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Biomedical subjects

H E Blum

Publications and source records attributed to H E Blum.

At least 19 recordsLinked to original sources
PubMed1997

[Whipple's disease: molecular biology--clinical aspects--therapy].

Whipple's disease is a rare systemic bacterial disease, affecting mostly middle-aged white men. Its clinical presentation is very variable. Arthralgias, fever of unknown origin or central nervous system symptoms may precede the more typical gastrointestinal manifestations with weight loss and chronic diarrhea. The diagnosis is based on the histopathologic demonstration of PAS-positive macrophages in duodenal or jejunal biopsies. In addition, it has become possible to detect the causative actinobacterium Tropheryma whippelii by amplification of a Whipple-specific PCR product. Therapeutic options are a sequential therapy with penicillin-streptomycin, followed by trimethoprim-sulfamethoxazole (TMP-SMX) or a monotherapy with TMP-SMX. These therapeutic modalities usually eradicate the infection and result in a rapid and sustained improvement of the Whipple-specific signs and symptoms. In view of the frequently uncharacteristic initial clinical presentation (arthralgias, fever, CNS symptoms), it is therefore of utmost importance to consider Whipple's disease in the differential diagnosis of the clinical signs and symptoms.

Actinobacteria↗
PubMed1997

[Molecular biology 1996: gastroenterology and hepatology].

Advances in molecular genetics have clearly improved our understanding of the pathogenesis as well as the diagnosis, therapy and prevention of gastrointestinal and liver diseases. The molecular diagnosis of a number of maglignant or potentially malignant gastrointestinal diseases as well as of several infectious liver diseases is on its way into clinical practice. Gene therapy and molecular preventive strategies, by comparison, have been less developed and need further refining before they will become integral part of the patient management.

Gastrointestinal Diseases↗
PubMed1997

Randomised trial of transjugular-intrahepatic-portosystemic shunt versus endoscopy plus propranolol for prevention of variceal rebleeding.

BACKGROUND: The transjugular-intrahepatic-portosystemic shunt is a new interventional treatment for portal hypertension. The aim of our study was to compare the transjugular shunt with endoscopic treatment for the prophylaxis of recurrent variceal bleeding. METHODS: Between March, 1993, and March, 1996, 126 patients with variceal bleeding were randomly assigned either transjugular shunt (n = 61) or endoscopic treatment (n = 65). Patients were followed up for a median of 14 (IQR 8-25) months and 13 (8-25) months, respectively. In 31 (51%) of the shunted patients, simultaneous transjugular-variceal embolisation was done at the time of shunt placement. Endoscopic treatment consisted of sclerotherapy and/or banding ligation and was combined with propranolol medication. FINDINGS: Technical success was achieved in all patients assigned to the shunt group. During follow-up, the cumulative 1-year variceal rebleeding rates in the shunted and endoscopically treated patients were 15% and 41% and the 2-year rates were 21% and 52% (p = 0.001), respectively. In nine (12%) patients from the endoscopic group treatment failed and the patients received the transjugular-shunt treatment. A total of 19 bleeding episodes from any source occurred in 15 patients in the shunt group compared with 100 episodes in 33 patients in the endoscopic group. There was no difference in survival with estimated 1-year survival rates for shunted and endoscopically treated patients of 90% and 89%, and 2-year survival rates of 79% and 82%, respectively. The incidence of clinically significant hepatic encephalopathy after 1 year was higher in the shunt group (36% vs 18%, p = 0.011). INTERPRETATION: These results suggest, that the transjugular shunt is more effective than endoscopic treatment in prevention of variceal rebleeding but has a considerable risk of hepatic encephalopathy. Survival is similar in the two groups.

Adult↗
PubMed1997

[Hepatitis C-associated vasculitic mononeuritis multiplex].

HISTORY AND CLINICAL FINDINGS: A 56-year-old woman with hepatitis C had symptoms of a polyneuropathy with asymmetrical distal pareses and painful sensory disturbances in the limbs. INVESTIGATION: In addition to positive serology for hepatitis C cryoglobulins were demonstrated and complement C4 was reduced. Biopsy of the sural nerve showed a vasculitic neuropathy. TREATMENT AND COURSE: The multiple neuropathy (cryoglobulinaemia neuropathy), associated with hepatitis C, was treated with corticosteroids (starting with 60 mg/d prednisolone) and the neurological abnormalities regressed well. CONCLUSION: Vasculitis associated with hepatitis C should be included in the differential diagnosis of peripheral neuropathy.

