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Biomedical subjects

V S Chadwick

Publications and source records attributed to V S Chadwick.

At least 55 records · Page 3Linked to original sources
PubMed1986

Differing acute phase responses in Crohn's disease and ulcerative colitis.

Thirty eight patients with Crohn's disease and 30 patients with ulcerative colitis have been assessed using the technique of faecal excretion of 111Indium granulocytes to quantify precisely acute inflammatory activity. At the time of each faecal granulocyte measurement the serum concentration of the acute phase protein C-reactive protein and the erythrocyte sedimentation rate were estimated. C-reactive protein concentration was significantly higher in Crohn's disease than ulcerative colitis both overall and particularly in relation to given levels of granulocyte excretion. No such distinction was observed between the erythrocyte sedimentation rates in the two diseases. The present findings show that the acute phase response differs significantly between Crohn's disease and ulcerative colitis. Patients with ulcerative colitis may be constitutionally different from those with Crohn's disease and unable to mount a major acute phase response to their own disease.

Adolescent↗
PubMed1985

Defective gallbladder emptying and cholecystokinin release in celiac disease. Reversal by gluten-free diet.

Normal volunteers (n = 6), patients with untreated celiac disease and subtotal villous atrophy (n = 6), patients with nonresponsive celiac disease (n = 2), and patients with celiac disease on a gluten-free diet with a virtually normal biopsy specimen (n = 6) drank a liquid fat meal after an overnight fast. Gallbladder emptying was monitored by using 99mTc-eHIDA, and blood samples were taken for cholecystokinin estimation by radioimmunoassay after high-performance liquid chromatography. The half-times of gallbladder emptying were 20.4 +/- 2.9 min (mean +/- SEM) for normals and 22.1 +/- 2.8 min in treated patients with celiac disease (NS). In patients with untreated celiac disease half-times were 154.3 +/- 10.3 min (p less than 0.02 vs. normals and treated patients with celiac disease), and in 2 nonresponsive patients, half-times were 40.7 and 37.3 min. Integrated plasma cholecystokinin responses were 473 +/- 87 and 436 +/- 137 pmol X L-1 X 30 min-1 in normals and treated patients with celiac disease (NS). In untreated patients with celiac disease values were 16 +/- 9 pmol X L-1 X 30 min-1 (p less than 0.001 vs. normals and treated patients with celiac disease), and in nonresponsive patients values were 442 and 322 pmol X L-1 X 30 min-1. In 2 patients studied before and during gluten-free diet half-times for gallbladder emptying changed from 168.9 and 302.4 min to 20.1 and 23.4 min, and cholecystokinin responses changed from 0 and 45 to 623 and 298 pmol X L-1 X 30 min-1. Cholecystokinin immunoreactivity cochromatographing with cholecystokinin-octapeptide was responsible for 50%-60% of circulating cholecystokinin in normals and in treated patients but the small amount of cholecystokinin that was released in untreated patients with celiac disease cochromatographed with cholecystokinin-33/39. We conclude that there is a reversible defect of gallbladder emptying and cholecystokinin release in celiac disease.

Adult↗
PubMed1985

Activated eosinophils in familial eosinophilic gastroenteritis.

Two siblings with eosinophilic gastroenteritis who presented with severe iron deficiency anemia and hypoalbuminemia associated with varying degrees of mucosal damage are described. Using a monoclonal antibody to the secreted form of eosinophil cationic protein, we demonstrated activated degranulating eosinophils in the gastrointestinal mucosa that correlated with the degree of histologic damage. This finding suggests that eosinophils may have a primary role in the tissue damage in this condition. Oral disodium cromoglycate (Nalcrom) failed to alter the clinical, radiologic, and histologic abnormalities. Prednisolone, however, was beneficial in 1 case but did not completely reverse the abnormalities.

Adolescent↗
PubMed1985

Human pancreatic and biliary responses to physiological concentrations of cholecystokinin octapeptide.

