Management of common bile duct stones.
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Cholangiopancreatography, Endoscopic Retrograde↗
Biomedical subjects
Eric S Hungness
Publications and source records attributed to Eric S Hungness.
Prospective analysis of the incidence of deep venous thrombosis in bariatric surgery patients.
BACKGROUND: Venous thromboembolism (VTE), manifest as deep venous thrombosis (DVT) or pulmonary embolus, remains an important complication in bariatric operation patients. Our purpose was to determine the incidence of VTE in a consecutive series of patients undergoing Roux-en-Y gastric bypass (RYGB) to guide appropriate therapy. METHODS: We prospectively examined a consecutive series of RYGB patients with bilateral lower-extremity venous duplex scan (DS) preoperatively, on postoperative day (POD)#2, and approximately POD#14. Preoperative clinical information including history of VTE, intraoperative data, postoperative course, and complications were recorded. Heparin 5,000 U subcutaneously was administered before the operation and every 12 hours throughout hospitalization along with sequential compression devices. Ambulation was instituted on POD#1. Temporary caval filters were placed in patients with a history of VTE. RESULTS: A total of 106 patients were examined. Body mass index was 51 +/- 8 kg/m2 (range, 40-73 kg/m2). Laparoscopic RYGB was performed in 75%. Hospital length of stay was 2.5 +/- 0.6 days. One hundred patients had no history of VTE; none had a positive DS preoperatively or on POD#2. One patient had a positive POD#14 DS and a second patient had a superficial thrombophlebitis, but a negative DS for DVT (both patients were symptomatic). Six patients had a prior history of VTE; all underwent preoperative placement of a temporary caval filter. Of these 6 patients, 1 developed a new postoperative DVT and another patient had thrombus on the caval filter with a negative lower-extremity DS. CONCLUSIONS: Occult DVT was not observed preoperatively in RYGB patients, suggesting that routine preoperative DS is not necessary in the absence of VTE history. Prophylaxis of heparin and sequential compression devices appears satisfactory in preventing DVT with only a 1% incidence in patients with no prior history of VTE. Two of the 6 patients with prior history of VTE showed evidence of thrombus postoperatively. Although a small number of patients, this finding suggests that a caval filter should be placed preoperatively in RYGB patients with a history of VTE.
Adult↗
Sodium arsenite downregulates transcriptional activity of AP-1 and CRE binding proteins in IL-1beta-treated Caco-2 cells by increasing the expression of the transcriptional repressor CREMalpha.
In recent studies, sodium arsenite (SA) inhibited IL-6 production in cultured intestinal epithelial cells, at least in part by downregulating the activity of nuclear factor-kappaB (NF-kappaB). The influence of SA on the activity of other transcription factors regulating the interleukin-6 (IL-6) gene in enterocytes is not known. We tested the effect of SA on the activity of CCAAT/enhancer binding protein (C/EBP), activating protein-1 (AP-1), and CRE binding proteins in IL-1beta-treated Caco-2 cells. DNA binding activity was determined by electrophoretic mobility shift assay (EMSA) and transcriptional activity by transfecting cells with luciferase reporter plasmids containing promoter constructs with binding sites for the individual transcription factors. DNA binding activity for all three transcription factors was increased after treatment with SA or IL-1beta. In contrast, SA inhibited transcriptional activity of AP-1 and CRE binding proteins but not C/EBP. Additional experiments provided evidence that the inhibition of AP-1 and CRE mediated transcriptional activity was associated with, and probably caused by, increased expression of the transcriptional repressor cyclic AMP response element modulator (CREM)alpha. The present results are consistent with the concept that SA inhibits IL-6 production in stimulated enterocytes by downregulating the transcriptional activity of several, but not all, IL-6-related transcription factors. Because of the multiple important biological functions of IL-6 in the enterocyte and gut mucosa, methods to regulate enterocyte IL-6 production have significant clinical implications.
Arsenites↗
Proteasome inhibitors activate the transcription factors C/EBP-beta and delta in human intestinal epithelial cells.
