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Biomedical subjects

J J Hoffmann

Publications and source records attributed to J J Hoffmann.

At least 37 records · Page 2Linked to original sources
PubMed1996

Hemostatic changes after thrombolytic therapy with saruplase (unglycosylated single-chain urokinase-type plasminogen activator) and urokinase (two-chain urokinase-type plasminogen activator).

Urokinase, or two-chain urokinase-type plasminogen activator (tcu-PA), is an effective thrombolytic agent. Its single-chain precursor (scu-PA), unlike tcu-PA, is able to selectively activate fibrin-bound plasminogen. The induced clot lysis is amplified by plasmin-triggered conversion of scu-PA to tcu-PA. The aim of our study was to compare the hemostatic effects of recombinant unglycosylated scu-PA, INN saruplase, and urokinase, at doses considered optimal (80 mg saruplase and 3 million units urokinase) in patients with acute myocardial infarction, within 6 h of onset of pain. Complete sample sets from more than 230 patients in each treatment group have been analyzed. The median hemostatic changes caused by saruplase and urokinase were virtually identical indicating that saruplase is converted early in vivo to its active tcu-PA derivative with the dose regimen used. Fibrinogen degradation products were higher for saruplase with a maximum at 2h. They rose markedly after saruplase from 0.43 mg/l at 0 h to a maximum of 160 mg/l at 2 h, whereas the increase after urokinase (from 0.45 mg/l to 89.0 mg/l) was significantly smaller (P < 0.001).

Double-Blind Method↗
PubMed1996

Flow cytometric analysis of consecutive lymph node samples from patients with Hodgkin's disease: reproducible within one biopsy?

In Hodgkin's disease DNA aneuploidy is not a prognostic factor. However, the prognostic significance of DNA content in Hodgkin's disease may be missed by either intratumor DNA heterogeneity or DNA analysis of limited samples. For flow cytometry usually one section of 40-60 microns is used for the analysis. In breast cancer this proved to be insufficient. In Hodgkin's disease no data are available. Therefore, we examined if analysis of more sections does increase the yield of aneuploidy. Archival, formalin-fixed, parafin embedded tissues were used. From 13 patients four sections of 50 microns could be analysed for DNA content. In 12 of 13 patients the results were consistent in all four sections of one patient case; seven diploid, four aneuploid and one multiploid. In one case ploidy status changed: two sections were diploid and two were aneuploid. The DNA-index of the aneuploid samples ranged from 0.75 to 1.38 and varied from 0.02 to 0.14 within one case. The S-phase fraction remained constant within all evaluable cases (sd: 0.5-1.5%), except for one (sd: 4.7%). In conclusion, in Hodgkin's disease the ploidy status of the first section can be regarded to represent the whole tissue sample. Therefore, the absence of prognostic value of ploidy status is not explained by sampling errors in tissues analysed.

Biopsy↗
PubMed1996

Characteristics of anti-Cob in vitro and in vivo: a case study.

Serologic and biologic properties of an example of anti-Cob were investigated. The antibody was of the IgG class, and it bound small amounts of complement. It reacted optimally in the albumin-antiglobulin test with little or no enhancement of its reactivity in tests using enzymes. Additional experiments indicated that the Cob antigen is resistant to treatment with chemicals known to destroy other antigens. The antibody caused shortened survival of radiolabeled Co(b+) donor red cells in our patient. At 24 hours, nearly 50 percent of the red cells were no longer detectable in the circulation. It is concluded that anti-Cob is a clinically relevant antibody, a fact that must be taken into account when transfusing patients with anti-Cob.

Journal Article↗
PubMed1995

[Determination of spectrin in erythrocytes: an important aid in the diagnosis of hereditary spherocytosis].