Chronic Disease↗
PubMed1997

[Nonsurgical therapy of focal liver lesions].

Indications for a local non-surgical therapy of focal liver lesions are the hepatocellular carcinoma (HCC) and metastases. The HCC is one of the most frequent malignant tumors worldwide with an incidence of 1 million cases per year. The prognosis of the untreated HCC is poor. For non-surgical cases there are local and systemic therapies available. A number of studies involving thousands of patients, have used treatment by PEI. Several of these studies have shown an increased survival in the PEI-treated patients. For patients primarily not treatable with PEI transarterial chemoembolization (TACE) with lipiodol in combination with a chemotherapeutic drug and gelfoam is a possibility. Studies of patients treated with PEI or TACE show a variability in survival, however, the trend is to prolonged survival. Improvement in efficacy of treatment and decreases in toxicities could be achieved through a combination of different interventions and an optimal patient selection. Both surgical and those cases unsuitable to local therapy should be treated with tamoxifen.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

A hepatitis B virus mutant with a new hepatocyte nuclear factor 1 binding site emerging in transplant-transmitted fulminant hepatitis B.

Hepatitis B virus (HBV) DNA was cloned from serum of a heart transplant recipient who died from fulminant hepatitis B transmitted by the donor. Restriction enzyme analyses of the clones obtained by conventional cloning yielded six HBV variants: a major species (pF-1) representing 88% and five minor species (pF-2 to pF-6), each representing 2% to 4% of the clones. The complete nucleotide sequence of these six variants revealed that five of the six viral genomes, including pF-1, carried a novel 11 base pair (bp) insertion in the core promoter region as well as an 18 bp and an 108 bp in-frame deletion in the pre-S1 region not present in the donor. One genome was identical to the sequence of the donor. Functional analyses of HBV clones generated by in vitro mutagenesis and cassette exchange showed that the 11 bp insertion is a strong binding site for hepatocyte nuclear factor 1 (HNF-1). In transient transfection experiments, the novel HNF-1 sequence motif was shown to result in enhanced viral replication. Immunohistochemical analyses revealed high levels of cytoplasmic and nuclear hepatitis B core antigen (HBcAg) and only scattered hepatitis B surface antigen (HBsAg) expression in the liver. The data in our immunosuppressed patient showed that HBV variants can rapidly accumulate in severe hepatitis B and suggest that the novel HNF-1 binding site may have contributed to the fulminant clinical course, possibly via enhanced viral replication.

Base Sequence↗
PubMed1997

Acute hemoperitoneum after large-volume paracentesis.

Hemoperitoneum resulting from rupture of mesenteric varices is a rare complication of portal hypertension with a high mortality of up to 70%. This case report describes the symptoms, clinical course, and treatment of 4 patients with acute hemoperitoneum caused by mesenteric variceal bleeding after large-volume paracentesis. Abdominal pain and/or hemorrhagic shock developed in 4 patients (age, 48-68 years), admitted for refractory ascites, 3 hours to 4 days after 1-4 large-volume paracenteses (> 4000 mL). Duplex sonography, performed in 3 of the 4 patients before onset of bleeding, showed retrograde flow in the mesenteric veins, suggesting large-caliber mesenteric collateralization. Treatment consisted of surgical ligation followed by transjugular intrahepatic portosystemic shunt (TIPS) (2 patients) and emergency TIPS with embolization of the bleeding vessel (1 patient). One patient died before any intervention could be initiated. In these 4 patients, the concurrence of large-volume paracentesis and hemoperitoneum suggests their causal relationship. The mechanism may be a sudden reduction in intraperitoneal pressure increasing the pressure gradient across the wall of the mesenteric varices, resulting in rupture and bleeding. The awareness of this complication may accelerate the diagnostic process and treatment.

Acute Disease↗
PubMed1997

Gene therapy: basic concepts and applications in gastrointestinal diseases.