To determine the functional significance of physiological plasma concentrations of cholecystokinin, five volunteers each received graded doses of intravenous infusions of cholecystokinin octapeptide (CCK-8). At each dose plasma concentrations of CCK-8 were determined and pancreatic and biliary outputs were measured. Threshold plasma concentrations of CCK-8 for augmenting pancreatic trypsin secretion were undetectable (less than 3 pmol/l), and maximal trypsin output of 21.9 +/- 1.95 k-i.u./30 min was produced by 17.1 +/- 6.4 pmol of CCK-8/1. Calculated halfmaximal output was produced by 4.7 pmol of CCK-8/1. Maximal trypsin output during infusions of CCK-8 was significantly less than that after a combination of the CCK-like peptide, caerulein, and secretin (32.95 +/- 2.16 k-i.u./30 min, P less than 0.001). Biliary bile acid and bilirubin outputs were significantly augmented only when plasma concentrations of CCK-8 were greater than 5 pmol/l. Plasma concentrations of CCK-8 in the low picomolar range exert significant effects on pancreatic and biliary secretion. CCK-8 fulfills the criteria for a circulating hormone.

Adult↗
PubMed1985

"Downhill" esophageal varices and occlusion of superior and inferior vena cavas due to a systemic venulitis.

A patient with a 10-year history of episodes of venous thrombosis, a high ESR, an elevated plasma polyclonal 1gG concentration, and bleeding from esophageal varices had obstruction of both superior and inferior vena cavas with "downhill" esophageal varices and a normal portal vein with normal portal pressure. Extensive investigations revealed no predisposing factor for the venous thromboses, but the patient made a good clinical response to steroids and dapsone, with no further episodes of bleeding nor evidence of major venous thrombosis. The causes and outcome of "downhill" varices are discussed.

Adult↗
PubMed1985

Granulocyte migration in ulcerative colitis.

Although histologically relapses in ulcerative colitis are characterized by an intense granulocyte infiltrate, there is evidence both from in vitro function tests and skin window migration studies in vivo that there is defective granulocyte function in ulcerative colitis. We have recently developed a method for non invasively monitoring granulocyte migration to sites of inflammation using indium-111-labelled granulocytes, and have used this technique in fifteen patients with ulcerative colitis. In all fifteen cases there was rapid migration of indium-111-labelled granulocytes to inflamed bowel within 10 min of return of the labelled cells. This study provides no support for a significant granulocyte migration defect in ulcerative colitis.

Adolescent↗
PubMed1985

Controlled trial comparing prednisolone with an elemental diet plus non-absorbable antibiotics in active Crohn's disease.

In a randomised clinical trial, patients with moderately active Crohn's disease received either prednisolone 0.5 mg/kg/day plus a normal diet, or an elemental diet plus oral framycetin, colistin and nystatin. Patients were assessed using the Crohn's disease activity index (CDAI), ESR, and faecal granulocyte excretion quantified by 111In-autologous leucocytes. Five patients were intolerant of the elemental diet plus antibiotics and were withdrawn from the trial within 72 hours. Sixteen patients completed 10 days treatment on each regime. Fifteen of 16 patients on elemental diet plus antibiotics and all 16 patients on prednisolone improved with marked, but statistically indistinguishable falls in CDAI, ESR, and faecal granulocyte excretion between the two groups. Thus a regime decreasing the intraluminal concentration of bacteria and complex food molecules, was associated with rapid improvement in activity of Crohn's disease. This suggests that these intraluminal factors play a role in maintaining inflammation and that their removal or alteration offers an approach to management.

Adult↗
PubMed1985

Circulating human leucocyte elastase in patients with inflammatory bowel disease.

The plasma concentration of human leucocyte elastase (HLE), measured by enzyme immunoassay as the complex with alpha 1-proteinase inhibitor, was determined in 94 patients with active and inactive inflammatory bowel disease. In Crohn's disease and in ulcerative colitis human leucocyte elastase levels were raised significantly above normal when the disease was active, and fell on remission. The mean human leucocyte elastase level in 31 cases of active Crohn's disease was significantly greater than the mean human leucocyte elastase level in 23 patients with active ulcerative colitis (p = 0.013). The values of human leucocyte elastase correlated significantly with Crohn's disease activity index scores (p = 0.05) and with the circulating concentration of C-reactive protein (p less than 0.05 and p less than 0.01 for ulcerative colitis and Crohn's disease respectively), but not with the erythrocyte sedimentation rate. These results indicate that the concentration of human leucocyte elastase in the plasma of patients with inflammatory bowel disease reflects the activity of their intestinal disease and suggest that serial measurements of human leucocyte elastase may be useful in the assessment and clinical management of these conditions.

