Colonic energy salvage in chronic pancreatic exocrine insufficiency.

BACKGROUND: Chronic pancreatic exocrine insufficiency results in maldigestion. As a result, increased amounts of undigested nutrients reach the colon, providing more substrate for bacterial fermentation to produce short-chain fatty acids, which could therefore provide additional energy supplement. METHODS: This study aimed to assess carbohydrate malabsorption in patients with chronic pancreatic exocrine insufficiency after ingestion of a standard diet and to calculate energy salvaged by colonic bacterial metabolism. A 72-hour stool collection was done on 10 adult patients receiving a 3-day standard diet containing 100 g fat, 329 g carbohydrate, and 154 g protein, and short-chain fatty acids, fat, carbohydrate, and nitrogen excretion were assessed. A breath hydrogen test after ingestion of 200 g (dry weight) cooked maize meal (test meal) and 10 g oral inulin (standard), respectively, was subsequently done on the patients and 15 healthy adult controls. RESULTS: Breath hydrogen production after ingestion of maize meal and inulin, respectively, and calculated carbohydrate malabsorption were significantly greater in patients (21.4% +/- 17%) than in controls (10.2 +/- 1.4%; p < .05). Patients malabsorbed 70.4 g/d (281.6 kcal) carbohydrate in the standard diet. Total carbohydrate loss in stool amounted to 8.1 g/d (2.4%), and 62.3 g/d (19%) was hence salvaged as short-chain fatty acids for energy provision. Colonic bacterial fermentation therefore converted 88.5% of malabsorbed carbohydrate to short-chain fatty acids, 92.8% of which was absorbed and 7.2% excreted. This suggests that 10.2% of energy expenditure/requirement in these patients is derived from salvage of malabsorbed carbohydrate. CONCLUSIONS: Colonic bacterial metabolism is a significant source of energy salvage in patients with pancreatic enzyme deficiency.

Comparison of inulin and lactulose as reference standards in the breath hydrogen test assessment of carbohydrate malabsorption in patients with chronic pancreatic exocrine insufficiency.

Although often used as a reference standard in the breath hydrogen test (BHT), lactulose fermentation produces more hydrogen, compared to starch, and may therefore not be ideal. This study compares inulin with lactulose as reference standard in the study of carbohydrate malabsorption. Seventeen patients with malabsorption due to chronic pancreatitis and 15 normal controls were studied. Following overnight fasts, BHTs were performed after ingesting 10 g lactulose, 10 g inulin, and 200 g (16 g highly resistant starch) maize meal. Lactulose fermentation produced significantly more hydrogen than inulin in patients with malabsorption (97 +/- 20 vs 45 +/- 22 ppm x hr; P < 0.05) and controls (43 +/- 18 vs 21 +/- 10 ppm x hr; P < 0.05). Patients produced more hydrogen than controls with both standards (lactulose, 97 +/- 20 vs 43 +/- 18 ppm x hr, P < 0.05; inulin 45 +/- 22 vs 21 +/- 10 ppm x hrs; P < 0.05), suggesting adaptation of the colonic flora. Calculated CHO malabsorption was 2.5 +/- 0.8 vs 5.2 +/- 3.8 g with lactulose and 5.2 +/- 3.1 vs 11.2 +/- 9.6 g with inulin as standards in controls and patients, respectively (P < 0.05). Lactulose produces more breath hydrogen than inulin. Calculation of CHO malabsorption using these standards is therefore not comparable.

The effect of severe undernutrition and subsequent refeeding on whole-body metabolism and protein synthesis in human subjects.

