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2.
BMJ Mil Health ; 166(2): 76-79, 2020 Apr.
Article in English | MEDLINE | ID: mdl-30012665

ABSTRACT

UK Defence Medical Services' personnel have experienced an intense exposure to patients injured during war over the last decade and a half. As some bitter lessons of war surgery were relearned and innovative practices introduced, outcomes for patients impr oved consistently as experience accumulated. The repository of many of the enduring lessons learnt at the Role 4 echelon of care remain at the Queen Elizabeth Hospital Birmingham (QEHB), with the National Health Service and Defence Medical Services personnel who treated the returning casualties. On 22 May 2017, a terrorist detonated an improvised explosive device at the Manchester Arena, killing 22 and wounding 159 people. In the aftermath of the event, QEHB was requested to provide support to the Manchester clinicians and teleconferencing and then two clinical visits were arranged. This short report describes the nature of the visits, outlines the principles of Military Aid to the Civil Authority and looks to the future role of the Defence Medical Services in planning and response to UK terrorism events.


Subject(s)
Bombs , Emergency Medical Services/organization & administration , Mass Casualty Incidents , Military Personnel , State Medicine , Terrorism , Humans , United Kingdom
3.
J Crit Care ; 30(5): 901-7, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26004031

ABSTRACT

PURPOSE: Patients recovering from critical illness may be left with significant muscle mass loss. This study aimed to evaluate whether a 6-week program of enhanced physiotherapy and structured exercise (PEPSE) and an essential amino acid supplement drink (glutamine and essential amino acid mixture [GEAA]) improves physical and psychological recovery. MATERIALS AND METHODS: Intensive care patients aged 45 years or older, with a combined intensive care unit stay/pre-intensive care unit stay of 5 days or more were recruited to a randomized controlled trial examining the effect of PEPSE and GEAA on recovery. The 2 factors were tested in a 2 × 2 factorial design: (1) GEAA drink twice daily for 3 months and (2) 6-week PEPSE in first 3 months. Primary efficacy outcome was an improvement in the 6-minute walking test at 3 months. RESULTS: A total of 93 patients were randomized to the study. Patients receiving the PEPSE and GEA had the biggest gains in distance walked in 6-minute walking test (P < .0001). There were also significant reductions in rates of anxiety in study groups control supplement/PEPSE (P = .047) and GEAA supplement/PEPSE (P = .036) and for GEAA supplement/PEPSE in depression (P = .0009). CONCLUSION: Enhanced rehabilitation combined with GEAA supplement may enhance physical recovery and reduce anxiety and depression.


Subject(s)
Ambulatory Care/methods , Amino Acids, Essential/administration & dosage , Critical Illness/rehabilitation , Physical Therapy Modalities , Analysis of Variance , Anxiety/prevention & control , Critical Care/methods , Depression/prevention & control , Dietary Supplements , Double-Blind Method , Exercise Therapy/methods , Female , Glutamine/administration & dosage , Humans , Intensive Care Units , Male , Middle Aged , Quality of Life , Walking/physiology
4.
Intensive Care Med ; 38(4): 598-605, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22278594

ABSTRACT

OBJECTIVES: To define a set of indicators that could be used to improve quality in intensive care medicine. METHODOLOGY: An European Society of Intensive Care Medicine Task Force on Quality and Safety identified all commonly used key quality indicators. This international Task Force consisted of 18 experts, all with a self-proclaimed interest in the area. Through a modified Delphi process seeking greater than 90% consensual agreement from this nominal group, the indicators were then refined through a series of iterative processes. RESULTS: A total of 111 indicators of quality were initially found, and these were consolidated into 102 separate items. After five discrete rounds of debate, these indicators were reduced to a subset of nine that all had greater than 90% agreement from the nominal group. These indicators can be used to describe the structures (3), processes (2) and outcomes (4) of intensive care. Across this international group, it was much more difficult to obtain consensual agreement on the indicators describing processes of care than on the structures and outcomes. CONCLUSION: This document contains nine indicators, all of which have a high level of consensual agreement from an international Task Force, which could be used to improve quality in routine intensive care practice.


