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Biomedical subjects

J J Veltkamp

Publications and source records attributed to J J Veltkamp.

At least 19 recordsLinked to original sources
PubMed1985

The functional defect of factor VIII Leiden, a genetic variant of coagulation factor VIII.

Factor VIII Leiden is a genetic variant of coagulation factor VIII which has been detected in the plasma of a patient with mild haemophilia A. In this patient's plasma factor VIII procoagulant antigen was in 5-fold excess over factor VIII procoagulant activity, indicating the presence of an abnormal factor VIII molecule. The variant factor VIII was isolated from the patient's plasma, and its functional properties were studied in a factor X-activating system consisting of purified components. The isolated factor VIII Leiden was normally activated by factor Xa and by thrombin, but the activity of the factor VIIIa was about 3% of normal. The defect of factor VIIIa Leiden was studied by comparison with normal factor VIIIa in kinetic experiments of factor Xa formation. The results support the hypothesis that factor VIIIa Leiden has a reduced affinity for phospholipid-bound factor IXa in the intrinsic factor X-activating complex.

Calcium↗
PubMed1985

Carrier detection of haemophilia B by using an intragenic restriction-fragment length polymorphism.

We analysed DNA from individuals of five families with haemophilia B, including nineteen potential carriers. A gene-specific probe was used to reveal a TaqI restriction-fragment length polymorphism. Segregation analysis of the polymorphic marker and the deleterious mutation within families allowed diagnosis at the gene level for 16 out of the 19 potential carriers, two proving to be carriers and 14 non-carriers. The obvious advantage is that lyonisation, which is a limiting factor when gene product (clotting factor IX) measurements are used for carrier detection, does not interfere with this procedure and that the result is a definitive diagnosis instead of a risk estimate. The method also permits prenatal diagnosis on chorionic villi in the first trimester of pregnancy. Restriction-fragment length analysis, based upon the probe and restriction enzyme used in this study, will be informative for approximately 45% of the individuals at risk of carrying or transmitting the haemophilia B mutation.

DNA Restriction Enzymes↗
PubMed1985

Intermediate and high-dose ARA-C and m-AMSA (or daunorubicin) as remission and consolidation treatment for patients with relapsed acute leukaemia and lymphoblastic non-Hodgkin lymphoma.

27 patients (aged 15-55 years) with relapsed acute myelogenous (AML) and lymphoblastic leukaemia (ALL), and with lymphoblastic non Hodgkin's lymphoma (NHL) have been treated with intermediate dose cytosine arabinoside (AraC, 1 g/m2 q 12 h X 12) and 3 d of m-AMSA (20 patients), 90-115 mg/m2 daily, or daunorubicin (7 patients). 18 of them attained a complete remission (AML 10/14, ALL 3/5, NHL 5/8). 7 patients received consolidation treatment with 1-2 courses comprising 4 d of AraC (3 g/m2 q 12 h X 8) and m-AMSA (90-115 mg/m2) on d 5 of each course. 2 patients underwent allogeneic bone marrow transplantation and 9 received no further treatment after remission induction. In addition to vomiting, fever and conjunctivitis, toxicity in 6 patients included a combination of severe diarrhoea, fever and signs of paralytic ileus. 3 of them died during the pancytopenic phase. The pancytopenic period ranged from 16-25 d (median 21 d) after the remission induction and 14-21 d (median 19 d) after the consolidation course. Median remission duration was 5 months for those patients who received no treatment after remission induction and greater than 9 months (4+ - 16+ months) for the patients who received consolidation courses. Increased dosages of AraC are active in relapsed leukaemia and lymphoma, although optimal dose and schedule are still undetermined.

Adolescent↗
PubMed1985

Coagulation factors in the premature infant born after about 32 weeks of gestation.

In plasma samples from 10 premature infants born after about 32 weeks of gestation, a number of coagulation factors have been determined. For 9 infants, who were healthy, mean values are given: fibrinogen-antigen, 311 mg/dl; factor II, +/- 0.46 U/ml; factor V, 0.80 U/ml; factor VII, 0.59 U/ml; factor VIII coagulant activity, 0.93 U/ml; factor VIII-related antigen, 1.66 U/ml; procoagulant factor VIII antigen, 1.15 U/ml; factor IX coagulant activity, 0.41 U/ml; factor IX antigen, 0.42 U/ml; factor X coagulant activity, 0.52 U/ml; factor X antigen, 0.61 U/ml, and antithrombin III-antigen (AT-III), 0.43 U/ml. In 5 infants a second sample was taken a week after the first one; for most values there was no significant rise, except for factor II and AT-III. The values we found in this group of premature infants are within the range of those reported in earlier literature. They are higher than the ones we found in early fetal samples and most of them are similar to those we found in early fetal samples and most of them are similar to those we found in the cord blood of full-term newborns.

Blood Coagulation Factors↗
PubMed1979

Metabolism of the coagulation factors of the prothrombin complex in hypothyroidism in man.

The metabolic rate of prothrombin, factors VII, IX and X, was studied in nine hypothyroid patients. Disappearance rates of the four vitamin-K-dependent factors, called the prothrombin complex, were measured after assumedly complete blocking of their synthesis with adequate doses of a coumarin congener (acenocoumarol). Reappearance rates were assessed by induction of synthesis with high doses of vitamin K1 (phytomenadion) when stable hypocoagulability had been achieved. Normal values for these rates were derived from earlier studies in our laboratory. In hypothyroid patients the rates of both disappearance and reappearance were significantly slower for all factors tested. Practical consequences of these observations are discussed. The initial level of factor-IX activity in all nine patients was substantially lower than in normal individuals. Therapy by thyroxine-substitution led to normal levels of factor-IX. This implies a divergency in the retardation of the breakdown and production rates in hypothyroidism. The reappearance rate was indeed found to be more retarded than the disappearance rate.

