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Biomedical subjects

D Meyer

Publications and source records attributed to D Meyer.

At least 109 records · Page 6Linked to original sources
PubMed2000

Reconstitution of NK cell activity in HIV-1 infected individuals receiving antiretroviral therapy.

We studied natural immunity mediated by natural killer (NK) cells in 62 HIV-1 infected individuals, 54 HIV-1 infected individuals receiving highly active antiretroviral therapy (HAART) for more than one year and 8 HIV-1 infected individuals without antiretroviral therapy. 22 individuals had a complete suppression of viral replication characterized by viral load values <50 copies/ml, whereas 32 individuals presented with persistent viral replication. The 8 untreated patients had an indication to start antiretroviral treatment. Lytic activity of NK cells was measured in a 51chromium release assay. In patients with persistent viral replication under HAART NK cell activity was significantly decreased compared to patients with effective control of HIV viremia. Patients with complete suppression of HIV replication displayed a similar NK activity to healthy control persons. Differences in antibody-dependent cellular cytotoxicity (ADCC) were not observed. Further studies will investigate whether decreased NK cell activity is a reason for or the consequence of persistent viral replication.

Antibody-Dependent Cell Cytotoxicity↗
PubMed2000

Immune reconstitution syndromes in human immuno-deficiency virus infection following effective antiretroviral therapy.

Effective antiretroviral therapy leads to rapid decrease in plasma HIV-1 RNA, frequently followed by an increase in CD4 T-helper cell counts. The improvement of immune function during highly active antiretroviral therapy has important impact on natural history of AIDS-related opportunistic disorders. Here we describe cases of unusual clinical inflammatory syndromes in CMV retinitis, hepatitis C, and atypical mycobacteriosis in HIV-1 infected patients associated with the initiation of antiretroviral therapy. Pathogenetic implications and therapeutic management of these new immunopathologic syndromes are discussed.

AIDS-Related Opportunistic Infections↗
PubMed2000

Retrograde flush perfusion with low-potassium solutions for improvement of experimental pulmonary preservation.

BACKGROUND: Optimal preservation of post-ischemic organ function is a continuing challenge in clinical lung transplantation. Retrograde instillation of preservation solutions has the theoretic advantage of achieving homogeneous distribution in the lung because of perfusing both the pulmonary and the bronchial circulation. So far, we have seen no experimental studies that include stereologic analysis of intrapulmonary edema concerning the influence of retrograde preservation on post-ischemic lung function after preservation with Perfadex and Celsior. METHODS: In an extracorporeal rat model, we perfused 8 lungs, each, using either antegrade or retrograde perfusion technique with Celsior (CE(ant)/CE(ret)) and Perfadex (PER(ant)/PER(ret)). Results were compared with low-potassium Euro-Collins. Post-ischemic lungs were reventilated and reperfused mechanically. We continuously monitored relative oxygenation capacity (ROC), pulmonary artery pressure, flush time, and wet/dry ratio. Furthermore, we used stereologic means to evaluate edema formation. Statistics comprised different analysis of variance models. RESULTS: Relative oxygen capacity of CE(ant)-protected lungs was superior to that of PER(ant) preservation (p = 0.05). Use of PER(ret) resulted in significantly higher ROC as compared with PER(ant) (p < 0.001) and was comparable to results obtained with CE-preservation, which was not further improved with retrograde application. CONCLUSIONS: Celsior provides better lung preservation than does Perfadex when administered antegradely. Retrograde application of Perfadex results in significant functional improvement as compared with antegrade perfusion, which reaches the standard of Celsior-protected organs. Additional in vivo experiments in combination with ultrastructural analysis are warranted to further evaluate retrograde delivery of preservation solutions, which could be used in clinical lung transplantation to further optimize current results.

Animals↗
PubMed2000

Thrombotic risk factors in pulmonary hypertension.

