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Biomedical subjects

A Morell

Publications and source records attributed to A Morell.

At least 37 records · Page 2Linked to original sources
PubMed1994

Relation between the resolution of HLA-typing and the chance of finding an unrelated bone marrow donor.

The chance of finding an unrelated bone marrow donor depends on the size of the donor registry, the frequency of the patient's HLA phenotype and the degree of histoincompatibility considered acceptable. We have studied 60 unrelated bone marrow donor searches and the probability of finding a donor when increasing HLA-compatibility requirements were applied. For 21 (35%) of the patients no donor could be identified who was (serologically) matched for all six ABDR antigens. For the remaining 39 (65%), a median of two (range 1-20) blood samples from serologically-matched potential donors was obtained for further analysis. Eighteen (30%) patients appeared to be mismatched with all the pre-selected donors because of DR (sub-)type mismatches detected by oligotyping. A further 7 (12%) patients did not have an MLC and/or cytotoxic T lymphocyte precursor (CTLp) negative donor. Thus, a 'perfectly matched' donor was found for 11 (18%) patients. To find a suitable donor for more patients we propose that many or all the potential donors identified in the various registries for a particular patient are simultaneously evaluated as many of the serologically ABDR-matched donors will appear to be incompatible after high resolution HLA-typing. This strategy will not only allow selection of the best matched donor more rapidly but the consequent use of high resolution typing might also lead to the definition of a certain number of acceptable mismatches.

Bone Marrow Transplantation↗
PubMed1994

Clinical relevance of IgG subclass deficiencies.

Patients with primary or secondary IgG subclass deficiencies suffer from infections due to encapsulated microorganisms such as H influenzae and pneumococci. In addition to relapsing infections, some patients with primary subclass deficiencies may have autoimmune disorders. The best characterized defect in IgG2 deficiency, either isolated or combined with IgG4 deficiency. It is frequently associated with IgA deficiency or with ataxia telangiectasia. IgG1 deficiency occurs mostly in combination with disturbances of other immunoglobulin isotypes, and probably represents a form of common variable immune deficiency. Decreased IgG3 levels were reported in association with lung dysfunction and viral diseases. Except in IgG1 deficiency, total IgG serum levels in primary as well as secondary IgG subclass deficiency states may be normal or even increased. It is assumed that IgG subclass deficiencies represent an indicator of more basic immunologic abnormalities. There is evidence that antibody defects correlate better with the clinical symptoms than the total serum IgG subclass concentrations. In patients with severe recurrent infections and IgG subclass deficiency, intravenous immunoglobulin treatment at dosages of 0.3 to 0.4 g/kg body weight every 3-4 weeks is indicated.

Autoimmune Diseases↗
PubMed1993

[Seroprevalence of hepatitis C virus in hemophiliacs in Switzerland].

The sera of patients with hemophilia and von Willebrand factor deficiency, collected during clinical trials with virus-inactivated coagulation factor preparations, were retrospectively screened for the presence of antibodies against hepatitis C virus (HCV). Using the anti-HCV c100-3 assay, 10 out of 35 study patients had no HCV antibodies when entering the studies. The samples originally negative for anti-HCV were retested with a second-generation assay: all negative samples except two were positive on retesting. We conclude that the HCV seroprevalence in Swiss hemophiliacs must be of the order of > 90%. These results confirm that the first-generation assay for HCV antibodies is not sensitive enough; to obtain more accurate information on the seroprevalence of hemophiliacs, second-generation tests should be used.

Hemophilia A↗
PubMed1993

Diffusion of immunoglobulins into rabbit cornea after subconjunctival injection: experimental demonstration and mathematical model.

To determine whether immunoglobulins of the IgG class diffus up to the corneal center after subconjunctival injection, rabbits were injected with fluorescein-isothiocyanate-labeled human IgG. The inoculum diffused from the entire periphery centrepetally towards the corneal center. The progression of the diffusion front slowed down as the distance to the limbus increased. The first increase of fluorescence in the corneal center was observed on day 6. The intensity increased during the following 10 days despite resorption in the corneal periphery due to the flow of IgG from paracentral toward central areas. The diffusion coefficient of 0.003-0.004 cm2/day was calculated by computer simulation using Fickian diffusion equations adapted for corneal geometry. We conclude that after subconjunctival application, IgG diffuses up to the corneal center with a delay of several days and that the penetration speed decreases as the distance to the limbus increases. This kinetics contributes to our understanding of the role of IgG in corneal pathology and may help to design therapeutic schedules for immunotherapy with IgG.

