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Biomedical subjects

J Fehr

Publications and source records attributed to J Fehr.

122 records · Page 7Linked to original sources
PubMed1978

[Granulocyte substitution in febrile leukemia patients with bone marrow aplasia. 1. Results of a prospective study].

A prospective, randomized study was performed in aplastic, granulocytopenic, infected patients with acute leukemia during induction therapy. 12 patients received antibiotics alone, and 13 received antibiotics plus 1.7-14.7 X 10(10) (MEAN 6.6 X 10(10) granulocytes by 1-5 (mean 2.7) daily transfusions. In 10 of 12 controls the infection resolved and remission was achieved with granulocyte counts greater than 500/mm3 15 +/- 9 days after randomization. In the transfused patients, infection was brought under control in 10 out of 13 and remission was achieved with granulocyte counts greater than 500/mm3 25+/- 11 days after randomization. Only one death due to infection was observed (6 days after randomization, control).

Anemia, Aplastic↗
PubMed1977

[Efficiency of the blood cell separator Haemonetic 30 in the separation of platelets from single donors].

By means of the Haemonetic 30 separator we were able to collect 4.1 +/- 0.94 X 10(11) (X +/- 1 SD) platelets in 57 procedures consisting of 5-6 cycles. The platelet yield was significantly influenced by the blood volume processed and by initial platelet counts in donors. Augmenting platelet collection volume in the red colored part of the buffy-coat from 10-20 ml did not increase the yield. Transfusion of collected platelets into 27 non-sensitized patients showed normal recovery of 43% at one hour and shortening of bleeding time from over 30 min to a mean of 5 min 20 sec in 12 patients tested. Autotransfusion of 51Cr-labeled platelets into 8 healthy donors revealed identical recoveries (42 +/- 12%) and a normal survival time (9.2 +/- 0.7 days).

Cell Separation↗
PubMed1977

In vitro granulocyte adherence and in vivo margination: two associated complement-dependent functions. Studies based on the acute neutropenia of filtration leukophoresis.

To study mechanisms and mediators regulating the distribution of intravascular granulocytes between circulating and marginated pools, a human model with extreme transient margination, the neutropenia of continuous flow filtration leukophoresis, was analyzed. Studies in animals demonstrated the existence of a complement (C)-derived granulocytopenia-inducing factor. Thus, autologous plasma, exposed to nylon fibers (NF) of the filtration system, produced an acute selective decrement of circulating granulocytes and monocytes. This phenomenon was blocked by decomplementing plasma, by pretreatment of plasma with EDTA or hydrazine, and by preheating at 56 degrees C, but did occur after recombination of heat-inactivated and hydrazine-treated plasma before NF exposure. Preheating plasma at 50 degrees C did not inhibit the neutropenic response, suggesting involvement of the classical pathway of C activation. Ultrafiltration studies indicated that the NF-provoked neutropenia-inducing factor has a mol wt in the range of 10,000-30,000, and is heat stable (56 degrees C). To analyze the hypothesis that C- induced neutrophil margination might be consequent to increased cell adhesiveness to endothelial surfaces, the role of C in promoting granulocyte adherence was evaluated in vitro. Measured with a plastic Petridish assay, granulocyte adherence was significantly reduced in heat- inactivated (56 degrees C) and hydrazine-treated plasma, but adherence promoting capacity was restored by mixing the two plasmas, or by adding purified C3 to hydrazine-treated plasma. After exposure to activated C, neutrophils showed significantly increased adhesiveness which was maintained when cells were resuspended in heat-inactivated plasma, but progressively lost when resuspended in fresh plasma. On the basis of these results we conclude that granulocyte adhesiveness in vitro and margination in vivo are closely associated, C-dependent phenomena.

Agranulocytosis↗
PubMed1977

Complement and leukocyte-mediated pulmonary dysfunction in hemodialysis.

During hemodialysis, cardiopulmonary decompensation may appear in uremic patients, possibly caused by plugging of pulmonary vessels by leukocytes. In 34 patients we noted leukopenia (20% of initial levels) during hemodialysis that in 15 was associated with impaired pulmonary function. When we infused autologous plasma, incubated with dialyzer cellophane, into rabbits and sheep, sudden leukopenia and hypoxia occurred, with doubling of pulmonary-artery pressures and quintupling of pulmonary-lymph effluent. Histologic examination showed severe pulmonary-vessel-leukostasis and interstitial edema. The syndrome was prevented by preinactivation of complement but was reproduced by infusions of plasma in which complement was activated by zymosan. Thus, acute pulmonary dysfunction from complement-mediated leukostasis may play a major part in the acute cardiopulmonary complications of cellophane-membrane hemodialysis.

Adolescent↗
PubMed1977

Hemodialysis leukopenia. Pulmonary vascular leukostasis resulting from complement activation by dialyzer cellophane membranes.

