Biomedical subjects

C W Wu

Publications and source records attributed to C W Wu.

At least 19 recordsLinked to original sources

PubMed2001

p53 amino acids 339-346 represent the minimal p53 repression domain.

The p53 tumor suppressor protein functions as an activator and also as a repressor of gene transcription. Currently, the mechanism of transcriptional repression by p53 remains poorly understood. To help clarify this mechanism, we carried out studies designed to identify the minimal repression domain that inhibits p53 transcriptional activities. We found only eight amino acids (339) of the COOH-terminal domain (termed P53MRD) that possess activities of repression. The exact location of this minimal domain is on the E6-binding region, and it lacks the ability of tetramerization. P53MRD is able to repress the transcription of p53 while not affecting VP16. The mutants (amino acids M340P and F341D) of native p53 also lost transcriptional repression of the thymidine kinase chloramphenicol acetyltransferase promoter. These results suggest that this eight-amino acid element is required for the repression of p53.

Binding Sites↗

PubMed2000

Tyrosine kinases and gastric cancer.

Carcinoma of the stomach is one of the most prevalent cancer types in the world today. Two major forms of gastric cancer are distinguished according to their morphological and clinicopathological classifications (well differentiated/intestinal type and poorly differentiated/diffuse type), characteristics that could also be attributed to the altered expression of different types of oncogenes or tumor suppressor genes. Significant differences exist for gastric cancer incidence comparing people of different ethnic origins, implicating various genetic and epigenetic factors for gastric oncogenesis. There are only a limited number of molecular markers available for gastric cancer detection and prognostic evaluation, among which are tyrosine kinases. There is convincing evidence that tyrosine kinases are involved in oncogenesis and disease progression for many human cancers. Amplifications of certain tyrosine kinases (c-met, k-sam and erbB2/neu) have been associated with human gastric cancer progression. Alternatively spliced transcripts and enhanced protein-expression levels for some of these tyrosine kinases are correlated with clinical outcomes for gastric cancer patients. With advent of high throughput techniques, it is now possible to detect nearly all expressed tyrosine kinases in a single screen. This increases the chance to identify additional tyrosine kinases as predictive markers for gastric cancers. In this article, we will first review the literature data concerning certain tyrosine kinases implicated in gastric carcinogenesis and then summarize more recent work which provide comprehensive tyrosine kinase profiles for gastric cancer specimens and cell lines. Two new gastric cancer molecular markers (tie-1 and mkk4) have been identified through the use of these profiles and demonstrated effective as clinical prognostic indicators.

Humans↗

PubMed2000

Binding of a de novo designed peptide to specific glycosaminoglycans.

The binding of glycosaminoglycans to a synthetic peptide (SKAQKAQAKQAKQAQKAQKAQAKQAKQW-CONH(2)), consisting of a hybrid consensus heparin binding sequence, is studied using circular dichroism, fluorescence anisotropy and nuclear magnetic resonance techniques. The results unveil certain novel features, most importantly, the peptide binds preferentially to iduronic acid containing glycosaminoglycans and the dissociation constant for the peptide-heparin complex was found to be 30 nM. Interestingly, higher order intermolecular association(s)/aggregation was not observed, especially at saturating concentrations of the ligand. The helical structure of the peptide backbone, induced upon binding to a particular glycosaminoglycan is directly related to their binding affinity. In our opinion, studies on such unconventional hybrid peptide sequences containing low density basic amino acid residues would lead to the design of sequence specific glycosaminoglycan binding peptides.

Amino Acid Sequence↗

PubMed2000

Converging evidence from microstimulation, architecture, and connections for multiple motor areas in the frontal and cingulate cortex of prosimian primates.

