Biomedical subjects

G Pedersen

Publications and source records attributed to G Pedersen.

At least 19 recordsLinked to original sources

PubMed2006

The outcome of occluded above-knee femoropopliteal prostheses implanted for critical ischaemia.

OBJECTIVES: To investigate the impact of patient characteristics and treatment modality (graft thrombectomy vs thrombolysis) on the results of redo procedures for occluded above-knee prosthetic femoropopliteal grafts implanted for critical ischaemia. MATERIAL AND METHODS: Fifty-five procedures (thrombolysis 24 and thrombectomy 31) were performed on 24 prostheses (23 patients, 24 limbs) between January 1990 and December 2001. All cases were prospectively registered. Graft patency, limb salvage and survival rates were studied and subgroups of patients were compared. Risk factors were analysed with the use of log rank test and Cox proportional hazard analysis. RESULTS: Half of the 24 initial procedures to restored patency failed within one month. The outcome of second- or third-time redo procedures was similar. The primary patency rates of all 55 redo procedures were 32% at three months, 28% at six months and 12% at 12 months. The results of thrombectomy and thrombolysis were similar. Re-opened grafts additionally treated for an underlying anastomotic stenosis had significantly better patency as compared with re-opened grafts without a pre-existing stenosis on both univariate analysis (p = 0.024) and multivariate analysis (p = 0.027, hazard ratio 2.813). The one-year limb salvage rate was 76%. The one- and five-year survival rates were 87% and 52%, respectively. CONCLUSIONS: The results of redo procedures for occluded above-knee prosthetic grafts were disappointing. Grafts in which a graft-related stenosis was treated performed better than grafts in which occlusion could not be attributed to an underlying stenosis. Such cases should most likely be offered conservative treatment, amputation or a new arterial reconstruction.

Aged↗

PubMed2006

Submarine landslides: processes, triggers and hazard prediction.

Huge landslides, mobilizing hundreds to thousands of km(3) of sediment and rock are ubiquitous in submarine settings ranging from the steepest volcanic island slopes to the gentlest muddy slopes of submarine deltas. Here, we summarize current knowledge of such landslides and the problems of assessing their hazard potential. The major hazards related to submarine landslides include destruction of seabed infrastructure, collapse of coastal areas into the sea and landslide-generated tsunamis. Most submarine slopes are inherently stable. Elevated pore pressures (leading to decreased frictional resistance to sliding) and specific weak layers within stratified sequences appear to be the key factors influencing landslide occurrence. Elevated pore pressures can result from normal depositional processes or from transient processes such as earthquake shaking; historical evidence suggests that the majority of large submarine landslides are triggered by earthquakes. Because of their tsunamigenic potential, ocean-island flank collapses and rockslides in fjords have been identified as the most dangerous of all landslide related hazards. Published models of ocean-island landslides mainly examine 'worst-case scenarios' that have a low probability of occurrence. Areas prone to submarine landsliding are relatively easy to identify, but we are still some way from being able to forecast individual events with precision. Monitoring of critical areas where landslides might be imminent and modelling landslide consequences so that appropriate mitigation strategies can be developed would appear to be areas where advances on current practice are possible.

Computer Simulation↗

PubMed2006

Risk of bacteraemia and mortality in patients with haematological malignancies.

