Severe Gastrointestinal Symptoms Research Articles

Gastointestinal-Specific Patient-Reported Outcome Instruments Differentiate Between Renal Transplant Patients With or Without GI Complications

Background Gastrointestinal (GI) complications are frequently reported postrenal transplant and are often associated with immunosuppressant regimens including mycophenolate mofetil (MMF). This study evaluated the ability of two GI-specific patient-reported outcome (PRO) instruments to differentiate between patients with and without GI complaints. Methods Discriminant validity of the Gastrointestinal Symptom Rating Scale (GSRS) and Gastrointestinal Quality of Life Index (GIQLI), as well as two generic instruments (Psychological General Well-Being Index (PGWB) and EQ-5D, was assessed in a multinational study of renal transplant recipients. Patients received therapy that included a calcineurin inhibitor and MMF. Both t-tests and ANOVAs were used to examine differences between patients with and without GI complaints, among levels of severity, and between patients reporting presence/absence of specific GI side effects. Results Of 96 patients recruited (56% male), 43% had none, 39% mild, 13% moderate, and 6% severe GI symptoms. All GSRS subscales and the GIQLI total and four of the five subscale scores significantly differentiated between patients with/without GI complications ( P < .05). The PGWB total score and three subscales, the EQ-5D significantly differentiated between the two groups ( P < .05). Only GI-specific instruments discriminated between some severity levels; for example, the GSRS abdominal pain subscale discriminated between patients at all levels of severity ( P < .05). The GIQLI total score and symptoms subscale differentiated between patients with no symptoms and those with mild or moderate or severe symptoms ( P < .05). Conclusions The GSRS and GIQLI differentiated between patients with/without GI side effects and by symptom severity better than did generic instruments, demonstrating excellent discriminant ability in this population.

GI-SPECIFIC PATIENT-REPORTED OUTCOME INSTRUMENTS DIFFERENTIATE BETWEEN RENAL TRANSPLANT PATIENTS WITH OR WITHOUT GI COMPLICATIONS

P872 Background: Gastrointestinal (GI) complications such as diarrhea, vomiting and dyspepsia associated with immunosuppressant use are frequently reported by patients post-renal transplant. Mycophenolic acid (MPA) has been associated with an increased incidence of GI side effects. Studies also show that GI complications can lead to MPA dose reduction/discontinuation and may affect patient Quality of Life (QoL). The purpose of this study was to assess the discriminant validity of 2 GI-specific and 2 generic patient-reported outcome (PRO) instruments for use in future research on the effect of immunosuppressive regimens. Methods: By cross-sectional study design, the discriminant validity of the Gastrointestinal Symptom Rating Scale (GSRS) and Gastrointestinal Quality of Life Index (GIQLI) was assessed in renal transplant recipients (with or without GI complications) recruited from 5 clinical centers in 4 countries. Patients were required to be receiving therapy which included a calcineurin inhibitor and mycophenolate mofetil. Patients completed the GSRS and GIQLI and two generic instruments, the Psychological General Well-Being Index (PGWB) and EQ-5D. t-tests and ANOVAs were used to examine differences between patients with and without GI complaints, among differing levels of severity, and between patients reporting presence/absence of specific GI side effects. Results: Of 96 patients recruited (mean age: 47.4 ± 12.3 years; male: 56%; mean duration since transplant: 3.6 ± 3.6 years), 41 (42%) had none, 35 (39%) mild, 12 (13%) moderate, and 6 (6%) severe GI symptoms (clinician ratings). Patients with GI complaints had worse scores on all questionnaires than those without GI complaints. All 5 GSRS subscales and the GIQLI total and 5 subscale scores significantly differentiated between patients with and without GI complications (p<0.05). The PGWB total score, self-control, general health, and vitality subscales and the EQ-5D significantly differentiated between the two patient groups (p<0.05). Generic instruments were unable to discriminate between severity level, while disease specific instruments were able to discriminate among some levels, e.g., GSRS abdominal pain subscale discriminated between patients at all levels of severity (p<0.05). Other GSRS subscales discriminated between some but not all severity levels. The GIQLI symptoms subscale was the best discriminator, as it differentiated between patients with no symptoms and those with mild or moderate or severe symptoms–although it did not discriminate among severity levels. The GSRS diarrhea subscale was able to significantly discriminate between patients who reported diarrhea as a side effect and those who did not (p<0.0001). Conclusions: The GSRS and GIQLI differentiated between patients with/without GI side-effects and by symptom severity better than generic instruments, demonstrating excellent discriminant ability in the renal transplant population. They can be used for further research to investigate effects on QoL caused by GI complications due to immunosuppressant therapies.

