Colonic polyps, occult blood, and chance.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to J B Simon.
Explore the source record for details and available documents.
A 31-yr-old man presented with the Budd-Chiari syndrome. A liver biopsy specimen demonstrated noncaseating centrilobular granulomas and an idiopathic necrotizing granulomatous venulitis involving hepatic vein radicles with superimposed thrombotic occlusion. High-dose prednisone therapy produced dramatic clinical improvement with resolution of the hepatomegaly, ascites, and portal hypertension and normalization of the hepatic venous angiogram. A repeat liver biopsy specimen showed resolution of the venulitis and disappearance of the hepatic vein thrombosis. Idiopathic granulomatous venulitis that is reversible with prednisone therapy should be considered in the differential diagnosis of the Budd-Chiari syndrome.
Testing feces for occult blood is widely recommended as a means of detecting subclinical colorectal tumors. Guaiac tests such as Hemoccult are the most widely used, but chemical sensitivity is relatively low and the tests are affected by dietary peroxidases, the state of fecal hydration, and certain drugs. The newly devised HemoQuant and immunologic techniques appear more sensitive and specific, but they require further evaluation before widespread clinical usage can be recommended. Occult blood screening has both merits and weaknesses. Testing does uncover subclinical colorectal cancer, often at a relatively early stage, but whether this actually improves the prognosis remains to be proven. Benign neoplastic polyps are also detected, although it is debatable whether this is a valid rationale for screening. Test sensitivity for malignancy varies from good to moderate, but is poor for benign polyps. Specificity is usually around 97%-98%, yet the predictive value of a positive test for cancer is only about 10%; hence most test-positive individuals are needlessly subjected to invasive colonic investigations. Reported figures on public compliance with occult blood testing vary widely from excellent to poor. Published costs of screening are usually quite low, but these overlook important indirect and hidden expenses and are therefore misleading. On balance, the problems of occult blood testing currently appear to outweight the merits. This could change, however, with the newer testing techniques and with awaited mortality data from controlled clinical trials now underway.
Explore the source record for details and available documents.
The efficacy of cimetidine in the prevention of gastrointestinal haemorrhage in a general intensive care unit was evaluated in 221 patients by a placebo controlled double blind randomised study. Criteria for bleeding were (i) haematemesis or gastric aspirate greater than 50 ml fresh blood, (ii) melaena or fresh blood per rectum with an upper source verified by endoscopy if the gastric aspirate was clear, (iii) a fall in haemoglobin level greater than 2 g/dl in a 24 hour period associated with either 4+ occult blood in stools, or coffee ground gastric drainage of at least 100 ml. The drug and placebo groups were similar for age, sex, duration of study and risk factors. One hundred and fourteen received cimetidine and 107 placebo. Only 8% of the patients bled with no significant difference between the two groups (6/114 cimetidine, 11/107 placebo; p = 0.16). There was no correlation between the frequency of bleeding and either the number of risk factors per patient or the duration of intensive care unit stay. Thirteen patients died in each study group, resulting in overall mortality of 12%. The low incidence of haemorrhage, the lack of statistical benefit from cimetidine and the similar mortality all argue against the routine use of this drug in intensive care unit patients.
Colorectal cancer is an important disease with high mortality. Clinical features are usually nonspecific and vary with the location of the tumor. Diagnosis depends on colonic investigations initiated by a high index of clinical suspicion. Rectal examination, sigmoidoscopy, air-contrast barium enema, and colonoscopy are the crucial diagnostic tools. Clinical judgment dictates the extent of work-up in individual symptomatic patients. Screening of asymptomatic middle-aged and elderly persons is widely advised but less widely practiced. More evidence is needed to clarify the value of screening, especially by occult blood testing. CEA testing is unsuitable for screening and of only limited value for monitoring patients with known colorectal cancer. Surgical resection is the mainstay of treatment. Radiotherapy is useful for palliation of rectal cancer and may delay postoperative tumor recurrence. Chemotherapy for disseminated disease generally gives disappointing results, since only a minority of tumors respond and survival benefit is marginal. Periodic colonic surveillance is important after tumor resection, primarily to detect premalignant new growths.
Explore the source record for details and available documents.
Swallowing is considered a rare cause of syncope. The five patients described in this report had a spectrum of gastrointestinal tract or cardiovascular disease. For each patient there was a clear association between swallowing and the onset of syncope. Prompt diagnosis of this potentially lethal condition is essential, and electrocardiographic monitoring during swallowing is advisable in all cases in which syncope is suspected.
The author reviews the literature on occult blood surveillance for colorectal carcinoma. The guaiac-based Hemoccult (SmithKline Diagnostics, Sunnyvale, Calif.) test is the most reliable and widely used. However, testing is complicated by several technical issues that can affect clinical results, and even successful screening programs will miss a high proportion of tumors. Public compliance is often poor, and a number of indirect and "hidden" costs make surveillance programs much more expensive than is usually claimed. Almost all published screening trials are uncontrolled. They generally detect about 3-20 colorectal malignancies for every 10,000 people enrolled, but only about 5%-10% of occult blood reactions are due to cancer. Though screen-detected tumors tend to be at a relatively early stage, this does not imply any benefit of surveillance because of lead time and length biases inherent in the screening process. Only controlled trials can answer the central question of whether screening decreases mortality from bowel cancer. Two such trials are underway, but mortality data are not yet available from either.
Explore the source record for details and available documents.
