HIV antibody status and immunological abnormalities in Polish haemophiliacs.

Sera of 520 multitransfused haemophiliacs were examined for antibody to HIV; 447 patients had haemophilia A and 73 had haemophilia B. In 382 patients with haemophilia A and in 62 with haemophilia B solely Polish-made blood products were used for replacement therapy. The remaining haemophiliacs had also received imported clotting factor concentrates prior to the investigation. Only 8 patients (haemophilia A - 7, haemophilia B - 1) developed anti-HIV and all of them had been exposed to commercial concentrates. The analysis of T-cell subsets demonstrated an inverted T4/T8 ratio (less than 1.0) in 7 (30%) of the 23 haemophiliacs treated solely with domestic cryoprecipitate and in 3 (37%) of the 8 seropositive recipients of commercial concentrates. The most frequent alteration in both subgroups was a reduced ratio with either normal absolute numbers or an increase in T8 cells. Increased serum IgG levels were found in 82% of the users of cryoprecipitate and in 75% of the seropositive patients. Serum beta-2-microglobulin level was elevated in 69 and 62% of each subgroup, respectively. The observed immunological abnormalities, at least in the cryoprecipitate treated subgroup, may be causally related to factors other than HIV infection.

The comparison of susceptibility of two target cells (HuRBC and L1210) to antibody dependent lymphocyte cytotoxicity.

Antibody-dependent lymphocyte cytotoxicity was compared in two test procedures. Human erythrocytes (group O R1R1 or R2R2) and mouse lymphoma cells (line L1210) were used as target cells. Anti-Rh (anti-C + D) serum obtained from a hyperimmunized blood donor and serum obtained from rabbit immunized with L1210 cells were used as the source of antibody specific for target cells. In both tests, lymphocytes (PBL) or mononuclear cells (MNC) isolated from heparinized or defibrinated blood were used as effectors. In both tests comparable results were obtained.

Sensitivity of automated red cell antibody detection.

The principle of detecting red cell antibodies by automated technique using the two-channel Technicon Auto-Analyser with some modification is described. The sensitivity of automated methods in detecting antibodies of different specificities was determined. The study was carried out with 76 diagnostic human sera produced by the Institute of Hematology, Transfusion Centers and commercial firms: anti-RhD, -C, -E, -CW, -c, -e, anti-K, -k, Kpa, anti-Fya, -Fyb, anti-Jka, -Jkb, anti-M, -S, -s, anti-P1, anti-Lua, anti-Lea, -Leb, anti-H, -A1, anti-I, anti-Lua and anti-Vel. A majority of the antibodies were detected by both automated methods with greater sensitivity than by manual methods. Greatest sensitivity was observed in the detection of anti-S, -Vel and antibodies of the Rh system. Anti-Leb and anti A1 antibodies were not detected. The studies are the basis for introduction of the automated technique into routine use for antibodies in blood donors and recipients.

[Liver scanning in diffuse liver disease (author's transl)]. / Leberszintigraphie bei diffusen Leberparenchymerkrankungen

The results of liver scans performed with 99mTc-sulphur colloid in 169 patients suffering from diffuse liver diseases and in 48 normal controls were evaluated. The patients with reactive hepatitis, acute hepatitis, chronic persistent hepatitis, fatty liver and fibrosis of the liver show only minimal deviations from the scintigraphic pattern. On the contrary, highly increased colloid uptake in the spleen is found in cases of chronic aggressive hepatitis, whilst the intrahepatic distribution of the colloid is approximately normal. In cases of liver cirrhosis, increased colloid uptake is found in the left lobe of the liver as well as in the spleen and in the bone marrow. Either normal findings or cirrhosis-like changes of the colloid distribution are observed in patients with alcoholic hepatitis.

[Prostacyclin (PGI2) activity in the rectal mucosa of patients with ulcerative colitis (author's transl)]. / Prostacyclin-(PGI2-)Aktivität in der Rektumschleimhaut bei Colitis ulcerosa.

PGI2 synthesis was investigated in rectal mucosa of 8 patients with active ulcerative colitis, 4 in remission and 16 controls. Determinations were carried out using Moncada's bioassay. The results demonstrated enhanced PGI2 synthesis in rectal mucosa in active ulcerative colitis. Further clinical studies should clarify whether or not selective inhibiton of PGI2 synthetase might be a useful therapeutic approach in ulcerative colitis.