P0411 USING RADIOLIGAND BINDING ASSAYS TO MEASURE TISSUE TRANSGLUTAMINASE ANTIBODIES IN YOUNG CHILDREN

Introduction: Celiac disease (CD) is a chronic small bowel disease affecting 1% of children in Sweden (1). The clinical presentation may range from severe gastrointestinal symptoms to asymptomatic variants defined as silent CD. In this prospective screening two methods were used for identifying young children with potential CD: Immunoglobulin (Ig) A antibodies against endomysium (EMA) together with total-IgA and the combination of IgA and IgG antibodies against tissue transglutaminase (tTG). The aim was to determine if IgA-tTG and IgG-tTG analysed with radioligand binding assays (RBA) can be used as an alternative method to conventional EMA and total-IgA in screening of children for silent CD. Methods: Blood samples were obtained from 652 normal children (320 girls, 332 boys) aged 2.9 (2.5–4.2) years without previously known CD. Sera were analysed for EMA by indirect immunofluorescence and for total IgA with a nephelometric assay. The RBA method measured IgA-tTG and IgG-tTG. A second blood sample was obtained from antibody positive children. Children with persistently high antibody levels were offered intestinal biopsy. Results: In total, 3.2% (95% CI=1.9–4.6%) (21/652) children were positive for at least one antibody at baseline: 2.5% (95% CI=1.3–3.7%) (16/652) for IgA-tTG, 1.7% (95% CI=0.7–2.7%) (11/652) for IgG-tTG and 2.9% (95% CI=1.6–4.2%) (19/652) for EMA, respectively. Ten children were positive for all three antibodies, 5 for both IgA-tTG and EMA, 4 for EMA only, 1 for IgA-tTG and 1 child with IgA deficiency for IgG-tTG. A second blood sample were taken after 1.2 (0.2–1.9) years from all but one child with antibodies at baseline. Seven of 20 children remained positive for all three antibodies, 3 for IgA-tTG only, 1 for both IgA-tTG and EMA, 1 for IgA-tTG and IgG-tTG and 1 child refused further participation. Three biopsies showed villous atrophy, 2 increased intraepithelial lymphocytes and 2 normal findings. Biopsy was not performed in 4 children with low or declining tTG antibody levels at follow-up and in 1 child who declined. CD was evident in 0.5% (95% CI=0.0–1.0%) (3/652). Conclusion: A high number of young children were found to be positive for both tTG antibodies, as well as EMA, in this prospective screening for CD. The majority showed declining levels in antibodies over time and children with transient seropositivity were detected. RBA could be used as an alternative method for quantitative measurement of IgA-tTG and IgG-tTG when change in antibody levels is studied in children.

Alexithymia and Psychopathology in Patients with Psychiatric and Functional Gastrointestinal Disorders

