H. J. F. Hodgson

Serum levels of C-reactive protein in Crohn's disease and ulcerative colitis

Abstract. Prospective measurements were made of serum C‐reactive protein levels and erythrocyte sedimentation rate in sixty‐four patients with Crohns disease and fifty with ulcerative colitis. The results were related to clinical assessment of disease activity. C‐reactive protein levels were raised in both groups but were significantly higher in Crohns disease than ulcerative colitis for all categories of disease severity: with mild disease the median and range of C‐reactive protein concentration were 4, 0–65 mg/l in Crohns disease v. 0, 0–15 mg/l in ulcerative colitis, P<0·01; in moderate disease the values were 15, 1–100 mg/l v. 3, 0–29 mg/l respectively, P<0·05 and in cases of severe disease, 85, 15–183 mg/l v. 12, 2–33 mg/l respectively, P<0·001. Erythrocyte sedimentation rate was also higher in Crohns disease but did not closely reflect disease activity in individual patients. C‐reactive protein levels corresponded closely with clinical and pathological indices of relapse, remission and response to therapy in patients with Crohns disease. The precise assay of serum C‐reactive protein provides an objective criterion of inflammatory activity, which may be useful in the assessment, management and study of Crohns disease.

NEUROTENSIN SECRETION BY FIBROLAMELLAR CARCINOMA OF THE LIVER

Serum neurotensin concentrations were supranormal in 5 out of 20 patients with carcinoma of the liver. Liver specimens from 4 of these 5 patients demonstrated features typical of fibrolamellar carcinoma. Neurotensin may be suitable as a tumour marker for fibrolamellar carcinoma and may be useful for the detection of recurrences after treatment.

Visualising E-selectin in the detection and evaluation of inflammatory bowel disease.

Background—Vascular endothelial E- selectin expression is induced by proinflammatory cytokines and contributes to accumulation of leucocytes in tissues. Aims—To investigate the role of E-selectin in inflammatory bowel disease (IBD). Methods—E-selectin expression was assessed in patients with ulcerative colitis and Crohn’s disease by measuring the concentration of circulating soluble E-selectin (sE-selectin) using ELISA, by immunohistochemistry of colonic biopsy specimens, and by abdominal immunoscintigraphy after injecting radiolabelled F(ab′)2 fragment of a monoclonal anti-E-selectin antibody. The value of scintigraphy using anti-E-selectin was judged by a prospective comparative study of autologous leucocyte scanning and E-selectin antibody scanning in 17 patients with IBD. Results—Circulating sE-selectin was elevated in patients with clinically active disease. Tissue expression of E-selectin was enhanced in patients with active inflammation, with weak or absent expression in inactive disease and healthy controls. In-111 labelled anti-E-selectin scintiscans were compared with Tc-99m labelled leucocyte scans performed 24 hours earlier. Twelve patients had areas of active inflammation on leucocyte scan while 11 patients had positive E-selectin scans. The results of the two scans were concordant in 14 patients, with those positive for both (10/17) showing similar disease localisation and extent. Conclusions—Tissue E-selectin and circulating sE-selectin are increased during active inflammatory bowel disease. Anti-E-selectin imaging with radiolabelled monoclonal antibody identified areas of inflammation in Crohn’s disease and ulcerative colitis. The technique should prove useful clinically for identifying the site and extent of disease.

Phosphorus-31 magnetic resonance spectroscopy of the human liver using chemical shift imaging techniques

Phosphorus-31 magnetic resonance spectroscopy of the human liver was undertaken in 28 healthy adult individuals and in 49 patients with liver disease of varying aetiology. Data localised to the liver were obtained using chemical shift imaging techniques. The mean (+/- 1 S.D.) of the peak area ratio phosphomonoesters (PME)/phosphodiesters (PDE) in healthy adult individuals, from spectra obtained with pulse angle 45 degrees and repetition time 1 s, was 0.24 +/- 0.07. The intra-examination variability of this ratio was 20%, the intra-subject variability 27% and the inter-subject variability 32%. An increase in the PME/PDE was observed in the 31P hepatic MR spectrum from primary or secondary tumours in all 17 patients studied, which invariably represented an increase in PME/ATP and, in some cases, a reduction in PDE/ATP. The spectra did not show aetiological characteristics. A non-specific elevation in PME/PDE was also observed in the 31P hepatic MR spectra of 10 (40%) of 25 patients studied who had diffuse liver diseases, such as cirrhosis and infiltrating malignancies. The spectral pattern did not distinguish between diseases of varying aetiologies, but there was a linear correlation between increasing PME/PDE and a reduction in plasma albumin concentrations (p = 0.03). In three patients with hepatic malignancy and abnormal hepatic 31P-MRS, marked spectral changes were observed after successful treatment to debulk the tumour. Only minor changes were observed in the abnormal spectrum of a fourth patient in whom treatment was unsuccessful. Hepatic 31P-MR spectroscopy may prove useful for monitoring disease processes and treatment effects in well characterised patient populations.

