Biomedical subjects
Publications and source records attributed to G Lanzer.
Low basal hemoglobin and functional iron deficiency are the limiting factors in autologous blood donation program. Treatment with recombinant human erythropoietin can increase the volume of autologous blood and makes donation of > or = 3 units possible-even in patients with low basal hemoglobin. Best results are obtained if stimulation begins already one week before first donation.
One drawback of a 'medium resolution' generic dotblot oligonucleotide typing of the HLA-DRB locus has been the time consuming evaluation of the collected SSO-hybridisation datas. We developed a program on the basis of MS-ACCESS, written in visual basic, called HIDE (HLA Intelligent Data Evaluation) to manage this problem. HIDE offers a complete data management for the donor and the incoming sample, supports a membrane based data entry of the hybridisation-reactions and multiple testing of a sample. If an evaluation shows more than one matching allele combination, the result is summarized according to the main DRB-groups. The flexible structure of the program allows the entry of additional allelspecific reaction-patterns as well as the adaption to different SSO-typingsets.
The safety of blood and blood components is an important aspect of transfusion medicine. Even if absolute safety of blood products cannot be achieved, this goal has come closer due to significant improvements. These include: (1) exact donor registration; (2) component preparation according to legal requirements and GMP guidelines; (3) determination of all relevant diagnostic parameters according to GMP/GLP guidelines; (4) adequate storage of products; and (5) and often underestimated parameter ensuring safety, strict guidelines for the use of blood products in the treatment of patients. Some of the results of the first Graz Consensus Conference on Transfusion Medicine are presented.
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BACKGROUND: Hepatitis C virus (HCV) is responsible for the majority of post-transfusion hepatitis cases. We compared the correlation and reproducibility of different screening and confirmatory tests. MATERIAL AND METHODS: 1,406 samples of voluntary blood donors were tested in parallel using 3 enzyme-linked immuno sorbent assays (ELISA) for HCV antibodies. Those samples that were positive in at least 1 of the 3 tests were additionally tested in a 3rd-generation ELISA as well as in 3 different confirmatory tests. RESULTS: 13 samples (0.92%) were repeat reactive in at least 1 of the ELISAs with different results in the confirmatory tests. Only 3 samples (0.21%) with high sample/cutoff ratios in the ELISAs were positive in all 3 confirmatory tests. CONCLUSIONS: The reproducibility of the tested ELISAs and the correlation with confirmatory tests were good only in samples with a high signal to cutoff ratio. Two different high-positive ELISA results can be regarded as confirmation.
The typing results of 212 dialysis patients could be improved by 13%, using polymerase chain reaction and hybridization with SSOs for defining HLA DR B polymorphism. So far 19 organ donors were also typed using a more rapid method: PCR with SSP.
Small numbers of leukocytes cannot be counted by automated methods. So we performed fluorescent staining of leukocyte DNA and analyzed 50 samples of single-donor PC by FACS. In 72% of these PC we found white blood cells (WBC) < 5/microliter = WBC < 10(6)/U. Nevertheless we do filter our PC. Should fresh frozen plasma (FFP) be irradiated for immunocompromised patients to prevent TA-GvHD? To evaluate the number and distribution of WBC in FFP we stained WBC with moAb and performed FACS analyses. We found WBC 7.164 +/- 5.66 x 10(6)/U, lymphocytes, 3.032 +/- 3.66 x 10(6)/U and T lymphocytes 2.135 +/- 2.02 x 10(6)/U. According to these data it should be considered to irradiate FFP for immunocompromised patients.
In vitro aggregation of stored platelet concentrates is significantly influenced by high platelet counts and the resulting metabolic changes. The definition of an optimal platelet count seems to be of marked importance for platelet storage and functionality.
This study describes clinical experience with a rapid method for diagnosis of cytomegalovirus infection in organ-transplanted patients, based on the detection of CMV-specific antigens in peripheral polymorphonuclear cells with a mixture of monoclonal antibodies. This CMV-pp65 assay was formerly called the "CMV immediate early antigen assay." A group of 180 organ-transplanted patients were examined with this assay; 75 of them could be observed from the date of transplantation. These 75 patients consisted of two groups: 59 kidney transplant patients receiving no CMV hyperimmunoglobulin prophylaxis (group I), 13 heart-transplanted patients, and 3 liver transplanted patients receiving prophylaxis (group II). Group III consisted of 105 patients who had been transplanted ca. 2 years before starting this study. In group I, 26 (44%) were CMV-pp65-positive (13 primary and 13 secondary infections). Fifteen of these 26 (58%) positive patients showed clinical symptoms of CMV infection. Eleven of these 15 (73%) were primary infections. Symptomatic patients had significantly more CMV-pp65-positive cells than asymptomatic patients; 12 patients showed a high number of positive cells and 11 of them developed severe CMV illness. Thirty-three patients were CMV-pp-65-negative (22 CMV IgG-sero-positive, 11 CMV IgG-seronegative). None of them had symptoms of CMV infection. In all patients of group I there were 36 periods of graft dysfunction in which CMV infection had to be differentiated from transplant rejection. In 10 out of 36 there was a CMV-pp65-positive test result and subsequent seroconversion. Treatment of viral infection resulted in improvement of clinical problems. In the remaining 26 episodes no CMV-pp65-positive cells were detected: in 17 cases graft dysfunction was caused by rejection, in 9 cases by other complications. In group II, 13 of 16 patients (81%) were positive in the CMV-pp65 assay (6 primary infections, 7 secondary infections). However, none of them showed clinical signs of CMV infection, regardless of the number of positive cells. No CMV-related graft dysfunction was observed. In group III, CMV infections did not play an important role. The experiences described suggest that this test is a valuable tool in early CMV diagnosis and in differentiating CMV-dependent graft dysfunction from other graft dysfunctions. It allows prompt therapeutic intervention.
