Stig Larsen
NMBU, Production Animal Clinical Sciences, Faculty Member
The study was conducted double blind in 12 healthy volunteers, average age 30 years (23-48). On separate days they were allocated at random to either two tablets of Trimipramine, 25 mg each, or two tablets of Placebo, one and a half hours... more
The study was conducted double blind in 12 healthy volunteers, average age 30 years (23-48). On separate days they were allocated at random to either two tablets of Trimipramine, 25 mg each, or two tablets of Placebo, one and a half hours before introduction of a Levine tube into the stomach. The volunteers had on the day of starting the experiment performed their normal duties, and consumed the last meal, the dinner, at 5 pm. The gastric juice was collected continuously in half hour samples from 11 pm until 7 am the next morning. The average recovery was 87% in 4 tested experiments. The volume of gastric juice was 448 ml/8 h for the series receiving Placebo compared to 418 ml/8 h for those treated with Trimipramine (Table 1). During the first half hour a relative high volume was aspirated, whereas in the following 3 half hours portions the volume decreased to a fairly stable level of about 15-23 ml. A significant lower volume was observed in the Trimipramine treated series in some of the morning portions. A significant lower concentration and output of HCl was found during the middle of the night and in some morning portions in the subjects given Trimipramine. Similarly the concentration and output of pepsin were lower in the Trimipramine series than in the Placebo treated subjects.
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To study the protective effect of Sucralfate on Naproxen-induced mucosal lesions, 16 healthy, male volunteers were given Naproxen 500 mg b.i.d. together with Sucralfate 2 g b.i.d. or placebo in a double-blind, crossover study. Drug... more
To study the protective effect of Sucralfate on Naproxen-induced mucosal lesions, 16 healthy, male volunteers were given Naproxen 500 mg b.i.d. together with Sucralfate 2 g b.i.d. or placebo in a double-blind, crossover study. Drug periods were 1 week, with a 3-week wash out in between. Mucosal lesions in stomach and duodenum were assessed by upper endoscopy before and after each drug period, using a visual analogue with separate scoring of mid- and distal duodenal lesions. 51Cr-EDTA absorption tests were performed to demonstrate possible changes in distal gut permeability. In addition, subjective symptoms were registered. Both drug periods induced significant lesions in the stomach and duodenum. Statistically speaking, fewer changes were found in the stomach and duodenal bulb after Sucralfate co-administration, whereas no significant reduction of lesions was seen in the distal duodenum. The 51Cr-EDTA absorption was increased in both periods, indicating deleterious effects to distal parts of the gut, but our results did not demonstrate Sucralfate-mediated protection from these changes. Symptoms were modest, and equal in the two periods. We conclude that Sucralfate may offer protection in the gastric and proximal duodenal mucosa, but no such protective effect was seen distally to the duodenal bulb.
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The use of visual analogue scales in the evaluation of mucosal lesions may reduce sample size requirements in clinical trials, but they may be complex to use, and adding guide points may reduce their informative value. We found that two... more
The use of visual analogue scales in the evaluation of mucosal lesions may reduce sample size requirements in clinical trials, but they may be complex to use, and adding guide points may reduce their informative value. We found that two investigators with differing levels of endoscopic experience reached comparable conclusions in 4 clinical trials (738 scores), and their scores were highly correlated, with similar dispersion characteristics. With guide texts along the scales, thus avoiding points on the actual scales, no tendency towards accumulation was seen in 1449 scores. These results encourage the use of visual analogue scales in endoscopic studies.
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The development of the SADE database manager was commenced in 1985 since no commercially available systems were suited for the needs of a large endoscopy unit. Over a period of five years, this database was programmed, revised and... more
The development of the SADE database manager was commenced in 1985 since no commercially available systems were suited for the needs of a large endoscopy unit. Over a period of five years, this database was programmed, revised and enhanced through the joint efforts of gastroenterologists and programmers, the SADE system being implemented for daily use on 1 January 1989. The patient administration and medical record modules are fully implemented and functional, while the statistical module has only recently been finished. The present features of the system are described, and the limitations discussed. Instant report generation and direct access to previous medical data are the most immediate benefits of the system. The initial intention to have structured anamnestic data had to be modified to suit the need for flexibility and ease of free text input by the users.
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The time aspects of daily use of a clinical database system in an endoscopy department were studied. The SADE database system for endoscopic procedures was introduced for daily use at Ullevål Hospital on 1 January 1989. The average weekly... more
The time aspects of daily use of a clinical database system in an endoscopy department were studied. The SADE database system for endoscopic procedures was introduced for daily use at Ullevål Hospital on 1 January 1989. The average weekly programme of the endoscopy unit includes 57 gastroduodenoscopies, 23 colonoscopies and 12 ERCP/EPTs. During three consecutive weeks of the study the mean physician input time was 4 min 17 sec per patient (range 57 sec to 15 min), individual variation depending mainly on the extent of the report. Assistants spent a mean time of 4 min 23 sec for each patient. Thus, a total of 8 min 40 sec was spent for every patient seen. Endoscopic units should analyze their routines and needs before introducing an electronic data base manager.
