RESUMEN
Acute liver failure is a severe condition with a very unfavourable prognosis. One of the common complications and limiting factors for the outcome is the development of the intracranial hypertension. The etiology and the pathogenetic pathways leading to the development of this fatal complication of acute liver failure is still not completely understood. The aim of this review is to inform about the actual knowledge of pathogenesis of the intracranial hypertension in acute liver failure. Finally, a new method of tissue metabolism monitoring--microdialysis--is shortly discussed as a perspective method in monitoring and research on acute liver failure.
Asunto(s)
Hipertensión Intracraneal/fisiopatología , Fallo Hepático Agudo/complicaciones , Microdiálisis , Amoníaco/metabolismo , Edema Encefálico/etiología , Edema Encefálico/fisiopatología , Glutamina/metabolismo , Humanos , Hipertensión Intracraneal/etiología , Fallo Hepático Agudo/fisiopatologíaRESUMEN
BACKGROUND: The aim of the study was to determine the influence of fractionated plasma separation and absorption (FPSA) on intracranial pressure (ICP) in acute liver failure (ALF). METHODS: A surgical model of ALF in pigs (35-40 kg) was used. We compared laboratory data and haemodynamic parameters from the ALF control group to the ALF group treated by Prometheus using ANOVA with repeated measures and grouping factors, by calculating the area under the curve, and by the Mann-Whitney rank test. RESULTS: Bilirubin levels differed significantly in favour of the FPSA treatment group: after 6 h 12.81 +/- 6.54 versus 29.84 +/- 9.99, after 9 h 11.94 +/- 4.14 versus 29.95 +/- 12.36 (p < 0.01) and after 12 h 13.88 +/- 6.31 versus 26.10 +/- 12.23 mmol/l (p < 0.05). ICP values differed significantly in favour of the FPSA treatment group: after 9 h 19.1 +/- 4.09 versus 24.1 +/- 2.85 (p < 0.01), after 10 h 21.9 +/- 3.63 versus 25.1 +/- 2.19, after 11 h 22.5 +/- 3.98 versus 26.3 +/- 3.50, and after 12 h 24.0 +/- 4.66 versus 29.8 +/- 5.88 mm Hg (p < 0.05). CONCLUSION: The authors demonstrated that a significant decrease in ICP was found in pigs with ALF following treatment by FPSA.
Asunto(s)
Hemodiafiltración , Presión Intracraneal , Fallo Hepático Agudo/terapia , Animales , Fallo Hepático Agudo/fisiopatología , PorcinosRESUMEN
BACKGROUND: Development of biological and non-biological artificial liver devices in the previous 20 years enabled effective treatment of acute liver failure (ALF) of patients waiting for liver transplantation or for spontaneous liver parenchyma regeneration. Aim of the study was the evaluation of the effectiveness of biological (BAL - bioartificial liver) and non-biological (FPSA - Fractionated plasma separation and adsorption) methods in the treatment of experimental ALF on large laboratory animal. METHODS AND RESULTS: Surgical model of ALF with liver devascularization in pigs (weight 25-40 kg) was provided following monitoring of ALF markers (AST, ALT, bilirubin, ammoniac, glycaemia, INR) including intracranial pressure (ICP). Control group included animals without treatment of ALF. Results of both experimental groups were compared and statistically worked-out with that of controls by T-test and Mann-Whitney non-parametric test by EXCEL and QUATRO. BAL group: 10 pigs (weight 30 +/- 5 kg) with ALF were treated by BAL with isolated hepatocytes. When plasma bilirubin was compared, significant differences (p < 0.05) in 6 and 9 hours interval were found favouring BAL group (18.1 vs. 13.1, 22.9 vs. 13.2 mmol/l). The value of ICP in both groups was no significant. Prometheus group: 14 pigs weight 35 kg (35 +/- 5 kg) with the identical ALF were treated by Prometheus (FPSA). Level of serum bilirubin in experimental group when compared to control group was significantly lower (p < 0.01) at 6 hour interval 12.81 +/- 6.54 vs. 29.84 +/- 9.99 at 9 hour 11.94 +/- 4.14 vs. 29.95 +/- 12.36 and at 12 hour 13.88 +/- 6.31 vs. 26.10 +/- 12.23 mmol/l. No significant difference in serum ammonia level was found. ICP was significantly different from 9 hour to 12 hour interval in favour of FPSA group (p < 0.01): 9 hour 19.1 +/- 4.09 vs. 24.1 +/- 2.85, 10 hour 21.9 +/- 3.63 vs. 25.1 +/- 2.19, 11 hour 22.5 +/- 3.98 vs. 26.3 +/- 3.50 and 12 hour 24.0 +/- 4.66 vs. 29.8 +/- 5.88 mm Hg. CONCLUSIONS: Significant improvement of bilirubin and ICP levels resulting from the treatment with fractionated plasma separation and adsorption (Prometheus) were observed in the case of experimental ALE Except the bilirubin levels, bioartificial liver provided by O. liver Performer with isolated hepatocytes did not bring any significant improvement of laboratory markers, including ICP.
