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Biomedical subjects

L Holmberg

Publications and source records attributed to L Holmberg.

At least 253 records · Page 14Linked to original sources
PubMed1986

von Willebrand's disease characterized by increased ristocetin sensitivity and the presence of all von Willebrand factor multimers in plasma.

In eight members of one family, platelets in platelet-rich plasma aggregated at much lower ristocetin concentrations than normal. Ivy bleeding time was variously prolonged, and von Willebrand factor antigen (vWF:Ag), ristocetin cofactor activity, and factor VIII coagulant activity were decreased. Most of the affected members had had slight to rather severe bleeding symptoms. Platelet-type von Willebrand's disease (vWD) could be ruled out. All multimers of vWF:Ag were found in plasma as well as platelets. Administration of 1-desamino-8-D-arginine vasopressin (DDAVP) to the propositus did not cause thrombocytopenia, and platelet-poor plasma obtained immediately after did not aggregate normal platelets. The molecular defect in this family, inherited as an autosomal dominant, resembles the one in type IIB because of the response to ristocetin but differs from IIB because all vWF:Ag multimers are present in plasma and the response to DDAVP is atypical. We conclude that this family has a new subtype of vWD and propose that structural as well as functional criteria should be used for a proper classification of vWD.

Blood Platelets↗
PubMed1985

Comparison of renal excretion of pethidine (meperidine) and its metabolites in old and young patients.

In a previous study old subjects were found to eliminate pethidine and its active metabolite norpethidine more slowly than young people. To investigate whether this was due to the decline in renal function with age, the urinary output of pethidine and its metabolites pethidinic acid, norpethidine and norpethidinic acid was compared in old and young patients. The cumulative urinary excretion of pethidine and pethidinic acid over 24 h was similar in old and young patients. The slower elimination rate of pethidine from plasma might therefore be due to slower biotransformation of pethidine to norpethidine and norpethidinic acid. The cumulative urinary excretion of norpethidine and norpethidinic acid during 24 h was significantly lower in old patients than in young: 2.7% versus 7.1% (p less than 0.001), and 5.5% versus 10.5% (p less than 0.001). The renal clearance of norpethidine was inversely correlated with age. Thus, the slower disappearance of norpethidine from plasma in old patients is due to slower renal excretion of this metabolite. The renal clearance of pethidine showed pH-dependence and was usually smaller than the creatinine clearance. In contrast, renal clearance of norpethidine was correlated with creatinine clearance and was of the same magnitude. The difference in renal handling may be explained by the more polar character of norpethidine compared to its parent compound. The present study shows that not only the excretion of unchanged drugs may decline with increasing age but also that of drug metabolites, which may therefore reach higher plasma levels in old patients. If they are pharmacologically active they will increase and prolong the response to medication and possibly increase the risk of side effects.

Adolescent↗
PubMed1985

Long-term survival in 406 males with breast cancer.

Survival was analyzed during a follow-up period of up to 20 years in 406 (97%) of all 420 males in whom breast cancer was diagnosed in Sweden in 1960-1978. After correction for the expected mortality in the general population, cumulated survival rates (with 95% confidence limits) of 66 (58.7-72.5)% and 52 (42.0-62.1)% at 5 and 10 years respectively were found. These figures and the general pattern of relative survival rates were in close accordance with those noted in a concomitant series of female breast cancer. There was a trend toward slightly improved survival rates during the period of study and the median survival times were 3.9, 4.8 and 7.2 years for patients diagnosed in 1960-64, 1965-69 and 1970-74 respectively. Age at diagnosis was seemingly unrelated to the long-term relative survival. We conclude that, except for a slightly higher mean age at diagnosis in males, there is a striking similarity in the natural history of breast cancer between men and women after initial treatment, with an excess death rate which still persists at long-term observation.

Adolescent↗
PubMed1985

Polymorphism of normal factor IX detected by mouse monoclonal antibodies.

