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Biomedical subjects

S A Pedersen

Publications and source records attributed to S A Pedersen.

At least 19 recordsLinked to original sources
PubMed2005

Isolation and characterization of hemolymph antifreeze proteins from larvae of the longhorn beetle Rhagium inquisitor (L.).

We describe a simple and effective procedure to isolate antifreeze proteins (AFPs) from the hemolymph of larvae of the longhorn beetle Rhagium inquisitor, and present some characteristics of their structures. Several AFPs were isolated from the hemolymph of this species by heat and acid extraction followed by cation exchange. The hemolymph contains at least six AFPs ranging in size from 12.5 to 12.8 kDa. Of these, three were separated to purity by the ion exchange step, as indicated by mass spectrometry. The remaining three forms were further separated by size exclusion chromatography, but could not be isolated to purity. All AFPs in the hemolymph of this species appears to have isoelectric points above 8.00. The dominant form, RiAFP(H4), was purified by the ion exchange step. Its amino acid composition reveals a lower level of cysteine and a higher level of threonine, arginine, alanine and glycine than seen in other insect AFPs. Its trypsin fingerprint does not match that of any known protein. It interacts with ice both in the anionic and cationic state.

Alanine↗
PubMed2001

[Diagnostic benefit of gastrointestinal endoscopy in infants under one year of age--a two-year survey].

INTRODUCTION: Gastrointestinal endoscopy in children is a well-established procedure. We reviewed our experience of endoscopy in infants below one year of age to evaluate indications, endoscopic findings, histology, and complications. MATERIAL AND METHODS: Twenty-eight infants were studied over a two-year period. Of these, 18 underwent upper endoscopy, six recto/sigmoidoscopy or colonoscopy, and four both procedures. RESULTS: The most common indication (10/22) for upper endoscopy was vomiting and suspicion of gastrooesophageal reflux disease. In these infants, 24-hour continuous monitoring of the oesophageal pH followed the procedure. Indications for lower endoscopy were rectal bleeding (n = 6) and intractable diarrhoea (n = 4). There were no complications to anaesthesia, endoscopy, or biopsy. Overall, there were endoscopic abnormalities in 82% and histological abnormalities in 75% of the infants. The diagnostic findings included rare disorders, such as eosinophilic gastroenteritis, microvillous inclusion disease, and chylomicron retention disease. Diagnosis of these diseases requires gastrointestinal biopsy. DISCUSSION: Gastrointestinal endoscopy is a safe procedure, which is a valuable part of the diagnostic work-up in a selected group of infants with long-lasting or severe gastrointestinal symptoms.

Colonoscopy↗
PubMed2001

Continued (5-year) followup of a randomized clinical study comparing antireflux surgery and omeprazole in gastroesophageal reflux disease.

BACKGROUND: The efficacy of antireflux surgery (ARS) and proton pump inhibitor therapy in the control of gastroesophageal reflux disease is well established. A direct comparison between these therapies is warranted to assess the benefits of respective therapies. STUDY DESIGN: There were 310 patients with erosive esophagitis enrolled in the trial. There were 155 patients randomized to continuous omeprazole therapy and 155 to open antireflux surgery, of whom 144 later had an operation. Because of various withdrawals during the study course, 122 patients originally having an antireflux operation completed the 5-year followup; the corresponding figure in the omeprazole group was 133. Symptoms, endoscopy, and quality-of-life questionnaires were used to document clinical outcomes. Treatment failure was defined to occur if at least one of the following criteria were fulfilled: Moderate or severe heartburn or acid regurgitation during the last 7 days before the respective visit; Esophagitis of at least grade 2; Moderate or severe dysphagia or odynophagia symptoms reported in combination with mild heartburn or regurgitation; If randomized to surgery and subsequently required omeprazole for more than 8 weeks to control symptoms, or having a reoperation; If randomized to omeprazole and considered by the responsible physician to require antireflux surgery to control symptoms; If randomized to omeprazole and the patient, for any reason, preferred antireflux surgery during the course of the study. Treatment failure was the primary outcomes variable. RESULTS: When the time to treatment failure was analyzed by use of the intention to treat approach, applying the life table analysis technique, a highly significant difference between the two strategies was revealed (p < 0.001), with more treatment failures in patients who originally were randomized to omeprazole treatment. The protocol also allowed dose adjustment in patients allocated to omeprazole therapy to either 40 or 60 mg daily in case of symptom recurrence. The curves subsequently describing the failure rates still remained separated in favor of surgery, although the difference did not reach statistical significance (p = 0.088). Quality of life assessment revealed values within normal ranges in both therapy arms during the 5 years. CONCLUSIONS: In this randomized multicenter trial with a 5-year followup, we found antireflux surgery to be more effective than omeprazole in controlling gastroesophageal reflux disease as measured by the treatment failure rates. But if the dose of omeprazole was adjusted in case of relapse, the two therapeutic strategies reached levels of efficacy that were not statistically different.