Adult↗
PubMed1979

Detection of carriers of haemophilia B.

Plasma levels of factor IX activity and factor IX antigen were determined in 18 definite carriers of haemophilia B-, 10 definite carriers of haemophilia B+ and 40 control subjects. Factor IX antigen was determined by the electroimmunoassay technique of Laurell using a rabbit antiserum against factor IX. In haemophilia B-, statistical tolerance regions were constructed containing 90% of the factor IX activity and factor IX antigen values for the carriers and the control subjects. Of the 18 carriers, 10 were outside the tolerance region for the control subjects, and of the 40 control subjects, 17 were outside the tolerance region for the carriers. A better separation of the probabilities of being a carrier was obtained for the B- carriers and the control subjects when factor IX antigen was determined in addition to factor IX activity. In haemophilia B+, factor IX antigen was present in excess of factor IX activity in nine of the 10 carriers. The values for factor IX activity and factor IX antigen for these nine carriers fell outside the 90% tolerance region for the control subjects. It is concluded that the quantitative determination of factor IX antigen may be of value in the detection of carriers of both haemophilia B+ and haemophilia B-.

Adult↗
PubMed1979

A genetic variant of factor IX with decreased capacity for Ca2+ binding.

A genetic variant of factor IX is described that behaves identically to PIVKA/IX (the precursor factor IX molecule induced by the absence of vitamin K or presence of vitamin K antagonists, acarboxy factor IX). It shows an increased electrophoretic mobility in the presence of Ca2+, a low affinity for adsorption to A1(OH)3 and a very low specific coagulant activity. This variant of factor IX has been demonstrated in the plasma of a patient with severe haemophilia B and in the plasmas of a number of possible carriers from the probands' pedigree.

Binding Sites↗
PubMed1978

The abnormal factor IX of hemophilia B+ variants.

A rather large proportion of the hemophilia B patients can be characterized as hemophilia B+ because of the presence in their plasma of a protein which is immunologically identical with human factor IX. In a group of 33 hemophilia B patients we found 14 cases of hemophilia B+ belonging to 11 independent pedigrees. The variant factor IX molecules of these families have been compared with respect to the following properties: 1) factor IX activity and its dependence on phospholipid concentration; 2) factor IX antigen; 3) prolongation of prothrombin time with an ox brain thromboplastin; 4) electrophoretic mobility; 5) Ca(+) binding capacity; 6) affinity for binding to heparin and 7) susceptibility of the factor IX antigen to contact-induced activation. In the study of these parameters the use of a precipitating antibody against highly purified human factor IX showed to be of great value. According to our criteria at least 7 different factor IX variants were present in the 11 families with hemophilia B+ studied. Because of this rather high heterogeneity a suitable nomenclature for subclassification of hemophilia B+ variants is proposed.

Antigens↗
PubMed1978

Acquired antithrombin III deficiency and thrombosis in the nephrotic syndrome.

Antithrombin III levels were studied in relation to the occurrence of thromboembolism in 48 patients with various degrees of proteinuria. Nine of these patients had clinical signs of thrombosis, including four with renal vein thrombosis. In eight of these nine patients, antithrombin III concentrations were below 70 per cent. There was a significant negative correlation between the antithrombin III concentration and the urinary protein excreation (P less than 0.001). Antithrombin III was found in the urine of 32 of 42 patients. There was a significant correlation between the renal clearance and the degree of antithrombin III serum deficiency (P less that 0.001). The clearance and serum level of albumin closely paralleled these changes. We conclude that thrombosis in patients with severe proteinuria is associated with a deficiency of antithrombin III due to urinary excretion of this protein.

Adolescent↗
PubMed1978

Head injury and coagulation disorders.

Coagulation studies (plasma fibrinogen, ethanol gelation test, and fibrin/fibrinogen degradation product concentration) were done in 150 patients who were admitted after blunt head injury. Results were abnormal in 60 patients and were found to be correlated with the level of consciousness and with the presence of neurological signs. Many of these patients had fractures, but findings in a control group of 26 patients with major fractures without head injury indicate that fractures were not of paramount importance in causing clotting changes. Conclusive evidence of disseminated intravascular coagulation was found in 12 patients. Cases with a fatal clinical course were mostly associated with very high fibrin/fibrinogen degradation product concentrations. Some case histories are reported, confirming the hypothesized correlation between coagulation results and brain tissue destruction rather than brain compression. It was concluded that some degree of disseminated intravascular coagulation in patients with blunt head injury occurs more often than expected and that coagulation studies might have both diagnostic and prognostic value.

Adolescent↗
PubMed1977

Electro-rentinal abnormalities in heterozygotes of renal-retinal dysplasia.

The relatives of two patients with medullary cystic disease associated with retinitis pigmentosa were studied. A new case was found in one of these families, and consanguinity of the parents was established in another. Conventional fundoscopic examination of relatives without renal disease did not show retinal abnormalities, but electro-ophthalmologic investigation demonstrated retinal dysfunction in three relatives, including two of the four parents who may be considered obligatory heterozygotes under the assumption of autosomal recessive inheritance of this syndrome. Less severe electro-ophthalmological abnormalities were observed in the other two parents. It is considered highly probable that all three patients are homozygous for a mutant gene causing both the renal and the retinal abnormalities. The results of this study support the view that medullary cystic disease associated with retinitis pigmentosa is transmitted as an autosomal recessive trait, in contrast to the dominant form, which is reported not to be associated with eye abnormalities. With respect to genetic couseling and donation of kidneys by relatives, it is important to establish the mode of inheritance of cystic medullary disease in a given family. Electro-ophthalmologic examination should therefore be included in the examination of families in which medullary cystic disease occurs.

Adolescent↗