Hemophilia B is an X-chromosomal recessive disease due to deficiency of coagulation factor IX. Three monoclonal antibodies against factor IX were prepared and used to develop immunoradiometric assays (IRMAs) of factor IX antigen (IX-Ag). IX-Ag was measured in 65 normal individuals with one IRMA based on polyclonal anti-IX antibodies and two IRMAs based on three monoclonal anti-IX antibodies. One of the monoclonal antibodies differed in specificity since it neutralized less than 50% of the clotting activity of factor IX (IX-C), whereas the other two monoclonal antibodies neutralized 80-95%. When the former antibody was used as the solid phase in IRMA, two groups of normal individuals were distinguished: group A with measurable IX-Ag, and group B without demonstrable IX-Ag. There were no differences between the groups either in IX-C or in IX-Ag measured with polyclonal antibodies. A subgroup comprising only women could be distinguished in group A, in whom intermediate IX-Ag concentrations were found. Family studies showed the group B variant of normal factor IX to be transmitted according to the pattern of X-linked recessive inheritance. The allelic frequency of group A was 0.66, and that of group B was 0.34.

Adolescent↗
PubMed1985

Platelet--von Willebrand factor interactions in type IIB von Willebrand's disease.

Type IIB von Willebrand's disease (vWD) is a distinct form of this disorder in which the largest multimers of the von Willebrand factor (vWF) are lacking in plasma but present in platelets. When the vasopressin analogue, 1-deamino-8-D-arginine vasopressin (DDAVP), is given to patients with type IIB vWD, an abnormal vWF is released to plasma. This vWF causes thrombocytopenia in vivo and platelet aggregation in vitro. Aggregation occurs in the plasma milieu and thus at physiological fibrinogen concentration. In this study we demonstrate that IIB post-DDAVP vWF aggregated only metabolically active platelets. The platelet aggregation was completely inhibited by EDTA and PGE1, and either inhibited or greatly weakened by ASA, demonstrating the role of divalent cations and thromboxane A2 formation. In spite of inhibiting platelet aggregation, EDTA, PGE1 and ASA did not prevent platelet binding of IIB post-DDAVP vWF. An antiserum against GP Ib made normal platelets less responsive to the IIB vWF although neither platelet aggregation nor vWF binding were completely prevented. The aggregation was fibrinogen-dependent and platelets from patients with Glanzmann's thrombasthenia were unresponsive. The studies provide evidence that IIB post-DDAVP vWF is bound to unstimulated platelets and that the interaction between vWF and platelets in type IIB vWD is different from ristocetin-induced as well as thrombin- and epinephrine-induced binding to platelets of normal vWF.

Blood Platelets↗
PubMed1985

The use of monoclonal antibodies in measuring factor VIII/von Willebrand factor.

Here we report the production of four different monoclonal antibodies against factor VIII/von Willebrand factor (F VIII/vWF) and the use of these antibodies in immunoradiometric assay (IRMA), crossed immunoelectrophoresis (CIE) and multimeric sizing (MS) for analysing the various types of von Willebrand's disease. None of the antibodies inactivated factor VIII coagulant activity and one (R1) of them partly inhibited the ristocetin co-factor activity. One monoclonal antibody (R2) was radiolabelled and compared with 125I rabbit affinity purified antibody against F VIII/vWF. The two IRMA techniques gave similar results in 26 normals and 22 samples representing all variants of von Willebrand's disease. This monoclonal antibody could also be used in multimeric sizing and not only produced patterns identical to those obtained with the rabbit affinity purified antibody, but also gave better resolution. Further advantages of using monoclonal antibodies in these tests are: practically unlimited access to the same specific antibody, time-consuming affinity purification of the rabbit antibody can be avoided and the overall use of radioactivity reduced. This study demonstrates that one (R2) of the four monoclonal antibodies is suitable for routine analysis of F VIII/vWF and the use of this antibody simplifies the laboratory work in classifying von Willebrand's disease.

Animals↗
PubMed1985

Significant reduction in advanced breast cancer. Results of the first seven years of mammography screening in Kopparberg, Sweden.

A population-based, randomized, controlled breast cancer screening trial with single-view mammography as the only means of primary detection has been under way in Kopparberg county, Sweden, since October 1977. The 7-year results of the study show (1) a significant change in the stage distribution of breast cancers in the cohort invited to undergo screening (ASP) as compared to the control group. (2) This change is seen as an initial decrease in the proportion of advanced (stage II and more advanced) cancers in the ASP as compared to the control population, followed in the second and third round of screening by a significant decrease in the absolute number of these advanced cancers in the ASP relative to the control group. (3) A thorough follow-up of both populations will answer whether these preliminary findings will result in decreased breast cancer mortality in the population invited to screening.

