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On the standard perspective, anorexia nervosa and other eating disorders are caused by genetically determined, neurochemically mediated mental illnesses. Standard treatment, cognitive behavioral therapy (CBT), targets cognitive processes thought to maintain the disorders. Effective neurochemically based treatments are not available and the rate of remission is ≤25% 1 year after CBT, with unknown outcomes in the long-term. With starvation as the major threat in biological history, the evolutionary perspective focuses on foraging for food and eating behavior. A neural network, including hypothalamic arcuate peptide-neurons, brainstem serotonin- and dopamine-neurons and their prefrontal cortical projections, mediates (rather than controls) the behavioral adaptations to variations in food availability; activation of the network is associated with opposing behavioral outcomes depending upon external variations. In the clinic, the control of eating behavior is therefore outsourced to a machine that provides feedback on how to eat. Hundreds of eating disorders patients have recovered by practicing eating; the rate of remission is 75% in on average 1 year of treatment, the rate of relapse is 10% over 5 years of follow-up and no patient has died. A two-parameter asymptotic exponential growth curve modeled the eating behavior of 17 healthy women but not that of 17 women with anorexia nervosa. When in remission, the eating behavior of the anorexic women approached that of the healthy women. It is suggested that the treatment of eating disorders should focus on eating behavior.

Eating disorders (anorexia nervosa, bulimia nervosa, binge-eating disorder, and other specified eating or feeding disorders) have a combined prevalence of 13% and are associated with severe physical and psychosocial problems. Early diagnosis, which is important for effective treatment and prevention of undesirable long-term health consequences, imposes problems among non-specialist clinicians unfamiliar with these patients, such as those working in primary care. Early, accurate diagnosis, particularly in primary care, allows expert interventions early enough in the disorder to facilitate positive treatment outcomes. Computer-assisted diagnostic procedures offer a possible solution to this problem by providing expertise via an algorithm that has been developed from a large number of cases that have been diagnosed in person by expert diagnosticians and expert caregivers. A web-based system for determining an accurate diagnosis for patients suspected to suffer from an eating disorder was developed based on these data. The process is automated using an algorithm that estimates the respondent's probability of having an eating disorder and the type of eating disorder the individual has. The system provides a report that works as an aid for clinicians during the diagnostic process and serves as an educational tool for new clinicians.

Mental causation takes explanatory priority over evolutionary biology in most accounts of eating disorders. The evolutionary threat of starvation has produced a brain that assists us in the search for food and mental change emerges as a consequence. The major mental causation hypothesis: anxiety causes eating disorders, has been extensively tested and falsified. The subsidiary hypothesis: anxiety and eating disorders are caused by the same genotype, generates inconsistent results because the phenotypes are not traits, but vary along dimensions. Challenging the mental causation hypothesis in Feighner et al. (1972) noted that anorexic patients are physically hyperactive, hoarding for food, and they are rewarded for maintaining a low body weight. In 1996, Feighner's hypothesis was formalized, relating the patients' behavioral phenotype to the brain mechanisms of reward and attention (Bergh and Södersten, 1996), and in 2002, the hypothesis was clinically verified by training patients how to eat normally, thus improving outcomes (Bergh et al., 2002). Seventeen years later we provide evidence supporting Feighner's hypothesis by demonstrating that in 2012, 20 out of 37 patients who were referred by a psychiatrist, had a psychiatric diagnosis that differed from the diagnosis indicated by the SCID-I. Out of the 174 patients who were admitted in 2012, most through self-referral, there was significant disagreement between the outcomes of the SCID-I interview and the patient's subjective experience of a psychiatric problem in 110 of the cases. In addition, 358 anorexic patients treated to remission scored high on the Comprehensive Psychopathological Rating Scale, but an item response analysis indicated one (unknown) underlying dimension, rather than the three dimensions the scale can dissociate in patients with psychiatric disorders. These results indicate that psychiatric diagnoses, which are reliable and valid in patients with psychiatric disorders, are less well suited for patients with anorexia. The results are in accord with the hypothesis of the present Research Topic, that eating disorders are not always caused by disturbed psychological processes, and support the alternative, clinically relevant hypothesis that the behavioral phenotype of the patients should be addressed directly., (Copyright © 2019 Södersten, Brodin, Zandian and Bergh.)