Background: Alexithymia and psychopathology may influence the way individuals experience psychological distress and somatic symptoms. This study evaluated patients referred to psychiatric and gastroenterologic outpatient settings in order to investigate the levels of alexithymia and psychopathology, and the possible role of alexithymia in symptom perception and health care utilization. The association between psychiatric disorders and functional gastrointestinal disorders (FGIDs) was also assessed. Methods: Psychopathology (by the Revised 90-item Symptom Checklist), alexithymia (by the 20-item Toronto Alexithymia Scale), and gastrointestinal symptoms (by the Gastrointestinal Symptom Rating Scale) were evaluated in 52 psychiatric outpatients and 58 medical outpatients with FGIDs. Two comorbid subgroups of 25 psychiatric patients with FGIDs and 38 FGID patients with psychiatric disorders were formed and compared. Results: Forty-eight percent of the psychiatric patients had associated FGIDs, and 65.5% of the FGID patients had associated psychiatric disorders. The FGID patients had significantly less psychopathology, but significantly higher alexithymia and more severe gastrointestinal symptoms, than the psychiatric patients. In the comparison of the two subgroups with comorbidity, FGID patients with psychiatric disorders were still more alexithymic and had less psychopathology than psychiatric patients with FGIDs, but gastrointestinal symptoms were not significantly different. Conclusion: Patients with ‘functional’ gastrointestinal symptoms attending a medical care service are likely to be highly alexithymic, whereas those attending a psychiatric care service are likely to show severe psychopathology. Alexithymia seems to influence the presentation of ‘functional’ somatic symptoms and the type of health care utilization.

Efficacy and Tolerability of Pantoprazole Compared with Misoprostol for the Prevention of NSAID-Related Gastrointestinal Lesions and Symptoms in Rheumatic Patients

Aim: To compare the efficacy and tolerability of pantoprazole 20 mg once daily (o.d.) with misoprostol 200 µg twice daily (b.i.d.), administered for 6 months to rheumatic patients who required long-term therapy with nonsteroidal anti-inflammatory drugs (NSAIDs) and who were at increased risk of developing gastrointestinal lesions. Methods: This randomized, double-blind, multicenter, parallel group comparison study was performed with rheumatic patients (n = 515) who were likely to take NSAIDs continuously for at least 6 months. Patients were 55 years or older, at risk to develop gastrointestinal lesions, had less than five erosions/petechiae in the stomach and duodenum, no ulcers, no reflux esophagitis (endoscopy-proven), and gastrointestinal symptoms of at most moderate intensity. A minimum daily dose was defined for NSAIDs (COX-2 inhibitors were not available at the time). Patients were randomized to take either pantoprazole 20 mg o.d. (n = 257) or misoprostol 200 µg b.i.d. (n = 258) for 6 months while continuing NSAID therapy. Endoscopy was performed at baseline, 3, and 6 months. Results: Pantoprazole was superior to misoprostol (p < 0.001) with regard to ‘therapeutic failure’ (occurrence of a peptic ulcer, ten or more erosions/petechiae in the stomach/duodenum, reflux esophagitis, severe gastrointestinal symptoms, and/or ‘likely’ or ‘definitely’ related adverse event leading to study termination). Estimated remission rates at 3 and 6 months (Kaplan-Meier life-table analysis) were, respectively, 93 and 89% (pantoprazole) and 79 and 70% (misoprostol). Pantoprazole was superior to misoprostol (p = 0.005) with regard to ‘endoscopic failure’ (occurrence of a peptic ulcer, ten or more erosions/petechiae in the stomach/duodenum, or reflux esophagitis) after 6 months. Estimated remission rates at 3 and 6 months were, respectively, 98 and 95% (pantoprazole) and 95 and 86% (misoprostol). Patients discontinuing the study early due to adverse events ‘likely’ or ‘definitely’ related to the study drug accounted for 13/257 (5%) in the pantoprazole and 33/258 (13%) in the misoprostol treatment groups. Conclusion: Pantoprazole 20 mg o.d. is superior to misoprostol 200 µg b.i.d. in the prevention of NSAID-induced gastrointestinal lesions and symptoms in patients on continuous long-term treatment with NSAIDs due to rheumatic diseases and at risk to develop such lesions or symptoms.