BACKGROUND: To determine the consequences of severe undernutrition and refeeding on whole-body metabolism and protein synthesis. METHODS: Respiratory quotient (RQ), resting energy expenditure (REE), and whole-body protein synthesis (WBPS) were assessed in undernourished patients, with anorexia nervosa (n = 8) or with coexistent disease (n = 17). Results were compared with 17 healthy controls. Six anorexic patients and 13 disease patients consented to study after nutrition support. RESULTS: Mean body mass index was 12.46 +/- 0.53 kg/m2 in the anorexia patients and 13.81 +/- 0.40 kg/m2 in the disease patients (controls 23.71 +/- 0.72 kg/m2; p < .001). Compared with controls, RQ was similar in anorexia patients (0.85 +/- 0.05 vs 0.90 +/- 0.05) but lower in the disease patients (0.76 +/- 0.03 vs 0.90 +/- 0.05; p = .02). REE was lower in the patients (anorexia 1058 +/- 134.0 kcal/d, disease 1189 +/- 101.4 kcal/d vs 1828 +/- 89.76 kcal/d; p < .001); however, expressed as kcal/kg/d, it was higher (anorexia 32.17 +/- 4.25, disease 31.30 +/- 2.14 vs 25.07 +/- 1.00; p < .05). WBPS was lower in the patients (anorexia 140.9 +/- 10.54 g/d, disease 119.8 +/- 8.57 g/d vs 305.0 +/- 21.64 g/d; p < .001); however, when expressed as g/kg/d, the anorexia patients were similar to controls, whereas the disease patients were lower (3.11 +/- 0.24 vs 4.27 +/- 0.32; p < .05). Refeeding increased RQ in the disease patients (0.84 +/- 0.03 vs 0.76 +/- 0.03; p < .05), and normalized REE (anorexia 27.65 +/- 3.05 kcal/kg/d, disease 28.90 +/- 1.85 kcal/kg/d). WBPS increased in the disease patients (173.6 +/- 16.38 g/d vs 116.5 +/- 10.15 g/d; p < .01). CONCLUSIONS: Undernutrition is associated with increased REE (kcal/kg/d). Reduction in RQ and protein synthesis (g/kg/d) was evident in those patients with coexistent disease. Refeeding resulted in normalization of RQ, REE (kcal/kg/d), and protein synthesis (g/kg/d).

Intravenous CDP870, a PEGylated Fab' fragment of a humanized antitumour necrosis factor antibody, in patients with moderate-to-severe Crohn's disease: an exploratory study.

BACKGROUND: CDP870 is a PEGylated Fab' fragment of a humanized monoclonal antibody that neutralizes tumour necrosis factor-alpha. AIM: To evaluate the safety and efficacy of a single intravenous dose of CDP870 or placebo over a 12-week period in patients with moderate-to-severe Crohn's disease. METHODS: Ninety-two adult patients with Crohn's disease (Crohn's Disease Activity Index: 220-450 points) were randomized to receive CDP870 [1.25 (n = 2), 5 (n =26), 10 (n = 17) or 20 mg/kg (n = 23)] or placebo (n = 24). Crohn's Disease Activity Index scores were determined at weeks 0, 2, 4, 8 and 12. The primary end-point was the percentage of patients achieving clinical response [i.e. a decrease in Crohn's Disease Activity Index score > or = 100 points or remission (Crohn's Disease Activity Index score: < or =150 points)] at week 4 in the intent-to-treat population. RESULTS: The percentage of patients achieving the primary end-point was comparable across all treatment groups (56.0%, 60.0%, 58.8% and 47.8% for placebo, CDP870 5, 10 and 20 mg/kg, respectively). The remission rate at week 2 was 47.1% with CDP870 10 mg/kg vs. 16.0% for placebo (P = 0.041). All treatments were well-tolerated: adverse events, reported by 43 patients treated with CDP870 and 15 patients treated with placebo, were mainly mild-to-moderate in intensity. There were no infusion reactions. CONCLUSIONS: A single intravenous dose of CDP870 was well-tolerated by patients with Crohn's disease. While no statistically significant difference in clinical response rates between CDP870 and placebo was observed, clinical benefit in terms of remission was demonstrated.

Impaired gastric acid and pancreatic enzyme secretion in patients with Crohn's disease may be a consequenece of a poor nutritional state.

INTRODUCTION: Impaired pancreatic function has been reported in Crohn's disease, the cause of which is uncertain. This study investigated the effect of malnutrition, and subsequent re-feeding, on digestive function and protein synthesis in Crohn's disease patients. METHODS: Gastric acid and pancreatic secretion studies were performed on malnourished Crohn's patients before, and after a period of intensive nutritional support. Whole body, as well as pancreatic enzyme protein synthesis was investigated by [14C]leucine isotope incorporation studies. Results were evaluated in comparison to normal healthy volunteers. RESULTS: The mean body mass index (BMI) of the Crohn's patients was 14.14 kg/m2. The Crohn's patients had reduction in the secretion of gastric acid (7.36 versus 25.53 mEq/h; P < 0.01), and the pancreatic enzymes, amylase (759.6 versus 2305 U/h; P < 0.01), lipase (33.01 versus 118.6 U/h; P < 0.01) and trypsin (97.43 versus 341.4 U/h; P < 0.01). Resting energy expenditure (REE), expressed in relation to body mass, was greater in the malnourished Crohn's disease patients (38.25 versus 25.36 kcal/kg/d; P = 0.01). Total body protein synthesis was reduced (2.82 versus 4.39 g protein/kg/d; P < 0.05), with significant impairment in the synthesis of pancreatic enzymes, and reduction of zymogen stores. Following re-feeding, the BMI of the Crohn's patients improved to 16.80 +/- 0.66 kg/m2. Pancreatic enzyme synthesis improved, with significant increase in pancreatic enzyme stores and secretion, to levels similar to control values. Gastric acid secretion also improved, although still lower than the control value. CONCLUSION: Malnutrition may play a significant role in the impairment of gastric acid and pancreatic secretion in Crohn's disease patients.

Impaired pancreatic secretion in severely malnourished patients is a consequence of primary pancreatic dysfunction.

Severe undernutrition has been associated with reduced secretions of gastric acid and pancreatic enzymes. This may be the result of an impaired gut mucosal response to food and primary gastric parietal and pancreatic acinar cell secretory dysfunction as a consequence of the poor nutritional state. To investigate the relative contributions of these factors, severely undernourished patients underwent enteral-meal-stimulated (ES; n = 7) or intravenous hormone (pentagastrin and cholecystokinin-8)-stimulated (HS; n = 12) gastric acid and pancreatic enzyme secretion before and after a period of nutritional support. Results were evaluated in comparison with normal healthy control subjects (ES = 7, HS = 10). In the control subjects, enteral-meal and cholecystokinin-8 stimulation resulted in similar outputs of the pancreatic enzymes amylase (2213 versus 2305 U/h), lipase (84.93 versus 118.6 U/h), and trypsin (498.9 versus 341.4 U/h), whereas acid output was significantly lower in the ES group (10.90 versus 25.53 mEq/h; P < 0.01). Compared with controls, malnourished groups had significantly reduced secretions of amylase (ES = 870.1 U/h, HS = 686.5 U/h; P < 0.02), lipase (ES = 30.68 U/h, HS = 25.96 U/h; P < 0.02), and trypsin (ES = 175.6 U/h, HS = 109.3 U/h; P < 0.01). The response to enteral-meal or CCK-8 stimulation was comparable. Gastric acid was similarly reduced in the undernourished patients (ES = 4.39 mEq/h, HS = 5.04 mEq/h; P < 0.01). After refeeding, secretion of amylase (ES = 2351 U/h, HS = 2228 U/h) and lipase (ES = 58.83 U/h, HS = 84.91 U/h) improved to levels not significantly different from controls, whereas trypsin (ES = 226.4 U/h, HS = 213.1 U/h; P < 0.03) and acid secretion (ES = 3.52 mEq/h, HS = 11.85 mEq/h; P < 0.01) remained significantly impaired. Severe undernutrition was associated with primary gastric parietal and pancreatic acinar cell dysfunction, which, at least in the case of pancreatic enzymes, appeared to be the determining factor controlling secretion in these patients.

The effect of severe undernutrition, and subsequent refeeding on digestive function in human patients.