On the standard perspective, anorexia nervosa and other eating disorders are caused by genetically determined, neurochemically mediated mental illnesses. Standard treatment, cognitive behavioral therapy (CBT), targets cognitive processes thought to maintain the disorders. Effective neurochemically based treatments are not available and the rate of remission is ≤25% 1 year after CBT, with unknown outcomes in the long-term. With starvation as the major threat in biological history, the evolutionary perspective focuses on foraging for food and eating behavior. A neural network, including hypothalamic arcuate peptide-neurons, brainstem serotonin- and dopamine-neurons and their prefrontal cortical projections, mediates (rather than controls) the behavioral adaptations to variations in food availability; activation of the network is associated with opposing behavioral outcomes depending upon external variations. In the clinic, the control of eating behavior is therefore outsourced to a machine that provides feedback on how to eat. Hundreds of eating disorders patients have recovered by practicing eating; the rate of remission is 75% in on average 1 year of treatment, the rate of relapse is 10% over 5 years of follow-up and no patient has died. A two-parameter asymptotic exponential growth curve modeled the eating behavior of 17 healthy women but not that of 17 women with anorexia nervosa. When in remission, the eating behavior of the anorexic women approached that of the healthy women. It is suggested that the treatment of eating disorders should focus on eating behavior.

Purpose: The aim was to investigate the quality of life and bowel function in children with low anorectal malformations (ARM)., Additional Aim: To evaluate the Swedish version the Hirschsprung's Disease/Anorectal Malformation Quality of life Questionnaire (HAQL)., Methods: Forty-four children and their parents were invited to complete the HAQL and the Bowel Function Score (BFS). Healthy children participated as controls and completed the HAQL., Results: Seventeen children and 18 mothers completed the HAQL. The children reported impaired function in the physical symptom (PH) fecal continence (FC) and laxative diet (LD) domains compared to controls. Compared with their mothers, they reported impaired physical function and more symptoms in the emotional functioning (EMF) and PH domains. 27 families completed the BFS; 63% reported normal bowel function, 33% moderate outcome and one patient, comprising 4%, poor outcome. Evaluation of the HAQL, FC, EMF and PH domains showed no obvious conflicts., Conclusions: The children did not differ much regarding their QoL, even though they appeared to have impaired bowel function and worse emotional functioning compared to controls. The mothers underestimated their children's physical symptoms and overestimated their emotional functioning. Evaluated domains in the HAQL appear to work as intended, but the questionnaire needs further development.

Background: Questionnaires and surveys are used throughout medical education. Nevertheless, measuring psychological attributes such as perceptions of a phenomenon among individuals may be difficult. The aim of this paper is to introduce the basic principles of Mokken scale analysis (MSA) as a method for the analysis of questionnaire data and to empirically apply MSA to a real-data example., Methods: MSA provides a set of statistical tools for exploring the relationship between items and latent traits. MSA is a scaling method of item selection algorithms used to partition an array of items into scales. It employs various methods to probe the assumptions of two nonparametric item response theory models: the monotone homogeneity model and the double monotonicity model. The background and theoretical framework underlying MSA are outlined in the paper. MSA for polytomous items was applied to a real-life data example of 222 undergraduate students who had completed a 50-item self-administered inventory measuring the educational environment, the Dundee Ready Educational Measure (DREEM)., Results: A pragmatic and parsimonious approach to exploring questionnaires and surveys from an item response theory (IRT) perspective is outlined. The use of MSA to explore the psychometric properties of the Swedish version of the DREEM failed to yield strong support for the scalability and dimensional structure of the instrument., Conclusions: MSA, a class of simple nonparametric IRT models - for which estimates can be easily obtained and whose fit to data is relatively easily investigated - was introduced, presented, and tested. Our real-data example suggests that the psychometric properties of DREEM are not adequately supported. Thus, the empirical application depicted a potential and feasible approach whereby MSA could be used as a valuable method for exploring the behavior of scaled items in response to varying levels of a latent trait in medical education research.

We examine the science and evidence supporting cognitive behavior therapy (CBT) for the treatment of bulimia nervosa and other eating disorders. Recent trials focusing on the abnormal cognitive and emotional aspects of bulimia have reported a remission rate of about 45%, and a relapse rate of about 30% within one year. However, an early CBT trial that emphasized the normalization of eating behavior had a better outcome than treatment that focused on cognitive intervention. In support of this finding, another treatment, that restores a normal eating behavior using mealtime feedback, has an estimated remission rate of about 75% and a relapse rate of about 10% over five years. Moreover, when eating behavior was normalized, cognitive and emotional abnormalities were resolved at remission without cognitive therapy. The critical aspect of the CBT treatment of bulimia nervosa therefore may actually have been the normalization of eating behavior., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

We report the results of a study based on 1,428 patients with eating disorders treated at 6 clinics. These patients were consecutively referred over 18 years and used inpatient and outpatient treatment. The subjects were diagnosed with anorexia nervosa, bulimia nervosa, or an eating disorder not otherwise specified. Patients practiced a normal eating pattern with computerized feedback technology, they were supplied with external heat, their physical activity was reduced, and their social habits restored to allow them to return to their normal life. The estimated rate of remission for this therapy was 75% after a median of 12.5 months of treatment. A competing event such as the termination of insurance coverage, or failure of the treatment, interfered with outcomes in 16% of the patients, and the other patients remained in treatment. Of those who went in remission, the estimated rate of relapse was 10% over 5 years of follow-up and there was no mortality. These data replicate the outcomes reported in our previous studies and they compare favorably with the poor long-term remission rates, the high rate of relapse, and the high mortality rate reported with standard treatments for eating disorders.

