Increased intestinal permeability during cytomegalovirus infection in renal transplant recipients

Cytomegalovirus (CMV) infections in renal transplant recipients can affect the gastrointestinal tract, but significant clinical manifestations are seldom seen. We hypothesize that subclinical involvement of the gastrointestinal tract may be quite frequent during CMV infection. In order to study this, we measured intestinal permeability by calculating the urinary lactulose mannitol (LM) excretion ratio after oral administration of lactulose and mannitol (normal<0.030) in patients with symptomatic and asymptomatic CMV infection. A total of 111 patients were enrolled in the study, 104 of whom were tested on postoperative day (POD) 10. Twenty-nine patients developed CMV infection, 12 of whom could be studied with the permeability test (median POD 40). Another nine patients without CMV infection were also studied at day 40 and served as controls. The LM ratio increased significantly during CMV infection compared to measurements before active infection (median 0.060 vs. 0.030, P<0.01) and was significantly higher during the infection than in the control group (median 0.007, P<0.01). No correlation could be found between the LM ratio and viral load, humoral response to the virus, or symptomatology of infection. We conclude that an increased intestinal permeability is found in a substantial number of patients with an active, albeit asymptomatic, CMV infection after renal transplantation. Pathophysiological mechanisms and clinical implications remain speculative but will be subject to further study.     

Increased gut permeability following burn trauma

Twenty female Hartley guinea pigs, weighing 350 to 400 g, were given a 30% full-thickness burn injury. Gastrointestinal permeability was assessed before burn and on postburn days 1 through 3, 7, and 14 by administering 5 mL of an isotonic mixture of 8% lactulose and 1.15% L-rhamnose by gavage and measuring the urinary excretion for the next 7 hours. In normal guinea pigs, lactulose (molecular weight, 342d) is mostly absorbed by the paracellular route, whereas L-rhamnose (molecular weight, 164 d) is mostly absorbed by the transcellular route. Gut permeability to L-rhamnose did not increase after burn injury (211 micrograms before burn vs 230, 260, 180, 238, and 221 micrograms on days 1, 2, 3, 7, and 14, respectively, after burn). By contrast, gut permeability to lactulose increased significantly and was greatest in the first 48 hours after burn injury (60 micrograms before burn vs 380, 354, 203, 364, and 279 micrograms on days 1, 2, 3, 7, and 14, respectively, after burn). Gut permeability to low-molecular-weight compounds increases immediately after burn trauma, and this may be by a paracellular rather than transcellular mechanism.     

Limb intracompartmental sepsis in burn patients associated with occult infection

Background

Intracompartmental sepsis (IS) is a rare complication in burn patients. IS presents in patients with inadequate perfusion of intracompartmental tissues with subsequent ischaemic necrosis and infection. Contributing factors include high-volume resuscitation, delayed escharotomies and previous bacteraemias. We describe the profile of a series of patients who developed IS in our Intensive Care Burn Unit (ICBU).

Methods

We carried out a retrospective chart review of patients admitted to an ICBU over a 5-year period.

Results

Seven patients of 659 admissions (1.0%) developed IS involving the extremities. Diagnosis was based on the identification of purulent drainage and local swelling associated with signs of sepsis of unknown origin. Total body surface area (TBSA) burned averaged 67.4% and full-thickness body surface area (FTBSA) burned averaged 48.4%. All patients were sedated and mechanically ventilated. The first 24-h fluid requirements averaged 6.0 ml kg^–1 per %TBSA burn (range 3.5–7.0 ml kg^–1 per %TBSA). Escharotomies were performed in five patients within the first 24 h of admission. Median time of diagnosis of IS was 23 days from admission (range 11–45 days). Four patients developed bacteraemia caused by the same microorganism infecting the soft tissue. In five cases, the infecting microorganism had previously colonised the overlying burned skin. Three patients required amputation of the affected limb.

