Search PubMed⌕ Search

Biomedical subjects

V S Chadwick

Publications and source records attributed to V S Chadwick.

At least 73 records · Page 4Linked to original sources

Atropine inhibits meal-stimulated release of cholecystokinin.

To examine the effect of atropine on cholecystokinin (CCK) release, we studied CCK concentrations after a liquid fat meal in five volunteers both with and without pretreatment with atropine. In control studies peak plasma CCK 8 concentrations were 15.0 +/- 6.2 pmol l-1, and the integrated plasma CCK 8 response was 415 +/- 216 pmol l-1(2)h-1. Peak plasma CCK 33/39 concentrations were 16.5 +/- 4.6 pmol l-1, and integrated CCK 33/9 response was 469 +/- 200 pmol l-1(2)h-1. After pretreatment with atropine postprandial CCKs were undetectable (p less than 0.05 versus control studies). The abolition of measurable CCK release by atropine may entirely account for its inhibitory effects on biliary secretion and in part for its effect on the pancreas.

Adult↗

Pancreatic exocrine and endocrine responses in chronic pancreatitis.

To test the discriminatory potential of certain indices of pancreatic function we performed duodenal perfusion studies and measured trypsin, bicarbonate, and lactoferrin outputs, and plasma concentrations of pancreatic polypeptide and motilin in the basal state and during continuous intravenous stimulation with 100 ng kg-1h-1 Ceruletide and 1 CU kg-1h-1 secretin. The following groups were studied: 12 normal volunteers (NV), seven patients with chronic pancreatitis with steatorrhea (CPS), and seven without steatorrhea (CP). Stimulated trypsin outputs, after 45 min of stimulation, were the best discriminant among the groups (NV versus CPS, p less than 0.0005; NV versus CP, p less than 0.005; CP versus CPS, p less than 0.05). Basal trypsin outputs showed similar patterns but failed to discriminate between NV and CP. Bicarbonate outputs were less discriminatory than trypsin outputs. Lactoferrin outputs failed to discriminate, but transient high peak outputs occurred in the initial stimulation period in all four patients with calcific chronic pancreatitis, suggesting a washout phenomenon. Basal motilin levels were elevated in both groups of pancreatitis (p less than 0.05). Stimulated pancreatic polypeptide levels were lower in CPS (NV versus CPS, p less than 0.05) but higher in CP (NV versus CP, p less than 0.005). These differences were also apparent in the basal state. We conclude that the best discrimination among the three groups was achieved by measurement of trypsin outputs, after 45 min of stimulation. In addition, the pancreatic polypeptide response may be used as a marker of residual pancreatic function in chronic pancreatitis.

Adult↗

Noninvasive investigation of the gastrointestinal tract in collagen-vascular disease.

We have investigated the use of 111Indium granulocyte scanning, which would be expected to identify areas of perivascular or generalized neutrophil infiltration, in patients with collagen-vascular diseases suffering from either gastrointestinal symptoms (diarrhea or abdominal pain in 15 patients) or otherwise unexplained fever (six patients). Among patients with gastrointestinal symptoms, seven of 15 had positive scans suggesting large or small bowel involvement--three of three patients with Behcet's syndrome, four of five with vasculitis, no patient in six with systemic lupus erythematosus, and no patient with Churg-Strauss syndrome. Among patients without gastrointestinal symptoms, only one patient with polyarteritis nodosa had a positive scan, showing both large and small intestinal involvement. White cell scanning offers a noninvasive, readily tolerated technique for identifying inflammatory involvement of the intestine in patients with collagen-vascular disorders. Gastrointestinal involvement is rare in the absence of symptoms; and among symptomatic patients, inflammatory involvement of the gut is more likely to be found in patients with vasculitis or Behcet's.

Abdomen↗

111Indium leucocyte scanning in ampicillin-associated right-sided hemorrhagic colitis.

Hemorrhagic colitis is a rare but well-recognized complication with ampicillin or penicillin derivative treatment. Early colonoscopy has been advocated in establishing the diagnosis by demonstrating the characteristic pattern of only right-sided involvement and so distinguishing it from other colitides. We report a patient who developed colitis after amoxycillin therapy in whom 111Indium leucocyte scan demonstrated right-sided colitis which alerted us to the diagnosis. Discontinuation of the antibiotic resulting in rapid improvement, and return of the 111Indium leucocyte scan to normal in this patient suggests that ampicillin-associated colitis should not be considered purely as a hemorrhagic disease but may in some cases have an inflammatory component.

Acute Disease↗

Sham feeding and pancreatic secretion. Evidence for direct vagal stimulation of enzyme output.