OBJECTIVE: Assay of spectrin in erythrocytes as a diagnostic test in hereditary spherocytosis (HS). DESIGN: Validation of a diagnostic test. SETTING: Central Laboratory of the Netherlands Red Cross Blood Transfusion Service in Amsterdam, the Netherlands. METHOD: A radiolabelled rabbit antiserum against human spectrin was used to determine the amount of spectrin in erythrocytes from 64 patients with proven or supposed HS, suffering from inborn, sometimes familial anaemia and a decreased osmotic resistance of the erythrocytes. These amounts of spectrin were compared with those of 12 patients with decreased osmotic resistance suffering from haemolytic anaemia of unknown cause, 16 patients with various other erythrocyte disorders and 30 healthy blood donors. RESULTS: The intradonor and interdonor variations in the amount of spectrin in erythrocytes from healthy blood donors were found to be less than 7%. In 56 of the 64 patients with HS (88%), the erythrocytes contained less than 86% of the normal amount of spectrin. A similar result was found in 4 of the 12 patients suffering from non-characterised haemolytic anaemia (33%). In contrast, a normal amount of spectrin was found in the erythrocytes of patients with other erythrocytic disorders. CONCLUSION: The radio-immunoassay of spectrin in erythrocytes is more specific for the diagnosis of HS than the osmotic fragility test of the erythrocytes. The normal amount of spectrin found in 8 of the 64 patients possibly suffering from HS may be due to a rare molecular origin of HS not leading to a decreased spectrin level or may be related to other causes of anaemia than HS.

Anemia↗
PubMed1995

Systemic blood activation with open and closed venous reservoirs.

In 20 patients undergoing coronary artery bypass grafting, we studied prospectively systemic blood activation, blood loss, and the need for donor blood when using an extracorporeal circuit equipped at random with one of two different venous reservoirs. In 10 patients we used an open venous reservoir system (ORS) consisting of a hard shell venous reservoir with an integral cardiotomy filter, and in 10 patients we used a closed reservoir system consisting of a collapsible venous reservoir and separate cardiotomy reservoir. Concentrations of complement 3a, elastase, thromboxane B2, and fibrin degradation products showed a biphasic course, especially in ORS patients. During bypass, we observed a first peak of levels of complement 3a, thromboxane B2, fibrin degradation products, and elastase, which was higher in ORS patients than in patients with the closed system, because their blood continuously contacted the foreign materials of the filter and air in the open reservoir, which was avoided in the closed reservoir. Intensive blood-foreign material contact also caused the highest (p < 0.05) hemolysis in ORS patients. The larger amount of hemolytic products in ORS patients theoretically resulted in a temporary decrease in capacity of their Kupffer cells to clear endotoxin released after aortic declamping. This theory might explain the significantly (p < 0.01) higher second peak of activated products after declamping that was observed in ORS patients. Due to increased blood activation, the largest (p < 0.001) amount of shed blood loss, greatest (p < 0.05) need for colloid-crystalloid infusion, and largest (not significant) need for donor blood were found in ORS patients (0.8 +/- 0.4 versus 0.2 +/- 0.2 units of packed cells).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1995

Flow cytometric phenotyping of platelet HPA-1a antigen: donor screening for a case of neonatal alloimmune thrombocytopenia due to anti-HPA-1a antibodies.

Neonatal alloimmune thrombocytopenia can effectively be treated by transfusing compatible platelets to the affected newborn, but typed, compatible platelets are not generally available. For a case of probable neonatal alloimmune thrombocytopenia due to anti-HPA-1a, part of the donor population of the regional blood bank was phenotyped to find HPA-1a-negative platelets. A flow cytometric technique was used, which is reliable, rapid, and relatively simple and therefore well suited for large-scale screening. Using this method, several HPA-1a-negative donors were identified, and one of them donated platelets that were successfully transfused to the thrombocytopenic newborn.

Journal Article↗
PubMed1995

Identification and genetic analysis of a common molecular variant of histidine-rich glycoprotein with a difference of 2kD in apparent molecular weight.

