bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential effects of recombinant human colony stimulating factor (rh G‐CSF) on stem cells in marrow, spleen and peripheral blood in mice
Authors: Bungart B. , Loeffler M. , Goris H. , Dontje B. , Diehl V. , Nijhof W. 
Published: March 2008

Summary Previously it has been hypothesized that the granulopoietic and erythropoietic lineages may compete for differentiating stem cells. According to this hypothesis one would expect that a stimulation of granulopoiesis by G‐CSF administration would lead to a reduction of the stem cell pool and be followed by a decline of erythropoietic progenitor numbers. In addition one would expect an enhanced response of granulopoiesis if G‐CSF administration were combined with suppression of erythropoiesis by red cell transfusion.To evaluate whether this hypothesis holds true C57bl mice were injected subcutaneously for 6 d with 3. 75 μg rh G‐CSF/ mouse/d (150 μg G‐CSF/kg body weight/d). Marrow CFU‐S numbers showed an increase to 160% on day 2, followed by a decrease to 50% of control on day 6. Splenic and peripheral blood CFU‐S increased 20‐fold and 10‐fold, respectively. Marrow CFU‐E declined to 40% of the control value. Splenic CFU‐E increased 10‐fold. The increase in marrow CFU‐GM numbers ranged between 140% and 180%. CFU‐GM obtained from the spleen and the peripheral blood increased 60‐fold and 15‐fold. respectively. Regarding the CFU‐S and CFU‐GM a similar pattern of response was found in an experiment where rh G‐CSF administration was combined with an additional red cell transfusion. These data do not provide convincing evidence for an exhaustion of haemopoietic stem cells during treatment with G‐CSF. They rather suggest that an important side effect of G‐CSF treatment is a release of CFU‐S and progenitors from the marrow to the peripheral blood and a reseeding in the spleen.
CD4 and CD8 subpopulation changes during high dose intravenous immunoglobulin treatment
Authors: Macey M. G. , Newland A. C. 
Published: March 2008

Summary High doses of immunoglobulin, when given intravenously (IVIgG), influence lymphocyte subset numbers and function. T‐lymphocytes may be subdivided into two functionally different groups. helper/inducer (CD4+) and suppressor/cytotoxic (CD8+). Considerable functional as well as phenotypic heterogeneity exists within the two major subsets. CD4+ cells have been further subdivided into helper/inducer and suppressor/inducer sets by the differential binding of two monoclonal antibodies 4B4 (CDw29) and 2H4 (CD45R). Similarly, the CD8 + subset may be subdivided into suppressor and cytotoxic populations by the differential binding of monoclonal antibodies which identify the C3bi receptor (CD11).During IVIgG treatment of patients with autoimmune thrombocytopenic purpura (ATP) the change in CD4/CD8, due to an absolute increase in CD8 + cells, has been shown to correlate with the response to treatment as determined by platelet increase. However, the total CD4+ and CD8 + numbers may not reflect changes in their constituent subpopulations. To examine this possibility the CD4 and CD8 subpopulations were analysed in 15 ATP patients, during IVIgG treatment, using a double fluorescence technique. In 10 of these patients the in vitro response to pokeweed mitogen (PWM) and Staphylococcus aureus Cowan I (STA Cowan I) was determined. There was no correlation between the change in CD8 + subpopulations and response to treatment but there was a correlation between the CD4 + change and platelet increment. In addition there was a correlation between the 4B4/2H4 change and the in vitro response to PWM but no correlation with the response to STA Cowan I. These findings suggest that during IVIgG treatment the CD4 + 4B4 + helper/inducer population is influenced resulting in reduced T‐dependent B‐cell activation.
Enhanced complement‐susceptibility and dysfunction of lymphocytes in paroxysmal nocturnal haemoglobinuria (PNH)
Authors: Tomiyama Junji , And Haruhiko Ninomiya , Abe Tsukasa 
Published: March 2008

Summary We investigated the complement‐susceptibility of paroxysmal nocturnal haemoglobinuria (PNH) lymphocytes in relation to their dysfunction. When assessed by complement‐mediated lysis induced by monoclonal antibodies (CD5 or CD20) and rabbit complement, the complement‐susceptibility of lymphocytes from patients with PNH, both CD5+ (Tcells) and CD20+ (B cells). was greater than that from controls (P<0.001). This susceptibility was further enhanced, both in normal controls (P<0.01) and in patients with PNH (P<0.001). when the activity of decay‐accelprating factor (DAF) on the lymphocytes was blocked with anti‐DAF monoclonal antibody. DAF amounts in mono‐nuclear cells (MNC) from patients with PNH, measured by an enzyme‐linked immunosorbent assay (ELISA), were lower than those of the controls (P<0.001). The expressions of DAF on T cells and on B cells from patients with PNH were significantly decreased (P<0.05 in T cells: P<0.01 in B cells). MNC from patients with PNH responded less to phytohaemagglutinin (PHA) and concanavalin A (Con A) than MNC from the controls (P<0.001). In contrast. the responses of PNH MNC to poke weed mitogen (PWM) or lipopolysaccharide (LPS) were not impaired. MNC from a normal donor preincubated with anti‐DAF became less responsive to PHA or Con A.We conclude that PNH lymphocytes show enhanced complement‐susceptibility and that they are involved in their own expression of DAF as well as in other types of peripheral blood cells. The results of the responses to various lectins suggest the dysfunction of T cells in PNH.
A clinical trial on efficacy and safety of teicoplanin in combination with beta‐lactams and aminoglycosides in the treatment of severe sepsis of patients undergoing allogeneic/autologous bone marrow transplantation
Authors: Lang E. , And J. Schmid , Fauser A. A. 
Published: March 2008