Probiotics

The colonic flora is thought to play a key role in human health. Gut bacteria produce desirable as well as undesirable metabolites from fermentation and sometimes they may act as pathogens. Composition as well as activities of the gut bacteria can be influenced by nutrition. Prebiotics are food ingredients that selectively stimulate the growth of colonic bacteria regarded as beneficial, i. e. bifidobacteria and lactobacilli. Fructose polymers (fructo-oligosaccharides, inulin), galacto-oligosaccharides and soya oligosaccharides were shown to exert prebiotic activities. In adults, the growth of bifidobacteria was stimulated especially by inulin and fructo-oligosaccharides. Infant formulas containing galacto-oligosaccharides and inulin promoted the growth of bifidobacteria in faeces of bottle-fed infants and resulted in stool characteristics similar to those found in breast-fed infants. However, at present there is only limited knowledge on the long-term health consequences of increased counts of bifidobacteria. In adults, prebiotics can enhance the absorption of calcium from the colon. They can increase stool frequency and are mildly laxative. Prebiotic consumption is usually accompanied by mild flatulence and in sensitive persons by more severe gastrointestinal symptoms. In contrast to the results of animal experiments, a significant lipid-lowering action of fructo-oligosaccharides has not been found in humans. In animals, fructo-oligosaccharides have shown a favourable effect on experimental carcinogenesis. Whether or not these findings may apply to humans will be subject of future studies.

Traitement de la polyarthrite rhumatoïde par une dose hebdomadaire de leflunomide. Étude ouverte comparative

Aims. To assess the therapeutic effect of leflunomide in weekly dose of 100 mg in patients with refractory rheumatoid arthritis. Methods. Sixteen patients were included (18-72 years, disease duration 2-32 years). Eight patients received a weekly dose of 100 mg of leflunomide and 8 the conventional dose. Current treatment was not modified. All patients underwent a monthly evaluation for one year, applying the 1995 ACR preliminary definition of improvement in rheumatoid arthritis. Results. After 2 months, the group treated with the conventional leflunomide dose evidenced a remarkable improvement (7/8 patients achieving ACR 20), while the group receiving the weekly dose, the improvement was not as clearly evident (3/8 patients achieving ACR 20). By the fourth to sixth month, the response was comparable on both groups (6/6 and 6/8 patients achieving ACR 50 in the daily and weekly dose, respectively) and prevailed through the end of the study. There were no statistical differences between groups at any evaluation. Side effects made itself clear in 6 patients in the daily leflunomide group, and 2 patients withdrawn leflunomide because severe gastrointestinal symptoms and hepatotoxicity, respectively. In the group of weekly leflunomide 2 patients presented side effects which disappeared spontaneously. Conclusion. The use of leflunomide in a weekly dose of 100 mg proved to have similar therapeutic benefit as that of the conventional scheme and might represent a new option for the treatment of refractory rheumatoid arthritis patients.

Weekly dose of leflunomide for the treatment of refractory rheumatoid arthritis: an open pilot comparative study

Aims. To assess the therapeutic effect of leflunomide in weekly dose of 100 mg in patients with refractory rheumatoid arthritis. Material and Methods. Sixteen patients were included (18-72 years, disease duration 2-32 years). Eight patients received a weekly dose of 100 mg of leflunomide and 8 the conventional dose. Current treatment was not modified. All patients underwent a monthly evaluation for one year, applying the 1995 ACR preliminary definition of improvement in rheumatoid arthritis. Results. After 2 months, the group treated with the conventional leflunomide dose evidenced a remarkable improvement (7/8 patients achieving ACR 20), while the group receiving the weekly dose, the improvement was not as clearly evident (3/8 patients achieving ACR 20). By the fourth to sixth month, the response was comparable on both groups (6/6 and 6/8 patients achieving ACR 50 in the daily and weekly dose, respectively) and prevailed through the end of the study. There were no statistical differences between groups at any evaluation. Side effects made itself clear in 6 patients in the daily leflunomide group, and 2 patients withdrawn leflunomide because severe gastrointestinal symptoms and hepatotoxicity, respectively. In the group of weekly leflunomide 2 patients presented side effects which disappeared spontaneously. Conclusion. The use of leflunomide in a weekly dose of 100 mg proved to have similar therapeutic benefit as that of the conventional scheme and might represent a new option for the treatment of refractory rheumatoid arthritis patients.

