Antimitochondrial antibodies and antiphospholipid antibodies.
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Autoantibodies↗
Biomedical subjects
C N Williams
Publications and source records attributed to C N Williams.
Role of rectal formulations: suppositories.
Mesalazine (5-aminosalicylic acid) suppositories are safe, effective, well tolerated, and well retained in patients with active distal proctitis. The best results are seen in patients with idiopathic ulcerative proctitis. Approximately 85% of these patients are healed within 4 weeks and virtually 100% by 10 weeks, with mucosal healing and complete loss of symptoms. Suppositories cover the last 20 cm of the rectum, as shown by technetium labelling. Maintenance therapy using suppositories alone--in doses varying from 500 mg every second bedtime to 1000 mg per day in divided doses--is at least as effective as oral sulphasalazine. Mesalazine suppositories are also useful in treating patients with Crohn's disease affecting the rectum, although the response rate is slower and healing is incomplete in half the patients treated. In the rare solitary rectal ulcer syndrome, mesalazine suppositories may be as efficacious as mesalazine enemas. Patient compliance and dramatic response even when conventional therapy has failed make an excellent case for mesalazine suppositories being the treatment of choice for distal ulcerative proctocolitis.
Administration, Rectal↗
The role of heme oxygenase and aryl hydrocarbon hydroxylase in the protection by cysteamine from acetaminophen hepatotoxicity.
Administration of cysteamine to rats depressed hepatic aryl hydrocarbon hydroxylase (AHH) activity, cytochrome P-450, and total heme at 24 hr. Total heme remained decreased at 48 hr when all other parameters returned to control values. A significant 5-fold increase in heme oxygenase activity occurred in rat liver 5 hr after treatment, when AHH activity and total heme were unchanged. Histological examination of liver biopsies from rats treated with cysteamine revealed normal hepatic architecture. The observed effects of cysteamine on hepatic drug-metabolizing enzymes in vivo were not due to cysteamine-induced hepatotoxicity. Our results indicate that cysteamine increases heme oxygenase activity in rat liver, with a subsequent decrease in total heme, AHH activity, and cytochrome P-450 content. The depression of P-450 by cysteamine is likely to be an important mechanism for its protection in acetaminophen overdose. The protection studies illustrate this mechanism. Centrilobular hepatic necrosis and elevation in transaminase activity following a toxic dose of acetaminophen were prevented by treatment with cysteamine. The hepatoprotective effect of cysteamine was evident when acetaminophen was administered 24 hr after cysteamine but did not occur when acetaminophen was administered 5 hr after cysteamine or simultaneously. All groups of rats receiving cysteamine showed decreased mortality compared to the group receiving acetaminophen alone.
Acetaminophen↗
Lyophilized Clostridium perfringens 3 alpha- and Clostridium bifermentans 7 alpha-hydroxysteroid dehydrogenases: two new stable enzyme preparations for routine bile acid analysis.
Preparations of 3 alpha-hydroxysteroid dehydrogenase (EC 1.1.1.50) from Clostridium perfringens were successfully lyophilized into a stable powder form. Purification of the enzyme was achieved using triazine dye affinity chromatography. C. perfringens 3 alpha-hydroxysteroid dehydrogenase was purified 24-fold using Reactive Red 120 (Procion Red) -cross-linked agarose (70% yield). Quantitative measurement of bile acids with the purified enzymes, 3 alpha-hydroxysteroid dehydrogenase and 7 alpha-hydroxysteroid dehydrogenase (EC 1.1.1.159) from Clostridium bifermentans (strain F-6), was achieved spectrophotometrically. Standard curves with chenodeoxycholic acid (CDC) and cholic acid were linear within a concentration range of 20-100 microM. Analysis of mixtures of ursodeoxycholic acid and CDC showed the additive nature of the 3 alpha-hydroxysteroid dehydrogenase and showed also that 7 alpha-hydroxyl groups were independently quantified by the 7 alpha-hydroxysteroid dehydrogenase. Bile acids in Folch extracts of human bile samples were measured using purified preparations of Pseudomonas testosteroni 3 alpha-hydroxysteroid dehydrogenase, C. perfringens 3 alpha-hydroxysteroid dehydrogenase, Escherichia coli 7 alpha-hydroxysteroid dehydrogenase and C. bifermentans (strain F-6) 7 alpha-hydroxysteroid dehydrogenase. Statistical comparison validated the use of C. perfringens 3 alpha- and C. bifermentans 7 alpha-hydroxysteroid dehydrogenases for the quantification of bile acids in bile.
