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Biomedical subjects

G Stiegler

Publications and source records attributed to G Stiegler.

At least 37 records · Page 2Linked to original sources
PubMed1999

The rise of reticulated platelets after intensive chemotherapy for AML reduces the need for platelet transfusions.

We assumed that a recovery of thrombopoiesis after intensive chemotherapy for acute myelogenous leukemia (AML) could reduce the need for prophylactic platelet transfusions. We therefore assessed the start of platelet production by means of daily determination of reticulated platelets (RP). The increase in RP occurred on day 20 (median) after the start of chemotherapy and was followed by a rise of peripheral platelet counts 2-3 days thereafter. Consequently, a rise of RP during the period of recovery can be regarded as representing the reconstitution of the peripheral platelet count and may reduce or eliminate the need for prophylactic platelet transfusions.

Adult↗
PubMed1999

Safety issues of plateletpheresis: comparison of the effects of two cell separators on the activation of coagulation, fibrinolysis, and neutrophils and on the formation of neutrophil-platelet aggregates.

BACKGROUND: Although many donors undergo repeated plateletpheresis, data on the consequences of plateletpheresis for the donor's health remain scarce. Thus, the effect of plateletpheresis on the activation of coagulation, fibrinolysis, and neutrophils was investigated. STUDY DESIGN AND METHODS: Part 1: Sixteen healthy men were randomly assigned to undergo plateletpheresis on a cell separator (AMICUS, Fenwal Baxter; or MCS 3p, Haemonetics). The effects of plateletpheresis on plasma levels of prothrombin fragment (F(1+2)), D-dimer, plasmin-plasmin inhibitor (PPI) complexes, and plasminogen activator inhibitor (PAI-1); on the activation of neutrophils (% L-selectin+); and on the frequency of platelet-neutrophil aggregates (% CD41+ neutrophils) were compared. Part 2: Ten healthy men received infusions of ACD-A and placebo without apheresis in a randomized, double-blind crossover study to control for the pharmacologic effects of citrate. RESULTS: Part 1: No change in F(1+2) occurred (p>0.05), which indicated that plateletpheresis did not enhance coagulation. Levels of D-dimer, PPI, and PAI-1 decreased over time on the AMICUS (p<0.001). Plateletpheresis did not activate neutrophils (p>0.05), but it decreased the percentage of CD41+ neutrophils (p<0.003). An approximately 80-percent drop in mononuclear cells was observed in the extracorporeal circulation of the AMICUS (p<0.001 vs. baseline and p = 0.005 vs. MCS 3p), and circulating lymphocyte and monocyte counts decreased concomitantly. Part 2: Infusion of ACD-A slightly decreased D-dimer levels (p<0.05), and both infusions decreased the circulating lymphocyte counts. CONCLUSION: Plateletpheresis can be regarded as safe with respect to the activation of coagulation or neutrophils. The consequences for the donor's health of the decrease in D-dimer, PPI, and PAI-1 may deserve further investigation.

Adult↗
PubMed1999

The proportion of reticulated platelets is higher in bone marrow than in peripheral blood in haematological patients.

Since the detection that platelets originate from megakaryocytes (MK), the site of megakaryocyte fragmentation has been disputed. Some authors have even postulated that platelets are solely produced in the lungs. Thus, we have directly measured platelet generation in the bone marrow (BM) by comparing the relative number of young RNA-containing, so-called reticulated platelets (%RP) in the BM and in the peripheral blood (PB). Two separate prospective, cross sectional trials have been conducted in patients routinely undergoing BM biopsies for diagnostic purposes. In the first part of the study 30 patients with stem cell or bone marrow transplantation were examined. The second part of the study was performed in 62 haematological patients visiting the outpatient's clinic. Median %RP were higher in BM than in PB (p <0.001). In the second part of the study the difference averaged 133% (interquartile range: 30-383%). There was a moderate correlation between %RP in BM and in PB (r = 0.67; p <0.001). The absolute number of RP in PB correlated weakly with the number of megakaryocytes (0.42; p = 0.001), which was due to a correlation between the platelet counts and the megakaryocyte counts (r = 0.55; p <0.001 in biopsies). Two patients with autoimmune antibodies against GPIIb/IIIa exhibited 10% and 16% RP in PB, and had 29% and 59% RP in BM, respectively. It is concluded that the relative number of RP is significantly higher in BM than in blood. This supports the notion that platelets are at least in part released from MK in the bone marrow, particularly in patients suffering from immune thrombocytopenia.