Lymphonodular hyperplasia on the mucosa of the lower gastrointestinal tract in children: an indication of enhanced immune response?

To discover the prevalence and significance of lymphonodular hyperplasia (LNH) of the lower gastrointestinal tract, the authors did a retrospective analysis of a consecutive series of children using colonoscopy to evaluate persistent and severe gastrointestinal symptoms. The authors also sought to discover in more detail how often subjects with LNH of the terminal ileum (TI) or colon show an association with food allergy (FA). The analysis included a consecutive series of 140 children evaluated at the Oulu University Hospital using colonoscopy, which extended to the TI in 74 of these children. A total of 102 patients underwent gastroduodenoscopy. The disease category was assessed using endoscopic, histopathologic, and clinical information. To diagnose FA, a masked or an open food challenge was administered to all patients who aroused any suspicion of food-related exacerbation of symptoms. Of 140 patients, LNH of the colon was diagnosed in 46 subjects, 9 of 38 patients had colitis, 1 of 8 patients had Crohn disease, and 36 of the remaining 94 subjects did not have colitis. Twelve patients of the 22 with LNH of the colon (55%) showed concomitant LNH on the bulb of the duodenum. Lymphonodular hyperplasia of the TI was diagnosed in 53 of the 74 subjects in whom TI could be visualized. It was seen in most patients without colitis (80%), in one half the subjects with colitis (48%), and in one quarter of those with Crohn disease (25%). Among the whole study group 37 (26%) could be defined as having FA. It was more prevalent in patients with (52%) than in those without (13%) LNH of the colon ( P < 0.001). The presence of LNH in the TI also showed some association with FA ( P < 0.05), but less than did LNH of the colon. We consider LNH on the mucosa of the colon or TI common but not an innocent bystander. Significantly related to a diagnosis of gastrointestinal FA in this study, it is an expression of mucosal immune response. If detected on the colon, FA should be considered, whereas if present in TI, it may be related to FA but also to a variety of other immunologically active disease states.

Lymphonodular Hyperplasia on the Mucosa of the Lower Gastrointestinal Tract in Children: An Indication of Enhanced Immune Response?

ABSTRACTBackgroundTo discover the prevalence and significance of lymphonodular hyperplasia (LNH) of the lower gastrointestinal tract, the authors did a retrospective analysis of a consecutive series of children using colonoscopy to evaluate persistent and severe gastrointestinal symptoms. The authors also sought to discover in more detail how often subjects with LNH of the terminal ileum (TI) or colon show an association with food allergy (FA).MethodsThe analysis included a consecutive series of 140 children evaluated at the Oulu University Hospital using colonoscopy, which extended to the TI in 74 of these children. A total of 102 patients underwent gastroduodenoscopy. The disease category was assessed using endoscopic, histopathologic, and clinical information. To diagnose FA, a masked or an open food challenge was administered to all patients who aroused any suspicion of food‐related exacerbation of symptoms.ResultsOf 140 patients, LNH of the colon was diagnosed in 46 subjects, 9 of 38 patients had colitis, 1 of 8 patients had Crohn disease, and 36 of the remaining 94 subjects did not have colitis. Twelve patients of the 22 with LNH of the colon (55%) showed concomitant LNH on the bulb of the duodenum. Lymphonodular hyperplasia of the TI was diagnosed in 53 of the 74 subjects in whom TI could be visualized. It was seen in most patients without colitis (80%), in one half the subjects with colitis (48%), and in one quarter of those with Crohn disease (25%). Among the whole study group 37 (26%) could be defined as having FA. It was more prevalent in patients with (52%) than in those without (13%) LNH of the colon (P &lt; 0.001). The presence of LNH in the TI also showed some association with FA (P &lt; 0.05), but less than did LNH of the colon.ConclusionWe consider LNH on the mucosa of the colon or TI common but not an innocent bystander. Significantly related to a diagnosis of gastrointestinal FA in this study, it is an expression of mucosal immune response. If detected on the colon, FA should be considered, whereas if present in TI, it may be related to FA but also to a variety of other immunologically active disease states.