Background: This study investigates whether an analysis, based on Item Response Theory (IRT), can be used for initial evaluations of depression assessment instruments in a limited patient sample from an affective disorder outpatient clinic, with the aim to finding major advantages and deficiencies of the instruments., Methods: Three depression assessment instruments, the depression module from the Patient Health Questionnaire (PHQ9), the depression subscale of Affective Self Rating Scale (AS-18-D) and the Montgomery-Åsberg Depression Rating Scale (MADRS) were evaluated in a sample of 61 patients with affective disorder diagnoses, mainly bipolar disorder. A '3- step IRT strategy' was used., Results: In a first step, the Mokken non-parametric analysis showed that PHQ9 and AS-18-D had strong overall scalabilities of 0.510 [C.I. 0.42, 0.61] and 0,513 [C.I. 0.41, 0.63] respectively, while MADRS had a weak scalability of 0.339 [C.I. 0.25, 0.43]. In a second step, a Rasch model analysis indicated large differences concerning the item discriminating capacity and was therefore considered not suitable for the data. In third step, applying a more flexible two parameter model, all three instruments showed large differences in item information and items had a low capacity to reliably measure respondents at low levels of depression severity., Conclusions: We conclude that a stepwise IRT-approach, as performed in this study, is a suitable tool for studying assessment instruments at early stages of development. Such an analysis can give useful information, even in small samples, in order to construct more precise measurements or to evaluate existing assessment instruments. The study suggests that the PHQ9 and AS-18-D can be useful for measurement of depression severity in an outpatient clinic for affective disorder, while the MADRS shows weak measurement properties for this type of patients.

Background: Speed of eating, an important aspect of eating behaviour, has recently been related to loss of control of food intake and obesity. Very little time is allocated for lunch at school and thus children may consume food more quickly and food intake may therefore be affected. Study 1 measured the time spent eating lunch in a large group of students eating together for school meals. Study 2 measured the speed of eating and the amount of food eaten in individual school children during normal school lunches and then examined the effect of experimentally increasing or decreasing the speed of eating on total food intake., Methods: The time spent eating lunch was measured with a stop watch in 100 children in secondary school. A more detailed study of eating behaviour was then undertaken in 30 secondary school children (18 girls). The amount of food eaten at lunch was recorded by a hidden scale when the children ate amongst their peers and by a scale connected to a computer when they ate individually. When eating individually, feedback on how quickly to eat was visible on the computer screen. The speed of eating could therefore be increased or decreased experimentally using this visual feedback and the total amount of food eaten measured., Results: In general, the children spent very little time eating their lunch. The 100 children in Study 1 spent on average (SD) just 7 (0.8) minutes eating lunch. The girls in Study 2 consumed their lunch in 5.6 (1.2) minutes and the boys ate theirs in only 6.8 (1.3) minutes. Eating with peers markedly distorted the amount of food eaten for lunch; only two girls and one boy maintained their food intake at the level observed when the children ate individually without external influences (258 (38) g in girls and 289 (73) g in boys). Nine girls ate on average 33% less food and seven girls ate 23% more food whilst the remaining boys ate 26% more food. The average speed of eating during school lunches amongst groups increased to 183 (53)% in the girls and to 166 (47)% in the boys compared to the speed of eating in the unrestricted condition. These apparent changes in food intake during school lunches could be replicated by experimentally increasing the speed of eating when the children were eating individually., Conclusions: If insufficient time is allocated for consuming school lunches, compensatory increased speed of eating puts children at risk of losing control over food intake and in many cases over-eating. Public health initiatives to increase the time available for school meals might prove a relatively easy way to reduce excess food intake at school and enable children to eat more healthily.

Background: The Affective Self Rating Scale (AS-18) is intended for the use in bipolar outpatients. It includes subscales for the rating of depressive and manic-type symptoms. It has previously been validated using methods from Classical Test Theory., Aims: The aim of this study was to evaluate the psychometric properties of the AS-18 when used at an outpatient clinic for patients with bipolar disorder at routine visits, and to analyze the potential for improvement of the scale., Methods: 231 patients with mainly bipolar I disorder doing ratings on routine visits at an affective disorder outpatient clinic were included. Ratings were analyzed using the Mokken non-parametric and the Rasch parametric model statistical methods., Results: In the Mokken analysis, both subscales of the AS-18 showed a strong ability to rank respondents according to their total score and all items contributed adequately to the measurement. In the Rasch model, there were no indications of disturbing influence from secondary dimensions in the subscales. The depression subscale had the capacity reliably to separate the sample in at most three levels and the mania subscale in two levels. The limited capacity to separate respondents can mainly be explained by a lack of items reflecting lower levels of depressive and manic symptoms., Conclusions: AS-18 has good basic psychometric properties for use of rating of symptoms in bipolar I patients at routine visits, but there is also room for improvement. Item Response Theory (IRT) methods are suitable tools for evaluation and construction of rating scales.

