Cost-utility of extracorporeal membrane oxygenation rewarming in accidentally hypothermic patients-A single-centre retrospective study.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) has become the treatment of choice for severely hypothermic patients in cardiac arrest or acute cardiac failure. Highly specialized ECMO centres have been established, however, no centre has ever reported the costs of extracorporeal rewarming. The aim of this study was to assess the costs of the treatment of patients in Swiss Stage III and IV rewarmed with veno-arterial ECMO. METHODS: A retrospective exploratory cohort study analysed twenty-nine consecutive patients treated for hypothermia in the Severe Accidental Hypothermia Centre in Cracow, Poland. The main outcome parameters were the overall and specific costs of the ICU treatment of patients rewarmed with veno-arterial ECMO. The secondary outcome parameter was cost utility, determined by the costs involved for every year of life gained. Costs were processed using the bottom-up method and classified into six categories. Survivors were followed up after 1 year. RESULTS: The mean cost of VA-ECMO was $5133 USD, which equalled 35% of all ICU expenditures ($14 668 USD). One year after discharge, 13 of 29 patients were still alive (45%). The overall gain of life of the thirteen 1-year survivors was 28 years, while the mean cost related to treatment with VA-ECMO for each year of life gained was 1138 USD. CONCLUSIONS: In this study, the costs of VA-ECMO rewarming and intensive care treatment per patient were substantially lower than in other studies reporting ECMO and intensive care treatment of other causes.

Hypothermia is associated with a low ETCO2 and low pH-stat PaCO2 in refractory cardiac arrest.

AIMS: The end-tidal carbon dioxide (ETCO2) is frequently measured in cardiac arrest (CA) patients, for management and for predicting survival. Our goal was to study the PaCO2 and ETCO2 in hypothermic cardiac arrest patients. METHODS: We included patients with refractory CA assessed for extracorporeal cardiopulmonary resuscitation. Hypothermic patients were identified from previously prospectively collected data from Poland, France and Switzerland. The non-hypothermic CA patients were identified from two French cohort studies. The primary parameters of interest were ETCO2 and PaCO2 at hospital admission. We analysed the data according to both alpha-stat and pH-stat strategies. RESULTS: We included 131 CA patients (39 hypothermic and 92 non-hypothermic). Both ETCO2 (p < 0.001) and pH-stat PaCO2 (p < 0.001) were significantly lower in hypothermic compared to non-hypothermic patients, which was not the case for alpha-stat PaCO2 (p = 0.15). The median PaCO2-ETCO2 gradient was greater for hypothermic compared to non-hypothermic patients when using the alpha-stat method (46 mmHg vs 30 mmHg, p = 0.007), but not when using the pH-stat method (p = 0.10). Temperature was positively correlated with ETCO2 (p < 0.01) and pH-stat PaCO2 (p < 0.01) but not with alpha-stat PaCO2 (p = 0.5). The ETCO2 decreased by 0.5 mmHg and the pH-stat PaCO2 by 1.1 mmHg for every decrease of 1° C of the temperature. The proportion of survivors with an ETCO2 ≤ 10 mmHg at hospital admission was 45% (9/25) for hypothermic and 12% (2/17) for non-hypothermic CA patients. CONCLUSIONS: Hypothermic CA is associated with a decrease of the ETCO2 and pH-stat PaCO2 compared with non-hypothermic CA. ETCO2 should not be used in hypothermic CA for predicting outcome.

A new cloning method for antibody-forming lymphoblastoid cells. Increase in cloning efficiency by inclusion of human fibroblasts into semisolid agarose growth layer.

We report the development of a method for cloning human EBV-transformed cells which has greater efficiency than techniques used presently. In this new method lymphoblastoid cells are cultured in semisolid agarose in close physical association with human fibroblasts. The results indicate a 10-fold increase in the cloning efficiencies. The average cloning efficiency, depending on the age of cell lines, was from 1 to 14%, and colonies appeared 7-9 days sooner than in the traditional soft agarose method. The new method has allowed us to develop several stable lymphoblastoid cell lines producing antibody cytotoxic to human B lymphocytes. This method may make it more practical to obtain monoclonal human antibodies from lymphoblastoid cell lines which had previously been unstable due to heterogeneity.

A supertypic HLA class II determinant shared by DR1 and DRw9, and crossreactive with DR2, defined by human monoclonal antibody.

A human monoclonal antibody Pez.2F5, produced by a lymphoblastoid cell line, has been established in vitro by Epstein-Barr virus (EBV) transformation of B lymphocytes isolated from the blood of a volunteer immunized with allogeneic peripheral blood leukocytes (PBLs). The antibody reacted with a new supertypic determinant expressed on all lymphoblastoid cell lines homozygous for HLA-DR1, -2, and -w9. The genetic linkage of the Pez.2F5 determinant to the HLA region was demonstrated by family segregation studies. Quantitative absorption studies indicated that DR2-positive cells required more Pez.2F5 antibody for lysis, and since their absorption capacity was significantly lower than that of DR1- or DRw9-positive cells, it is likely that the Pez.2F5 determinant of the DR2 haplotype is crossreactive but not identical with the determinant found on the latter haplotypes. In addition, on a test panel of HLA-typed B lymphocytes, Pez.2F5 showed perfect correlation with DR1 and DRw9, but reacted with only a fraction of DR2-positive cells. The Pez.2F5 determinant was found to be absent from resting T lymphocytes, but its expression could be identified on IL-2-dependent T-cell lines by cytotoxicity and flow cytofluorometric analysis. By sequential immunoprecipitation and SDS gel analysis of antigens of DR1 cells it was determined that the Pez.2F5 determinant is carried by HLA class II DR molecules. Thus, the Pez.2F5 is the first described human monoclonal antibody able to immunoprecipitate HLA class II-related molecules.

Extinction of hippocampal theta rhythm evoked by mid-brain stimulation after intracerebroventricular administration of substance P fragment and enkephalin administration in rabbits.

Repetitive stimulation of the midbrain reticular formation with electrical stimuli causes extinction of the hippocampal theta rhythm. This phenomenon was used as an indicator of the effect of intracerebroventricular administration of the C-terminal hexapeptide substance P fragment (SP6-11), Leu- and Met-enkephalin on hippocampal electrical activity in the experiments performed on rabbits. Intracerebroventricular administration of SP6-11 caused an increase in the number of trains of pulses required to produce the extinction of the theta rhythm. Both of the enkephalins had opposite effects, the effect of Met-enkephalin being more than twice as strong as Leu-enkephalin. Control administration of C-terminal pentapeptide substance P fragment (SP7-11) and 0.9% NaCl solution had no significant effect on the tested phenomenon.

In vivo identification of rabbit serum allotypes.

It was found that injection of an antiallotype serum into the skin of a rabbit of a homologous allotype produced a skin lesion at the injection site. The skin lesions generated by this procedure were shown to result from the formation of insoluble immunocomplexes of the antiallotype serum injected and circulating IgG immunoglobulins: neither homocytotropic immunoglobulins fixed to cells nor surface immunoglobulins of B lymphocytes were found to take part in this reaction. The allotype skin test (AST) was utilized for identification of rabbit serum allotypes Aa1, Aa2, Aa3 and Ab5. A high degree correlation was found between results of typing by this method and by the precipitin test.

Genetic approach to the problem of distinction between RLA and antigens eliciting skin reacting transplantation antibodies in the rabbit.

This paper is a continuation of the previous study on the relationship between rabbit antigens eliciting skin reacting transplantation antibodies (SRTA) and histocompatibility RLA antigens. In this study two groups of families were tested. In the first one, antigenic phenotypes were typed using sera defined during investigation of random population as anti-RLA 1, RLA 2 and anti-RLA 3 and sera defined as SRTA anti-A and anti-B. In the second group - the sera prepared by intrafamilial immunization were applied. In both groups of families independent segregation of RLA and antigens eliciting SRTA was found. It supports the hypothesis about the distinction between these two antigenic systems.