Adult↗
PubMed1983

Platelet aggregation induced by 1-desamino-8-D-arginine vasopressin (DDAVP) in Type IIB von Willebrand's disease.

Type IIB von Willebrand's disease is a distinct form of this disorder, in which there are abnormal factor VIII/von Willebrand factor multimers in plasma (but normal multimers in platelets) and heightened interaction between the von Willebrand factor and platelets in the presence of ristocetin. We have found that infusion of desmopressin acetate (1-desamino-8-D-arginine vasopressin [DDAVP]), an agent used in the treatment of von Willebrand's disease, causes platelet aggregation and thrombocytopenia in patients with Type IIB disease. In vitro, platelets in normal plasma and those obtained from patients with Type IIB disease before DDAVP infusion aggregated upon the addition of platelet-poor plasma from Type IIB patients treated with DDAVP. Platelet aggregation was associated with adsorption of multimers of factor VIII/von Willebrand factor onto the platelets and was inhibited by EDTA. We conclude that in Type IIB von Willebrand's disease, DDAVP releases an abnormal factor with platelet-aggregating properties. DDAVP should not be used to treat patients with Type IIB disease, since the presence of platelet aggregates in the circulation may be harmful.

Adult↗
PubMed1983

The effects of plasmin and protein Ca on factor VIII:C and VIII:CAg.

The effects of various concentrations of plasmin and activated protein C on the factor VIII procoagulant activity (VIII:C) and coagulant antigen (VIII:CAg) were studied in factor VIII concentrates and normal plasma. Small amounts (0.1 CTA U/ml) of plasmin rapidly destroyed VIII:C, and affected, but did not destroy VIII:CAg, in factor VIII concentrates. In normal plasma larger amounts of plasmin (1.8 CTA U/ml) was required to inactivate VIII:C in order to exceed the neutralizing capacity of alpha 2-antiplasmin. VIII:CAg was unchanged indicating a limited proteolysis. The difference between VIII:C and VIII:CAg was found also in urokinase-activated plasma. Activated protein C (5 micrograms/ml), in the presence of Ca2+ and phospholipids, inactivated VIII:C without affecting VIII:CAg in a high purity factor VIII concentrate. Higher concentrations of activated protein C (25 micrograms/ml) caused a slight decrease of VIII:CAg, even in the absence of Ca2+ and phospholipids, but did not change VIII:CAg in normal plasma or serum.

Animals↗
PubMed1983

A prenatal study of fetal platelet count and size with application to fetus at risk for Wiskott-Aldrich syndrome.

Platelet counts and platelet size were determined in midtrimester fetuses to obtain reference values to be used in prenatal diagnosis of inheritable platelet disorders. In 17- to 21-week fetuses, platelet counts ranged between 135 and 283 x 10(9)/L, and thus did not differ from those of newborn infants and adults. Mean platelet volume fell between 6.0 and 7.0 fl, which is in the range for adults. The data were used to exclude Wiskott-Aldrich syndrome in an 18-week fetus at 50% risk of being affected.

Blood Coagulation Disorders↗
PubMed1983

The drug-consuming patient and his drugs. I. The patient.

Patient characteristics and pre-hospital drug consumption have been studied in 506 consecutive patients acutely admitted to a department of medicine. Women were older (median 69 years) than men (median 63 years) and weighed less (mean 60 vs. 74 kg). Serum creatinine values were above the normal limits in 110 patients (22%). Forty-eight per cent of men and 26% of women were smokers. Heavy alcohol intake was found in 12% of men and 4% of women. It is concluded that a typical patient group shows much greater variations in age, weight, renal function, smoking and drinking habits--factors all known to influence the results of drug treatment--than is generally taken into account when routine drugs are prescribed.

Acute Disease↗
PubMed1983

The drug-consuming patient and his drugs. II. The drugs.