Long term follow-up of combined radiochemotherapy for locally advanced bladder carcinoma

The 5- and 10-year survival rates and the toxicity of combined radiochemotherapy for 53 consecutive patients with locally advanced bladder carcinoma were studied in a noncomparative trial. Between November 1986 and October 1987, 53 consecutive patients (mean age, 68 years) with muscle invasive and/or locally advanced bladder carcinoma were treated by simultaneous chemotherapy and hyperfractionated irradiation. Radiation was administered during the first to fourth week and during the ninth to tenth week as an interrupted treatment protocol. Cisplatin and epirubicin were used as radiosensitizers before radiation. The maximum dose of irradiation was 57.6 grays. Of 53 patients, 45 completed the planned treatment course. Causes for discontinuing therapy in 8 patients were pronounced myelosuppression (n = 2), severe gastrointestinal symptoms (n = 2), nephrotoxicity (n = 1), and severe radioproctitis (n = 1). Two additional patients stopped therapy due to vascular diseases independent of treatment-related toxicity. The overall survival for all 53 patients was 23% after 5 years and 8% after 10 years. Cause specific survival was 36% after 5 years and 29% after 10 years. Four patients are still alive after 10 years without disease progression. One of them received incomplete therapy due to toxicity. All four patients underwent transurethral resections for superficial, local tumor recurrences. The poor prognosis group of patients with invasive and/or locally advanced bladder carcinoma was found to have a limited disease specific survival after combined radiochemotherapy.

Inflammatory bowel disease.

Inflammatory bowel disease.

Severe gastrointestinal symptoms due to lead poisoning from indian traditional medicine

Severe gastrointestinal symptoms due to lead poisoning from indian traditional medicine

Do changes in gastrointestinal (GI) symptom patterns over time reflect changes in psychological distress levels in community subjects with functional abdominal pain?

Background:Functionai GI symptoms are reported to generally persist over time but little else is known about the natural history of these symptoms, including what factors influence GI symptom patterns over time. We hypothesised that changes in GI symptoms over a 12 month period will reflect changes in psychological distress levels amongst community subjects with functional abdominal pain. Methods: A random sample of subjects aged 18 years and over who reported having functional abdominal pain for greater than one month in a previous random population survey (n=360) were included in this study. Subjects were followed up prospectively via a questionnaire every four months over a 12 month period. The questionnaire asked about the presence of moderate to severe GI symptoms (abdominal and bowel symptoms) over the past week and psychological distress over the past 3 weeks (% abnormal psychological distress indicated by a cut off score of ~ 2 out of 12 on the GHQ-12). Response rates for each follow-up were 80%, 67% and 58%, respectively. Results: GI symptoms and psychological distress were common in this population and remained relatively stable over time (Table I). There was a modest significant correlation between changes in GI symptoms and changes in psychological distress between the 8 and 12 month follow-ups (correlation co-efficient 0.23, p<0.05), but not between the 4 and 8 month follow-ups. Conclusions: Psychological distress may playa modest role in influencing GI symptoms in subjects with functional abdominal pain over time, but other unknown factors are probably more important. o 029(+/.2.08) 1.03 (+I. 381) 6,31 (+1· 6,25) 0.35 (+/.1.85) 267(+1= 6.35) NSAID Users (N=6130) Controls (N=6130)

A Campylobacter Colifoodborne Outbreak in Belgium

In May 1995, the Scientific Institute of Public Health was informed of an outbreak of gastrointestinal illness in a congregational school in the Brussels area. The field investigation identified 24 cases with mild to severe gastrointestinal and general symptoms of acute bacterial enterocolitis. Campylobacter coli was detected in the stools of 5 patients. A retrospective cohort study suggested that a mixed salad (containing ham and feta cheese) was the probable source of infection, but the route of contamination remained unknown. The rapid investigation of such episodes of collective foodbome infections is essential for the implementation of adequate control measures.