Asunto(s)
Fallo Hepático Agudo/terapia , Hígado Artificial , Animales , Bilirrubina/sangre , Sus scrofaRESUMEN
BACKGROUND: There was an active interest in development of liver assist device in the last two decades. Using these devices to bridge patients with acute hepatic failure (AHF) to ortotopic liver transplantation (OLTx) or to liver regeneration might decrease the mortality rate. Several liver support systems have been described in different stages of experimental or clinical examination. METHODS: PubMed (1986-2008) was searched using the keywords "artifitial livers", "liver support", "bioartifitial liver" and "cell transplantation". The own experience presenting by authors are the conclusions of their publications. RESULTS AND DISCUSSION: Biological liver support (BAL) uses hepatocytes can support theoretically both detoxification and biosynthesis. Experimental study confirmed significant decrease in some of AHF metabolites. Nevertheless, randomized study didn't show any improvement in patient's survival. Source of viable hepatocytes and sufficient bioreactor capacity are some of unsolved problems. Nonbiological liver support as a plasma exchange, hemodialysis, hemofiltration, albumin dialysis or adsorbent recycling systems eliminate some of toxins, but other specific liver functions can't replace. MARS and Prometheus devices have been used successfully in treatment of AHF by human. However, the absence of randomized study still lasts. These devices remove some of toxins and cytokines unselectively and are also limited by adsorber capacity. Selective plasma filtration therapy and hybrid liver support systems which combine both of management advances present the possible solution. Authors themselves confirmed by application of both methods a significant decrease of bilirubin level. Intracranial pressure declines only by use of non-biological device - Prometheus. CONCLUSION: Effective liver assist device that gains a survival approval hasn't been developed till now. In confrontation with other current used cure possibilities, BAL didn't propose the original expectations. On the other hand, the non-biological devices seem to be perspective and their contribution has been proved by prospective studies. The randomized study is still absent. Authors' experiences confirm this trend.
Asunto(s)
Fallo Hepático Agudo/terapia , Hepatocitos/trasplante , Humanos , Hígado ArtificialRESUMEN
OBJECTIVE: To detect lymphocyte subpopulations and CD3+/DR + expression in sepsis. METHODS: In a prospective clinical study we evaluated subpopulations of lymphocytes and percentage of CD3+/HLA-DR+ lymphocytes using two-color flow cytometry in 40 patients with sepsis and compared them with 34 healthy adults. RESULTS: Septic patients, when compared with healthy controls, have significantly lower percentage and absolute numbers of total T lymphocytes and CD4 T lymphocytes (P < 0.01). Absolute numbers of CD8 T lymphocytes, NK cells, CD3+/DR + lymphocytes and CD4/CD8 ratio were also decreased (P < 0.01). The percentage of B lymphocytes was increased (P < 0.01). CONCLUSION: Our results are in agreement with previous findings in patients with sepsis after major surgery or trauma. The decreases in the percentage and absolute numbers of circulating lymphocyte subsets in non-surgical sepsis could represent a general reaction to stress. Increased percentage of B lymphocytes is most probably related to the bacterial etiology of the disease.