Adolescent↗
PubMed1985

In vivo assessment of granulocyte migration to diseased bowel in Crohn's disease.

It has been suggested, on the basis of impaired granulocyte migration to skin windows, that there is a fundamental granulocyte defect in Crohn's disease. In vitro tests of granulocyte function have, however, failed to confirm this. We have studied granulocyte migration to inflamed bowel in Crohn's disease using a new approach which utilises dynamic gamma camera imaging after injection of 111In labelled autologous granulocytes. In 20 of 22 studies there was rapid migration to diseased bowel, compatible with no migration delay. Only two patients showed delays in migration of 12 and 15 minutes respectively, but neither had any clinical characteristics to distinguish them from the other 20 patients. This study shows that the majority of patients with Crohn's disease in relapse have rapid granulocyte migration to diseased bowel and provides evidence against a significant migration defect in this condition.

Cell Movement↗
PubMed1985

111Indium autologous granulocytes in the detection of inflammatory bowel disease.

Indium leucocyte scanning and measurement of faecal Indium leucocyte excretion are techniques which have recently been introduced for assessing patients with inflammatory bowel disease. The methodology has recently been made more specific for acute inflammation by labelling pure granulocytes rather than the mixed leucocyte preparation. To determine the accuracy of this modified technique in detecting inflammatory bowel disease, we have prospectively compared Indium granulocyte scanning and faecal In granulocyte excretion with rectal histology and contrast bowel radiology as screening procedures in 100 patients with suspected inflammatory bowel disease. Thirty three patients were shown to have inflammatory bowel disease - 24 with Crohn's disease and nine with ulcerative colitis or indeterminate colitis. Overall the respective sensitivities for detecting inflammatory bowel disease were 97% for faecal Indium granulocyte excretion, 94% for Indium granulocyte scanning, 79% for radiology and 70% for rectal histology. The superiority of In granulocytes over radiology and rectal histology in detecting inflammatory bowel disease was, in the main, due to the difficulty in diagnosing Crohn's with conventional techniques. Although three of the patients with ulcerative colitis and indeterminate colitis had normal sigmoidoscopic appearances - all had abnormal rectal histology. No patient with a non-inflammatory bowel disorder had a positive In granulocyte scan or a raised faecal excretion. These results show that investigations using In granulocytes are accurate in identifying inflammatory bowel disease and offer important advantages over conventional procedures for detecting Crohn's disease.

Colitis, Ulcerative↗
PubMed1984

Reversed-phase high-performance liquid chromatography and separation of peptide hormones in human tissues and plasma with reference to cholecystokinins.

A reversed-phase high-performance liquid chromatographic method for the separation of peptide hormones has been applied to the measurement of large and small molecular forms of cholecystokinins in biological tissues. The method was validated for samples of human plasma and intestinal tissues, and for porcine gut extracts. The two-stage chromatographic process used semi-preparative reversed-phase packing for initial sample preparation, followed by gradient elution on a Hypersil ODS-5 column. Peptides in the fmol-nmol range were separated reproducibly, and recovered quantitatively. The method has been applied to the purification of a novel biologically active CCK peptide from a porcine gut extract.

Animals↗
PubMed1984

Comparison of fecal granulocyte excretion in ulcerative colitis and Crohn's colitis.

Impaired granulocyte migration has been suggested to be present in Crohn's disease on the basis of in vitro granulocyte function tests and in vivo skin window studies. This idea is supported by the impression histologically that the acute inflammatory infiltrate in diseased bowel is less in Crohn's disease than ulcerative colitis. We have developed a method of quantitating the acute inflammatory infiltrate in inflamed bowel by measuring fecal indium-111 granulocyte excretion and have compared this assessment in patients with ulcerative colitis and Crohn's colitis matched for disease activity. For equivalent disease groups in ulcerative colitis and Crohn's colitis, there was no significant difference between fecal granulocyte excretion. These findings provide no support for the contention that there is a reduced granulocyte infiltration in Crohn's disease.

Colitis, Ulcerative↗
PubMed1984

Differential distribution of molecular forms of cholecystokinin in human and porcine small intestinal mucosa.

