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Biomedical subjects

J Ludwig

Publications and source records attributed to J Ludwig.

At least 109 records · Page 6Linked to original sources
PubMed1995

Granulomas in primary sclerosing cholangitis.

Granulomas in liver biopsy specimens from adult patients with chronic ductopenic cholestatic liver disease are a characteristic feature of primary biliary cirrhosis. However, we found a similar combination of abnormalities in 7 out of 100 native livers (7%) from patients who had orthotopic liver transplantation for primary sclerosing cholangitis. In a control group of native livers from 100 patients with primary biliary cirrhosis, the prevalence of granulomas was exactly the same, 7%. In the primary sclerosing cholangitis group, 13 addition livers showed a granulomatous epithelioid cell response, with or without foreign body type giant cells, to extravasated bile. All granulomas were noncaseating and non-necrotizing; they consisted of epithelioid cells and often contained giant cells. Perigranulomatous lymphocytic infiltrates were generally mild to moderate. The granulomas involved portal tracts, scars, and hepatic parenchyma. Biopsy experience revealed that granulomas can be found in all stages of the disease. In contradistinction to the granulomas in primary biliary cirrhosis, the granulomas in primary sclerosing cholangitis did not represent granulomatous cholangitis--that is, they were not a feature of the duct destruction. The etiology of these lesions is not clear, but in some cases we found strong morphologic evidence that granulomas may form as a response to the leakage of bile or bile components. No evidence of infection or of sarcoidosis was found. Although adverse drug responses cannot be ruled out with certainty, review of the clinical histories made that mechanism unlikely. Thus, the presence of granulomas in chronic ductopenic cholestatic liver disease is not pathognomonic for primary biliary cirrhosis and, in rare instances (on average, in 3-4% of the biopsy samples), may be a feature of primary sclerosing cholangitis.

Adult↗
PubMed1995

Reliability and predictive value of the National Institute of Diabetes and Digestive and Kidney Diseases Liver Transplantation Database nomenclature and grading system for cellular rejection of liver allografts.

Pathologists participating in the National Institute of Diabetes and Digestive and Kidney Diseases Liver Transplant Database (LTD) created a histopathological grading system for acute liver allograft rejection, and tested it first for inter- and intra-rater reliability among a group of five pathologists experienced in liver and transplantation pathology. Specimens from post-transplantation biopsies from 48 patients with rejection, hepatitis, or other diagnosis(es) were reviewed. There was moderate to good (kappa = 0.40 to 0.55) inter-rater and good (kappa = 0.55 to 0.58) intrarater agreement for the diagnosis and exact grading of mild, moderate, or severe acute rejection, which improved when a short clinical history was provided. Thus, the scheme was reproducible, and few of the disagreements among the pathologists would have affected treatment decisions. Secondly, the ability of the grading system to predict an unfavorable short- or long-term outcome from the initial histopathological diagnosis of cellular rejection was tested on groups of 168 and 133 patients, respectively, from the three LTD clinical centers, who were followed up for at least 6 months after the first onset of rejection. This analysis showed that a higher histopathological grade of acute rejection on first biopsy diagnosis was significantly associated (P < or = .006) with both an unfavorable short-term outcome, defined by failure of the episode to resolve within 21 days or the need for aggressive immunosuppressive treatment, and a long-term outcome defined by death or retransplantation from rejection within 6 months of onset. Lastly, an analysis was performed to determine whether subjective rejection grading by the pathologist or certain "objective" histopathological features identified by logistic regression modeling were more accurate in predicting an unfavorable outcome.(ABSTRACT TRUNCATED AT 250 WORDS)

Databases, Factual↗
PubMed1995

Antimitochondrial antibody-negative primary biliary cirrhosis.