System of rabbit antigens which elicit skin-reacting transplantation antibodies and are different from RLA.

Relationship between the rabbit histocompatibility RLA system and antigens eliciting skin-reacting transplantation antibodies (SRTA) was studied. The rabbit sera obtained by alloimmunization with skin transplant were investigated in the dye-exclusion cytotoxic test with lymphocytes and in the skin test on a panel of the outbred rabbits. Basing on a pairwise analysis of reactions in the cytotoxic test, some of these sera were classified into three groups of significantly correlated anti-RLA 1, 2, 3 sera. Analysis of reactions in the skin test revealed two groups of significantly correlated sera different from anti-RLA 1, 2, 3, which were designated as anti-SA and anti-SB. All anti-SA and anti-SB sera were also examined in the agglutination test with a panel of red blood cells but none of them was capable of agglutination. Study on tissue distribution of RLA and antigens eliciting SRTA showed that both systems are shared by skin and lymphoid tissue but in the brain tissue only antigens eliciting SRTA were present.

Graft-versus-host reaction after allogeneic hemopoietic tissue transplantation in rabbits conditioned with cyclophosphamide.

Graft-versus-Host Reaction (GvHR) was investigated in rabbits conditioned with a cyclophosphamide, which was given as a single injection of 110 mg/kg of body weight or as 4 injections of 50 mg/kg given on each of four successive days, before allogeneic bone marrow or spleen cells transplantation. The GvHR was of a chronic type. Splenomegaly was significant in the animals receiving spleen cell grafts, but not in the recipients of bone marrow transplants. In each of experimental groups delayed body weight gain and autoallergic phenomena were observed. Autoantibodies against erythrocytes, tested by direct Coombs test, were found in almost all graft recipients. This was a long lasting phenomenon since sensitized erythrocytes were found even after six months after transplantation. Cytotoxic autoantibodies against lymphocytes were present in the sera of about 20% of the recipients, and not longer than 30 days after transplantation. They proved not to be anti-RLA antibodies.

Restricted chimerism of peripheral blood cells after transplantation of allogeneic hemopoietic tissue in rabbits.

Allogeneic bone marrow or spleen cells were transplanted in rabbits treated with a single dose of 110 kmg/g of cyclophosphamide or four doses of 50 mg/kg. Chimerism of peripheral blood cells occurred in about 50% of the recipients, lasting from about the 14th day until 180 days after transplantation. The chimerism was limited to some kinds of cells since dissociation of proliferation of hemopoietic cells and split chimerism of lymphocytes were observed. Dissociation of proliferation of hemopoietic cells consisted in the appearance of only one cell line, namely lymphocytes, whereas the erythrocyte cells did not proliferate. Split chimerism occurred within lymphocytes, manifested by the presence of the donor's T lymphocytes but absence of proliferation of the donor's B lymphocytes.

A rabbit used as a model for testing hematopoietic tissue transplants.

Allogenic transplantations of bone marrow or spleen cells were carried out on rabbits treated with cyclophosphamide. About 50% of the recipients developed chimerism of peripheral blood cells. Chimerism was a passing phenomenon prevailing from 14 to 180 days after grafting. A phenomenon indicating that not all cell lines develop after transplantation from the donor stem cells, was observed. This phenomenon has been called "restricted chimerism". The GvH reaction was of a chronic type. Relative spleen weights were significantly increased in animals receiving the spleen cell grafts, but not in animals receiving bone marrow grafts. A direct positive erythrocyte Coombs test was found in almost all graft recipients. In addition cytotoxic autoantibodies against lymphocytes were present in sera of about 20% of the recipients.

Effects of intracerebroventricular administration of vasopressin and oxytocin on the extinction of hippocampal theta rhythm in rabbits.

