[The history of lithium]. / De geschiedenis van lithium.

Background Lithium is the first choice for maintenance treatment of bipolar disorder. How was discovered that lithium is such an effective treatment for mood episodes? Aim To gain understanding in how lithium obtained its value in the pharmacotherapeutic treatment of bipolar disorder. Method Literature research into the use of lithium in the history of psychiatry. Results In 1949 John Cade discovered the usability of lithium in the treatment of mania. Subsequently, it was discovered that lithium prevents mood episodes in bipolar disorder, can be used in the treatment of unipolar depression as an addition to an antidepressant, and lowers the risk of suicidality. Conclusion Since the nineteenth century lithium is used in psychiatry. Mid twentieth century the therapeutic value of lithium was discovered in the treatment of bipolar disorder and many international guidelines consider lithium as ‘a golden standard’. However, with the arrival of other psychopharmaca lithium is prescribed less in the last decades. It is important to teach psychiatrists and nurse specialists how to use lithium because of its important value in the treatment of bipolar disorder.

How to make online mood-monitoring in bipolar patients a success? A qualitative exploration of requirements.

BACKGROUND: The Life-Chart Method (LCM) is an effective self-management treatment option in bipolar disorder (BD). There is insufficient knowledge about the consumers' needs and desires for an e-monitoring solution. The first step towards a new mood monitoring application is an extended inventory among consumers and professionals. METHODS: The aim of the current study was: to identify opinions about online mood monitoring of patients with BD and professionals and to identify preferences on design, technical features and options facilitating optimal use and implementation of online mood monitoring. This study used a qualitative design with focus-groups. Participants were recruited among patients and care providers. Three focus-groups were held with eight consumers and five professionals. RESULTS: The focus-group meetings reveal a shared consciousness of the importance of using the Life-Chart Method for online mood monitoring. There is a need for personalization, adjustability, a strict privacy concept, an adjustable graphic report, and a link to early intervention strategies in the design. Due to the fact that this is a qualitative study with a relative small number of participants, so it remains unclear whether the results are fully generalizable. We can't rule out a selection bias. CONCLUSIONS: This study demonstrates the importance of involving stakeholders in identifying a smartphone-based mood charting applications' requirements. Personalization, adjustability, privacy, an adjustable graphic report, and a direct link to early intervention strategies are necessary requirements for a successful design. The results of this value specification are included in the follow-up of this project.

[Earlier recognition of bipolar disorder - necessity and advice for clinical practice]. / Tijdige herkenning van bipolaire stoornissen; noodzaak en praktijkadviezen.

BACKGROUND: There is an average 10-year delay in diagnosing bipolar disorder, hampering the application of effective therapeutic interventions.
AIM: To investigate factors contributing to early recognition.
METHOD: We give a stage-oriented overview of the opportunities for early recognition.
RESULTS: Recognition in stage 0 (at-risk) and stage 1 (prodromal) is yet impossible. In stage 2 (syndromal) there are opportunities for better recognition in patients presenting with depression by conducting a thorough (collateral) psychiatric assessment, family history and by applying additional screening tools. CONCLUSIONS There are opportunities for better recognition of bipolar disorder in the syndromal stage.

Abnormal bone turnover in long-standing Crohn's disease in remission.

BACKGROUND: A high prevalence of osteoporosis is found in patients with Crohn's disease. The pathogenesis of this condition seems to be multifactorial and its pathophysiology is still not completely understood. AIM: To elucidate the pathophysiology of osteopenia in quiescent Crohn's disease. METHODS: Bone turnover was studied in 26 patients (13 males and 13 females) with long-standing quiescent Crohn's disease and small bowel involvement. Bone mineral density was assessed by dual energy X-ray absorptiometry. Biochemical markers for bone formation (osteocalcin and bone-specific alkaline phosphatase) and for bone resorption (deoxypyridinoline and collagen type I C-terminal crosslinks) were measured. Urinary calcium excretion was determined. RESULTS: Markers for bone formation were significantly lower in patients than in controls (osteocalcin: P= 0.027, bone-specific alkaline phosphatase: P < 0.001), but both bone resorption markers were not significantly different. Urine calcium excretion was significantly decreased in patients (P=0.002) compared to controls. Bone mineral density of the lumbar spine was significantly and inversely correlated with bone-specific alkaline phosphatase and collagen type I C-terminal crosslinks. CONCLUSIONS: Bone turnover in long-standing Crohn's disease in clinical remission is characterized by suppressed bone formation and normal bone resorption. Urine calcium excretion is decreased. Hence, interventions and therapy should be directed towards the improvement of bone formation.

