Osteopenia in anorexia nervosa: specific mechanisms of bone loss.

Osteopenia is a well recognized medical complication of anorexia nervosa (AN). The mechanism of bone loss is not fully understood and there is uncertainty about its management. New markers of bone turnover have been developed. C-terminal type 1 propeptide (PICP) is a measure of bone formation and urinary pyridinolines such as deoxypyridinoline (DPYRX) and serum carboxyterminal crosslinked telopeptide (ICTP) are markers of bone resorption. The aim of this study was to examine these bone markers in patients with AN. Twenty female patients with AN and 12 healthy controls were included in the study. Bone mineral density (BMD) of AN patients was measured by dual energy X-ray absorptiometry (DEXA). Lumbar bone density was significantly reduced in the AN group compared to standardised values of thirty year old adults (t-score 83.2%, S.D. 12.1). Femoral neck bone density showed an even greater reduction (t-score 79.4%, S.D. 13.5). We found a significant negative correlation between femoral BMD and the duration of the illness. Femoral BMD correlated significantly with minimal body weight (r(16) = 0.504, p = 0.033). The markers of bone resorption were significantly higher in the patients with AN compared to the values of the control group (ICTP t(30) = -2.15, p = 0.04, DPYRX t(25) = -2.26, p = 0.033), whereas the markers of bone formation did not differ significantly between the groups. AN appears to be a low turn over state associated with increased bone resorption without concomitant bone formation. This pattern differs from osteopenia in menopausal women and should, therefore, lead to the development of specific therapeutic strategies in AN associated osteopenia. Hormone replacement therapy as well as calcium and vitamine D-supplementation are so far discussed controversially. Long-term treatment studies are warranted.

Globus sensation: pharyngoesophageal function, psychometric and psychiatric findings, and follow-up in 88 patients.

BACKGROUND: The globus sensation has been widely regarded as psychogenic, but organic disorders were found to be etiologically significant. OBJECTIVE: To investigate the structural, functional, psychological, and psychiatric factors possibly eliciting the globus sensation and influencing its course. METHODS: Eighty-eight patients, 67 women and 21 men (aged 22-71 years), referred to 2 tertiary care centers underwent history taking, otolaryngological examination, pharyngoesophageal videofluoroscopy and manometry, psychosocial evaluation, psychometric tests, psychiatric interview, and when indicated, esophagogastroduodenoscopy, esophageal bolus transport, gastroesophageal reflux, and gastric emptying studies. According to revealed disorders, therapy was initiated, and the outcome was studied. RESULTS: Only 15 patients had normal pharyngoesophageal function; of these 15, 6 had chronic tonsillitis or pharyngitis, 3 had thyroid adenomata, 4 had cervical spondylosis, and 1 each had dry oropharyngeal mucosa and chronic bronchitis. Of the other 73 patients, 2 had pharyngeal dysfunction, 24 had achalasia, 1 had diffuse esophageal spasms, 3 had "nutcracker esophagus," 30 had nonspecific esophageal motor disorders, and 13 had gastroesophageal reflux. Psychometry revealed no more anxiety and depression than in general medical outpatients. Of 58 patients interviewed, 37 met criteria for psychiatric disorders. Psychometric scores and psychiatric characteristics were unrelated to the sensation's course. Therapy was recommended, but only 26 patients were treated accordingly; 22 received nonspecific treatment. Follow-up 3 to 59 months later revealed that the sensation had vanished in 13 patients who had received specific treatment, 5 who had received nonspecific treatment, and 6 who had received no treatment; it was alleviated in 10 who had received specific treatment, 13 who had received nonspecific treatment, and 9 who had received no treatment; and it was unchanged in 3 who had received specific treatment, 5 who had received nonspecific treatment, and 23 patients who had received no treatment. CONCLUSIONS: Pharyngoesophageal disorders may be sensed only vaguely, inducing the globus sensation. Psychological and psychiatric characteristics could be relevant to the discomfort experienced but are unlikely to be etiologically significant.

Pain sensitivity, alexithymia, and depression in patients with eating disorders: are they related?

A decreased sensitivity to painful stimuli and high scores for alexithymia and depression have been observed in patients with eating disorders. We investigated the relationship between these factors in 22 patients with anorexia nervosa, 18 patients with bulimia nervosa, and 32 healthy subjects. Alexithymia was assessed using the 20-item Toronto Alexithymia Scale and depression using the Beck Depression Inventory. Patients with bulimia exhibited significantly higher thresholds to mechanically induced pain than healthy subjects. Thresholds to thermally induced pain in patients with anorexia or bulimia were similar and significantly higher than in the healthy subjects. Alexithymia and depression scores were significantly higher in anorexic and bulimic patients than in the healthy subjects. Analyses of covariance revealed that the degree of alexithymia did not influence thresholds to thermally and mechanically induced pain, whereas the severity of depression affected to some extent the threshold to thermally induced pain.

Gastric emptying, body weight and symptoms in primary anorexia nervosa. Long-term effects of cisapride.

In a double-blind trial, 12 out-patients with primary anorexia nervosa received, for six weeks, either 10 mg cisapride or placebo, three times a day. Cisapride accelerated gastric emptying of a radiolabelled semisolid meal in all six patients; five gained weight and symptoms of gastric retention ameliorated in four. With placebo, three of six had emptying enhanced, four gained weight, and one's symptoms improved. For another six weeks, all patients received cisapride. In five of the patients who had received cisapride, emptying further accelerated or remained stable; in one it slowed. Of the six patients who received placebo, four had emptying accelerated, five gained weight, and symptoms improved in four. Longer administration of cisapride may, by enhancing gastric motor activity, alleviate symptoms of retention and thus help to change eating behaviour.

Erythromycin effects on gastric emptying, antral motility and plasma motilin and pancreatic polypeptide concentrations in anorexia nervosa.

In primary anorexia nervosa, gastric motility is often impaired and ensuing symptoms further discourage eating. Prokinetic agents have been shown to accelerate gastric emptying in affected patients. This study investigated whether emptying of a radiolabelled semisolid 1168 kJ meal and antral contractility were enhanced by intravenous erythromycin. Eight women and two men with anorexia nervosa (21-46 years, 50-75% of ideal body weight) received 200 mg erythromycin or placebo under crossover double blind conditions. Gastric emptying and antral contractility were recorded scintigraphically for 90 minutes. In addition, plasma motilin and pancreatic polypeptide concentrations were determined. With placebo, antral contractions were of regular 3 cycles/minute frequency. With erythromycin, less frequent and partly arrhythmic long duration contractions set in and emptying was accelerated: after 90 minutes, the activity remaining in the stomach was markedly less than with placebo in all patients (Sign test, p < 0.002). Basal motilin and pancreatic polypeptide concentrations were normal and showed a normal response to the meal in all patients. Motilin concentrations decreased slightly more and pancreatic polypeptide concentrations increased markedly more with erythromycin than with placebo, possibly because the meal reached the intestine earlier. In conclusion, erythromycin accelerated emptying markedly and in most patients induced an antral motor activity characterised by long duration contractions occurring at often irregular intervals.

Lack of systematic effects of the 5-hydroxytryptamine 3 receptor antagonist ICS 205-930 on gastric emptying and antral motor activity in patients with primary anorexia nervosa.

1. The 5-hydroxytryptamine 3 receptor antagonist, ICS 205-930, has been reported to have potent effects on gastric smooth muscle and to enhance gastric emptying in animals, but findings in man have been inconsistent. 2. This study investigated the effects of ICS 205-930 on gastric emptying of an isotopically labelled semisolid 1168 kJ meal and on antral contractility in patients with primary anorexia nervosa, a condition frequently associated with impaired gastric motor function. 3. Thirteen female patients (age 18-39 years, median 22 years; percentage of ideal body weight 52-90%, median 66%) participated each in two studies, in which 0.15-0.18 mg kg-1 ICS 205-930 or placebo were infused i.v. in crossover, double-blind fashion. Gastric emptying and antral contractility were recorded scintigraphically for 50 min. 4. ICS 205-930 did not affect gastric emptying: the mean percentage of meal remaining in the stomach after 50 min (69.6% +/- 3.2 s.e. mean) was nearly identical to that after placebo (70.7 +/- 3.3%). 5. Amplitude, frequency and propagation velocity of antral contractions differed only little after ICS 205-930 and placebo, respectively. 6. The results show that ICS 205-930 has no effect on the impaired gastric motor activity in primary anorexia nervosa and thus provide further evidence that the compound does not have prominent prokinetic effects in man.

Metabolism of cortisol in anorexia nervosa.

