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Biomedical subjects

G Pedersen

Publications and source records attributed to G Pedersen.

At least 37 records · Page 2Linked to original sources

Patient characteristics, operative complications and long-term survival of patients aged 75 years or older subjected to carotid endarterectomy.

AIM: The aim of this study is to report risk factors, operative results and long-term survival of old patients operated on for carotid stenosis in order to evaluate their candidature for surgery. METHODS: Fifty-two patients aged 75 years or older subjected to 56 carotid endarterectomies performed during the years 1992 to 2001 were examined and compared to data concerning 161 younger patients (172 operations) operated during the same period. RESULTS: Preoperatively registered hypertension, cardiac disease, renal impairment, diabetes mellitus, cerebrovascular symptoms and involvement of the contralateral carotid artery distributed similarly among the old and young patients. The older patients suffered an operative combined stroke and mortality rate non-significantly higher than the younger. The older patients experienced a 3-year survival rate of 92%. This was significantly superior to that of a demographically matched population, and similar to the survival of the younger patients. The younger patients had a survival rate significantly inferior to the expected. CONCLUSION: Patients aged 75 years or older operated on for carotid stenosis appear to have similar preoperative characteristics, similar early operative complication rates and a significantly better long-term relative survival, as compared to younger patients going through carotid endarterectomy.

Adult↗

Phenol toxicity and conjugation in human colonic epithelial cells.

BACKGROUND: Colonic epithelial cells are exposed to a range of potentially harmful luminal factors. including phenols, but it is unresolved whether these compounds impair the integrity of the epithelium. The aim of this study was to describe the effect of phenol exposure on human colonic epithelial cells in vitro and the conjugation pathways involved in detoxification. METHODS: Primary human colonic epithelial cell cultures or HT-29 cell cultures were exposed to paracetamol, dinitrophenol or phenol (0.1-5 mM) for 24 h. Cell viability was measured using the methyltetrazoleum test. Phenol conjugation products released from cell cultures were identified by high-pressure liquid chromatography. Phenol glucuronidase (PGD) and sulphotransferase (PST) enzyme activities were measured in isolated cell homogenates. RESULTS: Paracetamol, dinitrophenol and phenol (>1.25 mM) significantly impaired the viability of primary colonic epithelial cell cultures. No differences between cell cultures from ulcerative colitis and control patients were observed. Paracetamol (5 mM) also induced significant cell damage in HT-29 cells. Glucuronidation was the preferred conjugation pathway in both cell models, despite the presence of PGD and PST activity. CONCLUSION: Phenols have a direct toxic effect on human colonic epithelial cells in vitro, which supports the view that dietary fermentation metabolites may be involved in the modulation of chronic bowel inflammation.

Adult↗

Tumour necrosis factor alpha converting enzyme (TACE) activity in the colonic mucosa of patients with inflammatory bowel disease.

BACKGROUND: Anti-tumour necrosis factor alpha (TNF-alpha) antibodies are effective in Crohn's disease and perhaps ulcerative colitis but antigenicity and the high cost have raised interest in other strategies to block TNF-alpha. These include the TNF-alpha converting enzyme (TACE) which releases soluble TNF-alpha from transmembrane pro-TNF-alpha. AIM: To investigate whether TACE activity is present in human colonic mucosa. MATERIALS AND METHODS: Detergent extracts of cell membranes from colonic biopsies were obtained from 12 controls and 28 patients with inflammatory bowel disease. Enzyme activity was measured by hydrolysis assays using pro-TNF-alpha or oligopeptide substrates spanning the known pro-TNF-alpha cleavage site at Ala(76)-Val(77). Cleavage products were identified by western blotting, high pressure liquid chromatography, or mass spectrometry. TACE protein was localised by immunohistochemistry and identified by western blotting of detergent extracts from purified lamina propria mononuclear cells (LPMNC) or epithelial cells. RESULTS: Detergent extracts released TNF-alpha from pro-TNF-alpha and cleaved a model oligopeptide as predicted. Substrate hydrolysis was sensitive to known TACE/matrix metalloproteinase (MMP) inhibitors, but not trocade which has low activity against TACE. The median TACE level was increased in active ulcerative colitis (147 arbitrary units (AU)/mg; p<0.01) but not in Crohn's disease (81 AU/mg) compared with controls (79 AU/mg). Both the full length proform and the active form of TACE protein were expressed in LPMNC cells and epithelial cells. CONCLUSIONS: Functional TACE activity is ubiquitously expressed in the human colon and increased in ulcerative colitis, raising interest in MMP inhibitors targeting TACE.

