Quality of life after pancreatectomy.
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Anastomosis, Surgical↗
Biomedical subjects
C D Johnson
Publications and source records attributed to C D Johnson.
Suprapubic catheterization at laparotomy.
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Drainage↗
Quality of life after surgery for chronic pancreatitis.
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Humans↗
Obesity is a definitive risk factor of severity and mortality in acute pancreatitis: an updated meta-analysis.
BACKGROUND/AIMS: Obesity is considered a risk factor in patients with acute pancreatitis. However, the relationship between obesity and mortality in this disease has not been confirmed definitively even in a previous meta-analysis. Since the publication of our previous meta-analysis, one study has been reported about the prognostic value of obesity in acute pancreatitis. We have performed a new meta-analysis to confirm the relationship between obesity and the outcome of acute pancreatitis. DATA SOURCES: A MEDLINE search using 'pancreatitis', 'obesity' and 'body mass index' as search terms. REVIEW METHODS: Clinical studies which investigated the prognostic value of obesity in acute pancreatitis with the following criteria: (a) inclusion of mild and severe acute pancreatitis; (b) use of body mass index (BMI) as the measure of obesity; (c) definition of obesity as BMI >or=30 kg/m(2); (d) definition of severity of acute pancreatitis according to the criteria established in the Atlanta Symposium. Five studies including patients with mild and severe acute pancreatitis and obesity measured by BMI were analyzed. The end points of the meta-analysis were the severity of acute pancreatitis, local complications, systemic complications and mortality. Pooled odds ratio (OR) and confidence intervals (CI) were calculated according to the Mantel-Haenszel method, and heterogeneity was assessed by the multiplicative inverse variance method. RESULTS: Seven hundred and thirty-nine patients were included. There was no heterogeneity for the variables severity, systemic complications, local complications and mortality among the included studies. Severe acute pancreatitis was significantly more frequent in obese patients (OR 2.9, 95% CI 1.8-4.6). Furthermore, those patients developed significantly more systemic (OR 2.3, 95% CI 1.4-3.8) and especially local complications (OR 3.8, 95% CI 2.4-6.6). In this new analysis, mortality was also higher in obese patients (OR 2.1, 95% CI 1.0-4.8). CONCLUSION: Obesity is not only a risk factor for the development of local and systemic complications in acute pancreatitis: it also increases the mortality of this disease.
Acute Disease↗
A meta-analysis comparing suprapubic and transurethral catheterization for bladder drainage after abdominal surgery.
BACKGROUND: Although bladder drainage is widely used for general surgical patients undergoing laparotomy, there is little consensus on whether suprapubic or transurethral catheterization is better. METHOD: A systematic database search was undertaken to find all studies of suprapubic catheterization. Randomized controlled trials were identified for inclusion. Endpoints for analysis were bacteriuria, patient satisfaction and recatheterization rates. A meta-analysis was performed using fixed-effect or random-effect models as appropriate, depending on heterogeneity. RESULTS: After abdominal surgery, transurethral catheterization is associated with significant bacteriuria (relative risk (RR)=2.02, P<0.001, 95 percent confidence interval (c.i.) 1.34 to 3.04) and pain or discomfort (RR=2.94, P=0.004, 95 percent c.i. 1.41 to 6.14). Recatheterization rates using the transurethral method were not increased significantly (RR=1.97, P=0.213, 95 percent c.i. 0.68 to 5.74) with heterogeneity between studies. CONCLUSION: The suprapubic route for bladder drainage in general surgery is more acceptable to patients and reduces microbiological morbidity.
Abdomen↗
Performance demands of professional male tennis players.
