Biomedical subjects
Publications and source records attributed to C B Campbell.
Subfractions of gluten from two genetically different New Zealand wheats were injected intradermally in 16 patients with coeliac disease and 20 healthy controls. The coeliac patients as a group exhibited greater skin reactions when examined at seven hours than the controls. However, the skin test did not give sufficient discrimination to make it clinically useful as a screening test for coeliac disease.
Serum bile acids were measured in 28 patients with established liver disease. The peak serum level after a meal was as sensitive an index of liver disease as a combination of serum bilirubin, aspartate amino transferase, alkaline phosphatase and gamma glutamyl transpeptidase and was more often abnormal than any one of the four tests. Serum bile acid measurements may be of most value in detecting cirrhosis when the activity of disease is minimal.
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A series of 62 patients referred for endoscopic retrograde cholangiopancreatography is reported. The pancreatic or biliary ductular systems were demonstrated in 42, the success rate of cannulation improving with experience. The technique was diagnostic in 25 of 31 patients referred with hepatobiliary problems and in 3 of 11 with suspected pancreatic pathology. In a further seven patients in this latter group the examination was helpful in management. Duodenoscopy, without duct cannulation, demonstrated carcinoma of the periampullary region in two patients. Pancreatitis occurred in two patients and cholangitis in one. There are few contra-indications to the examination which should be undertaken early in the investigation of patients with cholestasis.
A diagnosis of coeliac disease was confirmed in 57 patients referred to a gastroenterology clinic over a 5 1/2-year period. Although diarrhoea was present in two-thirds of the patients, this was the major symptom leading to referral in less than half of them. When present, diarrhoea was usually intermittent and frequently not typical of steatorrhoea. Symptoms were of less than six months' duration in half the patients, but a review of the past and family history strongly indicated the possibility of coeliac disease in 39 of the 57 patients. A high spontaneous abortion rate during pregnancy was noted. The frequent absence of the classical features of malabsorption, diarrhoea with typical steatorrhoea and chronic debility was noted. All screening tests for malabsorption were found to be unreliable and their routine use was rarely justified. A random serum folate and carotene assay proved as valuable as more expensive and troublesome tests. It is stressed that in any case in which there is a clinical suspicion of this diagnosis, a small intestinal biopsy should be undertaken.
A ten-year-old boy persented with a prolonged cholestatic liver disease 5 weeks after starting diphenylhydantoin therapy. The initial phase of his illness was characterized by hepatocellular damage with swollen liver cells and centrilobular cholestasis. Severe hyperlipoproteinemia with eruptive xanthomata developed within 3 weeks of his initial jaundice. The second phase of his illness was characterized by portal tract inflammation with bile ductular proliferation and chronic cholestasis gradually resolving over a period of 15 months. It is postulated that diphenylhydantoin sensitivity produced swollen hepatocytes with hypertrophy of the smooth endoplasmic reticulum, reducing hepatic sinusoidal blood flow and the clearance of secondary bile salts. A fall in clearance of lipoproteins, including the cholesterol precursor of primary bile acid synthesis, may have been responsible for a reduction in serum bile acid concentration. High levels of serum lithocholic acid, largely unsulfated presumably due to decreased hepatic uptake, may have produced the prolonged second phase of this illness when histological changes resembled that seen in experimental animals following lithocholic acid administration.
Bile salts are synthesized in the liver from cholesterol, conjugated with glycine or taurine and secreted in bile with cholesterol and lecithin. The molar concentrations of these three lipids determine solubility of cholesterol in bile. Within the gastrointestinal lumen bile salts play an essential role in lipid absorption and faty transport. An efficienct entero-hepatic circulation maintains hepatic bile salt secretion and provides a "feed-back" control of the bile salt and cholesterol metabolism. Potentially hepatotoxic lithocholic acid formed in the intestinal lumen by bacterial action on chenodeoxycholic acid is sulphated in the liver thus decreasing intestinal reabsorption. The total faecal excretion of bile salts balances hepatic synthesis and represents a major catabolic path in cholesterol metabolism.