The cephalic phase of pancreatic secretion in humans was investigated using modified sham feeding and a duodenal perfusion system. Studies performed in 5 normal volunteers were designed so that trypsin and bicarbonate outputs during sham feeding, with or without pretreatment with atropine, were compared to "maximal" pancreatic secretory response to exogenous stimulation with caerulein and secretin. The role of gastric acid entry to the duodenum in mediating cephalic responses was assessed by a comparison between outputs observed when gastric aspiration (congruent to 80% efficient) was used alone and when acid entry was completely abolished by combining gastric aspiration with cimetidine pretreatment. To evaluate the role, if any, of gut hormone release in the pancreatic secretory response to sham feeding, plasma gastrin and cholecystokinin concentrations were monitored throughout. Trypsin outputs during sham feeding were 31.9 +/- 10.45 kallikrein inactivator units per 30 min, equivalent to four times basal output and 92% of maximal, but were only 54% maximal in subjects pretreated with cimetidine. Atropine suppressed basal trypsin output and abolished the response to sham feeding (4.98 +/- 3.89 kallikrein inactivator units per 30 min). A modest increase in bicarbonate secretion during sham feeding (3.30 +/- 1.97 mmol/30 min versus basal of 0.68 +/- 0.74 mmol/30 min, p = 0.5) was not influenced by atropine but was abolished by cimetidine pretreatment. No significant changes in plasma gastrins were observed in these studies and plasma cholecystokinins remained undetectable throughout. We conclude that there is tonic vagal stimulation of trypsin secretion, and that sham feeding markedly increases trypsin output, which is augmented further by acid entry into the duodenum. There is no direct effect of cephalic stimulation on bicarbonate secretion or on gastrin or cholecystokinin release.

Adult↗

Assessment of disease activity in inflammatory bowel disease: a new approach using 111In granulocyte scanning.

111In leucocyte scanning yields images of diseased bowel in patients with inflammatory bowel disease. The technique has recently been improved by being made more specific for acute inflammation by the isolation and labelling of a pure granulocyte preparation. The value of 111In granulocyte scanning in monitoring response to steroid treatment was assessed in 22 patients with Crohn's disease or ulcerative colitis. After steroid treatment there was agreement between the change in the scan grade and the change in clinical disease activity in 18 of the 22 patients. Overall there was a significant correlation between the change in the scan grade and clinical improvement (r = 0.775, p less than 0.001). This study suggests that 111In granulocyte scanning can provide a rapid assessment of disease activity in inflammatory bowel disease.

Colitis, Ulcerative↗

Role of hepatic arterial embolisation in the carcinoid syndrome.

Eighteen patients with severe symptoms of the carcinoid syndrome were assessed for hepatic embolisation. Four were too ill, and one had mild symptoms; thus 13 received a periembolisation regimen of cyproheptadine, fenclonine, aprotinin, methylprednisolone, tobramycin, flucloxacillin, and metronidazole. Embolisation was not performed in one patient with an occluded portal vein and was unsatisfactory in two others, in one because she was moribund and in the other because the hepatic artery had been ligated. Dramatic improvement in symptoms occurred in the nine patients in whom embolisation was successfully carried out, with abolition of flushing, severe abdominal pain, and wheeze and reduction in diarrhoea from 10.5 (SD 7.6) to 1.6 (0.9) stools/day. Urinary excretion of 5-hydroxyindole acetic acid fell from 1048 (716) to 289 (184) mumol/24 h (200 (137) to 55 (35) mg/24 h). Complications included one death from septicaemia, a hepatic abscess requiring surgical drainage, abdominal pain in three patients, pleural effusion in two, and transient encephalopathy in one. Relief of symptoms lasted for one to 24 months, and second embolisation in two patients produced further remissions of four to six months. Five patients died, one to 40 months after embolisation, in four cases because of metastases or heart failure. Hepatic embolisation is the treatment of choice for symptoms of the carcinoid syndrome resistant to medical treatment.

Adult↗

Peptide histidine isoleucine (PHI). A secretagogue in porcine intestine.

PHI (peptide histidine isoleucine) is a recently identified porcine peptide, present in large quantities in the intestine, which has sequence homologies with VIP, an established intestinal secretagogue, and with secretin, glucagon, and GIP. The effects of PHI on jejunal, ileal, and colonic fluid and electrolyte transport were studied in the pig. PHI appears to be an intestinal secretagogue inducing a reversible net secretion of fluid and electrolytes in jejunum and ileum and less marked effects in the colon.

Animals↗

An evaluation of a duodenal perfusion technique in human studies.