In recent studies, induction of the heat shock response by hyperthermia upregulated the expression and DNA binding activity of the transcription factor C/EBP. This is an important observation because it may at least in part explain why the heat shock response upregulates IL-6 production in the intestinal mucosa and in the enterocyte. A novel method to induce the heat shock response is proteasome inhibition. The influence of this treatment on the expression and DNA binding activity of C/EBP is not known. We treated cultured Caco-2 cells, a human intestinal epithelial cell line, with one of the proteasome inhibitors, MG-132 or lactacystin, and measured C/EBP-beta and delta DNA binding activity by electrophoretic mobility shift assay and supershift analysis. In addition, nuclear levels of C/EBP-beta and delta protein were determined by Western blot analysis. Treatment of the cells with the proteasome inhibitors resulted in increased cellular levels of heat shock protein 72, consistent with induction of the heat shock response. Treatment also resulted in increased DNA binding activity and nuclear protein levels of C/EBP-beta and delta. The effects of the proteasome inhibitors on C/EBP were inhibited by treating the cells with quercetin, a substance known to block the heat shock response. The results suggest that proteasome inhibition activates the transcription factors C/EBP-beta and delta in human intestinal epithelial cells and that this response, at least in part, is caused by induction of the heat shock response. The observations are important because they provide support for a novel method to influence gene activation in the enterocyte.
Acetylcysteine↗
Arsenite stabilizes IkappaBalpha and prevents NF-kappaB activation in IL-1 beta-stimulated Caco-2 cells independent of the heat shock response.
Recent studies suggest that sodium arsenite downregulates NF-kappaB activity by inhibiting phosphorylation and subsequent degradation of IkappaBalpha. Many effects of sodium arsenite are secondary to induction of heat shock proteins. The role of the heat shock response in arsenite-induced inhibition of NF-kappaB, however, is not known. We examined the involvement of the heat shock response in arsenite-induced inhibition of NF-kappaB activity in IL-1beta-stimulated Caco-2 cells, a human colorectal adenocarcinoma cell line with enterocytic properties. Treatment of the cells with IL-1beta resulted in increased IkappaB kinase activity, reduced levels of IkappaBalpha and increased NF-kappaB DNA binding activity. Sodium arsenite blocked all of these responses to IL-1beta without inducing changes in heat shock factor activity or heat shock protein levels. Results from additional experiments showed that the protective effect of sodium arsenite on IkappaBalpha was not influenced by the oxygen radical scavenger catalase or by inhibitors of the MAP-kinase signaling pathway. The present results suggest that sodium arsenite stabilizes IkappaBalpha and prevents NF-kappaB activation in IL-1beta-stimulated Caco-2 cells independent of the heat shock response. In addition, stabilization of IkappaBalpha by sodium arsenite does not require oxygen radical formation or activation of the MAP kinase signaling pathway.
Arsenites↗
Transcription factors C/EBP-beta and -delta regulate IL-6 production in IL-1beta-stimulated human enterocytes.
In recent studies, treatment with IL-1beta of cultured Caco-2 cells, a human intestinal epithelial cell line, resulted in transcriptional upregulation of IL-6 production. The role of C/EBP-beta and -delta in enterocyte IL-6 production is not known. Stimulation with IL-1beta of Caco-2 cells transiently transfected with a luciferase reporter plasmid containing a wild-type IL-6 promoter resulted in an approximately 3.5-fold increase in luciferase activity. This effect of IL-1beta was reduced by approximately 30% when the C/EBP binding site in the IL-6 promoter was mutated, supporting a role of C/EBP in the regulation of IL-6 production. When Caco-2 cells were treated with IL-1beta in the presence of the MAPK inhibitor, PD-98059, IL-6 mRNA and protein levels were reduced by the same concentrations of PD-98059 that inhibited C/EBP DNA binding activity in previous studies. Finally, overexpression of C/EBP-beta and -delta in IL-1beta-treated Caco-2 cells resulted in a 10-12-fold increase in IL-6 production. The results suggest that the beta and delta isoforms of the C/EBP family of transcription factors at least in part regulate IL-6 production in human intestinal epithelial cells.
CCAAT-Enhancer-Binding Protein-beta↗
Early debridement for necrotizing pancreatitis: is it worthwhile?
