Upper bound on the tau -neutrino mass from the previously unobserved decay mode tau -->KK pi nu tau.
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Journal Article↗
Biomedical subjects
J Ludwig
Publications and source records attributed to J Ludwig.
Charged D production in e+e- annihilation at 29 GeV and a limit on D0-D-bar 0 mixing.
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Journal Article↗
Hepatitis B virus replication in steroid-treated severe HBsAg-positive chronic active hepatitis.
To determine the effect of corticosteroids on the replication of hepatitis B virus and to assess the relationship between virus replication and prognosis, the behavior of serum and tissue HBcAg was evaluated in 16 patients with severe HBsAg-positive chronic active hepatitis who were treated with prednisone and followed for up to 10 years (mean +/- SEM, 66 +/- 9 months). Hepatitis B virus replication was assessed in serum by a solid-phase radioimmunoassay of Dane particle-associated HBcAg and in liver tissue by indirect immunoperoxidase staining for HBcAg. Despite the presence of severe inflammatory activity, only low levels of hepatitis B virus replication were demonstrated. Mean serum HBcAg levels were low at accession and remained essentially unchanged or gradually decreased during corticosteroid therapy. Serum HBcAg appeared in only one patient in whom no virus replication was detected prior to therapy. HBeAg was frequently detected at low titers by radioimmunoassay when serum HBcAg was undetectable. Loss of HBcAg preceded loss of HBeAg by radioimmunoassay, and disappearance of both markers was a prerequisite for sustained histologic remission. In eight patients, inflammation was present despite absence of serum or tissue HBcAg; in three of these, disease activity continued after loss of HBeAg. We conclude that low levels of hepatitis B virus replication may be associated with severe inflammatory activity, and these levels are not increased by long-term corticosteroid therapy. Inflammation can continue despite loss of HBeAg and absence of detectable virus replication.
Adrenal Cortex Hormones↗
Diagnostic and prognostic implications of plasma amino acid determinations in chronic active hepatitis.
To further assess the molar ratio of branched-chain to aromatic amino acids as a measure of disease activity, we correlated results of this test with histologic features of inflammation, standard biochemical tests, and prognosis in 68 patients with severe chronic active hepatitis. An abnormal molar ratio (less than 3.0) reflected histologic findings of chronic active hepatitis in 26 of 35 instances. A normal molar ratio (greater than or equal to 3.0), however, was associated with histologic features of chronic active hepatitis in nine of 14 instances. Molar ratio abnormalities occurred more frequently in patients with cirrhosis than without cirrhosis (95% vs 45%, P less than 0.01). Only one of 20 patients with cirrhosis had a normal ratio, and none of 12 followed serially during therapy improved the ratio to normal. No correlation was seen between the molar ratio and severity of inflammation or serum levels of aspartate aminotransferase, albumin, bilirubin, and gamma globulin. When corticosteroids were discontinued, relapse occurred as frequently in patients with a normal molar ratio as in others (80% vs 71%), and the presence of an abnormal ratio did not preclude a sustained remission after treatment. We conclude that the plasma molar ratio does not reflect histologic activity, correlate with standard liver function tests, or indicate disease behavior after treatment withdrawal. A normal molar ratio during or after treatment, however, may exclude cirrhosis.
Adolescent↗
Abnormalities in tests of copper metabolism in primary sclerosing cholangitis.
