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Biomedical subjects

J Hermans

Publications and source records attributed to J Hermans.

At least 595 records · Page 33Linked to original sources

Splenectomy in hairy cell leukemia: a retrospective multicenter analysis.

To study the effect of splenectomy in hairy cell leukemia, we initiated a retrospective multicenter analysis. A series of 391 patients, contributed by 22 centers (median: 15 cases per center, range 2--130), was analyzed. Since comparison of the data from these centers showed few significant differences, the data were pooled. Factors that proved to have prognostic value at the time of diagnosis was significantly longer in the splenectomy group (n = 225) than in the nonsplenectomy group (n = 166) (P less than 0.0001). When subgroups were analyzed, no difference in survival time was found between splenectomized and splenectomized patients having an age greater than 60 years, symptoms greater than 12 months, spleens less than 4 cm under costal margin, hemoglobin levels greater than 12 g/dl, neutrophils greater than 500/mm3, or platelets greater than 100,000/mm3. After the operation, the platelet count usually increased to acceptable values, whereas the neutrophil count increased less often. Patients with Hb greater than 11 g/dl, neutrophils greater than 1,000/mm3, and platelets greater than 100,000/mm3 after splenectomy, survived longer than patients with a less complete response to the operation (P less than 0.01). In patients with definite splenomegaly and pancytopenia, splenectomy seems to be beneficial. However, in patients without distinctly enlarged spleens, other therapeutical modalities should be considered.

Adult↗

Structure of the fibrin protofibril.

We identified the two-stranded fibrin protofibril and studied its structure in electron micrographs of negatively stained specimens. Based on these images and on considerations of symmetry, we constructed a model of the protofibril in which the two strands of trinodular fibrin molecules are related by a two-fold screw axis between the strands and two-fold axes perpendicular to them. The two strands are held together by staggered lateral contacts between the central nodules of one strand and outer nodules of the other. The molecules within a strand are joined by longitudinal contacts between outer nodules. This interpretation of the structure of protofibrils is supported by images of trimer complexes whose preparation and structure are described here, in which the central nodule of a fibrin monomer is attached to the crosslinked outer nodules of two other molecules. We conclude that the association of protofibrils to form thicker fibers must involve a second type of lateral contact, probably between outer nodules of adjacent, in-register strands. In total, we identify three intermolecular contacts involved in the polymerization of fibrin.

Fibrin↗

Prospective double-blind clinical trial of bovine, human, and rabbit thromboplastins in monitoring long-term oral anticoagulation.

A prospective double-blind trial was performed to investigate the safety of long-term oral anticoagulant control when dosaged adjustment depends on the prothrombin times assessed with one type of thromboplastin being calculated as if assayed by another type. The three main types of thromboplastin, i.e., bovine (Thrombotest), human (British Comparative Thromboplastin), and rabbit (Simplastin Automated) were tested. Before entering the actual trial, patients had been checked with the bovine type of thromboplastin. During the actual comparison study, prothrombin times obtained with the human and the rabbit types of thromboplastin were translated, using the appropriate calibration data, into terms of the bovine type of thromboplastin, which were used for dosage prescription. After six months, all patients returned to bovine-type thromboplastin control. No substantial difference among the three groups was observed in the prothrombin times, the dosage of the anticoagulant, the bleeding complications, and the dropouts. It was concluded that the safety of monitoring patients receiving long-term oral anticoagulation was independent of the type of thromboplastin used.

Administration, Oral↗

Factor VII deficiency: immunological characterization of genetic variants and detection of carriers.

Twenty-one patients with congenital factor VII deficiency belonging to 16 different kindreds were investigated. The existence of three immunochemical variants on the ground of factor VII activity (VII:C) and factor VII-related antigen (VII:Ag) levels (VII-, VII+ and VIIR) was established. There was no correlation between the presence of factor VII:Ag and either the clinical picture or the specific function as studied with the Km calculations. Genetically the model of inheritance is the same whatever the immunological variant, but the identification of carriers is simplified when the presence of factor VII-related antigen is assayed throughout a kindred.

Antigens↗

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↗

Immunity to diphtheria, pertussis, tetanus, and poliomyelitis in children with acute lymphocytic leukemia after cessation of chemotherapy.

Antibody titers to diphtheria, pertussis, tetanus, and poliomyelitis (types I to III) were measured in previously vaccinated children with acute lymphocytic leukemia in remission after cessation of therapy. The response to revaccination one year after therapy was stopped was also studied. The patients' antibody titers were compared with those of healthy children, matched for age and sex. Two groups of patients were studied: one group (group A, N = 30) was given two drugs (6-mercaptopurine, methotrexate); the other group (group B, N = 19) was given three drugs (6-mercaptopurine, methotrexate, and cyclophosphamide) for maintenance treatment. In general, the patients' antibody titers were lower than those of healthy children, but in most patients they were still at levels considered to be protective. No significant differences in antibody levels between the two patient groups were found. A spontaneous rise in antibody titers in the first year after termination of therapy was not observed. After revaccination the rise in antibody titers was correlated with preexisting antibody titers in the same way in patients as in healthy children, and the antibody titers in patients and in healthy control subjects were on roughly the same level.

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↗

Fibrin assembly: a comparison of electron microscopic and light scattering results.