Background: In medical education research, various questionnaires are often used to study possible relationships between strategies and approaches to teaching and learning and the outcome of these. However, judging the applicability of such questionnaires or the interpretation of the results is not trivial., Methods: As a way to develop teacher thinking, teaching strategy profiles were calculated for teachers in a research intensive department at Karolinska Institutet. This study compares the sum score, that was inherent in the questionnaire used, with an Item Response Theory (IRT) approach. Three teaching dimensions were investigated and the intended sum scores were investigated by IRT analysis., Results: Agreements as well as important differences were found. The use of the sum score seemed to agree reasonably with an IRT approach for two of the dimensions, while the third dimension could not be identified neither by a the sum score, nor by an IRT approach, as the items included showed conflicting messages., Conclusions: This study emphasizes the possibilities to gain better insight and more relevant interpretation of a questionnaire by use of IRT. A sum score approach should not be taken for granted. Its use has to be thoroughly evaluated.

Unlabelled: The origin of the present study was to develop the liaison work between the disciplines of child and adolescent psychiatry and paediatric surgery and nursing, so as to improve the quality of treatment and care of a group of children with imperforate anus (IA) and their families. Imperforate anus is a congenital disease involving a deformity of the anorectum. The early surgery and invasive follow-up treatment associated with IA may affect the child psychosocially, including the child-parent relationship. By developing and testing a questionnaire for children born with anorectal anomalies, a tool for measuring psychosocial functioning can be realized., Methods: First, a literature review on "Imperforate Anus" was performed. Second, an exploratory interview study was conducted with patients/adolescents with IA and their parents. The findings from these interviews were the foundation for construction of the questionnaire. The Imperforate Anus Psychosocial Questionnaire (IAPSQ) was tested and revised three times before its completion. It contains 45 items on Likert scales. A total of 87 children completed the IAPSQ: 25 children with IA and two comparison groups. Face and content validity were considered. The Rasch approach, an item response theory model, was used to evaluate the psychometric properties of the IAPSQ, where item difficulty and person ability are concurrently approximated., Results: The findings of the Rasch analysis revealed that the psychological dimension was reasonable, and that person reliability (0.83) was moderate and item reliability (0.95) was sufficient. The social dimension showed satisfactory item reliability (0.87). The person reliability (0.52) of the social dimension was weak. Content validity seemed to be established and construct validity was recognized on the psychological dimension., Conclusion: The IAPSQ provides a reasonably valid and reliable measure of psychosocial functioning for clinical use among children with IA, although some revisions are suggested for the next version of the IAPSQ. By using the Rasch model, we discovered that specific items should be discarded and other items should be reformulated to make the questionnaire more "on target". The social dimension has to be expanded with further items to reasonably capture a social dimension.

Women were divided into those eating at a decelerated or linear rate. Eating rate was then experimentally increased or decreased by asking the women to adapt their rate of eating to curves presented on a computer screen and the effect on food intake and satiety was studied. Decelerated eaters were unable to eat at an increased rate, but ate the same amount of food when eating at a decreased rate as during the control condition. Linear eaters ate more food when eating at an increased rate, but less food when eating at a decreased rate. Decelerated eaters estimated their level of satiety lower when eating at an increased rate but similar to the control condition when eating at a decreased rate. Linear eaters estimated their level of satiety similar to the control level despite eating more food at an increased rate and higher despite eating less food at a decreased rate. The cumulative satiety curve was fitted to a sigmoid curve both in decelerated and linear eater under all conditions. Linear eaters rated their desire to eat and estimated their prospective intake lower than decelerated eaters and scored higher on a scale for restrained eating. It is suggested that linear eaters have difficulty maintaining their intake when eating rate is dissociated from its baseline level and that this puts them at risk of developing disordered eating. It is also suggested that feedback on eating rate can be used as an intervention to treat eating disorders.

Psychosocial development in children with chronic disease is a key issue in paediatrics. This study investigated whether psychosocial adjustment could be reliably assessed with the 42-item Adolescent Adjustment Profile (AAP) instrument. The study mainly focused on adjustment-to-obesity measurement, although it compared three patient groups with chronic conditions. All phenylketonuria (PKU) patients in Sweden between ages 9 and 18 and their parents and teachers were invited to participate. Patients with neurobehavioural syndromes and obesity were age- and gender-matched with PKU patients. Healthy children constituted a reference group. Psychosocial adjustment was measured using the AAP, which is a multi-informant questionnaire that contains four domains. Information concerning parents' socio-economic and civil status was requested separately. Respondents to the three questionnaires judged the PKU patients to be normal in all four domains. Patients with neurobehavioural syndromes demonstrated less competence and the most problems compared with the other three groups. According to the self-rating, the parent rating and the teacher rating questionnaires, obese patients had internalizing problems. The parent rating and the teacher rating questionnaire scored obese patients as having a lower work capacity than the reference group. Compared with the reference group, not only families with obese children but also families with children with neurobehavioural syndromes had significantly higher divorce rates. Obese patients were also investigated with the Strength and Difficulties Questionnaire (SDQ), another instrument that enables comparison between two measures of adjustment. The AAP had good psychometric properties; it was judged a useful instrument in research on adolescents with chronic diseases.