Thrombotic lesions are consistently observed in chronic thromboembolic pulmonary hypertension (CTEPH) and frequently found in primary pulmonary hypertension (PPH). It remains unknown, however, whether thrombosis is related to defects of the antithrombotic pathway or to previous vascular injury. This study therefore analysed the frequency of both hereditary and acquired thrombotic risk factors in CTEPH and PPH. One hundred and forty-seven consecutive patients with CTEPH investigated in the author's institution were compared to 99 consecutive patients with PPH. In 116 CTEPH patients and 83 PPH patients, phospholipid-dependent antibodies (antiphospholipid antibodies and lupus anticoagulant) were analysed by both immunological and clotting assays. In patients enrolled since 1994 (46 CTEPH and 64 PPH), hereditary thrombotic risk factors were also determined. Antithrombin, protein C and protein S activities were measured by functional assays. Mutations of factor V and factor II were identified by polymerase chain reaction. The prevalence of hereditary thrombotic risk factors was not increased in patients with either PPH or CTEPH. In contrast, a high frequency of phospholipid-dependent antibodies was observed in PPH (10%) and more notably in CTEPH (20%). Moreover, in PPH, antibodies were present only in low titre whereas in CTEPH, half of the patients with antiphospholipid antibodies had high titres. In addition, in CTEPH all but one of the patients with lupus anticoagulant also had antiphospholipid antibodies. The most striking finding of this study was the high prevalence of phospholipid-dependent antibodies but their clinical relevance appears to be different in primary pulmonary hypertension and chronic thromboembolic pulmonary hypertension. In primary pulmonary hypertension, these antibodies in low titre probably reflect endothelial dysfunction. In contrast, in chronic thromboembolic pulmonary hypertension the presence of antibodies in high titre associated with lupus anticoagulant, underlines the role of thrombosis in the pathogenesis of this condition.

Antibodies, Antiphospholipid↗
PubMed2000

von Willebrand factor binding to heparin in various types of von Willebrand disease.

INTRODUCTION: The purpose was to study von Willebrand factor (vWF) binding to heparin in different types of von Willebrand disease (vWD). MATERIALS AND METHODS: Plasma samples from 92 patients were representative of most vWD subtypes as they included 13 type 1, ten type 2N, 27 type 2A, 23 type 2B, and 19 type 2M patients. We selected assay conditions suitable for the screening of plasma vWF concentrations as low as 15 U/dl vWF:Ag. We determined the range of vWF concentrations in plasma where the percentage of (125)I-MAb/vWF complexes bound to heparin-agarose beads was constant. This range of dilution allowed circumvention of potential competition by other plasma heparin-binding proteins. RESULTS: The multimeric composition of vWF had hardly any influence on the ability of vWF to bind to heparin. Results were expressed as the ratio of heparin-binding capacity of patients' plasma to that of normal pool plasma. We found a ratio of 0.99+/-0.004 (mean+/-s.e.m.) for 23 normal individual donors. Furthermore, when comparing the mean values of plasma vWF-heparin binding ratios by ANOVA F-test in the six groups (one normal and five vWD), we found significant differences between them (P<0.0001). Pairwise comparison of multiples by the Scheffe's test indicated that the mean values of ratios in type 2A on the one hand and type 2M on the other, were significantly lower than in normal plasma, type 2N, type 2B and type 1. CONCLUSION: Our data suggest a relationship between the ability of vWF to bind to heparin and to the platelet GPIb receptor, since type 2B and 2N patients have an increased or normal ability to bind to GPIb whereas type 2A and 2M patients have an impaired interaction with that receptor.

Antibodies, Monoclonal↗
PubMed2000

The role of coenzyme Q10 in the pathophysiology and therapy of experimental congestive heart failure in the dog.

BACKGROUND: Coenzyme Q10 (CoQ10) is essential for ATP generation and has antioxidant properties. Decreased CoQ10 levels have been reported in human heart failure (CHF), but it remains unclear if this is a conserved feature of CHF. The objective of the study was to determine if tachycardia-induced CHF in the dog is associated with reduced CoQ10 levels. Furthermore, it was hypothesized that CoQ10 supplementation may improve CHF severity by preventing CoQ10 deficiency (if present) or via antioxidant effects. METHODS AND RESULTS: Serum and myocardial levels of CoQ10 were examined in normal dogs (n = 6), dogs with CHF (control, n = 5), and dogs with CHF treated with CoQ10 (CoQ10; 10 mg/kg/day, n = 5). Serum CoQ10 levels did not change with CHF in control dogs, and myocardial levels were similar to those of normal dogs. CoQ10 therapy increased serum but not myocardial levels of CoQ10. In early CHF, CoQ10-treated dogs had lower filling pressures, and, in severe CHF, CoQ10-treated dogs had less hypertrophy as compared with untreated dogs. Other indices of CHF severity were similar in control and CoQ10-treated dogs. CONCLUSION: These data indicate that CoQ10 deficiency is not present in this model of CHF. Although dramatic effects on hemodynamics were not observed, CoQ10 supplementation did appear to attenuate the hypertrophic response associated with CHF. Key words: enzymes, cardiomyopathy, hormones, antioxidant.

Animals↗
PubMed2000

Different kinetics of donor cell populations after isolated liver and combined liver/small bowel transplantation.

