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Biomedical subjects

J Ludwig

Publications and source records attributed to J Ludwig.

At least 19 recordsLinked to original sources
PubMed1992

Lack of association between cytomegalovirus infection, HLA matching and the vanishing bile duct syndrome after liver transplantation.

In this study we evaluated the association between cytomegalovirus infection alone or in relation to human leukocyte antigen matching and the development of vanishing bile duct syndrome, a form of chronic hepatic allograft rejection. A total of 81 consecutive liver transplant recipients were studied. Cytomegalovirus infection developed in 46 recipients (57%), and vanishing bile duct syndrome occurred in 9 recipients (11%). Cytomegalovirus infection developed in only five of the nine patients with vanishing bile duct syndrome. Univariate analysis of pretransplant recipient/donor cytomegalovirus serological tests and human leukocyte antigen typing showed they were not significant risk factors for the development of vanishing bile duct syndrome. Time-dependent analysis of cytomegalovirus infection after transplantation as a risk factor for vanishing bile duct syndrome, in a multivariate analysis with human leukocyte antigen match, showed no statistical significance. In our study, no association was found between cytomegalovirus infection alone or in relation to class I or II human leukocyte antigen match and the subsequent development of vanishing bile duct syndrome.

Acyclovir↗
PubMed1992

Estimation of noradrenaline concentrations in the axoplasm of noradrenergic neurones in man.

The plasma concentrations of noradrenaline (NA) and its primary neuronal metabolite, dihydroxyphenylglycol (DOPEG), were examined during graded orthostasis and NA infusion in 13 healthy subjects to estimate the NA concentration difference between the site of neuronal DOPEG formation and that in plasma. Stimulation of NA release by graded orthostasis resulted in similar absolute increments in plasma NA and DOPEG with both plasma concentrations being dependent on the degree of orthostasis. The mean value of the delta DOPEG/delta NA ratio amounted to 0.999 (0.745; 1.341). NA was infused i.v. during two consecutive 30-min periods at constant rates of 0.43 and 0.86 nmol kg-1 min-1, respectively. This infusion resulted in a delta DOPEG/delta NA ratio of 0.048 (0.036; 0.064) for the first and 0.078 (0.067; 0.090) for the second infusion period (p less than 0.01). For each individual subject, the factor quantifying the NA concentration difference between the site of neuronal DOPEG formation and plasma was calculated from the square root of the ratio of 'delta DOPEG/delta NA during orthostasis to delta DOPEG/delta NA during the low rate of NA infusion'. The average NA concentration at the site of neuronal DOPEG formation (i.e. the axoplasm of noradrenergic neurones) was found to be 4.6-fold higher than that in plasma.

Adult↗
PubMed1992

Relapsing hairy cell leukemia presenting as fulminant hepatitis.

PURPOSE: We report the first known case of fulminant hepatitis due to hairy cell infiltration. CASE REPORT: A 43-year-old woman with hairy cell leukemia returned 1 year after diagnosis with spider angiomata of the face and neck, palmar erythema, and diffuse telangiectasias. The liver span was normal. Laboratory studies included: aspartate aminotransferase, 56 U/L; alkaline phosphatase, 283 U/L; gamma-glutamyltransferase, 157 U/L; and normal bilirubin. A liver biopsy demonstrated modest infiltration of hairy cells with hemosiderosis and intact hepatocytes. RESULTS: The patient responded to interferon-alpha with resolution of the angiomata, decreased palmar erythema, and improved liver function tests. Five months later, she presented with right upper quadrant pain, anorexia, fatigue, and diffuse myalgias. The physical examination was unchanged. Laboratory studies included: aspartate aminotransferase, 299 U/L; alkaline phosphatase, 1,388 U/L; total bilirubin, 43 mumol/L; and direct bilirubin, 29 mumol/L. Two weeks later, she was admitted to the hospital. Her liver span was 15 cm. Laboratory studies showed the following values: aspartate aminotransferase, 618 U/L; alkaline phosphatase, 2,319 U/L; total bilirubin, 311 mumol/L; direct bilirubin, 233 mumol/L; and alanine aminotransferase, 462 U/L. Intensive investigation of contributing causes was not revealing. A subsequent liver biopsy demonstrated extensive portal and intralobular hairy cell infiltration with loss of normal architecture. Liver function deteriorated as shown by the following values: aspartate aminotransferase, 1,100 U/L; alkaline phosphatase, 3,645 U/L; bilirubin, 477 mumol/L; and ammonia, 47 mumol N/dL. The patient died 9 days after admission. CONCLUSIONS: Although liver infiltration is often present and mild elevations of liver function tests have been noted, evidence of such extensive hepatic injury caused by hairy cell leukemia has not been reported previously. Hairy cell infiltration of the liver can cause typical cutaneous changes of liver disease and even fulminant hepatitis.