[Bilirubin metabolism (author's transl)]. / Bilirubinstoffwechsel I. Physiologie

The degradation of haemoglobin haeme of senescent red blood cells - involving NADPH-dependent haeme oxygenase and biliverdin reductase - in the reticuloendothelial cells of the spleen, bone marrow and liver accounts for 80 to 90% of the 250 to 300 mg of bilirubin formed in 24 hours. The remaining 10 to 20% derive from catabolism of other haemoproteins and from the destruction of maturing red blood cells in the marrow. In studies with isotopically-labelled metabolic precursors of haeme this fraction can be found in the early-labelled peak. In plasma virtually all the bilirubin is tightly bound to plasma proteins, largely albumin, because it is only sparingly soluble in aqueous solutions at physiological pH. In the sinusoids unconjugated bilirubin dissocates from albumin, enters the liver cells across the cell membrane through non-ionic diffusion and is bound by the two cytoplasmic proteins Y (or ligandin) and Z. Little is known about the transfer of unconjugated bilirubin from these binding proteins to the smooth endoplasmatic reticulum, where it is converted to a water-soluble ester glucuronide by bilirubin UDP-glucuronyl transferase. The physiological significance of non-glucoronide conjugates (sulphate, disaccharides) is only of minor importance. Following conjugation, bilirubin is transferred rapidly across the canalicular membrane into the bile canaliculi. This process is energy-dependent and occurs against a concentration gradient. The epithelial lining of the intestine and of the gall bladder, which can easily reabsorb lipid-soluble unconjugated bilirubin, is virtually impermeable to organic anions of the size and charge of conjugated bilirubin, thereby ensuring efficient excretion of this pigment. In the intestinal tract bilirubin is reduced to urobilinogen, which is subsequently reabsorbed to some extent into the enterohepatic circulation, removed from plasma by the liver and excreted unchanged in the bile. This rapid bacterial reduction of bilirubin makes it unlikely that unconjugated bilirubin is formed and absorbed to an appreciable degree. The residual part of urobilinogen is further reduced to urobilin, stercobilin and dipyrrolmethenes and excreted in the faeces.

[Prostaglandin I2 (PG I2; prostacyclin) synthesis by human gastric mucosa (author's transl)]. / Prostaglandin-I2-(PG-I2-; Prostacyclin-)Synthese in der menschlichen Magenschleimhaut.

The human gastric mucosa generates prostacyclin (22 +/- 6 ng PG I2/g). There is no age or sex difference in PG I2 formation by normal gastric mucosa. The properties of the substance are the same as reported in other tissues.

[Influence of cimetidine, pentagastrin and somatostatin on prostacyclin synthesis of gastric mucosa in vitro]. / Einfluss von Cimetidin, Pentagastrin und Somatostatin auf die Prostazyklinsynthese der Magenschleimhaut in vitro.

In the presence of cimetidine, pentagastrin and somatostatin prostacyclin formation does not differ significantly from the value obtained with the buffer control, whereas cimetidine alone is able to inhibit ADP-induced platelet aggregation in vitro to a small degree. It is concluded that the in vivo action of the drugs if not primarily mediated by prostacyclin.

[Prostacyclin formation in human cancer tissue of the gastrointestinal tract (author's transl)]. / Prostazyklinsynthese menschlicher Tumoren des Gastrointestinaltrakts.

Prostacyclin synthesis was studied by means of bioassay in histologically classified biopsy material derived from the human gastrointestinal tract. Tumour tissue generated significantly more prostacyclin than normal tissue. Whether this enhanced PGI2 formation is due to an increased number of endothelial cells in tumour tissue, or represents a characteristic property of the tumour cell itself is not yet clear. This property could be used in future for the detection and control follow-up of malignant disease by means of radioimmunological determination of stabile metabolites as a tumour marker.

[Serum concentrations of thyroid hormones in severe non-thyroidal illnesses (author's transl)]. / Das verhalten von Schilddrüsenhormonkonzentrationen im Serum von Patienten mit schweren nichttyreoidalen Erkrankungen.

Pathologically low serum total triiodothyronine (T3) concentrations are a characteristic finding in patients with severe non-thyroidal illnesses. No adequate explanation has yet been offered for this phenomenon. We have, therefore, investigated the serum concentrations of total thyroxine (T4), total T3 and total 3,3',5'-triiodothyronine (reverse T3)--the metabolically-inactive metabolite of thyroxine--and of TSH in 13 patients with acute myocardial infarction, in 12 patients with compensated liver cirrhosis, in 9 patients with decompensated liver cirrhosis and in 15 patients with chronic renal failure on chronic intermittent haemodialysis by radioimmunoassay. The values obtained were compared to corresponding values of a normal control group (n - 23). According to our results the decrease in serum T3 combined with normal T4 concentrations in severe non-thyroidal illnesses seems to be a consequence of an alteration in thyroxine degradation. Two different possibilities of alteration can be considered: 1. inhibition of the overall deiodinationof T4, leading to low total T3 serum concentrations with concomitant normal to low reverse T3 serum concentrations (chronic uraemia), 2. a shift in the monodeiodination of T4 towards enhanced reverse T3 production, leading also to low total T3 concentrations, but with a concomitant increase in reverse T3 serum concentrations (myocardial infarction, liver cirrhosis). The results obtained in our patients with liver cirrhosis show, moreover, that this alteration of T4 metabolism depends on the severity of the illness.

[Prevention of hepatitis B by passive immunization of children with chronic hematologic disease immunoglobulin]. / Zapobieganie metoda biernej immunizacji zakazeniu wirusem zapalenia watroby typu B u dzieci chorych na przewlekle choroby krwi.