Subject(s)
Critical Care/standards , Critical Illness , Patient Safety , Quality Improvement , Quality Indicators, Health Care , Advisory Committees , Delphi Technique , Europe , Humans , Prospective Studies
5.
Br J Pharmacol ; 165(6): 1737-1747, 2012 Mar.
Article in English | MEDLINE | ID: mdl-21827450

ABSTRACT

BACKGROUND AND PURPOSE: Inhaled corticosteroids (ICS) are the cornerstone of asthma pharmacotherapy and, acting via the glucocorticoid receptor (GR), reduce inflammatory gene expression. While this is often attributed to a direct inhibitory effect of the GR on inflammatory gene transcription, corticosteroids also induce the expression of anti-inflammatory genes in vitro. As there are no data to support this effect in asthmatic subjects taking ICS, we have assessed whether ICS induce anti-inflammatory gene expression in subjects with atopic asthma. EXPERIMENTAL APPROACH: Bronchial biopsies from allergen-challenged atopic asthmatic subjects taking inhaled budesonide or placebo were subjected to gene expression analysis using real-time reverse transcriptase-PCR for the corticosteroid-inducible genes (official gene symbols with aliases in parentheses): TSC22D3 [glucocorticoid-induced leucine zipper (GILZ)], dual-specificity phosphatase-1 (MAPK phosphatase-1), both anti-inflammatory effectors, and FKBP5 [FK506-binding protein 51 (FKBP51)], a regulator of GR function. Cultured pulmonary epithelial and smooth muscle cells were also treated with corticosteroids before gene expression analysis. KEY RESULTS: Compared with placebo, GILZ and FKBP51 mRNA expression was significantly elevated in budesonide-treated subjects. Budesonide also increased GILZ expression in human epithelial and smooth muscle cells in culture. Immunostaining of bronchial biopsies revealed GILZ expression in the airways epithelium and smooth muscle of asthmatic subjects. CONCLUSIONS AND IMPLICATIONS: Expression of the corticosteroid-induced genes, GILZ and FKBP51, is up-regulated in the airways of allergen-challenged asthmatic subjects taking inhaled budesonide. Consequently, the biological effects of corticosteroid-induced genes should be considered when assessing the actions of ICS. Treatment modalities that increase or decrease GR-dependent transcription may correspondingly affect corticosteroid efficacy.


Subject(s)
Adrenal Cortex Hormones/therapeutic use , Anti-Inflammatory Agents/therapeutic use , Asthma/genetics , Bronchodilator Agents/therapeutic use , Budesonide/therapeutic use , Gene Expression/drug effects , Administration, Inhalation , Allergens/pharmacology , Asthma/drug therapy , Cell Line, Tumor , Cross-Over Studies , Dual Specificity Phosphatase 1/genetics , Epithelial Cells/drug effects , Epithelial Cells/metabolism , Humans , Lung/cytology , Lung/drug effects , Lung/metabolism , Myocytes, Smooth Muscle/drug effects , Myocytes, Smooth Muscle/metabolism , RNA, Messenger/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Tacrolimus Binding Proteins/genetics , Transcription Factors/genetics
6.
Postgrad Med J ; 87(1032): 694-9, 2011 Oct.
Article in English | MEDLINE | ID: mdl-21788232

ABSTRACT

BACKGROUND: The incidence and prevalence of obesity are increasing world wide. In the UK, obesity governmental strategy has primarily focused on prevention measures, with less focus on the demands of treating obese patients in hospital. Increasing service demand by obese patients coupled with a lack of adequate provision for care of these patients may lead to an increase in patient safety incidents. By classifying patient safety incidents associated with obesity reported to the National Patient Safety Agency, this report aims to identify areas for improvement in the quality and safety of care of the obese patient. METHODS: A search of the National Reporting and Learning System database was conducted for all incidents caused by or relating to obesity for the period 1 January 2005 to 31 August 2008. The keywords 'obesity', 'overweight', 'BMI' (body mass index), and 'bariatric' were used. The relevant free text fields of the resulting set of incidents were then searched for the terms designed to isolate incidents occurring in anaesthesia, critical care, and surgery. Reported incidents were analysed and subsequently categorised to identify incident themes. Levels of harm were also established. RESULTS: 555 patient safety incidents were identified; 388 met inclusion criteria for analysis. 148 incidents were related to assessment, diagnosis or treatment, 213 related to infrastructure and 27 related to staffing. The majority of incidents were classified as no or low harm. Three deaths were reported, all within the domain of anaesthesia. CONCLUSIONS: This report identifies that the majority of safety incidents associated with obesity were related to infrastructure, suggesting that there is inadequate provision in place for the care of obese patients. While levels of harm were mostly low, the occurrence of incidents resulting in severe harm or death highlights the specific dangers associated with the care of the obese patient. A global approach to improving the safety of care delivery for obese patients is recommended, including obesity specific training, management structures, care pathways, and equipment provisioning.Further planning and development of operation policies is needed to ensure the safe delivery of healthcare to obese patients in the future.