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With no commercially available endoscopy database manager available, a standalone system for gastroenterological endoscopy departments has been developed since 1985 through joint efforts of gastroenterologists and dedicated programmers.... more
With no commercially available endoscopy database manager available, a standalone system for gastroenterological endoscopy departments has been developed since 1985 through joint efforts of gastroenterologists and dedicated programmers. The present system was implemented for daily use January 1989 and, to date, approximately 19,000 examinations have been recorded. Nurses and office assistants carry out administrative work, but the physician enters the endoscopic data, partly as free text, partly as structured data via automated menus and a mouse. In addition to the immediate printout of the result, valuable data are stored in the computer for administrative and research purposes. Mean data entering time for the physician was four minutes 17 seconds, and altogether eight minutes 40 seconds was spent on the computer system for each patient served.
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ABSTRACT
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Play-the-Winner (PTW) design was compared with Weighted-Play-the-Winner (WPW) design with regard to sensitivity to discriminate between treatments. In total, 231 patients undergoing digestive surgery were included in a PTW study comparing... more
Play-the-Winner (PTW) design was compared with Weighted-Play-the-Winner (WPW) design with regard to sensitivity to discriminate between treatments. In total, 231 patients undergoing digestive surgery were included in a PTW study comparing safety of enoxaparin and dextran-70 in the prevention of venous thrombo-embolism. In the PTW model each patient was classified as a 'winner' or 'loser'. The treatment was changed when a patient was classified as 'loser', otherwise the same treatment was continued for the next patient. The study was performed by using a PTW design, but with all assessments needed for a WPW simulation. In the WPW design, a 'loser score' was calculated for each patient and summarized to a 'loser index' for consecutive patients given the same treatment. When this index exceeded a predefined value, treatment was changed and the 'loser index' set to zero. The WPW model with inheritance (WPWI) is identical to WPW, except that the overload of 'loser index' from the previous sequence with the same treatment was used as the starting value for the next. The PTW study revealed superiority of enoxaparin. This was enforced in the WPW model and further increased by WPWI. Changing from the PTW to WPW design and further to WPWI increased the sensitivity of the model, but at the same time the complexity of the design.
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Sixty patients with endoscopically confirmed duodenal ulcers were treated with 50 mg of trimipramine daily. After the end of the treatment 45 patients showed healed ulcers. Ulcer healing was not related to serum concentration of... more
Sixty patients with endoscopically confirmed duodenal ulcers were treated with 50 mg of trimipramine daily. After the end of the treatment 45 patients showed healed ulcers. Ulcer healing was not related to serum concentration of trimipramine, but seemed to be influenced by smoking habits and duration of the total and actual disease history.
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Sixty-two patients with healed duodenal or prepyloric ulcers completed a double-blind long-term trial with either 25 mg/day of trimipramine (32 patients) or placebo (30 patients). Endoscopy was performed when marked dyspeptic complaints... more
Sixty-two patients with healed duodenal or prepyloric ulcers completed a double-blind long-term trial with either 25 mg/day of trimipramine (32 patients) or placebo (30 patients). Endoscopy was performed when marked dyspeptic complaints occurred or after a 1-year follow-up study. Eleven patients in the trimipramine-treated group and 18 patients in the placebo group had relapses, with endoscopically confirmed ulcers or erosions with duodenitis and severe symptoms, revealing a statistically significant difference between the groups in favour of trimipramine. Twenty-one patients (66%) receiving trimipramine and 12 patients (40%) receiving placebo were in remission at the end of the study. The probability of having a relapse increased with the time from start of placebo but decreased in the group that received trimipramine. No serious side effects occurred. In conclusion, 25 mg of trimipramine daily reduced significantly the recurrence rate of duodenal ulcer disease, when compared with placebo.
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The increases in medan scoresfluence on gastroduodenal mucosa of naproxen, 500 mg/day, and diclofenac, 100 mg/day, for 1 wk was investigated in 14 subjects in a double-blind randomized crossover study. Endoscopic examination of the... more
The increases in medan scoresfluence on gastroduodenal mucosa of naproxen, 500 mg/day, and diclofenac, 100 mg/day, for 1 wk was investigated in 14 subjects in a double-blind randomized crossover study. Endoscopic examination of the gastroduodenal mucosa was carried out before and after each drug with regard to gastritis and hemorrhagic and erosive lesions. A 20-cm visual analogue scale was used for grading severity of mucosal changes. Naproxen caused statistically significant increases inmedian scores for all 3 variables, and 10 subjects showed a score increase in at least 1 variable; reaction to diclofenac occurred in only 4 subjects and the changes in median scores were not significant.
