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Biomedical subjects

U Spengler

Publications and source records attributed to U Spengler.

At least 145 records · Page 8Linked to original sources
PubMed1995

Activation of a heterogeneous hepatitis B (HB) core and e antigen-specific CD4+ T-cell population during seroconversion to anti-HBe and anti-HBs in hepatitis B virus infection.

Overcoming hepatitis B virus infection essentially depends on the appropriate immune response of the infected host. Among the hepatitis B virus antigens, the core (HBcAg) and e (HBeAg) proteins appear highly immunogenic and induce important lymphocyte effector functions. In order to investigate the importance of HBcAg/HBeAg-specific T lymphocytes in patients with acute and chronic hepatitis B and to identify immunodominant epitopes within the HBcAg/HBeAg, CD4+ T-cell responses to hepatitis B virus-encoded HBcAg and HBcAg/HBeAg-derived peptides were studied in 49 patients with acute and 39 patients with chronic hepatitis B. The results show a frequent antigen-specific CD4+ T-cell activation during acute hepatitis B infection, a rare HBcAg/HBeAg-specific CD4+ T-cell response among HBeAg+ chronic carriers, and no response in patients with anti-HBe+ chronic hepatitis. An increasing CD4+ T-cell response to HBcAg/HBeAg coincides with loss of HBeAg and hepatitis B virus surface antigen (HBsAg). Functional analysis of peptide-specific CD4+ T-cell clones revealed a heterogeneous population with respect to lymphokine production. Epitope mapping within the HBcAg/HBeAg peptide defined amino acids (aa) 1 to 25 and aa 61 to 85, irrespective of the HLA haplotype, as the predominant CD4+ T-cell recognition sites. Other important sequences could be identified in the amino-terminal part of the protein, aa 21 to 45, aa 41 to 65, and aa 81 to 105. The immunodominant epitopes are expressed in both proteins, HBcAg and HBeAg. Our findings lead to the conclusion that activation of CD4+ T lymphocytes by HBcAg/HBeAg is a prerequisite for viral elimination, and further studies have to focus on the question of how to enhance or induce this type of T-cell response in chronic carriers. The immunodominant viral sequences identified may have relevance to synthetic vaccine design and to the use of peptide T-cell sites as immunotherapeutic agents in chronic infection.

Acute Disease↗
PubMed1995

Gallbladder emptying during high-dose cholecystokinin infusions. Effect in patients with gallstone disease and healthy controls.

BACKGROUND: Impaired gallbladder emptying is a pathogenetic factor in gallstone formation. To test whether gallbladder motility can be improved by high-dose cholecystokinin (CCK), gallbladder emptying was measured sonographically in 21 patients with cholesterol gallstone disease and 6 healthy controls. METHODS: The effects of CCK infusions of 0.06 IDU/kg.min (group A, n = 11) and 0.12 IDU/kg.min (group B, n = 10) were compared with the response to a standard CCK infusion (0.02 IDU/kg.min). Controls received CCK at all infusion rates. RESULTS: The ejection fraction was smaller after CCK infusion of 0.06 IDU/kg.min than after the standard stimulus (group A, 52 +/- 10 versus 64 +/- 10%, p < 0.05; controls, 66 +/- 10 versus 91 +/- 3%, p < 0.05). After infusion of 0.12 IDU/kg.min CCK ejection fractions decreased even more (group B, 44 +/- 16 versus 65 +/- 12%, p < 0.05; controls, 54 +/- 12 versus 91 +/- 3%, p < 0.05). High-dose CCK infusions shortened the ejection period markedly, whereas the ejection rate remained unaltered. CONCLUSIONS: High-dose CCK does not improve gallbladder motility but blocks the ejection process early, leading to reduced gallbladder emptying in gallstone patients and healthy subjects.

Case-Control Studies↗
PubMed1995

[Interferons as therapy in viral hepatitis: are promises kept?].

Due to their antiviral and immunomodulatory properties, interferons constitute the only efficacious therapy against chronic viral hepatitis. Type-1 interferons are used for therapy with doses ranging between 3 and 10 million units on three days a week. Duration and dose vary with the various forms of viral hepatitis and have not been defined for all instances. In chronic hepatitis B, continued suppression of viral replication can be achieved in 40 to 50% of patients and leads to loss of HBV-DNA and HBe in the serum. 10 to 15% of patients also loose HBs-Ag later on. By carefully selecting patients, even higher success rates can be achieved; however, good selection criteria do not exist for chronic hepatitis C. With this hepatitis, interferons normalize aminotransferases frequently, but sustained elimination of viral infection is still a rare event. Finally, most patients have a relapse of their hepatitis when interferon therapy is terminated. Thus, only 20% of patients with chronic hepatitis C have a sustained benefit from their interferon treatment. Interferon therapy of chronic hepatitis D is even more difficult. Side effects increase with dose and duration of therapy. Fortunately, they only rarely require discontinuation of interferon and are fully reversible, when interferon is stopped. In conclusion, as there exist no therapeutic alternatives, patients with chronic hepatitis B and hepatitis C should be treated with interferon, even though only 20 to 40% of treated patients benefit in the long term.