In the present study, somatotopic organization, architectonic features, and patterns of connections were used to define motor areas in the frontal and cingulate cortex of the prosimian primate Galago garnetti. Sites throughout portions of the motor cortex were electrically stimulated with microelectrodes at the approximate depth of layer V. In some of the same animals, injections in primary motor cortex (M1), and in the spinal cord, revealed patterns of connections with physiologically identified motor areas. Results were related to cortical architecture in brain sections processed for Nissl, myelin, cytochrome oxidase, acetylcholinesterase, or neurofilaments. Evidence was obtained for a number of fields previously identified in simian primates, including M1, dorsal premotor field with caudal (PMDc) and rostral (PMDr) divisions, ventral premotor area (PMV), supplementary motor area (SMA), presupplementary motor area (pre-SMA), frontal eye field (FEF), and cingulate motor areas, CMAr and CMAc located rostrally and caudally, respectively. In addition, we distinguished area 6Ds of Preuss and Goldman-Rakic (1991a) between PMV and PMDc, and a more posterior cingulate sensorimotor area (CSMA) with motor connections that may correspond to the supplementary sensory area of monkeys. Areas M1, SMA, PMDc, PMV, CMAr, CMAc, and CSMA projected to the spinal cord, while all of these areas and 6Ds projected to M1. Although area M1 had the lowest stimulation thresholds for evoked movements, movements were also evoked from the other motor areas, as well as from somatosensory areas 3a and 3b. These results indicate that prosimian galagos have a complex of motor areas that closely resembles that in monkeys and suggest that at least 10 motor fields emerged early in primate evolution.

Action Potentials↗

PubMed2000

Genome-wide search for loss of heterozygosity using laser capture microdissected tissue of breast carcinoma: an implication for mutator phenotype and breast cancer pathogenesis.

Breast cancer is considered to display a high degree of intratumor heterogeneity, without any obvious morphological and pathological steps to define sequential evolution, and its progression may vary among individual tumors. In an attempt to elucidate these etiological and phenotypic complexities, the present study, based on the fundamental concept that genomic instability is the engine of both tumor progression and tumor heterogeneity, was conducted to test the hypothesis that breast cancer pathogenesis is driven by double-strand break (DSB)-initiated chromosome instability (CIN). The rationale underlying this hypothesis is derived from the clues provided by family breast cancer syndromes, in which susceptibility genes, including p53, ATM, BRCA1 and BRCA2, are involved within the common functional pathway of DSB-related checkpoint/ repair. Because genomic deletion caused by DSB is reflected in the genetic mechanism of loss of heterozygosity (LOH), this genome-wide LOH study was conducted, using 100 tumors and 400 microsatellite markers. To minimize the effect of heterogeneity within tumors, the experimental technique of laser capture microdissection was used to ensure that genetic and phenotypic examinations were based on the same tumor cells. Support for our hypothesis comes from the observations that: (a) the extent of DSB-initiated CIN in tumors significantly increased as tumors progressed to poorer grades or later stages; (b) in the sequential steps toward CIN, the loci of p53 and ATM, the key checkpoint genes against DSB, were lost at the earliest stage; and (c) many loci identified to be important in breast tumorigenesis were the genomic sites possibly harboring the genes involved in DSB-related checkpoint/repair (including RAD51, RAD52, and BRCA1) or CIN (including FA-A, FA-D, and WRN), and a higher number of these loci showing LOH was significantly associated with increased level of DSB-initiated CIN (P < 0.0001). Breast cancers are thus considered to be sequentially progressive with CIN. However, CIN might also cause genetic heterogeneity, which was revealed by the findings that LOH at some markers was observed only in the component of ductal carcinoma in situ but not in the invasive component of the same tumors. In addition, some markers were found to preferentially lose at specific tumor grades, implying their contribution to genetic heterogeneity during tumor development. Therefore, this study suggests that breast cancer progression is clonal with regard to CIN, but different breast cancers would present distinct molecular profiles resulting from genetic heterogeneity caused by CIN.

Adult↗

PubMed2000

Histone deacetylases specifically down-regulate p53-dependent gene activation.

p53, the most commonly mutated gene in cancer cells, directs cell cycle arrest or induces programmed cell death (apoptosis) in response to stress. It has been demonstrated that p53 activity is up-regulated in part by posttranslational acetylation. In agreement with these observations, here we show that mammalian histone deacetylase (HDAC)-1, -2, and -3 are all capable of down-regulating p53 function. Down-regulation of p53 activity by HDACs is HDAC dosage-dependent, requires the deacetylase activity of HDACs, and depends on the region of p53 that is acetylated by p300/CREB-binding protein (CBP). These results suggest that interactions of p53 and HDACs likely result in p53 deacetylation, thereby reducing its transcriptional activity. In support of this idea, GST pull-down and immunoprecipitation assays show that p53 interacts with HDAC1 both in vitro and in vivo. Furthermore, a pre-acetylated p53 peptide was significantly deacetylated by immunoprecipitated wild type HDAC1 but not deacetylase mutant. Also, co-expression of HDAC1 greatly reduced the in vivo acetylation level of p53. Finally, we report that the activation potential of p53 on the BAX promoter, a natural p53-responsive system, is reduced in the presence of HDACs. Taken together, our findings indicate that deacetylation of p53 by histone deacetylases is likely to be part of the mechanisms that control the physiological activity of p53.