Antigens, Surface↗
PubMed1999

Protection of Macaques against pathogenic simian/human immunodeficiency virus 89.6PD by passive transfer of neutralizing antibodies.

The role of antibody in protection against human immunodeficiency virus (HIV-1) has been difficult to study in animal models because most primary HIV-1 strains do not infect nonhuman primates. Using a chimeric simian/human immunodeficiency virus (SHIV) based on the envelope of a primary isolate (HIV-89.6), we performed passive-transfer experiments in rhesus macaques to study the role of anti-envelope antibodies in protection. Based on prior in vitro data showing neutralization synergy by antibody combinations, we evaluated HIV immune globulin (HIVIG), and human monoclonal antibodies (MAbs) 2F5 and 2G12 given alone, compared with the double combination 2F5/2G12 and the triple combination HIVIG/2F5/2G12. Antibodies were administered 24 h prior to intravenous challenge with the pathogenic SHIV-89.6PD. Six control monkeys displayed high plasma viremia, rapid CD4(+)-cell decline, and clinical AIDS within 14 weeks. Of six animals given HIVIG/2F5/2G12, three were completely protected; the remaining three animals became SHIV infected but displayed reduced plasma viremia and near normal CD4(+)-cell counts. One of three monkeys given 2F5/2G12 exhibited only transient evidence of infection; the other two had marked reductions in viral load. All monkeys that received HIVIG, 2F5, or 2G12 alone became infected and developed high-level plasma viremia. However, compared to controls, monkeys that received HIVIG or MAb 2G12 displayed a less profound drop in CD4(+) T cells and a more benign clinical course. These data indicate a general correlation between in vitro neutralization and protection and suggest that a vaccine that elicits neutralizing antibody should have a protective effect against HIV-1 infection or disease.

AIDS Vaccines↗
PubMed1998

Elevated numbers of reticulated platelets in hyperthyroidism: direct evidence for an increase of thrombopoiesis.

We studied thrombopoietic activity in hyperthyroidism by determination of reticulated platelet counts. At the time of hyperthyroidism 14/15 patients had higher reticulated platelets than after achievement of euthyroidism (P<0.001). There was no difference in peripheral platelet counts and mean platelet volumes at the time of hyperthyroidism when compared to euthyroidism. Three patients had pan- and auto-reactive platelet antibodies during hyperthyroidism. These antibodies were directed against GPIIb/IIIa in two patients and against GPIb/IX in one patient. Our findings provide direct evidence that hyperthyroidism is associated with increased platelet production, as reflected by an increase in reticulated platelets.

Adult↗
PubMed1998

Direct evidence for an increase in thrombopoiesis after liver transplantation.

BACKGROUND: In advanced liver cirrhosis, thrombocytopenia results from 'hypersplenism' due to increased platelet sequestration and platelet 'pooling' in the enlarged spleen and/or from reduced platelet production in the bone marrow. We sought to differentiate between these two mechanisms by studying thrombopoiesis before and after orthotopic liver transplantation by the determination of reticulated platelets, direct indicators for the thrombopoietic activity in the bone marrow. METHODS: Reticulated platelets, peripheral platelet counts, mean platelet volumes and platelet-reactive antibodies were determined in 15 patients suffering from advanced liver cirrhosis before and during an observation period of 14 days after orthotopic liver transplantation (OLT). Thrombopoietin levels of ten patients were determined before transplantation and consecutively for 14 days after surgery. RESULTS: All patients except one were thrombocytopenic before transplantation (median count 94 x 10(9) L-1, range 69-114 x 10(9) L-1). Although levels of reticulated platelets rose 2 days after surgery from baseline values of 1.0% (range 0.2-1.6%) to peak values of 4.6% (range 1.7-17.9%, P < 0.05) on day 6, platelet counts declined during the first 5 days after transplantation. When peripheral platelet counts increased to the normal range (median day 11, range day 8-33), reticulated platelets were again at pretransplant levels. Thrombopoietin levels before OLT were within the normal range (< 85 pg mL-1). On day 5 post surgery, a maximum increase of 5.8-fold (range 2.2- to 28-fold) over baseline values was observed. Mean platelet volume did not show any significant deviation from the baseline values and platelet antibodies could not be detected during the observation period. CONCLUSION: Our findings provide direct evidence for an increase in de novo platelet production after orthotopic liver transplantation. As the elevation of reticulated platelets precedes platelet recovery, it could serve as an early indicator to predict thrombopoiesis as a result of reconstituted liver function.