Summary Early institution of empiric therapy with a broad‐spectrum antibiotic has markedly reduced the morbidity and mortality from infections complicating severe or prolonged cytopenia in patients receiving either an allogeneic or autologous hone marrow transplant. Ceftazidime in combination with an aminoglycoside, i.e. netilmicin, has been established as a combination schedule offering low or even avoiding therapy‐related toxicity.We evaluated teicoplanin for suspected Gram‐positive infections after inadequate response to initial beta‐lactam and aminoglycoside combination therapy. All 11 patients so far included in this study received either an allogeneic (five patients) or an autologous (six patients) bone marrow transplant for acute myeloid leukaemia (AML). non‐Hodgkin lymphoma (NHL. high grade) or other malignant diseases. All patients developing a primary septicaemia of unknown origin (10 patients) or a catheter related septicaemia (one patient) were treated with 400 mg teicoplanin, administered i.v. once daily in combination with a cephalosporin and an aminoglycoside (ceftazidime 2 g. i.v., t.i.d., netilmicin 400 mg once daily). All 11 patients responded to therapy. 10 patients were clinically cured, one patient improved under therapy. The therapeutic regimen was well tolerated and adverse drug reactions did not occur. We have not observed any delayed take or prolonged neutropenia or thrombocytopenia with this therapeutic regimen when compared to other bone marrow transplant patients who did not receive this antimicrobial therapy.Our preliminary results suggest that teicoplanin is a potentially effective and well‐tolerated antimicrobial agent in bone marrow transplant patients with infections not responding primarily to beta‐lactams and aminoglycosides.
Prophylactic teicoplanin during insertion of Hickman catheters
Authors: Lim S. H. , Smith M. P. , Machin S. J. , Goldstone A. H. 
Published: March 2008

Summary With the extensive use of Hickman catheters in patients requiring cytotoxic chemotherapy there is now a resurgence of Gram‐positive septicaemia among these patients during the neutropenic periods. We are currently running a prospective randomized study of prophylactic teicoplanin during insertion of Hickman catheters to determine if it reduces the incidence of Gram‐positive septicaemia. A total of 44 patients have completed the study (23 in the teicoplanin group and 21 in the control group). The diagnoses were: acute myelogenous leukaemia (13). non‐Hodg‐kin'slymphoma (16). Hodgkin's disease (11), chronic granulocytic leukaemia (3) and acute lymphoblastic leukaemia (1). The number of days between insertion of Hickman catheters and the development of neutropenia was: teicoplanin group: mean 14.7, median 11, range 0–53; control group: mean 11.8, median 10. range 0–37.In the treated patients, there were four episodes of line‐associated Gram‐positive septicaemia and a total of four organisms were isolated. In the control group, 10 organisms were isolated from a total of nine episodes of line‐associated Gram‐positive septicaemia. The organisms were: coagulase‐negative staphylococci (8). Streptococcus B, (1), Strep. faecalis (1), Strep. mitis (1). alpha streptococcus (1). diphtheriods (1) and Staphylococcus aureus (1). All organisms were sensitive to teicoplanin. No adverse reaction was observed in any patient.Prophylactic teicoplanin during insertion of Hickman catheters may therefore reduce the incidence of line‐associated Gram‐positive septicaemia in neutropenic patients.
A randomized prospective study of ceftazidime and ciprofloxacin with or without teicoplanin as an empiric antibiotic regimen for febrile neutropenic patients
Authors: Lim S. H. , Smith M. P. , Goldstone A. H. , Machin S. J. 
Published: March 2008

Summary Febrile neutropenic patients were randomized to receive ceftazidime and ciprofloxacin with the addition of teicoplanin in cases with clinical suspicion of a Hickman line‐associated infection. At 48 h both clinical and bacteriological analyses were made. Patients were categorized as: success, in cases of improvement or stability in the clinical condition: failure, if there was a deterioration of the clinical condition; and non‐evaluable, in cases of protocol violation or death due to other causes.A total of 86 patients have completed the study so far: 43 patients were randomized to the ceftazidime and 43 to the ciprofloxacin group. Teicoplanin was added to the mono‐therapy in 12 patients in the ceftazidime group and 15 in the ciprofloxacin group. The diagnoses were: acute myelogenous leukaemia (25), non‐Hodgkin's lymphoma (34), Hodgkin's disease (17); acute lymphoblastic leukaemia (9) and chronic granulocytic leukaemia (1).Forty‐eight hour clinical assessment showed a response rate in the ceftazidime group of: success 18/31 (58%). failure 13/31 (42%): in the ceftazidime and teicoplanin group: success 8/12 (67%), failure 4/12 (33%): in the ciprofloxacin group: success 23/28 (82%). failure 5/28 (18%): and in the ciprofloxacin and teicoplanin group: success 11/15 (73%), failure 4/15 (27%).Blood cultures were positive in 48/86 (56%) cases, with more than one organism isolated in seven of these 48 cases. Organisms isolated were: coagulase‐negative staphylococci (20), Escherichia coli (13), Pseudomonas aeruginosa (4). Staphylococcus aureus (3), diphtheroids (3), Klebsiella sp. (3), