Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.3.1 (alkaline phosphatase)
 47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated the effects of once-daily oral administration of 10 mg/kg ursodeoxycholic acid (generic name, ursodiol) on elevated serum enzyme activities, bilirubin, cholesterol, bile acids and symptoms in patients with primary sclerosing cholangitis. A 30-mo, open-label, pilot trial was designed to cover four periods: (a) 3 mo of pretreatment observation (period 1), (b) 6 mo on ursodiol (period 2), (c) 3 mo withdrawal of treatment (period 3) and (d) 18 mo of extended retreatment (period 4). Diagnosis was confirmed by cholangiography and liver biopsy specimens. We enrolled 12 patients with persistently elevated pretreatment alkaline phosphatase and gamma-glutamyltransferase levels (at least twice the upper limit of normal), and observed them for a median of 37 mo. Significant reductions in serum total cholesterol levels and in serum enzyme activities indicating cholestasis and hepatocellular injury occurred during ursodiol treatment in both treatment periods 2 and 4 and relapsed with treatment interruption in period 3. Elevated serum bilirubin and symptoms of disabling fatigue, pruritus and diarrhea were improved by ursodiol. Improvements have continued after 2 yr of treatment in 10 patients (1 patient had a transplantation after he relapsed on withdrawal of ursodiol therapy; another died of postoperative complications of colon resection for carcinoma). No other cases of clinical deterioration were observed in the retreatment period. The longer term reductions of alkaline phosphatase, transaminases, bilirubin and cholesterol after 2 yr of treatment were even greater than the initial reductions after 6 mo of treatment. These results justify initiation of larger, controlled clinical trials, with serial morphological evaluations of the liver and biliary tree.
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PMID:Ursodeoxycholic acid for the treatment of primary sclerosing cholangitis: a 30-month pilot study. 193 90

We informed four cases of primary sclerosing cholangitis associated with chronic ulcerative colitis, diagnosed in the Gastroenterology Department, Hospital de Especialidades del CM Siglo XXI Mexico City, during 1987 to 1988. The mean age was 30.2 years and the evolution of colitis was 6.6 years. Two patients were females and two males, all presented active colitis and three presented hepatic symptoms. The laboratory abnormalities were hypertransaminasemia, increased alkaline phosphatase and hyperbilirubinemia. In three patients endoscopic retrograde cholangiopancreatography was done, in all cases diagnosis was established by histology. The frequency of primary sclerosing cholangitis associated with chronic ulcerative colitis was 13.3%.
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PMID:[Primary sclerosing cholangitis. A report of 4 cases]. 194 18

To identify the types of liver disease in which osteopenia is a prominent feature and to understand the mechanisms of bone loss, bone mineral density was measured in the lumbar spine and hip, bone alkaline phosphatase, osteocalcin, and biochemical markers of calcium homeostasis were measured in 42 women, aged 33 to 52, with chronic liver disease and in 299 healthy women of similar age. In control women, bone alkaline phosphatase and osteocalcin correlated negatively with bone density at all sites (p less than 0.05). In women with liver disease, osteocalcin correlated negatively with bone density in the lumbar spine (p less than 0.007), whereas bone alkaline phosphatase did not correlate with bone density at any site. Bone alkaline phosphatase correlated positively with osteocalcin in control women (p = 0.001) and negatively with osteocalcin in women with liver disease (p = 0.03). Serum bone alkaline phosphatase in women with liver disease was increased significantly over serum bone alkaline phosphatase of control women, probably because of decreased clearance owing to defective function or decreased numbers of hepatic asialoglycoprotein receptors. Bone density was lower in the lumbar spines and hips of women with primary sclerosing cholangitis, primary biliary cirrhosis, and chronic active hepatitis or fibrosis without cirrhosis than in the lumbar spine and hips of control women. However, the differences were not significant, possibly because of the small sample size. It is concluded that, in liver disease, osteocalcin is a more reliable marker of osteoblastic function than bone alkaline phosphatase. Although our results show that bone density may decrease in women with cholestatic liver disease, larger studies are needed to determine the degree of osteopenia.
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PMID:Osteocalcin and bone alkaline phosphatase in the serum of women with liver disease. 195 79

The effects of ursodeoxycholic acid (UDCA, 750-1250 mg/day) were evaluated prospectively in 15 patients with primary sclerosing cholangitis (PSC). Five patients had associated inflammatory bowel disease. After 6 months of treatment, the proportion of patients suffering from fatigue or pruritus decreased from 60% to 20% and from 33% to 20%, respectively. No exacerbation of associated disorders was observed. Serum alkaline phosphatase levels (normal less than 100 IU/l) decreased from 401 +/- 53 to 222 +/- 42 (mean +/- S.E.; p less than 0.001), those of gamma-glutamyl transpeptidase, (normal less than 40 IU/l) from 520 +/- 89 to 185 +/- 32 (p less than 0.001) and those of alanine aminotransferases, (normal less than 30 IU/l) from 79 +/- 12 to 42 +/- 6 (p less than 0.02). In three patients, the discontinuation of UDCA was associated with an aggravation of the liver test results. In conclusion, this study shows that 6 months of treatment with UDCA leads to clinical and biochemical improvements in patients with PSC. These results suggest that UDCA could be an effective treatment for PSC, and may justify a controlled therapeutic trial.
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PMID:Ursodeoxycholic acid for primary sclerosing cholangitis. 197 18

All patients greater than or equal to 16 years old with a diagnosis of ulcerative colitis were identified in five well-defined catchment areas, representing 12.7% of the Swedish population. Exactly 1500 patients were retrieved, giving a point prevalence of 170/10(5) inhabitants. It was possible to obtain liver function test results less than 2 years old in 94% of the patients and to obtain endoscopic retrograde cholangiographic results in 65 of the 72 patients with abnormal serum alkaline phosphatase values. Primary sclerosing cholangitis was diagnosed in 55 of the patients (3.7%). The prevalence of the disease was 5.5% in patients with substantial colitis and 0.5% in patients with distal colitis. There was a marked male predominance in cholangitis patients compared with colitis patients without cholangitis. Ninety-five percent of the patients with cholangitis had substantial colitis, which was more than the 62% of patients without cholangitis who had colitis. Female patients with cholangitis were older than male patients at the time of diagnosis of both cholangitis and colitis, which contrasted to the equal age at diagnosis of colitis in male and female patients without cholangitis.
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PMID:Prevalence of primary sclerosing cholangitis in patients with ulcerative colitis. 201 75

Ten patients with well-documented primary sclerosing cholangitis who had no signs of portal hypertension or liver failure were treated with oral pulse methotrexate for at least 1 yr. The methotrexate dose averaged 15 mg/wk (0.2 mg/kg/wk). All six patients who were symptomatic became asymptomatic within 1-5 months of starting methotrexate. Biochemical tests of liver function improved in all patients. The alkaline phosphatase value decreased from a mean (+/-SD) of 373 +/- 210 IU to 140 +/- 77 IU (p = 0.0008), the mean alanine aminotransferase (ALT) from 115 +/- 74 to 76 +/- 79 U/L (p = 0.005), and the mean aspartate aminotransferase (AST) value from 88 +/- 37 to 57 +/- 40 U/L (p = 0.007). The improvement in mean bilirubin (1.19 +/- 1.41 to 0.67 +/- 0.25 mg/dl) was not statistically significant. Serum albumin remained normal (3.97 +/- 0.46 to 4.22 +/- 0.36 g/dl). Nine patients had a repeat liver biopsy after 1 yr of methotrexate therapy. Six of the nine showed histologic improvement with a reduction in inflammation. The other three liver biopsies were unchanged. Repeat cholangiograms were done in six patients. Two showed improvement. In one of the two, who had early disease, the cholangiogram became normal, and the liver biopsy was markedly improved. The other four cholangiograms showed no progression of disease. No toxicity was detected in these 10 patients. These results suggest that low-dose oral methotrexate therapy is effective in primary sclerosing cholangitis if treatment is begun before signs of portal hypertension or liver failure occur.
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PMID:Treatment of primary sclerosing cholangitis with oral methotrexate. 202 43

