bluuebunny/crossref_metadata_2025 huggingface dataset:
Hyperglycaemia is associated with fungaemia and an increased mortality rate in severely burned children
Authors: Gore D , Chinkes D , Herndon D N , Heggers J , Desai M , Wolf S
Published: March 2003

Background

Hyperglycaemia may have detrimental effects on immunity. The purpose of this study was to assess any relationship between hyperglycaemia and clinical outcome following injury.

Methods

The records of children with burns covering 60 per cent or more of the body surface admitted after 1996 were reviewed. Patients were categorized as having poor glucose control if 40 per cent or more of all plasma glucose determinations were 7·8 mmol l−1 or greater and were compared with patients with adequate glucose control (less than 40 per cent of glucose values 7·8 mmol l−1 or greater).

Results

Despite similar age, burn size and caloric intake, the extent and severity of hyperglycaemia was significantly greater in the 33 patients categorized as having poor glucose control than in the 25 patients with adequate glucose control. Patients with hyperglycaemia had a significantly higher proportion of blood cultures positive for yeast (mean(s.d.) 3·7(10·0) versus 0·1(0·7) per cent; P < 0·05, Student's t test). Nine of 33 patients with persistent hyperglycaemia died, compared with only one of 25 with adequate glucose control (P ≤ 0·05, Fisher's exact test).

Conclusion

This association between hyperglycaemia, fungaemia and subsequent death in severely burned children may be related to a hyperglycaemia-induced deterioration in immune function. This suggests that aggressive manoeuvres to normalize plasma glucose may be warranted.
Treatment of Candida infection in patients with infected pancreatic necrosis
Authors: Farkas G , Márton J , Leindler L , Nagy E
Published: March 2003

Background

The purpose of this review was to determine the incidence of Candida infection in patients with infected pancreatic necrosis, to determine the most frequent risk factors and to assess the best treatment approach for disseminated candidal infections.

Methods

Of 145 patients with infected pancreatic necrosis identified, 30 (21 per cent) were infected with C. albicans. Risk factors identified in patients with Candida infection included the presence of necrotic tissue, and the use of broad-spectrum antibiotics, intravascular catheters and parenteral nutrition.

Results

With one exception, all cases involved mixed bacterial and fungal infections. The positive fungal result was obtained either during or after operation. Sixteen of the 30 patients displayed fungal colonization, while the other 14 had disseminated fungal infection. There were two deaths in the disseminated group, but none in the colonization group. In both fatal cases, flucytosine was applied. When fluconazole was used against disseminated fungal infection, no death was noted. Recently, prophylactic fluconazole has also been used in 20 patients with infected pancreatic necrosis, with no evidence of fungal infection after operation.

Conclusion

The combination of adequate surgical treatment with effective antibiotics and early antifungal therapy is the ideal management approach for infected pancreatic necrosis with Candida infection. Fluconazole may be regarded as an efficient drug for the prophylaxis of candidiasis.
Role of cytokines of the tumour necrosis factor family in the immune response to disseminated Candida albicans infection
Authors: Netea M G , Van der Meer J W M , Meis J F G M , Kullberg B J
Published: March 2003

Background

Tumour necrosis factor (TNF) α, lymphotoxin (LT) α, CD40L and FasL are members of the TNF family that play a crucial role in modulation of the immune response. Their role in the defence against infection with Candida albicans was investigated in mice deficient in either TNF-α and LT-α (TNF–/– LT–/– mice), CD40L (CD40L–/– mice) or Fas (MRL/lpr mice).

Methods

Mortality rates were compared in mice infected intravenously with 106 colony-forming units of C. albicans per mouse.

Results

After infection with C. albicans the TNF–/– LT–/– mice had a significantly increased mortality rate compared with control mice (100 versus 40 per cent; P < 0·01). This was due to a 10–1000-fold increased outgrowth of the yeasts in the kidneys and liver of TNF–/– LT–/– mice (P < 0·01). Defective recruitment and phagocytosis, but not Candida killing, were responsible for these effects. CD40L–/– mice were also more susceptible to systemic candidiasis than the wild-type controls (mortality rate 80 versus 50 per cent; P < 0·05), and the growth of Candida in the kidneys was one order of magnitude higher in the deficient than in control mice (P < 0·05). Neutrophil function in the CD40L–/– mice was normal, whereas decreased Candida killing by macrophages through nitric oxide-dependent mechanisms was responsible for the effect of CD40/CD40L interactions. In contrast, Fas-defective MRL/lpr mice were significantly more resistant to disseminated candidiasis (mortality rate 50 versus 100 per cent; P < 0·01); this was mediated by the facilitation of neutrophil migration to the site of infection.

Conclusion

Cytokines of the TNF family play a crucial role in the modulation of host defence against fatal C. albicans infection. Their effects are exerted selectively at the level of neutrophil or macrophage function.
Role of tumour necrosis factor α in intra-abdominal abscesses caused by Candida albicans
Authors: Vonk A G , Kullberg B-J , Netea M G , Van der Meer J W M
Published: March 2003

Background

The incidence of various Candida spp. as a cause of nosocomial infections has increased. Patients undergoing abdominal surgery are at risk of intra-abdominal and invasive candidiasis. The mortality rate among patients with abdominal Candida sepsis is high. The proinflammatory cytokine tumour necrosis factor (TNF) α plays a pivotal role in the pathogenesis of sepsis and septic shock. Animal experiments have shown that neutralization of endogenous TNF-α using monoclonal antibodies has a beneficial effect on the mortality rate associated with bacteraemia. However, clinical trials using anti-TNF-α monoclonal antibodies or soluble TNF-α receptors in patients with sepsis are disappointing. The requirement of TNF-α for mounting a host defence and its beneficial effect on granuloma formation may explain these results. During disseminated candidiasis in mice, the mortality rate is increased in absence of endogenous TNF-α and lymphotoxin (LT) α. TNF-α and LT-α promote the recruitment of granulocytes at the site of infection and phagocytosis of Candida blastospores.