BACKGROUND: Severe undernutrition may adversely affect gut function. AIMS: To investigate the effects of severe undernutrition and subsequent refeeding on human digestive function. METHODS: Severely undernourished patients (body mass index (BMI) < 17 kg/m2) were studied before, and after a period of intensive nutritional support. Standard intestinal absorption tests (faecal fat and urinary xylose excretion), pentagastrin-stimulated acid secretion, and cholecystokinin octapeptide (CCK-8)-stimulated pancreatic enzyme secretion tests were performed. In addition, duodenal biopies were taken to assess gut mucosal morphology. Findings were evaluated in comparison to a group of normal healthy volunteers. RESULTS: Mean BMI of the patients prior to nutritional support was 13.41 kg/m2, with improvement to 16.12 kg/m2 after. Duodenal histology showed evidence of villous atrophy in six of 14 (43%) undernourished patients. Mean xylose excretion following a 5 g oral dose was 0.62 g/5 h in the group of undernourished patients prior to nutritional support (normal > 1 g/5 h), with improvement to 1.40 g/5 h (P < 0.01) after feeding. Maximal gastric acid output was significantly impaired in the undernourished group, as compared to the controls (6.94 mEq/l vs 25.53 mEq/l, P < 0.02), with a significant improvement to 12.30 mEq/l (P < 0.05) following nutritional support. Pancreatic enzyme output was significantly reduced (amylase 830.9 U/h vs 2304 U/h, P < 0.01; lipase 38.0 U/h vs 118.6 U/h, P < 0.01; trypsin 119.7 U/h vs 341.4 U/h, P < 0.01). Following a period of nutritional support there was a significant improvement in amylase and lipase outputs to 1819 U/h and 85.5 U/h, respectively (P < 0.01). These levels were not significantly different from the normal controls. Trypsin output, however, remained significantly impaired at 174.3 U/h (P < 0.01). CONCLUSIONS: Severe undernutrition is associated with significant impairment of digestive function, with improvement occurring following nutritional support. These changes may affect initial tolerance to enteral feeding, particularly in those patients with co-existent gut disease.

Sucralfate and methylprednisolone enemas in active ulcerative colitis: a prospective, single-blind study.

In order to investigate the role of sucralfate in active ulcerative colitis, 60 patients were randomized to receive either sucralfate enemas (20 g/100 ml) or methylprednisolone enemas (20 mg/100 ml). The enemas were administered twice daily for one week, and then once daily for three weeks. Clinical evaluation was documented at entry and at two weeks and four weeks. The sigmoidoscopic appearance of the rectal mucosa was scored, and rectal biopsies taken at entry and at four weeks. Results indicated similar reduction in diarrhea and rectal bleeding at two weeks and at four weeks. Sigmoidoscopy demonstrated similar significant improvement in the macroscopic appearance of the rectal mucosa in both groups (8.28 to 6.20 in sucralfate group, P < 0.02; and 8.72 to 6.36 in the methylprednisolone treated group, P < 0.04). Histologic assessment, likewise, showed similar improvements in the two groups. This study indicates that sucralfate enemas may be useful in the treatment of ulcerative proctosigmoiditis.

Basal and pentagastrin stimulated acid secretion in duodenal ulcer subjects before and after Helicobacter pylori eradication: a 12-month follow-up study.