OBJECTIVE: To quantify the performance demands in professional male tennis. METHODS: Games from three grand slam tournaments were analysed by an elite tennis player from video recordings. Game related data were collected on 22 players (French Open, 8 (186 games); Wimbledon, 11 (206 games); US Open, 9 (224 games)). Total number of strokes per game was quantified separately for service and return games. Strokes were categorised by type and designated as forehand or backhand. Differences in the types of strokes in a game were analysed using one factor (type of stroke) repeated measures analysis of variance. Differences in total strokes and stroke distributions between playing surfaces were analysed by analysis of variance (surface type) with Tukey's post hoc pairwise comparisons. RESULTS: For service games there were more serves per game than any other type of stroke (p<0.001), with topspin forehand and topspin backhand the only other strokes averaging more than one per service game. For return games there were more forehand and backhand returns and topspin forehands and backhands than other types of stroke (p<0.01). Total number of strokes per game was greater in the French Open than Wimbledon (p<0.01), with more topspin forehands (p<0.01) and more topspin backhands (p<0.01). Total strokes per game in the US Open were not different from the other two tournaments. CONCLUSIONS: The serve was the predominant stroke accounting for 45% (French Open) to 60% (Wimbledon) of strokes during service games. The greater number of strokes per game on clay v grass may contribute to earlier fatigue.
Analysis of Variance↗
Toxicogenomic profile of 2,3,7,8-tetrachlorodibenzo-p-dioxin in the murine fetal heart: modulation of cell cycle and extracellular matrix genes.
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and similar environmental contaminants have been demonstrated to be potent cardiovascular teratogens in developing piscine and avian species. In the present study, we investigated the effects of TCDD on gene expression during murine cardiovascular development. C57Bl6N pregnant mice were dosed with 1.5, 3.0, or 6.0 microg TCDD/kg on gestational day (GD) 14.5, and microarray analysis was used to characterize the global changes in fetal cardiac gene expression on GD 17.5. TCDD significantly altered expression of a number of genes involved in xenobiotic metabolism, cardiac homeostasis, extracellular matrix production/remodeling, and cell cycle regulation. Interestingly, while the AhR-responsive genes Cyp1A1, Cyp1B1, Ugt1a6, and Ahrr, were all induced by TCDD in the fetal murine heart, other AhR-responsive genes, Cyp1a2, Nqo1, and Gsta1, were not. Quantitative real-time polymerase chain reactions confirmed the changes in expression of several G1/S-type cyclins and extracellular matrix-related genes. These results demonstrate the global changes in cardiac gene expression that result from TCDD exposure of the fetal murine heart and implicate genes involved in cell cycle and extracellular matrix regulation in TCDD-induced cardiac teratogenicity and functional deficits.
Animals↗
Novel genomic targets in oxidant-induced vascular injury.
To study the complex interaction between oxidative injury and the pathogenesis of vascular disease, vascular gene expression was examined in male Sprague-Dawley rats given 35 or 70 mg/kg allylamine, a synthetic amine converted to acrolein and hydrogen peroxide within the vascular wall. Vascular lesions and extensive vascular remodeling, coupled to increased production of 8-epi-PGF2alpha, nuclear localization of NFkappaB, and alterations in glutathione homeostasis, were observed in animals treated with allylamine for up to 20 days. Transcriptional profiling, immunohistochemistry, and in situ hybridization showed that genes involved in adhesion and extracellular matrix (ECM) (alpha(1) integrin, collagen), cytoskeletal rearrangements (alpha-smooth muscle actin, alpha-tropomyosin), and signal transduction (NFkappaB, osteopontin, and LINE) were altered by oxidant treatment. To evaluate mechanisms of gene dysregulation, cultured aortic smooth muscle cells were challenged with allylamine or its metabolites and processed for molecular analysis. These agents increased formation of reactive oxygen species and elicited changes in gene expression similar to those observed in vivo. Oxidative stress and changes in gene expression were inhibited by N-acetyl cysteine, a precursor of glutathione. These results indicate that genes along the ECM-integrin-cytoskeletal axis, in addition to LINE, are molecular targets in oxidant-induced vascular injury.
Acetylcysteine↗
Influence of cytokine and ICAM-1 gene polymorphisms on susceptibility to chronic pancreatitis.
AIMS: To test the hypothesis that single nucleotide polymorphisms (SNPs) within genes (or their promoter regions) encoding cytokines, growth factors, and intercellular adhesion molecules modulate the risk of development of chronic pancreatitis (CP). METHODS: DNA was extracted from peripheral blood leucocytes or formalin fixed, paraffin wax embedded tissue from 53 patients with CP and 266 healthy controls. SNPs within the interleukin 1beta (IL-1beta), IL-6, IL-8, tumour necrosis factor alpha (TNFalpha) and vascular endothelial growth factor (VEGF) gene promoter regions and the transforming growth factor beta1 (TGFbeta1) and intercellular cell adhesion molecule 1 (ICAM-1) genes were genotyped by the amplification refractory mutation system polymerase chain reaction or 5' nuclease (Taqman) techniques. Patient-control comparisons were made using 2 x 2 contingency tables and chi2 analyses. RESULTS: A non-significant decrease in the frequency of the IL-8 -251 AA genotype and a non-significant increase in the frequency of the ICAM-1 +469 GA genotype was seen in patients compared with controls. No associations were identified between SNPs in the promoter regions of the IL-1beta, IL-6, or TNFalpha proinflammatory cytokines genes or the TGFbeta1 and VEGF genes and susceptibility to CP. CONCLUSIONS: This preliminary study suggests that genetic polymorphism within several cytokine genes is unlikely to influence susceptibility to CP, but the possible role of IL-8 and ICAM-1 polymorphisms in the development of this disease requires further investigation.
Adolescent↗
Combination of APACHE-II score and an obesity score (APACHE-O) for the prediction of severe acute pancreatitis.
BACKGROUND: The advent of specific therapeutic or preventive treatments for severe acute pancreatitis creates a need to determine the risk of complications for each individual. Scoring systems used in acute pancreatitis identify groups of patients at risk of complications, but the pancreatitis-specific scores require 48 h of hospital admission to give full information. The APACHE-II score is useful within 24 h, but ignores simple clinical features, such as obesity, known to predict severity. The aim of this study was to evaluate a combination of the APACHE-II score with an obesity score in patients with acute pancreatitis, to predict severity using information available during the first 24 h of hospital admission. METHODS: Data were collected prospectively from 186 consecutive patients with acute pancreatitis, to allow calculation of the APACHE-II score and body mass index (BMI). BMI was categorised as normal (score = 0), overweight (BMI 26-30: score = 1), or obese (BMI >30: score = 2). A logistic regression model was used to identify factors significantly associated with complications (Atlanta criteria; 104 complications in 60 patients). RESULTS: Age, BMI and the acute physiology score independently predicted complications. Addition of the score for obesity to the APACHE-II score gave a composite score (APACHE-O) with greater predictive accuracy. At cut-off of >8, APACHE-O had sensitivity 82%, specificity 86%, positive predictive value 74%, negative predictive value 91% and overall accuracy 85%. CONCLUSIONS: This study confirms that age, obesity and APACHE-II measured in the first 24 h of hospital admission can predict complications in acute pancreatitis. Combination of the APACHE-II and obesity scores by simple addition improved categorical prediction of severity (mild or severe) in patients with acute pancreatitis.
APACHE↗
Urinary trypsinogen activation peptide as a marker of severe acute pancreatitis.
BACKGROUND: Trypsinogen activation peptide (TAP) may be an early marker of severe pancreatitis. Previous studies have included all patients with organ failure in the group with severe pancreatitis, although patients with transient organ failure may have a good prognosis. The aim of this study was to determine the value of urinary TAP estimation for prediction of severity of acute pancreatitis, and to validate use of several markers of prediction of severity against a new, stringent definition of severity. METHODS: Patients with acute pancreatitis were recruited within 24 h of onset of symptoms. Urine and blood samples were collected for 24 h, and Acute Physiology And Chronic Health Evaluation (APACHE) II (24 h), Ranson (48 h) and Glasgow (48 h) scores were calculated. Severe acute pancreatitis was defined by the presence of a local complication or the presence of organ failure for more than 48 h. RESULTS: Urinary TAP levels were significantly greater in patients with severe pancreatitis than in those with mild disease during the first 36 h of admission. The highest of three estimations of TAP in the first 24 h was as effective as APACHE II at 24 h in predicting severity. At 24 h after admission, urinary TAP was better than C-reactive protein (CRP) in predicting severity. The combination of TAP and CRP at 24 h allowed identification of high- and low-risk groups. The new definition of severity excluded 24 of 190 patients with transient organ failure; none of these patients died. CONCLUSION: Use of TAP improved early prediction of the severity of acute pancreatitis. Organ failure that resolves within 48 h does not signify a severe attack of acute pancreatitis.
