum sol measurements following antibiotics. There was a significant increase in the percentage of blood neutrophils with minimal CD11b staining, 28 (4.1) mean percentage (SEM) versus41 (2.9) and a decrease in the percentage showing maximal staining 30 (0.5) versus 15 (2.5). There was a significant increase in the percentage of blood neutrophils without CD95 staining, 43 (5.4) mean percentage versus 52 (5.1). Conclusion: These data suggest a modifiable systemic response to IV antibiotics but a local sustained inflammatory response in the lung.

Utilization of analgesics, sedatives, and pain scores in infants with a prolonged hospitlaization: A prospective descriptive cohort study

Aim
Describe the utilization of analgesic and sedative medications and documentation of pain scores in a cohort of critically ill infants in a neonatal intensive care unit.

Method
A prospective, longitudinal, cohort study of infants with a predicted length of stay =28 days. Dosages and routes of administration of analgesic and sedative medications and documentation of pain scores were collected on a daily basis.

Results
55 infants were enrolled into the study. Oral sucrose was administered to all 55 infants, 51 infants (93%) were administered enteral acetaminophen and 50 (91%) infants were administered morphine during their hospitalization. Sedatives were administered to 42 infants (76%); 36 (65%) were administered chloral hydrate and 32 (58%) were administered intravenous midazolam. With the exception of the first week of admission, when there was highest utilization of opioids and lower use of sucrose, acetaminophen and sedatives, the pattern of administration of analgesic and sedative agents remained relatively constant throughout the hospitalization. Pain scores were documented for 36 (65%) infants during their hospitalisation, however for these 36 infants, pain scores were infrequently recorded.

Conclusion
There was substantial and varied analgesic and sedative use in this cohort of infants, yet infrequent documentation of pain assessment scores. These practices highlight important clinical implications for sick infants requiring careful consideration of pain and distress management.

Quality of life and inflammation in exacerbations of bronchiectasis.

Patients with bronchiectasis often have impaired quality of life (QoL), which deteriorates with exacerbations. The aim of this study was to investigate changes in QoL and how these were influenced by changes in airway physiology and inflammation in patients with bronchiectasis before and after resolution of an exacerbation. Sputum induction and a QoL questionnaire were undertaken on the first day, day 14, and 4 weeks after completion of intravenous antibiotics (day 42). Eighteen patients (12 female) were recruited, median (IQ range) age of 54 (47–60) years. There was a trend towards an improvement in lung function from visit 1 to visit 2, but this was not statistically significant. C-reactive protein (CRP) [mean (SEM)] reduced between visit 1 and visit 2 [55.4 (21.5) vs 9.4 (3.1) mg/L, P = 0.03] but did not increase significantly on visit 3 [44.4 (32.9) mg/L, P = 0.27]. The median (interquartile range) sputum cell count (×106 cells/g of sputum) decreased from visit 1 to visit 2 [21.6 (11.8–37.6)–13.3 (6.7–22.9) × 106 cells/g, respectively, P = 0.008] and increased from visit 2 to visit 3 [26.3 (14.1–33.6) × 106 cells/g, P = 0.03]. All soluble markers of inflammation significantly reduced from visit 1 to visit 2 but increased on visit 3 with the exception of TNF-a. Regarding QoL, three of the four domains (dyspnoea, emotional, mastery) significantly improved from visit 1 to visit 2 but did not change between visit 2 and visit 3. The improvements in QoL scores could not be explained by the improvements in lung function or inflammatory markers.

Incorporation of novel 1-alkylcarbonyloxymethyl prodrugs of 5-fluorouracil into poly(lactide-co-glycolide) nanoparticles

Incorporation of 1-alkylcarbonyloxymethylprodrugs of 5FU into poly(lactide-co-glycolide) nanoparticles using nanoprecipitation methods gave increased loading efficiencies over that obtained using the parent drug substance. SEM studies revealed spherical nanoparticles of around 200 nm in diameter, corresponding well with measurements made using photon correlation spectroscopy. The C-7 prodrug gave the best mean loading of 47.23%, which compared favourably to 3.68% loading achieved with 5FU. Loading efficiency was seen to follow the hydrophilic-lipophilic balance in the homologue series, where increases in lipophilicities alone were not good predictors of loading. Drug release, in terms of resultant 5FU concentration, was monitored using a flow-through dissolution apparatus. Cumulative drug release from nanoparticles loaded with the C-5 prodrug was linear over 6h, with approximately 14% of the total available 5FU dose released and with no evidence of a burst effect. The flux profile of the C-5-loaded nanoparticles showed an initial peak in flux in the first sampling interval, but became linear for the remainder of the release phase. C-7-loaded nanoparticles released considerably less (4% in 6 h) with a similar flux pattern to that seen with the C-5 prodrug. The C-9-loaded nanoparticles released less than 1% of the available 5FU over 6 h, with a similar zero-order profile. The C7 prodrug was deemed to be the prodrug of choice, achieving the highest loadings and releasing 5FU, following hydrolysis, in a zero-order fashion over a period of at least 6 h. Given the lack of burst effect and steady-state flux conditions, this nanoparticulate formulation offers a better dosing strategy for sustained intravenous use when compared to that arising from nanoparticles made by direct incorporation of 5FU. (c) 2007 Elsevier B.V. All rights reserved.