A retrospective evaluation was carried out on the standard duodenal perfusion technique in human subjects. Polyethylene glycol (PEG 4000), non-labelled or labelled with 14C, and phenol red were used as duodenal and gastric recovery markers, respectively. The evaluation was limited to the 2-h equilibration period in each study. The studies were carried out on the subjects sitting in an armchair. Multi-perforated wide-bore aspiration tubes accompanied with air ventiles were used for duodenal and gastric aspiration. High perfusion flow rates (less than or equal to 13.5 ml min-1) and a long perfusion segment (15-20 cm) were applied in the duodenum and the collection periods were kept short. An efficient gastric and duodenal aspiration was obtained in most studies with a limited gastro-duodenal and duodeno-gastric flux. On average, the fluctuations in concentration of the duodenal marker (PEG 4000) ('steady state'), expressed as a coefficient of variation (CV), were 13.1 +/- 1.0% (SEM, n = 66). Correlation analysis suggested that the 'steady state' conditions in the duodenum were improved by an efficient gastric and duodenal aspiration and a high perfusion flow rate. This was supported by an inverse correlation found between the magnitude of the gastro-duodenal flux and the marker's fluctuations, the efficiency of the gastric aspiration and the magnitude of the gastro-duodenal flux, and the efficiency of the duodenal aspiration and the magnitude of the duodeno-gastric flux. A high correlation was found between the two duodenal perfusion markers used, PEG 4000 and 14C PEG 4000.

Adult↗

111Indium autologous leucocytes in inflammatory bowel disease.

A non-invasive method of imaging and assessing inflammatory bowel disease is described. 111Indium labelled leucocyte scans were performed on 33 patients with a wide variety of inflammatory bowel diseases and 25 control patients. All patients with moderate or severe inflammatory bowel disease had positive scans with localisation of abnormal activity corresponding to the sites assessed to be diseased by radiology in either small or large bowel. No false positives were recorded in the control patients. Faecal excretion of 111In labelled leucocytes was increased in patients with inflammatory bowel disease according to disease severity and correlated with disease activity assessed by serum C-reactive protein levels (r = 0.74, p less than 0.001) or in those patients with Crohn's disease by Crohn's Disease Activity Index (r = 0.78, p less than 0.001). These data suggest that 111In labelled leucocytes may be used to provide a safe, non-invasive method of imaging diseased bowel and objectively assessing disease activity.

Colitis, Ulcerative↗

Malignant histiocytosis and encephalomyeloradiculopathy complicating coeliac disease.

A 62 year old Irish woman with an eight year history of probable coeliac disease developed brain stem signs, unilateral facial numbness and weakness, wasting and anaesthesia in both lower limbs. Over the next two years, a progressive deterioration in neurological function and in intestinal absorption, and the development of anaemia led to a suspicion of malignancy. Bone marrow biopsy revealed malignant histiocytosis. Treatment with cytotoxic drugs led to a transient, marked improvement in intestinal structure and function, and in power of the lower limbs. Relapse was associated with bone marrow failure, resulting in overwhelming infection. Post mortem examination confirmed the presence of an unusual demyelinating encephalomyelopathy affecting the brain stem and the posterior columns of the spinal cord.

Brain Diseases↗

SeHCAT absorption: a simple test of ileal dysfunction.

A new selenium-labelled synthetic bile salt SeHCAT (taurine conjugate of 23-[75Se]-25-homocholic acid) was assessed as a test of ileal dysfunction in 20 patients with inflammatory bowel disease (IBD). Whole body retention of SeHCAT was compared with tests of vitamin B12 absorption (Schilling test and whole body retention) and the cholylglycine-1-14C breath test and faecal isotope excretion. Clear differentiation, with no overlap was obtained between 10 normal subjects and patients with ileal disease/resection in the SeHCAT 7-day retention results. The Schilling test was more sensitive; enabling discrimination between patients with limited and extensive ileal disease/resection. An unexpected rise in SeHCAT retention was observed in patients with colonic IBD. The 7-day SeHCAT retention is a safe, simple screening test for ileal dysfunction and has practical advantages compared with the Schilling test.

Adult↗

Physiochemical studies on indocyanine green: molar lineic absorbance, pH tolerance, activation energy and rate of decay in various solvents.

Physiochemical studies were carried out on the tricarbocyanine dye indocyanine green in biological fluids and organic solvents. The molar lineic absorbance epsilon of the compound was highest in organic solvents (methanol, 1.2-propanediol, dimethylformamide) and bile, but lowest in water and duodenal fluid. Indocyanine green remained stable in methanol and bile (t1/2 greater than 1 year) but was rapidly decomposed to a colourless derivative in duodenal fluid and distilled water (t1/2 3.6 days and 1.4 days, respectively). It was thermostable (120 degrees C) in methanol and 1.2-propanediol but thermolabile in water and dimethylformamide where the activation energy for the decomposition reaction was low. At ambient temperature (20 degrees C) indocyanine green was particularly labile at pH less than 5 and pH greater than 11. The rate of decay of indocyanine green in various solvents indicated that the rate limiting step in the decay process was either a first or zero order reaction.

