Mesalazine induced lupus-like syndrome.
Explore the source record for details and available documents.
Adult↗
Biomedical subjects
C D Holdsworth
Publications and source records attributed to C D Holdsworth.
99Tcm HMPAO-labelled leucocyte imaging in Crohn's disease: a subtraction technique for the quantification of disease activity.
A new technique for the quantitative analysis of labelled leucocyte images from patients with inflammatory bowel disease is described. The method involves the computer generation of a 'background' image which, after appropriate registration, is subtracted from the patient's image to leave a residue which represents abnormal uptake in the bowel. Quantification of the residual activity yields a scan score which can be related to the level of disease activity in patients with Crohn's disease. In 54 investigations on 33 patients the scan scores correctly agreed with a clinical assessment of disease activity in 16 of 20 cases with inactive disease and 32 out of 34 cases with active disease. Most of the discrepancies reflected inaccuracies in the clinical assessment of activity rather than shortcomings of the imaging technique.
Crohn Disease↗
Clinical tolerance to three 5-aminosalicylic acid releasing preparations in patients with inflammatory bowel disease intolerant or allergic to sulphasalazine.
The clinical tolerance to three 5-aminosalicylic acid (5-ASA) releasing preparations (mesalazine, olsalazine and balsalazide) was assessed in a consecutive series of 43 patients with inflammatory bowel disease who were intolerant to sulphasalazine. The relative contributions to the side-effects of sulphasalazine made by its two components, 5-ASA and sulphapyridine, were also assessed in these patients. Thirty-nine (91%) patients were able to tolerate at least one of the three 5-ASA preparations. Only four (9%) patients were intolerant to all preparations, having adverse reactions previously experienced with sulphasalazine and presumably related to 5-ASA rather than sulphapyridine. The clinical tolerance to mesalazine (63%), olsalazine (70%) and balsalazide (70%) was similar, and tolerance to one drug only was found in nine (18%) patients. The commonest adverse reactions associated with 5-ASA preparations were gastrointestinal. Diarrhoea was a problem in five patients during treatment with olsalazine and three each while on mesalazine and balsalazide. Allergic reactions from 5-ASA preparations were uncommon; of ten patients with rash following sulphasalazine only one developed a rash with mesalazine. The results of this study indicate that the vast majority of patients with inflammatory bowel disease can be managed with at least one of these four 5-ASA containing preparations and that the side-effects of sulphasalazine are multifactorial in aetiology, some being due to the parent molecule, and some to one of its two metabolites, 5-ASA and sulphapyridine.
Aminosalicylic Acids↗
Improved maintenance of remission in ulcerative colitis by balsalazide 4 g/day compared with 2 g/day.
The efficacy of two doses of balsalazide for the maintenance of remission in patients with ulcerative colitis was compared in a double-blind multicentre trial. Sixty-five patients received a 2 g daily dose, and 68 a 4 g dose. The patient groups were similar at entry for sex, age, and disease distribution. Clinical assessment was carried out at 3-monthly intervals, with sigmoidoscopy, rectal biopsy, and blood tests on entry and at 26 and 52 weeks. Clinical relapse over twelve months was significantly less common on the 4 g dose (36%), than on the 2 g dose (55%), P less than 0.01. There were eight withdrawals on 2 g daily and 13 on 4 g daily, six and nine respectively being mainly due to gastrointestinal intolerance. It is concluded that balsalazide is a well-tolerated drug, and is effective for the maintenance of remission in patients with ulcerative colitis, the optimal dose being greater than 2 g daily.
Adult↗
Virulence properties of Escherichia coli strains isolated from patients with inflammatory bowel disease.