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Dietary calcium and antioxidants have been suggested as protective agents against colorectal cancer. This has been supported by animal experimental studies, case control and cohort studies. In a prospective intervention study of... more
Dietary calcium and antioxidants have been suggested as protective agents against colorectal cancer. This has been supported by animal experimental studies, case control and cohort studies. In a prospective intervention study of colorectal adenomas, and intermediary stage in colorectal carcinogenesis, 116 polyp-bearing patients received a placebo-controlled daily mixture of beta-carotene 15 mg, vitamin C 150 mg, vitamin E 75 mg, selenium 101 microg, and calcium (1.6 g daily) as carbonate for a period of 3 years with annual colonoscopic follow-up to test if the mixture was able to reduce polyp growth or recurrence. All polyps of < 10 mm at enrollment or follow-up were left unresected until the end of the study. 87-91% of the patients attended the annual endoscopic follow-up investigations, and 19% of the patients dropped out of the medical intervention. The rest consumed 85% of the total amount of tablets over the 3 years. The fecal calcium concentration was 2.3-2.7 times higher i...
Research Interests: Diet, Family history, Logistic Regression, Colorectal cancer, Cell Division, and 25 moreDiarrhea, Antioxidants, Vitamin A, Prospective studies, Humans, vitamin C, Constipation, Female, Digestion, Male, Cohort Study, Patient Compliance, Follow-up studies, Dyspepsia, Animal Experimentation, Clinical Sciences, Aged, Middle Aged, Ascorbic Acid, Kaplan-Meier, Time Factors, Intervention study, Adenoma, Dietary Calcium, and Energy Intake
Introduction BP-C1 is a novel antitumor agent of low dose Cisplatinum combined with benzo-polycarbonic acid. Good tolerability and antitumor effect has been shown in similar human study of metastatic breast cancer patients. The aim of... more
Introduction BP-C1 is a novel antitumor agent of low dose Cisplatinum combined with benzo-polycarbonic acid. Good tolerability and antitumor effect has been shown in similar human study of metastatic breast cancer patients. The aim of this study was to estimate the Maximum Tolerable Dose (MTD) and the pharmacokinetic (PK) profile in dogs. Materials Two healthy dogs and nine with mammary cancer were planned to be included with five dogs included by now. The study was performed as an open within patient 3-level Response Surface Pathway design trial. Based on human data the cumulative dose-window was predefined as 0.07- 0.45 mg/kg resulting in an initial cumulative dose of 0.26 mg/kg. The dogs received one daily intramuscular injection in three 7-days-periods. Platinum concentration was measured by blood sampling 30 minutes after each injection and by serial sampling during 48 hours following first and last injection in the first treatment period. Adverse effect was evaluated using VCO...
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Canine herpes virus-1 (CHV1) causes a fatal hemorrhagic disease in neonatal puppies and is associated with reproductive problems in female dogs. This serologic study was conducted to assess the seroprevalence of CHV1 infection in Norway.... more
Canine herpes virus-1 (CHV1) causes a fatal hemorrhagic disease in neonatal puppies and is associated with reproductive problems in female dogs. This serologic study was conducted to assess the seroprevalence of CHV1 infection in Norway. Blood samples were collected from clinically healthy dogs (n = 436) one yr of age and older of both genders, supplied by four small animal clinics (A, B, C and D) in different parts of the country. The immunoperoxidase monolayer assay was used for testing of CHV1 antibodies. Serum titers were recorded as the reciprocal value of the highest dilution producing specific cell staining. Titers equal to or above 80 were considered positive for exposure to CHV1. In total, 80.0% of the dogs had titers ≥80 and were classified as positive. Mean age for seronegative dogs was 4.7 yrs (95% CI 4.1-5.4) and for seropositive dogs 5.0 yrs (95% CI 4.7-5.4). Of the dogs, 32.8% displayed a weakly positive titer of 80, whereas 41.5 and 5.7% fell into the moderately (tit...
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The purpose of this study was to investigate the need for and choice of stratification factors, and the effects of blinding and placebo in a clinical experiment. Eighty dogs with canine hip dysplasia (CHD) were included in a randomized,... more
The purpose of this study was to investigate the need for and choice of stratification factors, and the effects of blinding and placebo in a clinical experiment. Eighty dogs with canine hip dysplasia (CHD) were included in a randomized, placebo-controlled and double blind clinical trial with stratified parallel group design, in which body weight and degree of CHD were used as stratification factors. Thirty-eight dogs were allocated to gold bead implantation and 42 to placebo. After six months, 33 of the 42 placebo-treated dogs received gold bead implantation in an open study lasting a further 18 months. The main outcome variable in the study was change in pain signs of CHD as assessed by the owner. No significant difference in the main outcome variable, regardless of the treatment given, could be detected in the two chosen stratification factors. The only factor to influence the main outcome variable significantly was age. The blinding procedure used in the study, in which 60% of th...