Alterations of bile salt metabolism have been shown in numerous diseases. Liver damage results in elevated serum bile salt concentrations which may be useful as a sensitive index of hepatocellular disease. Changes in the relative proportions of the individual bile salts in serum occur with cholestasis. Urinary excretion of bile salts, largely in the form of sulphates, increases as a compensatory mechanism. Ileal disease or resection causes bile salt melabsorption. The increase in colonic bile salts produces a watery diarrhoea while the decrease in duodenal levels may cause steatorrhoea. Cholelithiasis may result from alteration in the relative proportions of cholesterol, lecithin and bile salts in bile. The mechanism apparently differs in various conditions predisposing to gallstone formation. A primary alteration of bile salt metabolism has been postulated in several other conditions. Considerable interest centres on the importance of metabolites of bile salts in the pathogenesis of colonic carcinoma. Chenodeoxycholic acid is a successful though costly treatment for selected patients with cholesterol gallstones. Bile salt binding agents, such as cholestyramine, are extremely useful especially in the control of pruritus in patients with cholestasis.
The consequences of occlusion of a major upper extremity vein were evaluated in eight patients with effort thrombosis, ten with thrombosis secondary to intimal injury, six with extrinsic compression, and one hypercoagulable patient, all of whom were followed for an average of 4 years. Twenty-two patients had venography, which confirmed the diagnosis but often failed to define the proximal extent of obstruction. Thirteen patients had noninvasive hemodynamic studies which did not corroborate chronic morbidity, but which were valuable in assessing the effect os specific therapy. Twelve patients were treated with anticoagulants, and six had operative removal or bypass of the obstruction. Three patients had pulmonary emboli; two embolized while on anticoagulants and both died. Swelling, pain, prominent veins, and easy fatigability of the affected extremity were the late sequelae of occlusion. Chronic morbidity was more dependent on etiology than on initial treatment. Thrombosis secondary to intimal injury caused no persistent symptoms, whether treated with anticoagulants or not. Effort thrombosis was intermediate: three fourths complained that their affected arm tired easily and half had prominent veins or persistent swelling. All of those with obstruction secondary to extrinsic compression had easy fatigability. The majority also had concomitant swelling, pain, and prominent collaterals. Operative treatment produced objective improvement in venous outflow but often was unsuccessful in relieving symptoms, particularly in patients with obstruction from extrinsic compression.
Anterograde degeneration resulting from small lesions placed in either the insular or temporal cortex were traced with the Fink-Heimer reduced silver procedure. In neocortical regions ipsilateral to the lesion axonal degeneration was present in auditory subdivisions AI, AII, Ep, I, T, in the second somatosensory area (SII), in the anterior and middle suprasylvian gyrus, in the posteromedial suprasylvian and posterior lateral gyri, in the posterior splenial gyrus, in the anterior two-thirds of the cingulate gyrus and in the orbitofrontal regions. With respect to interhemispheric connections, evidence was obtained for a dual pattern of projection. In addition to significant amounts of axonal and terminal degeneration in the corresponding insular or temporal fields, axonal degeneration was also present in posterior AII. In the thalamus degeneration was found in the medial dorsal, suprageniculate, and lateral posterior-pulvinar nuclei. In the posterior nuclear group (Po) and the principal division of the medial geniculate (GMp) evidence was obtained for a topographic pattern of projection; significantly more degeneration occurred in caudal Po following insular lesions whereas with temporal lesions more degeneration occurred in caudal GMp. Degeneration was also found in the dorsal cortex of the ipsilateral inferior colliculus, bilaterally in the deep layers of the superior colliculus and the periventricular central gray region, ipsilaterally in the ventromedial aspects of the head and body of the caudate nucleus, and in the lateral and central nuclei of the amygdala. These findings are discussed in terms of their significance for a possible role for the insular and temporal neocortex (I-T) in both multimodal sensory discrimination and sensory-visceral integrative functions.
Two complications of diagnostic colonoscopy are reported. One patient had a perforation which was recognized immediately, and the other had a serosal tear discovered fortuitously at elective surgery. Previous reports of colonoscopic complications are reviewed, and factors predisposing to such complications are discussed.
The xylose absorption and excretion test has been reassessed in controls and patients with coeliac disease. Xylose has been assayed in both serum and urine colorimetrically and by liquid scintillation counting using xylose-1-14C. The excretion of 14CO2 in breath following administration of xylose-1-14C has been measured. Liquid scintillation counting is a simple and reliable method for the measurement of xylose absorption. Serum xylose levels, urinary xylose excretion, or breath 14CO2 in isolation were poor screening tests for mucosal disease. The use of serum levels and urinary excretion in combination improved the discriminatory value of the test though small gut biopsy was more reliable.