This study examined the association between type of haematological malignancy, risk of bacteraemia and risk of mortality, with emphasis on the impact of bacteraemia type on mortality. A population-based cohort design was used, and all patients aged > or = 15 years with an incident haematological malignancy who were living in North Jutland County, Denmark, during 1992-2002 were included in the study. Among 1666 patients with an incident haematological malignancy, 358 (21%) suffered an episode of bacteraemia during a median follow-up period of 1.1 years (quartile 0.2-3.4) from the date of cancer diagnosis (overall incidence rate of 96/1000 person-years). In comparison to Hodgkin's disease, adjusted incidence rate ratios (IRRs) were 23.3 (95% CI, 10.0-54.5) for acute myeloid leukaemia, 3.8 (95% CI, 1.5-9.3) for multiple myeloma, and 2.2 (95% CI, 0.9-5.1) for non-Hodgkin's lymphoma or chronic lymphatic leukaemia. Overall cumulative 30-day mortality was 32% (95% CI, 27-37), and 90-day mortality was 50% (95% CI, 44-55). In comparison with acute myeloid leukaemia, adjusted mortality rate ratios (MRRs) were close to 1.0 for other haematological malignancies. In comparison to bacteraemia caused by Gram-positive bacteria, adjusted MRRs were 1.0 (95% CI, 0.6-1.5) for Gram-negative bacteraemia, and 1.9 (95% CI, 1.1-3.3) for polymicrobial bacteraemia or fungaemia. Thus, the risk of bacteraemia varied greatly according to the type of malignancy, while mortality rates were similar for these diseases, although dependent on the type of bacteraemia. Polymicrobial bacteraemia or fungaemia was associated with higher mortality.

Adolescent↗

PubMed2005

Homocysteine levels, haemostatic risk factors and patency rates after endovascular treatment of the common iliac arteries.

OBJECTIVES: To investigate the impact of clinical risk factors, plasma homocysteine and haemostatic variables on the results after endovascular treatment of symptomatic atherosclerosis of the common iliac artery. DESIGN: Prospective observational study. SETTING: University hospital. PATIENTS AND METHOD: The study included 139 technically successful interventions in 103 patients. Technical success was defined as < or = 30% residual stenosis as seen on the post treatment angiogram. Blood samples for analyses of fasting plasma values of homocysteine, fibrinogen, D-dimer, activated protein C resistance were drawn upon admission. Median follow-up for all procedures was 22 months (range 0-55 months). Patency was defined as freedom from > or = 50% restenosis or reocclusion. RESULTS: The technical success rate for all procedures was 93%. The 1-year cumulative primary patency rate based on intention to treat was 85%. Multivariate analysis revealed a significant independent association between patency rates and levels of fibrinogen and homocysteine and the nature of the lesion treated (stenosis vs. occlusion). CONCLUSION: The aetiology of restenoses and reocclusions is probably multifactorial. Procoagulant activity, the nature of the lesion treated and homocysteine levels within and above the upper range of normal limits are important risk factors for failure after endovascular treatment of the common iliac arteries.

Adult↗

PubMed2005

The data quality of haematological malignancy ICD-10 diagnoses in a population-based hospital discharge registry.

The objectives of this study were to estimate the data quality of haematological malignancy diagnoses in a hospital discharge registry, and to quantify the impact of any misclassification of diagnoses on survival estimates. We included all patients > or = 15 years living in North Jutland County, Denmark with a first-time discharge diagnosis of a haematological malignancy registered in the Hospital Discharge Registry and the Danish Cancer Registry, the reference standard, from 1994 to 1999. We estimated completeness and positive predictive value (PPV) of haematological malignancies and specific subcategories, as a measure of data quality, and compared mortality rates based on data from the two registries by Cox regression analysis. Completeness in the Hospital Discharge Registry for all haematological malignancies was 91.5% (95% confidence interval (CI) 89.6-93.1) and PPV was 84.5% (95% CI 82.2-86.5). Reviews of the pathological files showed misclassified cases in both registries and thus indicated that both completeness and PPV of the Hospital Discharge Registry were underestimates. Mortality rate ratio for all haematological malignancies when registered in the Hospital Discharge Registry compared with being registered in the Danish Cancer Registry was 0.98 (95% CI 0.88-1.09). Discharge data had some misclassifications but these had no major impact on survival estimates.

Adolescent↗

PubMed2005

Expression of Toll-like receptor 9 and response to bacterial CpG oligodeoxynucleotides in human intestinal epithelium.

