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Biomedical subjects

J Ludwig

Publications and source records attributed to J Ludwig.

At least 199 records · Page 11Linked to original sources
PubMed1989

Endotheliitis in hepatic allografts.

Endotheliitis (EN) is a feature of hepatic allograft rejection, characterized by the adherence of immunocytes to the endothelium of veins, often leading to endothelial damage, endophlebitis, and, sometimes, panphlebitis. We found EN at least once in 28 of 41 allografts (68%) that had survived 6 months or longer. In approximately half the affected cases, the condition recurred. The EN was mild in most instances; moderate or severe manifestations were found in only 13% of the cases. The histologic changes were present for about 1 week in approximately half the cases; a duration of more than 2 weeks was noted in 17%, and then EN usually persisted. After retransplantation, recurrence of EN was observed in all of nine cases. We were unable to establish specific clinicopathologic and laboratory correlations for EN. The immunocytes in EN consisted mainly of helper and suppressor/cytotoxic T cells as well as natural killer cells. Sometimes, the immunocytes assumed a blastlike appearance; in these instances, the condition was severe. Such blastlike changes may be specific for EN. The immunocytes were attached to the endothelium by pseudopodia, broad bases, or both; some also were interconnected by cytoplasmic bridges. Underlying endothelial cells often showed evidence of cytoplasmic damage. The pathogenesis of EN is not completely understood; the immunocytes probably attach themselves to antigenic epitopes. Their nature, however, has not been clearly identified; HLA-A, B, and C and HLA-DR were displayed in areas of EN, but the antigens also were found in vessels without EN.

Endothelium, Vascular↗
PubMed1989

Acute hepatic failure: the emerging role of orthotopic liver transplantation.

From 1985 through 1987, we diagnosed acute hepatic failure in 13 patients. Spontaneous recovery occurred in three of these patients. Eight patients underwent liver transplantation, five of whom survived and three of whom died. In addition, two patients died before undergoing transplantation. The survival rate of 62% was better than that among our previous series of similar patients. This improvement seems to be related to the use of orthotopic liver transplantation as a therapeutic alternative among these patients. One of the three patients who died after liver transplantation had normal liver function, but respiratory failure caused by Pneumocystis carinii developed 4 months after the transplantation. The surgical procedure was less difficult in patients with acute fulminant hepatitis than in those with chronic liver disease because fewer problems arose from adhesions, venous collaterals, and ascites. The emerging role of orthotopic liver transplantation in patients with acute hepatic failure is demonstrated by the improvement of survival rates observed by various groups, including ours, when this therapeutic modality is available.

Acute Disease↗
PubMed1989

Cytomegalovirus hepatitis in liver transplantation: prospective analysis of 93 consecutive orthotopic liver transplantations.

Ninety-three consecutive orthotopic liver transplantations in 78 patients were followed prospectively to study the incidence of cytomegalovirus (CMV) hepatitis. CMV hepatitis occurred in 13 (17%). The diagnosis was established by both histology and culture in 5, only by histology in 6, and only by culture in 2. All 13 patients had CMV viruria and 9 had viremia at diagnosis. CMV hepatitis developed in 64% of CMV-seronegative (pretransplantation) patients who received a liver from a CMV-seropositive donor, compared with 3% or 6% of CMV-seropositive patients who received a liver from a CMV-seronegative or CMV-seropositive donor, respectively (P less than .001). CMV hepatitis was not a cause of fulminant or irreversible liver dysfunction in any of the 13 cases. Ganciclovir was administered to 6 of the 13 patients and was associated with clinical and virologic cure in 5. CMV hepatitis was self-limited in patients not treated with ganciclovir (illness less severe). The presence of inclusions within the liver tissue correlated with active disease.

Age Factors↗
PubMed1989

Surgical pathology of the syndrome of primary sclerosing cholangitis.

The diagnosis of primary sclerosing cholangitis (PSC) is based on the characteristic cholangiographic manifestations of the condition. Surgical biopsy specimens from extrahepatic bile ducts are not diagnostic. They should be obtained only if the presence of bile duct carcinoma must be ruled out. If liver transplantation is anticipated, even that procedure may be contraindicated. Gallbladder disease in PSC is common but again, histologic findings are not diagnostic. Intrahepatic cholangiectases in combination with bile duct obliteration are characteristic for PSC, but tissue samples with these lesions usually are unavailable during work-up of patients. Histologic changes in routine needle or wedge biopsy specimens from the liver may strongly support the diagnosis of PSC. The most important histologic abnormality is the absence of interlobular bile ducts in some portal tracts (ductopenia), which often coexists with evidence of ductal proliferation in other portal tracts. Portal edema and ductular proliferation frequently accompany these changes. Liver biopsy study in PSC is recommended not only for diagnostic purposes but also because the procedure allows staging of the liver disease and thus helps to determine the prognosis of patients, contributes to the decision-making process for liver transplantation, and facilitates therapeutic trials.