Aged↗
PubMed2001

The cost of long term therapy for gastro-oesophageal reflux disease: a randomised trial comparing omeprazole and open antireflux surgery.

BACKGROUND AND AIM: To comprehensively assess the relative merits of medical and surgical therapy for gastro-oesophageal reflux disease (GORD), health economic aspects have to be incorporated. We have studied the direct and indirect costs of medical and surgical therapy within the framework of a prospective randomised multicentre trial. METHODS: After initial treatment of reflux oesophagitis with omeprazole to control symptoms and to heal oesophagitis, 154 patients were randomised to continue treatment with omeprazole (20 or 40 mg daily) and 144 patients to have an open antireflux operation (ARS). In case of GORD relapse, patients allocated to omeprazole were offered ARS and those initially operated on had either a reoperation or were treated with omeprazole. The costs were assessed over five years from randomisation. RESULTS: Differences in cumulative direct medical costs per patient between the two therapeutic strategies diminished with time. However, five year direct medical costs per patient when given omeprazole were still significantly lower than for those having ARS in Denmark, Norway, and Sweden (differences were DKK 8703 (US$1475), NOK 32 992 (US$ 5155), and SEK 13 036 (US$ 1946), respectively). However, in Finland the reverse was true (the difference in favour of ARS amounted to FMK 7354 (US$ 1599)). When indirect costs (loss of production due to GORD related sick leave) were also included, the cost of surgical treatment increased substantially and exceeded the cost of medical treatment in all countries. CONCLUSIONS: The total costs of medical therapy for chronic GORD were lower than those of open ARS when prospectively assessed over a five year period, although significant differences in cost estimates were revealed between countries.

Aged↗
PubMed2000

[Acute disseminated encephalomyelitis in children].

Acute disseminated encephalomyelitis (ADEM) is a demyelinating autoimmune inflammatory disease of the central nervous system. It is most often seen in children a few days to several weeks after certain infections or vaccinations. Clinically, ADEM can hardly be distinguished from primary viral encephalitis. The diagnosis is most frequently established on the basis of characteristic findings on MRI of the brain. Mostly the disease seems to be self-limiting, but in untreated patients the mortality rate may be as high as 20% and the risk of permanent neurological deficits 10-33%. Treatment with glucocorticoids seems to be effective in the majority of patients and should at least be started in all patients with an affected level of consciousness. Treatment with intravenous immunoglobulin has recently been given in a few patients with apparent success.

Child↗
PubMed2000

[Treatment of severe acute disseminated encephalomyelitis with intravenous immunoglobulin].

A three year-old boy with severe acute disseminated encephalomyelitis (ADEM) responding dramatically to treatment with intravenous immunoglobulin (IVIG) 1 g/kg/day is described. Initial treatment with intravenous methylprednisolone 2 mg/kg/day had failed. This and two earlier case reports indicate that IVIG might be efficient in the treatment of ADEM, and we believe that its use should be considered, at least in cases of severe ADEM with insufficient treatment effect of steroids. A synergistic effect of treatment with steroids and IVIG in ADEM is possible.

Acute Disease↗
PubMed2000

Tiagabine adjunctive therapy in children with refractory epilepsy: a single-blind dose escalating study.