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Endoscopic findings are essential in evaluating the disease activity in ulcerative colitis. The aim of this study was to evaluate how endoscopists assess individual endoscopic features of mucosal inflammation in ulcerative colitis, the... more
Endoscopic findings are essential in evaluating the disease activity in ulcerative colitis. The aim of this study was to evaluate how endoscopists assess individual endoscopic features of mucosal inflammation in ulcerative colitis, the inter-observer agreement, and the importance of the observers' experience. Five video clips of ulcerative colitis were shown to a group of experienced and a group of inexperienced endoscopists. Both groups were asked to assess eight endoscopic features and the overall mucosal inflammation on a visual analogue scale. The following statistical analyses were used; Contingency tables analysis, kappa analysis, analysis of variance, Pearson linear correlation analysis, general linear models, and agreement analysis. All tests were carried out two-tailed, with a significance level of 5%. The inter-observer agreement ranged from very good to moderate in the experienced group and from very good to fair in the inexperienced group. There was a significantly b...
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This paper is the first report of systemic tuberculosis involving the eyes in a horse. The animal lost condition and gradually became increasingly blind in both eyes; it was eventually euthanased. The pathological findings included... more
This paper is the first report of systemic tuberculosis involving the eyes in a horse. The animal lost condition and gradually became increasingly blind in both eyes; it was eventually euthanased. The pathological findings included bilateral, mycobacterial granulomatous uveitis with unilateral retinal detachment and necrosis, and disseminated, mycobacterial granulomatous foci in the myocardium, lungs, bronchial lymph nodes, kidneys, liver, pancreas, colon and visceral serosal surfaces, with the most extensive lesions in the myocardium. The mycobacteria were identified as Mycobacterium avium.
Research Interests: Kidney, Pancreas, Animals, Male, Heart, and 6 moreHorses, Lung, Eye, Myocardium, Veterinary Sciences, and Mycobacterium avium
Computed tomography (CT) and ultrasound (US) were performed on 47 patients with a normal pancreas. CT was a significantly better method than US to demonstrate the pancreatic body and tail. The pancreatic head was also shown more often... more
Computed tomography (CT) and ultrasound (US) were performed on 47 patients with a normal pancreas. CT was a significantly better method than US to demonstrate the pancreatic body and tail. The pancreatic head was also shown more often using CT than US, but this difference was not statistically significant. The diameters of the different parts of the pancreas measured at CT were significantly larger than measured at US. The explanation is most probably that the widths of the splenic and superior mesenteric veins are added to the diameters of the pancreas measured at CT, while using US, these vessels are clearly differentiated from the pancreatic tissue. US was a significantly better technique than CT to register the vascular structures surrounding the pancreas, except from the left renal vein, which was more often demonstrated at CT.
Research Interests: Adolescent, Probability, Humans, Ultrasonography, Pancreas, and 7 moreFemale, Male, Aged, Middle Aged, Adult, X ray Computed Tomography, and Duodenum
The Norwegian MEPS (musculoskeletal--visual--psychosocial--stress) study included 3 groups: data entry, data dialogue (female) and data dialogue (male). Before intervention, the data entry group reported significantly more symptoms and... more
The Norwegian MEPS (musculoskeletal--visual--psychosocial--stress) study included 3 groups: data entry, data dialogue (female) and data dialogue (male). Before intervention, the data entry group reported significantly more symptoms and signs of musculoskeletal illness and had longer periods in front of the video display terminal (VDT) without a break. The ergonomic intervention consisted mainly of ergonomic information and training. After intervention, the data dialogue female group reported a significant reduction in shoulder pain in parallel with a reduction in trapezius load. Increasing the understanding in how to adjust the work stand and chair may have been contributing factors to reducing the pain level. There was a significant reduction in eye problems in all groups; the greatest reduction in eye symptoms was seen in the groups who had new optometric corrections.