Recognition of repeat CpG motifs, which are common in bacterial, but not in mammalian, DNA, through Toll-like receptor (TLR)9 is an integral part of the innate immune system. As the role of TLR9 in the human gut is unknown, we determined the spectrum of TLR9 expression in normal and inflamed colon and examined how epithelial cells respond to specific TLR9 ligand stimulation. TLR9 expression was measured in human colonic mucosal biopsies, freshly isolated human colonic epithelial cells and HT-29 cells by reverse transcriptase-polymerase chain reaction or Western blotting. Colonic epithelial cell cultures were stimulated with a synthetic CpG-oligodeoxynucleotide (ODN), exhibiting strong immunostimulatory effects in B cells. Interleukin (IL)-8 secretion was determined by enzyme-linked immunosorbent assay, nuclear factor-kappaB (NF-kB) activity by electrophoretic mobility shift assay and IkB phosphorylation by Western blotting. TLR9 mRNA was equally expressed in colonic mucosa from controls (n = 6) and patients with ulcerative colitis or Crohn's disease disease (n = 13). HT-29 cells expressed TLR9 mRNA and protein and responded to CpG-ODN (P < 0.01), but not to non-CpG-ODN stimulation, by secreting IL-8, apparently in the absence of NF-kB activation. Primary epithelial cells isolated from normal human colon expressed TLR9 mRNA, but were completely unresponsive to CpG-ODN stimulation in vitro. In conclusion, differentiated human colonic epithelial cells are unresponsive to TLR9 ligand stimulation in vitro despite spontaneous TLR9 gene expression. This suggests that the human epithelium is able to avoid inappropriate immune responses to luminal bacterial products through modulation of the TLR9 pathway.

Adult↗

PubMed2005

The impact of comorbidity on long-term results of above-knee prosthetic femoropopliteal bypass for intermittent claudication.

AIM: The aim of this work was to report the impact of comorbidity on long-term results of prosthetic above-knee femoropopliteal bypass for intermittent claudication. METHODS: One hundred and forty-one consecutive operations (129 patients) between January 1990 and December 2001 in one single vascular unit were analyzed. All cases were prospectively registered. Survival and assisted primary patency rates were studied and subgroups of patients were compared. RESULTS: The 5-year survival was 77%, which is significantly lower than the survival of a demographically matched population (85%). Preoperative serum-creatinine >125 mmol/L was significantly associated with reduced survival (P<0.01). The assisted primary patency rates were 62% at 2 years and 44% at 5 years. The 5-year patency rate for smokers was 24% versus 67% for non-smokers (P<0.01). A previous history of cerebral infarction was significantly associated with reduced graft patency (P=0.02). CONCLUSIONS: Careful selection of patients submitted to surgical treatment of intermittent claudication is mandatory to achieve the optimal gain of the operation. Patients with intermittent claudication and renal impairment reveal poor survival. The reduced graft patency rates of patients with a history of a cerebral insult need further studies to be verified. Smokers should be treated conservatively due to their inferior graft patency rates.

Aged↗

PubMed2005

The impact of patient characteristics on long-term results of above-knee prosthetic femoropopliteal bypass for critical ischemia.

AIM: The aim of this paper was to study the impact of risk factors on long-term results of above-knee prosthetic femoropopliteal bypass for critical ischemia. METHODS: One hundred and eleven consecutive operations (108 patients) were done between January 1990 and December 2001. All cases were prospectively registered. The patient characteristics were subjected to univariate analysis using the log rank test for impact on survival, limb salvage and patency rates. Variables approaching significance (P<0.1) were included in multivariate analyses performed with the Cox proportional hazard model. RESULTS: The 30-day mortality rate was 5.5%. The 2- and 5-year survival was 72% and 42%, respectively. Twenty-seven limbs were subjected to major amputations during follow-up. The limb salvage rates at 2 and 5 years were 83% and 73%. The 2- and 5-year assisted primary patency rates were 45% and 17% versus 52% and 27% for the secondary patency. The 2-year primary patency rate for smokers was 38% versus 62% for non-smokers (P=0.018, hazard ratio 2.18). Smoking and tissue loss were significantly associated with reduced secondary patency rates on multivariate analysis. CONCLUSIONS: The inferior primary patency rates of smokers indicate that prosthetic femoropopliteal bypass for critical leg ischemia should not be the primary treatment option for these patients. The poor secondary patency rates for smokers as well as for patients with tissue loss suggest that these patients may benefit from alternative treatment modalities, instead of reopening an occluded bypass.