Bone mineral density in patients with recently diagnosed inflammatory bowel disease.

BACKGROUND & AIMS: A high prevalence of osteoporosis is reported in inflammatory bowel disease (IBD), and its pathogenesis is not completely resolved. We investigated whether bone mineral density (BMD) in patients with IBD at diagnosis is lower than in population controls, and whether BMD differs between patients with Crohn's disease and those with ulcerative colitis. METHODS: In 68 patients and 68 age- and gender-matched population controls, BMD of total body, spine, and hip was assessed using dual-energy x-ray absorptiometry within 6 months after establishing the diagnosis. Determinants for low BMD were assessed. RESULTS: There were no significant differences in BMD (g/cm(2)) between patients and controls, and no significant differences in BMD between patients with either Crohn's disease or ulcerative colitis. Multivariate regression analysis showed that duration of complaints longer than 6 months before diagnosis (P = 0.041), age (P = 0.019), and body mass index less than 20 kg/m(2) (P = 0.006) significantly correlated with low BMD. CONCLUSIONS: BMD in patients with recently diagnosed IBD was not significantly decreased compared with population controls. Subsequent development of osteoporosis in patients with IBD seems to be a phenomenon related to the disease process and/or the treatment modalities of IBD.

Nutrition in Crohn's disease.

Nutrition plays an important role in Crohn's disease. This review provides further insights into the relationship between nutrition and Crohn's disease and focuses on three different aspects: dietary aetiological factors, nutritional status and nutritional therapy in Crohn's disease.

Comprehensive nutritional status in recently diagnosed patients with inflammatory bowel disease compared with population controls.

OBJECTIVE: Malnutrition is observed frequently in patients with inflammatory bowel disease (IBD). Knowledge of the nutritional status in patients with recently diagnosed IBD is limited. The aim of this study was to establish a comprehensive picture of the nutritional status in recently diagnosed IBD patients. SUBJECTS: Sixty-nine IBD patients (23 Crohn's disease (CD) and 46 with ulcerative colitis (UC)) within 6 months of diagnosis and 69 age- and sex-matched population controls were included in the study. METHODS: The nutritional status was assessed by: (1) body composition (anthropometry and dual-energy X-ray absorptiometry); (2) dietary intake (dietary history); (3) biochemical indexes of nutrition; and (4) muscle strength (isokinetic dynamometer). RESULTS: Body weight and body mass index were significantly lower in UC patients compared with controls. The mean daily intake of carbohydrates was significantly higher in CD patients and the intakes of protein, calcium, phosphorus, and riboflavin were significantly lower in UC patients compared with controls, respectively. Serum concentrations of several nutrients (beta-carotene, magnesium, selenium and zinc) were significantly lower in UC patients compared with controls. Serum vitamin B12 concentration was significantly lower in CD patients. Muscle strength did not significantly differ between IBD patients and controls. CONCLUSIONS: This study showed that the nutritional status of IBD patients was already affected negatively at time of diagnosis. It needs to be elucidated whether nutritional supplementation in recently diagnosed IBD patients may improve the clinical course of the disease.

Nutritional supplementation with N-3 fatty acids and antioxidants in patients with Crohn's disease in remission: effects on antioxidant status and fatty acid profile.

In patients with Crohn's disease (CD), malnutrition is frequently observed and is generally accepted to be an important issue. The aim of this study was to investigate the effects of 3 months of supplementation with a liquid formula containing either antioxidants (AO) or n-3 fatty acids plus AO on the antioxidant status and fatty acid profile of plasma phospholipids and adipose tissue, respectively, in patients with long-standing CD currently in remission. In a randomized, double-blind placebo-controlled study, CD patients received either placebo, AO, or n-3 fatty acids plus AO for 3 months in addition to their regular diet. In all, 25/37 CD patients completed the study. AO status was assessed by blood biochemical parameters. A statistical per-protocol analysis was performed. Serum concentrations of selenium, vitamin C, and vitamin E, the activity of superoxide dismutase and total antioxidant status were significantly (p < 0.05) increased after AO supplementation. Furthermore, compared with controls, serum concentrations of beta-carotene, selenium, and vitamin C and the activity of glutathione peroxidase (GPx) were significantly (p < 0.05) lower before supplementation; however, after AO supplementation these levels were not significantly different from controls (except for GPx). N-3 fatty acids plus AO supplementation significantly (p < 0.05) decreased the proportion of arachidonic acid, and increased the proportion of eicosapentanoic acid and docosahexanoic acid in both plasma phospholipids and adipose tissue. Supplementation with antioxidants improved antioxidant status in patients with CD in remission. In addition, supplementation with n-3 fatty acids plus antioxidants significantly changed the eicosanoid precursor profile, which may lead to the production of eicosanoids with attenuated proinflammatory activity. This study indicates that an immunomodulating formula containing n-3 fatty acids and/or AO may have the potential to play a role in the treatment of CD.