Faecal Elastase Reflects Disease Activity in Active Ulcerative Colitis

Alpha-1-proteinase inhibitor-bound elastase (EPIC) was measured in plasma and fresh stool samples from 20 patients with Crohns disease (CD), 16 patients with ulcerative colitis (UC), and 10 controls. Median EPIC values were significantly higher than normal in active CD and UC. EPIC was virtually undetectable in the stool samples of control subjects. Median faecal EPIC in 14 patients with active CD (478 ng/ml) or 10 patients with active UC (1159 ng/ml) was significantly higher than in quiescent disease (p less than 0.05) and in control subjects (p less than 0.001 in each case). The difference in the median values between active CD and UC was not significant (p = 0.065). The median faecal EPIC levels were identical in active UC (1159 ng/ml) and patients with large-bowel CD (LBCD) (1015 ng/ml) (p = 0.9), and each was significantly higher than the value of 168 ng/ml in small-bowel CD (SBCD) (p less than 0.01 in each case). In active LBCD but not in SBCD, faecal EPIC correlated significantly with Crohns disease activity index (R = 0.78, p less than 0.05), plasma C-reactive protein (CRP) (R = 0.9, p less than 0.01), and erythrocyte sedimentation rate (ESR) (R = 0.74, p less than 0.05). In active UC, faecal EPIC correlated significantly with a numerical disease activity index (R = 0.9, p less than 0.01) but not with plasma EPIC and CRP, ESR, and leucocyte counts. Faecal EPIC values may be a better reflection of disease activity in active UC than plasma levels of markers of inflammation.

MR imaging and spectroscopy of the basal ganglia in chronic liver disease: Correlation of T1-weighted contrast measurements with abnormalities in proton and phosphorus-31 MR spectra

The purpose of this study was to correlate the hyperintensity in the globus pallidus seen on T1-weighted magnetic resonance imaging (MRI) of the brain in chronic liver disease with changes in metabolite ratios measured from both proton and phosphorus-31 magnetic resonance spectroscopy (MRS) localised to the basal ganglia. T1-weighted spin echo (T1 WSE) images were obtained in 21 patients with biopsy-proven cirrhosis (nine Childs grade A, eight Childs grade B and four Childs grade C). Four subjects showed no evidence of neuropsychiatric impairment on clinical, psychometric and electrophysiological testing, four showed evidence of subclinical hepatic encephalopathy and 13 had overt hepatic encephalopathy. Signal intensities of the globus pallidus and adjacent brain parenchyma were measured and contrast calculated, which correlated with the severity of the underlying liver disease, when graded according to the Pughs score (p<0.05). Proton MRS of the basal ganglia was performed in 12 patients and 14 healthy volunteers. Peak area ratios of choline (Cho), glutamine and glutamate (Glx) and N-acetylaspartate relative to creatine (Cr) were measured. Significant reductions in mean Cho/Cr and elevations in mean Glx/Cr ratios were observed in the patient population. Phosphorus-31 MRS of the basal ganglia was performed in the remaining nine patients and in 15 healthy volunteers. Peak area ratios of phosphomonoesters (PME), inorganic phosphate, phosphodiesters (PDE) and phosphocreatine relative to BATP (ATP) were then measured. Mean values of PME/ATP and PDE/ATP were significantly lower in the patient population. No correlation was found between the T1WSE MRI contrast measurements of the globus pallidus and the abnormalities in the metabolite ratios measured from either proton or phosphorus-31 MR spectra. Our results suggest that pallidal hyperintensity seen on T1WSE MR imaging of patients with chronic liver disease is not related to the functional abnormalities of the brain observed in hepatic encephalopathy.

Corticosteroids reduce regenerative repair of epithelium in experimental gastric ulcers.