Aged↗

PubMed2004

Lifetime gain related to cost of repair of ruptured abdominal aortic aneurysm in octogenarians.

OBJECTIVE: To report cost related to gained life years after repair of ruptured abdominal aortic aneurysms in patients aged 80 or older. DESIGN: A retrospective study based on prospectively registered data. PATIENTS AND METHODS: Fifty-three patients aged 80 or older were operated on for ruptured abdominal aortic aneurysm over a 20-year period from 1983 to 2002. Thirty-one (58%) patients had systolic BT <80 mmHg. Operative mortality (<30 days) and long-term survival were studied. The number of life-years gained from the operations was estimated. Based on diagnose related group (DRG) values, the cost of each gained life-year was calculated. RESULTS: The operative mortality was 47%. Long-term survival of those patients who survived the operation was similar to that of an age and sex matched population. The 53 operations resulted in 145 gained life-years, which leaves a mean survival of 2.7 years of all the patients and 5.2 years of those who survived the operation. The estimated cost per gained life year was euro6817. CONCLUSIONS: The operative mortality of ruptured abdominal aortic aneurysm remains high. The long-term survival of patients who survive the operation is acceptable. The price of each gained life-year is low, as compared to other established treatment modalities. Improved results with endovascular treatment may even decrease the cost per gained life year.

Aged↗

PubMed2004

Homocysteine levels, haemostatic risk factors and patency rates after endovascular treatment of the above-knee femoro-popliteal artery.

OBJECTIVES: To investigate the relationship between plasma homocysteine and other haemostatic variables and restenoses or reocclusions after endovascular treatment of symptomatic atherosclerosis of the above-knee femoro-popliteal artery. DESIGN: Prospective observational study. SETTING: University hospital. PATIENTS AND METHODS: The study included 103 patients (116 limbs), treated with subintimal angioplasty in 58 cases (50%) and with intraluminal PTA in 58 (50%): 39 (34%) patients were treated for critical limb ischaemia. Blood samples for analyses of fasting plasma values of homocysteine, fibrinogen, D-dimer, activated protein C resistance were drawn upon admission. Median follow-up for all procedures was 11 months (range 0-42 months). Outcome events (arterial patency) were defined as > or =50% restenosis or reocclusion in the treated arterial segment. Patency rates were estimated with the product limit method and Kaplan-Meier curves. Variables found to be related significantly to patency were included in multivariate analysis performed with the Cox proportional hazard model. RESULTS: The 1-year cumulative primary patency rate for all procedures was 48%. One-year limb salvage rate in cases of critical ischaemia was 74%. Multivariate analysis demonstrated significant independent associations between patency rates and plasma D-dimer, diabetes mellitus, the nature of the lesion treated (stenosis vs. occlusion) and antithrombotic therapy with aspirin after the procedure. Plasma levels of homocysteine, fibrinogen or activated protein C resistance were not associated with patency rates. Homocysteine levels were higher in patients with critical limb ischaemia than those with intermittent claudication. CONCLUSIONS: Early restenosis or reocclusion after endovascular intervention of lesions in the above-knee femoro-popliteal artery was more frequent following treatment of occlusion (versus stenosis), for patients with diabetes, patients with elevated D-dimer and those without antithrombotic therapy after the procedure. Plasma homocysteine did not appear to influence the outcome of endovascular intervention.

Aged↗

PubMed2004

Homocysteine levels, haemostatic risk factors and restenosis after carotid thrombendarterectomy.