BACKGROUND: The timing for debridement of necrotizing pancreatitis is controversial. We reviewed our experience with early and delayed surgical debridement in patients with necrotizing pancreatitis. STUDY DESIGN: The records of patients diagnosed with acute necrotizing pancreatitis from January 1993 through June 2000 were reviewed retrospectively. Data were analyzed with respect to Ranson's, APACHE II, and multiple organ failure scores, etiology, presence of infection, overall and ICU length of stay, time to first debridement, number of debridements, fluid requirements, days to enteral feeding, transfusion requirements, complications, and mortality. RESULTS: Twenty-six patients (18 males, 8 females, mean age 51 years) were diagnosed with acute necrotizing pancreatitis. The admission Ranson's score was 4.8, the APACHE II score was 11.7, and multiple organ failure score was 4.2. All but one patient underwent pancreatic debridement (4.3 debridements per patient). Eighteen patients (69%) had infected pancreatic necrosis. The timing of debridement was based on patients' condition and surgeon's preference. The presentation and demographics of patients who underwent early (<2 weeks) or late (>2 weeks) debridement did not differ significantly. Patients debrided early had a trend toward higher mortality (29% versus 18%) and experienced a higher number of major complications (p < 0.05). The six patients (23%) who died were older, had multiple organ failure scores, and more often had Candida in the infected necrosis (p < .05). CONCLUSIONS: Early debridement for acute necrotizing pancreatitis might not improve survival and might even be associated with increased number of complications. Most patients diagnosed with necrotizing pancreatitis eventually need debridement, but it might be beneficial to delay debridement if the patient's condition allows for it.
Age Factors↗
Hyperthermia-induced heat shock activates the transcription factor c/EBP-beta and augments IL-6 production in human intestinal epithelial cells.
BACKGROUND: Interleukin (IL)-6 production is increased in gut mucosa during sepsis and endotoxemia. The heat shock response augments IL-6 production under these conditions, but the mechanism is not known. We hypothesized that heat shock stimulates IL-6 production in enterocytes by increasing expression and activity of the transcription factor C/EBB. STUDY DESIGN: Cultured Caco-2 cells, a human intestinal epithelial cell line, underwent induction of the heat shock response by hyperthermia (43 degrees C for 1 hour). Other cells were kept at 37 degrees C. Cells were then treated with 0.5 ng/mL human recombinant IL-1beta for 4 hours. C/EBP-beta and delta DNA binding activity was determined by electrophoretic mobility shift assay and supershift analysis. In additional experiments, Caco-2 cells were transfected with expression plasmids for C/EBP-beta and delta, after which cells were subjected to hyperthermia and treatment with IL-1beta. RESULTS: C/EBP-beta, but not delta, protein levels and DNA binding activity were increased in Caco-2 cells expressing the heat shock response. Induction of the heat shock response augmented IL-6 production in IL-1beta-treated cells overexpressing C/EBP-beta, but not delta. CONCLUSIONS: Increased IL-6 production in IL-1beta-treated enterocytes expressing the heat shock response might be caused by upregulated expression and activity of CIEBP-beta. Because recent studies suggest that IL-6 might be an antiinflammatory cytokine and might exert protective effects in gut mucosa and enterocytes, understanding mechanisms by which the heat shock response augments IL-6 production might have important clinical implications.
CCAAT-Enhancer-Binding Proteins↗
IL-1beta activates C/EBP-beta and delta in human enterocytes through a mitogen-activated protein kinase signaling pathway.
The enterocyte is an active participant in the inflammatory and metabolic response to sepsis, endotoxemia and other critical illnesses and is the site for cytokine and acute phase protein production in these conditions. The role of the CCAAT/enhancer binding protein (C/EBP) family of transcription factors in the response to inflammatory stimuli in the enterocyte is not well understood. In the present study, we treated Caco-2 cells with IL-1beta and determined C/EBP DNA binding activity by electrophoretic mobility shift assay. The involvement of the alpha, beta, and delta isoforms was determined by supershift analysis and Western blot analysis of proteins from the nuclear fraction. The role of the mitogen-activated protein kinase (MAPK) signaling pathway was assessed by treating cells with the MAPK inhibitor PD-98059. Treatment of the Caco-2 cells with IL-1beta resulted in increased CCAAT/enhancer binding protein DNA binding activity. Supershift analysis and Western blotting indicated that this response to IL-1beta mainly reflected the delta isoform, and to a lesser degree the beta isoform. Treatment of the cells with PD-98059 inhibited the IL-1beta-induced increase in beta and delta activity. The results suggest that members of the CCAAT/enhancer binding protein family of transcription factors are activated in enterocytes during inflammatory conditions characterized by high levels of IL-1beta.