Subject(s)
Databases, Factual/statistics & numerical data , Obesity/complications , Patient Safety/statistics & numerical data , Practice Guidelines as Topic/standards , Safety Management/organization & administration , Delivery of Health Care/standards , Delivery of Health Care/statistics & numerical data , Humans , State Medicine , United Kingdom/epidemiology
7.
Int Immunopharmacol ; 7(14): 1880-7, 2007 Dec 20.
Article in English | MEDLINE | ID: mdl-18039525

ABSTRACT

Increased levels of kinins have been detected within the airways during upper respiratory viral infections (URIs). Rhinovirus, the major URI associated with acute exacerbations of asthma, is an ssRNA virus that primarily infects the airway epithelium and produces dsRNA during replication. We asked whether dsRNA could increase the expression of kinin receptors in airway epithelial cells, thereby potentiating the inflammatory consequences of kinin generation. Human airway epithelial cell line BEAS-2B was stimulated with the dsRNA analog Poly I:C and kinin receptor expression detected by quantitative RT-PCR as well as radioligand binding. Poly I:C induced an increase in B1 and B2 receptor mRNA levels in BEAS-2B and primary human normal bronchial epithelial cells. At the cell surface, only B1 receptor expression was increased by Poly I:C. Furthermore, pretreatment of BEAS-2B cells with Poly I:C enhanced the induction of phospho-ERK following B1 receptor ligand stimulation. To investigate whether these finding had potential in vivo relevance, we assessed B1 receptor expression in nasal tissue obtained from 8 normal human subjects with URIs and 3 control subjects. Five of the URI subjects demonstrated increased B1 receptor mRNA compared to the 3 control subjects. We suggest that increased expression of B1 receptor in the human airway following a URI could increase the risk of an exacerbation of asthma by contributing to increased inflammation in the airway.


Subject(s)
Bronchi/metabolism , RNA, Double-Stranded/physiology , Receptor, Bradykinin B1/genetics , Respiratory Mucosa/metabolism , Cell Line , Cells, Cultured , Dose-Response Relationship, Drug , Extracellular Signal-Regulated MAP Kinases/metabolism , Gene Expression/genetics , Humans , Picornaviridae Infections/metabolism , Picornaviridae Infections/virology , Poly I-C/pharmacology , RNA, Double-Stranded/pharmacology , RNA, Messenger/biosynthesis , RNA, Messenger/drug effects , Receptor, Bradykinin B1/drug effects , Receptor, Bradykinin B1/metabolism , Receptor, Bradykinin B2/drug effects , Receptor, Bradykinin B2/genetics , Receptor, Bradykinin B2/metabolism , Respiratory Mucosa/cytology , Respiratory Tract Infections/metabolism , Respiratory Tract Infections/virology , Rhinovirus/metabolism , Up-Regulation
9.
Scand J Gastroenterol ; 38(12): 1262-7, 2003 Dec.
Article in English | MEDLINE | ID: mdl-14750647

ABSTRACT

BACKGROUND: To observe outcome in a cohort of patients with severe acute pancreatitis receiving multiple anti-oxidant therapy. METHODS: An observational study was carried out in 46 consecutive patients with acute pancreatitis fulfilling current Atlanta consensus criteria for severe disease. All patients received multiple anti-oxidant therapy based on intravenous selenium, N-acetylcysteine and ascorbic acid plus beta-carotene and alpha-tocopherol delivered via nasogastric tube. Principal outcomes were the effect of anti-oxidant supplementation on anti-oxidant levels, morbidity and mortality in patients on anti-oxidant therapy, case-control analysis of observed survival compared to predicted survival derived from logistic organ dysfunction score (LODS), logistic regression analysis of factors influencing outcome and side effect profile of anti-oxidant therapy. RESULTS: Paired baseline and post-supplementation data were available for 25 patients and revealed that anti-oxidant supplementation restored vitamin C (P = 0.003) and selenium (P = 0.028) toward normal. In univariate survival analysis, patient survival to discharge was best predicted by admission APACHE-II score with relative risk of death increasing 12.6% for each unit increase (95% CI 6.0% to 19.6%). The mean LODS calculated on admission to hospital was 3.7 (standard error of the mean 4.1) giving a predicted mortality for the cohort of 21%. The observed in-hospital mortality was 43%. CONCLUSIONS: Case-control analyses do not appear to demonstrate any benefit from the multiple anti-oxidant combination of selenium, N-acetylcysteine and ascorbic acid in severe acute pancreatitis.


Subject(s)
Acetylcysteine/administration & dosage , Antioxidants/administration & dosage , Ascorbic Acid/administration & dosage , Pancreatitis/drug therapy , Selenium/administration & dosage , Acute Disease , Adolescent , Adult , Aged , Aged, 80 and over , Antioxidants/adverse effects , Antioxidants/metabolism , Drug Therapy, Combination , Female , Humans , Infusions, Intravenous , Male , Middle Aged , Oxidative Stress , Pancreatitis/metabolism , Pancreatitis/mortality , Survival Rate , alpha-Tocopherol/administration & dosage , beta Carotene/administration & dosage
10.
J Vasc Surg ; 33(4): 758-63, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11296329

ABSTRACT

PURPOSE: Colonic ischemia after aortic surgery is associated with increased mortality and morbidity rates. This study was conducted as a single-center side arm to a multicenter, randomized, placebo-controlled study to evaluate the effect of dopexamine hydrochloride on its incidence. METHODS: Thirty patients, mean age 65.1 years (range, 46-84), undergoing elective infrarenal aortic surgery were entered. Preoperative hemodynamic and respiratory parameters were optimized. Patients were then randomly assigned to receive a perioperative infusion of dopexamine at 2 microg/kg per minute (n = 12) or 0.9% saline placebo (n = 18). All patients underwent colonoscopy and biopsy preoperatively and 1 week postoperatively. Specimens were assessed for evidence of mucosal ischemia, presence of mast cell tryptase, myeloperoxidase activity, and both the inducible and endothelial isoforms of nitric oxide synthase. RESULTS: There was no significant difference in perioperative fluid and blood requirements or hemodynamic and respiratory parameters between the two groups. However, there was significantly less evidence of mucosal ischemic changes in dopexamine-treated patients (n = 1) compared with placebo (n = 8) (P =.049). Furthermore, when preoperative biopsies were compared with those performed 1 week postoperatively, nine (50%) patients in the placebo group and two (16.7%) in the dopexamine group scored worse. Although there was no significant difference in inflammatory markers between the two groups, both mast cell tryptase and myeloperoxidase expression were increased in patients with histologic evidence of ischemia (P <.05). Furthermore, inducible nitric oxide synthase staining within the vascular (P =.001) and lamina propria (P <.05) components of the mucosa was also significantly greater. CONCLUSION: A perioperative dopexamine infusion affords significant histologic protection to colonic mucosa after aortic surgery.


Subject(s)
Aorta, Abdominal/surgery , Colon/blood supply , Dopamine Agonists/administration & dosage , Dopamine/analogs & derivatives , Dopamine/administration & dosage , Intestinal Mucosa/blood supply , Ischemia/prevention & control , Perioperative Care , Postoperative Complications/prevention & control , Vasodilator Agents/administration & dosage , Adult , Aged , Aged, 80 and over , Biopsy , Colon/enzymology , Colon/pathology , Colonoscopy , Female , Humans , Immunohistochemistry , Inflammation Mediators/analysis , Infusions, Intravenous , Intestinal Mucosa/enzymology , Intestinal Mucosa/pathology , Ischemia/etiology , Ischemia/pathology , Male , Middle Aged , Neutrophils/pathology , Nitric Oxide Synthase/analysis , Nitric Oxide Synthase Type II , Nitric Oxide Synthase Type III , Peroxidase/analysis , Prospective Studies , Serine Endopeptidases/analysis , Tryptases
11.
Crit Care Med ; 28(10): 3417-23, 2000 Oct.
Article in English | MEDLINE | ID: mdl-11057795

ABSTRACT

OBJECTIVE: To test the hypothesis that dopexamine reduces postoperative mortality and morbidity in high-risk, major abdominal surgery patients, when given to fluid-resuscitated patients starting before the operation and continued for 24 hrs after surgery. DESIGN: Prospective, randomized, controlled, double-blind multicenter trial. SETTING: Intensive care units in 13 hospitals from six European countries. PATIENTS: A total of 412 patients with predefined high-risk criteria, undergoing major abdominal surgery with an expected duration of at least 1.5 hrs. INTERVENTIONS: The patients received placebo (n = 140), dopexamine at 0.5 microg/kg/min (n = 135), or dopexamine at 2.0 microg/kg/ min (n = 137) starting after preoperative hemodynamic stabilization and continued for 24 hrs after surgery. MEASUREMENTS AND MAIN RESULTS: The primary outcome variable was mortality at 28 days. Analysis was by intention to treat. Dopexamine had no effect on mortality (at 28 days, 13%, 7%, and 15%, for the groups receiving placebo, dopexamine at 0.5 microg/kg/ min, and dopexamine at 2.0 microg/kg/min, respectively), despite the expected dose-dependent hemodynamic responses. No effect was observed on the occurrence of organ dysfunction, duration of intensive care unit stay, or length of hospital stay. CONCLUSION: We conclude that dopexamine in doses that result in increased cardiac output and oxygen delivery after preoperative stabilization with fluids does not improve outcome after major abdominal surgery compared with fluids alone. Based on post hoc subgroup analysis and stratification according to the number of risk factors, we suggest that the concept should be further tested in patients at higher risk of complications or undergoing emergency surgery.


