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Glucose intolerance often occurs in liver cirrhosis; therefore a long-term control of plasma glucose levels appears to be important. For this purpose glycated hemoglobin A (HbA1c) determination is proposed as a suitable method, while no data are available on fructosamine test. In 98 cirrhotic patients serum fructosamine and HbA1c levels were compared with those of normal controls and among cirrhotic patients grouped in non glucose-intolerant and with non insulin-dependent (NIDDM) or insulin-dependent diabetes mellitus (IDDM). The mean HbA1c values of cirrhotic patients with normal glycemic control were significantly lower than normal, and only a few IDDM and NIDDM cirrhotic patients showed high values of HbA1c, indicating that HbA1c is often underestimated in these patients. On the contrary, serum fructosamine levels were on the average higher than normal in nondiabetic patients, but they were significantly higher in IDDM and NIDDM patients than in nondiabetics, and the 72% of NIDDM and 85% of IDDM patients had fructosamine levels higher than the upper normal value. In conclusion, in diabetic patients with liver cirrhosis fructosamine seems to be a more suitable test than HbA1c for monitoring blood glucose levels.

Manufacturers are attempting to increase the purity of FVIII concentrates. A strategy pursued by some is that of including a purification step (gel filtration, ion-exchange or affinity chromatography) that yields concentrates with an intermediate or final specific activity of 35 to 250 IU FVIII/mg of protein. The specific activity of the final product may be lower because serum albumin is added to some concentrates to stabilize FVIII. In hemophiliacs treated with these concentrates, FVIII recovery and half-life are at least as good as those for less pure concentrates. In patients with von Willebrand disease, these concentrates increase plasma levels of FVIII, but their capacity to normalize the bleeding time is not well established. The hypothesis that their reduced alloantigen load might slow the progression of human immunodeficiency virus (HIV) infection is still not validated, but a few prospective studies are now attempting to address this issue. All the concentrates undergo virucidal procedures based on pasteurization or treatment with solvent/detergent. It is well established that these virucidal methods and donor screening avoid HIV transmission. A recent large study has shown that a pasteurized concentrate carries a low risk of transmitting viral hepatitis. The assessment of safety from hepatitis of concentrates treated with solvent/detergent is based on favorable preliminary results.

We studied the behavior of some biochemical markers of fibrosis, the aminoterminal propeptide of type III procollagen (P-III-P), laminin, hyaluronate and fibronectin, in the sera of patients with primary biliary cirrhosis (PBC). Significant increases were found in serum laminin, hyaluronate and P-III-P and, more important, a significant correlation was found between the histological stage of the disease and serum hyaluronate. This parameter seems to distinguish between early PBC (I and II stages) and advanced disease with fibrosis. Moreover, a correlation between the histological stage and serum levels of both laminin and P-III-P was observed. Serum laminin, however, increases particularly in advanced disease, whereas high levels of sP-III-P are already present in the early stage. Finally, no significant differences were found between the plasma fibronectin levels of patients with primary biliary cirrhosis and those of controls.

Activated intralobular macrophages were quantified as their lysozyme contents in liver biopsies from patients with chronic HBV and nAnB active hepatitis, and subjects with no evident liver histological damage. There were more macrophages (0.62 +/- 0.06/2,500 mu 2) with a larger area (20.36 +/- 0.87 mu 2) in HBV-related chronic active hepatitis than in controls (0.21 +/- 0.04/2,500 mu 2 and 16.01 +/- 1.48 mu 2), whereas in nAnB chronic active hepatitis their numbers were similar to that in the controls (0.22 +/- 0.03/2,500 mu 2) and their area was smaller (11.68 +/- 0.79 mu 2).

In patients with acute myocardial infarction (AMI) treated with streptokinase (SK) or recombinant tissue-type plasminogen activator (rtPA) we found high levels of thrombin-antithrombin (TAT) complexes signalling a significant activation of the coagulation cascade. In the SK-treated group the median pretreatment TAT complexes levels were 5.0 micrograms/l and in all patients, whatever the pretreatment level, TAT complexes increased following treatment. A statistically significant increase (medians = 20.3 and 12.0 micrograms/l) was observed 90 and 180 min after starting SK. The mean pretreatment level in the rtPA-treated group was also 5.0 micrograms/l and in all but one patients TAT complexes increased following treatment. A statistically significant increase (medians = 37.0 and 30.5 micrograms/l) was observed 90 and 180 min after starting rtPA. There was no statistically significant difference between TAT complexes in the two groups of patients either before or 90 min after treatment, whereas at 180 min the median concentration of TAT complexes was significantly higher for rtPA- than for SK-treated patients. We did not find an association between coronary vessels patency after thrombolysis and concentrations of TAT complexes; however, the rate of occluded vessels was very low (4 out of 30 patients), so that a difference was perhaps lost due to the insufficient size of the sample. In conclusion, we found thrombin activity during thrombolytic therapy in patients with AMI. There is no important difference in this respect between rtPA and SK. Whether or not this phenomenon is responsible for early rethrombosis remains to be explored by larger studies.