Vasopressin and oxytocin were administered intracerebro-ventriculary to rabbits in order to test their effects on the brain electrical activity. The effects were manifested by an increase or decrease in the amount of energy of electrical pulse trains required to produce habituation which is known to occur after repetitive stimulation of the midbrain reticular - formation. Vasopressin inhibited the extinction of hippocampal theta rhythm, while oxytocin facilitated it.

[A case of migraine associated with paralysis of the hypoglossal nerve]. / Przypadek migreny skojarzonej z porazeniem nerwu podjezykowego.

The authors report a 52-year-old woman with migraine in whom transient hypoglossal nerve paralysis developed during an attack. Similar cases published in the literature, including those of Rushton et al. 1978 and Domzal et al. 1982 are analysed.

Beta2-ADR haplotypes/polymorphisms associate with bronchodilator response and total IgE in grass allergy.

Association and linkage studies of beta2-adrenergic receptor (beta2-ADR) polymorphisms in relation to the expression of asthmatic phenotypes and immune regulatory mechanisms have shown inconsistent results. In order to analyse the relevance of particular combinations of single nucleotide polymorphisms (SNPs) or haplotypes of beta2-ADR gene to bronchial asthma, bronchodilator response and total immunoglobulin E (IgE) we determined by direct DNA sequencing five SNPs (in positions: -47, -20, 46, 79, 252) in a group of 180 Caucasian subjects (110 patients with grass allergy and 70 nonatopic controls). The eight different beta2-ADR haplotypes were identified, with three the most common of them representing 92% of the studied cohort. Significantly higher (pcor = 0.0045) bronchodilator response was observed in patients with homozygotic genotype 46A/A in comparison with respective homo- and hetero-zygotes. There was no significant difference in bronchodilator response when beta2-ADR haplotypes were analysed. Significantly higher (pcor = 0.0005) total IgE levels were found in patients with beta2-ADR haplotype -47T/-20T/46A/79C/252G and homozygotic carriers of 46A (pcor = 0.0015) and 79C (pcor = 0.003) genotypes. No significant associations were found in regards to asthmatic phenotype and atopy. These results indicate that depending on phenotype studied, either an individual beta2-ADR SNP or beta2-ADR haplotype might affect disease manifestation.

The effect of intracerebroventricular administration of substance P fragment and met-enkephalin on the transmission of nervous impulses between the midbrain reticular formation and two generators of the hippocampal theta rhythm in rabbits.

The effect of intracerebroventricular administration of Substance P fragment and met-enkephalin on the excitability of two generators of hippocampal theta rhythm was investigated in the experiments performed on chronic rabbits. Substance P had a strong facilitatory effect on the threshold of the generator of the hippocampal theta rhythm of the frequency 4-7 c/s and an inhibitory effect on the threshold of the generator of the 7-12 c/s frequency evoked by stimulation of the midbrain reticular formation. These effects were dose dependent. The effects of met-enkephalin were opposite. They increased the threshold of the 4-7 c/s hippocampal generator and decreased the threshold of the other generator. The effect of these two compounds was evaluated according to the energy of electrical trains of pulses maintaining the continuous arousal pattern in the hippocampus.

[Role of fungi in house dust allergy in patients with bronchial asthma]. / Rola grzybów w uczuleniu na kurz domowy u chorych na astme oskrzelowa.

The aim of the study was to evaluate the contribution of skin hyperreactivity to fungi in patients with bronchial asthma and demonstrating skin sensitivity to house dust. In 50 patients skin tests with 24 allergen solutions of fungi found most often in house dust. Positive skin tests were found in 92% of the evaluated patients. Reactions to fungi allergens were seen more often than to Dermatophagoides pteronyssimus. Most often skin reactivity toward the following fungal allergens were seen: Candida albicans, Aspergillus fumigatus, Fusarium culmorum and Aureobasidium pullulans. It seems that skin hypersensitivity to fungi is very common in patients with bronchial asthma and sensitive to house dust. Clinical verification of this hypersensitivity should be studied further.