Subject(s)
Adrenergic beta-Agonists/therapeutic use , Dopamine/analogs & derivatives , Laparotomy/adverse effects , Laparotomy/mortality , Vasodilator Agents/therapeutic use , Adrenergic beta-Agonists/pharmacology , Aged , Dopamine/pharmacology , Dopamine/therapeutic use , Dose-Response Relationship, Drug , Double-Blind Method , Female , Fluid Therapy/methods , Hemodynamics/drug effects , Humans , Male , Middle Aged , Morbidity , Perioperative Care/methods , Proportional Hazards Models , Prospective Studies , Resuscitation/methods , Risk Factors , Survival Analysis , Treatment Outcome , Vasodilator Agents/pharmacology
12.
Crit Care Med ; 28(7): 2293-9, 2000 Jul.
Article in English | MEDLINE | ID: mdl-10921555

ABSTRACT

OBJECTIVE: To assess survival, morbidity (physical and psychological), quality of life (QOL), and employment status of intensive care survivors up to 12 months after discharge from the intensive care unit (ICU). DESIGN: Prospective study. SETTING: University hospital adult ICU. PATIENTS: Between August 1, 1995, and July 31, 1996, 370 patients were admitted. Of these patients, 29% died in the ICU. Three months after discharge from the ICU, 227 patients were alive, and 143 agreed to participate. Cumulative mortality was calculated using the original complete cohort. MEASUREMENTS AND MAIN RESULTS: Demographic data, severity of acute illness (Acute Physiology and Chronic Health Evaluation [APACHE] II), admitting specialty, primary diagnosis, and length of stay were recorded. Physical and ICU-related psychological morbidity (Hospital Anxiety and Depression scale score) were recorded. Health-related QOL was assessed using the Short-Form 36. All the questionnaires were completed in the clinic at 3 months. Assessment of physical morbidity and employment status at 6 and 12 months were conducted by telephone. The cumulative mortality was 39% at 3 months, 41% at 6 months, and 43% at 12 months. Deaths after 3 months occurred in the group who refused follow-up. The median age for the follow-up group was 51 yrs; the gender split was 68 women and 75 men; the mean admission APACHE II score was 18.79 (SD 6.15); and the median length of ICU stay was 3.8 days. At 3 months, approximately 80% of all patients interviewed were satisfied with their QOL. Older men (>65 yrs) and younger women (<65 yrs) demonstrated significantly better health with respect to some subdomains of the Short-Form 36 compared with their counterparts. The prevalence of psychological distress (Hospital Anxiety and Depression scale score, > or =8) was low: 11.9% had heightened anxiety, and 9.8% were depressed. There were high levels of fatigue, poor concentration, and sleep disturbance; the latter was more marked in women (p = .022). Improvement in all three symptoms occurred during the next 9 months. Significantly more women reported loss of hair (p < .0001). Men were slower to return to employment; 75% of women had returned by 6 months compared with only 65% of men at 1 yr. CONCLUSION: Assessment of outcome after ICU stay must include QOL measurements. Three months after discharge, there is a low incidence of ICU-related psychological or psychiatric illness and the majority of patients are satisfied. Differences in the incidence and nature of morbidity exist between the genders.


Subject(s)
Health Status , Intensive Care Units , Morbidity , Patient Satisfaction , Quality of Life , APACHE , Aged , Employment , Female , Health Surveys , Hospital Mortality , Humans , Length of Stay , Male , Mental Health , Middle Aged , Patient Discharge , Prospective Studies , Sex Distribution , Surveys and Questionnaires , Survival Rate
13.
Crit Care Med ; 27(9): 1787-93, 1999 Sep.
Article in English | MEDLINE | ID: mdl-10507599

