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Biomedical subjects

H L Haak

Publications and source records attributed to H L Haak.

At least 55 records · Page 3Linked to original sources

The in vitro growth pattern of human bone marrow in methylcellulose stimulated by different concentrations of conditioned medium.

The proliferation of human bone marrow in methylcellulose stimulated by various concentrations of conditioned medium (CM) and observed at various intervals was studied. The growth kinetics of granulocytic aggregates was found to differ from monocytic clusters and colonies. Granulocytic aggregates showed a consistent and reproducible dose-response relationship; at day 7, the maximum number of granulocytic aggregates was found at 4% CM. At higher levels, the total number of aggregates decreased, while the number of cells per aggregate increased. The number of macrophage aggregates was far less, depending on the CM concentration. Photographic interval studies showed that at high concentrations of CM, clusters and colonies were formed earlier, but also coalesce to form one colony. Our results suggest that the proliferation kinetics of granulocytic aggregates are complex and preclude simple statements about sensitivity to colony-stimulating activity.

Bone Marrow↗

Immunological investigations in aplastic anemia patients.

In 53 patients with aplastic anemia (AA) a number of parameters concerning immune responsiveness were analyzed. Severe monocytopenia and B-lymphocytopenia was detected in most patients, especially in those with diffuse lymphocyte infiltration in the bone marrow. T-inducer (OKT4)/T-suppressor (OKT8) ratios were normal. The mean IgG level was significantly decreased. The frequency of specific antibodies to common viruses was comparable to that of healthy donors except for cytomegalovirus to which antibodies were less frequently found. The responding capacity in MLC was normal but patients' lymphocytes were often less stimulating than control lymphocytes. Radioresistant suppressor cells were found in 1 patient. In vitro lymphocyte reactivity to mitogens and antigens was severely impaired, related to the numbers of monocytes present. When allogeneic monocytes were added, mitogen responses could be restored.

Anemia, Aplastic↗

The factor VIII ratio in normal and pathological pregnancies.

The factor VIII ratio was measured in 102 pregnant women (43 uncomplicated pregnancies, 19 with pre-eclampsia without fetal growth retardation, 8 pre-eclampsia complicated by fetal growth retardation, 12 with only fetal growth retardation and 20 with gestational diabetes). The pathological pregnancies showed a statistically significant elevation of the factor VIII ratio compared to the normal pregnancies. The group of pre-eclampsia complicated by fetal growth retardation showed the most marked increase of the factor VIII ratio. The results are discussed in relation to the hypothesis that the elevated factor VIII ratio is mainly due to the release of factor VIII antigen by various forms of vascular stress.

Antigens↗

Teratoma of the lung in a hemophilic patient.

We describe a patient with hemophilia A and primary malignant teratoma of the lung. Hemothorax and pseudotumor in hemophilia are rare disorders and can raise many differential diagnostic problems.

Adult↗

Busulphan aplasia in rabbits: a model for human aplastic anaemia.

Bone marrow histology plays a crucial role in the clinical diagnosis of aplastic anaemia. The nature of the disease means that few studies are available on the histological changes which occur in the early stages of the development of aplasia. We describe here an animal model which may have some relevance in this respect. Rabbits were chronically exposed to busulphan (BU) to induce aplasia. Sequential histological monitoring of the bone marrow was performed to obtain information about the events preceding full-blown aplasia. There was an early decrease and ultimate disappearance of granulo- and megakaryopoiesis with relative sparing of erythropoiesis which showed severe displasia. Increasing lymphoplasmacytoid infiltrate resembling that seen in human aplasia could be observed in the majority of the animals, together with a decrease of the peripheral lymphocyte number. Lymph nodes and spleen did not show lymphocyte depletion and serum gamma-globulin remained stable. Fibrosis was observed in 50% which is in contrast with human aplasia at diagnosis. In half of the animals there was a rise in MCV, which was not correlated with reticulocytosis or degree of dyserythropoiesis. BU-induced aplasia in rabbits, which resembles long-standing grade II human aplasia in many respects, might be a suitable model for the study of aplastic anaemia due to stem cell defects.

Anemia, Aplastic↗

Anti-thymocyte globulin treatment for aplastic anemia.