Animals↗
PubMed1993

Topical immunoglobulins for epithelial herpes simplex keratitis.

A new immunoglobulin preparation for topical administration in the eye has been developed. The tolerance to this preparation was tested in a phase I/II study, in combination with the antiviral drug trifluorothymidine, in 5 patients with untreated episodes of herpes simplex epithelial keratitis. The clinical course of these patients was within usual limits, with a mean healing time of 6.6 days (range 2-15 days). No undesirable effects were observed. Our findings suggest that this new treatment modality is safe and offers a new perspective, but additional studies are required to determine its efficacy.

Adult↗
PubMed1993

[The stability of antibiotics administered in "and" with a parenteral nutrition mixture enriched with branched-chain amino acids. II. The cephalosporins].

Part I of these stability studies commented on the benefits, in terms of care and therapy, of the Y administration of antibiotics and parenteral nutrition. The aim of this study is to determine the stability of the cephalosporins ceftazidime, ceftriaxone, ceftizosime and cefotaxime in vitro, at therapeutic concentrations, infused together with a parenteral nutrition mixture with polyols, enriched in branched chained amino acids, and without lipids. A microbiological stability analysis was carried out on the antibiotics in the parenteral nutrition, and an HPLC aminogram was done to determine the concentration of amino acids in the infusion together with the antibiotic. As well, pH, osmolarity and colour change were measured in the antibiotics, in the parenteral nutrition used and in the joint infusion mixtures. It is concluded that parenteral nutrition can be jointly infused with cefotaxime and ceftazidime, at the concentrations studied, given the stability results obtained both with HPLC (antibiotics and amino acids) and microbiologically (antibiotics). At the same time, the microbiological analysis of ceftriaxone with the nutrition showed its stability in the study conditions. Its joint infusion with parenteral nutrition, studied by HPLC, confirmed the stability of the amino acids. The ceftizoxime analysed by HPLC remained stable during joint infusion with the parenteral nutrition.

Amino Acids, Branched-Chain↗
PubMed1993

[The stability of antibiotics administered in and with a parenteral nutrition mixture enriched with branched-chain amino acids. I. Amikacin and gentamycin].

The combined infusion of antibiotics and parenteral nutrition makes it possible to maintain plasmatic nutrient concentrations over time, in turn facilitating the administration of the antibiotics in the dilution and infusion time recommended according to their pharmacokinetic parameters. On the other hand, this type of administration has care benefits for the patient, reducing the risk of infections, and adding to comfort. The technique is also cost-effective, reducing the cost of drug administration, saving on administrative personnel and nursing staff time. The stability of amikacin and gentamicin are determined in vitro at therapeutic concentrations jointly infused with a mixture of parenteral nutrition with polyols and enriched in ramified chain amino acids. A microbiological stability analysis was carried out of the antibiotics in the parenteral nutrition, along with an HPLC aminogram, in order to determine the concentration of amino acids in the combined infusion with the antibiotic. pH measurements were also taken, along with osmolarity and colour change. Both of the antibiotics and the parenteral nutrition employed, and of the combined infusion mixtures. Amikacin and Gentamicin are stable at a concentration of 5 mg/ml and 1.6 mg/ml respectively in a parenteral nutrition mixture enriched in ramified chain amino acids.

Amikacin↗
PubMed1991

[No HCV seroconversion in hemophilia following substitution with virus-inactivated coagulation factor VIII and IX concentrates].

Since 1986 the factor VIII and IX concentrates of the Central Laboratory, Swiss Red Cross Blood Transfusion Service have been virus inactivated with tri-(n-butyl) phosphate and Tween 80. Clinical studies had shown that both preparations were well tolerated and hemostatically effective; no HIV infection was transmitted. However, safety from transmission of non-A/non-B hepatitis could not be shown since the study included no previously untreated patients. In the meantime, a laboratory test has become available which allows retrospective testing for anti-hepatitis C antibodies in frozen sera of the study patients. 5 of the 26 patients, observed during a 2-year follow-up study, had no HCV antibodies before entering the long-term trial. During this trial, each of these 5 patients substituted an average quantity of 40,200 coagulation factor units (7500-69,000) from 45 production lots. None of these 5 patients developed anti-HCV antibodies, nor did any of them show clinical signs of infection with hepatitis. This suggests that virus inactivation using solvent/detergent treatment reduces the risk of transmission of HCV.

Blood Coagulation Disorders↗
PubMed1991

[Clinical testing of Premofil M SRK, a blood coagulation factor VIII concentrate purified from human plasma using monoclonal an antibodies].

Premofil M SRK, licensed in Switzerland by the IKS since mid-1990, was clinically tested in close collaboration with 7 hemophilia treatment centers. Up to May 1991, we collected results of in vivo recovery from 17 patients, half-life determinations from 12, and safety data from 9 who were exclusively treated with the preparation for several months. The mean in vivo recovery of factor VIII was calculated to be 77 +/- 14%; the rise in factor VIII activity in plasma following injection of one unit/kg body weight was 1.6 +/- 0.3 units/dl. The mean halflife was 11.9 +/- 4.6 hours. No side reactions were registered throughout the study period. None of the patients showed any signs of HIV or hepatitis infection. It can bei concluded that Premofil M SRK fulfills the requirements related to tolerance, efficacy and safety for a factor VIII concentrate.

Adolescent↗
PubMed1991

Semliki Forest virus envelope proteins function as proton channels.

It has been shown that isolated nucleocapsids of Semliki Forest virus (SFV) contract upon low pH exposure (Soederlund et al., 1972). This contraction of the nucleocapsids has been used as an indicator to demonstrate that the spike proteins of SFV can translocate protons into the interior of the virus particle upon low pH (5.8) exposure. Spikeless virus particles obtained after bromelain digestion, which were used as a control, did not translocate protons. This implies that the ectodomain of the spike plays a crucial role for the proton translocation.

Aedes↗
PubMed1991

Influence of IgG1 and IgG2 antibodies to streptococcal group A carbohydrate on neutrophil chemiluminescence.

IgG antibodies to streptococcal group A carbohydrate (A-CHO) were isolated from normal human serum and from pooled Cohn fraction II using N-acetyl-D-glucosamine affinity chromatography columns. They consisted of the subclasses IgG1 and IgG2 in variable proportions depending on the pH of the elution buffer and on the subclass composition of anti-A-CHO in the starting material. Streptococcal group A particles exposing the antigen A-CHO were opsonized with various concentrations of these antibodies and incubated with normal human polymorphonuclear leukocytes (PMN). The luminol-enhanced chemiluminescence (CL) elicited with these particles was recorded over a 60-min period. With 12 of the 14 antibody preparations tested, the observed CL signal was dose-dependent. When used at comparable concentrations for opsonization, the antibodies enriched in IgG1 induced markedly stronger CL signals than those consisting predominantly of IgG2. It was concluded that the observed CL differences reflect mainly the preferential recognition of IgG1 molecules by Fc gamma receptors of PMN.

Antibodies, Anti-Idiotypic↗
PubMed1991

Virus inactivation during production of intravenous immunoglobulin.

The effect of pepsin treatment at pH 4 on the infectivity of several enveloped viruses was assessed under the conditions used during the production of intravenous immunoglobulins. It was shown that the prototypes of four virus families--human immunodeficiency virus (Lentivirinae), herpes simplex virus type 1 and human cytomegalovirus (Herpesviridae), Semliki Forest virus (Togaviridae), and vesicular stomatitis virus (Rhabdoviridae)--were inactivated by this procedure. With vesicular stomatitis virus as a model, the contributions of both low pH and pepsin were demonstrated, and pepsin had a synergistic or additive action.

Animals↗
PubMed1991

Safety of intravenous immunoglobulin preparations: a prospective multicenter study to exclude the risk of non-A, non-B hepatitis.