ABSTRACT

OBJECTIVE: To evaluate the effect of dopexamine on the incidence of acute inflammation in the stomach/duodenum in patients undergoing abdominal surgery > or =1.5 hrs with a minimum of one high-risk criterion. DESIGN: Prospective, randomized, double-blind, placebo-controlled study. This study was conducted as a side arm to a multicenter, multinational study. SETTING: University hospital in an adult intensive care unit. PATIENTS: Thirty-eight patients. INTERVENTIONS: Patients were stabilized with fluid, blood products, and supplementary oxygen to achieve predetermined goals: cardiac index > 2.5 L/min/m2, mean arterial blood pressure of 70 mm Hg, pulmonary arterial occlusion pressure of 10 mm Hg, hemoglobin of 100 g/L, and arterial saturation of 94%. After stabilization, the study drug (either placebo [group A], dopexamine 0.5 microg/kg/min [group B], or dopexamine 2.0 microg/kg/min [group C]) was commenced. The study drug infusion was started 2 to 12 hrs before surgery and infused for 24 hrs after surgery. Estimation of upper gut blood flow was assessed using a gastric tonometer, and gastroscopy with biopsy was performed before surgery (after induction of anesthesia) and 72 hrs after surgery. Comparisons were made between endoscopic findings and histologic proof of acute inflammatory changes. In addition, biopsies were assessed for the presence in the mucosa of mast cells, myeloperoxidase activity, and inducible nitric oxide synthase. MEASUREMENTS AND MAIN RESULTS: Intramucosal pH decreased significantly with time in all three groups (p < .001), reaching the lowest point at the end of surgery. There was no difference among the groups. Endoscopy visualized acute inflammatory changes in 58.3% of group A patients, 46.2% of group B patients, and 53.90% of group C patients after hemodynamic optimization. At 72 hrs, dopexamine-treated patients compared with placebo-treated patients had a significantly lower incidence of gastric and duodenal acute inflammatory changes, as defined by myeloperoxidase activity (37.5% in groups B and C vs. 86% in group A; p < .05). CONCLUSION: Dopexamine in doses of 0.5 and 2.0 microg/kg/min affords significant histologic protection to the upper gastrointestinal tract mucosa 72 hrs after operation in high-risk surgical patients undergoing abdominal surgery.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Dopamine/analogs & derivatives , Gastric Mucosa/drug effects , Inflammation/prevention & control , Intestinal Mucosa/drug effects , Postoperative Complications/immunology , Abdomen/surgery , Adult , Aged , Aged, 80 and over , Dopamine/therapeutic use , Double-Blind Method , Endoscopy, Gastrointestinal , Europe , Female , Gastric Mucosa/blood supply , Gastric Mucosa/immunology , Gastric Mucosa/pathology , Humans , Immunohistochemistry , Inflammation/immunology , Intestinal Mucosa/blood supply , Intestinal Mucosa/immunology , Intestinal Mucosa/pathology , Male , Mast Cells/metabolism , Middle Aged , Multicenter Studies as Topic , Neutrophils/metabolism , Nitric Oxide Synthase/metabolism , Postoperative Complications/prevention & control , Reperfusion Injury/etiology , Reperfusion Injury/metabolism , Systemic Inflammatory Response Syndrome/metabolism , Systemic Inflammatory Response Syndrome/prevention & control
14.
Br J Surg ; 86(5): 698, 1999 May.
Article in English | MEDLINE | ID: mdl-10361328

ABSTRACT

BACKGROUND: Mechanisms involved in the development of colon- ic ischaemia are not fully understood and there are conflicting reports regarding predisposing factors. The aim of this study was to evaluate the effect of dopexamine hydrochloride on the incidence of colonic ischaemia following aortic surgery and to correlate immunohistochemical markers of inflammatory activation in its pathogenesis. METHODS: Thirty patients, of mean age 65 (range 46-84) years, undergoing elective infrarenal aortic surgery were randomized to receive a perioperative infusion of either dopexamine 2 &mgr;g kg-1 min-1 (n = 12) or 0.9 per cent saline placebo (n = 18). All patients underwent colonoscopy and biopsy following induction of anaesthesia and at 1 week after operation. Sections were stained with haematoxylin and eosin, and for mast cell tryptase (MCT), myeloperoxidase (MPO) and both the inducible (iNOS) and endothelial (eNOS) isoforms of nitric oxide synthase. Sections were analysed blindly and independently by two histopathologists. Patient and operative data were collected and stored separately. RESULTS: Colonic ischaemia was noted in nine patients based on microscopic findings. Endoscopy alone had a sensitivity of 56 per cent. There was a significantly lower incidence of colonic ischaemia in patients receiving dopexamine compared with placebo (P < 0.05). One death resulted from colonic infarction in the placebo group 11 days after operation. There was increased MPO and MCT expression in patients with histological evidence of ischaemia (P < 0.05); iNOS staining within the vascular (P = 0.001) and lamina propria (P < 0.05) components of the mucosa was also significantly greater. No association was found with eNOS. CONCLUSION: Perioperative dopexamine infusion confers a degree of protection to colonic mucosa following aortic surgery, possibly through an anti-inflammatory effect.