APACHE↗
An aqueous formulation of gamma-linolenic acid with anti-proliferative action on human pancreatic cancer cell lines.
Essential fatty acids, especially gamma-linolenic acid (GLA), have been shown to directly inhibit the growth of cancer cell lines in culture. The aim of this study was to see whether an aqueous formulation of GLA works as well as the lithium-based salt. We evaluated the effect of the 1-deoxy-1-methylamino-D-glucitol salt of GLA (MeGLA) on the growth of two human pancreatic cancer cell lines (Panc-1 and MIA PaCa-2) in vitro, and compared its effects with a previously studied formulation, lithium GLA (LiGLA). The effect of time exposure (2-7 days) and difference in concentration (0-1000 micromol/l) were studied using 96-well culture plates. Cell growth was assessed by MTT assay. Control experiments were performed with meglumine alone in similar concentrations. MeGLA had cytostatic and cytotoxic effects on pancreatic cancer cell lines with 50% growth inhibition at 30-100 micromol/l and cytotoxic effects at 60-250 micromol/l. The degree of growth inhibition increased with time of exposure to MeGLA. The anti-proliferative effects of MeGLA were similar to those previously observed with LiGLA. We conclude that MeGLA has equivalent anti-proliferative activity to LiGLA when tested in vitro against pancreatic cancer cell lines and is therefore a suitable alternative to LiGLA for investigation of the in vivo activity of GLA against pancreatic adenocarcinomas.
Cell Division↗
Persistent organ failure during the first week as a marker of fatal outcome in acute pancreatitis.
BACKGROUND: In predicted severe acute pancreatitis, many patients develop organ failure and recover without local complications, and mortality is only 14-30%. It has been suggested that half of patients with progressive early organ failure may die, but there are no data to relate death or local complications to duration of early (week 1) organ failure. AIMS: To determine mortality rates in patients with transient (<48 hours) and persistent (>48 hours) early organ failure and to show whether persistent organ failure predicts death or local complications. PATIENTS: A total of 290 patients with predicted severe acute pancreatitis previously studied in a trial of lexipafant, recruited from 78 hospitals through 18 centres in the UK. METHOD: Manual review of trial database to determine: the presence of organ failure (Marshall score > or =2) on each of the first seven days in hospital, duration of organ failure, and outcome of pancreatitis (death, complications by Atlanta criteria). RESULTS: Early organ failure was present in 174 (60%) patients. After transient organ failure (n = 71), outcome was good: one death and 29% local complications. Persistent organ failure (n = 103) was followed by 36 deaths and 77% local complications, irrespective of onset of organ failure on admission or later during the first week. CONCLUSION: Duration of organ failure during the first week of predicted severe acute pancreatitis is strongly associated with the risk of death or local complications. Resolution of organ failure within 48 hours suggests a good prognosis; persistent organ failure is a marker for subsequent death or local complications.
APACHE↗
Synergistic activity of gamma-linolenic acid and cytotoxic drugs against pancreatic adenocarcinoma cell lines.