Asunto(s)
Complejo CD3/inmunología , Antígenos HLA-DR/inmunología , Subgrupos Linfocitarios/inmunología , Sepsis/inmunología , Adolescente , Adulto , Anciano , Complejo CD3/sangre , Relación CD4-CD8 , Niño , Femenino , Citometría de Flujo , Antígenos HLA-DR/sangre , Humanos , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Sepsis/sangre , Estadísticas no Paramétricas , Linfocitos T/inmunologíaRESUMEN
BACKGROUND: The majority of meningococcal infections are characterized by nasopharyngeal carriership. In some patients invasive disease with a mild course develops, while some cases have a lethal outcome. The reasons of this wide variation range are not clear. The objective of the present work was to assess whether the development of invasive meningococcal disease or its prognosis are associated with HLA class I. METHODS AND RESULTS: The group of patients was formed by 40 patients (29 females, 11 males, mean age 16 years, range 8 months to 52 years). In 28 patients the disease was caused by N. meningitidis group C, in 9 cases group B, in three cases the serotype was not assessed. The etiology was confirmed by cultivation or latex agglutination. Twenty-three patients had a mild course of the disease, 8 a medium severe one, 9 patients a severe clinical course (score according to Stiehme, Damrosch and Rosenblat). The patients were compared with 227 non-related blood donors (114 women, 113 men, 18 to 50 years old). In patients and controls 24 lymphocytic HLA antigens class I were identified as to type. Typing was done using the standard microlymphocytotoxic test in the NIH modification. The results were processed by statistical methods using Fisher's exact test and the 2 x 2 test with Yates correction. In patients with a mild course HLA antigens B7 and B12 predominate (p = 0.03; p = 0.02), in medium severe cases antigen A11 (p = 0.03), in patients with the most severe course antigen A9 (p = 0.04). In invasive infections caused by N. meningitidis serotype B antigen B17 predominates (p = 0.05). CONCLUSIONS: The severity of meningococcal invasive infections is associated with HLA class I. Invasive disease caused by N. meningitidis serotype B are more likely to occur in carriers of HLA B17. No relationship was found between HLA class I and invasive disease caused by N. meningitidis regardless of serotype and with serotype C.
Asunto(s)
Antígenos de Histocompatibilidad Clase I/análisis , Infecciones Meningocócicas/inmunología , Neisseria meningitidis , Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , PronósticoRESUMEN
The prognostic value of HLA antigens in Hodgkin's disease was assessed by multivariate regression analyses. A significantly adverse prognostic impact for achieving complete remission by primary treatment and for its persistence was proved in four antigens locus B (B18, B5, B27 and B15). Five-year survival without signs of the disease, i.e. survival without relapse is significantly lower in subjects with antigen B5, as compared with the group of patients where the antigen was not detected (42% vs. 58%, p = 0.05). An independent prognostic impact of the selected HLA antigens was confirmed in models incl. also formerly tested risk factors for the relapse of Hodgkin's disease.
Asunto(s)
Antígenos HLA/análisis , Enfermedad de Hodgkin/inmunología , Adulto , Femenino , Enfermedad de Hodgkin/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Tasa de SupervivenciaRESUMEN
The Duffy system, Fya, Fyb, and HLA antigens were studied in 86 members, 39 affected, 47 healthy subjects, of 17 families with HMSN types I, II and III. The incidence of autosomal dominant as well as recessive, or sporadic forms was registered. In the autosomal dominant form of HMSN type I a close linkage was found between the genes coding the disease under study and the determinants Fya and Fyb. Recombination was found in only 9.1% of the cases. A study of HLA antigens revealed a major decrease in antigen B27 in the patients under scrutiny. An identical haplotype of most of the parents was a conspicuous feature in families with the autosomal dominant form of HMSN type I.