Acetylation↗

PubMed2000

Concomitant chemoradiation treatment in the management of patients with extrahepatic biliary tract recurrence of gastric carcinoma.

BACKGROUND: The aim of this study was to determine the role of concomitant chemoradiation in the alleviation of obstructive jaundice in patients with extrahepatic biliary tract metastases from gastric carcinoma. METHODS: Thirteen patients with good performance status who had obstructive jaundice resulting from extrahepatic biliary metastases after gastrectomy for gastric carcinoma were treated with palliative intent. Treatment consisted of insertion of a percutaneous transhepatic choledochal drainage (PTCD) catheter followed by external radiation up to a total dose of 40-60 grays in combination with chemotherapy (cisplatin 20 mg/m(2)/day, 5-fluorouracil 600 mg/m(2)/day, and leucovorin 90 mg/m(2)/day for 96 hours during the first and fifth weeks) on an outpatient basis. RESULTS: The concomitant chemoradiation produced a good palliative effect in all 13 patients. Hyperbilirubinemia continued to improve after treatment, patients' clay-colored stool resolved within an average of 4 weeks (range, 2-6 weeks), and bilirubin levels returned to normal. The PTCD catheter could be removed after treatment was completed (the seventh week); the mean duration of PTCD placement was 2 months. The entire treatment course was performed on an outpatient basis; hospital admission was necessary only for PTCD insertion and chemotherapy. Ten patients died of their disease, with an average survival of 14.4 months (range, 4-31 months) from the time of PTCD insertion. Three patients are still alive at 16, 21, and 8 months. Biliary tract patency was maintained until death. No serious treatment-related complications occurred, and no endoprothesis or intraluminal brachytherapy was needed in this study. CONCLUSIONS: Satisfactory palliation can be achieved by concomitant chemoradiation for patients with obstructive jaundice resulting from extrahepatic biliary metastases from gastric carcinoma, providing an alternative treatment choice for these patients.

Adult↗

PubMed2000

Prognostic significance of heat shock protein-27 expression in hepatocellular carcinoma and its relation to histologic grading and survival.

BACKGROUND: The expression of heat shock protein-27 (HSP-27) has been detected in some human tumors. In this study the authors investigated HSP-27 expression in patients with hepatocellular carcinoma (HCC) and examined its prognostic significance. METHODS: Expression of HSP-27 was studied in 58 HCC and adjacent noncancerous liver tissues by immunohistochemical stain. The relation between its expression and eight known prognostic factors was evaluated. RESULTS: Of the 58 HCC tissues studied, the presence of HSP-27 was demonstrated in 45 tissues (77.6%); low expression (</= 25%) was demonstrated in 17 tissues and high expression (> 25%) was demonstrated in 28 tissues. A significantly higher distribution of HSP-27 expression in HCC tissues compared with adjacent noncancerous liver tissues was obtained (P < 0.0001). Patients with high HSP-27 expression had a significantly higher histologic tumor grade than those with low HSP-27 expression (P = 0.001). The 5-year disease free survival rate of patients with high HSP-27 expression was 21.4% versus 59.3% for patients with low HSP-27 expression (P < 0.001). A similar relation was observed with overall survival (33.3% vs. 64. 8%; P = 0.009). HSP-27 expression was also identified to be a significant and powerful prognostic indicator for disease free survival (odds ratio = 2.25; P = 0.034) and for overall survival (odds ratio = 2.72; P = 0.015). CONCLUSIONS: The current study data suggest that HSP-27 expression is a powerful prognostic indicator and is related to histologic grade and survival of patients with HCC.

Adult↗

PubMed2000

Antagonism between members of the CNC-bZIP family and the immediate-early protein IE2 of human cytomegalovirus.