Biopsy↗
PubMed1989

Effect of proctocolectomy for chronic ulcerative colitis on the natural history of primary sclerosing cholangitis.

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.

Adult↗
PubMed1988

Plasma concentrations of noradrenaline and 3,4-dihydroxyphenylethyleneglycol under conditions of enhanced sympathetic activity.

Antecubital venous blood was sampled at rest and during orthostasis or supine bicycle exercise. The plasma was analyzed for noradrenaline and 3,4-dihydroxyphenylethyleneglycol (DOPEG) by HPLC. Orthostasis resulted in increases in plasma concentrations of both noradrenaline and DOPEG. The magnitude of changes in both was dependent on the degree of orthostasis. In conditions of supine rest, sitting, and standing the plot of the geometric mean values of plasma DOPEG (ordinate) against those of plasma noradrenaline was linear, had a slope of about unity, and intersected the ordinate at a finite value of plasma DOPEG. After administration of desipramine (to block uptake), plasma concentrations of DOPEG fell both at rest and during orthostasis. Moreover, desipramine abolished the plasma DOPEG response to orthostasis without affecting the plasma noradrenaline response. Hence, changes in plasma DOPEG brought about by changes in sympathetic tone are presynaptic in origin. The plasma concentration of DOPEG observed in the presence of desipramine was virtually identical with the ordinate intercept of the regression line relating plasma DOPEG to plasma noradrenaline in the absence of desipramine. This pool of plasma DOPEG (which amounted to about 75% of that observed at supine rest in the absence of desipramine) probably stems from intraneuronal noradrenaline leaking out of the storage vesicles of peripheral sympathetic neurones and may in part also be derived from the central nervous system. Supine bicycle exercise failed to increase plasma DOPEG. This may be due to the separation of the sampling site from the site of noradrenaline release (i.e. the exercising limbs) by organs involved in DOPEG extraction.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Prospective trial of penicillamine in primary sclerosing cholangitis.

We evaluated the therapeutic efficacy of penicillamine in primary sclerosing cholangitis. In a randomized, prospective, double-blind trial, 39 patients received penicillamine (250 mg t.i.d.) and 31 received a placebo. The two groups were highly comparable at entry with regard to clinical, biochemical, radiologic, and hepatic histologic features. Although a predictable cupruresis and a decrease in levels of hepatic copper were achieved in patients taking penicillamine, there was no beneficial effect on disease progression within 36 mo or on overall survival. Progressive symptoms, deterioration in serial hepatic laboratory values, or histologic progression on sequential liver biopsy specimens were similar in both groups, occurring in greater than 80% of the entire study population. The development of major side effects led to the permanent discontinuation of penicillamine in 21% of the patients taking the drug. We conclude that the use of penicillamine in primary sclerosing cholangitis is not associated with a beneficial effect on disease progression or survival, and has considerable toxicity. The study also suggests that primary sclerosing cholangitis is a progressive disease in many patients.

Adolescent↗
PubMed1988

Features reflective of early prognosis in corticosteroid-treated severe autoimmune chronic active hepatitis.

To identify features reflective of early prognosis in corticosteroid-treated severe autoimmune chronic active hepatitis, we compared the initial findings and immediate biochemical response of 5 patients who died soon after institution of corticosteroid therapy (mean survival, 2.5 +/- 0.7 mo) with those of 108 patients who survived for at least 6 mo after comparable therapy (mean survival, 94 +/- 6 mo). Early mortality could not be predicted before therapy by individual clinical, laboratory, or histologic findings. Patients who resolved at least one pretreatment laboratory abnormality, improved a pretreatment hyperbilirubinemia, or did not experience biochemical deterioration after 2 wk of corticosteroid treatment survived for at least 6 mo in 98% of instances. Patients who died early had multilobular necrosis at presentation and manifested at least one deficiency in their immediate biochemical response. Death invariably occurred in patients with multilobular necrosis and an unimproved hyperbilirubinemia after 2 wk of therapy. Only 3 of the 5 patients who died, however, could be identified in this fashion. We conclude that no individual abnormality at presentation predicts early mortality. Only patients with multilobular necrosis are at risk for an early demise and death can be predicted in those with an unimproving hyperbilirubinemia. Laboratory improvement after 2 wk of corticosteroid therapy virtually assures immediate survival.

Adult↗
PubMed1988

Assay of catecholamines and dihydroxyphenylethyleneglycol in human plasma and its application in orthostasis and mental stress.