OBJECTIVES: We reviewed our experience with patients who had biochemical and histological features of primary biliary cirrhosis in the absence of antimitochondrial antibodies (AMA) to better understand this variant of the syndrome. METHODS: During the period between 1976 to 1992, 597 patients with clinical and histological features of primary biliary cirrhosis were seen at the Mayo Clinic. Thirty-five (5.8%) of these patients were negative for antimitochondrial antibody and had normal cholangiographic studies. The records of these patients were reviewed for this study. RESULTS: No difference was found between the two groups with respect to age, gender, or biochemical features. IgM and gamma-globulin levels were higher in the antimitochondrial antibody-positive than the antimitochondrial antibody-negative patients. What is more important, 96% of the AMA-negative patients who could be tested were positive for antinuclear antibody or anti-smooth-muscle antibodies. These tests were positive in only 56% of the antimitochondrial antibody-positive group (p < 0.05). The response of five of these patients to ursodeoxycholic acid appeared comparable to the response seen in antimitochondrial antibody-positive patients. CONCLUSIONS: Patients with histological features of primary biliary cirrhosis, whether antimitochondrial antibody positive or negative, are quite comparable with respect to clinical and biochemical features. Other autoantibodies, such as antinuclear or anti-smooth-muscle antibodies, are more common in the antimitochondrial antibody-negative group. These two conditions might be part of a spectrum that has been termed "autoimmune cholangitis" and that is characterized by chronic cholestasis, histological features of chronic nonsuppurative destructive cholangitis, and the presence of any of a variety of serum autoantibodies.

Antibodies, Antinuclear↗
PubMed1994

Functional expression of a rat homologue of the voltage gated either á go-go potassium channel reveals differences in selectivity and activation kinetics between the Drosophila channel and its mammalian counterpart.

We have cloned a mammalian (rat) homologue of Drosophila ether á go-go (eag) cDNA, which encodes a distinct type of voltage activated potassium (K) channel. The derived Drosophila and rat eag polypeptides share > 670 amino acids, with a sequence identity of 61%, exhibiting a high degree of similarity at the N-terminus, the hydrophobic core including the pore forming P region and a potential cyclic nucleotide binding site. Rat eag mRNA is specifically expressed in the central nervous system. In the Xenopus oocyte expression system rat eag mRNA gives rise to voltage activated K channels which have distinct properties in comparison with Drosophila eag channels and other voltage activated K channels. Thus, the rat eag channel further extends the known diversity of K channels. Most notably, the kinetics of rat eag channel activation depend strongly on holding membrane potential. Hyperpolarization slows down the kinetics of activation; conversely depolarization accelerates the kinetics of activation. This novel K channel property may have important implications in neural signal transduction allowing neurons to tune their repolarizing properties in response to membrane hyperpolarization.

Amino Acid Sequence↗
PubMed1994

[Acquired heart valve defects. Diagnostic and therapeutic strategies].

BACKGROUND: Diagnostic and therapeutic strategies in patients with acquired valvular heart disease, are determined by clinical symptoms, hemodynamics and empirical information. DIAGNOSIS: A quantitative assessment of cardiac disease can made largely on the basis of echocardiography or Doppler echocardiography with consideration also being given to the results of clinical findings. As a rule, cardiac catheterization should be done only once, immediately prior to operation. OUTLINE OF THERAPY: In chronic mitral and aortic valve insufficiency, the surgical indication is based primarily on the clinical symptoms, while in aortic and mitral valve stenosis, it is based primarily on the hemodynamic findings. Promising interventional procedures such as balloon valvuloplasty, represent useful alternatives to valve replacement in the case of mitral valve stenosis alone. In the event of significant aortic valve stenosis alone. In the event of significant aortic valve stenosis, balloon valvuloplasty is not a promising procedure. In patients with aortic or mitral valve insufficiency, but normal left ventricular function, medical treatment should first be attempted.

Catheterization↗
PubMed1994

Oligonucleotide duplexes containing 2'-amino-2'-deoxycytidines: thermal stability and chemical reactivity.

Thermal stabilities of oligonucleotides containing 2'-amino-2'-deoxycytidines were determined and compared to those of the unmodified oligonucleotides. The presence of the 2'-aminonucleoside destabilized duplexes in a RNA as well as a DNA context at pH 7 as well as at pH 5. The pKa of the 2'-amino group was determined by 13C-NMR spectroscopy to be 6.2. The reactivity of an oligonucleotide containing a 2'-aminonucleoside was exploited for the incorporation of rhodamine by its isothiocyanate derivative.

Amines↗
PubMed1994

Ursodeoxycholic acid in the treatment of primary biliary cirrhosis.