Acute Disease↗
PubMed1992

Papillary bile duct dysplasia in primary sclerosing cholangitis.

A 62-year-old man with a 20-year history of chronic ulcerative colitis and a 9-year history of primary sclerosing cholangitis (PSC) underwent orthotopic liver transplantation because of symptoms related to PSC and cholangiographic features compatible with a biliary neoplasm. Study of the excised liver revealed papillary mucosal lesions in the common hepatic duct and the right and left hepatic ducts as well as cholangiectases and other features typically associated with PSC. The papillary lesions consisted of abundant fibrovascular stroma covered by biliary epithelium with low-grade and high-grade dysplasia. Some periductal glands were also dysplastic. These features distinguished papillary dysplasia from classic biliary papillomatosis. Only one focus of microinvasion was found; there were no metastases. Among 60 cases of PSC in whom the entire liver could be studied after orthotopic liver transplantation, this was the only instance of unequivocal dysplasia. However, in one specimen, papillary hyperplasia was found. Detailed macroscopic and microscopic rereview of 23 livers from our patients with the longest history of PSC (range, 5-24 years) failed to reveal any additional cases with dysplasia. It is concluded that (a) papillary mucosal lesions in PSC may represent papillary dysplasia without invasion; (b) these lesions may evolve from papillary hyperplasia; (c) the process may be largely, if not entirely, in situ; and (d) the prevalence of dysplasia and carcinoma of bile ducts may be less than the 7%-9% reported in the literature for malignancies associated with PSC.

Bile Ducts↗
PubMed1992

Primary sclerosing cholangitis: refinement and validation of survival models.

The natural history of primary sclerosing cholangitis was studied in 426 patients from five medical centers. The median follow-up time was 3.0 years (range, 0.01-16.6 years); 100 patients had died by the time of last follow-up. Survival analysis (Cox proportional-hazards regression) was used to identify the variables most useful in predicting survival of patients with primary sclerosing cholangitis. Serum bilirubin concentration, histological stage on liver biopsy, age, and the presence of splenomegaly were independent predictors of a high risk of dying. A mathematical model to predict survival of patients with primary sclerosing cholangitis (based on referral values of those predictors) was statistically validated using two methods. Confidence intervals for predicting patient-specific survival probabilities are also presented. This model to predict survival could be used to stratify participants in therapeutic trials, counsel patients and their families, decide on candidacy for and timing of liver transplantation, and provide mathematical controls for evaluating the efficacy of therapies for primary sclerosing cholangitis, including transplantation.

Adult↗
PubMed1992

Ischemic cholangitis in hepatic allografts.

In this report, our objectives are to introduce the term "ischemic cholangitis" as an etiologic designation and to describe its manifestations. Herein we use the label "ischemic cholangitis" as a collective term for ischemic bile duct necrosis, cholangitis caused by ischemia but without necrosis, and biliary fibrosis as a manifestation of ischemic damage. The condition was observed in 12 allografts, either at the time of retransplantation (9 cases) or at autopsy (3 cases). Ischemic cholangitis involved primarily perihilar extrahepatic and intrahepatic bile ducts. The findings included duct necroses (eight cases), strictures (four cases), and cholangiectases (four cases); some of these features coexisted. In addition, complicating ascending cholangitis and cholangitic abscesses were noted in three cases. Ischemic cholangitis was caused by hepatic artery thrombosis (in nine patients) or stenosis (in one) or by occlusion of parabiliary arteries by fibrointimal proliferations, probably attributable to old thromboses (in two, in conjunction with associated foam cell arteriopathy in one). Biopsy specimens before retransplantation or autopsy were obtained in 11 patients, only 1 of whom had an infarct as direct evidence of ischemia. Nine patients had evidence of biliary obstruction or bile flow impairment; in two cases, specimens were normal or nondiagnostic relative to cholangitis. Features of cellular rejection associated with the manifestations of bile flow impairment and ischemia were noted in five cases. Thus, biopsy features that suggest biliary obstruction, with or without cellular rejection, may be a manifestation of ischemic cholangitis. We conclude that ischemic cholangitis is an important cause of cholestatic graft failure but that this type of cholangitis is difficult to diagnose because of its misleading biopsy manifestations.