The HCMV IE2 protein negatively autoregulates its own expression as well as represses the transactivation activity of p53. Using the repression domain of IE2 as bait in the yeast two-hybrid system, Nrf1 and Nrf2, members of the CNC-bZIP family, were found to be IE2-interacting proteins. Residues 331-448 encompassing the DNA-binding and the dimerization domains of Nrf1 are sufficient for the interaction. The interaction was further confirmed in vitro by a glutathione S-transferase pull-down assay and in vivo by co-immunoprecipitation. In transient transfection studies, transcription driven by six copies of an NF-E2 site or by chimeric proteins between the DNA-binding domain of LexA and members of the CNC-bZIP family is repressed by IE2. Importantly, the DNA binding activity of the Nrf1/MafK heterodimer is not impeded by IE2. In a parallel study, CNC-bZIP factors attenuate the negative autoregulation of IE2. The attenuation could be explained by the finding that Nrf1 functions alone and synergistically with its heterodimerization partner, MafK, in inhibiting the DNA binding activity of IE2. Taken together, these results demonstrate the existence of antagonism between members of the CNC-bZIP family and IE2.

Cell Line↗

PubMed2000

Left main coronary artery aneurysm: sealing by stent graft and long-term follow-up.

We describe the implantation of a stent graft to seal off the left main coronary artery aneurysm of a 64-year-old man with guidance by intravascular ultrasound. The aneurysm was successfully sealed off. At 6-month and 1-year follow-up, a small residual aneurysm reappeared, which was treated conservatively. The technical issues in closing this aneurysm and the management of the residual aneurysm are discussed.

Blood Vessel Prosthesis Implantation↗

PubMed2000

Prospective study of gastric outlet obstruction in unresectable periampullary adenocarcinoma.

Controversy persists regarding the role of prophylactic gastrojejunostomy in patients with unresectable periampullary adenocarcinoma. In review of the retrospective series, presence of gastric outlet obstruction (GOO) has been claimed to be a bad prognostic sign. This prospective study aimed to clarify the necessity of routine prophylactic gastrojejunostomy in patients with unresectable periampullary adenocarcinoma. The incidence and prognostic significance of GOO were also evaluated. Sixty-six patients with unresectable periampullary adenocarcinoma were enrolled. They were divided into 2 groups to receive either a single biliary bypass or a double bypass (concomitant gastric and biliary bypasses) if they had GOO. The single bypass group was followed up to assess the incidence of GOO and subsequent need of a gastric bypass. Prognostic factors were evaluated by univariate and multivariate analyses. Forty-four (67%) of the overall 66 patients presented with GOO at the time of diagnosis. There was no statistical difference regarding the morbidity and mortality between the 2 groups, except longer (7 days) hospital stay in the double bypass group. Seven (31.8%) of the 22 patients in the single bypass group subsequently developed GOO an average of 6.2 +/- 1.0 months after their initial biliary bypass. By univariate analysis, significant prognostic factors for unresectable periampullary adenocarcinoma were: GOO (p = 0.0379), pancreatic head origin (p = 0. 0146 by univariate analysis), and distant metastasis (p < 0.0001). After multivariate analysis, only pancreatic head origin and distant metastasis remained significant independent factors of poor prognosis. In conclusion, gastrojejunostomy should be performed prophylactically in addition to a biliary bypass in patients with unresectable periampullary adenocarcinoma. The presence of GOO is not an independent factor of poor prognosis, but a reflection of the aggressive biologic behavior of pancreatic head adenocarcinoma.

Adenocarcinoma↗

PubMed2000

Surgical results in patients with hepatitis B-related hepatocellular carcinoma and positive hepatitis B early antigen.

Hepatitis B virus (HBV) infection is the major risk factor in the pathogenesis of hepatocellular carcinoma (HCC). Patients who are positive for hepatitis B early antigen (HBeAg) have active liver disease. The present study aimed to evaluate the possible role of HBeAg in patients with resectable HCC. A series of 249 HCC patients with complete preoperative hepatitis marker who had undergone potentially curative resection were enrolled. Patients with hepatitis C virus infection were excluded. Of these patients, 27 were positive for hepatitis B surface antigen (HBsAg) and HBeAg (group I), 171 were positive for HBsAg and negative for HBeAg (group II), and 51 were negative for hepatitis B markers (group III). The clinicopathologic features and postoperative survivals were compared among the three groups. The prevalence of HBeAg was 10.8%. Group I patients were significantly younger and had worse liver function, smaller tumors, and a higher incidence of liver cirrhosis and chronic active hepatitis than those in groups II and III. No increase in tumor invasiveness was noted in group I patients. The operative morbidity, mortality, and postresection survival were comparable among the three groups. Our findings indicated that HBeAg positivity is not a negative factor for resection in HCC patients and has no significant influence on postresection survival.

Aged↗

PubMed2000

Surgical mortality, survival, and quality of life after resection for gastric cancer in the elderly.