Primary sclerosing cholangitis is a chronic, cholestatic syndrome characterized by fibrosing inflammation of the bile ducts that may lead to cirrhosis and death from liver failure. Previous reports have suggested abnormal hepatic copper metabolism in this disease. Therefore, in 70 patients, we prospectively determined the levels of hepatic copper, serum copper, and serum ceruloplasmin, and the rate of urinary copper excretion to assess the diagnostic and prognostic usefulness of these tests. Virtually all patients had at least one abnormal copper test. Hepatic copper levels were elevated in 87% of patients [292 +/- 38 micrograms/g dry wt (mean +/- SE)] and 24-h urinary copper levels in 64% of patients [135 +/- 15 micrograms/24 h (mean +/- SE)] to values comparable to those seen in Wilson's disease or primary biliary cirrhosis. In advanced histologic stages of primary sclerosing cholangitis, progressively higher mean levels of hepatic and urinary copper were found. In the liver, mean copper content (in micrograms per gram dry weight) in disease stages I and II was 147 +/- 36 (mean +/- SE); in stage III (fibrosis), 302 +/- 68; and in stage IV (cirrhosis), 379 +/- 69. In the urine, mean copper excretion (in micrograms per 24 h) in stages I and II was 72 +/- 14 (mean +/- SE); in stage III, 100 +/- 14; and in stage IV, 207 +/- 30. Higher hepatic and urinary copper levels at initial evaluation were associated with decreased survival during a median follow-up period of 2.6 yr: patients with hepatic copper greater than 250 micrograms/g dry wt and urinary copper excretion greater than 200 micrograms/24 h at initial evaluation had an 18-mo survival of less than 60%. We conclude that abnormal copper metabolism is a universal feature of primary sclerosing cholangitis, that hepatic copper accumulates and urinary copper excretion increases as the disease progresses, and that the hepatic copper concentration and the 24-h urinary copper determination are useful prognostic indicators in this disease.
Ceruloplasmin↗
Frequency and significance of delta antibody in acute and chronic hepatitis B. A United States experience.
Of 560 hepatitis B surface antigen-positive patients who were tested for antibody to hepatitis delta-antigen by blocking radioimmunoassay, 29 (5%) were seropositive. Patients with chronic active hepatitis had a greater frequency of seropositivity than those with chronic persistent hepatitis (26% vs. 0%, p less than 0.05), and patients with symptomatic chronic disease harbored the antibody more commonly than asymptomatic counterparts (14% vs. 2%, p less than 0.01) or patients with acute hepatitis (14% vs. 1%, p less than 0.02). Of 8 patients with acute fulminant hepatitis, including 6 who died of liver failure, none were seropositive. Antibody was detected in drug users, dialysis patients, hemophiliacs, and transfusion recipients; in 17 patients, however, including 3 homosexuals, it occurred sporadically. Samples harvested in 1969 contained delta-antibody. Antibody was found in most ethnic groups, including Orientals, where it occurred only in relocated Vietnamese. We conclude that delta-antibody is detected infrequently in a diverse referral population within the United States. Seropositivity is associated with symptomatic chronic disease and histologic findings of chronic active hepatitis. Homosexuals and resettled Vietnamese are susceptible to sporadic delta-infection.
Acute Disease↗
Comparison of the clinicopathologic features of primary sclerosing cholangitis and primary biliary cirrhosis.
Primary sclerosing cholangitis and primary biliary cirrhosis are chronic cholestatic syndromes that may be difficult to differentiate clinically. Destructive cholangitis occurs in both diseases and leads to similar clinical and biochemical abnormalities. Therefore, we compared the clinical, biochemical, immunologic, radiologic, and hepatic histologic features of these syndromes in two large groups of patients prospectively selected by predefined criteria. Primary biliary cirrhosis (n = 258) occurred predominantly in middle-aged women who were usually symptomatic with fatigue and pruritus, commonly had keratoconjunctivitis sicca, and often were hyperpigmented. Tests for antimitochondrial antibodies were always positive, usually in very high titer. Although the extrahepatic bile ducts were normal radiographically, smooth tapering and narrowing of the intrahepatic bile ducts was occasionally noted. Hepatic histology was diagnostic when a florid duct lesion was present. In contrast, primary sclerosing cholangitis (n = 60) occurred primarily in young men who were usually symptomatic with fatigue and pruritus and frequently had chronic ulcerative colitis. Tests for antimitochondrial antibodies were nearly always negative and cholangiography demonstrated abnormalities of the extrahepatic and intrahepatic bile ducts in all cases. Although hepatic histology was often compatible with the diagnosis, it was usually not diagnostic, and considerable overlap existed with the abnormalities seen in primary biliary cirrhosis. Likewise, biochemical tests of copper metabolism were similar in both syndromes. These results call attention to the differences and similarities in the clinicopathologic features of these two cholestatic syndromes and provide a basis for a rational diagnostic strategy.