Adult↗
PubMed1992

Isolated antral narrowing associated with gastrointestinal cryptosporidiosis in acquired immunodeficiency syndrome.

A 33-year-old man with human immunodeficiency virus infection had severe protracted diarrhea. Radiologic assessment disclosed narrowing of the gastric antrum. Biopsy specimens revealed diffuse Cryptosporidium infection of the antral mucosa. Isolated antral narrowing due to Cryptosporidium gastritis should be added to the list of gastrointestinal complications associated with acquired immunodeficiency syndrome (AIDS).

AIDS-Related Opportunistic Infections↗
PubMed1992

Reye's syndrome in Olmsted County, Minnesota: did it exist before 1963?

In this study, our goals were to determine whether Reye's syndrome existed before the first published report of this entity in 1963 and to describe the long-term incidence and trend of this syndrome. Medical and pathologic records and pathologic specimens for Mayo Clinic patients, including those who were residents of Olmsted County, Minnesota, were reviewed through the facilities of the Rochester Epidemiology Project. On review, 12 cases were identified for the period 1920 through 1962; 2 of these cases were in Olmsted County residents. Of the 12 cases identified before 1963, 10 were in patients younger than 5 years of age. In addition to the aforementioned two cases, five others in Olmsted County were diagnosed between 1963 and 1989. Incidence rates were computed for the Olmsted County population. The number of cases and rates per 100,000 persons younger than 18 years of age in that population were 2 cases (0.3) for 1920 through 1962, 4 cases (0.7) for 1963 through 1980, and 1 case (0.4) for 1981 through 1989. Although cases found during the earlier periods may have included disorders that mimic Reye's syndrome, the recommended criteria from the Centers for Disease Control were applied to review of medical records and supported by pathologic findings in the liver. The data showed an age distribution tending toward young patients and no seasonality of occurrence. The incidence rates in Olmsted County, Minnesota, showed an increase for 1963 through 1980 over previous decades, followed by a decrease. The small numbers preclude any conclusion about trends in the incidence rates.

Child↗
PubMed1991

Control of ligand specificity in cyclic nucleotide-gated channels from rod photoreceptors and olfactory epithelium.

Cyclic nucleotide-gated ionic channels in photoreceptors and olfactory sensory neurons are activated by binding of cGMP or cAMP to a receptor site on the channel polypeptide. By site-directed mutagenesis and functional expression of bovine wild-type and mutant channels in Xenopus oocytes, we have tested the hypothesis that an alanine/threonine difference in the cyclic nucleotide-binding site determines the specificity of ligand binding, as has been proposed for cyclic nucleotide-dependent protein kinases [Weber, I.T., Shabb, J.B. & Corbin, J.D. (1989) Biochemistry 28, 6122-6127]. The wild-type olfactory channel is approximately 25-fold more sensitive to both cAMP and cGMP than the wild-type rod photoreceptor channel, and both channels are 30- to 40-fold more sensitive to cGMP than to cAMP. Substitution of the respective threonine by alanine in the rod photoreceptor and olfactory channels decreases the cGMP sensitivity of channel activation 30-fold but little affects activation by cAMP. Substitution of threonine by serine, an amino acid that also carries a hydroxyl group, even improves cGMP sensitivity of the wild-type channels 2- to 5-fold. We conclude that the hydroxyl group of Thr-560 (rod) and Thr-537 (olfactory) forms an additional hydrogen bond with cGMP, but not cAMP, and thereby provides the structural basis for ligand discrimination in cyclic nucleotide-gated channels.

Alanine↗
PubMed1991

Intraobserver and interobserver variation in the histopathological assessment of liver allograft rejection. The Liver Transplantation Database (LTD) Investigators.