20 patients with severe aplastic anemia were treated with anti-thymocyte globulin (ATG), 6 of them in combination with haplo-identical bone marrow. 7 patients (35%) showed a good clinical response within 6 months; they were off transfusions and had greater than or equal to 0.8 x 10(9)/l neutrophils. ATG had the greatest effect on red-cell production and the least on platelet production. The hematological recovery with ATG could not be predicted from the bone-marrow histology, CFU-c growth, or clinical data. However, patients with strong HLA antibodies seemed to respond more often. The actuarial survival was 55% at 5 years. Under intensive supportive care, even 7 out of 12 non-responders were alive after 1 year. ATG appears to be a useful form of therapy for patients with severe aplastic anemia who are not candidates for bone-marrow transplantation.

Adolescent↗

Inhibition of CFUE and BFUE by mononuclear peripheral blood cells during chronic benzene treatment in rabbits.

Peripheral blood cells from untransfused rabbits that were treated with a moderate dose of benzene during 2 months were cocultivated with autologous and normal bone marrow. In a significant number of experiments, CFUE and BFUE growth of both autologous and normal bone marrow was suppressed. Further experiments showed that this inhibition was associated with adherent mononuclear peripheral blood cells. It is concluded that benzene, an established myelotoxic agent, also induces CFUE and BFUE inhibiting activity in adherent peripheral blood cells.

Animals↗

Anti-thymocyte globulin (ATG) can eliminate platelet refractoriness.

Of the 14 patients with aplastic anaemia treated in our hospital with anti-thymocyte globulin (ATG), four were refractory to random platelets before therapy due to the presence of leucocyte antibodies. In contrast to the ten nonrefractory patients in whom no success was obtained, three of the four refractory patients showed haematological improvement after ATG. Additionally, two patients could be substituted again with random platelets. The other two hardly needed platelet-transfusions after ATG, and they were given HLA-compatible platelets. To determine the degree of immunosuppression, these four patients were tested for the presence of antibodies against leucocytes and two endemic viruses, i.e., mumps and rubella virus. Before ATG, all sera reacted with almost the whole leucocyte testpanel. After treatment, the leucocyte antibodies disappeared completely in three patients. In one patient there was no dramatic change. In all patients, however, the antibody-titre against the mumps and rubella viruses remained constant and there was only a slight decrease in total IgG content in the three "suppressed" patients. We conclude that it might be worthwhile to study systematically the selective immuno-suppressive effect of ATG.

Adult↗

111Indium-chloride bone marrow scintigraphy in aplastic anaemia.

Bone marrow scintigraphy, using 111Indium-chloride, was performed in 24 patients with acquired aplastic anaemia to investigate: (1) a possible relationship between bone marrow scintigraphy and peripheral blood cell values, (2) a possible relationship between scintigraphy and histology of the bone marrow and (3) the ability to distinguish various aplastic anaemia subtypes with bone marrow scintigraphy. For this purpose a semi-quantitative scoring of scintigraphic results was used. Only a weak correlation was found between the radionuclide studies and blood counts. It appeared that an abnormal 111In-scintigraphic activity in the pelvis was related to an abnormal quality and quantity of haematopoietic tissue. To study a correlation with histological subtype grading, the patients were grouped in 4 categories based on clinical-histological results. Thus it could be demonstrated that the presence of 111In-activity in long bones ('scintigraphic extension') is an important parameter in distinguishing patients who are believed to suffer from a primary stem-cell defect, from patients who may suffer from an auto-aggressive disorder.

Adolescent↗

Scintigraphic aspects of 111In-chloride bone marrow scintigraphy in aplastic anaemia.

In 25 patients and 11 follow-up studies the clinical usefulness of bone marrow scanning with 111In-chloride in aplastic anaemia is evaluated. Semi-quantitative scanning of bone marrow scan results and the presence of bone marrow extension have proven to be helpful in monitoring the disease and determining aetiological factors. This study shows that 111In-chloride is able to demonstrate regional difference in the bone marrow status of the patient suffering from aplastic anaemia, thereby offering a useful alternative for iron radionuclides.

Adolescent↗

Extreme potassium loss in a patient with severe graft versus host disease.

A 19-year-old male, suffering from post-hepatitis aplastic anaemia, was transplanted with bone marrow cells from his HLA-identical, MLC non-reactive brother. Haematological recovery ensued, but the patient also developed grade IV graft-versus-host disease (GVHD). In addition to involvement of skin, liver and gut, the kidney seemed affected by GVHD since the patient has hypokalaemia and severe hyperkaluria. Other causes of urinary potassium loss were excluded. The amount of potassium loss correlated well with the severity of the GVH-reaction. Although coagulation disorders prohibited a kidney biopsy, the clinical course suggested GVHD to be the cause of the urinary potassium loss.

Adult↗