Search PubMed⌕ Search

Biomedical subjects

H E Blum

Publications and source records attributed to H E Blum.

At least 19 recordsLinked to original sources
PubMed1995

The transjugular intrahepatic portosystemic stent-shunt procedure for refractory ascites.

BACKGROUND: Previous studies have suggested that the transjugular placement of an intrahepatic stent to establish a portosystemic shunt is an effective treatment of uncomplicated ascites accompanying variceal bleeding. We studied the stent shunt for use in patients with liver cirrhosis and ascites refractory to medical treatment. METHODS: Fifty of 62 consecutive patients with cirrhosis and refractory ascites (18 with Child-Pugh class B liver disease and 32 with class C) were treated with the stent shunt--an expandable stent of metallic mesh placed between a major branch of the portal vein and one of the hepatic veins. Patients were followed for a mean (+/- SD) of 426 +/- 333 days. Those with advanced cancer, severe heart failure, or severe liver failure were excluded. RESULTS: The stent shunt was successfully placed in all patients and reduced the pressure gradient between the portal vein and the inferior vena cava by an average of 63 percent. Thirty-seven patients (74 percent) had complete responses (total remission of ascites within three months), and nine patients (18 percent) had partial responses (ascites detected by ultrasound but with no need for paracentesis). Four patients did not respond, including two who died within two weeks of shunt placement. After the procedure, 25 patients had hepatic encephalopathy, as compared with 20 patients before the procedure; although encephalopathy improved in 3 patients, new encephalopathy developed in 8 patients. In the 28 of the 33 patients followed for more than six months who were evaluated, the mean serum creatinine concentration was 1.5 +/- 0.09 mg per deciliter (133 +/- 8 mumol per liter) before placement of the stent shunt, 1.5 +/- 1.6 mg per deciliter (133 +/- 141 mumol per liter) one week after the procedure, and 0.9 +/- 0.3 mg per deciliter (80 +/- 27 mumol per liter) after six months (P = 0.008 for the comparison of concentrations before and six months after the procedure). Renal function did not improve in the six patients with organic kidney disease. Procedure-related complications developed in 16 patients, including intraabdominal bleeding requiring blood transfusions in 2 patients. Thrombotic occlusion of the stent shunt occurred within two weeks in 5 patients, and later insufficiency of the shunt occurred in 16 patients, including 12 with recurrence of ascites after complete remission. During followup, an additional 29 patients died--10 of progressive liver disease and 19 of other causes. Survival for at least one year was associated with a patient's being under 60 years of age, having a serum bilirubin level before placement of the stent shunt of less than 1.3 mg per deciliter (22 mumol per liter), and having a complete response. CONCLUSIONS: Our findings in an uncontrolled prospective study suggest that the transjugular intrahepatic porto-systemic stent-shunt procedure was an effective treatment for many patients with liver cirrhosis and refractory ascites, but mortality from underlying diseases was substantial.

Ascites↗
PubMed1995

[Gene therapy--basic principles].

Recombinant DNA technology allows the cloning of genes and their expression in vitro. Cloned genes are central to human gene therapy. The principle of gene therapy is based on three different strategies: gene replacement in classic genetic diseases which are caused by a single gene defect that conforms to the rules of Mendelian inheritance; gene augmentation for the treatment of complex genetic diseases by providing the cell with a new function; block of gene expression in acquired genetic diseases such as infections and malignancies.

DNA, Recombinant↗
PubMed1995

[Gene therapy: medical and methodological aspects].

Molecular strategies of gene therapy are presently aimed at optimization of the efficiency of gene transfer, long-term expression of therapeutic genes and cellular as well as intracellular targeting of genes. Apart from these scientific aspects, safety considerations are of utmost importance.

Gene Expression Regulation↗
PubMed1995

Selective transmission of variant genomes from mother to infant in neonatal fulminant hepatitis B.