A study to determine the reproducibility of histopathological findings and diagnoses of rejection was carried out on a series of 42 liver allograft needle biopsy specimens by five pathologists practicing at four liver transplant centers. Pathologists from each of the four centers read each slide independently on two different occasions and were asked to assess 12 histopathological features and render a diagnosis. For all histological variables, the intrarater agreement was higher than the interrater agreement. Moderate to excellent agreement occurred among the pathologists about all histological variables thought to be important in establishing the diagnosis of acute rejection (i.e., portal tract inflammation, subendothelial inflammation and bile duct damage). Other variables such as lobular disarray, bile duct proliferation and particularly arteritis, however, were only fairly or poorly reproducible. Surprisingly, the diagnosis of acute rejection was more reproducible than the individual histopathological findings that were thought to be the basis for the diagnosis. The agreement for the diagnosis of chronic rejection, however, varied according to observer. We noted that relatively inexperienced observers within this group had some difficulties agreeing with more experienced observers in establishing a diagnosis of chronic rejection. These findings demonstrate that the histopathological diagnosis of acute cellular liver allograft rejection is highly reproducible within a group of experienced pathologists and that this diagnosis can be pooled in a common data base with confidence.

Biopsy, Needle↗
PubMed1991

Azathioprine hepatotoxicity after liver transplantation.

We report the first two cases of apparent azathioprine hepatotoxicity occurring after liver transplantation. The two patients exhibited jaundice, elevated serum transaminase activities and histopathological features of sinusoidal congestion and centrilobular hepatocellular degeneration 17 and 61 days after transplantation. After withdrawal of azathioprine, liver test results improved immediately in both patients. Recurrence of liver injury after another challenge with azathioprine was seen in the first case. Previously, fatal venoocclusive disease occurring after kidney transplantation had been attributed to azathioprine. Irreversible venoocclusive disease and the reversible hepatotoxicity described in this report (i.e., sinusoidal congestion with centrizonal necrosis) most likely represent different stages of hepatic endotheliitis caused by azathioprine. Thus early diagnosis of azathioprine hepatotoxicity is of great importance.

Adult↗
PubMed1991

Clinical aspects on presynaptic noradrenaline metabolism.

In healthy subjects, similar absolute increments in plasma noradrenaline (NA) and dihydroxyphenylglycol (DOPEG) were observed in response to upright posture or isoprenaline infusion. Blockade of neuronal uptake by desipramine abolished these plasma DOPEG responses and reduced plasma DOPEG per se. In essential hypertensives we found higher than normal plasma DOPEG levels at any given plasma NA. Evidence is provided that both the desipramine-sensitive and -resistant pool of plasma DOPEG contribute to this hypertensive-normotensive difference.

Chromatography, High Pressure Liquid↗
PubMed1991

Current concepts in cell-mediated hepatic allograft rejection leading to ductopenia and liver failure.

Hepatic allograft rejection is presently classified into acute and chronic rejection based on histological features, timing and reversibility. However, because features of both types of rejection can occur at any time, and in many combinations, the terms "acute" and "chronic" seem inappropriate in some instances. Thus the term "cellular rejection" better defines the histological features of portal hepatitis, nonsuppurative destructive cholangitis and endotheliitis, which are independent of time and response to therapy. Similarly, because progressive bile duct destruction leading to a decrease in the number of interlobular and septal bile ducts is the major histological feature of "chronic rejection," the term "ductopenic rejection," defined as the loss of bile ducts in 50% or more of portal tracts independent of time and reversibility, seems more appropriate. The pathogenesis of cell-mediated rejection has not been completely explained; however, direct immunocytic attack on small bile ducts and small arteries appear to be the major feature. The process may lead to bile duct loss ("ductopenia"). The pathogenetic role of foam-cell arteritis resulting in ischemic bile duct injury and the role of humoral mechanisms in causing ductopenic rejection awaits further clarification. In the past, irreversible ductopenic rejection occurred in approximately 10% of all patients who underwent their first liver transplantation; this figure, however, appears to be decreasing. The clinical features of irreversible rejection include persistent and progressive cholestasis; rising serum levels of bilirubin, alkaline phosphatase and gamma-glutamyltransferase; and a decrease in hepatic synthetic function. Ductopenic rejection can occur early (2 to 5 wk after liver transplantation) but most often develops between 6 wk and 6 mo after transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Small-duct primary sclerosing cholangitis.

Current evidence suggests that PSC may affect the entire biliary system from interlobular bile ducts to the ampulla of Vater. If the affected bile ducts are too small for cholangiographic identification, the best designation for the condition is small-duct PSC; cholangiographically identifiable duct changes are the hallmark of large-duct PSC. The term "small-duct PSC" should replace the name pericholangitis because that designation lacks a clear definition. Small-duct PSC may occur in combination with large-duct PSC or it may occur alone. The clinical course of patients with PSC depends on the hepatic changes related to small-duct PSC, not primarily on the classic large-duct disease. Therefore the features of small-duct PSC and its complications are used to determine the disease stages of PSC. The incidence of small-duct PSC still is not known and the natural history as well as the pathogenesis of the condition remains obscure. Nevertheless, the role of small-duct disease in the syndrome of PSC has come into focus and the themes for future studies are apparent. Work should commence.