Methods

To investigate the role of TNF-α in a model of localized Candida infection (i.e. abdominal sepsis and abscess formation), a mixture of sterile faeces and Candida albicans was injected into the peritoneal cavity of TNF/LT double knockout (TNF–/– LT–/–) mice and their wild-type (TNF+/+ LT+/+) counterparts.

Results

Similar to TNF+/+ LT+/+ mice, TNF–/– LT–/– mice developed intra-abdominal abscesses. However, while TNF+/+ LT+/+ mice tended to recover from infection, the number of abscesses and fungal load of the abscesses continued to increase in TNF–/– LT–/– mice.

Conclusion

TNF-α and LT-α are not critical to the process of abscess formation, except for the elimination of Candida from abscesses. These results suggest that anti-TNF-α therapy is not desirable in abdominal Candida sepsis.
Short- and long-term effects of perioperative homologous blood transfusion in surgical patients with cancer
Authors: Gianotti L , Braga M , Vignali A , Gentilini O , Radaelli G , Di Carlo V
Published: March 2003

Background

The immunosuppressive effect of transfusion with homologous blood is debated. The aim of this study was to find the potential correlation between the use of homologous blood in the perioperative period and postoperative infection (short-term effect) and survival (long-term effect) in patients undergoing gastrointestinal surgery for cancer.

Methods

A total of 1010 patients with a gastrointestinal neoplasm (316 gastric, 694 colorectal) having major surgical procedures were observed prospectively. The following variables were recorded: sex, age, type and duration of operation, operative blood loss, type and amount of blood transfusion, type and rate of postoperative complications, disease stage (tumour node metastasis (TNM) or Dukes), and use of adjuvant therapy (radiochemotherapy). The χ2 test was applied to correlate discrete variables. Cox multiple regression analysis was used to evaluate the impact of each single variable on survival. Five-year survival curves were studied by the Kaplan–Meier method and their correlation was made by the log rank test.

Results

According to the Cox model, in patients who underwent gastrectomy there was a significant correlation (P < 0·01) only between age, disease stage and 5-year survival rate. The odds ratio for the relationship between homologous transfusion and survival was 1·43 (P = 0·08). When overall 5-year survival was split by TNM class, homologous transfusion significantly affected the mortality rate for patients in stage II and III (P < 0·05), while survival in patients of stage I and IV was not influenced by the use of homologous blood. Similar results were obtained in subjects with colorectal cancer, with the difference that in the Cox multivariate analysis homologous transfusion was significantly correlated with the overall 5-year survival rate (P < 0·005). Again, the strongest correlation was observed for intermediate disease stages (Dukes B and C). The χ2 value for the linear trend also showed a significant relationship between the amount of blood transfused and 5-year survival rate. In this population there was also a statistically significant correlation between transfusion and the rate of postoperative infections (P = 0·001).

Conclusion

The correlation between homologous blood transfusion and short- and long-term immunosuppression appears to be valid dependent on the site of the neoplasm, particularly for patients with an intermediate disease stage.
Implementing a randomized controlled trial with granulocyte colony-stimulating factor prophylaxis to improve the outcome of high-risk patients with colorectal cancer in the complex clinical setting of multiple surgical interventions
Authors: Bauhofer A , Stinner B , Plaul U , Torossian A , Celik I , Lorenz W
Published: March 2003

Background

All large multicentre trials with immune modifiers in sepsis faded despite promising preclinical results. Several reasons for this have been discussed in the literature and include patient heterogeneity, different phases of pathophysiological state and trial errors. There are two additional and important points: the interaction of immune modifiers with the complex clinical management was not analysed preclinically and in multicentre trials the surgical management was not standardized.

Methods

Before implementing the clinical trial, the interaction of granulocyte colony-stimulating factor (G-CSF) with various surgical interventions was analysed in clinical modelling randomized trials (CMRTs) in rats, including different antibiotics, heparin, H1 and H2 antagonists, abdominal lavage, and management of preoperative and intraoperative bleeding. Good clinical practice rules were applied and the complexity of clinical reality was modelled in the CMRTs. In the clinical trial, high-risk patients (American Society of Anesthesiologists grades III and IV) with colorectal cancer were identified and randomized to the placebo and G-CSF groups (n = 40 per group). G-CSF prophylaxis (300 μg) was given subcutaneously 12 h before, and 12 and 36 h after operation. The three primary endpoints were health status measured with a modified McPeek index over 6 months, self-reported quality of life determined with the European Organization for the Research and Treatment of Cancer QLQ38 questionnaire and the true endpoint defined 6 months after operation.

Results

Implementation of the trial demonstrated that a high standardization of surgical management is not possible in multicentre trials since the surgical management of patients with colorectal cancer is heterogeneous and management of the most important complication, anastomotic leakage after colorectal surgery, is performed according to personal experience and is not based on high levels of evidence from clinical trials low evidence based medicine (EBM). For this reason the surgical management of patients in the trial should be defined, a centre-based clinical guideline for the management of anastomotic leakage applied and adherence to the guideline recorded.

Conclusion

Without CMRTs to analyse the interaction of immune modifiers in complex settings and defined clinical management of patients, no positive results will be obtained from such clinical trials.
Bacterial overgrowth and translocation in an experimental pancreatitis model
Authors: van Felius I , Bosscha K , Verheem A , Harmsen W , Visser M , van Dijk J , van de Gaag I , Gooszen H , Akkermans L
Published: March 2003

Background

A combination of secretory hyperstimulation and transduodenal intraductal bile acid exposure results in homogeneous pancreatitis with graded severity in a rat model. The model was modified by using an exteriorized common bile duct (CBD) as ductal infusion port while keeping the integrity of the gut intact. The objective was to determine whether bacterial translocation (BT) is present and relates to small bowel bacterial overgrowth (SBBO).

Methods

Fifty rats were divided into four groups: group 1, mild pancreatitis (intravenous caerulein); group 2, control (intravenous saline); group 3, necrotic pancreatitis (intravenous caerulein, intraductal glycodeoxycholic acid); and group 4, control (intravenous and intraductal saline). During infusion the CBD was clamped just above the papilla of Vater. Three days later samples from peripheral blood, peritoneal fluid and abdominal organs were harvested for quantitative microbial culturing. The splenic portion of the pancreas was removed for histopathological analysis.

Results

Histological examination showed minimal oedema in groups 2 and 4; group 1 was characterized by acinar vacuolization and group 3 had a combination of acinar necrosis with inflammation. BT to one or more abdominal organs took place. The difference in incidence of translocation between group 1 (six of 14) and group 2 (none of eight) was significant (P < 0·05). Furthermore, there was a significant difference in translocation between group 3 (six of eight) and group 4 (one of six) (P < 0·05), and in duodenal total bacterial counts between groups 3 and 4 (P < 0·05). Gram-negative rods and anaerobic bacterial counts were different between group 3 (mean(s.d.) 2·46(0·88)) and group 4 (0) (P < 0·05). However, total bacterial growth in the ileum did not differ significantly between groups.

Conclusion

In this pancreatitis model, without biliary obstruction, bacterial overgrowth of the duodenum occurred, accompanied by BT. Colonic bacteria were predominantly involved. This model offers the possibility of studying the relationship between SBBO, BT and the pathogenesis of necrotic (infected) pancreatitis.
Impaired ex vivo lipopolysaccharide-stimulated whole blood tumour necrosis factor production may identify patients in the intensive care unit with ‘sepsis’ and multiple system organ failure
Authors: Heagy W , Hansen C , Nieman K , Cohen M , Richardson C , Rodriguez J L , West M A
Published: March 2003

Background

There is currently no reliable diagnostic test to identify patients with sepsis in the intensive care unit (ICU) or patients with multiple system organ failure (MSOF). It was previously found that in vitro pretreatment of monocytes with lipopolysaccharide (LPS) induced blunted tumour necrosis factor (TNF) release to LPS rechallenge. It was hypothesized that patients exposed to LPS or septic stimuli in vivo would produce less TNF when stimulated ex vivo with LPS. This preliminary study sought to determine whether impaired ex vivo TNF release was associated with measurable differences in clinical outcome.

Methods

Heparinized whole blood was obtained from 27 ICU patients and five healthy controls, and incubated immediately with or without LPS 10 ng ml−1 at 37°C for 3 h, then centrifuged to recover serum. Serum TNF levels were measured using an enzyme-linked immunosorbent assay and expressed as mean(s.e.m.). Clinical data, such as ICU length of stay (LOS), duration of mechanical ventilation, white blood cell count and positive cultures, were obtained retrospectively. Quartiles (I, 0–25 per cent; II, 26–50 per cent; III, 51–75 per cent; and IV, 76–100 per cent) were identified on the basis of the distribution of plotted LPS-stimulated whole blood TNF values. Statistical analysis was by χ2 and Student's t tests.

Results

A wide range of LPS-stimulated whole blood TNF production was observed in ICU patients (5·1(0·7) ng ml−1) and controls (6·6(1·0) ng ml−1). Patients identified in the lowest quartile (n = 6) of TNF producers (less than 2 ng ml−1) had significantly lower TNF production and a higher incidence of infection (83 versus 38 per cent), and longer LOS (21·8 versus 9·0 days) and duration of mechanical ventilation (18·3 versus 6·0 days) than patients in quartiles II–IV (n = 21). Patients in the lowest quartile had significantly lower TNF production (1·1(0·2) ng ml−1) than normal controls (6·6(1·0) ng ml−1) (P < 0·05) or ICU patients in any other quartile (quartile II: 2·9(0·2) ng ml−1, quartile III: 5·3(0·3) ng ml−1, quartile IV: 10·4(1·3) ng ml−1) (P < 0·05).

Conclusion

The lowest levels of ex vivo LPS-stimulated whole blood TNF production were associated with a prolonged ICU stay, a higher incidence of positive cultures and a prolonged need for mechanical ventilation. Impaired TNF release may be a manifestation of monocyte endotoxin tolerance and may be a marker of monocytic dysfunction. Determination of whole blood ex vivo LPS-stimulated TNF production could be useful in the diagnosis of severe sepsis and MSOF in patients in the ICU.
‘Components separation technique’: a useful method for repair of (contaminated) abdominal wall defects
Authors: de Vries Reilingh T S , van Engeland M I A , van Goor H , Rosman C , Bemelmans M H A , de Jong D , Bleichrodt R P I
Published: March 2003

Background

Since 1994 the ‘components separation technique’ has been used for the repair of large abdominal wall defects, thus avoiding the use of prosthetic material.