Research Interests: Optometry, Research Design, Pain, Job Satisfaction, International Cooperation, and 18 moreTreatment Outcome, Poland, Sweden, Norway, Workplace, Humans, United States, Female, Male, Electromyography, Posture, Middle Aged, Questionnaires, Adult, Vision Disorders, Human Engineering, Physical examination, and Occupational Diseases
For the assessment of coccidial oocyst production by chickens, some modified form of the McMaster counting method is commonly used. The objective of this study was to evaluate a standard method and to compare it to a new, faster method,... more
For the assessment of coccidial oocyst production by chickens, some modified form of the McMaster counting method is commonly used. The objective of this study was to evaluate a standard method and to compare it to a new, faster method, in which all the preparative stages before counting are carried out in the same container into which the original faecal sample was collected. A stock suspension containing purified oocysts of all seven valid Eimeria species that parasitize chickens was prepared, from which seven concentrations of oocyst suspensions were made. Since the faecal material in a sample influences the ability of oocysts to float up in a McMaster chamber, the new method was tested to establish the optimal amount of faeces in the original sample. Control oocyst suspensions containing no faeces were also tested, and three series of counts using the new method were compared with the standard McMaster method. The results were statistically analysed by agreement analysis. Repeatability and between-operator variation of both methods were also tested by agreement analysis. Counting by the standard McMaster method underestimated the true number of oocysts. The new method gave counts in agreement with the true number of oocysts if using 1 g of faeces per sample. With 2 g of faeces, counts were obtained that agreed with counts by the standard McMaster method. Both methods showed agreement between repeated measurements. The new method used on a sample containing 2 g of faeces provides a convenient alternative to the standard modified McMaster method. A 1-g faecal sample increases agreement with the true numbers of oocysts. Processing of a sample with the new method is about nine times faster than with the standard method.
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The aim of the present study was to determine whether the intraperitoneal LD(50) for yessotoxin (YTX) in mice varies with strain or gender. Thirty-six male and 36 female mice, of body weight 16-20 g, from each of the strains ICR (CD-1),... more
The aim of the present study was to determine whether the intraperitoneal LD(50) for yessotoxin (YTX) in mice varies with strain or gender. Thirty-six male and 36 female mice, of body weight 16-20 g, from each of the strains ICR (CD-1), Swiss (CFW-1) and NMRI were employed. They were not fasted before YTX treatment. At each dose, nine mice were injected with YTX solutions at 1.0 mL/20 g body weight, and observed for 24h. Symptoms and time to death were recorded. Within each mouse strain and gender arm, the study was performed as a basic four level Response Surface Pathway designed trial with nine mice at each dose level. YTX was isolated from a culture of Protoceratium reticulatum. The LD(50) values for female and male mice, respectively, were estimated as 380 and 462 microg/kg for the ICR, 269 and 328 microg/kg for the Swiss, and 314 and 412 microg/kg for the NMRI strains. The increases in LD(50) from female to male mice were found to be 22% for ICR, 22% for Swiss and 31% for NMRI. The largest difference in LD(50) among mouse strains was detected between the ICR and Swiss strains, where the deviation was 41% in both females and males. The difference between mouse strains was found significant (p = 0.03). For all three strains, females were more susceptible than males, with a difference in LD(50) of 1.2-1.3-fold. The largest difference between the least- and most-susceptible strain was 1.4-fold for both females and males. The largest difference in LD(50), 1.7-fold, was observed between female Swiss and male ICR mice. The difference between genders was not significant (p = 0.12). These results indicate that other factors, like handling of the animals, and the source and handling of the toxin, may significantly influence the outcome of studies on acute toxicity since the reported differences in LD(50) vary by a factor of about seven.
Research Interests: Mice, Female, Animals, Male, Sex Factors, and 5 moreBody Weight, Lethal Dose, Acute Toxicity, Response surface, and Toxicon
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With the introduction of laparoscopic appendectomy a prospective study was started. Patients with suspected appendicitis were selected for conventional appendectomy or laparoscopy according to the preference of the surgeon on call. During... more
With the introduction of laparoscopic appendectomy a prospective study was started. Patients with suspected appendicitis were selected for conventional appendectomy or laparoscopy according to the preference of the surgeon on call. During a 1-year period 233 patients were included, of whom 97 underwent conventional appendectomy and 136 laparoscopy. Among the patients selected to laparoscopy, laparoscopic appendectomy was carried out in 72 cases, conventional appendectomy in 32, and only diagnostic laparoscopy in the remaining 32. Removal of a normal appendix was significantly more common in the group of patients directly selected for conventional appendectomy compared to laparoscopy (p &lt; 0.01). The duration of the operation was shorter (p &lt; 0.05) and the postoperative hospital stay and the convalescence longer (p &lt; 0.05) with conventional than with laparoscopic appendectomy. Peroperative problems and minor postoperative complications were more common (p &lt; 0.01) with laparoscopic than conventional appendectomy. However, the clinical impact of these problems were limited. The difference between the procedures regarding major complications was not significant. Laparoscopic appendectomy seems to be at least as good as conventional appendectomy. However, randomized controlled trials are needed to decide which of the procedures to recommend.