3-Hydroxysteroid Dehydrogenases↗
Omeprazole (20 mg daily) versus cimetidine (1200 mg daily) in duodenal ulcer healing and pain relief.
We conducted a double-blind, randomized, parallel group study in 169 patients with acute duodenal ulcers to compare omeprazole, 20 mg daily, with cimetidine, 600 mg twice daily. After 2 wk, 58% of the omeprazole-treated patients and 46% of the cimetidine-treated patients were completely healed (p = 0.056). After 4 and 6 wk 84% and 88% healed with omeprazole, and 80% and 89% healed with cimetidine (p = NS). After 2 wk, pain was completely gone in 62% of the omeprazole-treated patients versus 46% of the cimetidine-treated patients (p = 0.04). Clinical or laboratory adverse events were reported in 6 (7%) of the omeprazole-treated patients and 11 (13%) of the cimetidine-treated patients (p = NS). An adverse event caused withdrawal of 1 patient on omeprazole (anxiety and depression) and 2 patients on cimetidine (diarrhea and fall in hemoglobin). We conclude that omeprazole (20 mg daily) resulted in a trend toward more rapid ulcer healing compared with a relatively high dose of cimetidine (600 mg b.i.d.), and was preferred by patients for relief of ulcer pain.
Adult↗
Immediate and long-term management of gunshot wounds to the lower face.
The steadily increasing level of urban violence and attempted suicides in the recent past has resulted in large numbers of gunshot injuries to the face from small-caliber weapons. Our experience with 35 consecutive cases of civilian gunshot wounds involving primarily the lower face is presented. Initial management included securing of the airway, control of bleeding, and treatment of coexisting injuries. After clinical and radiologic evaluation and conservative debridement of all devitalized tissues, the mandibular fractures were reduced and stabilized appropriately. Large bony defects were treated by stabilization of the mandibular segments followed by secondary bone grafting. Intraoral soft tissues were then repaired with local mucosal flaps or tongue flaps when necessary. Finally, the soft tissues were repaired by primary closure or local flaps. Distant flaps were used only as a secondary procedure. Our results are presented, the differences between civilian and military injuries are discussed, and the principles of gunshot ballistics are described. We conclude that most of these wounds can be treated in a relatively conservative manner immediately after the injury with good functional and cosmetic results.
Adolescent↗
Double-blind, placebo-controlled evaluation of 5-ASA suppositories in active distal proctitis and measurement of extent of spread using 99mTc-labeled 5-ASA suppositories.
Patients with active distal proctitis received either 5-aminosalicylic (5-ASA) acid or identical placebo suppositories, 500 mg t.i.d. for 6 weeks. Activity at 3 and 6 wks was assessed using a Disease Activity Index (DAI), derived from four categories: number of daily evacuations more than usual, evacuations containing blood, sigmoidoscopy appearance, and physician's overall assessment. Each category was graded 0-3. There was thus 0-12 points scored ranging from complete remission to severe disease. A minimum score of 3 from two categories was necessary for study entry. Of 27 patients randomized, 14 received active medication and 13 placebo. Of the 14 patients, with initial mean DAI 7.1 +/- 1.8, 11 were in complete remission at 6 wks (78.6%). Whereas, there was no significant change in the placebo group, with initial mean DAI 7.1 +/- 1.8. An additional 6 patients with inflammatory bowel disease and 6 healthy volunteers were given 99mTc-labelled 5-aminosalicylic acid suppositories. The extent of spread was limited to the rectum, and the suppositories were retained for 3 hours. There was no absorbed radioactivity. 5-ASA suppositories are safe, well-tolerated, and effective treatment for active distal proctitis.
Administration, Rectal↗
Oxidation of primary bile acids by a 7 alpha-hydroxysteroid dehydrogenase elaborating Clostridium bifermentans soil isolate.
A gram-positive, rod-shaped anaerobe (strain F-6) was isolated from soil. This organism was identified by cellular morphology as well as fermentative and biochemical data as Clostridium bifermentans. Strain F-6 formed 7-ketolithocholic acid from chenodeoxycholic acid and 7-ketodeoxycholic acid from cholic acid in whole cell cultures, but did not transform deoxycholic acid, ursodeoxycholic acid, or ursocholic acid. This reaction is reversible. The structures of 7-ketolithocholic acid and 7-ketodeoxycholic acid were verified by mass spectroscopy and by thin-layer chromatography using Komarowsky's spray reagent. When incubated with the strain F-6 glycine and taurine conjugates of the primary bile acids were partially hydrolyzed and transformed to 7-keto products. Optimal yields of 7-ketolithocholic acid and 7-ketodeoxycholic acid were obtained after 78 h of incubation. Culture pH changed with time and was characterized by an initial drop (1.1 pH units) and a gradual increase back to the starting pH (7.3). Corroborating these observations, an inducible, NADP-dependent, 7 alpha-hydroxysteroid dehydrogenase was demonstrated in cell extracts of strain F-6. A trace of NAD-dependent 7 alpha-hydroxysteroid dehydrogenase was also found. A substantial increase in the specific activity of the NADP-dependent 7 alpha-hydroxysteroid dehydrogenase was observed when either 7-ketolithocholic acid, chenodeoxycholic acid, or deoxycholic acid was included in the growth medium. Optimal induction of the NADP-dependent 7 alpha-hydroxysteroid dehydrogenase was achieved with 0.3-0.4 mM 7-ketolithocholic acid. Production of the enzyme(s) was optimal at 6-8 h of growth and the 7 alpha-hydroxysteroid dehydrogenases had a pH optimum of approximately 11.(ABSTRACT TRUNCATED AT 250 WORDS)
Bile Acids and Salts↗
The aminopyrine breath test, an inadequate early indicator of methotrexate-induced liver disease in patients with psoriasis.
The aminopyrine breath test has been shown to be a sensitive noninvasive indicator of liver cell dysfunction. In a search for a noninvasive method of monitoring the effects of methotrexate therapy, we have investigated the use of the aminopyrine breath test in patients receiving methotrexate for the treatment of severe psoriasis. The [14C]-aminopyrine breath test was performed in 20 normal control subjects, 32 patients with psoriasis receiving methotrexate therapy, and 8 patients with histologically confirmed cirrhosis of differing etiology. Eighteen patients on methotrexate had liver biopsies classified as grade I changes, 6 patients as grade II, and 8 patients as grade III. The normal value for the breath test was 11.0 +/- 1.6% (mean +/- 1 SD). The mean [14C]-CO2 excretion (8.3 +/- 4.4%) of the 8 patients with grade III liver disease was significantly different from the control subjects (p less than 0.02), and those with grade I liver changes (p less than 0.04). The aminopyrine breath test was only able to detect the later severe stages of methotrexate hepatotoxicity, grade III, when fibrosis occurs, before established cirrhosis was present. Our data suggests that the aminopyrine breath test is not a sensitive indicator for the detection of early methotrexate-induced hepatotoxicity, (stages I and II), but will detect the precirrhotic stage III change. Consequently, we recommend that a liver biopsy should be performed annually in all psoriatic patients receiving methotrexate, to detect histological damage, especially when the aminopyrine breath test score falls below the 95% confidence limits of normal.
Aminopyrine↗
Dissecting cellulitis of the scalp.
Dissecting cellulitis of the scalp or perifolliculitis capitis abscedens et suffodiens is a rare, chronic, progressive, suppurative disease of the scalp of unknown etiology. It is characterized by painful nodules, purulent drainage, burrowing interconnecting abscesses, and cicatricial alopecia. The pathogenesis is unknown, although it is probably related to follicular occlusion, secondary infection, and deep inflammation. Black men in their second to fourth decade are predominantly affected. Treatment varies from systemic antibiotics to incision and drainage, x-ray epilation of the affected areas, systemic steroid administration, and surgical excision. Our experience with four patients with extensive scalp disease is presented. Wide excision of the affected areas and splitthickness skin graft are favored as our treatment of choice.
Adult↗
Studies of bile lipids and bile acids of wild North American black bears in Nova Scotia, showing a high content of ursodeoxycholic acid.
Does ursodeoxycholic acid (UDC) production protect hibernating species of Ursidae against gallstone disease? Five wild bears (Ursis Americana) were studied. Older bears had more UDC than younger ones, suggesting UDC production is an acquired phenomena. Bile salt pools were 10 times larger than that of man and were characteristically conjugated with Taurine alone. The relative composition of the principal lipids in bear bile fell well within the range of cholesterol solubility. Cholesterol gallstones are not reported in Ursidae, probably because of the large bile acid pool and high UDC content.
Animals↗
Overcoming barriers to identification and referral of alcoholics in a general hospital setting: one approach.
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Alcoholism↗
Bile acid induction of 7 alpha- and 7 beta-hydroxysteroid dehydrogenases in Clostridium limosum.
When grown in the presence of bile acids, two strains of Clostridium limosum were found to contain significant amounts of NADP-dependent 7 alpha/7 beta-hydroxysteroid dehydrogenase and NAD-dependent 7 alpha-hydroxysteroid dehydrogenase which were active against conjugated and unconjugated bile acids. No measurable activity could be found when deoxycholic acid (3 alpha, 12 alpha-dihydroxy-5 beta-cholan-24-oic acid) was used as substrate. No 7 beta-hydroxysteroid dehydrogenase activity and only a trace of 7 alpha-hydroxysteroid dehydrogenase activity could be demonstrated when bile acid was deleted from the growth medium. If bile acid was added after the time of inoculation, the amounts of 7 alpha/7 beta-hydroxysteroid dehydrogenase were greatly reduced. Enzyme enhancement was blocked by addition of rifampicin. The 7 alpha/7 beta-hydroxysteroid dehydrogenase components had pH optima of approximately 10.5. Both the 7 alpha/7 beta-hydroxysteroid dehydrogenase activities were heat-labile, with the 7 beta-component being the more stable of the two. When ranked according to the level of enzymes induced, the order in increasing bile acid induction power on an equimolar scale (0.4 mM) was: 7-ketodeoxycholic acid, cholic acid, chenodeoxycholic acid, and deoxycholic acid. Both 7-ketolithocholic acid and ursodeoxycholic acid were ineffective as enzyme inducers. Optimal induction was achieved with high concentrations of cholic acid (5 mM) and a harvest time of 24 hr. Addition of ursodeoxycholic acid to medium containing optimal concentrations of deoxycholic acid suppressed enzyme induction.(ABSTRACT TRUNCATED AT 250 WORDS)
Bile Acids and Salts↗
Formation of urso- and ursodeoxy-cholic acids from primary bile acids by a Clostridium limosum soil isolate.
A gram-positive, rod-shaped anaerobe (isolate F-14) was isolated from soil. This organism was identified by cellular morphology as well as by fermentative and biochemical data as Clostridium limosum. Isolate F-14 formed ursocholic acid (UC) and 7-ketodeoxycholic acid (7-KDC) from cholic acid (CA), and ursodeoxycholic acid (UDC) and 7-ketolithocholic acid (7-KLC) from chenodeoxycholic acid (CDC) in whole cell cultures, but did not transform deoxycholic acid (DC). No hydrolysis or transformation occurred when either taurine- or glycine-conjugated bile acids were incubated with F-14. The type stain of Clostridium limosum (American Type Culture Collection 25620) did not transform bile acids. The structures of ursocholic, ursodeoxycholic, 7-ketodeoxycholic, and 7-ketolithocholic acids were verified by mass spectroscopy and by thin-layer chromatography using Komarowsky's spray reagent. The organism transformed cholic and chenodeoxycholic acids at concentrations of 20 mM and 1 mM, respectively; higher concentrations of bile acids inhibited growth. Optimal yields of ursocholic and ursodeoxycholic acids were obtained at 9-24 hr of incubation and depended upon the substrate used. Increasing yields of 7-ketodeoxycholic and 7-ketolithocholic acids, and decreasing yields of ursocholic and ursodeoxycholic acids were observed with longer periods of incubation. Culture pH changed with time and was characterized by a small initial drop (0.2-0.4 pH units) and a subsequent increase to a pH (8.1-8.2) that was above the starting pH (7.4).(ABSTRACT TRUNCATED AT 250 WORDS)
Bile Acids and Salts↗
Estimation of ursodeoxycholic acid in human and bear biles using Clostridium absonum 7 beta-hydroxysteroid dehydrogenase.