ADAM Proteins↗

Poisoning at sea: injuries caused by chemicals aboard Danish merchant ships 1988-1996.

INTRODUCTION: Injuries involving chemicals occur aboard merchant ships, since such agents are carried commonly on board either as cargo or as needed for running the ship. In case of events involving chemicals, the crew may seek advice from the Medical First Aid Guide for Use in Accidents Involving Dangerous Goods published by the International Maritime Organization. The Guide is currently under revision. To improve knowledge of what is relevant in such a guide, a study was undertaken to identify all intoxications and corrosive incidents occurring aboard Danish merchant ships. METHODS: A retrospective study of all intoxications and corrosive incidents reported to the Danish Maritime authorities between 1988 and 1996. RESULTS: A total of 177 injuries were identified, of which 66 were systemic poisonings and 111 were due to corrosive damage to the eyes and skin. Thirteen of 66 systemic poisonings were fatal and almost three out of four corrosive injuries involved the eyes. CONCLUSIONS: This study and others show that the majority of injuries aboard merchant ships involving dangerous goods are amenable to first aid and symptomatic measures. Specific antidotes seem to have a limited role aboard merchant ships.

Denmark↗

Multiple myeloma following an episode of community-acquired pneumococcal bacteraemia or meningitis.

The risk of multiple myeloma subsequent to an episode of serious pneumococcal infection has not been ascertained. We identified 328 episodes of community-acquired pneumococcal bacteraemia and 77 episodes of pneumococcal meningitis in 227,000 persons over 40 years of age in the County of North Jutland, Denmark, in the period 1981 to 1996. The incidence rate of a subsequent diagnosis of multiple myeloma was determined by linkage to the Danish Cancer Registry. During 1,218 patient-years of follow-up in the bacteraemia cohort, 7 cases of multiple myeloma were diagnosed compared with 0.13 cases expected (standardized incidence ratio (SIR) 53.5, 95% confidence interval 21.4-111.4). During 444 patient-years of follow-up in the meningitis cohort, 4 cases of multiple myeloma were diagnosed compared with 0.05 cases expected (SIR 83.2, 95% confidence interval 22.6-214.8). Patients who survive an episode of community-acquired pneumococcal bacteraemia or meningitis are at increased risk of being diagnosed with multiple myeloma, but the absolute risk is low.

Adult↗

Cytokine-induced impairment of short-chain fatty acid oxidation and viability in human colonic epithelial cells.

Pro-inflammatory cytokines may directly influence the viability and metabolic function of colonic epithelial cells (CEC) as an early event in the development of inflammatory bowel disease. We report here that TNF-alpha+IFN-gamma induced a synergistic, concentration-dependent decline in butyrate oxidation, an essential energy supply, in HT-29 and DLD-1 cells. TNF-alpha+IFN-gamma induced a parallel profound decline in cell viability in HT-29 cells, but not in DLD-1 cells, where impairment of butyrate oxidation seemed to precede later occurrence of cell damage. TNF-alpha+INF-gamma induced CEC damage was independent on NO formation and involved the IFN-gamma signalling pathway as well as induction of apoptosis. If cytokines have similar effects in vivo, these may lead to energy deficiency and thus contribute to CEC damage and disturbance of the epithelial integrity.