Purified placental syncytiotrophoblastic membrane has been used in a radioreceptor assay to study the binding of tritium radiolabeled human thrombin. Binding was found to be saturable at higher membrane concentrations when using a fixed amount of ligand and showed a hyperbola analogous to enzyme-substrate binding. A Scatchard plot was linear and revealed homogeneous binding sites with a high-affinity constant Ka = 3 X 10(10) M-1 and capacity of 3.05 X 10(11) sites/mg of membrane protein. This high-affinity compares well with chick and embryo cell thrombin receptor which has homogeneous sites and high-affinity in contrast to platelet thrombin receptor which exhibits multiple binding sites and cooperative effects as previously noted. A thrombin receptor on the placenta might serve to mobilize thrombin into placental tissue leading to conversion of fibrinogen into fibrin, fibrinoid necrosis being so common in certain placentae. A receptor-mediated transplacental passage of thrombin into the fetal circulation is also proposed.

The advent of molecular genetics has had a significant impact on carrier detection and prenatal diagnosis in the haemophilias. Where phenotypic analysis can only identify with varying degrees of probability up to 90% of carriers and can only be used in prenatal diagnosis when fetal blood is obtained (18-20 weeks gestation), genotypic analysis gives a greater than 99% certainty of carrier status (when informative) and allows for prenatal diagnosis at 8-12 weeks utilising DNA obtained by chorionic villus sampling. Furthermore, the introduction of the technique of polymerase chain reaction (PCR) amplification of DNA into genotypic analysis either for the detection of the disease-causing defect itself, or to detect an intragenic informative polymorphism, has significantly increased the ease by which these procedures can be introduced into the laboratory. PCR based family studies in haemophilia will become increasingly available in both developed and developing countries. While in the former detection of the defect itself will become available, particularly for haemophilia B, in other countries simple PCR based DNA polymorphism analysis will become the mainstay of effective, practical haemophilia genetics.

Human peripheral blood lymphocyte (PBL) phenotypes have been analyzed before and after stimulation with phytohemagglutinin (PHA), concanavalin A (ConA) and pokeweed mitogen (PWM) for 3 days and in mixed lymphocyte culture (MLC) for 7 days. PBL labeled with each of 10 fluorescent monoclonal antibodies were automatically sampled for flow cytometry from 96-well microtiter plates using a microsample delivery system. The reference phenotypic ranges were determined in fresh cells and control cultures. PHA was mostly mitogenic for T PBL bearing the CD3, CD5, CD7, CD8 and CD25 differentiation clusters, and a low density of CD1 and CD4 had a small effect on human natural killer cells (HNK) and also did not stimulate B (CD19) and HLA-DR+ PBL. There was an incomplete phenotypic overlapping between PHA- and ConA-stimulated cultures, ConA being more mitogenic for CD4 and less mitogenic for CD8 PBL. The mitogenic effect of PWM was evident on CD3, CD5, CD7, CD4, CD25 and CD8, but not on HNK, HLA-DR and CD19 B PBL, which presumably had already differentiated into antibody-secreting cells. After MLC stimulation all T, B and HNK PBL subsets tested were increased, but the cells bearing CD1, CD4, CD5, CD7, CD25, HNK, CD19 and HLA-DR had the greatest proliferation with respect to the unmixed control PBL. The present approach to the phenotyping of PBL subsets could offer more complete and accurate data for monitoring and follow-up of patients in transplantation and immunopathology hospital wards.

This paper reports the results of a study organized by the Istituto Superiore di Sanità (Rome, Italy) and carried out in collaboration with several national laboratories. Its aim was to ascertain whether diagnostic kits for detecting anti-HIV antibodies in human serum can also be used to detect the same antibodies in human immunoglobulins. Thirty-three lots of immunoglobulins supplied by six pharmaceutical companies present in Italy were examined using different procedures. On the basis of the results of this study it can be concluded that i. anti-HIV antibodies can be detected in immunoglobulins by means of commercial reagents; ii. a preliminary dilution of immunoglobulin samples should not be made; iii. Western blot method appears to be the 'reference' test; however, competitive EIA tests are equally valuable if a negative control made up of anti-HIV-negative Igs is employed; iv. Igs examination for anti-HIV antibody represents an indirect control on a correct donors' screening procedure.

Factor VII (FVII) activity should be measured in order to evaluate the risk for coronary artery disease. The measurement of FVII by means of a standardized clotting method seems to be influenced by the thromboplastins used, while the FVII-deficient plasmas do not affect the results.