Asunto(s)
Mapeo Cromosómico , Sistema del Grupo Sanguíneo Duffy/genética , Ligamiento Genético/genética , Antígenos HLA/genética , Neuropatía Hereditaria Motora y Sensorial/genética , Adolescente , Adulto , Niño , Preescolar , Aberraciones Cromosómicas/genética , Trastornos de los Cromosomas , Femenino , Frecuencia de los Genes/genética , Genes Dominantes/genética , Genes Recesivos/genética , Antígeno HLA-B27/genética , Humanos , Masculino , Persona de Mediana Edad , LinajeRESUMEN
The authors investigated the dependence of the results of the crossover test with thrombocytes and lymphocytes of the donor and serum of the recipient on the rise of thrombocytes 1 and 24 hours following administration of a thrombocyte concentrate. The clinical condition of the patient at the time of thrombocyte administration was taken into account. The donor of thrombocytes isolated in a blood element separator was selected from a panel of cca 800 subjects with previously assessed HLA antigens. A total of 36 administered concentrates was evaluated. From the assembled findings it may be concluded that the result of thromboconcentrate transfusion is significantly influenced by adverse clinical factors in the patient such as splenomegaly, haemorrhage, febrile conditions. A positive crossover lymphocytotoxic test can predict reliably the ineffectiveness of thrombocyte administration. A positive crossover test with the donor's thrombocytes does not affect significantly the success of the transfusion. It seems thus that for the fate of administered thrombocytes the presence of HLA antibodies is decisive and not the presence of specific thrombocytic antibodies.
Asunto(s)
Tipificación y Pruebas Cruzadas Sanguíneas , Plaquetas/inmunología , Anticuerpos/análisis , Transfusión Sanguínea , Pruebas Inmunológicas de Citotoxicidad , Humanos , Transfusión de PlaquetasRESUMEN
The authors compare the classical method of typing of HLA antigens by the microlymphocytotoxic test (CTX) and the results obtained by flow cytometry (FCTX). They investigated agreement of results as regards estimation of 14 HLA antigens, loci A and B. in 42 sera. They compared possibilities of flow cytometry using microquantities of material and investigated changes of results obtained by cytotoxic reactions after 24 hours. The results evaluated by linear regression analysis proved the comparability of flow cytometry and the classical microlymphocytotoxic test.
Asunto(s)
Citometría de Flujo , Antígenos HLA/análisis , Prueba de Histocompatibilidad , Separación Celular , Pruebas Inmunológicas de Citotoxicidad , HumanosRESUMEN
The authors analyze the effect of transfusions of 211 thrombocyte concentrates to polytransfused patients in relation to the results of the crossover test between donor and recipient, using the lymphocytotoxic test (LCT). In negative LCT tests the adequate and inadequate effect was 50%. After elimination of non-immune influences (splenomegaly, febrile temperature) the percentage of adequate effects rose to 70%. In LCT positive results the effect of administration of thrombocyte concentrates declined to 30%. The authors discuss practical possibilities and ways to select suitable donors to achieve an optimal therapeutic effect of substitution therapy.
Asunto(s)
Transfusión Sanguínea , Pruebas Inmunológicas de Citotoxicidad , Antígenos HLA/análisis , Transfusión de Plaquetas , Humanos , Linfocitos/inmunologíaRESUMEN
Weak accessory HLA antibodies in HLA sera were assessed by three test--the microlymphocytotoxic, antiglobulin cytotoxic and fluorescent cytotoxic test. Most frequently they were detected by the antiglobulin cytotoxic test (69.64%), followed by the fluorescent cytotoxic test (55.73%) and least frequently by the microlymphocytotoxic test (45.77%). From the results ensues that the antiglobulin cytotoxic test is a suitable method of crossmatch before thrombocyte transfusions to patients who developed reactions after transfusions or where therapy failed although the crossmatch was performed by the microlymphocytotoxic test between the donor's lymphocytes and the patient's serum and the test was negative.