To test the validity of a proposed two step fibrin assembly mechanism and directly visualize the molecular species present at various stages of fibrin formation, we have carried out an electron microscopic investigation. Assembly conditions duplicated those of a recent light scattering study and specimens were prepared at different time points with the use of a negative staining technique recently employed to visualize the trinodular structure of fibrinogen. Under near-physiological buffer conditions, protofibrils structurally similar to those postulated by Ferry have been found at early stages of fibrin assembly. In parallel with the light scattering results, a dramatic increase in fiber diameter was found in specimens prepared during the postulated lateral association stage of gelation. Light scattering and electron microscopic results both showed that high ionic strength reduces the rate and extent of fiber formation. Reptilase cleavage is shown to result in typical cross striated fibrin.

Batroxobin↗

[Scintigraphy of biliary system (author's transl)].

Hepatobiliary functional scintigraphy (HBFS) using 99m Tc-labeled Diethyl-IDA was tested in 84 patients suffering from various hepatic and bile duct disorders. The investigated pathologies were: gall bladder dysfunction, parital bile duct obstruction, total obstruction, hepatocellular disease, cirrhosis and drug induced cholostastis. The diagnosis accuracy of the method was found to be 95 %, and the method proved to be useful for guiding the clinician in selecting those additional investigation techniques most apt to define the etiology of the pathological condition accurately. In conclusion, the non-invasive character of the technique, its usefulness even in the presence of elevated bilirubin levels and the information yielded by HBFS make it a method of choice to be placed in the beginning of the test series liver or duct patients are submitted to.

Acetates↗

Stability of international reference thromboplastins.

Long-term stability of the WHO International Reference Preparation (IRP) of thromboplastin 67/40 and of two secondary preparations, WHO IRP 68/434 and the Dutch RP 73/528 was assessed by two criteria on the basis of the basis of data obtained in the period 1969-79. The clotting times of normal plasmas determined with these preparations over this 10 year period did not show changes which were of practical importance. Moreover, the slopes of the lines relating clotting-time ratios of 67/40 to ratios obtained with 68/434 or 73/528 did not give any firm reasons to assume a systematic change of these slopes with time. These lines were determined by linear regression analysis of individual patient ratios. Corrections were applied to the original data for modifications of the assay technique made during the past 10 years.

Blood Coagulation Tests↗

Assembly of fibrin. A light scattering study.

Using stopped flow light scattering, we show that assembly of fibrin following activation with non-rate-limiting amounts of thrombin or reptilase occurs in two steps, of which the first is end-to-end polymerization of fibrin monomers to protofibrils and the second is lateral association of protofibrils to fibers, in agreement with Ferry's original proposal. Polymerization is found to proceed as a bimolecular association of bifunctional monomers; the overall rate varies as the inverse first power of the concentration; end-to-end association of two monomers, of a monomer and an oligomer, and of two oligomers occurs with the same rate constant. The value of the rate constant is 8.2 C 10(5) M-1 s-1 in 0.5 M NaCl, is three times larger in 0.1 M NaCl (0.05 M Tris, pH 7.4), and is the same following activation by reptilase and by thrombin. The onset of growth of fibers from protofibrils takes 12 times longer in 0.5 than in 0.1 M salt, i.e. thick fibers ("coarse" gels) form from short protofibrils, and thin fibers ("fine" gels) form from longer protofibrils. Jumps of salt concentration at times when protofibrils, but not fibers, have formed result in immediate growth of thick fibers at low salt from long protofibrils formed at high salt. The rate of fiber growth in these experiments varies as the inverse first power of the concentration. 3the instant of gelation (formation of a network of fibers) falls in the later half of the time during which the scattering rises due to fiber growth; the rise of gel rigidity after gelation is found to continue beyond the end of this period. Jumps from low to high salt result in retention of whatever fibers have formed at low salt and a very small additional increase of the scattering due to further fiber growth at high salt. From a variety of evidence, we conclude that the properties of fibrin are determined by kinetics and not equilibria of assembly steps. Results obtained here agree with the following scheme of fibrin assembly: monomers polymerize to protofibrils; long protofibrils associate laterally to fibers; occasionally a long protofibril associates with two different fibers to form an interfiber connection; fiber growth does not reverse to yield stabler, more compact, structures and terminates in formation of a network of fibers. The typical delay of fiber growth is the time during which protofibrils form from monomers. Measurements at rate-limiting concentrations of thrombin have allowed estimation of turnover rates of fibrinopeptides that agree with kinetic parameters obtained with direct assay of fibrinopeptide. Release of fibrinopeptide B causes more rapid fiber formation. Addition of thrombin after activation by reptilase, at a time when protofibrils, but not fibers, have formed, is followed rapidly by fiber formation; this proves that thrombin readily removes fibrinopeptide B from protofibrils. On the basis of these new results and earlier work (in particular, Blombäck, B., Hessel, B., Hogg, D., and Therkildsen, L...

Enzyme Activation↗

Detection of an abnormal plasma clot structure by a simple rigidity assay.

We report here on a patient whose abnormal fibrin clot was detected via the measurement of clot rigidity with a simple buoyant inner cylinder elastometer. The patient's clinical coagulation studies were all within normal limits except for prolonged thrombin and reptilase clotting times and high level of fibrin split products. The measured rigidity of the patient's clot was approximately ten times lower than that of a clot formed from normal pooled plasma. Light scattering studies indicated that this modified structure was not caused by a gross change in gel fiber morphology. Antithrombin activity was eliminated as a possible cause of the altered clot structure; this suggests the possibility of a modified fibrinogen. Abnormalities in the reptilase time and fibrinogen levels in two siblings support the hypothesis that the modification is an inherited defect. We suggest that the simple measurement of rigidity can be used rountinely to detect abnormalities in plasma clot structure. The screening for such disorders should be of importance to clinician, patient, and biochemical researcher.

Aged↗