Methods

The results of the method were evaluated retrospectively in 40 patients. There were ten women and 30 men, of mean age 50·3 years and mean body mass index 27·4 kg m−2. All had midline hernias that could not be closed primarily. Hernias occurred in 25 patients after acute surgery of whom 11 had open treatment of generalized peritonitis. Reconstruction was performed under clean conditions in 27 patients, clean contaminated in seven and contaminated or dirty in six. In 13 patients the reconstruction was combined with bowel surgery.

Results

The postoperative course was complicated in 15 patients: one case of wound dehiscence, five haematomas, two seromas, six wound infections and one case of respiratory insufficiency. One patient died 6 days after operation from mesenteric thrombosis. After a mean follow-up of 8·5 (range 0–20) months recurrent hernias were found in eight patients. One patient had an enterocutaneous fistula in a newly created umbilicus. All recurrences appeared after clean operations.

Conclusion

The ‘components separation technique’ is useful for the reconstruction of large abdominal wall defects, especially under contaminated conditions where the use of prosthetic material is contraindicated. Moreover the technique can be used to close the abdomen at an early stage after open treatment of peritonitis. Devascularization of the skin and a large wound surface created by mobilization of the skin and subcutis are major drawbacks. Release of the external oblique muscle via separate skin incisions can prevent these problems and makes the method applicable for patients with an enterostomy.
Adaptation of the vacuum-assisted closure system for laparostomy
Authors: Bergmann M , Burkart E , Sautner T , Függer R
Published: March 2003

Background

Laparostomy is a useful treatment option in selective cases of severe peritonitis. However, owing to the size, massive secretion and intestinal fistulas, the granulation of this wound is a long and troublesome process.

Methods

From 1994 to 1999 the vacuum-assisted closure (VAC) system has been used as the wound dressing for laparostomies.

Results

The VAC system has the following advantages compared with conventional dressings: (1) efficient drainage of the wound; (2) rapid induction of a macroscopically healthy granulation; (3) little irritation of the surrounding skin; (4) possibility of kinetic therapy in patients with acute respiratory distress syndrome; and (5) less psychological distress of the patient, owing to the closed dressing of an otherwise massively secreting wound. The major side-effect observed was erosion-induced bleeding. Bleeding always ceased after a pause of the VAC system for 24 h. The major complication of the system was clogging by fibrinous secretions and thickened intestinal fluids. These occlusions could be prevented by adding a rinsing line with 0·9 per cent sodium chloride. Interestingly, there was no increase in bacterial colonization of the abdomen.

Conclusion

Owing to multiple variables in patients with laparostomy an objective assessment of the advantages of VAC treatment compared with conventional dressings is almost impossible. However, it appears that the VAC system is a rational approach for the treatment of these large wound surfaces.
Intra-abdominal bacterial growth and detection of bacteria by fluorescence in situ hybridization in patients with secondary peritonitis
Authors: Buyne O R , Timens W , Kooi K , Degener J , Harmsen H J M , Rosman C
Published: March 2003

Background

Patients with secondary peritonitis are treated by surgery and intravenous antibiotics depending on the micro-organisms cultured from abdominal fluid samples. However, such samples may not be representative of the origin of the intra-abdominal infection. Therefore, this study determined (1) whether different micro-organisms are cultured from abdominal fluid, peritoneum and blood samples, and (2) whether fluorescence in situ hybridization (FISH), with 16S ribosomal RNA-targeted probes applied on peritoneum samples, is more efficient than standard culturing techniques.

Methods

In a pilot study, samples of abdominal fluid, peritoneum and blood were obtained from two groups of patients: six patients with secondary peritonitis (peritonitis group) and five patients without peritonitis (control group).

Results

Standard culturing techniques revealed coagulase-negative staphylococci (CNS) and yeast in abdominal fluid samples in three of six patients; Escherichia coli, enterococci, CNS and Citrobacter in peritoneum samples in five of six patients; and no micro-organisms in the blood samples from the peritonitis group. In the control group, CNS were cultured from the abdominal fluid samples in one of five patients, while no micro-organisms were cultured from peritoneum samples and CNS were cultured from the blood samples in one of five patients. The FISH technique revealed a large number of various anaerobic bacteria in peritoneum samples in one of six patients in the peritonitis group. In the control group no bacteria were detected.

Conclusion

Micro-organisms cultured from abdominal fluid differ from those cultured from peritoneum samples. The FISH technique confirmed these findings in only one case. However, it is a promising technique for the identification and localization of bacteria causing secondary peritonitis.
Chronic recurrent subareolar breast abscess: incidence and treatment
Authors: Versluijs F N L , Roumen R M H , Goris R J A
Published: March 2003

Background

Chronic recurrent subareolar breast abscesses (SBAs) are a distinct entity of non-puerperal breast abscesses. They are located in the retroareolar or periareolar area and occur as a result of obstruction of the lactiferous ducts by squamous metaplasia. Unfamiliarity with this entity often leads to inadequate treatment, and recurrences frequently appear with extended fistulas. For this reason, the incidence of and the treatment for SBAs were analysed retrospectively.