Although there were some studies on clinicopathologic characteristics, operative morbidity, and mortality in elderly patients with gastric cancer, no reports have specifically focused on survival and quality of life after resection. A total of 433 patients aged >/= 65 years (1987-1994) who underwent gastric resection for gastric adenocarcinoma were studied. Two groups were considered: patients aged 65 to 74 years and those > 74 years. Most of the patients (78.1%) had advanced diseases, and nearly half (41. 3%) had associated chronic disease(s). Resections with curative intention were performed in 362 patients (83.6%). The overall operative morbidity rate was 21.7% and mortality rate 5.1%. Although operative procedures were similar in both groups, patients aged >74 years had a higher mortality rate than those aged 65 to 74 years (10. 1% vs. 3.5%; p = 0.034). Age and extent of gastric resection were two independent factors negatively affecting mortality. The cumulative survival rates for patients who underwent curative resection were 86.2%, 72.4%, 67.2%, 62.9%, and 60.0% at 1, 2, 3, 4, and 5 years, respectively. Nearly all patients (96%) after surgery had normal work and daily activities. Some patients appeared to lack energy (16%) or experienced a period of anxiety or depression. There was no statistical difference in survival and quality of life assessed by the Spitzer index after curative resection between the two groups. Therefore resection with curative intention can be performed for the elderly with acceptable morbidity and mortality rates, possible long-term survival, and good quality of life, but a limited operation should be considered in the very elderly patients.

Activities of Daily Living↗

PubMed2000

Human gastric cancer kinase profile and prognostic significance of MKK4 kinase.

Alterations of protein tyrosine kinase are often associated with uncontrolled cell growth and tumor progression. Knowledge of the overall expression pattern of tyrosine kinases should prove beneficial in understanding the signaling pathways involved in gastric cancer oncogenesis and in providing possible biomarkers for gastric cancer progression. To establish a general tyrosine-kinase expression profile, degenerated polymerase chain reaction primers designed from the consensus catalytic kinase motifs were used to amplify protein tyrosine kinase molecules from gastric cancer tissues. We observed more than 50 tyrosine and serine/threonine kinases from matching pairs of gastric cancer tissue and normal mucosa. Based on this new kinase profile information, we selected the MKK4 gene for further immunohistochemical studies. Statistical analysis of MKK4 protein expression and clinicopathological features indicated that MKK4 kinase expression could serve as a significant prognostic factor for relapse-free survival and for overall survival. We demonstrated a simple and sensitive method for establishing protein tyrosine-kinase expression profiles of human gastric cancer tissues as well as for discovering novel and useful clinical biomarkers from such kinase expression profiles.

Aged↗

PubMed2000

Perioperative safety and prognosis in hepatocellular carcinoma patients with impaired liver function.

BACKGROUND: The benefits of liver resection for hepatocellular carcinoma (HCC) patients with concomitant impaired liver function were often considered questionable because of poor postoperative prognosis. This study will clarify whether an acceptable operative risk exists and whether limited resection will compromise the outcomes of these patients. STUDY DESIGN: Between July 1991 and December 1996, a total of 168 patients with HCC who underwent hepatectomies were enrolled and divided into normal (group A) and impaired (group B) liver function groups according to the value of indocyanine green retention rate at 15 minutes. Clinical features, surgical related features, pathologic features, and disease-free and overall survivals were compared between the groups. RESULTS: Operative morbidity and mortality in group A were 27.3% and 1.6%, and in group B were 40.0% and 2.5%, respectively (p = 0.129 and 0.506). Disease-free survival and overall survival at 5 years in group A were 43.2% and 59.6%, respectively, and in group B they were 30.6% and 56.8%, respectively (p = 0.607 and 0.378). CONCLUSIONS: Limited liver resection is safe and provides favorable prognosis in HCC patients with concomitant impaired liver function.

Adult↗

PubMed2000

Clinical significance of microscopic tumor venous invasion in patients with resectable hepatocellular carcinoma.