Acute leukopenia occurs in all patients during the first hour of hemodialysis with cellophanemembrane equipment. This transient cytopenia specifically involves granulocytes and monocytes, cells which share plasma membrane reactivity towards activated complement components. The present studies document that complement is activated during exposure of plasma to dialyzer cellophane, and that upon reinfusion of this plasma into the venous circulation, granulocyte and monocyte entrapment in the pulmonary vasculature is induced. During early dialysis, conversion of both C3 and factor B can be demonstrated in plasma as it leaves the dialyzer. Moreover, simple incubation of human plasma with dialyzer cellophane causes conversion of C3 and factor B, accompanied by depletion of total hemolytic complement and C3 but sparing of hemolytic C1. Reinfusion of autologous, cellophane-incubated plasma into rabbits produces selective granulocytopenia and monocytopenia identical to that seen in dialyzed patients. Lungs from such animals reveal striking pulmonary vessel engorgement with granulocytes. The activated complement component(s) responsible for leukostasis has an approximate molecular weight of 7,000-20,000 daltons. Since it is generated in C2-deficient plasma and is associated with factor B conversion, it is suggested that activation of complement by dialysis is predominantly through the altermative pathway.

Adult↗
PubMed1976

Complement-mediated granulocyte dysfunction in paroxysmal nocturnal hemoglobinuria.

In paroxysmal nocturnal hemoglobinuria (PNH), infection, both viral and bacterial, disproportionate to the mild neutropenia seen in many such patients is responsible for significant morbidity. We report impaired granulocyte chemotaxis efficiency which may contribute to the problems induced by bacterial infections. PNH (but not normal) granulocytes, after exposure to very small concentrations of activated serum complement components, migrate poorly, as documented by their inhibited chemotaxis toward bacterial products or activated complement components in Boyden chambers. The granulocytes remain intact, excluding trypan blue, phagocytosing, and killing bacteria, despite this activated complement exposure. It is also suggested that this chemotactic defect may involve only a clone of cells, analogous to the clonal lysis of PNH erythrocytes; those few granulocytes capable of migration after exposure to activated complement contain normal quantities of leukocyte alkaline phosphatase (LAP), in contrast to the LAP deficiency of the overall PNH granulocyte population. Since bacterial infection may initiate or potentiate hemolysis, one of the major symptoms of the disease, these results could explain much of the morbidity of PNH.

Alkaline Phosphatase↗
PubMedDate not supplied

Amplification of unknown DNA sequences by sequence-independent nested polymerase chain reaction using a standardized adaptor without specific primers.

A new procedure for sequence-independent PCR amplification of DNA fragments is described. DNA from pUC18 plasmid was used as a test DNA. It was digested with a frequently cutting restriction enzyme (Sau3A), generating sticky ends. The DNA was ligated to a synthetic, non-phosphorylated adaptor and subsequently amplified in a nested PCR using two oligonucleotides with sequences derived from the adaptor. As little as 1 fg of pUC18 DNA could be detected by this procedure. The product was analyzed on a gel and hybridized with a pUC18-specific probe. The sequence-independent nested PCR was repeated with different amounts of pUC18 DNA in the presence of an excess of non-specific DNA. In these experiments, pUC18 DNA fragments were amplified in a concentration-dependent manner. After hybridization with a digoxigenin dUTP-labelled pUC18 DNA probe, 1 fg of pUC18 DNA could still be detected. This method allows rapid screening of blood for low titred and mutated viruses in which primer binding sites are not conserved.

Base Sequence↗
PubMedDate not supplied

Evaluation of an optimal dose of low-molecular-weight heparin for thromboprophylaxis in pregnant women at risk of thrombosis using coagulation activation markers.

There is no consensus on the dose of low-molecular-weight (LMW) heparin for thromboprophylaxis in pregnant women at increased risk of thrombosis. Based upon monitoring with anti-factor Xa activity, the studies showed conflicting results suggesting either fixed dosages throughout the pregnancy or dosages adapted to the gestational age. We tested whether monitoring thromboprophylaxis with D-dimers and thrombin-antithrombin complexes (TAT) would provide additional information on the optimal dose of LMW heparin. Women (165 women and 202 pregnancies) with hereditary or acquired thrombophilia or a history of thrombosis were considered to receive prophylactic LMW heparin therapy. All women received initially 5,000 IU/day of dalteparin s.c. All further dosages were determined solely on the basis of TAT and/or D-dimer values which were determined every 2-3 weeks. As soon as one of these values increased above the normal range, the dose of LMW heparin was adjusted. In 84.6% of all pregnancies, TAT and/or D-dimer values increased above the normal range once or more during the pregnancy. Consequently, the dose of LMW heparin had to be adjusted at least once over the course of the pregnancy. The mean daily dose of LMW heparin increased from 5,000 to 11,200 U between the 6th and 40th week of gestation. Adverse effects included one major bleeding and six local complications, but no thromboembolic event. In conclusion, increasing doses of LMW heparin are needed to keep TAT and D-dimers within the normal range during pregnancy. Hence, to suppress thrombin generation, apparently, the dosage of LMW heparin should be adjusted to the gestational age rather than using fixed doses throughout the pregnancy. However, it remains to be further established whether elevated TAT and D-dimers truly reflect a prothrombotic state during pregnancy.

Adolescent↗