Methods

In two clinics all patients with non-puerperal breast abscesses were analysed during a 6-year period.

Results

Some 98 patients were included (in the same period 35 patients were treated for puerperal breast abscesses). In 85 patients a total of 204 SBAs occurred (the largest study known). The remaining 13 patients had other non-puerperal breast abscesses such as cystic breast disease, inflammatory breast carcinoma and fat necrosis. If treatment of the SBA did not include excising the ductus lactiferus, the recurrence rate was 72 per cent. If the ductus lactiferus was excised, the recurrence rate was 37 per cent.

Conclusion

If a patient presents with a non-puerperal breast abscess in a subareolar location, the first diagnosis to consider should be (chronic recurrent) SBA. Smoking appears to be an important precipitating factor. In a recurrent SBA most frequently anaerobic micro-organisms are cultured. The primary treatment of SBA may comprise only incision and drainage. However, this should be followed by excision of the affected ductus lactiferus, including a part of the mamilla. If the affected ductus is not sufficiently excised, the SBA is destined to become a problematic chronic recurrent abscess.
Mild endotoxaemia during low arginine plasma levels reduces blood flow to the small intestine
Authors: Prins H A , Houdijk A P J , Teerlink T , van Lambalgen A , Thijs L G , van Leeuwen P A M
Published: March 2003

Background

Arginine is the sole precursor in the generation of the vasodilating agent nitric oxide. Plasma levels of arginine are low in situations associated with endotoxaemia such as major trauma, sepsis and experimental obstructive jaundice. The aim of the study was to evaluate haemodynamics at low arginine plasma levels during low-grade endotoxaemia.

Methods

Rats were assigned randomly to receive (at t = 0 min) an intravenous infusion of 1·5 ml sodium chloride 0·9 per cent (SAL, n = 12) or 1·5 ml arginase solution (3200 units) (ASE, n = 17) over 20 min. After the SAL or ASE infusion, rats were randomly assigned to receive an intravenous endotoxin (lipopolysaccharide; LPS; 150 μg kg−1 in 1·0 ml 0·9 per cent sodium chloride) challenge (ASE-LPS, n = 10 and SAL-LPS, n = 6) or a control infusion of 1·0 ml 0·9 per cent sodium chloride (ASE-SAL, n = 7 and SAL-SAL, n = 6) at t = 30 min. Organ blood flow was measured at t = 270 min, using radiolabelled microspheres.

Results

At 270 min arginine plasma levels were lower in the ASE-treated rats (ASE-SAL versus SAL-SAL and ASE-LPS versus SAL-LPS, both P < 0·005). Cardiac output, mean arterial pressure and therefore total peripheral resistance were similar for all groups. In the LPS-treated animals (SAL-LPS and ASE-LPS) cardiac output was maintained by a higher heart rate compensating for the lower stroke volume. Organ blood flow to the small intestine and splanchnic blood flow were lower in the ASE-LPS-treated rats (both P < 0·05 compared with other groups). Total liver blood flow was similar for all groups; the lower splanchnic blood flow was compensated for by a higher hepatic arterial blood flow.

Conclusion

This study shows that low plasma levels of arginine do not influence organ blood flow while, during low-grade endotoxaemia, low arginine plasma levels result in reduced blood flow to the small intestine.
Pilot surveillance in the Netherlands of sepsis related to central vascular catheters
Authors: de Boer A S , Talsma E , Batenburg J , Geubbels E L P E , Mintjes-de Groot A J , van den Berg J M J
Published: March 2003

Background

The aim was to study the feasibility of surveillance of sepsis related to central vascular catheters (CVCs) in the PREZIES network of hospitals in the Netherlands.

Methods

A national expert team developed a surveillance protocol. Ten hospitals conducted the surveillance during 3 months in 1999. The plot was evaluated in an interview with the infection control practitioner (ICP) of each hospital and by analysing the data collected.

Results

ICPs considered this surveillance labour intensive and made recommendations on issues such as further clarifying the case definition and standardization of culturing of blood and catheters. Of 874 patients with one or more CVCs, 29 (3·3 per cent) had CVC sepsis. Most frequently infusion catheters were studied. Median length of stay was 5 days. Catheters in the femoral artery or vein, with more than one lumen, for parenteral feeding, or in place for more than 48 h were associated with CVC sepsis.

Conclusion

The surveillance of CVC sepsis in PREZIES hospitals is feasible and can generate useful reference values.
Moderate hypothermia prevents cell injury in rats with severe haemorrhagic shock
Authors: Güven H , Amanvermez R , Kaya E , Malazgirt Z , Altintop L , Özkan K
Published: March 2003

Background

This study aimed to evaluate a possible protective and therapeutic effect of mild to moderate hypothermia in severe haemorrhagic shock. Brainstem is one of the most sensitive tissues to oxidative stress in the early phase of haemorrhagic shock. The haemorrhagic oxidative stress at various core temperatures was studied using reduced glutathione (GSH) levels and thiobarbituric acid reactive substances (TBARS) as markers of lipid peroxidation in brainstem homogenate.

Methods

Forty rats were divided into four groups, of which one constituted the non-bleeding normothermia control group. In all of the three study groups, the rats were bled to 40 per cent of their estimated blood volume while they were being held at normothermia, mild (32°C) or moderate (28°C) hypothermia. Mean arterial pressure, rectal temperature, heart and breathing rates were recorded during the procedures. After 1 h of shock, tissue samples were removed by craniectomy.