15.
Genomics ; 56(2): 149-59, 1999 Mar 01.
Article in English | MEDLINE | ID: mdl-10051400

ABSTRACT

The Lp mouse mutant provides a model for the severe human neural tube defect (NTD), cranio-rachischisis. To identify the Lp gene, a positional cloning approach has been adopted. Previously, linkage analysis in a large intraspecific backcross was used to map the Lp locus to distal mouse chromosome 1. Here we report a detailed physical map of this region. The interval surrounding Lp has been cloned in a yeast artificial chromosome (YAC) contig consisting of 63 clones spanning approximately 3.2 Mb. Fifty sequence tagged sites (STSs) have been used to construct the contig and establish marker order across the interval. Based on the high level of conserved synteny between distal mouse chromosome 1 and human 1q21-q24, many of these STSs were designed from expressed sequences identified by cross-screening human and mouse databases of expressed sequence tags. Added to other known genes in the region, a total of 29 genes were located and ordered within the contig. Seven novel polymorphisms were identified within the region, allowing refinement of the genetic map and a reduction in the size of the physical interval containing the Lp gene. The Lp interval, between D1Mit113 and Tagln2, can be spanned by two nonchimeric overlapping YACs that define a physical distance of approximately 1 Mb. Within this region, 10 potential candidate genes have been mapped. The materials and genes described here will provide a resource for the identification and further study of the mutated Lp gene that causes this severe neural tube defect and will provide candidates for other defects known to map to the homologous region on human chromosome 1q.


Subject(s)
Chromosomes/genetics , DNA/genetics , Neural Tube Defects/genetics , Animals , Chromosomes, Artificial, Yeast , Cloning, Molecular , Contig Mapping , Female , Genetic Markers , Humans , Male , Mice , Mice, Inbred CBA , Mutation , Physical Chromosome Mapping
16.
Dev Genet ; 24(1-2): 165-77, 1999.
Article in English | MEDLINE | ID: mdl-10079519

ABSTRACT

Nhlh1 is a basic helix-loop-helix (bHLH) gene that has been implicated in mouse neurogenesis. Previous studies have shown it to be expressed in regions in which there are differentiating neurons during late embryonic and fetal development, but detailed studies of the role of Nhlh1 earlier in embryonic development have not been performed. In this paper, we examine the expression of Nhlh1 transcripts at early embryonic stages (E8.5-E10.5), at the onset of neurogenesis, and compare the pattern of expression with that of Islet-1, a marker of postmitotic neurons. We show that Nhlh1 is expressed in early postmitotic neurons but is down-regulated as these cells migrate from the ventricular zone. We have also determined the genomic structure of mouse Nhlh1 and have characterised the promoter sequence, as a first step towards identifying factors that may control Nhlh1 expression. Nhlh1 has been implicated previously as a candidate for the neural tube defect mutant loop-tail (Lp); here, we present sequence and expression data indicating that Nhlh1 is unlikely to be responsible for the Lp mutation.


Subject(s)
Central Nervous System/embryology , DNA-Binding Proteins/genetics , Embryo, Mammalian/metabolism , Ganglia/embryology , Gene Expression Regulation, Developmental , Helix-Loop-Helix Motifs/genetics , Neurons/metabolism , Amino Acid Sequence , Animals , Antisense Elements (Genetics) , Base Sequence , Basic Helix-Loop-Helix Transcription Factors , Central Nervous System/metabolism , Chromosome Mapping , DNA-Binding Proteins/chemistry , Exons , Female , Ganglia/metabolism , Homeodomain Proteins/genetics , Introns , LIM-Homeodomain Proteins , Male , Mice , Mice, Inbred CBA , Molecular Sequence Data , Nerve Tissue Proteins/genetics , Promoter Regions, Genetic , RNA, Messenger/genetics , RNA, Messenger/metabolism , Sequence Analysis, DNA , Transcription Factors
17.
Cytogenet Cell Genet ; 82(1-2): 46-8, 1998.
Article in English | MEDLINE | ID: mdl-9763658

ABSTRACT

The human LIM domain gene LIMS1 was used to identify a mouse homolog. The resulting mouse sequence was used to identify a polymorphism by SSCP analysis. Linkage studies performed in the EUCIB backcross placed Lims1l on the proximal portion of mouse Chromosome 10. This localisation makes it an interesting candidate for the deafness mutant, waltzer (v).


Subject(s)
Chromosome Mapping , DNA-Binding Proteins/genetics , Genetic Linkage , Homeodomain Proteins/genetics , Adaptor Proteins, Signal Transducing , Animals , Haplotypes , Humans , LIM Domain Proteins , LIM-Homeodomain Proteins , Membrane Proteins , Mice , Transcription Factors
18.
Eur J Anaesthesiol ; 15(4): 457-61, 1998 Jul.
Article in English | MEDLINE | ID: mdl-9699104

ABSTRACT

In a double-blinded study we examined the effect of supplementing patient-controlled morphine analgesia with intercostal nerve blockade to identify if this improved analgesia and reduced morphine requirements following renal transplantation. Fifty patients were randomized to receive unilateral intercostal nerve block with either 0.5% bupivacaine or saline to the lower five intercostal nerves. Each block was performed on the side of surgical incision following the completion of surgery. Patients receiving bupivacaine blockade reported reduced pain scores and used less morphine in the initial 4 h following renal transplantation, but did not demonstrate a significant reduction in overall pain scores, total 24 h morphine requirements, or sedation scores. Two patients developed a pneumothorax, neither of which were clinically apparent at the time of diagnosis, and only detected by chest radiography. A chest radiograph should therefore be considered mandatory after intercostal nerve blockade.


