Functional evidence against the existence of beta 2-adrenoceptors mediating positive intropic effects in guinea-pig right ventricular myocardium.

In guinea-pig isolated papillary muscles we studied the positive inotropic effects of the beta-adrenoceptor agonists isoprenaline, fenoterol and noradrenaline in the presence and absence of the beta 1-selective antagonist atenolol and the beta 2-adrenoceptor antagonist ICI 118.551. In Schild regression analysis pA2 values, for either atenolol (7.

Immunosuppression may lead to progression of hepatitis C virus-associated liver disease in hemophiliacs coinfected with HIV.

Objective: The aim of this study was to examine the interaction between HIV and hepatitis C virus (HCV) in hemophiliacs coinfected with the viruses and to investigate the possible relationship between immunosuppression and liver failure.

Methods: To identify risk factors for impending liver failure in hemophiliacs coinfected with HIV and HCV, we analyzed clinical and laboratory parameters, including CD4 count, aminotransferases (ALT, AST), cholinesterase, alkaline phosphatase, bilirubin, and gamma-glutamyltransferase, during 3 yr of follow-up (1990-1993) in four groups of patients: hemophiliacs with progressive immunodeficiency who were coinfected with HCV and HIV (group A, n = 49); hemophiliacs with stable immune function who were seropositive for HIV and HCV (group B, n = 95); hemophiliacs who were infected with HCV but not HIV (group C, n = 72); and homosexuals with progressive immunodeficiency who were infected with HIV but not HCV (group D, n = 24).

Results: Univariate analysis of data for group A showed a significant rise in gamma-glutamyltransferase and alkaline phosphatase (p < 0.

Results of a screening for von Willebrand disease type 2N in patients with suspected haemophilia A or von Willebrand disease type 1.

A screening program for the detection of patients with von Willebrand disease type 2N (VWD 2N) was carried out in 177 unrelated patients previously diagnosed with haemophilia A and in 199 unrelated patients with VWD type 1 in comparison. By measuring the factor VIII (FVIII) binding capacity of von Willebrand factor (VWF), we detected 13 patients with VWD 2N within 8 unrelated families. The former diagnosis has been haemophilia A in 5 index patients, and VWD in the remaining 3.

The prevalence of antibody to parvovirus B19 in hemophiliacs and in the general population.

The prevalence of antibodies to parvovirus B19 (B19) was measured in the sera of 566 hemophiliacs and 524 individuals of the general population by immunofluorescence assays, using antigen expressed by the baculovirus system. In the general population, anti-B19 IgG seroprevalence was found to continuously decline from 64 percent at birth to 0 percent in the age of 9-11 months and thereupon to increase to 61 percent in the age of 12 years. In younger adults and older people, IgG seroprevalence only slowly increased with age, reaching 77 percent in people aged 60 and above.

Characterization of the factor VIII defect in 147 patients with sporadic hemophilia A: family studies indicate a mutation type-dependent sex ratio of mutation frequencies.

The clinical manifestation of hemophilia A is caused by a wide range of different mutations. In this study the factor VIII genes of 147 severe hemophilia A patients--all exclusively from sporadic families--were screened for mutations by use of the complete panel of modern DNA techniques. The pathogenous defect could be characterized in 126 patients (85.

Haemophilia A: mutation type determines risk of inhibitor formation.

The formation of factor VIII antibodies is a major problem for replacement therapy of haemophilia A patients. Antibodies occur in 5-30% of patients with severe haemophilia A. The reason for antibody formation is still unknown.

The genetic diversification of the HIV type 1 gag p17 gene in patients infected from a common source.

An evolutionary analysis was undertaken of HIV-1 gag p17 sequences taken from a small cohort of hemophilia B patients infected from a common batch of clotting factor concentrate. The sequence population found at seroconversion was highly homogeneous, suggesting that the infecting batch also contained little sequence variation. Genetic diversification was found in follow-up sequences taken approximately 3 years later and was generally found to be complex.

Long-term surveillance for human anti-murine antibodies of a group of haemophiliacs treated only with immunoaffinity-purified FVIII concentrates.

An immunoaffinity purified, solvent/detergent virally inactivated factor VIII (FVIII) concentrate (Hemofil® M) has been in clinical use in persons with haemophilia A since March 1987 and under clinical trial prior to licencing in the USA, Europe and Japan. The specification set and consistently met for the monoclonal antibody (mAb) content of the final product is 0.1 ng/IU FVIII.

Male-to-female transmission of HIV in a cohort of hemophiliacs--frequency, risk factors and effect of sexual counseling.

The incidence of male-to-female transmission of HIV infection was studied in a population of 198 sexual partners of hemophiliacs who tested HIV positive since 1984. The follow-up observation period was 1987-1992. Transmission occurred in 20 (10%) cases.

Parallel evolution in the V3 region of HIV type 1 after infection of hemophiliacs from a homogeneous source.