Improved Gastrointestinal Tolerance and Patient Preference of Enteric-Coated Sulfasalazine Versus Uncoated Sulfasalazine Tablets in Patients with Rheumatoid Arthritis

Off-label use of uncoated sulfasalazine tablets (TAB) by rheumatoid arthritis (RA) patients in the United States has resulted in poor gastrointestinal (GI) tolerance and compliance. Two studies have shown that treatment of inflammatory bowel disease with enteric-coated sulfasalazine ([EN] Azulfidine ENtabs) resulted in significantly less frequent and severe GI symptoms, compared with treatment with TAB. The current study was conducted to compare GI tolerance of EN and TAB in rheumatoid arthritis (RA) patients. Fifty adult sulfasalazine-naive patients, who displayed stable RA and no significant GI toxicity with nonsteroidal anti-inflammatory drugs and disease-modifying anti-rheumatic drugs at baseline, were randomized to receive 2 g EN or TAB, in a prospective, 10-week, investigator-blinded, crossover study. After an initial 3-week dosing period with either EN or TAB and a 2-week washout, patients were crossed over to the alternative sulfasalazine formulation for a 2nd 3-week dosing period and 2-week follow-up. GI tolerance of EN and TAB in patients who completed both arms of the crossover was assessed bv frequency and intensity of reported adverse events (primary endpoints) and responses to health questionnaires (secondary endpoints).Twelve patients dropped out early because of adverse events and the discontinuation rate was similar in E\ and TAB-treated patients. Patients taking EN who completed the study reported significantly fewer (p < 0.001) GI adverse events (abdominal pain, anorexia, flatulence, diarrhea, heartburn, nausea, and vomiting), compared with those patients taking TAB. The intensity of adverse events was predominantly mild in patients treated with either EN or TAB. Responses to questionnaires were similar in patients taking either formulation of sulfasalazine. However, when asked which treatment period was preferred at the end of the study, 849 of patients completing the study (p < 0.001) chose EN. This study suggests that enteric-coating of sulfasalazine improved GI tolerance and RA patient preference.

Praziquantel side effects and efficacy related to Schistosoma mansoni egg loads and morbidity in primary school children in north-east Ethiopia

A total of 611 Schistosoma mansoni infected primary school children from three schools in north-east Ethiopia were treated with praziquantel at 40 mg/kg body weight in a single dose. Pre-treatment, 40.4% had no presenting symptoms and 30–40% had nausea, abdominal cramps and/or bloody-mucoid diarrhoea. None of the pre-treatment symptoms was related to nutritional status, intensity of S. mansoni egg excretion, or to the presence of other concomitant intestinal parasitic infections. During the first 4–6 h post-treatment observation period, 90 (14.7%) children self-presented with severe gastro-intestinal symptoms. Children who self-presented with severe symptoms had a higher mean age and mean S. mansoni egg excretion compared with children who did not self-present. The following day a total of 529 (86.6%) children, including all who self-presented during the first 4–6 h post-treatment, reported for clinical check-up and were subjected to a structured questionnaire interview on symptoms they had experienced over the time lapse following treatment. Among these, 91.5% reported one or more treatment related symptoms which were at times severe. Abdominal cramps (86.9%), diarrhoea with blood and/or mucus (49.5%), dizziness (31.2%) and vomiting (24.9%) were the most common treatment related symptoms. Skin rash with oedema were observed in four cases. Among treatment related symptoms, the combination of abdominal cramps with vomiting, bloody diarrhoea, vomiting alone and general weakness were significantly higher among the malnourished. A proportion of these symptoms increased with increasing categories of S. mansoni egg excretion before and after adjusting for nutritional status and concurrent intestinal parasitic infections. Overall, the cure rate of praziquantel, among 541 children who had stool examination 5 weeks after treatment was 83.2% and this rate decreased with increasing pre-treatment egg counts. In conclusion, most of the treatment related symptoms were mild. However, some of the objective symptoms were at times severe and may reduce drug compliance in primary health care based population chemotherapy.