Tiagabine, a specific gamma-aminobutyric acid-uptake inhibitor, has been shown to be reasonably well tolerated and efficacious as adjunctive treatment for partial seizures in adults and is now being investigated in children. This 4-month, single-blind study evaluated the tolerability, safety and preliminary efficacy of ascending doses (0.25-1.5 mg/kg/day) of tiagabine add-on therapy in 52 children over the age of 2 years with different syndromes of refractory epilepsy. Adverse events, mostly mild to moderate, were reported by 39% of children during the single-blind placebo period and by 83% of children during tiagabine treatment. The events predominantly affected the nervous system with asthenia (19%), nervousness (19%), dizziness (17%) and somnolence (17%) being the most common. Only three children (6%) withdrew because of adverse events. Tiagabine appeared to reduce seizures more in localisation-related epilepsy syndromes than in generalised epilepsy syndromes. Twenty-three patients with localisation-related epilepsy syndromes were included and 17 of these patients entered the fourth dosing period. The 17 patients had a median reduction of seizure rate in the fourth month of treatment of 33% compared with baseline. In comparison, 13 of 22 children with seven different generalised epilepsy syndromes entered the fourth dosing period with a median change of seizure rate of 0%. Two patients experienced single episodes of status epilepticus during treatment; both cases resolved. Tiagabine showed efficacy mainly in localisation-related syndromes and was well tolerated by most children in a group of very refractory patients and warrants further study in children with epilepsy.

Adolescent↗
PubMed2000

Long-term management of gastro-oesophageal reflux disease with omeprazole or open antireflux surgery: results of a prospective, randomized clinical trial. The Nordic GORD Study Group.

BACKGROUND AND AIM: The efficacy of antireflux surgery (ARS) and omeprazole treatment in the control of gastrooesophageal reflux disease (GORD) are well established. We have compared these two therapeutic options in a randomized, clinical trial. PATIENTS AND METHODS: Three hundred and ten patients with erosive oesophagitis were enrolled into the trial. After a run-in period when all patients had < or = 40 mg of omeprazole daily to heal the oesophagitis and relieve symptoms, 155 patients were randomized to continuous omeprazole therapy and 155 to open antireflux surgery, of whom 144 later had an operation. One hundred and thirty-nine and 129 in the omeprazole and antireflux surgery groups, respectively, completed the 3-year follow-up. Symptoms, 24-h pH monitoring and endoscopy were used to document the outcome. Quality of life was evaluated by the psychological general well-being (PGWB) index and the gastrointestinal symptom rating scale (GSRS). RESULTS: Analysis of time to treatment failure (defined as moderate to severe GORD symptoms for > or = 3 days during the last 7 days, oesophagitis or changed therapy) revealed a significant difference in favour of antireflux surgery (P = 0.0016). Seventeen patients originally submitted to antireflux surgery experienced symptom relapse alone, 14 had oesophagitis at endoscopy and another six had omeprazole for different reasons, leaving 97 patients in clinical remission after 3 years. The corresponding figures in the omeprazole arm were 50 relapses, 18 with oesophagitis, two had surgery, leaving 77 patients in remission. Allowing a dose adjustment in the case of relapse in those on omeprazole therapy to either 40 or 60 mg, the curves describing the failure rates were not significantly different from each other. Quality of life assessment showed a comparable outcome in the two study groups. CONCLUSION: In this randomized multicentre trial we found antireflux surgery to be very efficacious in controlling GORD, a level of control which could also be achieved by omeprazole provided that advantage was taken of the opportunity of adjusting the dose.

Adult↗
PubMed2000

Mathematical models behind advanced simulators in medicine.

The paper presents as an example the types of mathematical models that are used in a full scale anesthesia simulator. The models vary from detailed reference models, based on fundamental physiological laws and principles, to simple script based models. A few considerations on the implementation of the models are also given.

Anesthesiology↗
PubMed2000

Cognitive studies of ethical reasoning based on the KARDIO-simulator.