The distribution of the major subtypes of hepatitis B surface antigen (HBsAg) was examined in asymptomatic white Australian blood donors and patients with liver disease to attempt ot assess the biological significance of these subtypes in this relatively homogeneous Caucasian population. Since previous studies have shown a very low prevalence of HBsAg in white Australians, a highly sensitive solid phase radioimmunoassay (RIA) was developed and used to subtype the antigen. A total of 46 samples of hepatitis B-antigen positive sera, obtained from 21 asymptomatic volunteer blood donors and 25 patients with liver disease, were tested. Sixteen of these 21 asymptomatic carriers were shown to have subtype "ad" whereas only seven of the patients with liver disease had this subtype. This difference was significant (P less than 0.005) and supports the view that subtype "ad" is associated with a carrier state and subtype "ay" with liver disease in Australia.
A method is described to assay sulphated and non-sulphated bile acids in serum using gas-liquid chromatography. Previously described techniques have been substantially modified to allow analysis of free and conjugated salts of the four major bile acids with particular care to ensure quantitative recoveries of lithocholic acid, its conjugates and sulphate esters. Losses of lithocholic acid inherent in some methods have been reduced by avoidance of column chromatography with alumina and extraction of lipid contaminants into heptane. Assay of the proportion of serum bile acids present as sulphate esters is achieved by the routine use of column chromatography to separate sulphated bile acids from non-sulphated bile acids followed by solvolysis of the sulphated bile acids before deconjugation. Careful selection of the conditions of strong alkaline hydrolysis ensures deconjugation of all bile salt conjugates including lithocholic conjugates which are not completely hydrolysed in weaker alkaline solutions. The trifluoroacetate derivatives of the methyl esters of the bile acids are chromatographed using 5-beta-cholanic acid as an internal standard with clear separation of the four major bile acids from the internal standard. In 10 fasting control subjects the mean serum total bile acid concentration was 5.3 muM (RANGE 1.1-16.4) including 0.7 mum sulphated bile acid (range 0-1.8). In 10 patients with acute viral hepatitis the total bile acid concentration was elevated in some but normal in others (mean 44.9 muM, range 2.7-80.3). The percentage of the total bile acid sulphated was not significantly different in the hepatitis patients compared to controls (controls 13%, range 0-35; hepatitis 23%, range 0-52). Lithocholic acid made up 13% of the total bile acid in controls (0-32%) and 18% in hepatitis patients (0-53%). Most of this lithocholic acid was sulphated (controls 81%, range 30-100; hepatitis 67%, range 37-100). Unconjugated bile acids were demonstrated in the serum of a few patients with acute viral hepatitis but in no control subjects.
A 54-year-old man presented with the Guillain Barré syndrome (GBS) during the pre-icteric phase of acute type B viral hepatitis. This neurological syndrome has been infrequently described in the clinical course of viral hepatitis but only once previously during the prodromal period. Deposition of circulating immune complexes of the HBsAg have been implicated in the pathogenesis of arthritis, nephritis and polyarteritis associated with type B viral hepatitis. Although the relationship of GBS to type B viral hepatitis is uncertain, a similar immunopathological mechanism may be involved.
Faecal bile acid excretion was estimated in a clinical laboratory using gas liquid chromatography. The original method of Grundy et al was simplified so that quantitative thin layer chromatography was not required. Rigid dietary control or inpatient facilities were unnecessary for clinical studies. Control patients studied under these conditions had a daily faecal bile acid excretion of 0.37 +/- 0.13 g/day. Patients with ileal resections varied markedly with bile acid excretions ranging from 0.25--6.32 g/day (mean 2.36 +/- 1.11).
The leucocyte adherence inhibition test provides a rapid, reliable, and specific technique for the immunodiagnosis of primary hepatocellular carcinoma (malignant hepatoma). The patient's blood leucocytes are tested in vitro for cell-mediated immunity against tumour-associated antigens and the serum is tested for blocking factor which interferes with the immunological reaction. Specific reactivity of both leucocytes and serum was consistently detected in patients with malignant hepatoma, and negative reactions were obtained in other liver diseases including secondary tumours of the liver. The test has provided positive evidence for the presence of hepatoma when more conventional methods gave doubtful or negative results. A positive result preceded the clinical appearance of tumour by up to three years in two patients.