The hypothesis that treatment with neuropeptide Y (NPY) can increase running activity and decrease food intake and body weight was tested. Female rats with a running wheel lost more weight than sedentary rats and ran progressively more as the availability of food was gradually reduced. When food was available for only 1h/day, the rats lost control over body weight. Correlatively, the level of NPY mRNA was increased in the hypothalamic arcuate nucleus. This phenomenon, activity-based-anorexia, was enhanced by intracerebroventricular infusion of NPY in rats which had food available during 2h/day. By contrast, NPY stimulated food intake but not wheel running in rats which had food available continuously. These findings are inconsistent with the prevailing theory of the role of the hypothalamus in the regulation of body weight according to which food intake is a homeostatic process controlled by "orexigenic" and "anorexigenic" neural networks. However, the finding that treatment with NPY, generally considered an "orexigen", can increase physical activity and decrease food intake and cause a loss of body weight is in line with the clinical observation that patients with anorexia nervosa are physically hyperactive and eat only little food despite having depleted body fat and up-regulated hypothalamic "orexigenic" peptides.

We tested the hypothesis that neuropeptide Y (NPY) interacts with cholecystokinin octapeptide (CCK-8) in inhibition of intake of an intraorally infused solution of sucrose, a test of consummatory ingestive behavior. Both intracerebroventricular infusion of NPY (10 microg) and intraperitoneal injection of CCK-8 (0.5 micro/kg) reduced the intake of a 1M solution of sucrose infused intraorally at a rate of 0.5 ml/min in ovariectomized female rats, but the two peptides did not interact in inhibiting intraoral intake. By contrast, NPY increased intake if the sucrose solution was ingested from a bottle, a test demanding both appetitive and consummatory ingestive responses. CCK-8 inhibited intake in this test and its inhibitory effect was increased by simultaneous treatment with NPY. The activity in the nucleus of the solitary tract (NTS), a brainstem relay mediating inhibition of intake, judged by the expression of c-fos-like immunoreactivity, was significantly increased after treatment with CCK-8 or NPY to approximately the same extent. Combined treatment with NPY and CCK-8 did not increase the c-fos-like immunoreactivity in the NTS above treatment with NPY or CCK-8 alone. These results strengthen the hypothesis that NPY, like CCK-8, is an inhibitor of consummatory ingestive behavior and suggest that this inhibition is mediated via the NTS.

We present the case of an Australian girl with severe anorexia nervosa who had previously been resistant to treatment, and who was subsequently treated successfully by an innovative programme at the Karolinska Institute in Stockholm. The programme is based on a distinctive concept of causation of eating disorders in which it is postulated that they develop as a consequence of starvation rather than a primary mental disorder. The treatment focuses on relearning how to eat and perceive satiety using a unique feed-back system, together with provision of warmth, limitation of exercise and facilitating social adaptation.

Evidence for the effectiveness of existing treatments of patients with eating disorders is weak. Here we describe and evaluate a method of treatment in a randomized controlled trial. Sixteen patients, randomly selected out of a group composed of 19 patients with anorexia nervosa and 13 with bulimia nervosa, were trained to eat and recognize satiety by using computer support. They rested in a warm room after eating, and their physical activity was restricted. The patients in the control group (n = 16) received no treatment. Remission was defined by normal body weight (anorexia), cessation of binge eating and purging (bulimia), a normal psychiatric profile, normal laboratory test values, normal eating behavior, and resumption of social activities. Fourteen patients went into remission after a median of 14.4 months (range 4.9-26.5) of treatment, but only one patient went into remission while waiting for treatment (P = 0.0057). Relapse is considered a major problem in patients who have been treated to remission. We therefore report results on a total of 168 patients who have entered our treatment program. The estimated rate of remission was 75%, and estimated time to remission was 14.7 months (quartile range 9.6 > or = 32). Six patients (7%) of 83 who were treated to remission relapsed, but the others (93%) have remained in remission for 12 months (quartile range 6-36). Because the risk of relapse is maximal in the first year after remission, we suggest that most patients treated with this method recover.

