Hypernatraemia, acute diarrhoea, and oral rehydration therapy.
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Biomedical subjects
Publications and source records attributed to M J Farthing.
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Bleeding from duodenal varices in portal hypertension may not be recognized, resulting in a delay in diagnosis. Early detection is important as duodenal varices are a potential source of massive hemorrhage. We report two cases with recurrent upper gastrointestinal hemorrhage in whom accurate diagnosis was made only after extensive investigation including repeated endoscopic examination.
The spin-lattice (T1) and spin-spin (T2) relaxation times of liver in 42 normal volunteers (21 male and 21 female) were measured using a calibrated 0.08 T resistive imager capable of accurate and reproducible relaxometry. T1 was determined using an interleaved gradient echo saturation recovery and inversion recovery technique and T2 using a four-echo Carr-Purcell-Meiboom-Gill sequence. The ranges obtained were T1 = 213 +/- 14 ms and T2 = 66 +/- 5 ms. More specific ranges were obtained for each sex and for younger and older subjects. A small variation in T1 was found between older (greater than 40 years) and younger (less than 40 years) subjects, but no such effect was observed in the case of T2. No significant variations were found when female volunteers were imaged at weekly intervals through the menstrual cycle, when a male volunteer was imaged repeatedly over the course of several months or when male volunteers consumed small quantities of alcohol.
The codon usage of 10 E. histolytica genes comprising 4455 codons was analysed. The codon usage revealed an extremely biased use of synonymous codons with a preference for NNU (44%) and NNA (41.4%) codons. Codons CGG (arg), AGG (arg) and CCG (pro) were absent in the E. histolytica genes examined. The codon usage of E. histolytica resembled that of Plasmodium falciparum.
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Parasitic infection of the gut is highly prevalent in developing countries and contributes to the severe malnutrition associated with persistent diarrhoea in children. Using random faecal alpha 1-antitrypsin measurements as an index of protein-losing enteropathy, we examined children with and without parasitic infection of the gut. Seventeen percent of children with persistent diarrhoea had evidence of protein-losing enteropathy. This was found to be associated with hypoalbuminaemia in children infected with Strongyloides stercoralis. Only a minority (2 of 17) of children infected with Giardia lamblia had raised faecal alpha 1-antitrypsin excretion and this was not associated with hypoalbuminaemia. This study emphasises the need for rapid diagnosis and treatment of Strongyloides infection in children with persistent diarrhoea and severe nutrition.
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Secretory diarrhoea is a major cause of morbidity and mortality worldwide. However, there is no biologically relevant test system in man for assessing new anti-diarrhoeal therapies prior to clinical trial. We have used highly purified cholera toxin in combination with the triple lumen jejunal perfusion technique to establish a subclinical model of cholera in man. Cholera toxin was administered either by mouth with sodium bicarbonate or directly into a 30 cm 'open' or 'closed' (isolated between two inflated balloons) jejunal segment in healthy adult volunteers. Both oral dosing and direct delivery into an 'open' jejunal segment failed to produce consistent secretion of water and electrolytes. In contrast 15 micrograms or 25 micrograms of cholera toxin elicited secretion of water and sodium 3 h after instillation into the balloon occluded 'closed' jejunal segment (P less than 0.05 vs. controls). The rate of secretion was constant over the maximal period studied (4.5 h) and was similar to that reported in human cholera. None of the subjects experienced troublesome diarrhoea. We believe this model offers a relevant test system for assessing anti-diarrhoeal therapy in man.
The effect of osmolality on the efficacy of oral rehydration solutions (ORS) and the contribution of the amino acid glycine to water absorption from ORS have been studied in an animal model of secretory diarrhoea. After exposure to pure cholera toxin, rat small intestine (excluding the duodenum) was perfused in situ with seven different ORS. All ORS were derived from a "basic" solution containing Na 50, K 25, Cl 75 and glucose 50 mmol/l to which 25 or 50 mmol/l of glycine, glucose, or mannitol was added. All ORS reversed water secretion to absorption, but maximum water absorption was obtained with the "basic" solution with an osmolality of 200 mOsm/kg. When the osmolality of the "basic" solution was raised to 225 and 250 mOsm/kg by adding mannitol, water absorption decreased. At each of these osmolalities, substitution of mannitol by glycine or glucose resulted in similar increases in water absorption, but all modifications compared unfavourably with the "basic" solution. Net sodium secretion occurred with all ORS tested, despite net water absorption. These findings in a perfusion model of rat small intestine suggest that osmolality is a key factor influencing the efficacy of ORS and that addition of a second substrate, such as glycine, has no beneficial effects. Our results suggest that there is a maximal rate for water absorption from the small intestine which is inversely related to the osmolality of the perfusate.