BACKGROUND: Gamma-linolenic acid (GLA) is growth inhibitory both in vitro and in vivo, at doses non-toxic to non-cancer cells. Chemotherapeutic agents have limited activity in pancreatic cancer. Interactions between GLA and cytotoxic drugs have not previously been investigated; any synergy might improve the therapeutic effect of these agents. AIM: To investigate possible interactions between GLA and 5-fluorouracil (5-FU) or gemcitabine against pancreatic cancer cell lines in vitro. METHODS: Two pancreatic cancer cell lines were exposed to GLA alone and in combination with 5-FU or gemcitabine. Residual viable biomass was measured using the MTT assay and the results analysed by the median effect method of Chou and Talalay [Adv Enzyme Regul 1984;22:27-55]. RESULTS: GLA concentrations of 3.9- 125 microg/ml had a synergistic or additive growth inhibitory effect on all tested concentrations of gemcitabine. Synergism was demonstrated between GLA and 5-FU only at concentrations of 62.5-125 microg/ml of 5-FU. CONCLUSION: GLA has a synergistic effect with gemcitabine at concentrations that correspond to in vivo therapeutic doses. GLA with 5-FU is synergistic only at a tight range of high concentrations of 5-FU. GLA lacks toxic side effects and may be useful in combination with gemcitabine.
Animals↗
A randomised clinical trial to assess the effect of total enteral and total parenteral nutritional support on metabolic, inflammatory and oxidative markers in patients with predicted severe acute pancreatitis (APACHE II > or =6).
BACKGROUND: Total enteral nutrition (TEN) within 48 h of admission has recently been shown to be safe and efficacious as part of the management of severe acute pancreatitis. Our aim was to ascertain the safety of immediate TEN in these patients and the effect of TEN on systemic inflammation, psychological state, oxidative stress, plasma glutamine levels and endotoxaemia. METHODS: Patients admitted with predicted severe acute pancreatitis(APACHE II score >5) were randomised to total enteral (TEN; n = 8) or total parenteral nutrition (TPN; n = 9). Measurements of systemic inflammation (C-reactive protein), fatigue (visual analogue scale), oxidative stress (plasma thiobarbituric acid-reactive substances), plasma glutamine and anti-endotoxin IgG and IgM antibody concentrations were made on admission and repeated on days 3 and 7 thereafter. Clinical progress was monitored using APACHE II score. Organ failure and complications were recorded. RESULTS: All patients tolerated the feeding regime well with few nutrition-related complications. Fatigue improved in both groups but more rapidly in the TEN group. Oxidative stress was high on admission and rose by similar amounts in both groups. Plasma glutamine concentrations did not change significantly in either group. In the TPN group, 3 patients developed respiratory failure and 3 developed non-respiratory single organ failure. There were no such complications in the TEN group. Hospital stay was shorter in the TEN group [7(4-14) vs. 10 (7-26) days; p = 0.05] as was time to passing flatus and time to opening bowels [1 (0-2) vs. 2 (1-5)days; p = 0.01]. The cost of TEN was considerably less than of TPN. CONCLUSION: Immediate institution of nutritional support in the form of TEN is safe in predicted severe acute pancreatitis. It is as safe and as efficacious as TPN and may be beneficial in the clinical course of this disease.
APACHE↗
Genomic profiles and predictive biological networks in oxidant-induced atherogenesis.
Atherogenic stimuli trigger complex responses in vascular smooth muscle cells (VSMCs) that culminate in activation/repression of overlapping signal transduction cascades involving oxidative stress. In the case of benzo[a]pyrene (BaP), a polycyclic aromatic hydrocarbon present in tobacco smoke, the atherogenic response involves interference with redox homeostasis by oxidative intermediates of BaP metabolism. The present studies were conducted to define genomic profiles and predictive gene biological networks associated with the atherogenic response of murine (aortic) VSMCs to BaP. A combined oxidant-antioxidant treatment regimen was used to identify redox-sensitive targets during the early course of the atherogenic response. Gene expression profiles were defined using cDNA microarrays coupled to analysis of variance and several clustering methodologies. A predictor algorithm was then applied to gain insight into critical gene-gene interactions during atherogenesis. Supervised and nonsupervised analyses identified clones highly regulated by BaP, unaffected by antioxidant, and neutralized by combined chemical treatments. Lymphocyte antigen-6 complex, histocompatibility class I component factors, secreted phosphoprotein, and several interferon-inducible proteins were identified as novel redox-regulated targets of BaP. Predictor analysis confirmed these relationships and identified immune-related genes as critical molecular targets of BaP. Redox-dependent patterns of gene deregulation indicate that oxidative stress plays a prominent role during the early stages of BaP-induced atherogenesis.