Subject(s)
Analgesia/methods , Intercostal Nerves , Kidney Transplantation , Nerve Block , Pain, Postoperative/prevention & control , Adult , Aged , Analgesia, Patient-Controlled , Analgesics, Opioid/administration & dosage , Analgesics, Opioid/therapeutic use , Anesthetics, Local/administration & dosage , Anesthetics, Local/adverse effects , Bupivacaine/administration & dosage , Bupivacaine/adverse effects , Consciousness/drug effects , Double-Blind Method , Evaluation Studies as Topic , Female , Follow-Up Studies , Humans , Male , Middle Aged , Morphine/administration & dosage , Morphine/therapeutic use , Nerve Block/adverse effects , Pain Measurement , Pneumothorax/diagnostic imaging , Pneumothorax/etiology , Radiography , Sodium Chloride
19.
Genomics ; 51(1): 144-7, 1998 Jul 01.
Article in English | MEDLINE | ID: mdl-9693045

ABSTRACT

SM22alpha (TAGLN) is one of the earliest markers of differentiated smooth muscle, being expressed exclusively in the smooth muscle cells of adult tissues and transiently in embryonic skeletal and cardiac tissues. We have identified and mapped the mouse Tagln gene and a closely related gene, Sm22alpha homolog (Tagln2). The chromosomal localization for Tagln was identified by linkage analysis to distal mouse chromosome 9 between D9Mit154 and D9Mit330, closely linked to the anchor locus D9Nds10. The localization of Tagln2 was also determined and was found to map between Fcgr2 and D1Mit149 on distal mouse chromosome 1. This localization is homologous to a region of human 1q21-q25 to which an EST representing human TAGLN2 was previously mapped. The two regions, distal mouse chromosome 1 and proximal mouse chromosome 9, and the human regions with conserved synteny (1q21-q25 and 11q22-qter) are believed to be paralogous, reflecting either conserved remnants of duplicated chromosomes or segments of chromosomes during vertebrate evolution.


Subject(s)
Evolution, Molecular , Mice/genetics , Microfilament Proteins/genetics , Muscle Proteins/genetics , Amino Acid Sequence , Animals , Chromosome Mapping , Chromosomes, Human, Pair 1 , Crosses, Genetic , Genetic Linkage , Haplotypes , Humans , Molecular Sequence Data , Sequence Homology, Amino Acid
20.
Br J Anaesth ; 81(5): 713-7, 1998 Nov.
Article in English | MEDLINE | ID: mdl-10193281

ABSTRACT

In this prospective meta-analysis, we have evaluated the effect of epidural analgesia with ropivacaine for pain in labour on neonatal outcome and mode of delivery compared with bupivacaine. In six randomized, double-blind studies, 403 labouring women, primigravidae and multiparae, received epidural analgesia with ropivacaine or bupivacaine 2.5 mg ml-1. The drugs were administered as intermittent boluses in four studies and by continuous infusion in two. Apgar scores, neurological and adaptive capacity scores (NACS), degree of motor block and mode of delivery were recorded. The studies were designed prospectively to fit meta-analysis of the pooled results. Results showed similar pain relief and consumption of the two drugs. In the vaginally delivered neonates, NACS scores were approximately equal for both groups at 2 h, but at 24 h there were fewer infants with NACS less than 35 in the ropivacaine compared with the bupivacaine group (2.8% vs 7.6%; P < 0.05). Spontaneous vaginal deliveries occurred more frequently overall with ropivacaine than with bupivacaine (58% vs 49%; P < 0.05) and instrumental deliveries (forceps and vacuum extraction) less frequently (27% vs 40%; P < 0.01), while the frequency of Caesarean section was similar between groups. The intensity of motor block was lower with ropivacaine. There were no significant differences in adverse events.


Subject(s)
Amides , Analgesia, Epidural/methods , Analgesia, Obstetrical/methods , Anesthetics, Local , Delivery, Obstetric/methods , Adolescent , Adult , Bupivacaine , Double-Blind Method , Drug Administration Schedule , Female , Humans , Infant, Newborn , Labor, Obstetric/drug effects , Pregnancy , Pregnancy Outcome , Prospective Studies , Ropivacaine
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