Two forms of histidine-rich glycoprotein (HRG) were detected on SDS-PAGE by silver staining and immunoblotting after isolation of the protein from pooled plasma using immuno-affinity chromatography followed by chromatography with heparin-Sepharose. Both forms were single-chain molecules and the apparent molecular weights of form 1 and form 2 were 77 kD and 75 kD respectively. Mendelian inheritance of both HRG forms was observed in four families with 24 informative meioses, strongly suggesting that the two forms are encoded by different alleles. The frequency of form 1 and form 2 in a group of 36 individuals was 0.35 and 0.65 respectively. The difference between the two molecular variants was studied by direct sequence analysis of amplified exons of the HRG gene from 6 individuals who were homozygous either for form 1 or form 2. Five amino acid polymorphisms in three different exons were observed: Ile/Thr in exon4; Pro/Ser in exon 5; His/Arg, Arg/Cys and Asn/Ile in exon 7. Analysis of these polymorphisms in 20 volunteers showed that only the Pro/Ser polymorphism at position 186 in exon 5 was coupled to the form of the HRG protein. Ser was found in form 1 and Pro in form 2. The presence of Ser at position 186 introduces a consensus sequence for a N-glycosylation site (Asn-X-Ser/Thr). By removing N-linked sugars with N-glycanase, it could be demonstrated that the difference between the two forms of HRG is caused by an extra carbohydrate group at Asn 184 in form 1.

Amino Acid Sequence↗
PubMed1994

DNA aneuploidy in Hodgkin's disease: a multiparameter flow cytometric analysis.

Paraffin-embedded lymph nodes from patients with Hodgkin's disease were examined for flow cytometric DNA content. In order to increase the sensitivity of the assay we tried to enrich for the neoplastic cells by bivariate analysis using a polyclonal anti-nucleolar antibody (AN-AB) and the forward scatter (FSC). DNA aneuploidy was found to be present in 67 of all 137 cases (49%), in 24 cases only demonstrable by dual-parameter analysis. The DNA index varied from 0.69 to 1.89 with a total of 22 hypo-diploid cases. The number of aneuploid nuclei exceeded the expected frequency of Reed-Sternberg (RS) and Hodgkin (H) cells in most of the analysed specimens. In conclusion, flow cytometry in Hodgkin's disease appears to give useful information regarding the ploidy status and evidence has been provided that the malignant cell population in Hodgkin's disease is not limited to the classical RS/H cells.

Aneuploidy↗
PubMed1994

[Neuropathies of septic syndrome with multiple organ failure in burnt patients: 2 cases with review of the literature].

We report two cases of axonal sensori-motor polyneuropathies complicating sepsis and multiple organ failure (MOF) among severely burned patients (total burned surface area of 35 to 40 per cent) in which no other cause of neuropathy was retrospectively identified. No steroids or neuromuscular blocking agents had been given. The date of onset was not established but the diagnosis was late, between the 30th and 45th day, at the recovery of consciousness. Regression was incomplete, with severe sequellae especially in one patient who was unable to walk 10 months after the injury. Burned patients can present with many kinds of peripheral neuropathies. Postburn polyneuropathies with nerve conduction slowing were described by Henderson. Mononeuropathies can result from nerve compression complicating unfavorable postures in comatose patients or from nerve entrapment in ischemic limbs. Polyneuropathy in postburn sepsis with MOF does not appear to have been previously reported. Postburn sepsis usually occurs in young patients, without other cause of MOF; and therefore represents a relatively "pure" sepsis syndrome.

Axons↗
PubMed1994

Comparison of image (CAS 200) and flow cytometry determined DNA content of paraffin-embedded Hodgkin's disease tissue.

To assess the reliability of DNA estimation using image cytometry, deparaffinized lymph nodes from 70 patients with Hodgkin's disease were examined and the results obtained were compared with those from flow cytometry. Image analysis without discriminating between the various cell types, as found in Hodgkin's disease, revealed no separate aneuploid peak. Selecting on morphologically defined nuclear types DNA aneuploidy was detected in 20% of the cases (14/70). The aneuploid populations were limited to the population of nuclei defined as Reed-Sternberg (RS)-like or medium-sized lymphocytes. Benign lymph nodes DNA aneuploidy was not found in any of the controls. Comparison of DNA histograms obtained by image and flow cytometry showed aneuploid peaks using image cytometry in 4 of 30 diploid and 10 of 40 aneuploid flow histograms. In conclusion, image analysis using the CAS 200 system as compared to flow cytometry is more time-consuming and less sensitive to assess ploidy status, although it may provide extra information in some selected cases. Evidence is obtained that DNA aneuploidy in Hodgkin's disease is preferentially expressed by cells with the RS/H-like and medium-sized lymphocyte morphology.

Aneuploidy↗
PubMed1993

Hereditary increase of plasma histidine-rich glycoprotein associated with abnormal heparin binding (HRG Eindhoven).

Plasma histidine-rich glycoprotein (HRG) was found to be persistently increased in a patient with a history of recurrent arterial thromboembolic events. The mean concentration was 270% of normal pooled plasma. Increased HRG was found in eight of the 17 relatives studied, but none of them has experienced thrombo-embolism yet. Apparently, increased HRG was hereditary with autosomal dominant inheritance. A significant correlation was found between the increased plasma concentration of the protein and the age of the subjects (P < 0.02), whereas no such relation is present in a normal population. The plasma HRG of the proposita and 9 of her family members displayed abnormal binding to heparin, as assessed in a crossed affinity immuno-electrophoresis system: the usual increase in mobility after binding to heparin was absent. The binding of this variant HRG to plasminogen was normal. This case represents the first abnormal HRG variant reported and it is proposed to designate it: HRG Eindhoven.

Blood Proteins↗
PubMed1993

Blood viscosity during thrombolytic therapy with anistreplase in acute myocardial infarction.

It has been postulated that a reduction in blood viscosity due to degradation of plasma fibrinogen may be of benefit to patients with acute myocardial infarction (AMI), who are treated with thrombolytic agents. The aims of this study were to investigate the time course of rheologic parameters, to identify the principal factors determining blood viscosity, and to find possible correlations between viscosity and cardiac function during thrombolytic therapy with anistreplase. Therefore, the viscosity of whole blood and plasma and the hematocrit were measured before and at 10 time points after thrombolysis in 10 patients with AMI. In addition, plasma fibrinogen and fibrin(ogen) degradation products were determined. Immediately after the start of thrombolysis, the viscosity of blood (both at high and low shear rate) and plasma decreased significantly and continued to do so for 24 hours. The mean hematocrit also decreased markedly, and even after correction for these hematocrit changes, the reduction in blood viscosity remained significant: it decreased to 72% of pretreatment (measured at low shear rate), whereas the high-shear viscosity decreased to 95% of baseline. The viscosity of plasma significantly decreased from 1.39 +/- 0.13 mPa.s (mean +/- SD) before thrombolysis to 1.22 +/- 0.08 mPa.s after 2 hours. There was a rapid, nearly complete depletion in fibrinogen, followed by a striking rebound after the second day. The decrease in blood viscosity lasted for 2 days after anistreplase and was mainly accounted for by the reduction in hematocrit. The contribution of fibrinogen to blood viscosity appeared less prominent. Despite these rheologic changes, no improvement in cardiac output was noticed in the patients.

Aged↗
PubMed1993

Specificity effects of run versus cycle training on ventilatory threshold.

This study compared the effects of 9 weeks of run (RT) versus cycle (CT) training on ventilatory threshold (Thv) determined during treadmill (TM) and cycle ergometer (CE) graded exercise testing. Sixteen college age men were assigned to a RT or CT group and performed a TM and a CE test before and after training. Both training groups performed similar training protocols which initially consisted of continuous exercise 4 days.week-1 at 75-80% maximum heart rate (fc, max) for 45 min. Training intensity was later increased to 80-85% fc, max and interval training (90-95% fc, max) was incorporated 2 days.week-1 into the continuous training. Both groups showed significantly improved maximal oxygen consumption (VO2 max) on both TM and CE tests (P < 0.01) with no significant differences between the groups. Significant Thv increases (P < 0.05) were found on TM tests for RT (n = 8) and CT (n = 8) groups [mean (SD); 443 (438) and 373 (568) ml O2 x min-1, respectively] with no difference between the groups. Results from the CE tests revealed a significant Thv increase (P < 0.01) for the CT group [566 (663) ml O2 x min-1] with no change for the RT group. The Thv improvement noted for the RT group was significantly different (P < 0.05) comparing CE with TM tests but not for the CT group. The results indicate that CT and RT improvement in Thv for runners is dependent upon mode of training and testing, and there is an apparent dissociation of VO2 max and Thv specific to training.