OBJECTIVE: We assessed the effect of levothyroxine or iodine on thyroid size and on thyroid growth stimulating immunoglobulins in endemic goitre patients. DESIGN: Levothyroxine or iodine was given orally in an open randomized prospective study (100 and 200 micrograms respectively). PATIENTS: Thirty-seven euthyroid patients with diffuse iodine deficiency goitres and thyroid growth stimulating immunoglobulins were studied. MEASUREMENTS: Thyroid size, thyroid growth stimulating immunoglobulins (mitosis arrest assay), basal TSH, free T3, free T4, thyroid anti-microsomal antibodies, antithyroglobulin antibodies, anti-TSH receptor antibodies and urinary iodine excretion were measured. RESULTS: Thyroid size decreased significantly in both groups, in the levothyroxine group more than in the iodine treated group. Thyroid growth stimulating immunoglobulins levels also decreased significantly in both groups. Between groups there was no statistically significant difference. A statistically significant correlation between thyroid growth stimulating immunoglobulins reduction profiles and goitre size reduction could not be established. TSH levels became suppressed in the levothyroxine group while the T4 values rose; in the iodine treated group TSH levels stayed constant as did T4. None of the patients developed thyroid microsomal or thyroglobulin auto-antibodies and/or hyperthyroidism during the treatment. CONCLUSIONS: Levothyroxine as well as iodine was effective in reducing thyroid size as well as thyroid growth stimulating immunoglobulins levels in endemic goitre patients. Since in both groups TSH levels were not related to thyroid size reduction, other factors than TSH suppression must be responsible for the observed thyroid size reduction. Iodine itself by virtue of its antiproliferative action on thyrocytes may have had a direct action on the goitre reduction during iodine treatment; however, the levothyroxine dose, containing less iodine, had a similar effect. A complicated picture hence emerges with regard to factors involved in the shrinkage of iodine deficiency goitre during thyroxine or iodine therapy. These findings indicate that TSH and thyroid growth promoting immunoglobulins are not the only influences on the size of endemic goitres, although it cannot be excluded that these two factors contribute to influence the pathogenetic process.
The evaluation of a new Walkaway instrument (Behring Elisa Processor III) for testing HBsAG, anti-HCV and anti-HIV 1/2 in three blood transfusion services with different sample volumes (from 60,000 to 450,000/year) gave the following results: the instrument fulfills the promises of being a real Walkaway system under routine conditions, saving labor and gaining security. The instrument must work in agreement with GLP rules, and all test steps are documented. The organization of the laboratory becomes more transparent and less flexible.
Allogeneic bone marrow transplantation (BMT) was carried out on a 34-month-old boy with congenital sideroblastic anemia. The patient had been red blood cell transfusion dependent since the age of 7 weeks. He did not respond to therapy with pyridoxine and developed secondary progressive hemosiderosis. The preparatory regimen consisted of busulfan (3.5 mg/kg for 4 days) and cyclophosphamide (50 mg/kg for 4 days). Full engraftment of donor bone marrow was achieved and effective hemopoiesis is still maintained 3 years after BMT.
Regional variations in the human leucocyte antigen (HLA) distribution patterns of coeliac disease (CD) have been reported. This study focuses on phenotype frequencies of a cohort of Austrian paediatric CD patients in comparison with those recorded in the literature. HLA class I and II typing was performed in 136 CD patients and 667 healthy controls from the general population of the same geographical area. The HLA phenotypes of our controls agreed with those published for Caucasians. In our patients the relative risks (RR) were 6.43 for DR3 and 2.52 for DR7, the aetiologic fractions being 0.58 respectively 0.24. The highest RR (7.78) was found for DR3/DR7 heterozygotes. The RR for DR5 was increased in heterozygosities, either with DR3 (3.34) or DR7 (5.53), yet not for DR5 alone. Of our patients, 10% were lacking both DR3 and DR7 as well as B8, 82% of them were positive for DQw3. In these DR3 and DR7 negative patients, DR4 and DR5 were significantly more frequent than in the others. DR5 was also significantly more common in these patients compared to controls lacking the same antigens, whereas this did not hold true for DR4. Prospective studies are required to determine any link between these HLA heterogeneities and long-term progression of the disease.