Adult↗
Fulminant hepatitis: Mayo Clinic experience with 34 cases.
From 1974 through 1982, fulminant hepatitis was diagnosed in 34 patients at our institution. Of these patients, only two survived (survival rate, 6%). This syndrome was caused by viruses (B and non-B hepatitis and herpes simplex) in 23 patients, hepatotoxic drug in 6, Wilson's disease (hepatolenticular degeneration) in 3, and industrial poisons in 2. Most of the patients died within 10 days after the onset of encephalopathy. The poor prognosis in our group of patients was probably related to the preponderance of older patients and cases caused by non-B hepatitis virus. In our patients, the clinical course was complicated by renal failure, ascites, bleeding, sepsis, pancreatitis, and seizures. The major cause of death was hepatic failure.
Acute Disease↗
Hepatobiliary carcinoma associated with primary sclerosing cholangitis and chronic ulcerative colitis.
Hepatobiliary carcinomas were found in eight patients with chronic ulcerative colitis (CUC) and primary sclerosing cholangitis (large-duct PSC; five cases) or "pericholangitis" (small-duct PSC; three cases). The tumors were extrahepatic in five cases and intrahepatic in two; in one case the neoplasm affected both liver and gallbladder. The tumors in seven patients were glandular and, sometimes, cystic and papillary; in the remaining patient a combined hepatocellular carcinoma and cholangiocarcinoma was found. The latter tumor seemed to arise from regenerative nodules in secondary biliary cirrhosis complicating PSC. The presence of carcinoma in situ in areas of fibrous cholangitis, the multicentric origin of the tumor, the presence of tumor-free large-duct PSC or small-duct PSC (pericholangitis) at a distance from the carcinomatous areas, and the documentation, in some cases, of long-standing inflammatory hepatobiliary disease prior to the discovery of the tumors would seem to confirm the clinical impression that carcinomas may develop in pre-existing PSC. The appearance of hepatobiliary carcinomas in patients with classic PSC and in patients with pericholangitis supports previous evidence indicating that cholangiographically diagnosed large-duct PSC and histologically diagnosed small-duct PSC (pericholangitis) are manifestations of a shared condition that could be named PSC syndrome. The findings of the present study indicate that the PSC syndrome predisposes patients for the development of bile duct carcinoma. Most patients with CUC and bile duct carcinoma seem to have PSC prior to the development of the hepatobiliary tumor.
Adolescent↗
Diagnosis and treatment of primary sclerosing cholangitis.
PSC is a progressive chronic hepatobiliary disorder of unknown etiology for which no effective medical or surgical therapy now exists. This syndrome occurs most commonly in young men and is frequently associated with CUC. The diagnosis is best made utilizing endoscopic retrogradecopic retrograde cholangiography. Although liver histologic findings alone are infrequently diagnostic of PSC, it remains important to exclude other causes of chronic cholestasis. Although the etiology remains unknown, preliminary studies suggest that PSC is related to immunologic damage. Although viral infections can induce obliterative cholangitis in children, their role in the cause of PSC remains undefined. PSC progresses slowly from an asymptomatic stage to cirrhosis, portal hypertension, and premature death secondary to liver failure. Bile duct cancer appears to be a frequent complication of long-standing PSC. Since no therapy is of established efficacy, controlled clinical trials of both medical and surgical therapy should be encouraged. Fat-soluble vitamin deficiencies commonly occur in the advanced stages of PSC, and therefore serum levels of vitamins A, D, E, and prothrombin time should be monitored on a regular basis to prevent complications associated with these deficiencies. Liver transplantation is now a therapeutic option for the treatment of end-stage PSC. Palliative surgical biliary drainage procedures, proctocolectomy, and surgical decompressive shunts that increase the risk of liver transplants, therefore, should be avoided, if possible, in young PSC patients. If a total proctocolectomy is surgically indicated, we would strongly recommend performing a ileoanal pull-through procedure, thus, avoiding the formation of an abdominal ileostoma and the risk of developing bleeding peristomal varices.