To obtain information on the prevalence and clinical and laboratory correlates of osteopenia in patients with chronic liver disease, we measured bone densities and 30 selected laboratory variables in 133 subjects (70 men, 63 women) with liver disease. Thirty-two had alcoholic liver disease, 18 had primary biliary cirrhosis, 16 had primary sclerosing cholangitis, 48 had other forms of cirrhosis (cryptogenic, posthepatic) and 19 had chronic hepatitis or fibrosis without cirrhosis. Bone densities of the lumbar spine and three sites of the proximal femur (neck, Ward's triangle, greater trochanter) were estimated by dual-photon absorptiometry. Bone densities at all sites were significantly correlated to one another (r = 0.4 to 0.9; 95% confidence intervals = 0.24-0.54 to 0.81-0.90; p less than 0.0001 for all). Compared with an age- and gender-matched reference group, patients with liver disease had highly significant decreases in bone densities (greater than 2 standard deviations below control values; p less than 0.0008 at all sites). Decreases were particularly marked (24% to 42%) at Ward's triangle, the site of the femoral neck particularly prone to fracture. The prevalence of decreased bone densities ranged from 10% to 56%, depending on the site studied and the nature of the liver disease. Among 30 laboratory variables studied, there were significant (p less than 0.05) correlations with bone densities at more than one site for urinary creatinine (r = 0.21, 0.25), urinary calcium (r = -0.18, -0.23), serum total alkaline phosphatase (r = -0.18, -0.27) and the liver-1 isozyme of serum alkaline phosphatase (r = -0.19, -0.26).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prevalence and prediction of osteopenia in chronic liver disease. 239 Oct 68

In the period 1970 to 1987, 171 patients with small-intestinal mucosal atrophy have been hospitalized in our department. Of these, 132 patients fulfilled the diagnostic criteria of coeliac disease on the basis of histologic findings and clinical improvement on a gluten-free diet. Aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT), and alkaline phosphatase (ALP) were chosen as markers of hepatic involvement. Elevation above the normal range in one or more of these tests was seen in 62 patients (47.0%, group I). In 70 patients (53.0%, group II) of similar age the levels of these variables were normal. In group I, 14 (10.6%) patients had an elevation of ALP only, leaving 48 (36.4%) patients with pathologic values for one or both transaminases. In group I, 32 patients had their ASAT, ALAT, and ALP reexamined after at least 6 months of gluten-free diet. Among the patients with increased values of one or both transaminases 18 patients were tested before and at least 6 months after start of gluten-free diet. The variables were significantly reduced in all patients. Liver biopsies were performed in 37 patients, and findings were normal in 5. In 25 patients the changes were classified as non-specific. Chronic active hepatitis was demonstrated in five patients. In one of these patients primary sclerosing cholangitis and ulcerative colitis were also diagnosed. Concomitant malignant disease was found in 22 patients, of whom 16 had malignant lymphoma. Malignant disease was seen more often in group I than group II (p less than 0.01). In conclusion, liver lesions were found in a great proportion of the patients with coeliac disease.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hepatic lesions in adult coeliac disease. 239 80

The effect of proctocolectomy on the primary sclerosing cholangitis that frequently is associated with chronic ulcerative colitis in patients with both conditions is unknown. We have studied prospectively the progression of clinical, biochemical, cholangiographic, and hepatic histologic features in 45 patients with both primary sclerosing cholangitis and chronic ulcerative colitis to compare these variables in the 20 patients who had undergone proctocolectomy with the 25 who had not. The two groups were similar initially with regard to clinical, biochemical, cholangiographic, and hepatic histologic findings. All patients were followed for a minimum of 1 yr and overall duration of follow-up was similar in both groups (4.1 vs. 3.9 yr). Clinically, new onset of hepatomegaly, splenomegaly, esophageal varices, and ascites did not differ in patients with and without proctocolectomy. Biochemically, the serial changes in bilirubin, alkaline phosphatase, aspartate aminotransferase, prothrombin time, and albumin were similar. Histologic progression on liver biopsy did not differ between groups, nor did changes on serial cholangiograms. Proctocolectomy also had no effect on survival. We conclude that proctocolectomy for chronic ulcerative colitis has no beneficial effect on the primary sclerosing cholangitis in patients with both diseases.
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PMID:Effect of proctocolectomy for chronic ulcerative colitis on the natural history of primary sclerosing cholangitis. 291 41

Primary sclerosing cholangitis (PSC) is a chronic fibrous-obliterative inflammation of bile ducts of unknown origin. Genetic, infectious and immunological mechanisms are believed to be involved in the pathogenesis. The clinical signs and symptoms in the early stages are non-specific, laboratory evaluation shows a marked elevation of alkaline phosphatase and a lower rise of transaminases. The diagnosis is confirmed by endoscopic retrograde cholangiography. Histologic findings are non-specific. About 60% of patients with PSC have chronic inflammatory bowel disease, mainly ulcerative colitis. The risk of developing carcinoma of the bile ducts is also increased in patients with PSC. Therapy with glucocorticoids, colchicin, immunosuppressive agents, cholestyramin and penicillamin generally is unsatisfactory. In advanced stages liver transplantation should be performed.
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PMID:[Primary sclerosing cholangitis]. 306 8


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