Diet as a risk factor for the development of ulcerative colitis.

OBJECTIVE: Dietary factors have been considered as a possible risk factor for ulcerative colitis (UC). However, available data are inconsistent. The aim of the present study was to evaluate the etiological role of dietary factors in the development of UC. METHODS: Recently diagnosed (<6 Months) UC patients (n = 43) and age- and gender-matched population controls (n = 43) were studied in a case-control design. The crosscheck dietary history method was used to assess dietary intake of 5 yr before the study. Adipose tissue fatty acid composition was used as a biomarker of long-term fat intake. Conditional logistic regression-derived odds ratios (OR), and 95% confidence intervals (CI) were used for statistical analysis. Dietary intake ORs were adjusted for energy intake. RESULTS: High intakes of monounsaturated fat (OR: 33.9 [95% CI 2.6-443.1]), polyunsaturated fat (OR: 5.1 [95% CI 1.0-26.7]), and vitamin B6 (OR: 6.9 [95% CI 1.6-30.7]) were associated with an increased risk to develop UC. No other significant associations were found with UC risk. CONCLUSIONS: High intakes of mono- and polyunsaturated fat and vitamin B6 may enhance the risk of developing UC. Whether this observation is a true risk factor in the development of UC or rather a reflection of a certain dietary lifestyle needs to be investigated.

The relation between antioxidant status and alterations in fatty acid profile in patients with Crohn disease and controls.

BACKGROUND: A diminished antioxidant defence and alterations in the fatty acid profile may play a role in the pathophysiology of inflammation in Crohn disease (CD). METHODS: Antioxidant status (serum antioxidant vitamins and minerals, glutathione peroxidase, and superoxide dismutase activity), disease activity, dietary intake, and the fatty acid profile in plasma and erythrocyte phospholipids were studied in patients with active CD (n = 12), inactive CD (n = 50), and controls (n = 70). Eight patients with active CD were re-evaluated during the subsequent phase of clinical remission. The relation between the variables was assessed by multiple linear regression. RESULTS: We observed a significantly diminished antioxidant status in patients with active CD compared with inactive CD and controls. Furthermore, the antioxidant defence was depleted in patients with inactive CD compared with controls. An aberrant fatty acid profile in plasma phospholipids was found in active and inactive CD compared with controls. Multivariate analysis showed that the plasma phospholipid fatty acid indices were significantly associated with several antioxidants (beta-carotene, vitamin E, and glutathione peroxidase) in CD patients but not in controls. CONCLUSION: The fatty acid profile in CD patients is significantly associated with disease activity and serum antioxidant concentrations. This observation, along with the diminished antioxidant defence in patients with active and inactive CD, indicates that antioxidants should be considered in the therapy of inflammation in CD.

Nutrition and inflammatory bowel disease: an update.

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic inflammatory process, the aetiology of which remains unknown. Nutrition may play an important role in the pathogenesis and treatment of IBD. The evidence regarding the role of specific dietary components in the pathogenesis of IBD is still inconclusive. Many studies have been subject to methodological limitations; studies of better design are necessary to confirm the hypothesis that nutritional factors may indeed play a role in the development of IBD. Several studies have reported nutritional and functional deficiencies in IBD patients, especially in Crohn's disease. It is, however, hard to discriminate between disease-induced and malnutrition-induced changes in nutritional parameters. Maintaining adequate nutritional status has been suggested to be beneficial to the course of the disease in IBD. Studies have provided further insight into the possible beneficial effects of nutritional supplementation as primary and adjunctive therapy in IBD. The effects of specific nutritional therapy may be caused by alterations in intestinal flora and hence in the production of intraluminal proinflammatory substances. Immunonutrients such as n-3 fatty acids and antioxidants may also play a role in the treatment of IBD. In this paper, the relation between nutritional aetiological factors, nutritional status and nutritional therapy is discussed in detail.