Apoptosis↗

A simple method to establish short-term cultures of normal human colonic epithelial cells from endoscopic biopsy specimens. Comparison of isolation methods, assessment of viability and metabolic activity.

BACKGROUND: Abnormalities in colonic epithelial cell function have been implicated in the pathogenesis of various intestinal disorders, especially inflammatory bowel disease (IBD). The mechanisms, however, remain obscure owing to the lack of representative human colonic epithelial cell models. The aim of this study was to develop and validate a method for establishment of short-term culture of normal human colonic epithelial cells from endoscopic biopsies. METHODS: Epithelial cells were isolated from colonoscopic biopsies by means of ethylenediaminetetraacetic acid/ethylene glycol tetraacetic acid (EDTA/EGTA) (10 or 60 min) or by enzyme treatment and cultured in collagen-coated wells. Viability was measured with a methyltetrazoleum conversion assay, confocal laser, and electron microscopy. Metabolic function was measured by means of butyrate oxidation, 14C-leucine and 3H-glucosamine incorporation; DNA synthesis by means of 3H-thymidine incorporation, and apoptosis with an enzyme-linked immunosorbent assay (ELISA) for histone-associated DNA fragments. Cell types were identified by immunocytochemistry. RESULTS: Ten minutes of EDTA/EGTA treatment released intact crypts and was superior to both the 60-min treatment and enzymatic treatment in terms of viability and nonepithelial cell contamination, respectively. Despite activation of detachment-induced apoptosis, a median 51% of the isolated cells was viable after 24 h of culture and metabolically active as judged by 3H-thymidine, 14C-leucine, and 3H-glucosamine incorporation. Butyrate oxidation followed more complex kinetics (substrate activation) than observed previously in other models. The apparent Km values (medians) were 0.7 mM and 4.5 mM in low and high concentration ranges, respectively. CONCLUSION: We report a simple method to establish culture of human colonic epithelial cells from endoscopically obtained biopsy specimens, producing sufficient viable cells to perform metabolic studies pertinent to the pathogenesis of IBD and related human disorders.

Biopsy↗

Cultures of human colonic epithelial cells isolated from endoscopical biopsies from patients with inflammatory bowel disease. Effect of IFNgamma, TNFalpha and IL-1beta on viability, butyrate oxidation and IL-8 secretion.

Cytokine-mediated impairment of viability and metabolic function of epithelial cells has been suggested as a possible early pathogenic event in the development of inflammatory bowel disease (IBD). It is currently unknown whether pro-inflammatory cytokines have a direct effect on human nontransformed colonic epithelial cells. We investigated the effects of TNFalpha, IFNgamma and IL-1beta on viability, short chain fatty acid (butyrate) oxidation and IL-8 secretion in human colonic epithelial cell cultures in vitro obtained from macroscopically normal mucosa from IBD patients and controls. Colonic crypts were isolated from endoscopical biopsies by ultra-short (10 min) EDTA/EGTA treatment, and exposed to TNFalpha, IFNgamma and IL-1beta for 24 hours. The combination of TNFalpha+IFNgamma induced a significant decrease in cell viability as judged by methyltetrazoleum (MTT) metabolism which decreased to median 68% of unexposed cultures (P < 0.01). This effect was more pronounced than that observed after addition of TNFalpha (median 88%) (P < 0.05), but not IFNgamma alone (median 78%), whereas IL-1beta had no significant effect. Cells from IBD patients were significantly less sensitive to TNFalpha + IFNgamma exposure (median 74%) compared to cells from controls (median 58 %) (P < 0.05). Butyrate oxidation, as measured by entrapment of 14CO2, was not inhibited in cells exposed to TNFalpha + IFNgamma, neither from controls (median 112%) nor from IBD patients (median 108%), suggesting a relative increase of this specific metabolic function in living cells in response to immunoinflammatory stress. IL-8 levels in cell supernatants were increased by TNFalpha + IFNgamma, supporting the role of the epithelium in signalling between luminal factors and mucosal immune cells. In conclusion, we report that TNFalpha and IFNgamma damage and influence human colonic epithelial cell function in vitro and that such mechanisms, if operative in vivo, also may be involved in the pathogenesis of IBD.