Adult↗
PubMed1998

Differential induction of P-selectin expression on platelets by two cell separators during plateletpheresis and the effect of gender on the release of soluble P-selectin.

BACKGROUND: Though a number of studies have elegantly characterized platelet activation during storage, less attention has been paid to the initial activation caused by different collection procedures. STUDY DESIGN AND METHODS: The effects of two blood cell separators on the initial activation of platelets were measured by flow cytometric analysis of P-selectin expression in 13 male donors on one cell separator (CS 3000 Plus) and 11 men and 9 women on the other (MCS 3P). In addition, the storage and release of soluble P-selectin (circulating P-selectin [cP-selectin]) by platelets were quantified, to determine whether the change in cP-selectin is a more sensitive marker for initial platelet activation, and the influence of gender on measured endpoints was evaluated. RESULTS: The CS 3000 Plus increased the percentage of P-selectin-positive platelets from a median of 3.4 percent before apheresis to 7.6 percent (p = 0.006) in platelet concentrates (PCs), whereas the MCS 3P did not (p = 0.002 between the two cell separators). When preapheresis cP-selectin levels were compared to those in apheresis PCs, cP-selectin increased from 51 to 101 ng per mL in plasma of CS 3000 Plus PCs, whereas cP-selectin levels increased from 53 to 78 ng per mL in MCS 3P PCs (men) and from 48 to 99 ng per mL in MSC 3P PCs (women) (p<0.005 for all). The relative increase in cP-selectin was higher in women than in men in MCS 3P PCs (p = 0.013). Concomitantly, the amount of P-selectin stored in platelets before apheresis decreased (p<0.025 for all). When donors undergoing apheresis on the MCS 3P were compared, the amount of P-selectin stored in the platelets of PCs was higher in men than women (p = 0.026). CONCLUSION: This trial shows 1) that initial activation of platelets obtained with the MCS 3P is less than that of platelets obtained with the CS 3000 Plus; 2) that the increase in cP-selectin is a more sensitive marker for initial platelet activation than the expression of P-selectin on the surface; and 3) that the relative amount of cP-selectin is higher in women than in men given the same stimulus. Differences in platelet activation by various cell separators and the sex of the donor may contribute to variability of PC quality.

Blood Platelets↗
PubMed1998

Increase in endogenous thrombopoietin in healthy donors after automated plateletpheresis.

BACKGROUND: Thrombopoietin (TPO) is a key cytokine involved in the regulation of megakaryocytopoiesis and platelet production. The aim of the present study was to test whether platelet donation is associated with changes in the serum TPO levels in healthy donors undergoing plateletpheresis. STUDY DESIGN AND METHODS: The study group consisted of 23 healthy donors undergoing single-donor plateletpheresis for the first time. Serum TPO levels and platelet counts were determined before platelet collection, at the end of apheresis, and for 4 days thereafter. Serum TPO levels were determined by a TPO-specific enzyme-linked immunosorbent assay. RESULTS: In relationship to platelet donation, serum TPO levels showed a temporary increase from baseline levels of 69.2 +/- 7.1 pg per mL to 117 +/- 6.8 pg per mL 2 days after plateletpheresis (p < 0.05). Further evaluation revealed a decline in serum TPO levels as platelet counts increased. Female donors showed a delayed normalization of circulating platelet numbers and serum TPO levels as compared to male donors. There was no significant correlation between serum TPO levels and the absolute platelet number during normalization of the donors' platelet counts after plateletpheresis. CONCLUSION: Single-donor plateletpheresis results in a temporary increase in serum TPO levels in healthy platelet donors, which may be part of a compensatory response-boosting megakaryocytopoiesis after platelet collection.

Blood Donors↗
PubMed1998

Measurement of the levels of reticulated platelets after plateletpheresis to monitor activity of thrombopoiesis.