Algorithms↗
Arris & Gale lecture. Regulation and responses of gallbladder muscle activity in health and disease.
A complex relationship links biliary symptoms with the mechanisms of gallbladder emptying and the presence of gallstones. This relationship has been investigated by clinical studies of symptoms associated with gallstones, by investigation of gallbladder emptying and cholecystokinin (CCK) release in patients with gallstones, and after cholecystectomy, or truncal vagotomy, and in the irritable bowel syndrome (IBS). Laboratory studies examined receptor density on bovine gallbladder, and contractility of human gallbladder in response to a variety of stimuli was studied in vitro. A set of six symptoms associated with the presence of gallstones was identified; IBS appeared to be present in two-fifths of patients before cholecystectomy but only one-third of these patients had persistent IBS symptoms one year after operation. Gallbladder emptying studies confirmed the poor contraction of stone-bearing gallbladders; abnormal patterns of emptying were also found in patients with IBS. Gallbladder emptying and filling appear to be largely neurally regulated. CCK receptor density was very low in gallbladder tissue, suggesting that receptors on nerve cells might mediate the action of CCK. Relaxation of gallbladder muscle was mediated by adrenergic and nitrergic nerves. The inflammatory mediator bradykinin, however, had a strong direct action on muscle cells to cause gallbladder contraction. The work reported here gives an overview of the symptoms and mechanisms of disease associated with the presence of stones in the gallbladder.
Cholelithiasis↗
Apoptosis and proliferation of acinar and islet cells in chronic pancreatitis: evidence for differential cell loss mediating preservation of islet function.
BACKGROUND: Chronic pancreatitis is characterised clinically by early exocrine insufficiency, with diabetes mellitus occurring as a late phenomenon. This is mirrored pathologically by extensive acinar cell destruction and islet preservation. The mechanisms underlying this differential rate of cellular destruction are unknown. AIMS: To test the hypothesis that acinar loss and islet preservation in chronic pancreatitis occurs due to differential epithelial kinetics and investigate the role of inflammatory cells and cell cycle associated molecules. METHODS: Archival tissue from six chronic pancreatitis cases was compared with six normal controls using TUNEL and immunohistochemistry for CD3, CD20, CD68, MIB-1, Bcl-2, Bax, Fas, Fas ligand, retinoblastoma protein (Rb), and tissue inhibitor of metalloproteinases 1 (TIMP-1) and 2 (TIMP-2). RESULTS: The acinar cell apoptotic index (AI) and proliferation index were higher in chronic pancreatitis than controls. T lymphocytes diffusely infiltrated fibrous bands and acini but rarely islets. Acinar Bcl-2 expression exceeded islet expression in chronic pancreatitis and controls while Bax was strongly expressed by a subset of islet cells and weakly by centroacinar cells. Islet Fas and Fas ligand expression exceeded acinar expression in chronic pancreatitis and controls. Acinar Rb expression was higher in chronic pancreatitis than in controls. Islets in chronic pancreatitis and controls showed intense TIMP-1 and TIMP-2 expression. CONCLUSION: Apoptosis plays a significant role in acinar loss in chronic pancreatitis. Acinar Bcl-2 and islet Bax expression indicates complex AI control. Increased acinar Rb expression in chronic pancreatitis may differentially promote acinar loss. Fas ligand expression may be restricted to islet cell membranes through TIMP-1 expression and inhibit islet damage by promoting apoptosis of cytotoxic T lymphocytes.
Apoptosis↗