Conclusion

IS is a devastating infectious complication which appears late after large burns. Predisposing factors include high-volume resuscitation, delayed escharotomies, colonisation of the overlying skin and previous bacteraemias. Earlier diagnosis and management are needed to attain a better outcome.     

Analysis of intestinal microvascular permeability associated with cardiopulmonary bypass

BACKGROUND: Cardiopulmonary bypass (CPB) is associated with a generalized inflammatory response and splanchnic edema formation that are thought to be related to microvascular barrier injury. In particular, intestinal edema and dysfunction have been associated with sepsis and post-CPB complications. The purpose of this study was to measure the forces determining fluid flux induced by CPB across the intestinal microvascular barrier. MATERIALS AND METHODS: An anesthetized canine model was used for this study (n = 12). To determine mesenteric microvascular permeability, a mesenteric lymphatic was cannulated and mesenteric venous pressure was elevated to 33 +/- 1 mm Hg to reach a minimal lymph protein concentration (CL). With simultaneous measurement of plasma protein concentrations (CP), the reflection coefficient, sigma, was calculated using the formula: sigma = 1 - CL/CP. Capillary pressures (PC), lymph flow (QL), lymph protein flux, transvascular protein flux, and intestinal tissue water were all measured using standard techniques. Normothermic cardiopulmonary bypass with flows of 75-80 ml/kg/min was initiated after a steady state was achieved, and CPB was continued for 2 h and then discontinued. Measurements were repeated 30 min after CPB was discontinued. A second group (n = 5) was studied without mesenteric venous pressure elevation to evaluate the role of capillary pressure on the increased fluid flux seen with the initiation of CPB. RESULTS: Initiation of CPB was associated with an increase in intestinal microvascular permeability. Sigma decreased from 0.77 +/- 0.01 to 0.68 +/- 0.01 (P < 0.05) with the initiation of CPB. This corresponded with statistically significant increases in both transvascular protein flux from 310 +/- 22 to 465 +/- 39 ml/min at 30 min and intestinal tissue water from 82.8 +/- 0.7 to 84.3 +/- 0.5% after weaning from CPB. Capillary pressure did not significantly increase with the initiation of CPB. CONCLUSIONS: Initiation of CPB results in a moderate increase in intestinal microvascular permeability to protein and an increase in intestinal tissue water. The increases in tissue water are not due to increased capillary pressure. A better understanding of the microvascular changes associated with extracorporeal circulation will facilitate the search for clinical interventions to minimize the impact of CPB.     

肠瘘患者腔静脉导管感染的回顾性分析

目的了解肠瘘患者腔静脉导管感染的发生率、细菌菌谱及药敏情况。方法对1998年1月至2001年4月收治的使用腔静脉导管进行全肠外营养(TPN)的肠瘘患者进行回顾性分析。结果216例肠瘘患者,共进行了358次腔静脉置管,腔静脉导管尖端培养阳性的有88次(24.6%),腔静脉导管平均使用时间为(16.9±13.0)d。88次腔静脉导管感染的尖端共培养出95株细菌,其中革兰阴性菌54株,占56.8%;其次为革兰阳性菌35株,占36.8%;真菌6株,占6.4%。根据药物敏感试验结果及临床表现,有16例患者更换了抗生素,4例改用抗真菌药物,所有患者均治愈。结论对于肠瘘患者,腔静脉感染仍是实施静脉营养的主要并发症之一,革兰阴性细菌感染最常见。     

Fungal wound infection (not colonization) is independently associated with mortality in burn patients