Adolescent↗
Pericholangitis in chronic ulcerative colitis: primary sclerosing cholangitis of the small bile ducts?
Review of liver biopsy specimens, autopsy specimens, and clinical records of 107 patients with chronic ulcerative colitis and hepatobiliary diseases showed "pericholangitis" (defined as small-duct primary sclerosing cholangitis) in 37 (35%), primary sclerosing cholangitis (defined as large-duct primary sclerosing cholangitis) in 18 (17%), chronic active hepatitis in 14 (13%), cryptogenic cirrhosis in 12 (11%), and miscellaneous lesions including malignancies in 26 (24%). Documented cirrhosis was present or developed in 37 patients (35%). The spectrum of histologic features of small-duct primary sclerosing cholangitis was indistinguishable from that of confirmed large-duct primary sclerosing cholangitis. In 6 of the 18 patients who eventually developed the large-duct disease, biopsy evidence 1 to 12 years earlier had shown small-duct primary sclerosing cholangitis. Thus, small-duct and large-duct primary sclerosing cholangitis seem to be components of a disease spectrum.
Bile Ducts, Intrahepatic↗
Hepatocellular toxicity during the treatment of refractory acute leukemia with indicine N-oxide.
Indicine N-oxide is the first member of the large class of compounds comprised of pyrrolizidine alkaloids and their N-oxides to be studied in the treatment of cancer in humans. Twenty-two patients with refractory acute leukemia received indicine N-oxide daily for 5 consecutive days in a dose-seeking study. Of eight patients with refractory acute lymphocytic leukemia, one had a complete remission, and one had a partial remission. Of 11 patients with refractory acute nonlymphocytic leukemia, 2 patients had complete remissions. Of three patients with blast crisis of chronic granulocytic leukemia, one patient had a partial remission. Five patients had severe hepatic toxicity, probably due to veno-occlusive disease induced by the drug. Whether hepatotoxicity and antileukemic activity are a result of the same mechanism of action of indicine N-oxide is not known.
Acute Disease↗
Current concepts. Primary sclerosing cholangitis.
Primary sclerosing cholangitis is a progressive, ultimately fatal, chronic hepatobiliary disorder for which no effective medical or surgical therapy now exists. The syndrome occurs most commonly in young men and is characterized by a chronic cholestatic syndrome, frequent association with chronic ulcerative colitis, hepatic copper overload, a paucity of serologic markers, and characteristic abnormalities in some liver-biopsy specimens and most cholangiograms. The natural history of the syndrome is unclear; the disease is likely to progress slowly and relentlessly, over a decade or longer, from an asymptomatic stage to a condition characterized by symptoms of cholestasis and complicated by cirrhosis, portal hypertension, and possibly carcinoma of the bile ducts. Screening techniques based on automated biochemical analyses are likely to lead to a diagnosis of primary sclerosing cholangitis in increasing numbers of patients, perhaps in the early, preicteric stage. An increased level of serum alkaline phosphatase in a young man, particularly if he has chronic ulcerative colitis, should strongly suggest the presence of this syndrome and the need for additional diagnostic studies. Endoscopic retrograde cholangiography and liver biopsy should be considered under these circumstances.
Adult↗
Lipid abnormalities of xanthomatous nerves.