Rationale: One of the factors that terminate the ingestion of an intraorally infused solution of sucrose may be an increase in the perceived aversiveness of its taste., Objectives: We tested the hypothesis that dopamine D(2), as opposed to D(1), receptors in the brainstem or nucleus accumbens inhibit intraoral intake by enhancing the aversiveness of the taste of the infused solution., Methods: Male rats were infused intraorally with a 2 M sucrose solution (1 ml/min) and intake and the display of gapes and chin rubs, i.e. taste-related aversive behavior, was measured. Gapes and chin rubs were also measured in rats during and 40 s after brief intraoral infusion (1 ml/min during 20 s) of a 0.3 mM solution of quinine HCl. The full D(1) receptor agonist dihydrexidine (0.1-3.0 mg/kg) and antagonist SCH-23390 (0.03-0.1 mg/kg), the D(2) receptor agonist quinpirole (0.3 mg/kg) and antagonist raclopride (1.7 mg/kg) were injected IP. Quinpirole (14-55 microg) and raclopride (5 microg) were also infused into the fourth brain ventricle. In addition, quinpirole (2 or 10 microg) was infused into the shell region of the nucleus accumbens., Results: IP dihydrexidine and quinpirole inhibited the intraoral intake of sucrose and pretreatment with raclopride, but (in the case of dihydrexidine) not SCH-23390, attenuated this effect. Injection of quinpirole into the fourth ventricle produced raclopride-reversible inhibition of intraoral intake but did not stimulate the display of gapes and chin rubs. Infusion of quinpirole into the shell region of the nucleus accumbens had the opposite effects. The intake of sucrose was suppressed by the addition of quinine HCl but this suppression was unaffected by dopamine agonist or antagonist treatment., Conclusions: It is suggested that brainstem dopamine D(2) receptors mediate suppression of consummatory ingestive behavior and that D(2) receptors in the shell region of the nucleus accumbens mediate the display of gapes and chin rubs, but that neither of these D(2) receptor populations mediate the hedonic evaluation of taste.

Aims: To evaluate the prognostic implications of results from exercise testing, and of antianginal treatment among patients with chronic stable angina pectoris., Material and Methods: Out of 809 patients in the Angina Prognosis Study In Stockholm (APSIS), 731 (511 men) performed evaluable exercise tests before and after 1 month on double-blind treatment with metoprolol or verapamil. During a median follow-up of 40 months, 32 patients suffered a cardiovascular death and 29 a non-fatal myocardial infarction., Results: Prognostic implications of results from exercise tests were assessed in a multivariate Cox model which included sex, previous myocardial infarction, hypertension and diabetes mellitus. Maximal ST-segment depression, especially if >/=2 mm and occurring after exercise, as well as exercise duration independently predicted cardiovascular death. Similar results were obtained for the combined end-point of cardiovascular death+myocardial infarction. Among patients with a positive exercise test at baseline, verapamil reduced the maximal ST-depression more markedly than metoprolol (P<0. 01). However, when the treatment given and treatment effects on ST-segment depression were added to the Cox model, no impact on prognosis could be detected for either cardiovascular death alone or combined with myocardial infarction. Anginal pain carried no prognostic information., Conclusion: Marked ST-segment depression during and after exercise, and a low exercise capacity independently predicted an adverse outcome in patients with stable angina pectoris, whereas anginal symptoms had no predictive value. Short-term treatment effects on ischaemia did not seem to influence prognosis. Post-exercise ischaemia should be examined carefully when evaluating patients with stable angina pectoris., (Copyright 2000 The European Society of Cardiology.)

Amlodipine and felodipine are calcium antagonists of the dihydropyridine type. The elimination half-life of amlodipine is longer than that of felodipine. To study whether the different elimination rates of the drugs were reflected in different duration of blood pressure (BP) control, we compared amlodipine and felodipine extended release (ER) by both conventional clinic BP 24 h after drug intake and 24 h ambulatory BP monitoring (ABPM), with special reference to nighttime and morning blood pressure. Two hundred and sixteen patients with primary hypertension (supine diastolic BP, 95 to 115 mm Hg) were randomized to receive amlodipine or felodipine ER in a multicenter study. The starting dose of both drugs was 5 mg. If the target clinic diastolic BP (90 mm Hg) had not been achieved after 4 weeks the dose was increased to 10 mg. Twenty-four-hour ABPM was performed with the subjects taking placebo medication before randomization and after 4 and 8 weeks undergoing active treatment. Significantly more patients responded after 4 weeks of treatment with amlodipine (50%) as compared with felodipine (33%) (P = .013). ABPM during daytime (07:00 to 23:00) was similar during both treatments, but nighttime systolic (P = .026) and diastolic (P = .019) BP was more effectively reduced by amlodipine than by felodipine. After 8 weeks 82% achieved the target pressure with amlodipine and 69% with felodipine (P = .036 for the difference). Amlodipine seems to be more effective than felodipine when the drugs are compared in the same dose, with regard to the effect on clinic BP 24 h after dosing and to ambulatory BP during the night. The longer elimination half-life of amlodipine as compared to felodipine is the probable reason for this finding.