Contraindications↗
PubMed1995

Isolated tuberculosis of the pancreas masquerading as a pancreatic mass.

A 65-yr-old woman presented for evaluation of a pancreatic mass. She had been suffering from severe constitutional symptoms for 18 months; those symptoms included weight loss, increasing fatigue, night sweats, and recurrent fever attacks up to 40 degrees C. Later, bluish subcutaneous nodules developed on her lower limbs. Laboratory tests yielded signs of chronic inflammation and impaired glucose tolerance with elevated serum insulin and glucagon concentrations. Skin biopsy revealed lobular panniculitis. Ultrasonography and a CT scan demonstrated enlargement of the pancreas, and endoscopic retrograde pancreaticography disclosed displacement and stenosis of the main pancreatic duct. The patient was referred for explorative laparotomy, which was highly suggestive of a malignant pancreatic tumor. However, histological examination of the resected pancreatic and peripancreatic mass revealed tuberculous pancreatitis. This form of isolated tuberculous pancreatitis, associated with lobular panniculitis and laboratory features consistent with a tumor of the endocrine pancreas, has not been reported previously. Active tuberculosis should be a leading differential diagnosis in a patient with an enlarged pancreas when the usual diagnostic reasoning does not yield conclusive results.

Aged↗
PubMed1995

[Hepatitis and posthepatic cirrhosis in AIDS].

Liver biopsy (n = 35) and autopsy (n = 71) specimens from HIV infected HCV-positive and HCV-negative haemophiliacs and non-haemophiliacs and liver biopsies (n = 33) from HIV-negative HCV-infected haemophiliacs and non-haemophiliacs were studied by histo- and immunohistochemistry to investigate the influence of HIV-coinfection on chronic C hepatitis (> 10 years duration). Almost all HIV-infected patients had a CD4 cell counts < 200/microns3. In biopsies and autopsies HCV-infection lead to stronger portal, periportal and lobular inflammatory changes independent from HIV-infection and haemophilia. However, HIV-infected patients with HCV-coinfection showed much more granulocytic infiltrates, particularly in the small bile ducts. In biopsies and autopsies HCV infection was associated with a stronger (centrilobular) fibrosis, particularly in HIV-positive haemophiliacs, and significantly stronger compared to HCV-negative patients. In the autopsy group half of the HIV-infected and HCV-positive haemophiliacs (n = 20) had developed posthepatitic liver cirrhosis due to C hepatitis, contrasted by two liver cirrhosis in HCV-infected non-haemophiliacs (n = 6) due to chronic B and C hepatitis and chronic alcohol abuse; no liver cirrhosis was observed in HIV-positive HCV-negative non-haemophiliacs (n = 45). Cholestasis and mild granulocytic cholangiolitis was a predominant feature in HIV/HCV-coinfection and similar distributed in haemophiliacs and non-haemophiliacs. The findings are suggestive that HIV-coinfection aggravates the course of a preceding hepatitis C virus infection, by a more granulocytic inflammatory infiltrate, stronger (centrilobular) fibrosis followed by a high incidence of posthepatitic cirrhosis--particularly in multitransfused haemophiliacs--and by cholestatic hepatopathy.

Acquired Immunodeficiency Syndrome↗
PubMed1994

[Chronic hepatitis C in type-II cryoglobulinemia and cutaneous vasculitis].

Over a period of 2 years recurrent erysipelas-like skin eruptions developed over both lower legs of a 77-year-old woman. On examination there was a vasculitic purpura which histologically was like leukocytoclastic vasculitis. Further tests revealed a positive rheuma factor, a mixed type II cryoglobulinaemia of monoclonal IgM-kappa paraprotein and polyclonal IgG, as well as chronic hepatitis C with viral replication and demonstration of hepatitis C virus-RNA in the cryoprecipitates, diagnostic of chronic hepatitis C with mixed type II cryoglobulinaemia. Treatment was begun with prednisone, 25 mg/d orally, and cyclophosphamide, 100 mg/d orally. Once hepatitis C had been diagnosed, treatment was continued with interferon alpha-2b (initially 3 x 5 mill. IU, later 3 x 3 mill. IU, each weekly subcutaneously). The vasculitis quickly healed and the cryoglobulinaemia had disappeared within 5 weeks. So far, during the treatment of 9 months, the vasculitis has not recurred, but cryoglobulins have again been demonstrated. The signs and symptoms of hepatitis C were not affected by the interferon treatment.