A 25-year-old white woman who had previously undergone two operations for peptic ulcer disease, and was addicted to drugs and alcohol, had massive hemorrhage from the small intestine. Angiography pinpointed the jejunum as the source of bleeding. Because the patient had a coagulopathy she was considered a poor risk for surgery. Bleeding was controlled by embolization with sterile, commercially available Gelfoam (Upjohn) which was injected into the offending branch of the superior mesenteric artery. This is believed to be only the third documented case of embolization of small intestinal vessels. A review of the available literature is presented and the value of Gelfoam embolization as an adjunct in the control of hemorrhage in selected patients is stressed.
Lipoprotein-X (LP-X) is an abnormal lipoprotein characteristic of cholestasis. To assess recent claims that its serum concentration helps differentiate extrahepatic from intrahepatic cholestasis, we studied 42 consecutive LP-X-positive patients. The mean serum LP-X level was higher in 18 patients with extrahepatic obstruction than in 24 with intrahepatic cholestatis, 321 +/- 89 versus 130 +/- 31 SEM mg per dl (P less than 0.05). However, values overlapped in 38 of the 42 cases, and in the other 4 the diagnosis of extrahepatic obstruction was obvious anyway from clinical examination. LP-X concentration gave little more information than did free cholesterol of phospholipid levels, which it closely paralleled (r = 0.89 and 0.81, respectively, P less than 0.01). There was no correlation with standard liver function tests or with activity of lecithin-cholesterol acyltransferase, the enzyme responsible for cholesterol esterification in plasma. Contrary to recent claims, these findings suggest that serum LP-X quantitation has little or no clinical value in distinguishing extrahepatic from intrahepatic cholestasis.
Human liver contains an acid cholesterol ester hydrolase (CEH) of presumed lysosomal origin, but its significance is unknown. We developed a modified CEH radioassay suitable for needle biopsy specimens and measured hepatic activity of this enzyme in 69 patients undergoing percutaneous liver biopsy. Histologically normal livers hydrolyzed 5.80 +/- 0.78 SEM mumoles of cholesterol ester per hr per g of liver protein (n, 10). Values were similar in alcoholic liver disease (n, 17), obstructive jaundice (n, 9), and miscellaneous hepatic disorders (n, 21). In contrast, mean hepatic CEH activity was more than 3-fold elevated in 12 patients with acute hepatitis, 21.05 +/- 2.45 SEM mumoles per hr per g of protein (P less than 0.01). In 2 patients studied serially, CEH returned to normal as hepatitis resolved. CEH activity in all patients paralleled SGOT levels (r, 0.84; P less than 0.01). There was no correlation with serum levels of free or esterified cholesterol nor with serum activity of lecithin-cholesterol acyltransferase, the enzyme responsible for cholesterol esterification in plasma. These studies confirm the presence of CEH activity in human liver and show markedly increased activity in acute hepatitis. The pathogenesis and clinical significance of altered hepatic CEH activity in liver disease require further study.
Stokke has described a lysosomal cholesterol ester hydrolase (CEH) in human liver. To clarify the significance of this enzyme, we first modified Stokke's assay to enable CEH determination in hepatic needle biopsies. Studies established optimal pH of 4.6--5.2 and linearity of hydrolysis for at least 12 hours, using homogenates containing about 2 mg liver and radiolabeled cholesterol oleate as substrate. The assay was then applied to patients undergoing percutaneous needle biopsy. Hepatic CEH activity in alcoholic liver disease, obstructive jaundice and a variety of other hepatic disorders was not significantly different from that in histologically normal livers. In patients with acute hepatitis, however, mean CEH activity was more than 3-fold increased (P less than 0.01). Values paralleled SGOT levels, returned to normal as hepatitis resolved, and were unrelated to serum cholesterol levels or to lecithin:cholesterol acyltransferase activity. In contrast to CEH, activity of acid phosphatase, a standard lysosomal marker enzyme, was the same in hepatitic as in normal livers. We conclude that CEH can be assayed in needle biopsies of human liver, that its activity increases in acute hepatitis, and that this is probably not simply due to a nonspecific general increase in lysosmal enzymes.
Explore the source record for details and available documents.
1. Cholesterol ester hydrolytic activity (sterol-ester hydrolase EC 3.1.1.13) was detected in human red blood cells. Enzyme activity appeared confined to the cell membrane and was most marked in washed preparations of red cell ghosts. 2. Hydrolytic activity was stimulated by the anti-oxidants D-alpha-tocopherol and butylated hydroxytoluene. Marked inhibition was produced by erythrocyte hemolysate, sodium taurocholate, and Triton X-100. 3. Optimal pH for the reaction was 5.4--5.7. 4. Because red cell cholesterol is all unesterified, it is speculated that the hydrolase serves to maintain the erythrocyte membrane free of esterified cholesterol.
Explore the source record for details and available documents.
The relative distribution of storage iron between bone marrow and liver has not been adequately studied in patients with iron-loading disorders. To help clarify this we assessed iron metabolism in patients with iron overload and in control subjects with cirrhosis but no excess body iron. In 4 patients with advanced iron overload studied late in the course of their illness, excess hemosiderin was present in both bone marrow and liver, as expected. In contrast, 2 patients with idiopathic hemochromatosis whose excess iron had been depleted by phlebotomy subsequently developed progressive hepatic parenchymal and reticuloendothelial (RE) deposition of iron, yet marrow hemosiderin remained sparse. Moreover, surface radioactivity over the liver after an oral dose of 59Fe. These results suggest that during the initial stages of hemochromatosis there is a dissociation in the rate of iron accumulation between the bone marrow and liver. Excess hemosiderin appears to be deposited predominantly and preferentially in hepatic storage sites until the later stages of the disease.