Hepatitis B virus (HBV) nucleotide sequences isolated from mother/child pairs were analyzed in three cases of neonatal fulminant hepatitis B (FHB). Heterogeneous HBV sequences consistent with both adw2 and ayw subtype were found in all three mothers. In one case, in which the child survived, both subtypes were transmitted. By contrast, only the ayw subtype was present in the two other children with a fatal course of FHB. In one fatal case, studied in greater detail, multiple HBV variants (viral quasi-species) were identified in both mother and child. A direct sequence comparison showed that only a subfraction of the virus pool from the mother was transmitted and that multiple new mutations emerged in the child. These data suggest that a minor HBV subpopulation from the mother may prevail as the dominant species in the child and that neonatal FHB is associated with the selection of mutant strains.

Adult↗
PubMed1995

Identification of two separable modules in the duck hepatitis B virus core protein.

Hepadnavirus replication requires the concerted action of the polymerase and core proteins to ensure packaging of the RNA pregenome and DNA maturation. The arginine-rich C terminus of the core protein plays an essential role in both of these steps while being dispensable for nucleocapsid formation. In an attempt to identify other functional domains of the core protein, we performed a series of trans-complementation experiments analyzing the ability of duck and human hepatitis B virus (DHBV and HBV) core protein subunits to support the replication of a core-defective DHBV genome. Plasmids expressing the N-terminal amino acids 1 to 67 or the remaining C-terminal portion, amino acids 67 to 262, of the DHBV core protein were cotransfected into LMH cells along with a replication-deficient construct coding for the DHBV pregenome and polymerase. Neither the N nor the C terminus alone yielded replication-competent core particles. However, cotransfection of plasmids that separately expressed both regions restored a normal replication pattern. Furthermore, the DHBV C terminus but not the N terminus could be replaced by the corresponding domain of the HBV core protein in this assay. Finally, coexpression of the complete HBV core protein and the N terminus from DHBV resulted in DHBV replication, while the HBV core protein alone was not functional. Taken together, these findings suggest a modular organization of the DHBV core protein in which the C terminus is functionally conserved among different hepadnaviruses.

Amino Acid Sequence↗
PubMed1995

Budd-Chiari syndrome: technical, hemodynamic, and clinical results of treatment with transjugular intrahepatic portosystemic shunt.

PURPOSE: To evaluate use of the transjugular intrahepatic portosystemic shunt (TIPS) as a nonsurgical approach for the management of Budd-Chiari syndrome (BCS). MATERIALS AND METHODS: Twelve patients with fulminant (n = 2), subacute (n = 5), or chronic (n = 5) BCS underwent TIPS placement. Hepatic venous obstruction was demonstrated at computed tomography and color duplex sonography. BCS was confirmed histologically in all patients. Hemodynamic parameters and clinical characteristics were assessed. RESULTS: TIPS creation was successful in all patients. Treatment reduced the portal venous pressure gradient by 75% and resulted in a mean shunt flow of 2,300 mL/min +/- 650 (standard deviation). No serious procedure-related complications were observed. The two patients with fulminant BCS died of septicemia or progressive liver failure despite intervention. The other 10 patients showed clinical improvement with reduction or disappearance of ascites. During follow-up, shunt dysfunction occurred in five of 10 patients with recurrence of ascites requiring repeat intervention. CONCLUSION: TIPS placement is safe and effective in patients with portal hypertension caused by subacute or chronic BCS.

Acute Disease↗
PubMed1995

Variants of hepatitis B, C and D viruses: molecular biology and clinical significance.

Variants of hepatitis B virus (HBV), hepatitis C virus (HCV) and of the hepatitis Delta virus (HDV) have been identified in patients both with acute and chronic infections. In the HBV DNA genome, naturally occurring mutations have been found in all viral genes, most notably in the genes coding for the structural envelope and nucleocapsid proteins. In the HCV RNA genome, the regions coding for the structural envelope proteins 1 and 2 as well as the 3'-contiguous nonstructural region 1 were found to be hypervariable. Viral variants may be associated with a specific clinical course of the infection, e.g. acute-fulminant or chronic hepatitis. Specific mutations may reduce viral clearance by immune mechanisms ('immune escape') or response to antiviral therapy ('therapy escape'). Furthermore, mutations of envelope epitopes can lead to viral variants which are not recognized or neutralized by antibodies to wild-type virus, resulting in 'diagnosis escape' or 'vaccine escape'. The exact contribution, however, of specific mutations to the pathogenesis and natural course of HBV, HCV or HDV infection, including the development of hepatocellular carcinoma, remains to be established.