A strain of differentiated rat thyroid cells (FRTL5) in continuous culture was used to study the presence of thyroid growth-promoting immunoglobulins (TGI) in the serum of patients with endemic and sporadic euthyroid goiters. To identify true in vitro cell proliferation a microscopic mitotic arrest assay was used. Immunoglobulins G (IgGs) were prepared with QAE-Sephadex A-50 or protein-A-Sepharose. A positive growth stimulation index was found in IgG preparations of 65 of 71 patients with endemic goiter and in 9 of 14 IgG preparations of patients with sporadic goiter. IgG preparations of 15 control subjects from an area where endemic goiter due to iodine deficiency does not occur and of 18 subjects without iodine deficiency and without thyroid enlargement living in the endemic area did not stimulate FRTL5 cell growth. FRTL5 cell growth stimulation with IgGs of these euthyroid goiter patients could only be detected when IgG was tested in combination with a small dose of TSH. Immunoprecipitation with polyclonal and monoclonal antihuman IgG was able to abolish the growth-promoting effects. In 32 blinded samples the Feulgen cytobiochemical assay, formerly used to detect TGI, was compared with the FRTL5 mitotic arrest assay. The two methods showed similar results. Our observations of chromatographically purified IgG promoting thyroid cell proliferation in vitro provide good evidence that IgG was responsible for thyroid cell growth in vitro and suggest that autoimmune growth mechanisms may be involved in the pathogenesis of both endemic and sporadic goiters.
In this study a strain of differentiated rat thyroid cells in continuous culture was used to detect the presence of thyroid growth promoting immunoglobulins (TGI) in IgG preparations of serum of patients with endemic and sporadic euthyroid goiters. TGI was detected when FRTL5 cells were used in a mitotic arrest assay by costimulating the cells with IgG and a suboptimal dose of TSH. TGI was present in 65 of 71 endemic goter cases and in 9 of 14 sporadic goiter cases.
This study describes dendritic cells in thyroid sections of iodine deficient goiters. Cells were characterized by monoclonal markers and detected by immunohistochemistry and double labelling immunofluorescence. We observed dendritic cells located in focal aggregates in the interstitium and epitheloid cells as well as multinucleated giant cells filling thyroid follicles. All these cells showed strong positivity for the MHC class II molecules HLA-DR, -DQ, -DP and RFD1, a monoclonal marker for active antigen presenting cells.
Immunohistochemistry and immunofluorescence were performed on thyroid sections of 44 consecutive patients undergoing thyroid surgery for goiter due to iodine deficiency. Sections were compared with specimens from ten individuals without goiters from the same endemic area, with specimens from ten sporadic nontoxic goiter patients, and with specimens from an area with sufficient iodine supply from nine healthy subjects. Cells were characterized using monoclonal antibodies to the CR3 receptor (CD11b) and the p150/95 antigen (CD11c) present on macrophages, to HLA-DR, to antigen presenting cells (RFD1), to T helper (CD4) and to T suppressor/cytotoxic cells (CD8), and with a polyclonal antibody to human cytokeratin. In iodine deficient goiters, focal aggregates were found of RFD1-positive dendritic cells. Furthermore, RFD1-positive epitheloid cells were seen. In 27% of cases, these epitheloid cells completely filled the thyroid follicles. Within the epitheloid cell clusters, multinucleated giant cells could be detected that carried the macrophage markers. Dendritic cells, epitheloid cells, and giant cells were strongly HLA-DR positive. In nongoitrous thyroids from the endemic area such aggregates could also be seen but they were more sparse and were RFD1 negative. Giant cells were absent there. In normal thyroids with sufficient iodine supply, only a few isolated dendritic cells were seen. All except RFD1, which was negative, showed the same marker pattern. In sporadic nontoxic goiters from an area with sufficient iodine supply, dendritic cells occurred in much higher numbers than in the normal thyroids from that area, and they were RFD1 positive. They never aggregated as in iodine deficiency, and giant cells were not observed. These observations on iodine deficient goiter strongly suggest involvement of active antigen-presenting cells in this disorder. However, the immunohistologic difference between this disease and sporadic goiter suggests different underlying mechanisms.
An acute midbrain syndrome III/IV developed twice after tetanus immunization. The occurrence of nearly identical episodes was remarkable, as well as the relatively rapid return to normal consciousness and neurological status after deep coma. Special emphasis is placed upon the chronological relationship of the coma to the immunization and upon immunological tests (tetanus antibody titres) performed to confirm the diagnosis.