A high performance liquid chromatographic method involving electrochemical detection is described which permits the assay of noradrenaline (NA), adrenaline (A), dopamine (DA), and dihydroxyphenylethyleneglycol (DOPEG) in human plasma and brings about analytical recoveries of 70% and more. This method was used to assess the effects of graded orthostasis and mental stress on the plasma levels of these catechols. Orthostasis elicited increases in plasma NA and DOPEG, but did not cause any change in plasma A and DA. The increases in NA and DOPEG were dependent on the degree of orthostasis and correlated closely (rs = 0.724; n = 30, P less than 0.001). Pretreatment with desipramine abolished the DOPEG response to standing, indicating that orthostasis - induced increases in plasma DOPEG are presynaptic in origin. Mental stress evoked pronounced increases in plasma A, less pronounced increases in plasma NA and no changes in plasma DA and DOPEG. Hence, the simultaneous measurement of plasma NA and DOPEG may help to distinguish between various types of activation of the sympathetic nervous system.

Adult↗
PubMed1988

Frequency and significance of immunoglobulin M antibody to hepatitis B core antigen in corticosteroid-treated severe chronic active hepatitis B.

To assess the frequency and significance of immunoglobulin M (IgM) antibody to hepatitis B core antigen (anti-HBc) in corticosteroid-treated severe chronic active hepatitis B, we tested 96 serum samples from 16 patients who were seropositive for hepatitis B surface antigen (HBsAg) (group 1) and 8 HBsAg-negative, anti-HBc-positive patients (group 2) by enzyme-linked immunoassay. Samples obtained in the presence and absence of disease activity before, during, and after long-term corticosteroid therapy (mean duration, 42 +/- 7 months) were evaluated. Seropositivity for IgM antibody was demonstrated in 12 group 1 patients, including 9 tested before corticosteroid therapy; no group 2 patients were seropositive. Seropositivity was more common in serum samples obtained during active than during inactive disease (51% versus 22%; P less than 0.05) and more frequent in serum samples that contained hepatitis B e antigen (46% versus 11%; P less than 0.02) and hepatitis B virus deoxyribonucleic acid (50% versus 24%; P less than 0.05) than in those without these markers. In some patients, seropositivity persisted or recurred intermittently during corticosteroid therapy for up to 57 months. We conclude that seropositivity for IgM antibody can be demonstrated frequently by enzyme-linked immunoassay in corticosteroid-treated patients with severe disease. Seropositivity reflects active virus replication, and it is commonly associated with inflammatory activity. The duration of seropositivity may be protracted during long-term corticosteroid therapy.

Adrenal Cortex Hormones↗
PubMed1988

Idiopathic adulthood ductopenia. A cause of chronic cholestatic liver disease and biliary cirrhosis.

We describe three adult patients who had chronic cholestatic liver disease associated with unexplained loss of interlobular bile ducts; two of these patients eventually required orthotopic liver transplantation. We have named this condition 'idiopathic adulthood ductopenia' because (1) the etiology is unknown, (2) the age of the patients may be the only distinguishing feature between this newly described condition and neonatal or infantile nonsyndromatic paucity of intrahepatic bile ducts, and (3) morphologic demonstration of ductopenia is an indispensable finding. Our three patients, all males, had a negative drug history, absence of antimitochondrial antibodies, normal cholangiographic findings, and no evidence of inflammatory bowel disease. Idiopathic adulthood ductopenia may be a representation of (1) late onset of infantile paucity of intrahepatic bile ducts, (2) destructive viral cholangitis, and (3) isolated small-duct primary sclerosing cholangitis - that is, 'pericholangitis' unassociated with inflammatory bowel disease.

Adenocarcinoma↗
PubMed1988

Effects of the antiallergic drug ketotifen on bronchial resistance and beta-adrenoceptor density of lymphocytes in children with exercise-induced asthma.

In a parallel, double-blind, placebo-controlled study we investigated the effect of the antiallergic drug Ketotifen on bronchial resistance (determined body plethysmographically) and beta 2-adrenoceptor density of lymphocytes (determined by 125-iodo-cyano-pindolol binding) in asthmatic children suffering from exercise-induced asthma (EIA). In order to provoke EIA a test which involved running for 7 min was performed with 22 asthmatic children. 13 age-matched children not suffering from asthma served as controls. Control children showed a 30% increase in the number but not in the affinity of beta-adrenoceptors in response to a 7-min run. Asthmatic children with EIA showed no difference in the number and affinity of beta-adrenoceptors under resting conditions when compared with the controls. In contrast to what has been observed with control children, however, no increase in the number of beta-adrenoceptors in response to exercise was observed. A 1-week treatment with placebo neither affected the bronchoconstriction nor the number of lymphocyte beta 2-adrenoceptors. Ketotifen (2 X 1 mg/day for 1 week) protected asthmatic children from EIA, at least in part, and restored the up-regulation of beta-adrenoceptors in response to exercise in 9 of 14 children with EIA. However, no correlation between the serum concentration of Ketotifen and the number of binding sites could be found. It is therefore concluded that the preventive effect of Ketotifen in EIA might also involve mechanisms other than a recovery of the beta-adrenergic system.