BACKGROUND: Little is known about the effects of long-term plateletpheresis on the donors' health. The aim of this study was to examine the effect of plateletpheresis on the time course of reticulated platelet counts as an estimate for thrombopoiesis. STUDY DESIGN AND METHODS: The effect of moderate platelet depletion on the thrombopoietic capacity was evaluated prospectively by the measurement of reticulated platelets before and after plateletpheresis and on the following 4 days. Donors undergoing plateletpheresis for the first time were compared to those donating platelets every other week for more than 18 months. RESULTS: The median levels of reticulated platelets were significantly lower in frequent donors than in new donors. In new donors, there was a transient increase in the median levels of reticulated platelets on Day 3 after apheresis, and baseline values were reached again on Day 4. On the contrary, in repeat donors, there was a sustained rise in the percentage of reticulated platelets from Days 1 through 4. However, this increase in reticulated platelet counts was still less than that seen in new donors. There was no difference in the peripheral blood platelet counts in the two groups at any time point. CONCLUSION: These findings suggest that repeat platelet donation might lead to a relative exhaustion of thrombopoiesis, as evidenced by the low levels of reticulated platelets exhibited by repeat donors. The reticulated platelet count can be used to monitor the thrombopoietic capacity of long-term platelet donors.

Adult↗
PubMed1995

Soluble lipopolysaccharide receptor (CD14) is released via two different mechanisms from human monocytes and CD14 transfectants.

The receptor for lipopolysaccharide LPS (CD14) exists in a membrane-associated (mCD14) and a soluble form (sCD14). Previous studies indicate that monocytes produce sCD14 by limited proteolysis of the membrane-bound receptor. In this study we demonstrate that human monocytes also produce sCD14 by a protease-independent mechanism. To investigate the molecular nature of this second pathway we studied sCD14 formation in the monocytic cell line Mono Mac 6 (MM6) and in CD14 transfectants. Both MM6 and the CD14 transfectants constitutively produce sCD14 by a protease-independent mechanism. Structural analysis of sCD14 produced by the CD14 transfectants reconfirmed the presence of the COOH terminus predicted from the cDNA. Since glycosylphosphatidylinositol anchor attachment is associated with the removal of a hydrophobic C-terminal signal peptide, our finding demonstrates that the transfectants secrete sCD14 which escaped this posttranslational modification. Identical results obtained for sCD14 derived from peritoneal dialysis fluid of a patient with kidney dysfunction show the in vivo relevance of this pathway for sCD14 production.

Amino Acid Sequence↗
PubMed1986

Lentivirus genomic organization: the complete nucleotide sequence of the env gene region of equine infectious anemia virus.

The nucleotide sequence of the envelope (env) gene region of equine infectious anemia virus (EIAV), a member of the lentivirus subfamily of retroviruses, has been determined from a clone of integrated proviral DNA for which the gag and pol sequences have been reported previously. The env gene is 859 codons in length and the sequence reported here is consistent with the published biochemical properties of EIAV glycoproteins. The env gene region of EIAV shares considerable structural similarities but negligible sequence homologies with the env genes of other members of the lentivirus subfamily, visna virus, and human T-lymphotropic virus (HTLV-III) or lymphadenopathy virus (LAV). As in visna virus and HTLV-III, the polymerase (pol) and env genes of EIAV do not overlap. EIAV contains two short open reading frames (orf) of 50 and 66 codons in the pol-env intergenic region. However, unlike the orf Q regions reported for visna virus and HTLV-III, neither EIAV orf overlaps the 3' terminus of the adjacent pol gene. The EIAV genome also contains a third short open reading frame of 135 codons which is contained completely within the env gene, in contrast to the 3'-orf/orf F gene reported for HTLV-III/LAV which extends beyond the env gene terminus. These results provide a detailed description of the env gene region of EIAV and describe a number of characteristic features of genomic organization in lentiviruses which contrast with the genomic organization of oncogenic retroviruses.

Amino Acid Sequence↗
PubMed1985

[Secondary implantation of intraocular lenses].

Since 1980 a total of 1014 anterior chamber lenses, type Kelman II and Omnifit, have been implanted, 308 of them as a secondary procedure. Unilateral and bilateral implantation was performed in normal aphakic eyes, in aphakic glaucoma, after injuries, combined with keratoplasty, and in one case in keratophakia. The cases were not preselected. Implantation was successfully accomplished in 100% of the cases.

Adolescent↗
PubMed1982

[Laser Iridectomy (author's transl)].

During the period mentioned 150 laser iridectomies were performed using the pulsed argon laser (BRITT Corp). With the help of a specially developed three mirror glass, (Stiegler) it is possible, without exception, to penetrate the iris in one session, regardless of its color or the depth of the anterior chamber. The technique used, and the tonographic and histologic investigations and results are discussed. The findings provide a new insight into the mechanism of out flow in glaucoma.

Humans↗