Gender specific alterations of body composition in patients with inflammatory bowel disease compared with controls.

OBJECTIVE: To assess body hydration and the distribution of the body water compartments in defined populations of patients with inflammatory bowel disease (IBD) compared with those of matched healthy controls. SUBJECTS: Fifty-two patients with IBD at time of diagnosis (20 patients with Crohn's disease (CD-new) and 32 patients with ulcerative colitis (UC-new)), 40 patients with long-standing CD (CD-long) and 2 matched healthy control groups (n = 52 and n = 40) were recruited for the study. METHODS: Total body water (TBW) and extracellular water (ECW) were measured by deuterium oxide and bromide dilution, respectively. Intracellular water (ICW) was calculated as TBW-ECW. In addition, hydration of fat-free mass (FFM) and the ECW:ICW ratio were calculated. FFM, body fat (BF) and % body fat (%BF) were assessed by dual energy X-ray absorptiometry. RESULTS: In female IBD patients, the ECW:ICW ratio was significantly (P < 0.05) higher than in controls (CD-new: 0.89+/-0.11 vs 0.79+/-0.08, P < 0.01; UC-new: 0.85+/-0.15 vs 0.77+/-0.10, P < 0.05; CD-long: 0.86+/-0.14 vs 0.80+/-0.10, P < 0.05). In these female patients, the ICW:FFM ratio was significantly (P < 0.05) lower than in controls. Fluid shifts were especially pronounced in female patients with recently diagnosed CD. In male patients with recently diagnosed UC and in those with long-standing CD, body weight, body mass index, BF and %BF were significantly (P < 0.05) lower than in controls. No differences in body hydration or body water distribution were observed between male patients and controls. CONCLUSIONS: An altered body water distribution and body hydration was observed in female IBD patients, especially in female patients with recently diagnosed CD.

The sensitivity of the lactulose/rhamnose gut permeability test.

BACKGROUND: The lactulose/rhamnose (L/R) intestinal permeability test is widely used. However, different quantities and proportions of lactulose and rhamnose are used. The aim of this study was to determine whether a low dosage of lactulose is able to discriminate between normal and increased permeability. MATERIALS AND METHODS: Two groups of 10 healthy subjects were studied. In group 1, three different iso-osmolar test solutions were administered on 3 days. The solutions consisted of 10 g of L with 1 g of R, 5 g of L with 0.5 g of R and 1 g of L with 0.1 g of R in 65 mL of water. Group 2 ingested these solutions 1 h after ingestion of 750 mg of chenodeoxycholeic acid (CDCA), which is known to increase permeability. The urinary L/R ratio was determined using high-performance liquid chromatography. Data are presented as medians (range). RESULTS: In group 1, no differences were observed between the three solutions. In Group 2, there was a significant difference (P = 0.045) between the three solutions. The L/R ratios were 0.0079 (0.0024-0.0152) (1L to 0.1R), 0.0138 (0.0066-0.0192) (5L to 0.5R) and 0.0144 (0.0074-0.0374) (10L to 1R). The L/R ratio differed significantly between Groups 1 and 2 (P < 0.001) using the 5L to 0.5R and 10L to 1R solutions respectively. CONCLUSION: If the permeability is increased, the urinary L/R ratio depends on the quantity of lactulose and rhamnose administered in equal proportion. 5L to 0.5R is sufficient to discriminate between a normal and a moderately increased permeability.

Fat intake and fatty acid profile in plasma phospholipids and adipose tissue in patients with Crohn's disease, compared with controls.