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Five methods for measurement of phagocytosis and respiratory burst activity of bovine blood polymorphonuclear leukocytes (PMNs) were evaluated. Eight cows were repeatedly sampled over a two week period and parallel samples tested in all... more
Five methods for measurement of phagocytosis and respiratory burst activity of bovine blood polymorphonuclear leukocytes (PMNs) were evaluated. Eight cows were repeatedly sampled over a two week period and parallel samples tested in all five assays to assess the repeatability and stability of the methods. In the flow cytometric phagocytosis assay, ingestion of fluorescein labeled bacteria was measured, and in the flow cytometric assay for respiratory burst, oxidation of a dye by reactive oxygen species was recorded. In the classical assays, bactericidal effect on opsonized, live bacteria was quantified by the conversion of an indicator substance, superoxide anion production was assayed by the reduction of cytochrome c, whereas myeloperoxidase activity was determined with a radioactive iodination assay. The results showed that the Phagotest, Bursttest, cytochrome c and iodination assays gave repeatable results when samples were run in the same setup on the same day. Although day-to-day variability was significant in all assays, the described methods comprise a panel of useful tests for the evaluation of phagocytosis and respiratory burst activity in bovine PMNs. The flow cytometric methods represent a convenient alternative to the classical methods for measurement of phagocytosis and respiratory burst in bovine blood PMNs.
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Research Interests: Clinical Trial, Treatment Outcome, Veterinary Dermatology, Sweden, Finland, and 16 moreNorway, Dogs, Denmark, Female, Animals, Male, Statistical Significance, Fish Oil, Dietary Supplements, Prednisolone, Randomized Controlled Trial, Atopic Dermatitis, Veterinary Sciences, Glucocorticoids, Area Under Curve, and Plant Oils
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When substituting the mouse bioassay for lipophilic marine algal toxins in shellfish with analytical methods, science based factors of relative toxicity for all analogues that contribute to health risk to consumers are necessary. The aim... more
When substituting the mouse bioassay for lipophilic marine algal toxins in shellfish with analytical methods, science based factors of relative toxicity for all analogues that contribute to health risk to consumers are necessary. The aim of this paper is to establish the relative intraperitoneal toxicity of dinophysistoxin-2 (DTX-2) compared with okadaic acid (OA). The study was performed as an open, randomised parallel group trial with a four level response surface design within each of the two parallels. In accordance with the response surface design model, the LD50 for DTX-2 and OA was 338 and 206 microg/kg, respectively. By use of common regression analysis, the LD50 of DTX-2 and OA were estimated to 352 microg/kg and 204 microg/kg, respectively. The deviations between the LD50 estimates by the two methods was 4% for DTX-2 and less than 1% for OA. Taken together, these results indicate that the relative toxicity of DTX-2 is about 0.6, compared to OA. Results from the PP2A assay correspond very well with the results obtained by the mouse bioassay. The IC50 concentrations for DTX-2 and OA were 5.94 and 2.81 ng/mL, respectively. This indicates that OA is about twice as toxic as DTX-2. Since inhibition of PP2A is acknowledged as the main mechanism of toxicity of the OA group toxins, this supports the establishment of a relative toxicity factor of DTX-2 of 0.6 compared with OA.
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Toxins from the okadaic acid (OA) and azaspiracid (AZA) group cause considerable negative health effects in consumers when present in shellfish above certain levels. The main symptoms, dominated by diarrhoea, are caused by damage to the... more
Toxins from the okadaic acid (OA) and azaspiracid (AZA) group cause considerable negative health effects in consumers when present in shellfish above certain levels. The main symptoms, dominated by diarrhoea, are caused by damage to the gastrointestinal (GI) tract. Even though OA and AZAs exert toxicity via different mechanisms, it is important to find out whether they may enhance the health effects if present together since they act on the same organs and are regulated individually. In this study, the main issue was the possibility of enhanced lethality in mice upon combined oral exposure to OA and AZA1. In addition, pathological effects in several organs and effects on absorption from the GI tract were studied. Although the number of mice was small due to low availability of AZA1, the results indicate no additive or synergistic effect on lethality when AZA1 and OA were given together. Similar lack of increased toxicity was observed concerning pathological effects that were restricted to the GI-tract. OA and AZA1 were absorbed from the GI-tract to a very low degree, and when given together, uptake was reduced. Taken together, these results indicate that the present practice of regulating toxins from the OA and AZA group individually does not present an unwanted increased risk for consumers of shellfish.
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Monthly concentrations of diarrhetic shellfish poisoning (DSP) toxins and yessotoxin (YTX) in mussels from the coast to the inner part of the Sognefjord were determined. Mussels from nine locations were sampled from March to November... more
Monthly concentrations of diarrhetic shellfish poisoning (DSP) toxins and yessotoxin (YTX) in mussels from the coast to the inner part of the Sognefjord were determined. Mussels from nine locations were sampled from March to November 1997. The DSP toxins and YTX were analysed by a colorimetric protein phosphatase 2A (PP2A) inhibition assay or fluorometric HPLC, respectively. The mouse bioassay for DSP toxins was performed including either chloroform or diethyl ether in the final step of extraction. Using ether in the final step normally facilitated extraction of the DSP toxins, okadaic acid (OA) and dinophysis toxin-1 (DTX-1), while chloroform extraction included a wider spectrum of toxins, including YTX and a fast acting toxin(s) with neurotoxic effects. The concentrations of DSP toxins and YTX in mussels increased with distance from the coast. The highest concentrations of YTX (574 microg YTX/100 g mussel meat) and diarrhetic toxins (349 microg OA equivalents/100 g mussel meat) were measured in May and August, respectively, at locations in the inner part of the fjord. Since concentrations of DSP toxins and YTX in mussels increased with distance from the coast, the locations for mussel farming in the Sognefjord close to the coast, seem to be preferable.