Escherichia coli strains cultured from 74 patients with inflammatory bowel disease at different stages of disease activity (Crohn's disease (40), ulcerative colitis (34)) and 18 healthy controls were studied in relation to haemolysin and verotoxin production and enteroadherence. Disease activity was assessed by standard clinical and laboratory tests. Haemolytic E coli were isolated from 18% of patients with Crohn's disease, 24% with ulcerative colitis, and 11% of healthy controls. None of these differences was significant. No verotoxin producing strains were detected among the 216 E coli isolates examined but the extract from five strains (Crohn's (4), ulcerative colitis (1) produced a distinctive cytopathic effort on Vero cell monolayers which was later shown not to be due to verotoxin. The adhesion indices of E coli isolates cultured were: mean (SEM) 42.2 (6.4) for Crohn's disease, 43.3 (6.2) for ulcerative colitis, and 11.3 (2.0) for normal controls (p less than or equal to 0.0001). Adhesive E coli were isolated from 62% of patients with Crohn's disease and 68% with ulcerative colitis but from only 6% of normal controls (p less than or equal to 0.0002). Neither haemolysin production nor enteroadherence was dependent upon disease activity, disease location, sulphasalazine treatment, or previous intestinal resection. These results indicate that only enteroadherent E coli were frequently associated with inflammatory bowel disease; their relation to the pathogenesis of these conditions, however, remains uncertain.
Adult↗
Antibodies to Saccharomyces cerevisiae in patients with Crohn's disease and their possible pathogenic importance.
Saccharomyces cerevisiae (baker's yeast) may play an important part in the pathogenesis of Crohn's disease. Because of this the levels of IgG and IgA antibodies against three S cerevisiae strains (NCYC 77, NCYC 79, and NCYC 1108) were assayed in 49 patients with Crohn's disease, 43 with ulcerative colitis, 14 with coeliac disease, and 21 healthy controls. Coded serum samples were tested by ELISA. Similar antibody patterns to all three strains were found. IgG and IgA antibody levels were significantly raised in patients with Crohn's disease compared with healthy controls (p < 0.001 and p < 0.0001 respectively) and with ulcerative colitis patients (p < 0.0001 and p < 0.0006 respectively). Raised IgA, but not IgG, yeast antibody levels were found in two patients with Crohn's disease who were intolerant to yeast, but these values were similar to those in other patients without yeast intolerance. In ulcerative colitis, both IgG and IgA levels were similar to normal controls. Patients with small bowel Crohn's disease had significantly higher IgG antibody levels than those with colonic disease (p < 0.01). High levels of IgG, but not IgA, antibody were present in patients with coeliac disease, the antibody responses being indistinguishable from those found in Crohn's disease. It is concluded that the presence of IgG antibody to S cerevisiae is characteristic but not specific to Crohn's disease. Although raised IgA antibody levels are more frequently found in Crohn's disease, their pathogenic importance remains to be established.
Adult↗
Upper gastrointestinal endoscopy.
Explore the source record for details and available documents.
Barium↗
Upper gastrointestinal endoscopy: its effects on patient management.
Out of 95 patients referred for upper gastrointestinal endoscopy after a barium-meal examination, 44 underwent a change in management. Some changes were minor but in 12 patients a decision on surgery was required. Seven of these patients were among a group of 13 for whom the referring consultant would have recommended laparotomy had endoscopy not been available, while the other five were subjected to an unplanned laparotomy. These findings support the practice of performing endoscopy on patients whose symptoms are not fully explained by barium-meal examination, especially patients aged over 45. In such cases the procedure also seems to be cost-effective.
Adult↗
Uptake of 47Ca into the forearm in normal subjects and in patients with osteomalacia, primary biliary cirrhosis, and hyperparathyroidism.
Explore the source record for details and available documents.
Biological Transport↗
Fever, abdominal pain, and leucopenia during treatment with cimetidine.
Explore the source record for details and available documents.
Abdomen↗
The measurement of calcium absorption and absorption rate with an external arm radioactivity counter.
1. A large-volume scintillation counter was used to measure calcium absorption from the ratio of forearm uptake of 47Ca after oral 47CaCl2 (administered with milk) to forearm uptake after intravenously administered 47CaCl2. 2. In some subjects serial measurements of both forearm uptake of 47Ca and blood 47Ca radioactivity were also recorded, and by using deconvolution both total calcium absorption and calcium absorption rate were determined. 3. The forearm ratio determination of 47Ca absorption correlated well with that obtained by deconvolution of either serial blood 47Ca or forearm 47Ca measurements provided that the forearm radioactivity measurements were made at least 8 h after the administration of 47CaCL2. 4. Although the two deconvolution techniques gave similar estimates of total calcium absorption there were discrepancies between their measurements of calcium absorption rate. These discrepancies were reduced but not eliminated by the use of additional lead shielding around the Armac counter.