Ursodeoxycholic acid was estimated in bile samples from humans and wild North American black bears using 7 beta-hydroxysteroid dehydrogenase purified from Clostridium absonum by Procion Red affinity chromatography. The percentage ursodeoxycholic acid was calculated by two methods: (a) 7 beta-hydroxyl groups were quantified using 7 beta-hydroxysteroid dehydrogenase and 3 alpha-hydroxyl groups (total bile acids) were quantified using 3 alpha-hydroxysteroid dehydrogenase. The percentage ursodeoxycholic acid was calculated on the basis of [7 beta-hydroxyl groups]/[3 alpha-hydroxyl groups] X 100. (b) Bile was hydrolyzed with sodium hydroxide and subjected to thin-layer chromatography. Bands corresponding to cholic acid, chenodeoxycholic acid plus deoxycholic acid, and ursodeoxycholic acid were identified by the use of standards and Komarowsky's spray reagent. Total bile acids and total ursodeoxycholic acid were measured by elution of silica gel in unsprayed areas corresponding to the bile acid standards and quantification of the total bile acid in each eluate. Direct comparison of these methods validated the use of 7 beta-hydroxysteroid dehydrogenase in the estimation of ursodeoxycholic acid in the biles of black bears and of patients fed ursodeoxycholic acid for cholesterol gallstone dissolution. Relative percentages of ursodeoxycholic acid were 8-24% in four bears and 22 and 27% in the patients ingesting 500 and 750 mg ursodeoxycholic acid per day for 3 months, respectively. Predictably lower values were obtained in two control subjects and one patient ingesting 750 mg chenodeoxycholic acid per day for 3 months.
Animals↗
Biliary lipid, bile acid composition, and dietary correlations in Micmac Indian women. A population study.
The precursor state for cholesterol gallstone formation is cholesterol-saturated bile. We studied a high-risk group for cholesterol gallstones to determine whether dietary variables affect bile cholesterol. Bile samples were analyzed from 46 Micmac Indian women without gallstones and 13 with gallstones for molar percentage cholesterol (MPC) and bile acid composition. The data were analyzed by multiple regression analysis with MPC as the dependent variable and the dietary variables, obtained from four consecutive-day food records, and biliary bile acid composition as the independent variables. In the 46 women without gallstones, obesity, calorie range/calorie intake, and iron and calcium intake were, in their order of importance, significant factors. In normal weight subjects (ponderal index > 12.5) relative obesity was still a significant correlate. Obesity and iron intake were positive correlates while calorie range/calorie intake and calcium intake varied inversely. When the effect of obesity was controlled, these factors were still significant in this group, as they were in the gallstone group. In addition, the duration of overnight fast obtained by history, together with the proportions of deoxycholic and chenodeoxycholic acids in bile were correlates of the biliary molar percentage cholesterol.
Adolescent↗
Severe penicillin-induced cholestasis in a 91-year-old woman.
An elderly woman was admitted for treatment of severe stasis ulceration, associated with varicose veins. One course of cloxacillin was given orally followed by a second course of penicillin-G to eradicate persistant hemolytic streptococcal skin infection. Deep progressive jaundice subsequently developed due to intrahepatic cholestasis and persisted for several weeks before resolution. Having excluded a progressive extrahepatic malignant lesion by appropriate investigations, the diagnosis was substantiated by classical changes present in a percutaneous liver biopsy.
Acute Disease↗
Prevalence of gallstones and risk factors in Caucasian women in a rural Canadian community.
The prevalence of gallstones and gallbladder disease was studied in a rural Caucasian population. All the women aged 15 to 50 years were asked to complete a questionnaire, undergo cholecystography and keep a food record for 4 consecutive days. The gallbladder status was assessed in 73%. The prevalence of gallstones in this population, 167/1000, was considerably higher than that reported in the Framingham study (59/1000) but was not significantly different from that recently found in Micmac Indian women living nearby in Canada (211/1000). In contrast to all the other studies in Caucasian women, this study showed the prevalence of gallstones to peak between the ages of 30 and 39 years. The risk factors, controlled for age, were found to be obesity, a narrow range of daily energy intake, a low daily calcium intake and limited activity. Discriminant analysis showed that skinfold thickness and range of daily energy intake or all measures of obesity together correctly separated the persons with gallstones from those without.
Adolescent↗