Scandinavian journal of gastroenterology. Supplement
The study was conducted double blind in 12 healthy volunteers, average age 30 years (23-48). On s... 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.
To study the protective effect of Sucralfate on Naproxen-induced mucosal lesions, 16 healthy, mal... 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.
The use of visual analogue scales in the evaluation of mucosal lesions may reduce sample size req... 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.
The development of the SADE database manager was commenced in 1985 since no commercially availabl... 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.
The time aspects of daily use of a clinical database system in an endoscopy department were studi... 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.
With no commercially available endoscopy database manager available, a standalone system for gast... 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.
Scandinavian Journal of Clinical and Laboratory Investigation
Play-the-Winner (PTW) design was compared with Weighted-Play-the-Winner (WPW) design with regard ... 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.
Scandinavian journal of gastroenterology. Supplement
Sixty patients with endoscopically confirmed duodenal ulcers were treated with 50 mg of trimipram... 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.
Sixty-two patients with healed duodenal or prepyloric ulcers completed a double-blind long-term t... 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.
The increases in medan scoresfluence on gastroduodenal mucosa of naproxen, 500 mg/day, and diclof... 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.
Dietary calcium and antioxidants have been suggested as protective agents against colorectal canc... 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...
Introduction BP-C1 is a novel antitumor agent of low dose Cisplatinum combined with benzo-polycar... 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...
Canine herpes virus-1 (CHV1) causes a fatal hemorrhagic disease in neonatal puppies and is associ... 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...
The purpose of this study was to investigate the need for and choice of stratification factors, a... 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...
Scandinavian journal of gastroenterology. Supplement
The study was conducted double blind in 12 healthy volunteers, average age 30 years (23-48). On s... 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.
To study the protective effect of Sucralfate on Naproxen-induced mucosal lesions, 16 healthy, mal... 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.
The use of visual analogue scales in the evaluation of mucosal lesions may reduce sample size req... 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.
The development of the SADE database manager was commenced in 1985 since no commercially availabl... 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.
The time aspects of daily use of a clinical database system in an endoscopy department were studi... 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.
With no commercially available endoscopy database manager available, a standalone system for gast... 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.
Scandinavian Journal of Clinical and Laboratory Investigation
Play-the-Winner (PTW) design was compared with Weighted-Play-the-Winner (WPW) design with regard ... 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 &#39;winner&#39; or &#39;loser&#39;. The treatment was changed when a patient was classified as &#39;loser&#39;, 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 &#39;loser score&#39; was calculated for each patient and summarized to a &#39;loser index&#39; for consecutive patients given the same treatment. When this index exceeded a predefined value, treatment was changed and the &#39;loser index&#39; set to zero. The WPW model with inheritance (WPWI) is identical to WPW, except that the overload of &#39;loser index&#39; 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.
Scandinavian journal of gastroenterology. Supplement
Sixty patients with endoscopically confirmed duodenal ulcers were treated with 50 mg of trimipram... 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.
Sixty-two patients with healed duodenal or prepyloric ulcers completed a double-blind long-term t... 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.
The increases in medan scoresfluence on gastroduodenal mucosa of naproxen, 500 mg/day, and diclof... 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.
Dietary calcium and antioxidants have been suggested as protective agents against colorectal canc... 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...
Introduction BP-C1 is a novel antitumor agent of low dose Cisplatinum combined with benzo-polycar... 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...
Canine herpes virus-1 (CHV1) causes a fatal hemorrhagic disease in neonatal puppies and is associ... 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...
The purpose of this study was to investigate the need for and choice of stratification factors, a... 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...
Uploads
Papers by Stig Larsen