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An open, block randomised multi-centre clinical trial was performed in Norway during 1985 to 1987 to compare the therapeutic efficacy of three antibiotic regimens against clinical bovine mastitis caused by penicillin-sensitive bacteria.... more
An open, block randomised multi-centre clinical trial was performed in Norway during 1985 to 1987 to compare the therapeutic efficacy of three antibiotic regimens against clinical bovine mastitis caused by penicillin-sensitive bacteria. Two regimens consisted of procaine penicillin injected intramuscularly for either three or five days, and the third, the traditional Norwegian regimen, consisted of one intramuscular injection of a combination of procaine penicillin and dihydrostreptomycin followed by one intramammary treatment daily per infected quarter for four days. The study included 621 quarters with infectious mastitis from 439 cows. The most efficient regimen for all bacteria was five days systemic treatment (53.1 per cent cured), and the traditional regimen was second best (46.7 per cent cured). The least efficient regimen consisted of systemic therapy with procaine penicillin for three days (36.9 per cent cured). The difference between the therapeutic efficacies of the three regimens was reduced when the clinical mastitis was severe, and in severe mastitis caused by Staphylococcus aureus the difference was very small.
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Thomas Andreen, Karin Bengtsson, Katarina Lundman, et al. ... Pain relief in dogs with hip dysplasia ... References http://veterinaryrecord.bmj.com/content/162/24/796.2.full.html#ref-list-1 This article cites 1 articles, 1 of which can be... more
Thomas Andreen, Karin Bengtsson, Katarina Lundman, et al. ... Pain relief in dogs with hip dysplasia ... References http://veterinaryrecord.bmj.com/content/162/24/796.2.full.html#ref-list-1 This article cites 1 articles, 1 of which can be accessed free at: ... Pain relief in dogs with hip dysplasia
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We compared the protection offered by cimetidine 400 mg b.i.d. as tablets or suspension vs. placebo, in Naproxen-induced gastrointestinal damage in 17 healthy males. Upper endoscopy was performed before and after each drug period, with... more
We compared the protection offered by cimetidine 400 mg b.i.d. as tablets or suspension vs. placebo, in Naproxen-induced gastrointestinal damage in 17 healthy males. Upper endoscopy was performed before and after each drug period, with separate evaluation of duodenal mucosa distal to the duodenal bulb. 51Cr-EDTA absorption tests were done to assess distal mucosal integrity, and symptoms were registered. All regimens caused a significant increase in mucosal damage (p less than 0.01). Cimetidine tablets gave a significantly lower damage score than placebo for gastritis/duodenitis and hemorrhagic lesions in the stomach/duodenal bulb, and for the sum of scores in both scoring regions (p = 0.02). Cimetidine suspension was not significantly different from placebo for any of the endoscopic parameters. The 51Cr-EDTA absorption was significantly increased after all drug periods. However, there was no difference between the three drug combinations. Symptoms reported were mild and equal in the three groups. Cimetidine tablets offered protection against Naproxen-induced mucosal damage, primarily in the stomach and duodenal bulb, but lacked any effect on permeability changes. Cimetidine suspension was not significantly different from placebo in any respect.
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Research Interests: Immunology, Fish Diseases, Female, Animals, Male, and 5 moreAtlantic Salmon, Pedigree, Genotype, Salmo salar, and MHC class I
Colonoscopic 1-year control of polyps of less than 10 mm left in situ was carried out in 103 (89%) of 116 originally examined patients. Analysis showed an 85% recovery: 91% and 81% for polyps of 5-9 mm and &lt; 5 mm, respectively. The... more
Colonoscopic 1-year control of polyps of less than 10 mm left in situ was carried out in 103 (89%) of 116 originally examined patients. Analysis showed an 85% recovery: 91% and 81% for polyps of 5-9 mm and &lt; 5 mm, respectively. The recovery was significantly related to size and localization, whereas the growth rate was inversely correlated to the originally measured diameter. A linear relationship was demonstrated between anus-to-polyp distances 1 year apart, with a normalized agreement index of 0.70. In only 1 of 189 polyps, an increase of diameter to &gt; 10 mm was demonstrated. The 79 new polyps in 52 (50%) of the patients were significantly smaller, more often right-sided, and related to multiplicity of polyps at the initial examination but not to growth of recovered polyps or cleansing status. An acceptable recovery and growth rate of polyps &lt; 10 mm seems to justify the continuation of the study for the remaining 2 years.