Spontaneous tolerance induction after liver transplantation also supports additional transplants, e.g. a small bowel graft, from the same donor (tolerogenic effect). Chimerism serves as a possible explanation of this phenomenon. Isolated liver (LTx) and combined liver/small bowel transplantation (LSBTx) are compared. LSBTx and LTx were performed in the BN --> LEW rat strain combination without immunosuppression. Parenchymal damage during rejection was monitored by sequential standard histology. Donor/recipient populations were identified and further differentiated for immunohistochemical single and double staining. A small number of donor specific leukocytes can be detected on all days in host organs (microchimerism). A significantly larger donor leukocyte population survives long-term in the sinusoids of liver (graft chimerism). Sinusoidal donor leukocytes survive rejection and recover in number after tolerance induction. Rejection of liver allografts and infiltration by host leukocytes are more pronounced after LSBTx than after LTx. Accordingly, during rejection a steeper decline of sinusoidal donor leukocytes is observed after LSBTx and recovery after tolerance induction is not as marked. Microchimerism apparently plays no significant role in either transplantation model. The number of sinusoidal donor leukocytes, however, mirrors closely host immune responses.

Animals↗
PubMed2000

Effects of natriuretic peptides on load and myocardial function in normal and heart failure dogs.

The effects on myocardial function and loading conditions of clinically relevant doses of the natriuretic peptides (NP) have not been established. The actions of single doses (100 ng x kg(-1) x min(-1) iv over 30 min) of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP) were studied in conscious normal dogs and in dogs with pacing-induced heart failure. All three NP reduced end-diastolic pressure in normal dogs, and ANP and BNP reduced end-diastolic volume. In heart failure ANP and BNP reduced EDP, and ANP reduced EDV. Arterial elastance was unchanged in normal dogs and in dogs with heart failure. ANP increased end-systolic elastance (E(es)) in normal dogs, whereas BNP tended to increase E(es) (P = 0.06). In dogs with heart failure, no inotropic effect was seen. In normal dogs, all NP reduced the time constant of isovolumic relaxation (tau), and ANP and BNP reduced tau in dogs with heart failure. Increases in plasma cGMP in dogs with heart failure were blunted. The NP reduced preload and enhanced systolic and diastolic function in normal dogs. Effects of ANP and BNP on preload and diastolic function were maintained in heart failure. Lack of negative inotropic effects in heart failure supports the validity of the NP as therapeutic agents.

Animals↗
PubMed2000

Beneficial effect of lung preservation is related to ultrastructural integrity of tubular myelin after experimental ischemia and reperfusion.

Ischemia/reperfusion (I/R) injury results in the impairment of surfactant activity. The hypothesis that the differences in lung preservation quality obtained by EuroCollins (EC) and Celsior (CE) solutions were related to surfactant alterations was tested. To avoid extensive structural damage and edema formation, which can secondarily affect the surfactant system, lungs were stored for a short ischemic period (2 h at 10 degrees C) and reperfused (50 min) in an isolated perfused rat lung model after preservation with either potassium-reduced (40 mmol) EC40 or with CE. Using a modified stereological approach ultrastructure, total amount and distribution of phospholipid membranes composing tubular myelin (tm) and small (s) and large (l) unilameliar vesicles (ul) were investigated in the organ in lungs fixed by vascular perfusion either in situ (controls) or after I/R (n = 5 per group). The total amount of intraalveolar surfactant was increased after I/R. However, a significant amount (p = 0.008) of tm was displaced into the alveolar lumen and showed wider meshes of the tm lattices than did the controls (p = 0.023) where almost all tm was epithelial. In lungs preserved with EC40, epithelial tm was significantly reduced (p = 0.018), resulting in a higher ratio (p = 0.034) of surface-inactive small ul (0.05 to 0.3 microm) to surface-active epithelial tm. In the CE group approximately 50% of the total tm pool was epithelial. This was accompanied by higher parenchymal air space and improved functional parameters. Epithelial and endothelial cell-specific immunostaining did not reveal any gross damage of the blood-gas barrier. In summary, improved lung function during reperfusion was associated with beneficial effects of lung preservation on tm integrity after I/R. These observations suggest that preservation solutions ameliorate events leading to surfactant disturbance even before extensive lung injury is manifested.

Animals↗
PubMed2000

ADSA Foundation Scholar award. Dairying and the environment.

Increases in average herd size have resulted in increased concentrations of manure at dairies. Inadequate or insufficient manure management practices and greater focus on agricultural pollution from environmental groups have increased the need for scrutiny from regulatory agencies. An overview of the sequence of activities that led to the development and final approval of the National Animal Feeding Operation Strategy is presented. The Strategy and associated policy changes serve as the foundation for new enforcement and compliance goals and probable alterations to existing permit requirements. Lastly, identified research needs and educational opportunities are presented.