Adolescent↗
PubMed1988

Gallbladder disease in patients with primary sclerosing cholangitis.

We evaluated the gallbladders of 121 patients who had well-documented primary sclerosing cholangitis. Sonograms, cholangiograms, and CT scans were reviewed, and the findings were correlated with surgical or autopsy findings, when available. Pathologic examination of the gallbladder was available in 55 (45%) of the 121 patients; of these, 49 (89%) had abnormal gallbladders. Ninety-three of the 121 patients had one or more radiologic examinations of the gallbladder: 77 had sonograms, 80 had cholangiograms, and 18 had CT scans. Seventy-five (62%) of the 121 patients had abnormal gallbladders on histologic examination or had positive findings on one or more imaging study. By excluding 25 patients who had histologic changes of borderline significance and/or patients who had thick-walled gallbladders attributable to end-stage liver disease, we concluded that 50 (41%) of the 121 patients had intrinsic abnormalities of the gallbladder. Thirty-two (26%) had gallstones, 18 (15%) had probable primary sclerosing cholangitis involving the gallbladder, and five (4%) had benign or malignant neoplasms. Our study indicates that gallbladder abnormalities are common among patients with primary sclerosing cholangitis, and sonography is the most useful technique for evaluating these conditions.

Adult↗
PubMed1988

Etiology of biliary cirrhosis: diagnostic features and a new classification.

The current classification of biliary cirrhosis, in which only a "primary" and a "secondary" form are recognized, has lost its usefulness for diagnosis, patient management, and research. In this article, a new terminology and a new etiologic classification of biliary cirrhosis and its underlying conditions are proposed, based on the current understanding of small-duct and large-duct biliary diseases and their causes.

Autoimmune Diseases↗
PubMed1987

Late manifestation of chronic liver disease in adults with alpha-1-antitrypsin deficiency.

A review of 19 adult patients with alpha-1-antitrypsin deficiency (A1AT deficiency) and chronic liver disease revealed a late onset of symptomatic hepatic abnormalities in this condition. Thirteen patients (68%) were 60 years or older when the liver disease was discovered. The mean age of the patients with the ZZ, SZ, and MZ phenotypes was 58, 66, and 72.5 years, respectively; this suggested a later onset of the liver disease in the heterozygotes. At the time of diagnosis, the hepatic condition usually was advanced; in eight patients (42%) the survival was less than two years. The most important associated condition was chronic obstructive lung disease which was found in 10 patients (53%). We conclude that advanced age and the high incidence of obstructive lung disease make it unlikely that liver transplantation will become a common therapeutic option for adult patients with A1AT deficiency and associated liver disease. Periodic screening of liver function may be indicated in patients with A1AT deficiency so that chronic liver disease can be diagnosed early, particularly if current attempts to develop effective medical therapy for this condition are successful.

Adult↗
PubMed1987

Hepatitis B virus deoxyribonucleic acid in serum during hepatitis B e antigen clearance in corticosteroid-treated severe chronic active hepatitis B.

The relationship between hepatitis B virus deoxyribonucleic acid in serum and histologic activity was determined in 11 patients with corticosteroid-treated severe chronic active hepatitis B who underwent clearance of hepatitis B e antigen. All patients cleared hepatitis B virus deoxyribonucleic acid from the serum, and clearance preceded the loss of hepatitis B e antigen by 9-49 mo (mean 24 +/- 4 mo). Seropositivity for hepatitis B virus deoxyribonucleic acid was always associated with histologic features of chronic active hepatitis. Resolution of histologic activity followed the loss of hepatitis B virus deoxyribonucleic acid from the serum and it preceded clearance of hepatitis B e antigen in all patients. A transient elevation of serum aspartate aminotransferase activity occurred in 5 patients at the time that absence of hepatitis B virus deoxyribonucleic acid in serum was first demonstrated, and it was followed by resolution of histologic activity. The serum level of hepatitis B virus deoxyribonucleic acid slowly decreased or remained unchanged in all but 1 patient during long-term corticosteroid therapy. We conclude that hepatitis B virus deoxyribonucleic acid in serum is associated with histologic activity in corticosteroid-treated patients with severe chronic active hepatitis B. Disappearance of hepatitis B virus deoxyribonucleic acid from the serum precedes the loss of histologic activity and clearance of hepatitis B e antigen. Serum hepatitis B virus deoxyribonucleic acid levels usually do not increase during long-term corticosteroid therapy.

Adrenal Cortex Hormones↗