To determine the genetic diversification in the highly functional V3 loop, we followed up five hemophiliacs who were infected by a homogeneous HIV-1 population from a contaminated clotting factor lot. Initially, all patients displayed identical DNA sequences in this part of the proviral env gene. Therefore, this unique outbreak allows us to investigate the biological and genetic development of a common ancestor virus in different patients.

Serological and virological markers of human parvovirus B19 infection in sera of hemophiliacs.

It is known that parvovirus B19 (B19) is transmitted to hemophiliacs by clotting factors prepared from human plasma. However, it is not clear whether B19 is also transmitted by the more recently used inactivated clotting factor preparations. Therefore, we investigated 69 hemophiliacs, mostly children, receiving only virus-inactivated clotting factors.

Haemophilia A diagnosis by automated fluorescent DNA detection of ten factor VIII intron 13 dinucleotide repeat alleles.

Haemophilia A is a recessive X linked bleeding disorder caused by deficiency or functional abnormality of coagulation factor VIII. This disease usually has no visible phenotype in female carriers; hence, great efforts are made to offer all haemophilia A families accurate carrier diagnosis. Significant progress in this direction was made with the identification of the intron 13 variable number tandem repeat (VNTR), which is hitherto the most informative single marker within the factor VIII gene.

[HIV-associated parotid cysts].

20 seropositive HIV patients were examined for the detection of parotid cysts by means of B-mode sonography. In three cases bilateral cysts were found, in three cases unilateral. Only one patient showed clinical symptoms with a bilateral and painless parotideal mass.

[Hemophilia A: molecular biology and carrier diagnosis].

Objective: Within this review we give an overview of haemophilia A research concentrating on molecular biology and carrier diagnosis. Haemophilia A, located on X-chromosome and transmitted recessively, is caused by deficiency or functional abnormality of coagulation factor VIII.

Data Sources: For this review we used original papers as main sources, but also review articles as well as study results of our group.

[Hemophiliac arthropathy of the knee joint. Gd-DTPA-enhanced MRI; clinical and roentgenological correlation].

17 patients with hemophilic arthropathy of the knee joint were studied with static and dynamic MRT before and after i.v. bolus injection of Gadolinium-DTPA (0.

Characterization of resistance mechanisms to cis-diamminedichloroplatinum(II) in three sublines of the CC531 colon adenocarcinoma cell line in vitro.

Cisplatin resistance was developed in sublines of the CC531 rat colon adenocarcinoma cell line by continued low level drug exposure. Two relatively stable lines were obtained (RL2 and RL4) which were 6- and 20-fold more resistant to cisplatin. In addition, a subline more sensitive than the parent line by a factor of 2 (RLS) was obtained by subculture from a treated tumor.

Hepatitis A virus infection among the hemophilia population at the Bonn Hemophilia Center.

Following a publication on the sudden outbreak of hepatitis A (HAV) infections in Italian hemophiliacs after treatment with a solvent detergent (S/D) virus-inactivated factor VIII concentrate, we retrospectively examined our patients for HAV seroconversions and clinical symptoms of an acute HAV infection at our center. We found that between 1988 and 1992, 17 hemophilia A patients displayed HAV IgG seroconversions. Of these patients, 13 also had an HAV IgM seroconversion and 10 exhibited clinical symptoms of an acute HAV infection.

Direct and indirect estimation of the sex ratio of mutation frequencies in hemophilia A.

Carrier detection tests were carried out in 119 families with hemophilia A by using the data obtained with current DNA techniques (e.g., RFLP analysis and direct identification of mutations), conventional carrier detection tests (e.

Two years' experience with two recombinant factor VIII concentrates.

Transmission of infectious diseases via the use of plasma concentrates has lent special significance to the manufacture of recombinant coagulation factor concentrates. At present, two factor VIII concentrates manufactured by recombinant DNA technology, produced by Baxter (Recombinate) and Bayer/Miles (Kogenate), are undergoing clinical trials. At the haemophilia centres in Bonn and Frankfurt am Main a total of 4.

Mutations in haemophilia A.

In the present study DNA from 281 unrelated haemophilia A patients including 15 inhibitor patients has been analysed by Southern blotting technique. Using various restriction enzymes, cloned factor VIII cDNA probes and genomic fragments we have identified 14 mutations. Six of the mutations are novel partial factor VIII gene deletions.

Search for intrafamilial transmission of hepatitis C virus in hemophilia patients.

This study was performed to determine the risk of family members of anti-hepatitis C virus (HCV)-positive hemophilia patients (index patients) for infection with HCV compared with the risk of acquiring hepatitis B virus (HBV), human immunodeficiency virus (HIV), and hepatitis A virus (HAV) infection. All index patients (n = 141) were found to be positive by first and second generation anti-HCV enzyme immunoassays (EIAs). Among their household contacts (n = 228), 224 were negative and 1 positive by both assays.