OBJECTIVES: Fatty acid metabolism is involved in the immune response and inflammation processes in patients with Crohn's disease (CD). Fatty acid changes may be relevant to the clinical course of the disease. The aim of this study was to compare the qualitative and quantitative fat intake and fatty acid composition of plasma phospholipids and adipose tissue in a defined population of CD patients with those in matched controls. METHODS: Dietary fat intake and fatty acid profile of plasma phospholipids and adipose tissue were assessed in two patient populations: 20 patients with recently diagnosed CD and 32 patients with longstanding (> 10 yr) CD clinically in remission, matched for age and gender with healthy controls. RESULTS: We observed no significant differences in quantitative or qualitative fat intake between CD patients and controls. Percentages of linoleic acid and alpha-linolenic acid in plasma phospholipids or adipose tissue were not significantly different between patients and controls. However, we observed a significantly (p < 0.05) lower percentage of the sum of the n-3 fatty acids, with significantly (p < 0.01) higher levels of clupanodonic acid (22:5n-3) and significantly (p < 0.05) lower levels of docosahexaenoic (22:6n-3) and arachidonic acid (20:4n-6). The aberrant fatty acid profile was more evident in patients with longstanding CD than in patients with recently diagnosed CD. CONCLUSION: The aberrant fatty acid profile found in these CD patients is a result of altered metabolism rather than of essential fatty acid malabsorption. The reported findings may be important in the pathophysiology of CD and hence in the choice of fatty acids to be used when therapeutic supplementation is considered in CD patients.

Comprehensive nutritional status in patients with long-standing Crohn disease currently in remission.

Malnutrition is observed frequently and is an important complication in patients with Crohn disease (CD). The pathophysiology of malnutrition in this disorder is complex. To obtain a comprehensive picture of nutritional status in patients with long-standing CD that was clinically in remission, we assessed four measures of nutritional status in 32 patients (18 women and 14 men) and 32 matched healthy control subjects: 1) body composition, 2) dietary intake, 3) biochemical indexes of nutrition, and 4) and muscle strength (as a functional index). Mean daily intakes of fiber and phosphorus were significantly lower in CD patients than in control subjects. Serum concentrations of several nutrients (beta-carotene, vitamin C, vitamin E, selenium, and zinc) and activity of the enzyme glutathione peroxidase were also significantly lower in CD patients, as were antioxidant status and serum concentrations of magnesium and vitamin D. Percentage body fat and hamstring muscle strength were significantly lower in male CD patients than in control subjects, whereas muscle strength of the quadriceps was preserved. In conclusion, this study showed a variety of nutritional and functional deficiencies in patients with long-standing CD in remission, especially in male patients with a high lifetime prednisone dose. A comprehensive nutritional assessment seems superior to the assessment of a single dimension of nutritional status.

Initial and chronic gastric acid inhibition by lansoprazole and omeprazole in relation to meal administration.

In a placebo-controlled, double-blind, multiple crossover study, the initial and chronic acid-inhibitory effect of lansoprazole 30 mg, orally administered half an hour before breakfast or immediately after breakfast, and of omeprazole 20 mg, administered postprandially, respectively, was investigated in 16 healthy volunteers, using ambulant 24-hr intragastric pH monitoring. On the first day of medication, only preprandially administered lansoprazole reduced acid secretion significantly (median 24-hr pH 3.0; P < 0.05). On day 15, the median 24-hr intragastric pH of lansoprazole preprandial (pH 4.1), lansoprazole postprandial (pH 4.3), and omeprazole postprandial (pH 3.3), respectively, differed significantly (P < 0.05) from placebo (pH 1.2). It is concluded that the interaction between food intake and lansoprazole administration only is important at the start of oral therapy. Lansoprazole taken before breakfast is effective even on the initial day of treatment.

Fatness in relation to substrate oxidation during exercise.

The aim of this study was to test the hypothesis that differences in fuel utilisation during exercise, determined by muscle fibre-type profile, are an aetiological factor for obesity as proposed by Wade et al. (Lancet 1990, 335, 805-8). An investigation was carried out of relationships between body fatness (assessed by skinfolds, densitometry and dual X-ray absorptiometry) and fuel utilisation represented by the respiratory exchange ratio (RER, assessed by indirect calorimetry) during three cycle ergometer exercises. Exercise 1 was an exact replication of the Wade protocol (fixed 100 Watt load and unstandardised with respect to antecedent diet and activity). Exercises 2 (fasted) and 3 (fed) were highly standardised and adjusted to represent the same relative workload for each subject (45% VO2max). The subjects were 37 randomly-selected untrained men. None of the exercises yielded significant correlations between fatness and RER. The results refute the initial hypothesis linking substrate oxidation and body fatness. Inspection of the body composition data for Wade's subjects reveals that they were abnormally lean. This suggests that their findings may have been confounded by coincident correlations between fitness and fatness, and may not represent a true causal relationship.