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Gastrointestinal side effects caused by naproxen and oxindanac (a developmental non-steroidal anti-inflammatory drug) were compared by combined endoscopy and determination of faecal blood loss in 16 healthy male volunteers in a... more
Gastrointestinal side effects caused by naproxen and oxindanac (a developmental non-steroidal anti-inflammatory drug) were compared by combined endoscopy and determination of faecal blood loss in 16 healthy male volunteers in a randomized, double-blind, crossover study. Individual daily faecal blood loss was determined by means of 51Cr-labelled erythrocytes. Gastroduodenoscopy was performed before and after administration of naproxen, 750 mg/day, and oxindanac, 600 mg/day, for 1 week each. A washout period of at least 3 weeks was inserted between drug periods. Visual analogue scales (VAS) were used for endoscopic assessment of lesions and subjective complaints. Mean faecal blood loss increased from a base line 0.48 ml/24 h to 1.59 ml/24 h with naproxen (p less than 0.01) and from 0.56 ml/24 h to 1.31 ml/24 h with oxindanac (p less than 0.01). VAS scores for gastroduodenal lesions increased significantly with both drugs. Naproxen caused a significantly greater increase than oxindanac (p less than 0.05). There was no correlation between gastrointestinal blood loss and endoscopic findings. Subjective symptoms were correlated to faecal blood loss with naproxen, but not to endoscopic findings. No such correlations were observed for oxindanac. Naproxen caused a significant prolongation of bleeding time (p less than 0.01), whereas the increase caused by oxindanac was not significant (p = 0.09).
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A reliable and sensitive in situ method for measuring polyp size is fundamental for growth studies of colonic polyps. A measuring probe inserted through a colonoscope can give a visual assessment of polyp diameter, and from a picture of... more
A reliable and sensitive in situ method for measuring polyp size is fundamental for growth studies of colonic polyps. A measuring probe inserted through a colonoscope can give a visual assessment of polyp diameter, and from a picture of the polyp the area of the polyp on the picture can be calculated by computerized analysis. To test the reliability and sensitivity of these two in situ measurements, 43 colonic polyps (mean diameter, 8.5 mm; range, 4-20 mm) removed by snare diathermy resection were examined. The maximal diameter was measured, and two Polaroid pictures taken of each polyp. After polypectomy each polyp was subjected to extracorporeal reassessment of diameter and measurement of weight and volume. By computerized analysis of the pictures the following variables were estimated: 1) area of the polyp on the picture; 2) largest diameter; 3) maximum width 90 degrees on the largest diameter; 4) maximum distance from centre of gravity; and 5) minimum distance from centre of gravity. Results showed good correlation between diameter measured in situ and after removal (r = 0.93), diameter raised to the 3rd power and weight (r = 0.93), and also to volume (r = 0.77). Area analysis compared with weight was less good (r = 0.72). A very high correlation was demonstrated between weight and volume (r = 0.99). We conclude that the measurement of diameter in situ with a measuring probe is sensitive and somewhat more reliable than computerized analysis of size. The present 3-year follow-up and intervention study will show which of the two methods is preferable for evaluation of polyp growth.
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ABSTRACT
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We studied the gastrointestinal side effects of three formulations of naproxen in 18 healthy male volunteers. In a Latin-square design crossover study, the subjects received 500 mg naproxen twice daily for 7 days as plain tablets,... more
We studied the gastrointestinal side effects of three formulations of naproxen in 18 healthy male volunteers. In a Latin-square design crossover study, the subjects received 500 mg naproxen twice daily for 7 days as plain tablets, enteric-coated tablets, or enteric-coated granules in capsules. The 51Cr-EDTA absorption test was performed before and at the end of each drug period, to evaluate changes in the distal gut. The test dose was instilled distally in the duodenum to prevent lesions in the stomach from interfering with the evaluation. Upper endoscopy was performed at the same intervals, scoring changes in the middle and distal duodenum separately from findings in the stomach and duodenal bulb. The nature and severity of adverse effects were recorded for each treatment period. Non-parametric methods were used for statistical evaluation. All drugs induced a significant increase in 51Cr-EDTA absorption, but we did not detect any difference between the three formulations. All formulations were associated with a significant increase in all the endoscopic findings monitored. Enteric-coated tablets induced significantly less lesions than enteric-coated granules in the stomach and duodenal bulb, and an advantage over plain tablets was indicated. No difference was seen in the middle and distal duodenum. The proximal endoscopic scores were not correlated to those found in the middle and distal duodenum. Evaluation of the small and large bowel should probably be included in clinical studies of NSAIDs, but our findings suggest that the importance of transfer of mucosal lesions to the distal gut by enteric coating may have been overemphasized.