The association between corticosteroid treatment and gastric ulcer healing is controversial. The effects of corticosteroids on experimental ulcer healing in the rat were studied and the effect of coadministration of a prostaglandin E1 analogue was determined. Forty male adult rats were divided into five groups and pretreated for 10 days as follows: (a) control, (b) prednisolone (10 mg/kg), (c) prednisolone and misoprostol (300 micrograms/kg), (d) misoprostol, and (e) indomethacin (2 mg/kg) Gastric ulcer was induced by applying a cryoprobe to the serosal surface of the stomach. Healing was assessed by determining the ulcer size at three and six days. Mucosal regenerative activity at the ulcer edge was assessed by quantitating DNA synthesis in cells by immunohistochemical techniques using monoclonal antibodies to detect expression of proliferating cell nuclear antigen (PCNA) and incorporated 5-bromo-5-iododeoxyuridine (BrdU). Compared with control rats, the rate of healing and the mucosal regenerative activity were significantly reduced in rats treated with prednisolone and indomethacin (p < 0.05). Coadministration of misoprostol and corticosteroids reversed the delay in healing and the reduction in mucosal regeneration induced by corticosteroids alone. With misoprostol alone, the ulcer size and the number of epithelial cells that actively synthesised DNA did not differ from control animals. A comparison between the two immunohistochemical markers of cell proliferation showed a highly significant correlation between the two techniques (r = 0.64, p < 0.005), indicating that the simpler PCNA technique should prove valuable in assessing regeneration in experimental ulcer disease.

In vivo and in vitro hepatic phosphorus-31 magnetic resonance spectroscopy and electron microscopy in chronic ductopenic rejection of human liver allografts

Background—In vivo hepatic phosphorus-31 magnetic resonance spectroscopy (MRS) provides non-invasive information about phospholipid metabolism. Aims—To delineate MRS abnormalities in patients with chronic ductopenic rejection (CDR) and to characterise spectral changes by in vitro MRS and electron microscopy. Patients and methods—Sixteen liver transplant recipients (four with CDR; 12 with good graft function) and 29 controls (23 healthy volunteers; six patients with biliary duct strictures) were studied with in vivo 31P MRS. Peak area ratios of phosphomonoesters (PME) and phosphodiesters (PDE), relative to nucleotide triphosphates (NTP) were measured. In vitro MRS and electron microscopy were performed on biopsy specimens from five patients with CDR, freeze clamped at retransplantation. Phosphoethanolamine (PE), phosphocholine (PC), glycerophosphorylethanolamine (GPE), and glycerophosphorylcholine (GPC) concentrations were measured. Results—The 12 patients with good graft function displayed no spectral abnormalities in vivo; the four patients with CDR showed significantly elevated PME:NTP (p<0.01) and PDE:NTP ratios (p<0.005). Patients with biliary strictures had significant differences in PME:NTP (p<0.01) from patients with CDR, but not in mean PDE:NTP. In vitro spectra from CDR patients showed elevated PE and PC, mirroring the in vivo changes in PME, but reduced GPE and GPC concentrations were observed, at variance with the in vivo PDE findings. On electron microscopy, there was no proliferation in hepatocyte endoplasmic reticulum. Conclusions—The increase in PME:NTP reflects altered phospholipid metabolism in patients with CDR, while the increase in PDE:NTP may represent a significant contribution from bile phospholipid.

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 Crohns 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.

Growth hormone secretion dynamics in a patient with ectopic growth hormone-releasing factor production

A female patient with acromegaly, hypercalcemia, and Zollinger-Ellison syndrome was found to have a very high plasma concentration (average 2,300 pmol/liter; normal less than 50 pmol/liter) of growth hormone-releasing factor as measured by a radioimmunoassay to human pituitary growth hormone-releasing factor-1-44. The plasma concentration of growth hormone averaged 25 mIU/liter (normal less than 5 mIU/liter) and there was no rise following an intravenous 100 micrograms bolus of human pituitary growth hormone-releasing factor-1-44. Plasma growth hormone and growth hormone-releasing factor levels were unaffected by bromocriptine, insulin-induced hypoglycemia, and sleep. A long-acting somatostatin analogue lowered both the growth hormone-releasing factor and the growth hormone levels. Thyrotropin-releasing hormone stimulation and oral glucose tolerance tests produced significant increases in plasma growth hormone levels whereas the growth hormone-releasing factor level remained unchanged, suggesting that when normal somatotrophs are exposed to maximal growth hormone-releasing factor stimulation, thyrotropin-releasing hormone becomes a secretagogue of growth hormone from the pituitary. It is proposed that in the absence of a radioimmunoassay for growth hormone-releasing factor, a lack of growth hormone response to growth hormone-releasing factor in a patient with acromegaly is compatible with a source of ectopic growth hormone-releasing factor production.