OBJECTIVES: To investigate the effect of elevated serum homocysteine and haemostatic as well as clinical risk factors on the tendency to restenosis after carotid artery thrombendarterectomy. DESIGN: A prospective, observational study. PATIENTS AND METHODS: In the period from October 1999 to October 2002, 86 patients were subjected to 96 carotid endarterectomies because of internal carotid artery stenoses. The carotid stenoses were symptomatic in 86 cases (90%). Fasting plasma homocysteine, fibrinogen, D-dimer and activated protein C resistance were measured the day before surgery. Follow-up was done 1, 3, 6, 12 and 18 months postoperatively and yearly thereafter with clinical assessment and triplex ultrasonography. The median follow-up time was 17 months (range 9-42 months). Freedom from restenosis was estimated with Kaplan-Meier curves, using log-rank test for comparison between groups. Variables found to be significantly related to restenosis rates were included in a multivariate analysis performed with the Cox proportional hazards model. Comparison of means of continuous data between two groups was done with Student's t-test and more than two groups with one-way analysis of variance. RESULTS: Restenoses within 12 months of the operation occurred in 11 cases (11%). Univariate analysis revealed that plasma homocysteine values < or =10 micromol/l and freedom from ischaemic heart disease were both significantly associated with an increased risk of restenosis (p=0.0076 and 0.0059). However, multivariate analysis showed that only plasma homocysteine values <10 micromol/l were independently and significantly associated with an increased risk of restenosis (p=0.046). There were no associations between the degree of atherosclerotic affection of the precerebral circulation or symptoms on one hand and the levels of homocysteine, fibrinogen, D-dimer and activated protein C resistance on the other. CONCLUSION: There seems to be an independent, significant association between homocysteine values within the lower two thirds of the normal range and restenosis after carotid endarterectomy. Studies on the biological properties of human endothelial cells from different types of vasculature and different locations, specifically with respect to homocysteine metabolism and its effect, are warranted.

Adult↗

PubMed2004

An investigation of the prototype validity of the borderline DSM-IV construct.

OBJECTIVE: To investigate the prototype validity of the borderline personality disorder (BPD) DSM-IV construct. METHOD: Patients (n = 930) from the Norwegian Network of Psychotherapeutic Day Hospitals. Exploratory/confirmatory factor analyses, correlation and reliability statistics, chi-square, and frequency distributions. RESULTS: Number of BPD criteria showed no distinct threshold between No-BPD and BPD patients among whom 136 different combinations of criteria occurred. Both factor analyses supported that one component/latent variable accounted for the variance of the BPD criteria, showing a high convergent and discriminant validity. The criterion of unstable relationships displayed the highest diagnostic efficiency, and that of chronic feelings of emptiness the lowest. CONCLUSION: The prototype theoretical model for BPD fitted the data well and appeared to be satisfactory described by the current criteria. The emptiness criterion needs a more appropriate definition and the hierarchy of the criteria in DSM-IV should be revised.

Adult↗

PubMed2004

Tumour necrosis factor-alpha converting enzyme (TACE) activity in human colonic epithelial cells.

Tumour necrosis factor (TNF)-alpha converting enzyme (TACE) releases biologically active, soluble TNF-alpha from transmembrane pro-TNF-alpha and has attracted interest as a specific therapeutic target in inflammatory bowel disease (IBD). Strong immunoreactivity for TACE protein was demonstrated recently in human colonic epithelium, but the function is unknown. We investigated if human colonic epithelial cells express functional TACE activity and how TACE expression is regulated in response to cytokine stimulation. TACE and TNF-alpha mRNA and protein expression were measured in HT-29 and DLD-1 colonic epithelial cells by reverse-transcription polymerase chain reaction, western blotting or enzyme-linked immunosorbent assay. Monocytic THP-1 cells served as positive control. Functional TACE activity was identified and quantified in detergent extracts of cell lines and freshly isolated colonocytes from 14 IBD patients and five controls by a hydrolysis assay using an oligopeptide spanning the cleavage site in pro-TNF-alpha. HT-29 and DLD-1 cells spontaneously expressed TACE mRNA and the active form of TACE protein at levels similar to those of monocytic cells. Functional TACE activity was demonstrated in all cell lines and in cells of controls or IBD patients irrespective of disease activity. TACE mRNA expression and functional activity remained unchanged in cell lines after stimulation with TNF-alpha despite clear induction of TNF-alpha mRNA expression and release of soluble TNF-alpha protein. The release of soluble TNF-alpha protein was almost completely abolished by CH4474, a synthetic TACE inhibitor. We conclude that functional TACE activity is constitutively expressed in human colonic epithelial cells and responsible for processing of the mature, soluble form of TNF-alpha in response to cytokine stimulation.