OBJECTIVE: To analyze the occurrence of fungal wound infection (FWI) after thermal injury and its relationship to mortality. BACKGROUND: FWI is an uncommon but potentially lethal complication of severe thermal injury. METHODS: The records of patients with thermal burns admitted to a single burn center (1991-2002) were reviewed. Analyses accounted for total burn size (TBS, percentage body surface area), full-thickness burn size (FTBS, percentage body surface area), age, inhalation injury, sex, and fungal-status category. Fungal colonization and infection were determined histopathologically. RESULTS: Criteria for inclusion were met by 2651 patients. Each patient's fungal-status category was defined according to the deepest level of fungal involvement observed during the hospital course: no fungus (2476 patients), fungal wound colonization (FWC, 121 patients), or fungal wound infection (FWI, 54 patients). Median TBS (9%, 47%, 64%, respectively) and mortality (5%, 27%, 76%, respectively) varied significantly among fungal-status groups. Logistic regression was used to detect significant independent associations. FWI was associated with higher TBS. Mortality was associated with TBS, FTBS, inhalation injury, FWI, and age. Unlike FWI, FWC was not independently related to mortality, the greater observed mortality in FWC being explained by other variables such as TBS. The odds ratio for FWI (8.16) suggested about the same mortality impact as augmenting TBS by 33%. A midrange TBS of 30% to 60% was required for most of the detectable association of FWI with mortality. CONCLUSIONS: FWI accompanies larger burns and is associated with mortality in burn patients, particularly in those with TBS 30% to 60%. This association is independent of burn size, inhalation injury, and age.     

Increased intestinal permeability: Implications for thoracoabdominal aneurysm repair

Coagulopathy and massive bleeding plays a major role in the mortality of thoracoabdominal aneurysm repair. Increasing supraceliac aortic cross-clamp time from 0 to 90 minutes increases the degree of disseminated intravascular coagulation, which occurs as a result of occlusion and reperfusion of the superior mesenteric artery. The purpose of this study was to investigate the mechanism of the superior mesenteric artery reperfusion disseminated intravascular coagulation. Twenty dogs were divided into four groups: cross-clamp time of 30 minutes; cross-clamp time of 60 minutes; cross-clamp time of 90 minutes; and control. Permeability was determined by lactulose/mannitol absorption. The venous effluent was sampled for endotoxin, potassium, bacteria, and pH every hour and urine was collected for six hours. Lactulose absorption was significantly higher in all of the experimental groups. There was increased permeability in the 60 and 90 minute groups which correlated significantly with time. Venous endotoxin, potassium, and blood cultures for bacteria did not change significantly. The pH was significantly lower every hour for six hours in the 90 minute group. These data suggest that intestinal permeability is increased with supraceliac aortic clamping and can be kept to a minimum for clamp times of under one hour.Presented at the Fifth Annual Meeting of the Eastern Vascular Society.     

Increased peritoneal permeability is associated with decreased fluid and small-solute removal and higher mortality in CAPD patients

Background: Recent studies suggest that increased peritoneal membrane permeability is associated with higher morbidity and mortality in peritoneal dialysis patients. It is not known, however, whether the difference in clinical outcome among different peritoneal transport groups is due to differences in peritoneal fluid and solute removal. In the present study, we compared the peritoneal fluid and solute transport and clinical outcome in CAPD patients with high (H), high-average (H-A), low-average (L-A) and low (L) peritoneal transport patterns. Design: A 6-h study was performed in 46 patients with frequent dialysate and plasma samples using 21 of 3.86% glucose dialysate with ¹³¹I albumin as an intraperitoneal volume marker. The patients were divided into four transport groups according to their D/P of creatinine at 240 min. Results: The results showed that high transporters had significantly lower peritoneal fluid and small-solute removal but high glucose absorption and high protein loss during a 6-h exchange. The serum albumin was lower and blood pressure and triglycerides were higher in high transporters compared with the other groups. Two-year patient survival from the start of CAPD treatment was significantly lower for high transporters (64, 85, 90 and 100% for H, H-A, L-A and L respectively, P<0.01). The 1-year patient survival from the dwell study was also significantly lower in high transporters (16, 63, 90 and 100% for each group, P<0.01). Conclusion: Our results suggest that high transporters remove less fluid and small solutes and have higher protein loss and increased glucose absorption. These alterations may contribute to fluid overload, malnutrition and lipid abnormalities that perhaps contribute to the increased mortality among the high transporters. Key words: CAPD, adequacy, peritoneal transport, mortality      

Cardiac infection in acute burn patients

One thousand and one patients with acute burns admitted to the Shriners Burns Institute, Cincinnati Unit, between 1964 and 1977 were reviewed. The incidence of cardiac infection was 2 per cent. In 18 of 20 patients, diagnosis could be made only at autopsy. Persistent fever and repeated positive blood cultures were the only constant findings.The importance of neutrophil function has been emphasized and in cases where it is above the critical level, one should be more aggressive in treating septicaemia, as these patients are more prone to develop fatal complications such as cardiac infection.     