Adult↗

Community-acquired bacteraemia and antibiotic resistance. Trends during a 17-year period in a Danish county.

INTRODUCTION: The aim was to ascertain the prevalence of antibiotic resistance among blood isolates from patients with community-acquired bacteraemia and to relate it to antibiotic consumption. METHODOLOGY: Cases of community-acquired bacteraemia were identified in a regional bacteraemia register in the County of Northern Jutland. The study included 3974 episodes in 3805 patients during a 17-year period. Total regional consumption of antibiotics was expressed in Defined Daily Doses (DDD). RESULTS: The prevalence of antibiotic resistance was stable with few exceptions. The most notable time trend was noted for Escherichia coli for which the prevalence of resistance to ampicillin increased from 17% (95% confidence limits (CL) 12-23%) to 28% (95% CL 23-33%); for other Enterobacteriaceae the increase was from 73% (95% CL 61-83%) to 86% (95% CL 77-92%). The prevalence of resistance to aminoglycosides, fluoroquinolones and third-generation cephalosporins remained low among all isolates of Enterobacteriaceae. Regional antibiotic consumption ranged from 10.2 to 13.6 DDD/1000 inhabitants/day. Consumption of penicillins with Gram-negative spectrum reached a maximum of 4.6 DDD/1000 inhabitants/day in 1993 and decreased towards the end of the study period. The prevalence of ampicillin-resistant E. coli was positively correlated with consumption of penicillins with Gram-negative spectrum; the correlation was stronger when adjustment was made for co-selection by tetracyclines and sulphonamides. CONCLUSION: Therapeutic options for community-acquired bacteraemia have not yet become seriously limited by prevalence of acquired antibiotic resistance. Still we found some evidence that consumption of penicillins with Gram-negative spectrum, sulphonamides and tetracyclines promotes antibiotic resistance among Enterobacteriaceae.

Aged↗

Quantitative analysis of povidone (PVP) in drug-PVP matrix using multicomponent analysis.

A method for the quantification of povidone (PVP), in solid dispersions and physical mixtures of the polymer and a very slightly soluble drug substance, has been developed by multicomponent analysis using the concepts of chemometrics. Because the UV-absorbance spectra of PVP is completely overlapped by the UV-absorbance spectra of the drug substance, a direct spectrophotometric method of PVP is impossible. However, UV-spectrophotometric data were analyzed by the Quant + Perkin Elmer software for quantitative multicomponent analysis using chemometrics, and by the optimal method developed using a solvent of pH 7.4, a fast, reliable, and precise detection of PVP was obtained when the content of PVP in the powder sample exceeded 20% (m/m). Two methods were developed by the calibration procedure, using buffers of pH 7.4, respectively pH 8.5. By applying a solvent of pH 8.5, more sample could be taken into use because of the enhanced solubility of the drug substance, and hence it was believed that as more PVP was taken into use, a better prediction of PVP would be obtained. However, as more drug substance was taken into use the UV-absorbance spectrum of PVP was even more overlapped, and an inferior prediction was obtained.

Calibration↗

Risk of resistance related to antibiotic use before admission in patients with community-acquired bacteraemia.