CCAAT-Enhancer-Binding Protein-beta↗
Bilateral synchronous breast cancer and HER-2/neu overexpression.
Bilateral synchronous breast cancer appears to have a worse prognosis than comparable unilateral breast cancer. HER-2/neu expression in bilateral breast cancer has not been reported. The purpose of this study was to review the characteristics of patients with bilateral synchronous breast cancer and to report the incidence of HER-2/neu overexpression. Between 1984 and 1998, 58 patients were diagnosed with bilateral synchronous breast cancer (defined as both cancers diagnosed within 3 months). The paraffin blocks from both breast specimens were available and immunostained in 21 patients. Of 42 breast specimens, there were 31 invasive carcinomas and 11 noninvasive carcinomas. Of the 21 paired specimens immunostained for HER-2/neu, 11 were invasive cancers in both breasts, nine were invasive cancers in one breast and noninvasive cancers in the other breast, and one was noninvasive cancers in both breasts. Of the 31 invasive carcinomas, HER-2/neu was overexpressed (2-3+) in 22 (71%) and negative (0-1+) in nine (29%). In contrast, 35 of 101 (34.7%) consecutive unilateral invasive breast cancer specimens from our institution overexpressed HER-2/neu. The difference in HER-2/neu overexpression between patients with bilateral synchronous breast cancer and unilateral breast cancer (22/31 v.s. 35/101) was statistically significant (chi square = 11.3, p < 0.001). In cases where both breasts had invasive carcinoma, HER-2/neu overexpression could be either in one (six patients) or both breasts (four patients). The increased mortality of patients with bilateral synchronous breast cancer may be due to the higher incidence of HER-21neu overexpression.
Aged↗
Arsenite inhibits interleukin-6 production in human intestinal epithelial cells by down-regulating nuclear factor-kappaB activity.
Previous studies have suggested that the production of interleukin-6 (IL-6) is increased in the intestinal mucosa during inflammation, and that nuclear factor-kappaB (NF-kappaB) is an important regulator of the IL-6 gene in the enterocyte. We tested the hypothesis that sodium arsenite inhibits IL-6 production in stimulated enterocytes and that this effect of arsenite is caused by down-regulation of NF-kappaB activity. Cultured Caco-2 cells were treated with sodium arsenite and were then stimulated with IL-1beta. IL-6 production and gene expression were determined by ELISA and reverse transcriptase-PCR respectively. NF-kappaB DNA binding activity was determined by electrophoretic mobility shift assay. IL-1beta increased NF-kappaB DNA binding activity, IL-6 mRNA levels and IL-6 production. These effects of IL-1beta were inhibited by treatment of the cells with sodium arsenite in a dose- and time-dependent fashion. When cells were transfected with a plasmid expressing the p65 subunit of NF-kappaB, the inhibitory effect of sodium arsenite on NF-kappaB activity and IL-6 production was blunted. These results suggest that sodium arsenite inhibits IL-6 production in enterocytes subjected to an inflammatory stimulus, and that this effect, at least in part, reflects down-regulated NF-kappaB activity.
Arsenites↗
The stress response decreases NF-kappaB activation in liver of endotoxemic mice.