Relationships between apolipoproteins and other lipid parameters and cardiovascular (CV) prognosis were evaluated in the Angina Prognosis Study In Stockholm (APSIS). Out of 809 patients with stable angina pectoris, lipid variables were obtained in 786 patients at baseline, and after one month's double-blind treatment with metoprolol or verapamil, to evaluate treatment effects on these lipid variables. During a median follow-up time of 3.3 years (2663 patient years), 37 patients suffered a CV death, 30 suffered a non-fatal myocardial infarction (MI) and 100 underwent a revascularization. Apolipoprotein (apo) A-I, high-density lipoprotein cholesterol and triglycerides were predictors of CV death or non-fatal MI in univariate analyses, but only apo A-I remained as an independent predictor in multivariate analyses. All lipid variables except low density lipoprotein cholesterol were related to the risk of revascularization in univariate analyses, but only apo A-I and apo B were independent predictors of such events. Triglycerides were weakly, but not independently, associated with prognosis. Verapamil and metoprolol had differential short-term effects on lipids, with a shift towards a more atherogenic profile in metoprolol treated patients. However, there was no significant impact of the treatment given, or of these treatment effects on the risk of CV events. Results of the present study suggest that apolipoprotein levels were better predictors of CV events than other lipid parameters in patients with stable angina pectoris.

The efficacy, toxicity and possible steroid-sparing properties of auranofin in the treatment of elderly-onset rheumatoid arthritis (EORA) were studied in a 2 yr prospective double-blind placebo-controlled clinical trial. Sixty-five patients with onset of arthritis after the age of 60 yr were randomized to either auranofin 3 mg b.i.d. [n = 31, age 70 (61-84) yr, median (range)] or placebo tablets [n = 34, age 72 (60-81) yr]. Oral prednisolone, starting dose 7.5 or 20 mg daily, was used as a rescue drug in patients with intolerable joint pain and stiffness and with C-reactive protein (CRP) > or = 20 mg/l, and was tapered down according to protocol guidelines. Patients receiving auranofin continued therapy for a longer period of time (55% completers) than those on placebo medication (18% completers). The auranofin group consumed significantly less prednisolone, 2.64 (0-11.85) mg/day [median (range)], compared to 5.0 (0-18.33) mg/day in the placebo group (P = 0.006). No group differences at 2 yr follow-up were found for changes in joint pain (P = 0.49), number of swollen joints (P = 0.61), Health Assessment Questionnaire score (P = 0.18) and radiographic damage score (Larsen-Dale index) of the hands (P = 0.84). Within-group changes in radiographic scores were also insignificant. The drop-out rate due to adverse events was surprisingly higher in the placebo group (41%) than in the auranofin group (10%) and, as expected, higher due to lack of effect (29 and 16%). The results indicate that auranofin is safe, superior to placebo and has steroid-sparing capacity in the treatment of EORA. The favourable radiographic outcome in both groups needs confirmation in future studies.

Objective: To compare 2 treatment strategies in a prospective 5 year study of patients with rheumatoid arthritis (RA): early treatment with slow acting antirheumatic drugs (SAARD) versus a "wait and see" attitude., Methods: One hundred thirty-seven patients with RA of < 2 years' duration entered a double blind placebo controlled study: patients in the "early" (E) group were treated with auranofin within one year of diagnosis of RA, and SAARD treatment in the initially placebo treated group was delayed 8 months compared with the former group. [The results after 2 years clearly favored early treatment (Borg G, Allander E, Lund B, et al: J Rheumatol 1988; 15:1747-54)]., Results: After a total observation period of 5 years in 75 representative patients, continued improvement in the E group was demonstrated, and differences between the 2 groups were maintained with regard to clinical variables, outcome measures, and radiographic evaluation., Conclusion: The results indicate the existence of a therapeutic window in RA within the first 2 years of the disease.

Background: Topical treatment is effective in patients with distal ulcerative colitis. This trial compares the efficacy, safety, and practicality of 4 weeks' treatment with 500 mg mesalazine suppositories with those of 178 mg hydrocortisone foam, both given twice daily., Methods: Seventy-nine patients with distal ulcerative colitis were stratified on the basis of the extent of the disease (proctitis and proctosigmoiditis) and randomized to one of the treatment groups. A disease activity index (DAI) based on symptoms and endoscopic findings was calculated. The patients evaluated the practicality of the treatment regimens, patients compliance was measured, and histologic findings recorded., Results: Of all the patients 22% and 38% were complete responders after 2 and 4 weeks, respectively. Median DAIs in the mesalazine and hydrocortisone groups before and after 2 and 4 weeks' treatment were 14, 6, and 4, and 13, 8, and 6, respectively. The difference between the treatment groups was statistically significant (p = 0.02) due to a better effect of mesalazine in patients with proctitis. Patients' evaluation of practicality and patient compliance were statistically significantly better in the mesalazine group., Conclusions: Both treatment regimens are effective; mesalazine suppositories seem to be the preferred alternative.