Molecular analyses have become an integral part of biomedical research as well as clinical medicine. The definition of the molecular and genetic basis of many human diseases has led not only to a better understanding of their pathogenesis, but has in addition offered new perspectives for their diagnosis, therapy, and prevention. Genetically, human diseases can be classified as monogenetic, complex genetic, and acquired genetic diseases. Based on this genetic classification, gene therapy involves four concepts: gene substitution, gene augmentation, block of gene expression or function as well as somatic transgene vaccination. Despite exciting recent developments, various delivery, targeting, and safety aspects need to be addressed before gene therapy will enter clinical practice. Clearly, molecular diagnosis and gene therapy of gastrointestinal diseases will be increasingly part of our patient management, complementing existing diagnostic, therapeutic, and preventive strategies.

Gastrointestinal Diseases↗
PubMed1997

Theoretical and experimental selection parameters for HBV-directed antisense RNA are related to increased RNA-RNA annealing.

Annealing kinetics of antisense species against two different target regions of the hepatitis B virus (HBV) were measured by kinetic in vitro selection. Individual association rates were related to energies calculated for local sequence segments and predicted structures of the complete pregenomic target RNA. A relationship between the presence of external loops and joint sequences with fast pairing was observed whereas internal loops did not favor fast RNA-RNA annealing. The findings were used to predict a fast-annealing HBV-directed antisense oligodeoxyribonucleotide that turned out to pair with its target RNA at an association rate constant of k=9.2 x 10(4) M(-1) s(-1), which is substantially faster than the annealing rates of artificial antisense RNA so far included in in vitro selection assays.

Computer Simulation↗
PubMed1997

[Hepatitis B virus mutants--clinical significance].

Hepatitis B virus (HBV) mutants have recently been identified in patients with acute or fulminant as well as chronic infections. Naturally occurring mutations have been identified in all viral genes and regulatory elements, most notably in the genes coding for the structural envelope and nucleocapsid proteins. Mutations in the gene coding for the hepatitis B surface antigen (HBsAg) may result in infection or viral persistence despite the presence of antibodies against HBsAg (anti-HBs) ("vaccine escape" or "immune escape"). Mutations in the gene encoding the pre-core/ core protein (pre-core stop codon mutant) result in a loss of hepatitis B e antigen (HBeAg) and seroconversion to antibodies to HBeAg (anti-HBe) with persistence of HBV replication (HBeAg minus mutant). Mutations in the core gene may lead among others to an "immune escape" due to a T cell receptor antagonism. Mutations in the gene coding for the polymerase/reverse transcriptase can be associated with viral persistence or resistance to nucleoside analogues. Thus, HBV mutations may affect the natural course of infection, viral clearance and response to antiviral therapy. Apart from the precore/core stop codon mutations, the exact contribution of specific mutations to diagnosis and therapy of HBV infection as well as patient management in clinical practice remain to be established.

Antibody Formation↗
PubMed1996

[Current diagnosis of viral hepatitis].

The structure and genetic organization of the hepatitis viruses A-E are well characterized. HAV and HEV cause acute and sometimes fulminant hepatitis. By contrast, HBV, HCV and HDV infections frequently progress to chronic hepatitis, liver cirrhosis and hepatocellular carcinoma (HCC). The specific detection of the hepatitis viruses A-E is based on serological and molecular analyses. In clinical practice, it is possible in most cases to identify the viral infection by a single serological screening test. In particular clinical situations, the diagnostic workup requires additional serological or molecular analyses. Given the different diagnostic tests, it is possible today to specifically identify the etiologic agent in most patients with acute or chronic viral hepatitis.

Acute Disease↗
PubMed1996

[Diagnosis of hepatocellular carcinoma].

Hepatocellular carcinoma (HCC) is a frequent complication of chronic liver disease. The major causes of chronic liver diseases are hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, as well as chronic alcohol misuse. The clinical presentations of HCC patients are unspecific, with signs and symptoms of chronic liver disease. Early diagnosis of HCC in an asymptomatic and potentially curable stage is of highest priority. The present strategy for the detection of early HCC in patients with chronic liver disease is 6-monthly determination of alpha-fetoprotein (AFP) and ultrasound study of the liver. If these are abnormal, further diagnostic steps include computer tomography, magnetic resonance tomography, lipiodol-angiography and histopathology. By this sequential diagnostic strategy it should be possible to identify HCC in patients with chronic liver disease at an early and potentially curable stage.

Angiography↗