Aged↗
PubMed1994

Amanita phalloides intoxications in a family of russian immigrants. Case reports and review of the literature with a focus on orthotopic liver transplantation.

Alpha-amanitin, the main toxin of the death cap fungus (Amanita phalloides) is one of the most dangerous natural poison. This toxin damages eukaryotic cells by inhibiting their transcription. Lesions are seen in cells with rapid protein synthesis, particular in liver and renal cells, even at low toxin concentrations. Without adequate intensive therapy, the outcome of alpha-amanitin poisoning is very poor. This article reports various courses of amanitin intoxication in a family. In 3/4 patients, severe hepatic failure developed as assessed by a decrease of all coagulation factors, mainly Quick's test and factor V (< 10%-15%). Despite vigorous replacement of coagulation factors, in 1 of the patients orthotopic liver transplantation had to be performed on day 4, whereas in all other patients liver function improved spontaneously. All patients survived their intoxication. Both the pharmacological basis and clinical manifestations of Amanita intoxication are discussed. On this basis a treatment scheme is presented which the authors believe may be useful to clinicians.

Adult↗
PubMed1993

Increased frequency of CD8+ CD45R0+ memory T lymphocytes in acute hepatitis B virus infection.

CD8+ lymphocytes of the memory subset (= CD45R0+) encompass antigen-specific effector cells, which are believed to be decisive for virus elimination in several viral infections. To determine whether this can be extended to HBV infection naive and memory T cells were studied among CD(4+)- and CD(8+)-lymphocytes and used monoclonal antibodies in two-color flow cytometric analysis to quantitate functional T cell subsets in peripheral blood of patients with acute hepatitis B (n = 11), chronic hepatitis B (n = 24) and healthy individuals (n = 26). Compared to CD4+ populations of healthy individuals the number of total CD4+ lymphocytes in patients with both acute or chronic hepatitis was significantly reduced. In contrast CD8+ cells did not significantly change in either acute and chronic hepatitis. Analysis of naive and memory subsets demonstrated, however, a significant rise in CD45R0+ memory cells from 5 to 15% (70% of all CD8+ cells) in acute hepatitis. These changes within the CD8+ population were, however, restricted to the acute phase of hepatitis in that the frequency of CD8+CD45R0+ decreased within weeks post infection. Furthermore, patients with chronic hepatitis did exhibit normal values of CD8+ memory cells (30% of all CD8+ cells). These findings suggest that enrichment of CD8+CD45R0+ memory cells reflects an accumulation of functional effector cells, which may be specifically activated by viral antigens and determine the outcome of infection.

Acute Disease↗
PubMed1993

Gallbladder emptying is an important factor in fragment disappearance after shock wave lithotripsy.

The role of gallbladder emptying in fragment disappearance following shock wave lithotripsy of gallstones is poorly understood. We studied gallbladder motility in two groups of patients who had been treated by electrohydraulic shock wave lithotripsy and bile acid dissolution therapy. Group I (n = 20) consisted of patients with fragment disappearance within 18 months after lithotripsy, while patients in group II (n = 20) still harboured fragments in the gallbladder 18 months after lithotripsy. Fasting gallbladder volume was 19 +/- 10 ml (mean +/- S.D.) in group I, and 24 +/- 12 ml in group II (not significant). The residual volume was 8 +/- 9 ml in group I, but 18 +/- 14 ml in group II (p < 0.005). Thus, patients in group I ejected nearly twice as much of the fasting gallbladder volume as patients in group II. This difference in gallbladder emptying was still present if only the patients with single stones were compared in both groups. From the results of this retrospective study we conclude that gallbladder emptying is an important factor for complete fragment disappearance after gallstone disintegration by extracorporeally generated shock waves. Further prospective studies are needed to confirm these observations.

Adult↗
PubMed1992

Effect of ursodeoxycholic acid on the kinetics of the major hydrophobic bile acids in health and in chronic cholestatic liver disease.