Results

The tissue levels of TBARS increased significantly in normothermic and mildly hypothermic haemorrhagic shock groups (10·74 and 8·26 nmol g−1) compared with control (3·50 nmol g−1) (P < 0·001). However, the tissue TBARS level in the moderately hypothermic group was only minimally increased (4·53 nmol g−1). GSH levels fell slightly in normothermic and mildly hypothermic bleeding rats, and were unchanged in moderately hypothermic rats.

Conclusion

The TBARS level, which was a predictor of oxidant damage, changed slightly during severe haemorrhagic shock when the rats were moderately hypothermic. Hypothermia had a protective effect against cell injury during haemorrhagic shock. Tissue TBARS levels correlated well with the degree of tissue damage; lower levels suggested hypothermic protection.
Role of liver-produced prostaglandins in experimental intra-abdominal sepsis
Authors: Cokek A , Huseyinov A , Sevinc A , Coker I , Sagol O , Sokmen S , Terzi C
Published: March 2003

Background

While the cyclo-oxygenase (Cox) 1 pathway has physiological effects such as maintaining endothelial integrity, Cox-2 also has pathological effects. The role of liver-produced prostaglandins and their specificity were studied in an experimental sepsis model.

Methods

Some 28 male Wistar rats were divided into five groups. In all groups intra-abdominal sepsis was created by caecal ligation and puncture. Group 1 (IASG) comprised five rats and all had intra-abdominal sepsis only. In group 2 (MG; n = 5) all rats received meloxicam 5 mg kg−1. Group 3 (NG; n = 5) received nimesulid 2 mg kg−1. In group 4 (APG; n = 5) antiplatelet activating factor (PAF) agent was administered. Group 5 (MAPG) received meloxicam and anti-PAF. Following 24 h of intra-abdominal sepsis, all rats underwent reoperation. Peritonitis was confirmed pathologically and liver biopsies were performed. The levels of prostaglandin (PG) E2 and PGF2α as prototypic end-products of the Cox-1 and -2 pathway were measured in the biopsy specimens.

Results

The mean PGF2α levels were 539·2, 17·8, 194·4, 341·0 and 229·2 pg per mg liver tissue protein in groups 1–5 respectively. The respective mean PGE2 levels were 422·6, 438·0, 272·6, 331·4 and 205 pg mg−1. PGF2α values in MG were significantly different from those in all other groups (P < 0·001), and those in NG and MAPG were different from those in IASG and APG. On the other hand, PGE2 levels were significantly lower in NG, MAPG and APG than in IASG and MG. Liver tissue PAF was also detected in all groups except NG. Mean PAF levels in IASG, MG, APG and MAPG were 44·4, 33·2, 12·2 and 14·6 pg per mg tissue protein respectively.

Conclusion

(1) PAF is an important mediator in intra-abdominal sepsis. (2) Liver PGF2α may play a role in intra-abdominal sepsis independently from PAF. (3) Anti-PAF agent alone may help healing in peritoneal sepsis, but the main therapeutic agents are PGF2α blocking agents.
Cytokines and myeloperoxidase as markers of purulent-septic complications of acute pancreatitis
Authors: Perejaslov A , Chooklin S
Published: March 2003

Background

Purulent-septic complications often determine the outcome of severe acute pancreatitis. Unfortunately, there are no useful markers that can predict the contamination of necrotic foci.

Methods

Thirty-eight patients with severe pancreatitis were treated. The plasma levels of interleukin (IL) 1, IL-6, IL-8 and myeloperoxidase (MPO) were studied in all patients on days 1, 3, 7, 14 and 21 after the onset of acute pancreatitis.

Results

Raised levels of all inflammatory mediators were observed in all patients on the first day. A gradual decrease in cytokine and MPO levels was noted in patients with sterile necrosis and a favourable course of acute pancreatitis (17 patients). Contamination of the necrotic foci was accompanied by a rise in IL-8 (140·0 pg ml−1 or more) and MPO (11·0 nmol ml−1 or more) levels, which preceded the clinical manifestation of purulent complications. These results were confirmed by ultrasonographically guided aspiration. Two types of purulent-septic complications were identified: local and disseminating. Local purulent-septic complications (nine patients) were characterized by a moderate increase in cytokine levels and were associated with a good prognosis. The disseminating purulent-septic complications group (12 patients) was characterized by highest levels of proinflammatory cytokines, significant multiple organ failure and a poor prognosis. Eight patients with widespread purulent-septic complications died.

Conclusion

IL-8 and MPO plasma levels are valuable markers of infected necrosis in acute pancreatitis.
Dexamethasone in hyperdynamic sepsis in children
Authors: Martino F E , Klein S , Nasatsky E G , Martino G D
Published: March 2003

Background

A recent study analysed the usefulness of dexamethasone (DX) in hyperdynamic sepsis in children. This prospective study was performed in order to confirm or refute the conclusions obtained previously.

Methods

A prospective, randomized and sequential study was performed in 38 patients of both sexes with a mean age of 10 years. Patients had at least five of the following clinical features to be included in the study: hyperthermia, oliguria, tachycardia, tachypnoea, cyanosis or another sign of hypoxaemia, impaired consciousness (confusion, meningeal signs, psychomotor excitation, delirium) and digestive disturbance (haemorrhage, vomiting, diarrhoea). Criteria for exclusion were: previous organ failure (adrenal or renal insufficiency), diabetes, tuberculosis, systemic mycosis, corticosteroid sensibility and immunodeficiency. Patients were divided into two equal groups: placebo control and DX, the latter with forward contribution to the dose of 3 mg kg−1 each time, repeated at 12 and 24 h. In all cases, clinic and laboratory variables used commonly in intensive care were monitored. The evaluations were immediately before, and at 48 and 72 h after, the first dose of DX.