Absorption↗
Hyposplenism in inflammatory bowel disease.
Splenic function was assessed in 35 patients with ulcerative colitis and 20 patients with Crohn's disease. Hyposplenism was diagnosed if there were Howell-Jolly bodies in the peripheral blood film or if there was prolongation of clearance from the peripheral blood of injected 51-Cr-labelled heat-damaged red blood cells. Thirteen of the patients with ulcerative colitis had hyposplenism as compared with only one patient with Crohn's disease. Conversely, heat-damaged red cell clearance values faster than the normal range were found in six out of the 20 patients with Crohn's disease. Four patients with hyposplenism and ulcerative colitis developed life-threatening septicaemia in the early postcolectomy period, two of these being further complicated by disseminated intravascular coagulation.
Colectomy↗
Clinical trial of deglycyrrhizinised liquorice in gastric ulcer.
Ninety-six patients with gastric ulcer were randomly allocated to treatment either with deglycyrrhizinised liquorice or placebo. After four weeks no differences were found between the treatment groups in the proportions with complete healing, whether assessed by gastroscopy or radiology, or in the percentage reduction in ulcer area, or in clinical improvement.
Antacids↗
Unstirred layer and kinetics of electrogenic glucose absorption in the human jejunum in situ.
Using an electrical technique we estimated the thickness of the unstirred layer in the human jejunum during kinetic studies of electrogenic glucose absorption. The unstirred layer in seven healthy volunteers (632 +/- 24 mum: mean +/- SEM) was significantly thicker than in 10 patients with active coeliac disease (442 +/- 23 mum) but not significantly different in seven patients who had responded to treatment by gluten withdrawal (585 +/- 49 mum). There were similar differences in the values of ;Apparent Km' for electrogenic glucose absorption between healthy control subjects (36 +/- 6 mM) active coeliac patients (11 +/- 1 mM) and treated coeliac patients (31 +/- 5 mM). The changes in PDmax however, showed a different pattern. The PDmax in the active coeliac group (6.8 +/- 0.7 mV) was lower than in controls (7.6 +/- 0.6 mV) but not significantly so, while the PDmax in the treated coeliac group (10.6 +/- 0.9 mV) was significantly higher than in both the active coeliac and control groups. It should be noted that both operational kinetic parameters obtained in the present study are much lower than those obtained previously (Read et al., 1976b) because of the use of siphonage. Analysis of the results using a computer simulation indicates that the reduction in Apparent Km in active coeliac disease can be caused by the interaction of the decreased maximal absorption rate for glucose (Jmax) with the attenuated unstirred layer. In these circumstances it is not necessary to postulate any change in the affinity of the transport mechanism for glucose (;Real Km'). It is remarkable that the disease process produces an Apparent Km which is much closer to the Real Km than that found in health.
Celiac Disease↗
Relationship between changes in intraluminal pressure and transmural potential difference in the human and canine jejunum in vivo.