The drug consumption pattern and patients' knowledge about their drugs have been studied in 506 patients, acutely admitted to hospital. The patients took a mean of 3.2 drugs before hospitalization, the majority of them being used for more than one year. Calculated on all 506 interviewed patients, women took more drugs than men, but among the 406 users there was no significant difference in the number of drugs taken by men or women. The number of drugs increases markedly with age. The drugs most commonly used were digoxin (30% of the patients), nitrazepam (19%), furosemide (18%), potassium (17%) and nitroglycerin (14%). Dosage reduction with advancing age was registered i.a. for digoxin. Judging from the number of adverse drug reactions (ADRs) and subjective side-effects, the dosage reduction should probably have been even greater. Twenty-six patients (5%) were admitted because of an ADR, another 10 (2%) with an ADR. For the majority of drugs (84%) the patients had some understanding of the expected effect, but knowledge about possible side-effects was reported for 26% of the drugs only.

Acute Disease↗
PubMed1983

Suppression of secondary antibody response by intravenous immunoglobulin in a patient with haemophilia b and antibodies.

A 39-year-old patient, suffering from severe haemophilia B and antibodies against factor IX, has twice been treated with extracorporeal protein A-Sepharose adsorption followed by conventional substitution therapy in combination with immunosuppression (cyclophosphamide). On both occasions, separated by a 2-year interval, the same procedure was followed except that, on the second, administration of i.v. immunoglobulin (Gammonativ. KabiVitrum) was added. Within a week of the first treatment the patient developed a 15-fold increase in the antibody titre. Following the second treatment described here, no secondary antibody response could be detected, and after a further 12 weeks only traces of antibodies are demonstrable. It seems that antibody synthesis was suppressed by the i.v. immunoglobulin. No evidence was found to demonstrate that the effect was due either to a non-specific suppression of the immune and reticuloendothelial systems or to the action of interfering antibodies. It has not yet been established whether or not the protein A-Sepharose adsorption technique, or the immunosuppressive treatment, contributed in any way to the result. The observations suggest a new approach to the treatment of haemophiliacs with antibodies of the high-responding type.

Adult↗
PubMed1983

Immunological characterisation of plasminogen activators in the human vessel wall.

A histochemical technique was used to identify the activity of the plasminogen activator (PA) in the vessel wall of veins. Antibodies against melanoma cell activator and urokinase (UK), both raised in goats, were mixed into the fibrin film. The PA activity was quenched by the antibodies against melanoma activator but remained unchanged when antibodies against UK, or an IgG preparation of normal goat serum, was mixed in the fibrin film. The results of this study show that the PA activity in the vein vessel wall is immunologically similar to or identical to the PA derived from melanoma cells which has previously been shown to cross-react with the tissue-like PA. No UK-like activity was present in the vessel wall.

Antibodies↗
PubMed1983

Detection of factor IX inhibitors by immunoradiometric assay.

An immunoradiometric assay (IRMA) for the determination of factor IX inhibitors in haemophilia B was developed. The assay was based on competitive binding between radiolabelled anti-IX and inhibitors in the test material of immobilized IX:C. 5 haemophiliacs with known inhibitors were investigated with the new method and with a conventional neutralization test. An inhibitor titre as low as 5 X 10(-4) U/ml could be measured by IRMA, showing it to be about 500 times as sensitive as the conventional neutralization assay used, and in 2 cases the inhibitors could only be detected by IRMA. The new method is thus useful for the investigation of patients with low inhibitor titres, or when inhibitors with divergent properties are suspected.

Antibodies↗
PubMed1982

Kinetics of the reaction between urokinase and an inhibitor of fibrinolysis from placental tissue.

The interaction of urokinase (EC 3.4.21.31) and a protein proteinase inhibitor of fibrinolysis partially purified from placental tissue, which inhibits urokinase but not plasmin, was investigated. The preparations of the inhibitor contained no other known proteinase inhibitors. It was found that a 1:1 complex is formed and that the reaction proceeds as a second order, one step process, the association rate constant of which is 4.5 10(6) M-1 S-1 at pH 8.4, 37 degrees C and 3.0 10(6) M-1 S-1 at pH 7.3, 37 degrees C. The binding is very tight, the dissociation constant of the inhibitor-urokinase complex was estimated to be Ki less than or equal to 10(-11) M.

Blood Proteins↗