We analysed the association of antibiotic therapy before admission and antibiotic resistance of blood isolates in a total of 1717 community-acquired bacteraemias in the County of Northern Jutland during 1992-96. Antibiotics had been prescribed to 14% of the patients during the 30 days before admission and to 37% during the 6 months. The most frequently prescribed antibiotics within 30 days were ampicillin (28%), penicillin G (27%), sulphonamides and/or trimethoprim (16%) and macrolides (14%). The most frequent blood isolates were Escherichia coli (33%), other Enterobacteriaceae (8%), Streptococcus pneumoniae (23%) and Staphylococcus aureus (10%). Of the 575 isolates of E. coli, 425 (74%), 432 (75%) and 518 (90%) were susceptible to ampicillin, sulphonamides and trimethoprim, respectively. Previous antibiotic prescriptions were strongly associated with resistance to ampicillin, sulphonamides and trimethoprim in E. coli. The association was less pronounced for S. aureus and enteric rods other than E. coli. Antibiotic prescriptions within the last 3 months predicted antibiotic resistance, and this should be taken into account when selecting empirical antibiotic therapy of severe community-acquired infections.

Aged↗

One-year follow-up of day treatment for poorly functioning patients with personality disorders.

OBJECTIVE: The study evaluated the effectiveness of day treatment for poorly functioning patients with personality disorders who participated in day treatment consisting of analytically oriented and cognitive-behavioral therapy groups as part of a comprehensive group therapy program. METHODS: At admission, discharge, and one year after discharge, patients completed the Global Severity Index (GSI) of the Symptom Check List 90-R and the circumplex version of the Inventory of Interpersonal Problems (IIP-C) and were assessed using the Global Assessment of Functioning (GAF) scale. At one-year follow-up, patients also completed a questionnaire covering social adaptation and clinical information and participated in a telephone interview with a clinician. The clinician used the completed instruments and results of the interview to assign patients follow-up GAF scores. RESULTS: Follow-up data were available for 96 patients who completed the study, or 53 percent of the patients who were admitted to the study. Improvements in GAF, GSI, and IIP-C scores during day treatment were maintained at follow-up. Seventy-four percent of the treatment completers improved clinically from program admission to follow-up, as indicated by change in GAF scores, and 64 percent of the treatment completers continued in the outpatient group program. For the 26 percent of patients whose change in GAF score did not indicate clinical improvement, lack of improvement was most strongly predicted by the expression of suicidal thoughts during treatment. No patients committed suicide. CONCLUSIONS: The day treatment program appears to be effective in improving the symptoms and functioning of poorly functioning patients with personality disorders and in encouraging patients to continue in longer-term outpatient therapy.

Adult↗

Borderline and avoidant personality disorders and the five-factor model of personality: a comparison between DSM-IV diagnoses and NEO-PI-R.

A self-report measure of the Five-Factor Model (FFM) of personality, NEO-PI-R, was administered to a sample of patients with borderline (BPD, N = 29) or avoidant PD (AVPD, N = 34), admitted to a day treatment program, to investigate the NEO-PI-R profiles of the disorders, and the ability of NEO-PI-R to discriminate between the two disorders. The diagnoses were assessed according to the LEAD standard. AVPD was associated with high levels of Neuroticism and Agreeableness, and low levels of Extraversion and Conscientiousness. BPD was associated with high levels of Neuroticism and low levels of Agreeableness, Extraversion, and Conscientiousness. Eighty-eight percent of the AVPD group had high scores on Neuroticism and low scores on Extraversion, whereas 65% of the BPD group were high on Neuroticism and low on Agreeableness. The Extraversion and Agreeableness scales of NEO-PI-R discriminated between patients with BPD and those with AVPD. Patients with BPD scored significantly higher on the Angry Hostility and Impulsiveness subscales of Neuroticism and significantly lower on three Extraversion subscales, three Agreeableness subscales, and one Conscientiousness subscale. At the DSM-IV criterion level, there were more significant relationships between the subscales of NEO-PI-R and the AVPD criteria than with the BPD criteria. The findings suggest that the FFM has good discriminating ability regarding BPD and AVPD. However, there may be a closer conceptual relationship between the FFM and AVPD than between the FFM and BPD.

Adult↗

An analysis of seven different methods to diagnose Helicobacter pylori infections.

BACKGROUND: It has been debated which diagnostic test should be preferred for the diagnosis of Helicobacter pylori in patients with gastroduodenal diseases. METHODS: The H. pylori infection was diagnosed prospectively in 97 untreated patients. H. pylori was diagnosed by means of tests based on five different principles: 1) culture, 2) microscopy (HLO), 3) urease activity (urea breath test (UBT) and urease test on biopsy specimens (CLO test)), 4) DNA detection (polymerase chain reaction (PCR)), and 5) IgG antibody detection (enzyme-linked immunosorbent assay (EIA) and Western blotting (WB)). RESULTS: This study showed that two positive tests out of five tests, based on different principles, were most reliable for predicting the H. pylori infection. Most tests had specificities and predictive values for a negative result greater than 90%. The most important difference between the tests was the sensitivity and the predictive value for a positive result (PPV). WB, HLO, UBT, and PCR had sensitivities and PPV greater than 75%. CONCLUSIONS: The non-invasive tests UBT and WB are reliable, both alone and in combination, and they are recommended for the pre-endoscopic diagnosis of H. pylori. WB is recommended as a confirmative test for antibody detection by EIA. When patients have an upper endoscopy, we recommend taking biopsy specimens for culture and histology because of the additional information obtained about susceptibility, virulence determinants, and morphology, including the degree of inflammation.

Adult↗

Outcomes of poorly functioning patients with personality disorders in a day treatment program.

OBJECTIVE: Rates of completion, complications, and outcome were examined in a sample of poorly functioning patients who participated in a group-oriented day treatment program for patients with personality disorders. METHODS: The study was a naturalistic prospective study of 183 patients admitted to a day treatment program in Oslo, Norway. The program consists of a combination of group analytically oriented groups and cognitive-behavioral groups. The Global Severity Index (GSI) of the Symptom Check List, the circumplex version of the Inventory of Interpersonal Problems (IIP-C), and the Global Assessment of Functioning (GAF) were administered at admission and discharge. RESULTS: A total of 138 [corrected] patients (77 percent) completed the day treatment program. Few patients experienced treatment complications. Effect sizes for GAF, GSI, and IIP-C scores for treatment completers were in the medium-to-high range, indicating a fair level of improvement. Patients' rating of benefit was positive. CONCLUSIONS: The results are promising as a first step toward development of a cost-efficient comprehensive long-term treatment program for patients with severe personality disorders.

Adult↗

[The role of cell adhesion molecules in inflammatory bowel disease and colorectal cancer].

Adhesion molecules participate in a broad variety of biological processes, i.e. tumour progression and inflammation, through their involvement in cell-to-cell interactions and immunoinflammatory cell migration. This review describes the basic properties of adhesion molecules with reference to inflammatory bowel disease and colorectal carcinoma. Future therapeutic approaches in inflammatory and malignant disorders may include development of principles targeting adhesion molecules.

Annexins↗

[Prehospital emergency treatment in the county of Northern Jutland 1993].

As part of the community planning of prehospital treatment in Northern Jutland, a mixed rural and urban region with a population of 500,000 people, we estimated the prehospital treatment in connection with 1617 emergency ambulance services. The investigation included data collected by the ambulance staff, the hospital doctors and review of medical records. The frequency of use of the emergency ambulance per 1000 population was 41 annually, and rapid emergency transport using signals constitutes 65% of call-outs. In the rural region the time from ambulance call until the ambulance reached the patients was longer than in the urban region. The ambulance staff as well as the doctor at the hospital considered a minor number of the patients as seriously ill. In 60% of the emergency ambulance transports the ambulance staff performed therapeutic efforts, frequently oxygen treatment (34%). In 305 transports the staff would have liked to carry out other forms of prehospital service, most often electrocardiographic-monitoring and treatment of pain. Only a few patients had need of advanced prehospital services but political consideration should be given to the possibility of advanced prehospital service in both rural and urban regions.

Ambulances↗