Genotype↗
PubMed1994

[Polymerase chain reaction--principles and clinical relevance].

Molecular hybridization analyses and polymerase chain reaction (PCR) have substantially contributed to the diagnosis of infectious, genetic and malignant hepato-/gastroenterological diseases. While not generally informative, the detection of hepatitis-C-virus (HCV) RNA by PCR is at present the only means to demonstrate active HCV replication. Furthermore, PCR has for the first time allowed the identification of the infectious agent causing Morbus Whipple (Tropheryma whippleii), the noninvasive molecular detection of familial adenomatous polyposis (FAP) as well as of K-ras mutations in stool from patients with colorectal cancer. While in principle exquisitely sensitive and specific, PCR is a complex technique with a substantial risk and false-positive results, respectively. With a better understanding of the molecular pathogenesis, PCR-based diagnostics will be of increasing clinical significance for the sensitive and early detection, prevention or curative therapy of hepato-/gastroenterological diseases.

Adenomatous Polyposis Coli↗
PubMed1994

[Hepatitis B and C virus mutants--clinical relevance].

Hepatitis B virus (HBV) mutants and hepatitis C virus (HCV) genotypes have recently been identified in patients with acute and chronic infections. Mutations may be associated with a specific clinical course of infection, e.g. chronic active or fulminant-hepatitis as well as the development of hepatocellular carcinoma (HCC). Further, mutations may affect clearance of HBV or HCV infection and the response to antiviral therapy with alpha-interferon; however, the exact contribution of specific mutations organotypes to the course of HBV or HCV infection remains to be established.

Genome, Viral↗
PubMed1994

[Elevated liver enzymes of unknown etiology].

Elevated liver enzymes are a frequent clinical problem of varying significance. In otherwise healthy individuals the most frequent causes of elevated liver enzymes are toxins such as alcohol and drugs. In this situation, further studies are usually not needed; it is sufficient to control the relevant parameters after abstinence from alcohol or withdrawal of the drug(s). In patients with known, suspected or unknown nonhepatic diseases, elevated liver enzymes can be caused by cardiovascular diseases, obesity, endocrinopathies, infectious diseases, malignancies, collagen disorders, sarcoidosis and other diseases. In this situation, sonography or liver histology frequently will be diagnostic, revealing the cause of the underlying disease as well as of the elevated liver enzymes.

Clinical Enzyme Tests↗
PubMed1994

[Therapy and prevention of esophageal varices hemorrhage: current status].

Acute bleeding from esophageal varices is a medical emergency. It requires a structured therapeutic strategy adapted to local resources. The primary goal is to stop bleeding, preferably by endoscopic sclerotherapy or ligation. If endoscopic intervention is not possible as a first-line treatment, balloon tamponade or vasoactive drugs (terlipressin or octreotid) are therapeutic options to be followed as soon as possible by sclerotherapy or ligation. After successful hemostasis, the next goal is to prevent rebleeding. This is achieved primarily by eradicating sclerotherapy or ligation. In special situations, long-term therapy with a non-cardioselective beta receptor blocker is an alternative. The combined approach using sclerotherapy or ligation plus beta receptor blocker offers no significant advantage. Primary prophylaxis of bleeding from esophageal varices by long-term beta receptor blocker therapy is advised in patients with medium-sized or large varices. Apart from strategies aimed at the therapy or prophylaxis of bleeding from esophageal varices, measures to prevent or treat chronic liver diseases should be implemented in order to reduce the development of liver cirrhosis as the leading cause of esophageal varices.

Adrenergic beta-Antagonists↗
PubMed1994

[Eosinophilia in primary biliary cirrhosis: regression under therapy with ursodeoxycholic acid].