Aeromonas hydrophilia infection in burn patients

Aeromonas hydrophilia rarely infects burn wounds. Three cases of early A. hydrophilia burn wound infection, with one death, are reported. A history of extinguishing the fire with dirty water or by rolling in dirt should alert the physician to consider A. hydrophilia as a possible infection organism.     

Increased intestinal permeability and altered mucosal immunity in cholestatic jaundice.

OBJECTIVE: To examine the effects of cholestatic jaundice on gut barrier function. SUMMARY BACKGROUND DATA: Gut barrier failure occurs in animal models of jaundice. In humans, the presence of endotoxemia indirectly implicates failure of this host defense, but this has not previously been investigated in jaundiced patients. METHODS: Twenty-seven patients with extrahepatic obstructive jaundice and 27 nonicteric subjects were studied. Intestinal permeability was measured using the lactulose-mannitol test. Small intestinal morphology and the presence of mucosal immunologic activation were examined in endoscopic biopsies of the second part of the duodenum. Systemic antiendotoxin core IgG antibodies and serum interleukin-6 and C-reactive protein were also quantified. Intestinal permeability was remeasured in 9 patients 5 weeks after internal biliary drainage. RESULTS: The median lactulose-mannitol ratio was significantly increased in the jaundiced patients. This was accompanied by upregulation of HLA-DR expression on enterocytes and gut-associated lymphoid tissue, suggesting immune activation. A significant increase in the acute phase response and circulating antiendotoxin core antibodies was also observed in the jaundiced patients. After internal biliary drainage, intestinal permeability returned toward normal levels. CONCLUSIONS: A reversible impairment in gut barrier function occurs in patients with cholestatic jaundice. Increased intestinal permeability is associated with local immune cell and enterocyte activation. In view of the role of gut defenses in the modern paradigm of sepsis, these data may directly identify an important underlying mechanism contributing to the high risk of sepsis in jaundiced patients.     

Host immune responses and intestinal permeability in patients with jaundice

BACKGROUND: Systemic endotoxaemia is implicated in the development of complications associated with obstructive jaundice. The aims of these studies were to assess the systemic immune response to intervention in patients with jaundice and to compare the effects of surgical and non-surgical biliary drainage on host immune function and gut barrier function. METHODS: In the first study, 18 jaundiced and 12 control patients were studied to assess systemic immune responses before and after intervention. In the second study, immune responses and gut barrier function were assessed following surgical and non-operative biliary decompression in 45 patients with jaundice. RESULTS: Endotoxin antibody concentrations fell significantly in patients with jaundice immediately after surgical intervention, but not after non-operative biliary drainage. This decrease was associated with a significant increase in serum P(55) soluble tumour necrosis factor (sTNF) receptor concentration (5.3 versus 10.5 ng/ml; P < 0.001), urinary excretion of P(55) TNF receptors (21.4 versus 78.8 ng/ml; P = 0.002) and intestinal permeability (lactulose : mannitol ratio 0.032 versus 0.082; P = 0.048). Intestinal permeability was significantly increased in patients with jaundice compared with controls (0.033 versus 0.015; P = 0.002). CONCLUSION: These data suggest that obstructive jaundice is associated with impaired gut barrier function and activation of host immune function that is exacerbated by intervention. Surgery causes an exaggerated pathophysiological disturbance not seen with non-operative biliary drainage procedures.     