Asunto(s)
Transfusión Sanguínea , Antígenos HLA/análisis , Prueba de Histocompatibilidad/métodos , Transfusión de Plaquetas , Prueba de Coombs , Pruebas Inmunológicas de Citotoxicidad , HumanosRESUMEN
HLA-A, B antigens and the ABO group were examined in 184 patients with aplasia of bone marrow and leukaemia and in 373 of their relatives, mostly siblings. A HLA-A, B donor, identical or compatible, was found for 35.87% patients, a HLA-DR identical for 84.21% of 38 patients who had a HLA-A, B identical relative. Bone marrow was transplanted to 16 patients (10 with bone marrow aplasia, 6 with acute or chronic leukaemia), with one exception bone marrow from a sibling. The bone marrow was accepted in all patients but two where the transplantation was made despite MLC positivity. From the results ensues that it is essential for successful transplantation of bone marrow to ensure maximal identity between donor and recipient as regards the ABO group, HLA antigens and negativity of the MLC reaction. The negativity of the MLC reaction is more important than HLA-DR identity; when assessing only one HLA-DR antigen in a donor identical with the patient, it cannot be ruled out that on the lymphocytes of the donor there exists another one which was not detected. The authors discuss the causes of different results of the MLC reaction and HLA-A, B, DR typing.
Asunto(s)
Trasplante de Médula Ósea/inmunología , Sistema del Grupo Sanguíneo ABO/inmunología , Femenino , Antígenos HLA/análisis , Humanos , Prueba de Cultivo Mixto de Linfocitos , Masculino , Donantes de TejidosRESUMEN
The authors investigated 52 patients (22 men and 30 women) with acute anterior uveitis where they ruled out systemic autoimmune disease, metabolic disease and focal or chronic infection. At the time of the infection the patients had not been treated for several months by any immunosuppressive treatment. The authors investigated in these patients serum concentrations of immunoglobulins G, A and M, the concentration of the C3 component of complement and the concentration of circulating immune complexes. Before the onset of therapy they investigated the response to antigens of the Immunoskin test. They assessed also the ratio of transplantation antigens class I by the microlymphocytotoxic test. They compared furthermore immunological indicators in subjects with a first attack and relapse of the disease and in groups, classified by the severity of the inflammatory symptoms. The authors detected significantly more frequently (p = 0.0005) the incidence of HLA-B27 antigen. Those where it was present were more frequently affected with a severe inflammation, as compared with subjects who did not have this phenotype (p less than 0.04). The relapse of the disease was more frequent in women (p = 0.1). The immunological laboratory findings did not differ in the first attacks and relapses of the disease, differences were, however, found in groups which differed as to the severity of inflammatory symptoms. In these groups the response rate to tests of skin sensitivity differed also. Based on these findings the authors assume that the ratio of immune processes in the development of acute idiopathic anterior uveitis cannot be ruled out.
Asunto(s)
Uveítis Anterior/inmunología , Enfermedad Aguda , Adulto , Proteínas del Sistema Complemento/análisis , Femenino , Antígeno HLA-B27/análisis , Humanos , Inmunoglobulinas/análisis , MasculinoRESUMEN
HLA-A and B antigens were determined in a study of 162 patients (93 epidermoid type, 20 adenocarcinoma, 26 small-cell carcinoma and 23 undifferentiated types) with lung cancer. Differences between antigen frequencies in cancer and control populations were studied by chi 2Y analysis or Fisher's exact test. Survival data were analyzed using Cox's model for censored data. Cancer patients had a decreased frequency of the antigen HLA-B40 (chi 2Y = 14.15, P = 0.00018, Pc = 0.003, relative risk = 0.21). Patients with HLA-A10, A 11 and B27 had a shortened mean survival time. Patients with HLA-B12 had a prolonged survival time.