The lipid composition of nerves, with and without xanthomatous alteration, and other tissues, was investigated post-mortem in a 36-year-old man with cholestatic hepatitis of unknown cause and insulin-dependent diabetes mellitus (IDDM). Cholesteryl esters were found to be markedly increased in both endoneurium and epi- and perineurium of hepatic nerves (showing xanthomatous change), but not in sciatic nerve (without this change). Cholesteryl ester concentrations were also increased, but to a lesser degree, in kidney tissue. The fatty acid composition of stored cholesteryl esters in hepatic nerve endoneurium revealed that oleic acid was the most favoured substrate for esterification. A widespread depletion of triacylglycerol was also demonstrated in hepatic and sciatic nerves and liver and skin tissues obtained from this patient. This abnormality did not appear to be due to an alcoholic or biliary cirrhosis, or to inanition. Whether the depletion of triacylglycerol is drug-related or represents an endogenous metabolic error remains unclear.
Adult↗
Manifestations of nonsuppurative cholangitis in chronic hepatobiliary diseases: morphologic spectrum, clinical correlations and terminology.
The features of nonsuppurative cholangitis were studied in liver biopsy specimens from 185 patients with chronic active hepatitis (CAH), 280 patients with primary biliary cirrhosis (PBC), and 55 patients with primary sclerosing cholangitis (PSC). Specimens from patients with other liver diseases in which the presence of nonsuppurative cholangitis had been recorded were also studied. We identified four types of nonsuppurative cholangitis: granulomatous cholangitis, lymphoid cholangitis, fibrous cholangitis, and pleomorphic cholangitis. Granulomatous cholangitis almost always seemed to be destructive; the other types were either destructive or nondestructive. Granulomatous cholangitis was, for all practical purposes, diagnostic of PBC and the obliterative form of fibrous cholangitis was similarly diagnostic for the hepatic manifestations of PSC in adults and paucity of intrahepatic bile ducts in infants. All other types of cholangitis were found in CAH, PBC, PSC, and other liver diseases. Thus, the term "nonsuppurative cholangitis" describes a spectrum of morphologic lesions that differ in incidence, morphogenesis, usefulness for liver biopsy diagnosis, and, probably, pathogenesis.
Bile Ducts↗
Fulminant hepatitis. Mayo Clinic experience with 34 cases.
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Adolescent↗
Development and prognosis of histologic cirrhosis in corticosteroid-treated hepatitis B surface antigen-negative chronic active hepatitis.
To determine the frequency and prognosis of histologic cirrhosis developing during or after corticosteroid therapy of hepatitis B surface antigen-negative chronic active hepatitis, we followed 83 patients for 90 +/- 5 mo after administration of corticosteroids. Thirty-three patients satisfied histologic criteria for cirrhosis after 30 +/- 5 mo. In 25 patients, cirrhosis developed during treatment; in 8 patients, cirrhosis eventuated after remission and cessation of therapy. The probability of developing histologic findings of cirrhosis was 59% if remission had not been achieved after 3 yr of continuous therapy. Longer requirements for treatment and deterioration during therapy characterized these patients. Once remission was achieved, the mean annual incidence of cirrhosis was only 2.6%. Patients who manifested evidence of cirrhosis in their biopsy specimens could not be distinguished by initial clinical, biochemical, or histologic findings. Ascites, encephalopathy, and esophageal varices developed infrequently; 5-yr survival after documentation of cirrhosis was 93%. We conclude that histologic features of cirrhosis develop commonly during therapy, especially if remission is not achieved quickly. After remission, cirrhosis develops infrequently. The development of histologic cirrhosis does not influence immediate morbidity and 5-yr life expectancy.
Adult↗
Fatal rectus sheath hematoma.
Rectus sheath hematoma is an uncommon, often misdiagnosed, and usually self-limited condition. In a recent review of autopsy cases at the Mayo Clinic, Rochester, Minn, we found two patients in whom hemorrhages into the rectus sheaths were considered the immediate cause of death and one in whom the hemorrhage was considered a contributing cause of death. Rectus sheath hematoma should be included in the differential diagnosis of an abdominal mass of sudden onset, especially in patients who have been given anticoagulants. The condition may be fatal if the volume of the hemorrhage is large and if treatment is delayed.
Abdominal Muscles↗