Results

There was no significant difference between the two groups.

Conclusion

The application of macrodoses of DX in hyperdynamic sepsis in children is not indicated.
Macrophages that have ingested apoptotic neutrophils release tissue inhibitor of matrix metalloproteinase 1
Authors: Power C , Wang J H , Street J , Higgins G , Redmond H P
Published: March 2003

Background

Apoptosis of neutrophils (PMNs) in vivo is followed by their rapid uptake into adjacent phagocytic cells, a critical process in tissue remodelling, regulation of the immune response and resolution of inflammation. Tissue inhibitor of matrix metalloproteinase (TIMP) 1 is crucial in regulating the matrix-degrading properties of matrix metalloproteinases released by activated PMNs in inflammatory foci. The aim was to elucidate whether mononuclear-derived phagocytes (MDPs) release TIMP-1 and/or MMP-9 after phagocytosis of apoptotic PMNs.

Methods

MDPs were prepared from peripheral blood monocytes after isolation by culture in well plates for 7–10 days. PMNs were isolated from similarly healthy volunteers. PMN apoptosis was induced by 10 min of ultraviolet irradiation at 254 nm. After a further 6 h of incubation apoptosis was assessed and was routinely greater than 50 per cent. Apoptotic PMNs were then added to MDPs in specific ratios. After 1 h non-phagocytosed PMNs were washed away. RPMI was added to MDPs in well plates and 18 h later the supernatant was collected. Phagocytosis of opsonized zymosan, exposure to tumour necrosis factor (TNF) α and lipopolysaccharide (LPS), and finally MDPs alone were used as controls. TIMP-1 was quantified by enzyme-linked immunosorbent assay.

Results

TIMP-1 was released by MDPs after phagocytosis of apoptotic PMNs and opsonized zymosan. MDPs also produced TIMP-1 after stimulation with TNF-α–LPS. Levels of TIMP-1 from these MDPs were significantly different from those in MDPs alone.

Conclusion

Phagocytosis of apoptotic PMNs is an integral part of the host's attempt to resolve inflammation in altered immune states such as the systemic inflammatory response syndrome in which PMNs persistently release proinflammatory substances damaging the local microenvironment. This study has demonstrated that MDPs release TIMP-1 after phagocytosis of apoptotic PMNs and that this may play a role in the regulation of tissue remodelling and repair in response to inflammation.
Novel animal model of septic shock following smoke inhalation
Authors: Murakami K , Bjertnaes L J , Soejima K , Traber L D , Traber D L
Published: March 2003

Background

The lesions of smoke inhalation often progress in the context of sepsis and other complications of the burn illness to a critical state consistent with acute respiratory distress syndrome (ARDS). The aim of this study was to develop a standardized and reproducible model of sepsis after smoke inhalation in sheep.

Methods

Merino ewes (n = 21) were surgically prepared for the study. Five to seven days later, animals received a tracheostomy and 48 breaths of cotton smoke. Pseudomonas aeruginosa was suspended in 30 ml saline, which contained 2–5 × 1011 colony-forming units, and injected into the right lobe (20 ml) and into the left lobe (10 ml) using a bronchoscope. After the bacterial challenge, the animals were ventilated mechanically with 100 per cent oxygen. Body temperature, haemodynamic parameters, blood gas and blood culture were monitored for 48 h.

Results

The sheep showed a hyperkinetic response and fall in arterial partial pressure of oxygen similar to that seen in severe sepsis in humans. These changes were more severe than in animals with smoke inhalation alone (Fig. 1).

Conclusion

This would be a good animal model of sepsis and ARDS.
Improved survival of tumour necrosis factor-deficient mice during zymosan-induced multiple organ dysfunction syndrome
Authors: Volman T J H , Hendriks T , Kullberg B J , Goris R J A
Published: March 2003

Background

Tumour necrosis factor (TNF) is believed to be a crucial mediator in systemic inflammation and the multiple organ dysfunction syndrome (MODS). Previous studies in this laboratory with a murine model have shown that interventions directed at TNF could mitigate the symptoms of zymosan-induced MODS. The present study aimed to investigate the course of MODS in the absence of TNF.

Methods

Twenty-four TNF/LT-knockout (−/−) mice and 25 wild-type (+/+) mice received an intraperitoneal dose of lipopolysaccharide 40 μg, followed by zymosan 1 mg per g body-weight 6 days later (day 0). Survival, body-weight and body temperature were monitored. At day 22 ten −/− mice and five +/+ mice were killed, and organs were collected and weighed. The remaining animals were followed until day 48, when all were killed and their organs harvested for histological examination.

Results

In all animals zymosan induced an acute sterile peritonitis phase followed by an apparent recovery. From day 8 onwards the +/+ mice entered a third, MODS-like, phase, characterized by loss of body-weight, decreased body temperature and significant mortality rate. At day 22, survival in the −/− mice was 92 per cent, which was significantly (P < 0·05) higher than that in the +/+ mice (60 per cent). In addition, mean body temperature and mean relative body-weight (versus weight at day 0) were 33·3°C and 84 per cent respectively in the +/+ mice. Data for the −/− mice were 35·9°C and 100 per cent respectively (P < 0·05). However, at this time point, both the +/+ mice and the −/− mice showed significant and similar organ damage, indicated by an increase in absolute and relative (versus body-weight) weight of lung, spleen and liver (the last organ only in the −/− mice). Moreover, at day 48 histopathological examination of liver, lungs, spleen and kidneys from the surviving animals showed a similar degree of microscopic damage in both the −/− and +/+ mice.