In order to prevent the hepatitis virus B (HBV) infection, in 66 children aged from 6 months to 14 years with acute and chronic leukaemias, Hodgkin's and non-Hodgkin's lymphomas, testicular tumours, and aplastic anaemia a specific immunoglobulin was used intravenously (Hepatect made by Biotest). Hepatect was given every month to children with proliferative diseases throughout the whole time of intensive chemotherapy, and to children with aplastic anaemias during the administration of antilymphocytic globulin, prednisone, and Anapoln. Fourteen children were excluded from the analysis due to lack of systematic follow-up. Among 52 studied children, in most cases considerable fluctuations were observed of antibody concentration, the maximal values of which were of 150 mIU/ml. In 35 children, with the exception of sporadic falls, the anti-HBs antibody level remained level was noted, in two cases the presence of antibodies was revealed only sporadically. One of these children was infected with HBV. In all, three children were infected (5.76% of all children in the studied group). Perhaps the use of higher doses of Hepatect and its more frequent administration in children showing low anti-HBs level after routine doses might reduce further the incidence of infection.

[Antibody-dependent cytotoxic activity of peripheral blood lymphocytes in healthy subjects]. / Zalezna od przeciwcial aktywnosc cytotoksyczna limfocytów krwi obwodowej u zdrowych osób.

A method of determining the cytotoxic activity of peripheral blood lymphocytes against Rh-positive erythrocytes labelled with 51Cr and sensitized with anti-D antibody is described. A measure of this activity was the cytotoxic index reflecting the intensity of erythrocytolysis, and expressed as per cent of released 51Cr. The method was applied in investigations of lymphocytes of 54 blood donors. The values of the cytotoxic index ranged from 60% to 94%, the arithmetical mean was 76 +/- 10%. The obtained results are an introduction to further investigations on changes of lymphocytes K in blood diseases.

[Evaluation of screening and complementary tests for anti-HCV antibodies]. / Ocena testów przegladowych i uzupelniajacych, sluzacych do wykrywania przeciwcial anty-HCV.

Screening for antibodies to hepatitis C virus (HCV) in blood donors by second generation tests was started on May 1991. On July 1992 obligatory testing of every blood or plasma donation was implemented. The incidence of anti-HCV evaluated in the first period (236.590 sera) was 1.4%. In the second period (296,573 sera) the incidence dropped to 0.9%. 489 sera repeatedly positive in screening were examined by a complementary test, 4-RIBA. Compatible positive results were obtained in 72.8% of the sera. 9.4% of the sera were negative and 17.8% gave indeterminate results. Reactivity was most frequently (95.7%) encountered to the structural core HCV peptide. The value of 4-RIBA was discussed. In conclusion, it was pointed out, that blood donors deferral should be based on repeated screening.

[Detection of light chains of warm-type autoantibodies in autoimmune hemolytic anemia with the aid of an autoanalyzer]. / Wykrywanie lancuchów lekkich autoprzeciwcial typu cieplego w niedokrwistosciach autoimmunohemolitycznych przy uzyciu autoanalizatora.

A method was evolved for detection of light chains of erythrocyte autoantibodies using a Technicon II AutoAnalyser with properly selected dilutions of bromelin and methylcellulose and anti-kappa and anti-lambda sera. It was demonstrated that the method is superior to the direct Coombs test because it made possible detection of one or both light chains in warm autoantibodies coating the erythrocytes of 20 patients with autoimmunohaemolytic anaemias in whom they could not have been detected by the manual method. It was found that in warm-type autoantibodies light chains can be detected always and that in some cases only one light chain is found.

[Serological markers of hepatitis B virus and cytomegalovirus in patients with hemophilia]. / Serologiczne znaczniki wirusa zapalenia watroby typu B i wirusa cytomegalii u chorych na hemofilie.

In 100 adult patients with severe haemophilia A (78 patients) and B (22 patients) sera were screened for the presence of serological markers of hepatitis B virus (HBV) and of cytomegalovirus (CMV) and liver function tests were performed which included measurement of serum aminotransferase AST and ALT activities, total bilirubin concentration and plasma levels of factor VII and X. In all the patients at least one out of five determined HBV markers (HBsAg. HBeAg, anti-HBs, anti-HBc and anti-HBe) was detected. HBsAg was found in 10% of the patients, and its prevalence in haemophiliacs B was higher than than observed in haemophiliacs A (22.7% and 6.4%, respectively). HBsAg appeared more frequently in patients receiving factor VIII concentrates (16.7%) than in those treated with cryoprecipitate (4.5%). Anti-CMV antibody was detected in sera of 98% of the patients. In 1/3 samples of cryoprecipitate anti-HBc or anti-HBs were present, and in the half of samples anti-CMV occurred. Abnormal liver function tests indicating chronic hepatitis or liver cirrhosis were obtained in 8 patients. Raised ALT activity which could suggest chronic infection with non-A, non-B virus occurred in 6 cases. The present study indicates that haemophiliacs frequently transfused with plasma products are at high risk for viral infections leading to liver dysfunction.