Serum erythromycin levels in pregnancy

Erythromycin is the recommended therapy for pregnant women with chlamydial infection. Despite the fact that this drug has been available since 1952, relatively little is known about its pharmacokinetic behavior in pregnant women, and no investigations have been conducted in women who were in the third trimester of pregnancy. In this study, 10 women were treated with erythromycin for chlamydial infection during pregnancy; 7 of these women were in the third trimester of pregnancy, and 3 were in the second trimester. Serum samples were obtained at 0.5, 1, 2, 3, and 4 hours after a 500-mg oral dose of erythromycin base and were analyzed to determine absorption and peak serum levels of erythromycin. Results indicated that absorption was delayed and serum levels were diminished in comparison with values reported in the literature for patients in the second trimester of pregnancy. In 2 women, erythromycin serum levels were not detectable at any time during the 4 hours of the study; these 2 women also experienced the most severe gastrointestinal symptoms. Although the size of our study population was small and certainly not definitive, the data suggest that in patients in the third trimester of pregnancy, severe adverse gastrointestinal events may forewarn of subtherapeutic plasma concentrations of erythromycin, which could have consequences for the treatment outcome.

CMV infection detected in the upper gastrointestinal tract after liver transplantation.

As a pilot series on the frequency of gastroduodenal cytomegalovirus (CMV) involvement after liver transplantation, we examined forceps biopsies of 13 consecutive patients who underwent esophagogastroduodenoscopy during the first 3 months after transplantation. CMV was demonstrated in frozen sections by monoclonal antibody and immunoperoxidase staining. In parallel, peripheral blood was examined for CMV pp65 antigenemia. CMV antigens were detected in biopsies of ten patients, in ten cases in the duodenum and in four in the stomach. At the time of endoscopy, sic patients had CMV antigenemia, five of them had a simultaneous positive finding in the duodenum. Although all ten patients with the positive biopsy finding had some gastrointestinal symptoms, only one had severe enteritis. In liver transplant patients, CMV was commonly detected in leukocytes located in the mucosa of the upper gastrointestinal tract, especially in the duodenum. Further investigation is needed to determine the significance of positive CMV findings in the biopsies and their association with the development of severe gastrointestinal symptoms.

Effect of amitryptiline on symptoms, sleep, and visceral perception in patients with functional dyspepsia

Objective: Tricyclic antidepressants in low doses are widely used in the therapy of patients with functional gastrointestinal disorders, yet the mechanism(s) of action of these drugs in these disorders is not known. In the current study, we sought to determine in a group of patients with functional dyspepsia and associated poor sleep how amitryptiline affects digestive symptoms, perceptual responses to gastric distension, and subjective and objective measures of sleep. Methods: Patients were randomized to 4 wk of amitryptiline 50 mg taken at bedtime versus placebo. There was a 3-wk washout phase, followed by a cross-over to the alternate treatment. Perceptual sensitivity to gastric distention and sleep EEG were recorded at the end of each treatment period. Diaries of symptoms were maintained throughout. Results: Seven of seven patients reported significantly less severe gastrointestinal symptoms after 4 wk on amitryptiline compared to placebo. Five of seven patients had evidence for altered perception of gastric balloon distension during placebo. However, the subjective symptom improvement on amitryptiline was not associated with a normalization of the perceptual responses to gastric distension. Baseline sleep dysfunction in the form of reduced sleep efficiency, increased arousal, or abnormal amounts of REM sleep was found in all seven patients. Amitryptiline significantly reduced absolute and relative amounts of REM sleep, but had no effect on sleep parameters related to nonregenerative sleep. Conclusion: The beneficial effect of low dose amitryptiline seen in functional dyspepsia is not related to changes in perception of gastric distension, or to measures of arousal from sleep. An increased tolerance to aversive visceral sensations may play a role in the therapeutic effect.