ADAM Proteins↗

PubMed2004

Is SCL-90R helpful for the clinician in assessing DSM-IV symptom disorders?

OBJECTIVE: To investigate associations between six of the Symptom Check-List 90R (SCL-90R) subscales and specific DSM-IV symptom disorders in a sample of patients with high comorbidity of axis I and axis II disorders. METHOD: SCL-90R questionnaires from 1202 patients admitted for treatment in the Norwegian Network of Psychotherapeutic Day Hospitals. Mean score differences on subscales among diagnostic categories were investigated. With diagnoses as external criteria, cut-off scores for different diagnostic groups were used to calculate diagnostic efficacy. Multiple regressions were conducted in order to disentangle variance of the subscales accounted for by symptom disorders. Frequency distributions of subscales for patients with and without symptom disorders were compared. RESULTS: Poor diagnostic efficacy was found for most of the subscales, except for the phobic anxiety subscale. The strongest association with each subscale was with its associated symptom disorder, except for dysthymia. CONCLUSION: Diagnostic inferences about DSM-IV symptom disorders based on SCL-90R should be conducted with care.

Adult↗

PubMed2004

Surgical treatment of popliteal artery aneurysms.

OBJECTIVES: To report the results of surgical treatment of popliteal aneurysms with respect to symptoms and aneurysm size. DESIGN: A retrospective study based on prospectively registered data, in a single vascular unit. PATIENTS AND METHODS: Forty-nine patients were subjected to 57 operations from May 1974 to June 2000. Patency and limb salvage rates are compared for limbs with and without symptoms of ischaemia, and for small (2 cm or less) and large (> 2 cm) aneurysms. The long-term survival rate was calculated and compared with that of an age and sex-matched population. RESULTS: The overall 5 year graft patency was 60%. It was 83% for asymptomatic limbs and 49% for limbs with ischaemic symptoms. This difference was significant (p < 0.05). The overall 5 year limb salvage rate was 76%. It was 100% for asymptomatic and 64% for symptomatic limbs and this difference was significant (p < 0.05). Twenty-one of the aneurysms were 2 cm or less in diameter and 85% of these caused symptoms of ischemia. The operative mortality was 4%. The 5-year survival rate was 57% and significantly lower than that of a demographically matched population. CONCLUSION: The results of prophylactic operations for popliteal aneurysms on asymptomatic limbs are significantly better than those of operations done on limbs with ischaemic symptoms. The aneurysm size at which to recommend surgery is still not settled.

Adult↗

PubMed2003

Source of infection and other factors associated with case fatality in community-acquired bacteremia--a Danish population-based cohort study from 1992 to 1997.

OBJECTIVE: To examine the association between the source of infection, other factors and the 30-day case-fatality rate (CFR) in patients with community-acquired bacteremia. METHODS: We included in the study 1844 patients older than 15 years (median age 72 years) with a first episode of community-acquired bacteremia in the period 1992-97 from a population-based bacteremia database. Information on co-morbidity, antibiotic prescriptions and date of death was obtained from health registries through linkage with the patient's personal identification number. The outcome measure was the overall CFR. RESULTS: The mean CFR was 18% (20% in 1992-95, 15% in 1996-97). The commonest sources of infection were the urinary tract (29%) and the respiratory tract (20%); patients with an undetermined source accounted for 21% in 1992-95 and 13% in 1996-97. The most frequent bacteria were Escherichia coli (33%) and Streptococcus pneumoniae (22%). Thirty-two per cent of patients did not receive appropriate empirical antibiotic therapy. The following factors were associated with CFR: source of infection other than the urinary tract, first four years of the study, age >/=75 years, and presence of co-morbidity. An undetermined source showed the strongest association with CFR during the period 1996-97. CONCLUSIONS: As an undetermined source of infection was strongly associated with CFR, physicians should be aware of the significance of identifying and eliminating a source of infection, and more efforts should be directed at timely and appropriate empirical antibiotic therapy.