The risk of non-A, non-B hepatitis transmission by an intravenous immunoglobulin (IVIG) preparation was assessed in a prospective multicenter trial in 68 patients with primary immunodeficiency disorders (40 children or adolescents and 28 adults). During the 4-week prestudy evaluation period the clinical examinations and liver function tests including alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase, alkaline phosphatase, and bilirubin were normal in all patients. The treatment consisted of three infusions of 200 mg IVIG (pH 4; pepsin procedure) per kilogram body weight at 2-week intervals. During the observation period of 24 weeks following the first infusion of the study IVIG, the patients were monitored at regular time intervals. No clinical and laboratory signs of hepatitis or liver dysfunction were noticed. All patients completed the study. In 5 patients, one isolated alanine aminotransferase value and in another patient one gamma-glutamyl transpeptidase value were moderately elevated, but always below 2.5 times the upper limit of the reference range. Similar isolated and transient elevations were observed for aspartate aminotransferase and alkaline phosphatase. It was concluded that the IVIG preparation did not transmit non-A, non-B hepatitis or other viral liver diseases.

Adult↗
PubMed1990

Impaired antibody response to Haemophilus influenzae type b polysaccharide and low IgG2 and IgG4 concentrations in Apache children.

BACKGROUND AND METHODS: Because Native American children are at much higher risk for invasive Haemophilus influenzae type b infection than white children, we compared the antibody responses to H. influenzae type b polysaccharide vaccine in healthy Apache and white children. RESULTS: The concentrations of H. influenzae type b antibody after immunization with polysaccharide vaccine were approximately 10-fold lower in 24-month-old Apache children than in whites of a similar age (P less than 0.01). The decreased response involved H. influenzae type b antibodies of the IgG, IgM, and IgA classes. Concentrations of IgG antibody to tetanus toxoid did not differ significantly, and IgG antibodies to diphtheria toxoid were only twofold lower (P = 0.028). Although total IgG, IgM, and IgA levels were higher in two-year-old Apaches than in whites (all P less than 0.001), IgG2 and IgG4 subclasses were lower (both P less than 0.001). Among the Apaches, individual immunoglobulin levels and allotypes were not significantly correlated with their antibody responses to H. influenzae type b polysaccharide. CONCLUSIONS: Apache children have significant impairment of their antibody response to H. influenzae type b polysaccharide and little or no impairment of their antibody responses to protein toxoids. This immunodeficiency may explain the high incidence of H. influenzae type b infection in this population.

Antibodies, Bacterial↗
PubMed1990

Ontogeny of the humoral response to group A streptococcal carbohydrate: class and IgG subclass composition of antibodies in children.

We determined isotypes of natural antibodies to streptococcal group A carbohydrate (A-CHO) in sera from 101 children between 1 and 16 years of age, using a calibrated enzyme-linked immunosorbent assay system. Anti-A-CHO IgM could be detected in all but one sera. Median levels increased with age and were highest between 8 and 12 years. IgG antibodies were present at low concentrations up to the age of 4 years, and consisted predominantly of the IgG1 subclass. Between 4 and 8 years, concentrations of anti-A-CHO IgG markedly increased and median levels continued to increase through age 12-16. Anti-A-CHO IgG1 levels closely followed the pattern of IgG antibody concentrations. The number of IgG2 antibody positive sera was low in young children, as expected. In the 8-12 year age group and later, anti-A-CHO IgG2 was present in more than half of the samples, and in children between 12 and 16, medians of IgG2 and IgG1 antibodies were similar. Sera containing anti-A-CHO IgG3 were rare in children up to 4 years of age, but in the group of 4-8-year-old children, this subclass was detectable in 36% and later in up to 77% of the sera. Thus, the IgG response to A-CHO showed a clear maturation during childhood, involving the subclasses IgG1, IgG2 and IgG3. There were no significant differences in A-CHO levels between boys and girls.

Adolescent↗
PubMed1990

Semliki Forest virus induced cell-cell fusion at neutral extracellular pH.

Semliki Forest virus-induced cell-cell fusion from within was considered to exclusively occur at mildly acidic pH (less than 6.2). Data of this study show that such cell fusion can also be triggered by transient acidification of the cytoplasm of infected cells at an extracellular, neutral pH. Results were obtained by utilizing NH4Cl pulses combined with covalent modification of cell surface proteins. The observation implies a revision of the current consensus regarding the mechanism of Semliki Forest virus induced cell-cell fusion. We propose a model in which at least two peptide segments of the viral spike protein E1 may be involved in triggering the fusion event.

Aedes↗