BACKGROUND/AIMS: A double-blind, placebo-controlled trial of ursodeoxycholic acid (UDCA) was conducted in 180 patients with primary biliary cirrhosis (PBC) to define the efficacy and safety of UDCA. Efficacy was assessed by time to treatment failure defined as death; liver transplantation; histological progression; development of varices, ascites, or encephalopathy; doubling of total serum bilirubin levels; progression of fatigue or pruritus; drug toxicity; or voluntary withdrawal. METHODS: Patients with well-defined PBC underwent complete history, physical examination, liver chemistries, ultrasonography, upper endoscopy, and liver biopsy at entry as well as at 2 years. Liver chemistries were determined every 3 months. RESULTS: In patients receiving UDCA, treatment failure was delayed compared with the placebo-treated group (P = 0.0003, log rank test). Seven patients receiving UDCA died or required transplantation compared with 12 in the placebo group (P = 0.18). No patients discontinued UDCA because of side effects of toxicity. CONCLUSIONS: UDCA was extraordinarily safe and well tolerated, and its use was associated with delayed progression of the disease as defined in this study. However, the lack of effects on symptoms, histology, and the need for liver transplantation or survival indicate that further evaluation is necessary to determine the ultimate role of UDCA in the treatment of PBC.

Adult↗
PubMed1994

The eosinophil as an effector cell of the immune response during hepatic allograft rejection.

OBJECTIVE: To evaluate the role of the eosinophil granulocyte during hepatic allograft rejection. DESIGN: (a) A retrospective case-control study and (b) a prospective study of consecutive liver transplant recipients. PATIENTS: In the retrospective study, eight patients with severe rejection in the first month after liver transplantation were compared with six patients without rejection. In the prospective study, 20 consecutive patients were studied for the presence of liver allograft rejection between March 1989 and October 1989. MEASUREMENTS: Absolute eosinophil counts were determined whenever blood was drawn. Serum was analyzed for the presence of two eosinophil granule proteins, major basic protein and eosinophil-derived neurotoxin, on days 7, 14 and 21 after transplantation. Liver biopsy specimens were stained for the presence of major basic protein by means of immunofluorescence using a double-antibody staining technique. The degree of eosinophil infiltration and degranulation was graded using a panel of representative slides. RESULTS: Blood eosinophilia was increased in patients with hepatic allograft rejection (p < 0.05). Serum major basic protein and eosinophil-derived neurotoxin concentrations were similar in patients with and without rejection. Many portal tracts of patients with rejection contained an abundance of eosinophils, and staining for major basic protein revealed the presence of intact eosinophils. In addition, extracellular major basic protein was seen, sometimes in the absence of intact eosinophils or an extensive infiltrate. In patients with severe allograft rejection, major basic protein staining was present in littoral cells lining the sinusoids. CONCLUSIONS: Patients with severe rejection in the first month after liver transplantation often have blood eosinophilia and marked infiltration of portal tracts with eosinophils or evidence of eosinophil degranulation. The presence of major basic protein likely is direct evidence of tissue destruction and may indicate active rejection (major basic protein in eosinophils and extracellular major basic protein, presence of portal infiltrate) or the immediate postinflammatory rejection state (extracellular major basic protein and major basic protein inside littoral cells, absence of portal infiltrate and eosinophils, bile ducts damaged or vanished). These findings underline the importance of the eosinophil as an integral part of the rejection process. We conclude that the presence of eosinophils or their secretion products in the first month after liver transplantation is an indicator of ongoing or recent allograft rejection.

Antibody Formation↗
PubMed1994

Evidence for partial sympathetic cardiac reinnervation following cardiac transplantation.