Aged↗

PubMed2003

Subintimal angioplasty as a treatment of femoropopliteal artery occlusions.

OBJECTIVES: to report the results of subintimal PTA of femoropopliteal occlusions above the knee. DESIGN: a retrospective study. PATIENTS: in the period from January 1997 to January 2002, 109 patients were submitted to 124 interventions. The indication for treatment was intermittent claudication in 78 cases and critical ischaemia in 46. METHODS: all cases of subintimal angioplasty were prospectively registered. A review of all cases treated with subintimal PTA for above-knee femoropopliteal occlusions were done. Primary assisted haemodynamic patency rate was calculated on intention to treat basis and for successfully treated cases. Comparison of patency with respect to comorbidities, indication, runoff and occlusion length was done with univariate and multivariate analysis (Cox' regression). RESULTS: technical success rate was 90%. Primary assisted patency rates at 6, 12 and 18 months were 43, 37 and 31% calculated on basis of intention to treat and 48, 42 and 35% for successfully treated cases. Diabetes mellitus and critical ischaemia were found to be independent risk factors for re-occlusion. CONCLUSION: subintimal angioplasty is an alternative to open surgery for patients with femoropopliteal occlusions and intermittent claudication. The treatment is relatively atraumatic, complications are rare and in most cases treated with endovascular techniques. Patency rates are low. In cases of critical ischaemia, time can be important for outcome with respect to limb salvage. We therefore find that the poor patency rates of subintimal angioplasty of femoropopliteal occlusions contraindicate its use in the treatment of critical ischaemia with exception of cases unsuitable for surgical treatment.

Adult↗

PubMed2003

Superoxide production and expression of NAD(P)H oxidases by transformed and primary human colonic epithelial cells.

BACKGROUND: Superoxide (O(2)(-)) generation through the activity of reduced nicotinamide dinucleotide (NADH) or reduced nicotinamide dinucleotide phosphate (NADPH) oxidases has been demonstrated in a variety of cell types, but not in human colonic epithelial cells. AIMS: To measure O(2)(-) production and effects of modulators of NAD(P)H oxidase activity and inhibitors of potential O(2)(-) generating enzymes in cultures of human colonic epithelial cells. Expression of the catalytic subunits of NAD(P)H oxidase, Nox1 and gp91(phox) (phox, phagocytic oxidase), and the membrane bound subunit p22(phox) was assessed. METHODS: The transformed colonic epithelial cell lines (DLD-1, HT-29, and Caco-2) were studied at subconfluence, confluence, and after differentiation. Primary colonic epithelial cells were isolated from mucosal biopsies from the normal human colon. Extracellular O(2)(-) production was measured by the cytochrome c reduction assay or luminol enhanced luminescence. Nox1, gp91(phox), and p22(phox) mRNA expression was assessed in colonic epithelial cells and blood neutrophils by reverse transcriptase-polymerase chain reaction. RESULTS: Production rates of O(2)(-) were higher in subconfluent transformed cells (mean (SEM) 35.8 (4.2) nmol/mg of protein/h) and primary cells (40.4 (5.9)) than in confluent transformed cells (6.0 (0.9); p<0.01). The oxidoreductase inhibitor diphenylene iodonium significantly inhibited O(2)(-) production whereas NADPH and NADH increased production rates. In contrast, O(2)(-) was unaffected by phorbol myristate ester, N(G)-nitro-L-arginine methyl ester, indomethacin, or allopurinol. Nox1 mRNA was expressed in all colonic epithelial cells whereas gp91(phox) was detected only in HT-29 cells and neutrophils. p22(phox) was expressed in all cell types. CONCLUSIONS: Cultures of transformed and primary epithelial cells from human colon may produce extracellular O(2)(-) through an NAD(P)H oxidase expressing Nox1 and p22(phox).

Caco-2 Cells↗