BACKGROUND: The effect of infection by Helicobacter pylori on gastric physiology in duodenal ulcer subjects is controversial. There is evidence that the infection is associated with abnormalities in gastrin homeostasis. Consistent changes in pentagastrin-stimulated acid secretory status have proved difficult to establish. This may be because patients have been studied too soon after Helicobacter pylori eradication. AIMS: To study the immediate and longer term effect of Helicobacter pylori eradication on basal and pentagastrin-stimulated acid secretion in duodenal ulcer subjects. PATIENTS AND METHODS: Patients with active duodenal ulcer disease were studied. Ulcers were healed with sucralfate 2 g bd or ranitidine 300 mg nocte. Helicobacter pylori eradication was attempted with bismuth-based "Triple Therapy", and the nine patients in whom the organism was successfully eradicated were followed and studied over the 12-month period. Acid secretion was studied at entry (prior to the initiation of therapy), following healing, following eradication and 12 months later. Basal, low dose (0.1 microgram/kg) and high dose (6 micrograms/kg) pentagastrin-stimulated acid secretion was determined. RESULTS: Whilst there was a tendency for basal and low dose-stimulated acid secretion to fall following eradication, in this study only the reduction in high dose-stimulated acid secretion achieved significance following eradication (entry mean = 59.6, post eradication mean = 49.6, p < 0.03). This effect of eradication on high dose pentagastrin-stimulated acid secretion was also seen at the 12-month study (mean = 48.9, p < 0.02 versus entry). CONCLUSION: The findings of this study suggests that maximally stimulated acid secretion is modestly, albeit significantly, reduced following Helicobacter pylori eradication and that this effect persists.

Diabetic neuropathic cachexia: the importance of positive recognition and early nutritional support.

We report on a patient with acute painful diabetic neuropathy in whom abdominal pain and severe weight loss mimicked neoplastic disease. Positive recognition of the diabetic neuropathic cachexia syndrome might have avoided extensive invasive investigation. Intensive enteral nutritional support was associated with prompt resolution.

Small bowel intussusception and brown bowel syndrome in association with severe malnutrition.

Brown bowel syndrome is a rare condition characterized by deposition of lipofuscin in the smooth muscle cells of the gastrointestinal tract. The number of reported cases is small, but all are associated with malabsorptive states. Despite these small numbers, there is considerable evidence that vitamin E deficiency is important etiologically. We report here the case of a severely malnourished [body mass index 11.7 kg/m (2): normal range 20-25 kg/m (2)] 31-yr-old black male with a longstanding history of alcohol abuse, who was on anti-tuberculosis therapy. The patient presented with an acute abdomen and was found, at operation, to have a mid-ileal intussusception. Histological examination of the resected specimen demonstrated lipofuscin accumulation consistent with brown bowel syndrome, but no tumor. Subsequent investigations revealed no significant quantities of vitamin E in the blood and pancreatic steatorrhea. However, deficiency of other fat-soluble (vitamin A and D) and water-soluble vitamins (vitamin C and thiamine) also were detected. This report supports the association of brown bowel syndrome with vitamin E deficiency but cannot exclude the compounding effects of protein calorie malnutrition, multiple vitamin deficiencies, and chronic alcohol toxicity.

Helicobacter pylori eradication in the African setting, with special reference to reinfection and duodenal ulcer recurrence.

The aim of this study was to determine the effect of Helicobacter pylori eradication on the natural history of duodenal ulcer disease, and to determine the incidence of reinfection in adult patients where H pylori had been eradicated in a community with a high prevalence of the infection. An investigator blinded study, with 24 month endoscopic follow up, in subjects where H pylori had been eradicated, and similarly treated subjects where it had not been eradicated was conducted at a tertiary referral hospital. The patients consisted of a volunteer sample of 48 patients with endoscopically proved active duodenal ulcer disease. Duodenal ulcers were healed with omeprazole, 20 mg/day. After endoscopically confirmed healing, patients were treated with either one (17 patients) or two weeks (31 patients) of 'triple therapy'. H pylori status (urease reaction, histological tests, and culture of antral biopsy specimens) was determined at entry, four weeks after the finish of triple therapy and six, 12, and 24 months after this, or whenever an endoscopically proved recurrent duodenal ulcer was found. The main outcome measures were the recurrence of duodenal ulceration, over 24 months in the eradicated and non-eradicated groups and the incidence of reinfection by H pylori in the eradicated group during this follow up period. Five patients in the eradicated group experienced a duodenal ulcer relapse, of which only three were unexplained (1 = reinfected, 1 = gastrinoma). Fifteen of 21 patients in the non-eradicated group relapsed over the same period (p < 0.001). Only two of 27 patients in the eradicated group were reinfected during the 24 month follow up period. It is concluded that H pylori eradication is an effective treatment strategy for the longterm treatment of duodenal ulcer disease, even in the high prevalence, African setting. Reinfection is uncommon.