BACKGROUND: Tumor venous invasion in patients with resectable hepatocellular carcinoma (HCC) is frequent and can be macroscopic and microscopic or microscopic alone. Although macroscopic invasion is a well-established prognostic indicator, the clinical significance of microscopic invasion remains unclear. METHODS: There were 322 patients enrolled who had undergone curative resection for HCC. The clinicopathologic factors and prognostic significance associated with macroscopic and microscopic venous invasion were analyzed. RESULTS: Macroscopic invasion was observed in 50 patients (15.5%) and microscopic invasion in 190 (59.0%). The larger the tumor, the more the incidence of venous invasion. There were 140 patients with microscopic invasion only (Group 1). Patients with macroscopic invasion (Group 2, n = 50) also had microscopic invasion. Compared with patients without venous invasion (Group 3, n = 132), Group 1 had a higher alpha-fetoprotein level, a larger tumor size, and more tumors without encapsulation. For group 1, the 1-, 3-, and 5-year disease-free survival rates were 65.6%, 41.6%, and 30.8%, respectively. The 1-, 3-, and 5-year overall survival rates were 87. 8%, 60.0%, and 52.7%, respectively. The survival rates of group 1 were lower than those of group 3 and higher than those of group 2 (P <.05). Multivariate analysis indicated that microscopic and macroscopic venous invasion, surgical margin, indocyanine-green retention, and tumor size and number were significant predictors of postresectional survival. CONCLUSIONS: In HCC patients, microscopic venous invasion is frequent and related independently to postresectional outcome.

Aged↗

PubMed2000

Serum interleukin-10 but not interleukin-6 is related to clinical outcome in patients with resectable hepatocellular carcinoma.

OBJECTIVE: To evaluate the clinical significance of preoperative serum levels of interleukin-10 (IL-10) and interleukin-6 (IL-6) in patients with resectable hepatocellular carcinoma (HCC). SUMMARY BACKGROUND DATA: IL-10 is an immunosuppressive factor and IL-6 is a multifunctional cytokine that plays a role in host defense mechanisms. Both have been reported to be related to the disease prognosis in some human solid tumors. Their role in human HCC has not been investigated. METHODS: Preoperative serum samples of 67 patients with HCC who underwent potentially curative resection and 27 normal healthy donors were assayed. Levels of IL-10 and IL-6 were determined by enzyme-linked immunosorbent assay. The clinical significance of serum IL-10 and IL-6 was evaluated and compared with conventional clinicopathologic factors. RESULTS: Levels of IL-10 and IL-6 were significantly higher in patients with HCC than in healthy subjects. There was no correlation between IL-10 and IL-6 levels. Tumor resection resulted in a decrease in IL-10 and IL-6 levels. On univariate analysis, patients with high IL-10 levels had a worse disease-free survival, but IL-6 levels had no correlation with the disease-free survival. Multivariate analysis identified IL-10 levels as a predictor of postresectional outcome, in addition to the well-established clinical risk factors. CONCLUSIONS: In patients with HCC, the preoperative serum IL-10 level is related to the clinical outcome. IL-10 may play an important role in the progression of HCC.

Carcinoma, Hepatocellular↗

PubMed2000

Tumor necrosis factor gene polymorphism and septic shock in surgical infection.

OBJECTIVES: To evaluate the relationship of the genotype distribution of the tumor necrosis factor (TNF)-alpha polymorphism with regard to the plasma TNF-alpha concentration and the development of septic shock as well as mortality of infected patients in a surgical intensive care unit (SICU). DESIGN: A total of 112 postoperative critically ill infected patients were prospectively enrolled. SETTING: SICU of a tertiary university-affiliated medical center. PATIENTS: Patients who were consecutively admitted to the SICU because of surgical infection with sepsis. INTERVENTION: Blood sampling. MEASUREMENTS AND MAIN RESULTS: Blood sample was obtained 24 hrs after intensive care unit (ICU) admission or within 2 hrs after the onset of septic shock to determine the plasma TNF-alpha level and to analyze the genotype of the biallelic polymorphism of the TNF-alpha. RESULTS: The allele frequency of the TNF2 in our infected ICU patients was 12%. Forty-two (37.5%) patients admitted fulfilled the criteria of septic shock during their ICU stay. Patients carrying the TNF2 allele were not more likely to develop septic shock, nor did they have a higher mortality rate. In the patients with septic shock, those carrying the TNF2 allele had a significantly higher mortality rate than those with the homozygous TNF1 genotype (92% vs. 62%, p < .05). In those who developed septic shock, the TNF2 allele was significantly associated with higher TNF levels. CONCLUSION: In patients admitted to SICU with surgical infection, the frequency of TNF2 allele was higher than in the general population. SICU patients with TNF2 allele did not show a higher incidence of developing septic shock, nor was there a higher baseline TNF-alpha level after infection. However, once septic shock had developed, the mortality rate was higher in those patients carrying the TNF2 allele.

APACHE↗