Beneficial effects of ursodeoxycholic acid in chronic cholestatic liver diseases have been attributed to displacement of hydrophobic bile acids from the endogenous bile acid pool. To test this hypothesis, we determined pool sizes, fractional turnover rates, synthesis/input rates and serum levels of deoxycholic acid and chenodeoxycholic acid before and 1 mo after the start of treatment with ursodeoxycholic acid (13 to 15 mg/kg body wt/day) in four healthy volunteers and five patients with chronic cholestatic liver diseases (three with primary biliary cirrhosis and two with primary sclerosing cholangitis). Bile acid kinetics were determined by combined capillary gas chromatography-isotope ratio mass spectrometry in serum samples after administration of [2H4] deoxycholic acid and [13C]chenodeoxycholic acid. In healthy volunteers, deoxycholic acid pool sizes decreased during administration of ursodeoxycholic acid by 72%. In patients with cholestatic liver diseases, deoxycholic acid pool sizes before ursodeoxycholic acid treatment were only 13% of those in healthy volunteers and were unaffected by ursodeoxycholic acid treatment. Chenodeoxycholic acid pool sizes were not different in healthy volunteers and in patients with cholestatic liver disease, and were not altered by ursodeoxycholic acid treatment. In both healthy volunteers and patients with cholestatic liver disease, synthesis/input rates and serum levels of deoxycholic acid and chenodeoxycholic acid were not altered by ursodeoxycholic acid treatment. Because in our patients improvement of serum liver tests during short-term ursodeoxycholic acid treatment was noted without a decrease of the pool sizes of the major hydrophobic bile acids, we conclude that displacement of hydrophobic endogenous bile acids is not the mechanism of action of ursodeoxycholic acid in chronic cholestatic liver disease.

Adult↗
PubMed1992

Ursodeoxycholic acid for treatment of primary sclerosing cholangitis: a placebo-controlled trial.

The efficacy and safety of ursodeoxycholic acid for the treatment of primary sclerosing cholangitis were evaluated in a prospective, randomized, double-blind, placebo-controlled trial. Fourteen patients with primary sclerosing cholangitis documented by cholestatic serum enzyme pattern, liver histological appearance and endoscopic retrograde cholangiography were included in the trial. Six patients received ursodeoxycholic acid (13 to 15 mg/kg body wt/day), and eight patients received placebo. Two patients had to be withdrawn from the study, one because of UDCA-related diarrhea and the other because of worsening of the disease during placebo treatment. Patients in the ursodeoxycholic acid group improved significantly during 1 yr of treatment with respect to serum levels of bilirubin (median = -50%), alkaline phosphatase (median = -67%), gamma-glutamyltransferase (median = -53%), AST (median = -54%) and ALT (median = -36%) compared with the placebo group, but not with respect to serum levels of hydrophobic bile acids. During ursodeoxycholic acid treatment, histopathological features also improved significantly, as evaluated by multiparametric score. Expression of human leukocyte antigen class I molecules appeared to be markedly reduced on liver cells after ursodeoxycholic acid treatment. We conclude that ursodeoxycholic acid is beneficial in reducing disease activity in patients with primary sclerosing cholangitis.

Adolescent↗
PubMed1992

T lymphocytes from patients with primary biliary cirrhosis produce reduced amounts of lymphotoxin, tumor necrosis factor and interferon-gamma upon mitogen stimulation.

Primary biliary cirrhosis (PBC) is considered an autoimmune disease characterized by destruction of small intrahepatic bile ducts by lymphocytes. Altered functions of these lymphocytes might reflect an abnormal immune response leading to tissue damage. We investigated lymphokine secretion by mitogen-stimulated T lymphocytes from the liver biopsies of patients with PBC and for comparison also peripheral blood. In PBC, diminished synthesis of lymphotoxin (TNF beta), tumor necrosis factor (TNF alpha) and interferon-gamma (IFN gamma) was found both in T-cell lines from liver tissue and in peripheral blood. The reduction was most prominent for TNF beta in early histological stages of PBC, and appeared to be a stable phenomenon when T cells were tested after long-term tissue culture. Analysis of mRNA levels indicates a possible link between reduced TNF beta production and a defect in interleukin-2 transcription. The data suggest that diminished lymphokine production in patients with PBC may play an important role in the immunopathogenesis of this disease.

Adult↗
PubMed1992

Deterioration of cholestasis after endoscopic retrograde cholangiography in advanced primary sclerosing cholangitis.

Complications of endoscopic retrograde cholangiography specific to patients with primary sclerosing cholangitis have not yet been reported. We observed transient rises of serum bilirubin after diagnostic endoscopic retrograde cholangiography in five of 15 patients and persistent rises in three of 15 patients with primary sclerosing cholangitis examined consecutively by endoscopic retrograde cholangiography from 1985 to 1990. Deterioration of cholestasis was particularly associated with advanced disease. Seven of eight patients with deterioration after endoscopic retrograde cholangiography had septal fibrosis (stage III) or cirrhosis (stage IV) and a priori elevated serum bilirubin levels. In contrast, all patients with no deterioration of cholestasis following endoscopic retrograde cholangiography had early histological changes (stage I-II), and all but one patient had normal serum bilirubin levels. We conclude that the potentially harmful effects on biliary excretion must be taken into account when the use of endoscopic retrograde cholangiography is being considered in patients with advanced primary sclerosing cholangitis.

Adult↗