Empirical investigations in medical ethics are often questionnaire studies relying on the respondents' written responses about their attitudes and actions. This approach is valuable, but there may be quite large discrepancies between responses and actual behaviour. Unfortunately actual behaviour is often difficult to observe, especially where sensitive or very time dependent clinical decisions are concerned. We have tried to circumvent this problem by using a micro-world computer simulation of a cardiac care unit to study treatment decisions in "life or death" situations. The task facing the physician in this simulation is to be in charge of a 6-bed cardiac care unit for a period of 14 "days" controlling admissions, discharges, and treatment of all patients. The simulation dynamically generates the disease states of the patients in the unit including physical findings, laboratory findings, ECG, X-ray descriptions etc., as well as the patients responses to treatment. The simulation also presents new patients from the emergency room, thereby forcing the physician to decide whether the new patient should be admitted, and whether one of the present patients should be discharged or moved to another ward if no bed is free. The paper describes this simulator, the mathematical model underlying the simulation of patients with acute myocardial infarction, and the results of the initial studies using the simulator.

Computer Simulation↗
PubMed1999

Cholecystectomy in patients with normal gallbladder function did not alter characteristics in duodenal motility which was not correlated to size of bile acid pool.

Nine gallstone patients with normal gallbladder function as assessed by hepatobiliary scintigraphy were included. Fasting and postprandial duodenal motility were studied before and one month after an uncomplicated laparoscopic cholecystectomy. An ambulatory continuous pressure recording was obtained from 5 PM to 8 AM with a sampling frequency of 4 Hz. At 6 PM, the patients received a 1400-kJ standard meal. The size of the bile acid pool after cholecystectomy was measured according to the dilution principle using [C14]cholic acid as the marker. Preoperatively the migrating motor complex (MMC) cycle was 0.48/hr (quartiles 0.42-0.68) compared to 0.68/hr (0.43-0.77) postoperatively. This difference was not significant. An increase in the MMC cycle frequency was observed postoperatively in three patients, and a decrease was seen in four patients. The migration velocity was 5.61 cm/min (4.26-8.01) preoperatively and 7.16 cm/min (4.79-9.71) postoperatively, a difference that was not significant. The time period from meal ingestion to appearance of phase III was 297 min (218-431) at the preoperative examination and 443 min (192-494) at the postoperative examination. This difference was not significant. The size of the bile acid pool after cholecystectomy was 3.68 mmol (2.69-8.47) and was not significantly correlated to the frequency of the MMC cycle or the time period from food ingestion to phase III activity. It is concluded that in gallstone patients with a normally functioning gallbladder, cholecystectomy does not alter duodenal motility, which was not correlated to the size of the bile acid pool.

Adult↗
PubMed1999

On demand therapy with omeprazole for the long-term management of patients with heartburn without oesophagitis--a placebo-controlled randomized trial.

AIM: To observe the natural course of gastro-oesophageal reflux disease (GERD) in patients without oesophagitis following effective symptom relief, and to determine the place of acid pump inhibitor therapy in the long-term management of these patients. METHODS: We investigated the efficacy of on-demand therapy with omeprazole 20 mg or 10 mg, or placebo in a double-blind, randomized multicentre trial. It involved 424 patients with troublesome heartburn without endoscopic evidence of oesophagitis in whom heartburn had been resolved with short-term treatment. Patients were told to take study medication on demand once daily on recurrence of symptoms until symptoms resolved over a 6-month period. They also had access to antacids. The primary efficacy variable was time to discontinuation of treatment, due to unwillingness to continue. RESULTS: According to life-table analysis, after 6 months the remission rates were 83% (95% CI: 77-89%) with omeprazole 20 mg, 69% (61-77%) with omeprazole 10 mg, and 56% (46-64%) with placebo (P < 0.01 for all intergroup differences). The mean (s.d.) number of study medications used per day in these groups was 0.43 (0.27), 0.41 (0.27) and 0.47 (0.27), respectively. The use of antacids was highest in the placebo group and lowest in the omeprazole 20 mg group. Treatment failure was associated with more than a doubling of antacid use, and a deterioration in patient quality of life. CONCLUSIONS: Approximately 50% of patients with heartburn who do not have oesophagitis need acid inhibitory therapy in addition to antacid medication to maintain a normal quality of life. On-demand therapy with omeprazole 20 mg, is an effective treatment strategy in these patients.