Increased morbidity associated with chronic infection by an epidemic Pseudomonas aeruginosa strain in CF patients

BACKGROUND: Chronic pulmonary infection with transmissible Pseudomonas aeruginosa strains in individuals with cystic fibrosis (CF) has been reported, raising issues of cross infection and patient segregation. The first such strain to be described (the Liverpool epidemic strain, LES) is now widespread in many UK CF centres. However, whether such infection carries a worse prognosis is unknown. To address this, the clinical course of a group of CF patients chronically infected by LES was compared with that in patients harbouring unique strains. METHODS: Using P aeruginosa strain genotyping, two cohorts of CF patients attending the Liverpool CF service were identified who were LES positive or negative in 1998 and remained so until 2002. From these, two groups of 12 patients were matched in 1998 for age, spirometric parameters, and nutritional state and their clinical course was followed for 5 years. Patients chronically infected with Burkholderia cepacia were excluded. RESULTS: Patients chronically infected with LES had a greater annual loss of lung function than those not chronically infected by LES (mean difference between groups -4.4% (95% CI -8.1 to -0.9; p<0.02)), and by 2002 their percentage predicted forced expiratory volume in 1 second (FEV1) was worse (mean 65.0% v 82.6%, p<0.03). Their nutritional state also deteriorated over the study period (mean difference between groups in body mass index -0.7 (95% CI -1.2 to -0.2; p<0.01)), such that by 2002 they were malnourished compared with LES negative patients (mean BMI 19.4 v 22.7, p<0.02). CONCLUSIONS: Chronic infection with the Liverpool epidemic P aeruginosa strain in CF patients confers a worse prognosis than infection with unique strains alone, confirming the need for patient segregation. Since this strain is common in many CF units, strain identification in all CF centres is essential. This can only be carried out using genomic typing methods.     

烧伤后肠上皮通透性变化机制和对策

After a series of studies, we found that the intestinal permeability was increased, tight junction protein (zonula occluden-1 ) obviously decreased and redistributed, accompanied by an increase in expression of myosin light chain (MLC) phosphorylation in severely burned rats. After using inhibitor of MLC kinase ( ML-9 2mg/kg) or of Rho-associated kinase (Y-27632 2mg/kg), above-mentioned changes could be alleviated. Therefore, to regulate the MLC phosphorylation of tight junction protein and perijunctional actin-myosin ring may be one of the key links to lessen the intestinal epithelium permeability after burn injury.     

谷氨酰胺治疗肠梗阻的疗效分析

目的：谷氨酰胺（Gln）对肠梗阻肠黏膜通透性及细菌移位的影响。方法：将80例肠梗阻患者随机分为对照组和治疗组。对照组给予禁食、胃肠减压、纠正水电解质和酸碱平衡紊乱,全胃肠外营养以及抗生素等常规治疗;治疗组在常规治疗基础上,全胃肠外营养液中加用Gln。比较两组患者入院时、治疗5 d、治疗10 d的常规指标（体质量、血糖、血清白蛋白、血清前白蛋白、血清转铁蛋白）、免疫学指标（CRP、外周血白细胞计数I、gAI、gMI、gG、TNF-ɑI、L-6）和肠黏膜通透性评价指标[外周血浆Gln浓度、尿乳果糖甘露醇比值（L/M）、外周血细菌DNA阳性率]。结果：治疗后两组血清白蛋白、血清前白蛋白、血清转铁蛋白显著升高（P〈0.05）;血糖明显降低（P〈0.05）。对照组治疗10 d IgA较治疗5 d明显降低（P〈0.05）;治疗组无明显变化。治疗后治疗组血浆Gln浓度高于对照组（P〈0.01）,治疗组治疗10 d尿L/M、外周血细菌DNA阳性率低于对照组（P〈0.01）。结论：肠梗阻患者应用Gln有助于维护肠黏膜屏障功能、减少细菌移位。     

Increased plasma malondialdehyde in patients with small intestinal strangulation obstruction