Asunto(s)
Antígenos HLA-A/análisis , Antígenos HLA-B/análisis , Neoplasias Pulmonares/inmunología , Adenocarcinoma/inmunología , Quiste Epidérmico/inmunología , Humanos , Análisis de SupervivenciaRESUMEN
The author gives an account of the classification and use of HLA monoclonal antibodies. In experimental work the author demonstrates the contribution of investigations of the expressivity of histocompatible antigens class I and II and their changes in sound and tumourous tissues. In clinical practice they are important in particular in transplantology--cleaning of bone marrow, follow up of the GvH reaction, monitoring of patients. HLA monoclonal antibodies serve to reveal the polymorphism in the HLA sphere and the follow up of general biological laws.
Asunto(s)
Anticuerpos Monoclonales , Antígenos HLA/análisis , Antígenos HLA/inmunología , HumanosRESUMEN
The Duffa system (Fya Fyb) and HLA antigens were examined in 86 subjects (39 affected, 47 healthy) in 17 families with HMSN type I, II and III. They recorded the incidence of autosomal dominant as well as recessive (possibly sporadic) forms. In the autosomal dominant form of HMSN type I a close relationship was detected between genes coding the investigated disease and blood cell signs Fya and Fyb. Recombination was found only in 9.1% of the cases. Investigation HLA antigens revealed marked reduction of the B27 antigen in the investigated patients. A striking sign in families with the autosomal dominant form of HMSN type I was an identical haplotype of the majority of parents.
Asunto(s)
Antígenos de Grupos Sanguíneos/genética , Sistema del Grupo Sanguíneo Duffy/genética , Antígenos HLA/análisis , Neuropatías Hereditarias Sensoriales y Autónomas/genética , Neuropatía Hereditaria Motora y Sensorial/genética , Femenino , Antígenos HLA/genética , Neuropatías Hereditarias Sensoriales y Autónomas/sangre , Neuropatía Hereditaria Motora y Sensorial/sangre , Humanos , Masculino , LinajeRESUMEN
The authors compare the sensitivity of the testing methods for determining HLA-DR antigens on B-lymphocytes and monocytes (classical eosin technique) with the fluorescence cytotoxic tests (FCT). The assessment of results of DR specificity determination in blood donors and patients with blood disease showed comparability of the tests. The rate of concordance ranged from 88-89%. The paper discusses the advantages and disadvantages of each method.
Asunto(s)
Pruebas Inmunológicas de Citotoxicidad , Antígenos HLA-DR/análisis , Pruebas Inmunológicas de Citotoxicidad/métodos , HumanosRESUMEN
In 146 patients with haematological diseases changes in the assessment of HLA antigens after repeated examinations were investigated. In 68.49% of the specimens all HLA antigens were assessed correctly, 8.9% had antigen losses and 22.6% responded by a polyreactive reaction. Changes of the HLA expressivity in the sense of loss or polyreactivity during repeated examinations were followed up and possible causes of changes of HLA expression are discussed.
Asunto(s)
Antígenos de Histocompatibilidad Clase I/análisis , Enfermedad de Hodgkin/inmunología , Leucemia/inmunología , HumanosRESUMEN
This paper studies relations of 21 HLA antigens of the A and B loci to selected characteristics in a group of patients with Hodgkin's disease. The investigated characteristics are age, sex, histological patterns, clinical stage and symptomatology. The considered group consists of 68 patients, 37 males and 31 females aged from 19 to 66 years and from 26 to 63 yr, respectively. A comparison between antigen frequencies for patients and controls (301 unrelated blood donors) is carried out. The results confirm that there is no relation between HLA antigens and Hodgkin's disease. A significant increase of A11 is found for females under 40 yr. Certain HLA antigens show significant correlation neither with the patient age nor with clinical or histological stages. A significant increase of B5 is observed for 16 relapsed patients. For them, significant test characteristics are found in the presence of cross-reacting HLA-B5, B35.