Extracolonic manifestations of inflammatory bowel disease are common and diverse. Cardiac complications, however, are rare and of these pericarditis is the most frequently described association. A 57 year old man with a 20 year history of ulcerative colitis presented with a four day history of retrosternal chest pain and exertional dyspnoea. Electrocardiogram showed Wenckebach atrioventricular block. Three days later he developed bloody diarrhoea and sigmoidoscopy showed active proctocolitis. He was treated with oral prednisolone after which the chest pain and diarrhoea settled within 48 hours. At outpatient review two weeks later he was completely well and the electrocardiogram had returned to normal.
There seems to be a worldwide geographic variation in the prevalence of peptic ulcer disease, although there are few reliable population based studies. This study aimed to determine the prevalence of peptic ulcer disease in a community in southern India and to evaluate the relationship between dyspeptic symptoms, Helicobacter pylori infection, gastritis, and peptic ulcer disease. A sample population was selected randomly from a rural monastic settlement in southern India. Subjects were interviewed using a standardised symptom and demography questionnaire then underwent upper endoscopy and antral biopsy for histology and CLO rapid urease test. Altogether 197 subjects from a population of 1499 (13.1%) were studied. All were male monks and ethnically Tibetan. The median age was 28 years (range: 21-81). None smoked or took NSAIDs. The six month period prevalence of dyspeptic symptoms was 68.5%. Current symptoms were present in 58.9% of subjects. Dyspepsia was more common in subjects aged 40 years or younger (p < 0.0001). H pylori was detected in 77.2% subjects. There was no association between dyspepsia and the presence of H pylori or histological gastritis, although there was a strong correlation between symptoms and ulcer (p < 0.003). The point prevalence of active peptic ulcer was 6.6% (13/197). All ulcers detected were either prepyloric or pyloroduodenal in location. A further 6.6% of subjects had definite evidence of scarring or deformity indicative of ulceration in the past. Subjects with past or present ulcers comprised 17.8% of dyspeptic subjects. H pylori was present in all subjects with active ulcers and in 12/13 of those with scarring. Dyspepsia, H pylori infection, gastritis, and peptic ulcer are all more common in this population than in those from developed countries. Ulcer disease, however, accounts for only a small proportion of subjects with symptoms and neither H pylori infection nor gastritis are significantly associated with the presence of dyspepsia.
A 22 year old insulin dependent diabetic with high volume, secretory chronic diarrhoea refractory to standard andiarrhoeal drugs was treated with the somatostatin analogue octreotide, 50 micrograms twice daily by subcutaneous injection. She improved markedly with a decrease in mean stool weight from 1170 g/24 h range 440-2900 g) to 440 g/24 h (range 180-800 g) (p < 0.05). Stool frequency also decreased from six (range two to 12) to one (range one to three) bowel movements per day (p < 0.01). Mouth to caecum transit time increased from 45 minutes to > 210 minutes, although total gut transit time was unchanged and remained rapid at nine hours. Thus octreotide can reduce stool volume and frequency in high volume diabetic diarrhoea when conventional antidiarrhoeal agents have failed. Its therapeutic benefit appeared to be predominantly related to a marked increase in mouth to caecum transit time.
Controversy continues regarding the optimal composition of glucose electrolyte oral rehydration solutions for the treatment of acute diarrhoea. Four perfusion models (normal human jejunum, normal rat small intestine, cholera toxin treated secreting rat small intestine and rotavirus infected rat small intestine) have been developed and used to compare the efficacy of a hypotonic oral rehydration solution with standard United Kingdom British National formulary and developing world oral rehydration solutions (WHO). Despite obvious physiological and pathophysiological differences between these models there was general congruence in the water and solute absorption profiles of the different oral rehydration solutions. Hypotonic oral rehydration solution promoted significantly greater water absorption than other oral rehydration solutions in all rat models (p < 0.001) but apparently increased water absorption failed to achieve significance in human jejunum. British National Formulary-oral rehydration solution was unable to reverse net water secretion in both rotavirus and cholera toxin models. Net sodium absorption from hypotonic and WHO-oral rehydration solutions was significantly greater than from the low sodium British National Formulary-oral rehydration solutions (p < 0.001) except in the rotavirus model when absorption was similar to hypotonic-oral rehydration solutions. These findings show that there is agreement in the apparent efficacy of oral rehydration solutions in these animal and human perfusion models, and that improved water absorption with adequate sodium absorption may be achieved by reducing oral rehydration solution osmolality.