To examine the distribution of cholecystokinins (CCKs) along the small intestine we examined the nature of CCKs in samples of jejunum, mid-intestine and ileum from human and porcine intestine. CCKs in intestinal mucosa were extracted by boiling in both neutral and acid conditions, and subjected to high pressure liquid chromatography (HPLC) to separate the forms of CCK followed by radioimmunoassay of separate fractions. In neutral extracts of human intestine CCK immunoreactivity totalled 119.4, 22.9 and less than 1 ng/g in jejunum, mid-intestine and ileum, whilst in acid extracts the corresponding values were 65.3, 47.4 and less than 1 ng/g. Amounts of CCK extracted from porcine mucosa were of similar magnitude. In neutral extracts material co-chromatographing on HPLC with synthetic porcine CCK 8 predominated, whilst in acid extracts material co-chromatographing with CCKs 33/39 was the major form. These forms of human and porcine CCKs extracted from the mucosa behaved similarly to CCK 8 and CCK 33/39 standards on HPLC, in the radioimmunoassay and on molecular exclusion chromatography - suggesting marked similarity of the CCKs in the two species. In both species there was a marked change in the ratios of CCK 8: CCK 33/39 down the intestine from 1: 0.8 in human jejunum to 1: 5.6 in mid-intestine and from 1: 1.5 in porcine jejunum to 1: 5.8 in mid-intestine. These observations may explain the changing patterns of CCKs in circulation with time after ingestion of a fat meal and the greater impairment of CCK 8 than CCK 33/39 release observed in coeliac disease.

Animals↗
PubMed1984

Infusion of cholecystokinin octapeptide in man: relation between plasma cholecystokinin concentrations and gallbladder emptying rates.

To establish the sensitivity of the gallbladder in relation to plasma concentrations of cholecystokinin, a dose-response study was performed in five normal volunteers. Cholecystokinin octapeptide was infused in ascending incremental dose sequence, interval blood samples taken for estimation of plasma hormone concentrations and gallbladder emptying rates monitored continuously using 99mTc-HIDA. In five other volunteers, gallbladder emptying rates following a liquid fat meal were measured. Infusion rates of 0.0, 0.75 +/- 0.2, 6.8 +/- 0.5, 23.8 +/- 1.6 and 66.1 +/- 2.5 pmol cholecystokinin kg-1 h-1 produced plasma concentrations of less than 3.0 (undetectable), less than 3.0, 6.6 +/- 1.8, 13.3 +/- 1.5 and 26.9 +/- 2.9 pmol l-1 respectively and gallbladder emptying rates (% min-1) of 0.0, 0.0, 0.14 +/- 0.15, 1.57 +/- 0.38 and 4.29 +/- 1.12. Following the fat meal, peak plasma cholecystokinin concentrations reach 30 pmol l-1 and gallbladder emptying rates (% min-1) are 3.86 +/- 1.01. We conclude that the threshold of the gallbladder to circulating cholecystokinin octapeptide is around 6 pmol l-1, but that infusions which result in plasma levels of around 25 pmol l-1 produce gallbladder emptying rates comparable with those seen after oral fat. This suggests that the gallbladder is equally sensitive to endogenous and exogenous cholecystokinin and that plasma concentrations observed after oral fat can entirely account for the gallbladder response.

Adolescent↗
PubMed1984

Peptide histidine isoleucine: a secretagogue in human jejunum.

Peptide histidine isoleucine (PHI) is a newly discovered peptide from porcine intestine, which has sequence homologies with VIP, an established intestinal secretagogue. To study the effects of PHI in human jejunum, natural porcine PHI was infused intravenously at 10.7 +/- 1.7 pmol/kg/min (mean +/- SEM) in normal volunteers during steady state perfusion of the jejunum with an isotonic bicarbonate-electrolyte solution. Plasma PHI concentrations rose to 279 +/- 26 pmol/l (mean +/- SEM) in the first 20 minutes of the infusion reaching 417 +/- 45 at 40 minutes. At these concentrations PHI induced a net secretion of chloride and sodium and either decreased net absorption or increased net secretion of fluid and potassium, while bicarbonate transport remained unaffected. Peptide histidine isoleucine is a potent jejunal secretagogue in man.

Adult↗