Adult↗
PubMed1999

Lack of effect of acid suppression therapy on gastric atrophy. Nordic Gerd Study Group.

BACKGROUND & AIMS: A hypothesis suggesting that profound acid inhibition therapy facilitates and hastens the development of gastric glandular atrophy in patients infected with Helicobacter pylori was investigated in this randomized study comparing omeprazole therapy with antireflux surgery (ARS) for chronic gastroesophageal reflux disease (GERD). METHODS: Patients with esophagitis and/or chronic GERD were enrolled; 155 patients were randomized to ARS and 155 to long-term omeprazole therapy. Baseline data were obtained and repeated after 3 years in 131 ARS patients and in 139 omeprazole-treated patients. Histopathologic status of the oxyntic mucosa was assessed according to the Sydney system. RESULTS: Forty omeprazole-treated patients were infected with H. pylori compared with 53 in the ARS group. Basal gastrin levels were significantly higher in H. pylori-infected patients, particularly in the omeprazole group. No further increases in serum gastrin levels were observed during 3 years. Despite 3 years of therapy, only slight changes were found in the prevalence of inflammation in the corpus mucosa of H. pylori-infected subjects. A slow progression of gastric glandular atrophy was observed in these patients irrespective of therapy with no obvious difference between treatment regimens. Intestinal metaplasia (all of type I) was only exceptionally observed with no difference between the treatment arms. CONCLUSIONS: Acid-suppressive therapy in the form of omeprazole maintained for 3 years facilitates neither the development of gastric glandular atrophy of the corpus mucosa nor the occurrence of intestinal metaplasia in H. pylori-infected GERD patients.

Adolescent↗
PubMed1999

The effects of omeprazole on intragastric pH, intestinal motility, and gastric emptying rate.

BACKGROUND: The present study was designed to investigate whether omeprazole changes the characteristics and thereby the functions ascribed to fasting intestinal motility, postprandial motility, postprandial pH, and gastric emptying. METHODS: Ten healthy subjects were investigated. The studies were performed after 10 days of treatment with 40 mg omeprazole daily/placebo. Duodenal pressures and intragastric pH were detected by strain-gauge transducers and a pH electrode attached to a miniature computer. The meal consisted of an omelette labelled with 99mTc-sulphur colloids followed by 150 ml water labelled with 111In-diethylenetriamine pentaacetic acid. RESULTS: The difference in fasting intragastric pH between the two series was highly significant. The profile from the placebo series showed a relationship between phase activity and pH. The pH increased from phase I (median, 1.3; 95% confidence interval (CI), 0.9-1.6) to a maximum at 25% (1.8 (0.9-2.1)) and 50% (1.6 (1.1-3.8)) of cycle duration and decreased thereafter until the end of the cycle. The profile from the omeprazole series showed significantly higher values during the entire cycle but no relationship between phase activity and pH. Pretreatment with omeprazole was followed by a delay in gastric emptying of liquid at 30 min (64% (49%-66%) (omeprazole series) versus 78% (67%-83%); P < 0.01) and solid at 180 min (71% (48%-86%) (omeprazole series) versus 96% (87%-100%); P < 0.01). There was no significant difference in duration of postprandial motility (305 min (157-350 min) (omeprazole) versus 259 min (129-403 min)). CONCLUSIONS: Omeprazole eliminates the temporal relationship between intragastric pH and characteristics of the migrating motor complex and induces a delay in gastric emptying of both liquid and solid. A non-significant increase in duration of postprandial motility may represent a type-II error.

Adult↗
PubMed1999

The variability of the incremental postprandial portal vein flow response is partly caused by a relationship between fasting flow rate and phase activity of the migrating motor complex.

