bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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 &lt; 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 &lt; 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 &lt; 0·05), and the growth of Candida in the kidneys was one order of magnitude higher in the deficient than in control mice (P &lt; 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 &lt; 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

Abstract

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

Abstract

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 &lt; 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 &lt; 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 &lt; 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

Abstract

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

Abstract

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 &lt; 0·05). Furthermore, there was a significant difference in translocation between group 3 (six of eight) and group 4 (one of six) (P &lt; 0·05), and in duodenal total bacterial counts between groups 3 and 4 (P &lt; 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 &lt; 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

Abstract

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 &lt; 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 &lt; 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

Abstract

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

Abstract

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

Abstract

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

Abstract

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.