In patients with anorexia nervosa 24-h mean plasma concentration of cortisol were 0.44 +/- 0.09 mumol/l (normal less than 0.28 mumol/l). Following stimulation by ACTH (1-24) urinary excretion rates of cortisol were stimulated from 0.22 +/- 0.08 to 4.85 +/- 2.78 mumol/24 h. Similarly, plasma concentrations of the glucocorticoid metabolite, tetrahydrocortisone, increased from 23.3 +/- 9.0 to 47.3 +/- 30.2 nmol/l; urinary excretion rates of tetrahydrocortisone increased from 3.61 +/- 0.90 to 8.40 +/- 1.72 mumol/24 h. The relative share of the sulphate, glucuronide and free fractions of tetrahydrocortisone in the patients' urine did not indicate any defect in metabolization of this steroid metabolite. Excretion rates of the four glucocorticoid tetrahydro-metabolites, tetrahydrocortisone, allotetrahydrocortisone, tetrahydrocortisol, and allo-tetrahydrocortisol, expressed as percent of total steroid excretion, were similar in patients with anorexia and in healthy women under basal conditions (24 +/- 6 vs 23 +/- 6%) and during stimulation by ACTH (1-24) (36 +/- 10 vs 45 +/- 6%). The share of the two androgen metabolites, androsterone and etiocholanolone, was 24 +/- 5% of total steroid excretion (basal; healthy women: 27 +/- 8%) and 13 +/- 2% (ACTH stimulation; healthy women: 12 +/- 4%) in patients with anorexia nervosa. Thus, analysis of urinary steroid excretion rates did not indicate a shift in adrenocortical function. The results confirmed enhanced secretion of cortisol in patients with anorexia nervosa under basal conditions and during/following stimulation by ACTH. The ACTH-induced increase in the concentrations of the tetrahydro-glucocorticoid metabolites in urine was less pronounced than that of cortisol.(ABSTRACT TRUNCATED AT 250 WORDS)

Oesophageal and gastric motor activity in patients with bulimia nervosa.

Previous studies showed that symptoms of oesophageal motor disorders can be misinterpreted as indicating anorexia nervosa and that in primary anorexia nervosa gastric motility is frequently impaired. We investigated in 32 women with bulimia nervosa whether symptoms of oesophageal motor disorders could be obscured by or be mistaken as forming part of bulimic behaviour, and whether impaired gastric motility was frequent as well. Oesophageal motility was normal in 18 of 26 patients studied, another four had incomplete lower oesophageal sphincter relaxation. Two patients had vigorous achalasia and each one achalasia and diffuse oesophageal spasm, all of whom experienced two types of vomiting: one self-induced and one involuntary, in which the vomit was non-acidic and tasted as the preceding meal. Gastric emptying of a semisolid meal was studied in all patients except of the eight with oesophageal motor abnormalities. Emptying was significantly slower than in healthy controls and grossly delayed in nine of 24 patients. Antral contraction amplitudes were lower and increased less postcibally than in controls. In conclusion (i) bulimic behaviour can obscure symptoms of oesophageal motor disorders and (ii) gastric emptying is frequently delayed in bulimia nervosa.

Symptoms of achalasia in young women mistaken as indicating primary anorexia nervosa.

The case of a young women with dysphagia, regurgitation, and weight loss, who was diagnosed as having anorexia nervosa but in whom reevaluation showed that achalasia was causing the symptoms, is presented together with related observations. Misinterpretation of esophageal symptoms may occur not only as a consequence of inadequate history taking and of being biased by a patient's emaciation, age, and gender, which leads to view certain aspects of the patient's history and behavior as suggesting a pathologic attitude towards eating and body weight, but also as a consequence of a misinterpretation of the symptoms as indicative of an eating disorder by the patients themselves. In some cases a disordered attitude toward eating and body weight may develop together or coexist with achalasia. The clinical evaluation of patients with symptoms suggestive of anorexia nervosa but also of bulimia nervosa should include the taking of a thorough history regarding swallowing and vomiting in order to recognize a possible esophageal motor disorder.

Upper gastrointestinal endoscopy findings in patients with long-standing bulimia nervosa.

Bulimia nervosa, an eating disorder now recognized with increasing frequency, is receiving growing attention because of purported complications. Recent claims of a high frequency of erosions, ulceration, and bleeding in the esophagus, ascribed to repeated, self-induced vomiting, prompted us to investigate by endoscopy the upper gastrointestinal mucosa in 37 consecutive patients with long-standing bulimia nervosa. The endoscopic appearance of esophageal and gastric mucosa was normal in 23 patients. Signs of mild esophagitis observed in eight patients were not related to the duration or severity of bulimic behavior or to symptoms of gastroesophageal reflux; two of these eight patients had sliding hiatal hernias. The remaining six patients were found to have superficial mucosal erythema in the stomach or duodenum, but none showed actual erosions, ulcers, or bleeding. Our observations suggest that, in contrast to reports by others, mucosal injury consequent to chronic, self-induced vomiting in patients with bulimia nervosa is relatively infrequent and limited.