Eosinophilia can be observed in up to 40% of patients with primary biliary cirrhosis (PBC). Eosinophilia is transient, tends to occur in the early stages of the disease and seems to be associated with episodes of florid bile duct destruction [42-45]. 14 Patients with PBC were examined before and during treatment with ursodeoxycholic acid (UDCA) (10 mg/kg/d) for episodes of eosinophilia and the number of eosinophilic granulocytes in differential white blood cell counts. Group A consisted of 5 patients with one or several episodes of eosinophilia before the start of UDCA. Group B included 9 patients without known episodes of eosinophilia. Observation time before and after start of treatment for group A was 3-96 (mean 25) months and 6-24 (mean 14) months, and for group B 3-108 (mean 34) months and 6-27 (mean 19) months respectively. During treatment with UDCA the mean counts of eosinophilic granulocytes decreased in both groups from 309 +/- 47/mm3 to 135 +/- 14/mm3 (p < 0.001). In group A there was a decrease from 529 +/- 89/mm3 to 157 +/- 17/mm3 (p < 0.001) and in group B from 151 +/- 15/mm3 to 128 +/- 15/mm3 B (n.s.). In group A 9/18 differential white blood cell counts showed eosinophilia before UDCA medication (3 x relative [> or = 6%], 6 x absolute [> or = 500/mm3]) and 0/24 after the onset of UDCA (p < 0.001). In group B 0/25 differential white blood cell counts showed eosinophilia before UDCA and 2/72 after start of the therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

[Parietal cell antibodies in primary biliary cirrhosis: pathogenetic or diagnostic significance?].

24 patients with primary biliary cirrhosis (21 female, 3 male; mean age 51 years) were examined for the occurrence of autoantibodies to gastric parietal cells (APA). APA-titers were correlated with several hematological, chemical and immunological parameters. The results of upper GI-endoscopy were available from 12 patients. APA were positive in 24/24 PBC patients. None of the endoscopies revealed evidence for type A gastritis. No pathological decrease in serum vitamin B12 was found (n = 21). Hemoglobin was either normal (n = 18) or the anemia was microcytic with low serum ferritin (n = 6). Erythrocyte MCV was < or = 97 fl in all patients. No positive correlation was found between APA and erythrocyte sedimentation rate (r = 0.13, n = 24) or the titer of antinuclear antibodies (r = -0.18, n = 24) by linear regression. Correlation coefficient between APA and total serum-Ig was 0.67 (n = 24), 0.74 between APA and serum IgM (n = 24) and 0.13 between total serum-Ig minus IgM (n = 24), indicating that APA found in PBC patients belong to the IgM-isotype. Correlation between APA and anti-M2 was 0.65 (n = 21) and between APA and antimitochondrial antibodies (AMA) 0.96 (n = 24), suggesting recognition of identical epitope(s) by APA and AMA in PBC patients. APA were consistently negative in a control group of 40 patients with various forms of chronic liver disease. We conclude that parietal cell antibodies (APA) in PBC patients seem to be of diagnostic rather than pathogenic importance. Sensitivity for PBC appears comparable to that of AMA.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Molecular therapeutic strategies in hepatitis B virus infection.

Chronic infection with the hepatitis B virus is a major health problem worldwide. The only established therapy is interferon-alpha, with an efficacy of only 30-40% in highly selected patients. Nucleoside analogues do not show a significant clinical benefit. Molecular therapeutic strategies aimed at blocking gene expression include antisense DNA/RNA and ribozymes acting at the posttranscriptional level and triple helix formation blocking at the transcriptional level. In vitro, antisense oligodeoxynucleotides inhibit viral replication and gene expression in human hepatoma cell lines. In vivo, an antisense oligodeoxynucleotide directed against the 5'-region of the pre-S gene of the duck hepatitis B virus inhibited viral replication and gene expression in ducks. In vitro, ribozymes accurately cleave HBV substrate RNA. Triple helix formation is another very promising molecular approach. Results in hepadnaviral infection are not yet available, however.

Base Sequence↗