Heart transplantation causes total cardiac denervation. Measurements of plasma concentrations of the main presynaptic noradrenal metabolite, dihydroxyphenylglycol (DOPEG, exclusively neuronal in origin), were used to examine the possibility of sympathetic reinnervation of the transplanted human heart. We determined arterial and coronary-venous plasma concentrations of DOPEG in 15 heart transplant recipients (28-68 years of age at the time of transplantation with the transplant ageing from 0.5 to 4 years at the time of investigation) and in nine control patients (45-75 years of age). In each of the control patients the DOPEG concentration was higher in coronary venous plasma than in arterial plasma (mean arteriovenous increment: 60 +/- 10%; P < 0.001). In the heart transplant recipients nine patients showed an arteriovenous increment in plasma DOPEG. For the mean group results it was found that the ratio of the coronary-venous to arterial DOPEG concentration was positively correlated with the time after transplantation (r = 0.92; n = 5; P < 0.05). Thus, our data provide neurochemical evidence for partial sympathetic reinnervation in some of the heart transplants. Moreover, it is suggested that the time after transplantation is unlikely to be the only determinant for the occurrence and extent of sympathetic reinnervation.

Adult↗
PubMed1994

The liver biopsy diagnosis of Wilson's disease. Methods in pathology.

The authors present a simple liver biopsy protocol that is a reliable and cost-effective method of diagnosing hepatic Wilson's disease. Biopsy specimens are obtained in routine fashion, without the need for copper-free solutions or instruments. The samples are then embedded in paraffin, stained for copper and copper-associated protein, and studied by light microscopy. Subsequently, a sample of hepatic parenchyma is excised from the paraffin block for chemical quantitation of tissue copper. This combination of methods generally yields reliable results and allows confirmation of the diagnosis in cases of Wilson's disease in which special stains for copper are negative. In most instances, electron-microscopic studies are not necessary.

Adult↗
PubMed1994

[Analysis of the pressure-surface relation of the left ventricle with automatic echocardiographic contour detection].

UNLABELLED: Echocardiographic automatic border detection is a new on-line technique determinating the interface between blood and myocardial tissue thus having the potential to calculate cyclic changes in left ventricular cavity area in real time. It was the main purpose of the current study to evaluate left ventricular pressure-area relationship after administration of nitrates. In 12 patients with normal left ventricular function pressure-area relation was studied after a Swan-Ganz thermodilution catheter was placed in the wedge position and a high fidelity pig tail catheter was placed in the left ventricle. Left ventricular pressure and cyclic changes of cavity area were simultaneously analysed and displayed together as waveforms on the echo screen using a computer interfaced with the echo machine. All measurements were done before and five minutes after administration of 0.8 mg nitroglycerin. Mean systolic and diastolic blood pressure decreased significantly from 145/12 mmHg to 127/8 mmHg (p < 0.05). Mean systolic area decreased slightly from 10 cm2 to 9 cm2 (n.s.) whereas mean enddiastolic area decreased significantly from 18 cm2 to 15 cm2 (p < 0.05). Accordingly there was a downward and leftward shift of the diastolic pressure-area relationship following administration of nitroglycerin. CONCLUSION: Echocardiographic automated border recognition seems to be a promising new on-line method in the detection of left ventricular cavity area changes underlining its potential usefulness in the evaluation of left ventricular performance.

Adult↗
PubMed1994

The preparation of native livers for morphological studies.

We describe experiences with a perfusion fixation apparatus that was used for studies on approximately 500 native livers. Immediately after excision of the specimen, small samples from needle biopsy specimens are obtained for snap-freezing and the remaining portions of the specimens are fixed and embedded in paraffin. In the laboratory, the portal vein and, if possible, the hepatic artery or common hepatic duct are then cannulated and the livers are perfused for 3 days with Kaiserling's solution. An electric pump drives the perfusion apparatus and allows the formalin to cascade through stacked plastic containers, with the specimens attached to the inflow nozzles for the fixative. Eight or more livers (or other organs and specimens) can be accommodated simultaneously. Angiograms or cholangiograms can be prepared before or after fixation; we prefer the latter. The livers are then sliced with an extra-long knife, which minimizes cutting marks. Most preparations are thoroughly fixed and yield excellent specimens, not only for routine microscopic study but also for special methods such as scanning electron microscopy and trace metal analysis. The liver slices can be stored indefinitely, which allows long-range collection for routine review or research purposes. In approximately 5% of the cases, specimens cannot be perfused properly and thus are unsuitable for this type of preparation. With autopsy specimens this percentage is higher, probably because of postmortem clotting. Gravity perfusion of the livers before placement into the apparatus generally enables identification of specimens with incomplete filling of the vasculature.

Angiography↗