Lack of association between HLA antigens and anorexia nervosa.

Studies of the human leukocyte antigen (HLA) system were performed in 37 patients with anorexia nervosa to confirm an alleged association with HLA-B16 and haplotype HLA-A26,B38. No correlation between anorexia nervosa and HLA, including HLA-DR, could be found.

Intravenous cisapride accelerates delayed gastric emptying and increases antral contraction amplitude in patients with primary anorexia nervosa.

Delayed gastric emptying is common in primary anorexia nervosa. We investigated in 12 patients whether gastric emptying could be accelerated by the prokinetic drug cisapride. Patients were studied on two occasions 1 wk apart and received, under random double-blind conditions, 8 mg of cisapride and placebo intravenously. Gastric emptying of an isotopically labeled semisolid meal and antral motor activity were measured using a dual-headed gamma-camera for 50 min. Emptying was significantly slower (half-emptying time, 50-191 min; median, 121 min) than in 24 healthy volunteers (half-emptying times, 21-119 min; median, 47 min). Cisapride accelerated emptying significantly (p less than 0.001; half-emptying time after cisapride, 22-80 min; median, 42 min). Antral contraction amplitude increased and contraction frequency decreased significantly (p less than 0.001), whereas the propagation velocity of contractions remained unchanged. We concluded that intravenous cisapride accelerates gastric emptying and increases antral contraction amplitude in patients with anorexia nervosa. Whether or not these effects can prove beneficial in diminishing the patients' symptoms and in helping them to gain weight can only be answered from studies involving long-term treatment with cisapride.

Oesophageal and gastric motility disorders in patients categorised as having primary anorexia nervosa.

UNLABELLED: Gastrointestinal motor function in patients with primary anorexia nervosa has rarely been investigated. We studied oesophageal motor activity in 30 consecutive patients meeting standard diagnostic criteria for primary anorexia nervosa (Feighner et al; DSM III). Seven were found to suffer from achalasia instead of primary anorexia nervosa, one from diffuse oesophageal spasm and one from severe gastro-oesophageal reflux and upper oesophageal sphincter hypertonicity, while partly non-propulsive and repetitive high amplitude, long duration contractions prevailed in the lower oesophagus of another six. In four patients with oesophageal dysmotility not responding to therapy and in 12 of 15 patients with normal oesophageal manometry, gastric emptying of a semisolid meal was studied. Emptying was normal in only three but markedly delayed in 13 cases (half emptying times 97-330 min, median: 147 min, as compared with 21-119 min, median: 47 min, in 24 healthy controls). In eight patients, the effects of domperidone 10 mg iv and placebo were compared under random double blind conditions. Half emptying times were shortened significantly (p less than 0.01) by domperidone. CONCLUSIONS: symptoms of disordered upper gastrointestinal motor activity may be mistaken as indicating primary anorexia nervosa; clinical evaluation of patients with presumed primary anorexia nervosa should rule out the possibility that disordered oesophageal motor activity underlies the symptoms; delayed gastric emptying is a frequent feature in primary anorexia nervosa and might be returned to normal with domperidone.

Ulcerative colitis: a cyclothymic disorder?

While psychogenic aspects in ulcerative colitis have been comprehensively studied, much less attention has been given to sequence and interaction of psychic and somatic factors in psychopathological description. Onset of schizoaffective and cyclothymic symptomatology in 20 ulcerative colitis patients proved to occur only after somatic manifestation. As later on organic and psychic relapse never occurred simultaneously, further discussion should be centered on two points: Does schizoaffective cyclothymic axial syndrome occur separately from ulcerative colitis manifestation? Or is there a common etiological, pathogenic base for both somatic and psychic symptoms?

[Can western medicine resolve psychological problems in ethnic regions outside Europe? 2 cases from the region of Borneo-Sarawak]. / Kann die westliche Medizin psychologische Probleme bei aussereuropäischen Ethnien lösen? 2 Beispiele aus dem Bereich Borneo/Sarawak.

The case histories of two patients healed by animist treatment in the Iban tradition are reviewed by two psychiatrists. Both psychiatrists point to the difficulties in the evaluation of the background of the disease and of the mechanisms of its treatment by people not aware of the cultural and sociological aspects of eastern civilisation. The diagnostic classification of both patients by means of western medicine and the possible treatment of their disease are discussed. The failure of western medicine to understand the psychiatrical aspects of animist religions in the pathogenesis of diseases raises the question whether western medicine will be able to cope with the health problems of Iban (and other animists) sufficiently when their animist tradition will be replaced by western civilisation.