The effect of early vs delayed initiation of slow acting antirheumatic drug (SAARD) therapy on the ability to maintain regular work, was evaluated in 83 patients with early rheumatoid arthritis (RA) in a placebo controlled, double blind 24-month study. The estimated probability to maintain working ability was higher in the early treatment group, especially during the second study year. Predicting factors were age, type of work, degree of disability and number of swollen joints. Despite the difficulties in interpreting the results due to the complexity of the underlying socioeconomical and labor market situation, the study supports early treatment in RA with regard to the maintenance of normal life.

From a material of 18 obligate carriers of haemophilia A and 40 healthy females, a discriminant function was created, based on ratio of factor VIII related antigen (electroimmunoassay = EIA) to factor VIII activity (one-stage assay), factor VIII related antigen (radioimmunoassay = RIA) and number of bleeding symptoms. The standard deviation of p-values for carrier- and non-carrier state (less than 0.05) was estimated by a procedure built on the 'jack-knife' method. By combined information of pedigree- and discriminant analysis data, 43 possible carriers were classified as carriers/noncarriers with about 95% confidence. Carriers were significantly older, had more bleeding symptoms, longer APTT, lower factor VIII activity, factor VIII procoagulant antigen, and higher ratio of factor VIII related antigen (EIA) to factor VIII activity (one-stage) and to factor VIII related antigen (RIA) respectively, than classified noncarriers. Individuals with blood group A, B, AB had significantly higher levels of factor VIII related antigen (EIA) and (RIA), and ristocetin cofactor, compared with blood group O. Obligate carriers with severe haemophilia A in their families had more bleeding symptoms than corresponding group with moderate haemophilia.

The effect of psychological counseling on 1-year ulcer relapse rate of recurrent duodenal and prepyloric ulcer disease was evaluated in 148 patients randomly allocated into three treatment groups; psychological counseling group, maintenance cimetidine (400 mg at bedtime), and placebo cimetidine at bedtime. Ulcer relapses were monitored by endoscopy at 6 and 12 months after inclusion and at symptomatic recurrence. The estimated proportion of relapse-free patients after 12 months follow-up in the psychological counseling group (0.43 +/- 0.08) did not differ significantly from the placebo group (0.47 +/- 0.07), whereas the corresponding value for the cimetidine group (0.70 +/- 0.07) was significantly higher (p less than 0.01). The effect of cimetidine on ulcer recurrence, however, was confined to smokers; relapse risk among nonsmokers did not differ significantly between the treatment groups. The negative outcome of psychological counseling raises doubts as to whether duodenal or prepyloric ulcer recurrences can be prevented by such a therapeutic approach.

Two hundred and ten patients were defined as having dyspepsia of unknown origin. At endoscopy 11% had body gastritis, 46% antral gastritis, and 19% bulbitis (two thirds combined with antral gastritis). Histologically, 22% had chronic corpus gastritis (79% superficial, 21% atrophic), which was combined with chronic antral gastritis in 84%, 33% had chronic antral gastritis (82% superficial, 18% atrophic); and 14% had duodenitis, which was combined with antral gastritis in 65%. Polymorphonuclear leukocytes were found in specimens from the body mucosa in 6%, from the antral mucosa in 13%, and from the duodenal cap in 4%. The endoscopic findings correlated significantly with the histologic findings in the duodenal bulb (kappa = 0.33) but not in the stomach. The frequency of endoscopic antral gastritis and the frequency of histologic chronic body and antral gastritis increased with age. Endoscopic bulbitis and histologic duodenitis and gastric metaplasia were commoner in men than in women. Peak acid output was higher in patients with than in those without endoscopic bulbitis and higher in smokers than in non-smokers when the significant sex differences in peak acid output were taken into account. Gastric metaplasia of the bulb was predominantly correlated to higher peak acid output and to some extent also to sex and smoking. Episodic pain was correlated to histologic duodenitis. Other dyspeptic symptoms and the intragastric bile acid concentration were not associated with any endoscopic or histologic findings. Of the 210 patients, 172 were reexamined after a double-blind 6-week treatment period with cimetidine, antacid, or placebo. The symptomatic outcome of these treatments was not associated with any significant change in endoscopic or histologic findings.

Patients with dyspepsia of unknown origin were randomly allocated to a controlled double-blind study to examine the symptomatic effect of cimetidine and antacid especially on the relief of pain, nausea, and bloating. Two hundred and twenty-two patients with no previous history of peptic ulcer disease and no evidence of other organic causes of dyspepsia were treated for 6 weeks with placebo, cimetidine, or antacid. The results showed that cimetidine was superior to both placebo and antacid in relieving pain and nausea but not bloating. Certain background factors, such as epigastric pain and symptoms relieved by solid food, had a significant positive influence on the outcome of treatment. When the impact of background factors was taken into account, cimetidine was found to be more effective than both placebo and antacid also with regard to the number of patients who improved in general well-being.