Chemical Phenomena↗

Assessment of disease activity in ulcerative colitis using indium-111-labelled leukocyte faecal excretion.

A new method of assessing disease activity in ulcerative colitis has been developed utilizing indium-111-labelled granulocytes. Faecal 111In excretion after intravenous administration of labelled granulocytes ranged from 1.1% to 45% of the injected dose in patients with ulcerative colitis, showing significant differences between mild, moderate, and severely active groups. There was a significant correlation between faecal 111In excretion and a clinical index based on the Crohn's disease activity index (r = 0.79, p less than 0.001) and the erythrocyte sedimentation rate (r = 0.73, p less than 0.001). Quantitative faecal 111In-labelled granulocyte excretion is an objective and specific method of assessing disease activity in ulcerative colitis.

Adolescent↗

Gastrointestinal manifestations of systemic vasculitis.

Systemic vasculitis is known to affect the gastrointestinal tract but the nature of the complication is poorly characterized. Out of 65 patients with systemic vasculitis, the majority of whom had renal disease, the intestine was found to be affected in 18. These comprised four of eight patients with polyarteritis nodosa, nine of seventeen with microscopic polyarteritis, four of thirty-six with Wegener's granulomatosis and one of four with Churg-Strauss syndrome. The features included abdominal pain (85 per cent), diarrhoea (50 per cent), gut haemorrhage (44 per cent) and abnormal liver function tests (50 per cent). Manifestations of gastrointestinal disease were evident at presentation in half the patients and led to a fetal outcome in five. Ileus, mucosal abnormalities, perforation and slow transit were evident radiographically, and selective visceral angiography showed aneurysms or organ infarcts in five patients. Histological assessment of gut biopsies (chiefly rectal) revealed non-specific inflammation or ulceration in nine patients and intramucosal haemorrhage in two. Focal areas of necrosis and ulceration in colonoscopic biopsies were highly suggestive of vasculitis whereas arteritis was only found in one full thickness biopsy. Hence the diagnosis of gastrointestinal complications depends largely on clinical evidence. In patients who survived, the gastrointestinal features remitted as the systemic illness improved following treatment with steroids, cyclophosphamide or plasma exchange.

Abdomen↗

Quantitative fecal indium 111-labeled leukocyte excretion in the assessment of disease in Crohn's disease.

The assessment of disease activity in Crohn's disease involves determination of either clinical indexes (e.g., Crohn's disease activity index) or laboratory measurements (e.g., C-reactive protein and erythrocyte sedimentation rate). These have the disadvantage of being indirect and nonspecific correlates of gut inflammation. We have assessed disease activity in Crohn's disease by measurement of fecal leukocyte excretion after intravenous administration of either 111In-labeled mixed leukocyte or pure granulocyte preparations. With mixed leukocyte preparations, fecal excretion of radioactivity correlated with Crohn's disease activity index (r = 0.78, p less than 0.001) and C-reactive protein (r = 0.74, p less than 0.01). Using pure granulocytes, fecal 111In excretion (range 1.5%-52%) was much higher than with mixed leukocytes (range 0.1%-11.0%), showing significant correlations with Crohn's disease activity index (r = 0.731, p less than 0.001), C-reactive protein (r = 0.716, p less than 0.001), and erythrocyte sedimentation rate (r = 0.676, p less than 0.001). Quantitative fecal excretion of 111In-leukocytes is a new method of assessing disease activity in Crohn's disease, specific for bowel inflammation and suitable for objective assessment of disease activity in therapeutic trials.

Blood Sedimentation↗

Physiochemical studies of indocyanine green (ICG): absorbance/concentration relationship, pH tolerance and assay precision in various solvents.

Indocyanine green (ICG) obeyed the Beer-Lambert law within the concentration range 1.25 micrograms/ml-10.0 micrograms/ml in distilled water, methanol, dimethylformamide (DMF), 1.2-propanediol and aqueous buffers (pH 9.0), but only up to 7.5 micrograms/ml in human bile and 0.5% human albumin, and only to 5.0 micrograms/ml in human duodenal fluid. ICG was rapidly (less than 1 h) decomposed to a colorless derivative at pH less than 5 and greater than 11, but remained relatively stable for 48 h at pH 8-10. ICG is an indicator and a weak acid with a pKa of 3.27. In bile stabilized with 25% methanol, the precision of the method (CV) is 5% and the accuracy is 106-127%.

Bile↗