Recordings of transmural potential difference (PD) across the jejunum of conscious man in situ are characterised by spontaneous fluctuations of up to 10 mV. In 25 of 31 subjects (comprising seven normal controls and 24 patients under investigation for malabsorption, six of whom had coeliac disease) we observed a clear association between these fluctuations and changes in intraluminal pressure recorded at the same site. The most frequent PD changes were associated with type III pressure waves. These consisted predominantly of large waver (3-1 +/- 0-1 mV; mean +/- SEM, n = 317) which reached maximal amplitude approximately 45 seconds after the pressure peak and had a duration of 120 +/- 3 s, but also included less frequent spikes (0-5 +/- 0-1 mV; n = 110) concurrent with the pressure wave with a duration of 5 +/- 1 s. Although by recording at two sites in the jejunum 10 cm apart we were able to demonstrate that type III pressure waves appeared to be propagated aborally at a median rate of 60 cm per minute, the apparent rates of propagation of the corresponding PD waves were much more variable. The largest PD changes (7-8 +/- 0-4 mV; n = 19), lasting several minutes, were found in association with runs of type I waves (basic rhythm) superimposed on a type III wave. Both pressure and PD activities were suppressed by intramuscular propantheline bromide. Intraluminal pilocarpine caused a transient rise in PD not always accompanied by a change in pressure. Distention of the jejunum by rapid injection of a bolus of isotonic sodium chloride produced a delayed rise in the PD which could be prevented by prior administration of propantheline bromide. Experiments using Thirty-Vella loops of proximal jejunum in conscious dogs confirmed the effect of jejunal distension on the PD and also demonstrated that spontaneous retching is preceded by an increase in the PD. Consideration of these results in conjunction with data from other workers suggests the hypothesis that the larger spontaneous fluctuations in transmural PD in the jejunum of conscious man are caused by changes in electrogenic secretion associated with intestinal motility and mediated by cholinergic mechanisms. The possible association of increased secretory activity with motility may have functions of lubrication as well as diluting and mixing the chyme for easier digestion and absorption.
Animals↗
Electrical assessment of functional lactase activity in conscious man.
Using an electrical technique for measuring transjejunal potential differences (PDs) in conscious man, we have estimated the electrogenic absorption of the hexoses liberated by hydrolysis of lactose which was infused into the jejunum of one normal control and 21 patients with diarrhoea. The results were compared with jejunal lactase levels determined from biopsy specimens taken from the recording site immediately after infusion. The PD evoked by 100 mM lactose was very significantly lower in patients with lactase levels below 4 units (lactase deficient) compared with subjects with normal lactase levels. There was also a significant correlation (r = 0.87, P less than 0.005) between the magnitude of the lactose potential (expressed as the ratio of the maximum glucose transfer potential) and the mucosal lactase level in the hypolactasic subjects but not in patients with normal lactase levels. Thus, in the subjects with lactase deficiency, the electrogenic transfer of hexose is clearly limited by the rate of lactose hydrolysis. Unlike other assessments of functional lactase activity, the electrical test provides a specific index of jejunal function and, moreover, can be adapted to investigate the possible disorders of small intestinal motility and secretion associated with hypolactasia.
Adolescent↗
Cerebral involvement with disseminated intravascular coagulation in intestinal disease.
Over a two-and-a-half-year period at the Sheffield Royal Infirmary, six patients developed disseminated intravascular coagulation as a serious complication of intestinal disease. There was clinical evidence of cerebral involvement in all six patients, and small vessel thrombi were demonstrated in the brains of all three cases examined post mortem. Where the true significance of the cerebral disorder was not recognised, this led to delay in the diagnosis with serious risk to the patient. In the single case in which the diagnosis was made early, the intravascular coagulation was completely reversed with heparin therapy.
Adult↗
Electrogenic glucose absorption in untreated and treated coeliac disease.
Using a method for measuring changes in transmural potential difference across the human jejunum in vivo, the operational kinetic parameters of 'Apparent Km' and PD max for the active electrogenic component of glucose absorption were estimated in a group of healthy volunteers and in patients with coeliac disease. Both the 'Apparent Km' (17+/2mM; mean +/SEM) and the PD max (8.6+/0.7 mV) in nine patients with untreated coeliac disease were significantly lower (p less than 0.005) than in the control group ('Apparent Km' = 74+/5mM; PD max 12.8+/0.9mV, n=20). Treatment of five coeliac patients by gluten withdrawal for less than three months increased significantly the values of both the "Apparent Km (35+/6mM) and the TPD max (11.4+/1.2mV). Treatment of five patients for more than six months caused a further increase in the values of both kinetic parameters ('Apparent Km' = 108+/13mM; PD max =15.6+/2.7mV) to levels which exceeded those in healthy subjects. The possible interpretations of the differences in the kinetic characteristics of electrogenic glucose transport between coeliac patients and healthy subjects are discussed.
Celiac Disease↗