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While oral rehydration therapy with glucose-electrolyte solutions is highly effective, the optimal formulation has not yet been defined. Recent clinical studies suggest that stool volume, and thus water losses, may be reduced if glucose is replaced by a polymeric substrate which reduces osmolality. It is possible that the efficacy of glucose monomer based oral rehydration solutions (ORS) will also improve if osmolality is decreased. Using jejunal triple lumen perfusion in healthy adult volunteers net water and solute absorption were studied from three hypotonic solutions with different sodium concentrations (46, 60, 75 mmol/l) but identical glucose concentrations (90 mmol/l), thus allowing osmolality to rise (210, 240, and 270 mOsm/kg, respectively). Results from these solutions (ORS 45:210, ORS 60:240, and ORS 75:270) were compared with the World Health Organisation oral rehydration solution (WHO-ORS). Greatest water absorption was seen with ORS 60:240 (p less than 0.01). Sodium absorption from ORS 60:240 and WHO-ORS was similar and greater than sodium absorption from ORS 45:210 (p less than 0.05). Potassium and glucose absorption were greater from ORS 60:240 than from any of the other hypotonic solutions (p less than 0.05) and were equal to absorption from WHO-ORS). These results in a short segment of healthy human jejunum suggest that hypotonic ORS containing monomeric glucose may increase water absorption.
Six patients with jejunostomies and residual jejunal lengths of 105 to 250 cm took the same food and water each day for eight study days. In random order, three methods of salt replacement were tested, each over 48 hours, against a period without added salt. During the three test periods the patients took 120 mmol of sodium chloride daily, as salt in gelatine capsules, as an isotonic glucose electrolyte (280 mOsmol/kg; 30 kcal) solution, and as a glucose polymer (Maxijul) solution (280 mOsmol/kg; 200 kcal). The daily stomal output remained constant for each patient during the four test periods but varied between patients from 0.60 to 2.84 kg (daily intestinal fluid balance 0.74-2.61 kg). Without a salt supplement, three patients lost more sodium from the stoma than they took in by mouth (-25, -94, and -101 mmol/day) and the mean sodium balance for all six subjects was -16 mmol (range -101 to 79) daily. Extra salt was absorbed with each form of supplement (p less than 0.05); no patient with the glucose electrolyte solution (mean 96, range 0 to 226 mmol), but one patient with the glucose-polymer solution (mean 96, range -25 to 164 mmol) and two with the salt capsules (mean 66, range -8 to 145 mmol) were in negative balance. Two patients vomited with the salt capsules. There was only a small increase in energy absorption (mean 115 kcal) with the glucose polymer solution compared with the glucose electrolyte solution. A sipped glucose electrolyte solution seems to be the optimal mode of sodium replacement in patients with a high output jejunostomy.
Corticosteroid or 5-aminosalicylic acid enemas are the treatment of choice for distal ulcerative colitis but up to one third of patients may be unresponsive. As an alternative therapy might be advantageous, the efficacy of six weeks' treatment with 2 g 4-aminosalicylic acid (4-ASA) (n = 24) and 20 mg prednisolone enemas (n = 21) were compared in a double blind, randomised trial in patients with acute distal (less than 30 cm from the anus) ulcerative colitis. Baseline demography and clinical severity were similar in both groups. Five of 24 patients receiving 4-ASA and 4 of 21 receiving prednisolone did not complete the trial because of deteriorating symptoms, failure to improve, or side effects. At the time of leaving the trial, 24 hour stool frequency, the presence of blood in the stools, and histological and sigmoidoscopic appearances were similar in both groups. Symptomatic improvement occurred in 17 of 24 patients receiving 4-ASA compared with 11 of 21 receiving prednisolone (chi 2 = 1.62, NS). Complete symptomatic improvement occurred in 9 of 24 patients receiving 4-ASA compared with 5 of 21 receiving prednisolone (chi 2 = 0.98, NS). Histological improvement was seen in 9 of 24 patients on 4-ASA compared with 7 of 21 on prednisolone (chi 2 = 0.08, NS). One patient receiving 4-ASA was considered to have an idiosyncratic reaction to the drug but other side effects were not considered to be drug related. Thus, 4-ASA, previously used in the treatment of tuberculosis (para-aminosalicyclic acid), is as good as prednisolone in the treatment of distal ulcerative colitis and should be considered in patients unresponsive to steroids or in whom steroid treatment is undesirable.