Recent studies suggest that the stress (heat shock) response protects cells and tissues from inflammatory and other noxious insults. The transcription factor nuclear factor-kappa B (NF-kappaB), normally sequestered in the cytoplasm by its inhibitory protein IkappaB, regulates many genes involved in the inflammatory response to critical illness. Endotoxemia is associated with increased NF-kappaB activity in liver but the effect of the stress response on endotoxin-induced NF-kappaB activation in the liver is not known. We hypothesized that the stress response inhibits NF-kappaB DNA binding activity in liver during endotoxemia. The stress response was induced in mice by hyperthermia (42 degrees C for 3 min) or sodium arsenite (10 mg/kg) and resulted in increased hepatic heat shock protein-72 levels. After induction of the stress response, mice were injected subcutaneously with endotoxin (12.5 mg/kg) or a corresponding volume of sterile saline. NF-kappaB DNA binding activity in the nuclear fraction of liver tissue increased and cytoplasmic IkappaB-alpha levels decreased after endotoxin injection, with a maximal effect seen at 60 min. The endotoxin-induced increase in NF-kappaB DNA binding activity and decrease in IkappaB-alpha levels were inhibited by prior induction of the stress response. In additional experiments, treatment of mice with sodium arsenite after induction of endotoxemia blunted the increase in NF-kappaB activity, indicating a therapeutic potential of sodium arsenite, in addition to its preventive effect. The present results suggest that the protective effects of the stress response in vivo may, at least in part, be due to inhibited NF-kappaB activation.
Animals↗
Proteasome inhibitors induce heat shock response and increase IL-6 expression in human intestinal epithelial cells.
In previous studies, the heat shock response, induced by hyperthermia or sodium arsenite, increased interleukin (IL)-6 production in intestinal mucosa and cultured human enterocytes. A novel way to induce the heat shock response, documented in other cell types, is treatment with proteasome inhibitors. It is not known if proteasome inhibition induces heat shock in enterocytes or influences IL-6 production. Here we tested the hypothesis that treatment of cultured Caco-2 cells, a human intestinal epithelial cell line, with proteasome inhibitors induces the heat shock response and stimulates IL-6 production. Treatment of Caco-2 cells with one of the proteasome inhibitors MG-132 or lactacystin activated the transcription factor heat shock factors (HSF)-1 and -2 and upregulated cellular levels of the 72-kDa heat shock protein HSP-72. The same treatment resulted in increased gene and protein expression of IL-6, a response that was blocked by quercetin. Additional experiments revealed that the IL-6 gene promoter contains a HSF-responsive element and that the IL-6 gene may be regulated by the heat shock response. The present results suggest that proteasome inhibition induces heat shock response and IL-6 production in enterocytes and that IL-6 may be a heat shock-responsive gene, at least under certain circumstances. The observations are important considering the multiple biological roles of IL-6, both locally in the gut mucosa and systemically, and considering recent proposals in the literature to use proteasome inhibitors in the clinical setting to induce the heat shock response.
Acetylcysteine↗
Home oxygen therapy: adjunct or risk factor?
The use of home oxygen therapy has become increasingly commonplace and is frequently prescribed by medical specialists. In this study, we have identified a generally unexpected risk of home oxygen therapy. We performed a retrospective review of 3673 consecutive patients treated at our adult burn center over a 10-year period from 1992 to 2001. We identified 27 patients with burns directly attributable to oxygen therapy and also noted an increased incidence of these injuries over the study period. The average age of the patients was 68.1 +/- 9.2 years (range, 40-82 years). Twenty-three were using oxygen at home, three in nursing homes, and one was an inpatient in an acute care facility. Twenty-five patients (93%) were receiving oxygen therapy for the diagnosis of chronic obstructive pulmonary disease. Twenty-four patients (89%) were smoking while using oxygen, two were lighting pilot lights, and one was lighting his wife's cigarette. Four patients (15%) sustained burns greater than 10% TBSA. Seventeen patients (63%) had only partial thickness burns. Thirteen patients (48%) required admission for treatment of their burn injuries. The average length of stay for those admitted was 4.4 days. The average hospital charge for admitted patients was US dollars 8055. There were four deaths (15%), all of which were correlated only with the extent of injury. Although intuitively obvious to most health care professionals, not all patients understand that oxygen therapy and cigarettes or open flame can result in a significant injury. Although some practitioners have advocated not prescribing home oxygen for those who continue to smoke, an alternative means of reducing the incidence of this preventable complication appears warranted. Prevention efforts should focus on the counseling of patients and their caregivers as well as educating primary care physicians, nurses, and home health providers as to the dangers of oxygen use.
Accident Prevention↗