Bile Ducts↗
PubMed1991

Great Lakes embryo mortality, edema, and deformities syndrome (GLEMEDS) in colonial fish-eating birds: similarity to chick-edema disease.

Several species of colonial fish-eating birds nesting in the Great Lakes basin, including herring gulls, common terns and double-crested cormorants, have exhibited chronic impairment of reproduction. In addition to eggshell thinning caused by high levels of DDT and metabolites, the reproductive impairment is characterized by high embryonic and chick mortality, edema, growth retardation, and deformities, hence the name Great Lakes embryo mortality, edema, and deformities syndrome (GLEMEDS). The hypothesis has been advanced that GLEMEDS in colonial fish-eating birds resembles chick-edema disease of poultry and has been caused by exposure to chick-edema active compounds that have a common mode of action through the cytochrome P-448 system. Detailed evidence has been collected from the following three groups of studies on herring gulls in the lower Great Lakes during the early 1970s; Forster's terns in Green Bay, Wisconsin in 1983; and double-crested cormorants and Caspian terns in various locations in the upper Great Lakes from 1986 onwards. It has proved difficult to establish not only the onset of the disease in the various species at various locations but also the period in which chick-edema active compounds were released. Anecdotal evidence suggested that serious egg mortality in Lake Ontario herring gulls first occurred in 1966, through the signs of chick-edema disease were not looked for until 1974. Only indirect evidence is available on the date of the release of one of the presumed causal agents, 2,3,7,8-tetrachlorodibenzo-p-dioxin, but highest levels may have occurred in the early to mid 1960s. More reliable data show that the onset of the improvement of reproduction of Lake Ontario herring gulls coincided with the declines in organochlorine compounds and particularly 2,3,7,8-TCDD and PCB. Similarly, information on the onset of the disease and exposures in the Forster's tern and double-crested cormorants in Green Bay is uncertain but bird banders did not observe deformities until the 1970s, which corresponds with the onset of high levels of PCB. If the disappearance of the Caspian tern from Saginaw Bay in the mid 1960s corresponds with the onset of GLEMEDS at that location, then there is a close temporal relationship to the onset of high PCB levels. Chick-edema disease is difficult to diagnose because there is no specific lesion, but rather there is a suite of lesions.(ABSTRACT TRUNCATED AT 400 WORDS)

Abnormalities, Drug-Induced↗
PubMed1991

Plasma norepinephrine and dihydroxyphenylglycol in essential hypertension.

The aim of the present study was to examine whether essential hypertension is associated with altered plasma concentrations of dihydroxyphenylglycol, the principal presynaptic metabolite of norepinephrine. Forearm venous plasma dihydroxyphenylglycol and norepinephrine were determined at rest and during graded orthostasis in 47 normotensive control subjects and 58 outpatients with essential hypertension. There was no group difference in age. At supine rest as well as during sitting and standing, hypertensive subjects had plasma norepinephrine concentrations similar to those in normotensive control subjects, but plasma dihydroxyphenylglycol concentrations were higher than those in normotensive control subjects. Both groups showed a linear relation between plasma dihydroxyphenylglycol (ordinate) and plasma norepinephrine (abscissa). The resulting regression line was steeper (p less than 0.02) and its ordinate intercept higher (p less than 0.01) in hypertensive than in control subjects. Eleven normotensive and 14 hypertensive subjects were also tested 3 hours after desipramine (1.5 mg/kg orally) was administered to inhibit neuronal norepinephrine reuptake. The drug did not alter plasma norepinephrine, but did reduce plasma dihydroxyphenylglycol and did abolish plasma dihydroxyphenylglycol responses to upright posture in both groups of subjects. The mean plasma dihydroxyphenylglycol concentration observed in the presence of desipramine again was higher in the hypertensive than in the control group (p less than 0.01) and closely agreed, in both groups, with the dihydroxyphenylglycol concentration given by the ordinate intercept of the dihydroxyphenylglycol versus norepinephrine regression line in the absence of desipramine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