Effect of sucralfate on Helicobacter pylori and severity of gastritis in patients with duodenal ulcer.

BACKGROUND: Duodenal ulcer relapse rates have been reported to be lower following healing with sucralfate. The question arises whether this is related to an effect on Helicobacter pylori. METHODS: In order to investigate this possibility, 43 patients with active duodenal ulcer were entered into a study. Endoscopy was performed at entry, following 6 weeks' treatment with sucralfate 1 g q.i.d., and at 4 and 12 weeks of post-documented healing. Antral and gastric corpus biopsies were taken for assessment of H. pylori status (CLOtest), density of infection, and severity of gastritis. In addition, 14C urea breath tests (UBT) were performed. RESULTS: Sucralfate therapy induced a significant decrease in the density of H. pylori infection, with a trend to improvement of the gastritis in the antrum, but not in the corpus. However, all patients remained CLOtest positive, and the overall gastric urease activity was unchanged following therapy. These effects did not appear to influence either initial duodenal ulcer healing or subsequent relapse rates. CONCLUSION: Sucralfate has a suppressive effect on H. pylori infection in the gastric antrum but the clinical relevance of this is uncertain.

Severe hypophosphataemia in anorexia nervosa.

In addition to well-described acid-base and electrolyte disturbances, anorexia nervosa may be complicated by severe hypophosphataemia. We report a case of anorexia nervosa complicated by life-threatening hypophosphataemia manifesting as generalized muscle weakness and bulbar muscle dysfunction, resulting in an aspiration pneumonia and cardiorespiratory arrest.

Cyclosporin A retention enemas in refractory distal ulcerative colitis and 'pouchitis'.

The aim of this study was to evaluate the use of cyclosporin enemas in patients with distal ulcerative colitis and 'pouchitis' resistant to all conventional medical therapy. In an trial 12 patients with distal ulcerative colitis unresponsive to treatment with topical and oral corticosteroids, 5-aminosalicylic acid, and oral immunosuppressive therapy together with 1 patient with 'pouchitis' unresponsive to repeated courses of antibiotics, topical corticosteroids, and oral mesalazine received 250 mg cyclosporin administered daily as a retention enema. Changes in symptoms and the sigmoidoscopic/histologic appearances of the rectal mucosa were assessed at monthly intervals. Seven of 12 patients with ulcerative colitis improved. There was a strong correlation between clinical and histologic improvement (p < 0.005). Four of 12 patients showed no response. Three of these required colectomy, two of whom had more extensive disease than had previously been documented. The patient with pouchitis showed improvement in symptoms and 'pouchoscopy' appearance but not in histologic score. Cyclosporin blood concentrations were very low and side effects negligible. Cyclosporin A retention enemas are safe and may be useful in the treatment of severe refractory distal ulcerative colitis. A controlled trial would now seem warranted.

An assessment of registrars and their training programmes at the University of Cape Town Teaching Hospitals.

In order to describe the registrar population and to highlight their problems, a study using an anonymous questionnaire was conducted in August 1988 at the University of Cape Town Group of Teaching Hospitals. The average age of respondents was 32 years and the majority had family responsibilities (60% married, 41% with dependents). They had significant medical experience and postgraduate qualifications. Registrars work long hours (mean 66 +/- 13.7 h/wk), with duty shifts that can extend for up to 34 hours. Most of their time at work was devoted to patient care, with time for study and research virtually non-existent. Although the majority (61%) felt that the 'registrar experience' was worthwhile, a significant proportion of respondents (45%) had considered leaving the rotation. The study revealed several shortcomings that need to be addressed if candidates of good calibre are to be attracted, academic standards are to be maintained and sufficient specialists produced to serve the needs of our population adequately.