OBJECTIVE: Results from studies on portal flow rate (PFR) have demonstrated a considerable intra- as well as interindividual variability of the incremental integrated response (IIR). We hypothesized that part of the variation of the IIR might be related to variability of the fasting PFR caused by a relationship between PFR and characteristics of the migrating motor complex (MMC). DESIGN: We examined 12 healthy men and PFR was recorded by using the percutaneous colour Doppler technique. Gastric emptying (GE) was determined by scintigraphy and the meal consisted of an omelette of 100 g (1400 kJ; 60% fat, 20% protein, 20% carbohydrates) tagged with 99mTc sulphur colloids followed by 150 ml water mixed with 111In DTPA. The design included recording of PFR in phase II as well as in phase III of the MMC. Meal ingestion took place in the following duodenal phase I. Postprandial recordings of GE and PFR were performed at 10 min intervals for the following 2 h. RESULTS: Median (95% confidence limits) amount of solid emptied at 120 min was 68% (59-81%). PFR in phase III was significantly higher than in phase II (1.56 l/min (1.35-1.93 l/min) vs 0.96 l/min (0.84-1.12 l/min), P< 0.001). PFR increased after the meal and a peak flow of 2.19 l/min (1.58-2.46 I/min) was recorded 10 min after ingestion (P< 0.01 vs phase III). Based on these characteristics a difference in IIR is to be expected, and the calculations revealed that IIR is considerably higher in the phase II series than in the phase III series (50 l/min x 120 min (8-90 l/min) vs -26 l/min x 120 min (-55 to 1 l/min), P< 0.001). In both series a weak but significant inverse relationship was demonstrated between amounts emptied during a 20-min period and the corresponding IIR (n = 72; r = -0.27, P< 0.05 (III); r = -0.29; P< 0.05 (II)). CONCLUSION: We conclude that fasting PFR is related to phase activity of the MMC and characteristics of the postprandial IIR depend upon MMC activity at the time of recording of the fasting value. Future studies on PFR need to be performed with phase related recording of fasting flow and meal ingestion in relation to preselected characteristics of the MMC.

Adult↗
PubMed1999

Quality of life in patients with heartburn but without esophagitis: effects of treatment with omeprazole.

OBJECTIVE: Because improvement in quality of life (QoL) is an important therapeutic goal in patients with heartburn but without esophagitis, the aim of the present study was to compare the impact of omeprazole 20 mg or 10 mg daily with that of placebo on QoL in patients with heartburn as the predominant symptom. METHODS: QoL was measured at baseline and after 4 wk using two validated questionnaires, the Psychological General Well-Being (PGWB) index and the Gastrointestinal Symptom Rating Scale. RESULTS: The two questionnaires were completed by 163 patients in the omeprazole 20 mg group, 163 in the omeprazole 10 mg group, and 82 in the placebo group. The reflux dimension of the Gastrointestinal Symptom Rating Scale showed a significant improvement in terms of reflux symptoms on omeprazole 20 mg versus omeprazole 10 mg and placebo, and on omeprazole 10 mg compared with placebo. The total score of the PGWB index improved significantly more on both doses of omeprazole than on placebo. The mean scores rose from 96.8 to 103.9 on omeprazole 20 mg, from 98.4 to 106.0 on omeprazole 10 mg, and from 98.0 to 100.6 on placebo. All dimensions of the PGWB index improved on treatment with omeprazole, but the improvements were most pronounced in the dimensions depicting anxiety, depressed mood, and self-control. CONCLUSIONS: It is concluded that treatment with omeprazole 20 mg and omeprazole 10 mg restores QoL to a level comparable with that observed in a healthy population.

Adolescent↗
PubMed1998

Comprehensive 1-year cost analysis of open antireflux surgery in Nordic countries. Nordic GORD Study Group. Gastro-oesophageal reflux disease.

BACKGROUND: Antireflux surgery is a highly effective treatment option in patients with severe gastro-oesophageal reflux disease. However, because of the increasing pressure of cost containment within health care, cost aspects must also be added to the decision-making process. METHODS: The aim of this analysis was to assess the total cost of open antireflux surgery during the first year after operation in 178 patients with chronic reflux, who were recruited into a controlled, prospective clinical trial. The study was carried out in 17 hospitals in the Nordic countries. RESULTS: The cost of the operation represented more than 90 per cent of the direct medical costs which amounted to approximately US $5700. For a patient in the work force the indirect cost, i.e. loss of production, represented 47 per cent of the total cost, which was about US $10800. CONCLUSION: The total cost profile of open antireflux surgery has now been established prospectively and can form a basis for future comparisons.

Adolescent↗