Plasma malondialdehyde (MDA) was evaluated as an index of lipid peroxidation in 20 patients with small intestinal obstruction, with or without strangulation. The gut proved to be strangulated in nine cases--irreversibly in five and reversibly in four--while 11 patients had simple obstruction. The MDA levels in these cases were compared with values obtained from 29 healthy control subjects. The mean MDA level in the control group was 2.3 +/- 0.7 (range 1.5-4.0) mumol/l. In the patients with strangulation obstruction the MDA concentration was 6.7 +/- 1.6 mumol/l, and in those with simple obstruction it was 2.9 +/- 0.5 mumol/l. The difference between the MDA level in strangulation and in the other investigated groups was statistically significant. Values above 4 mumol/l were found in all the patients with intestinal strangulation, whereas those with simple obstruction had lower values. The heightened MDA level in patients with intestinal strangulation may be used for diagnostic purposes.     

Increased risk of infection associated with polyurethane dialysis grafts

Conventional polytetrafluoroethylene (PTFE) dialysis grafts cannot be cannulated for 2-3 weeks following their creation. Polyurethane grafts, made of a self-sealing material, can be cannulated within 24 hours of implantation, representing a potential advantage in patients with limited catheter options. However, early cannulation may increase the risk of graft infection. We retrospectively queried a prospective, computerized access database to identify 31 patients receiving a polyurethane graft, and 56 date-matched controls with a PTFE graft. Survival techniques were used to plot graft survival. Thrombosis-free graft survival (from creation to first thrombosis or failure) was similar for polyurethane and PTFE grafts (1-year survival, 28%, vs. 32%, p = 0.98). Cumulative graft survival (from creation to permanent failure) was also similar (1-year survival 42% vs. 52%, p = 0.40). Finally, the cumulative risk of graft infection was 37.5% for polyurethane thigh grafts, 23% for polyurethane upper extremity grafts, 21% for PTFE thigh grafts, and 5% for PTFE upper extremity grafts (p = 0.06 for polyurethane vs. PTFE grafts). The likelihood of thrombosis and failure is similar for polyurethane and PTFE grafts. However, polyurethane grafts may have a higher risk of infection, particularly when they are placed in the thigh. In patients with an access emergency, implantation of a polyurethane graft incurs a tradeoff between earlier cannulation and a higher risk of infection.     

肠上皮通透性变化及其在烧伤休克发病中的作用

The intestinal epithelial barrier serves a dual role: to keep harmful external agents out of the body and to allow beneficial nutrients to enter the body. Tight junction (TJ) is of crucial importance for the barrier function. Over the past 15 years, some of the molecular events underlying the epithelial barrier regulation have been described. This forum introduces briefly the molecular structure of TJ and its regulation in gut barrier. It was shown that gut barrier function was impaired as early as 5 minutes post burn and became worst by 4 hours. In this forum the mechanism of gut barrier injury in burns is described,and it includes 4 aspects: the phosphorylation of TJ protein and perijunctional actin-myosin ring, the reduction of TJ proteins expression, the endocytosis of TJ proteins, and the apoptosis and necrosis of the epithelial cells. It is well known that the increase in gut permeability promotes bacterial translocation in burns.Moreover, a new auto-digestion theory of gut in shock and MODS was recently raised. Therefore, protection against gut barrier damage has again been recognized as a therapeutic target in shock and MODS treatment.     

Aeromonas infection in critically ill burn patients

Aeromonas infection in burn patients is extremely uncommon. Here we report on four cases of Aeromonas infection in burn patients admitted to the BICU at the Singapore General Hospital burn unit between June 2001 and May 2006. Two patients had positive blood cultures, and the other two had tissue samples with growth. There was no history of exposure to soil or fresh water in all patients. The average age of patients was 35 years (range 24-41) and the average % TBSA was 48% (range 35-80). Cultures were isolated between days 2 and 4 post burn. There was one mortality in the series. Increasing antibiotic resistance was noted among isolates of Aeromonas. Continued vigilance is essential to detect infection early, even in the absence of a suggestive history, with adequate debridement and appropriate antibiotic therapy.