Animals↗
PubMed2000

Fast and efficient mutation detection method using multiplex PCR and cycle sequencing--application to haemophilia B.

A method using multiplex PCR followed by cycle-sequencing has been developed to detect mutations in the FIX gene. The procedure was evaluated in 45 severe or mild haemophilia B patients from 45 unrelated families. At least one deleterious mutation was identified in every haemophiliac demonstrating the efficiency of the method. Furthermore the described procedure offers many advantages compared to other screening detection methods: it is fast (less than 48 h), simple (partly automated) and of relatively low cost (it requires only one PCR).

Codon, Nonsense↗
PubMed2000

Mapping and functional studies of two alloantibodies developed in patients with type 3 von Willebrand disease.

Inhibitors against von Willebrand factor (vWF) developed in two unrelated multitransfused patients (patients 1 and 2) with severe (type 3) von Willebrand disease (vWD) were analyzed. Both inhibitors were identified as antibodies of the IgG class by ELISA using immobilized purified vWF and either serum or purified Ig from the patients. Typing, mapping and functional studies of both antibodies revealed significantly distinct properties. Patient 1 antibody contained all subclasses of IgG (1, 2, 3 and 4) whereas antibody from patient 2 was a mixture of only IgG1 and 4. By ELISA using a series of immobilized purified proteolytic fragments of vWF, patient 1 antibody mainly bound to fragment SpIII and, to a lower extent, to fragments SpII and SpI; it poorly bound to P34 and the 39/34 kDa fragment. In contrast, patient 2 antibody only bound to fragments corresponding to the N-terminal portion of vWF but failed to bind to SpII. Functional studies were performed by testing the capacity of each antibody to inhibit vWF binding to its various ligands. Both antibodies blocked vWF binding to Factor VIII (FVIII), fibrillar type III collagen, bitiscetin and the subsequent induced binding to GPIb. Patient 1 antibody also blocked vWF binding to platelet GPIb when induced by ristocetin. However it failed to block vWF binding to GPIb when induced by botrocetin as well as the binding of botrocetin itself to vWF. Our data thus suggest that this inhibitor does not recognize the GPIb-binding site on vWF but the sites of vWF involved in its interaction with ristocetin. In contrast, we observed that patient 2 antibody blocked vWF binding to platelet GPIb induced by either agonist as well as vWF binding to botrocetin. Finally, the effect of the antibodies was tested on vWF binding to GPIIb/IIIa. As expected from the mapping experiments, only IgG from patient 1 blocked the interaction while IgG from patient 2 had no effect. In conclusion, we have shown that two multitransfused patients with type 3 vWD have developed alloantibodies with similar properties to those of polyclonal antibodies but with distinct effects on the functions of vWF.

Adult↗
PubMed2000

Acquired von Willebrand syndrome: data from an international registry.

The acquired von Willebrand syndrome (AvWS) is a rare bleeding disorder with laboratory findings similar to those of congenital von Willebrand disease (vWD). Despite the numerous cases reported in the literature until 1999 (n = 266), large studies on AvWS are not available. Moreover, diagnosis of AvWS has been difficult and treatment empirical. These considerations prompted us to organize an international registry. A questionnaire, devised to collect specific information on AvWS, was sent to all the members of the International Society on Thrombosis and Haemostasis (ISTH), who were invited to respond if they had diagnosed cases with the AvWS cases. 156 members answered the questionnaire and 54 of them sent information on 211 AvWS cases from 50 centers. Data were compared with those already published in the literature and 25 cases already described or not correctly diagnosed were excluded. The 186 AvWS cases that qualified for the registry were associated with lymphoproliferative (48%) and myeloproliferative disorders (15%), neoplasia (5%), immunological (2%), cardiovascular (21%) and miscellaneous disorders (9%). Ristocetin cofactor activity (vWF:RCo) or collagen binding activity (vWF:CBA) were usually low in AvWS (median values 20 U/dL, range 3-150), while factor VIII coagulant activity was sometimes normal (median 25 U/dL, range 3-191). FVIII/vWF inhibiting activities were present in only a minority of cases (16%). Bleeding episodes in AvWS were mostly of mucocutaneous type (68%) and were managed by DDAVP (32%), FVIII/vWF concentrates (37%), intravenous immunoglobulins (33%), plasmapheresis (19%), corticosteroids (19%) and immunosuppressive or chemotherapic agents (35%). Based upon the data of this international registry, it appears that AvWS is especially frequent in lympho- or myeloproliferative and cardiovascular diseases. Therefore, AvWS should be suspected and searched with the appropriate laboratory tests especially when excessive bleeding occurs in patients with these disorders. On the basis of the information provided by this registry guidelines for diagnosis and management of the AvWS are given.

Adolescent↗