Adult↗
PubMed1993

DNA aneuploidy and cell proliferation in relation to histology and prognosis in patients with Hodgkin's disease.

BACKGROUND: Aneuploidy and S-phase fraction are well recognized prognostic features of solid tumors and non-Hodgkin's lymphoma. However, only limited data on Hodgkin's disease are available. PATIENTS AND METHODS: In this study flow cytometric data on ploidy status and S-phase fraction are analyzed in relation to clinical characteristics and prognosis in 137 patients with Hodgkin's disease. RESULTS: The presence of DNA aneuploidy was not associated with other clinical characteristics. When the histologic subtypes were clustered according to a higher number of Reed-Sternberg/Hodgkin cells into two classes (LP + NSI and the histologic NSII + MC + LD), it appeared that cases with an SPF > or = 7.5% had the histologic subtypes NSII + MC + LD significantly more frequently than those with an SPF < 7.5% (P = 0.001). There was no significant difference in complete remission rates, relapse-free or overall survivals between the patients with diploid and those with aneuploid lymph nodes. The complete remission rate for patients with and SPF < 7.5% was higher than for those with an SPF > or = 7.5%, 95% (56/59) and 76% (50/66), respectively (P = 0.006). The 10-year survival rate was 78% for patients with an SPF < 7.5% and 48% for those with an SPF > or = 7.5% (P = 0.04). However, by multivariate analysis only the ESR, age and clinical stage proved to be of independent prognostic importance. CONCLUSION: DNA aneuploidy did not correlate with known prognostic factors or survival, but the SPF might turn out to be an indicator of patients who will have less favourable outcomes.

Adult↗
PubMed1993

Effects of stair-climbing vs run training on treadmill and track running performance.

Physically active college age women were evaluated to determine the effects of 9 wk of stair-climbing (Stairmaster Gauntlet) vs run training on 2414-m run time and treadmill measured aerobic capacity (VO2max) and submaximal physiological parameters. Subjects were randomly assigned to a stair-climbing (STAIR N = 11) (43.8 +/- 1.5 ml.kg-1.min-1) (mean +/- SEM) or run training (RUN N = 12) (44.2 +/- 1.8) group, training 4 d.wk-1 at 70-80% of maximum heart rate (MHR) for 30 min progressing to 85-90% MHR for 45 min. The STAIR group significantly increased (P < 0.01) their VO2max by 12% and decreased (P < 0.01) their 2414-m run time of 12.8 min by 8%. The RUN group increased (P < 0.01) their VO2max 16% and decreased run time (P < 0.01) 11% from 13.1 min. Submaximal treadmill runs at the same speed and grade demonstrated significant decreases in %VO2max and % MHR (P < 0.01) for both groups. The data support the use of stair-climbing exercise as an alternative mode to running with similar treadmill and running performance results subsequent to 9 wk of training.

Adult↗
PubMed1992

Interactions between thrombolytic agents and platelets: effects of plasmin on platelet glycoproteins Ib and IIb/IIIa.

The mechanisms by which thrombolytic agents affect platelet function are not yet elucidated. The aim of the present study was to investigate the effects of plasmin, generated by thrombolytic agents in plasma, on platelet glycoproteins (GP) Ib and IIb/IIIa. Platelet-rich plasma was incubated with pharmacological amounts of streptokinase, anistreplase and tissue-type plasminogen activator and the platelet surface GP's were investigated with a panel of monoclonal antibodies using flow cytometry. As assessed from the mean fluorescence intensity of incubated and control platelets, no significant changes in the binding of antibodies to GP Ib and GP IIb/IIIa were found. The functional integrity of these glycoproteins was severely impaired by treatment with the thrombolytic agents, as shown by significant inhibition of ADP- and ristocetin-induced platelet aggregation. Experiments with purified plasmin and washed platelets indicated significant degradation of GP IIb/IIIa and upregulation of GP Ib, which is in agreement with previous findings. In addition, platelet activation by plasmin was shown using two monoclonal antibodies to activation-specific antigens. We conclude that degradation of platelet GP's by plasmin offers no likely explanation for the defect in platelet function, which is induced by thrombolytic agents in platelet-rich plasma.

Anistreplase↗