Conclusion

TNF-deficient mice exhibit significantly improved survival during zymosan-induced MODS and their clinical condition appears to be better than that of wild-type animals. However, surviving animals from both groups eventually display a similar degree of organ damage. Thus, in this murine model, the absence of TNF does not completely protect against MODS.
Experimental model of anorectal transplantation
Authors: O'Bichere A , Shurey S , Sibbons P , Green C , Phillips R K S
Published: March 2003

Background

Anorectal transplantation with pudendal nerve anastomosis after rectal excision is a possible strategy that would avoid a colostomy and recreate potentially normal anorectal function. This study investigates the technical feasibility of anorectal transplantation with pudendal nerve and inferior mesenteric artery and vein anastomosis in a porcine model.

Methods

Four female pigs (22–42 kg) provided donor anorectum for four male recipients (29–39 kg) under standard general anaesthesia. The donor operation involved abdominoperineal excision of rectum (APR) taking the anal sphincter, pudendal neurovascular bundle and inferior mesenteric vessels. The recipient underwent APR, transperineal introduction of the donor graft, anastomoses of the rectum, inferior mesenteric vessels and pudendal neurovascular bundle, and perineal closure. Recorded variables were duration of each step of transplantation, ischaemic time, dimensions of anastomosed structures and postoperative graft viability. Animals were killed at 24 h, the state of the graft was noted and tissue was taken for confirmatory histology.

Results

Mean operation time was 372 (range 303–435) min. Mean ischaemic time was 118 (100–130) min. Before death, observation at laparotomy revealed two pink grafts, one slightly dusky but healthy graft and one outright failure, reflecting the state of the mesenteric vessels, which were patent in three and thrombosed in one. Histological examination showed no difference between control biopsies and the three cases with satisfactory mesenteric flow. Gross ischaemia was present histologically in the failed case.

Conclusion

Anorectal transplantation is technically feasible in a pig model. Longer-term studies are now needed to assess return of function and overcome rejection issues.
Surgical treatment of adult primary hepatic sarcoma
Authors: Poggio J L , Nagorney D M , Nascimento A G , Rowland C , Kay P , Young R M , Donohue J H
Published: March 2003

Background

Primary sarcomas of the liver are extremely rare in adults. Optimal therapeutic approaches remain unclear.

Methods

Twenty consecutive adult patients who had surgical treatment for primary hepatic sarcomas were reviewed. Patient age ranged from 23 to 80 years. Other than one patient with primary hepatic angiosarcoma who had a history of thorium dioxide colloid (Thorotrast) exposure 23 years before diagnosis, no predisposing causes were apparent. Nineteen patients had hepatic resection and one patient had an orthotopic liver transplant. No patient received neoadjuvant chemotherapy or radiotherapy but radiotherapy was delivered intraoperatively in one patient.

Results

Leiomyosarcoma was the most common histological type of sarcoma diagnosed (five of 20 patients), followed by malignant solitary fibrous tumour (four) and epithelioid haemangioendothelioma (three). Fourteen tumours were high-grade sarcomas and six were low grade malignancies. Thirteen patients developed a recurrence. Distant metastases (ten patients) and intrahepatic recurrence (six) were the predominant sites of initial treatment failure. Six patients received salvage chemotherapy. Histological grade was the only factor significantly associated with overall patient survival (P = 0·03). With complete resection, patients with high-grade tumours had a 5-year survival rate of 18 (95 per cent confidence interval 5–62) per cent compared with 80 (52–100) per cent for patients with low-grade tumours. The 5-year survival rate for all 20 patients was 37 (20–60) per cent.

Conclusion

Surgical resection is the only effective therapy for primary hepatic sarcomas at present. Better adjuvant therapy is necessary, especially for high-grade malignancies, owing to the high failure rate with operation alone.
Safety of a single duplex scan to exclude deep venous thrombosis
Authors: Wolf B , Nichols D M , Duncan J L
Published: March 2003

Background

Guidelines advocate that a negative ultrasonographic scan needs to be followed by venography, or a repeat scan after 1 week, to detect potentially missed calf vein thrombosis. This study aimed to evaluate whether anticoagulation can safely be withheld on the basis of a single negative duplex scan in patients presenting with suspected deep venous thrombosis (DVT).

Methods

Duplex scan reports, case notes and questionnaires returned by general practitioners of patients with suspected DVT were analysed retrospectively. The main outcome measure was occurrence of an adverse thromboembolic event, a symptomatic DVT or a pulmonary embolism, within 3 months after a negative duplex scan.

Results

Some 537 patients had 706 leg scans performed, the majority because of leg symptoms or to look for indirect evidence of pulmonary embolism. Among 352 patients, who had 429 negative leg scans, four possible adverse events were identified. The rate of adverse outcome was therefore 1·1 per cent per patient and 0·9 per cent per leg.

Conclusion

Withholding anticoagulation in patients who had a single, complete, negative duplex scan is safe. A repeat scan should be performed if there is ongoing high clinical suspicion and considered in patients in whom the calf veins could not be visualized.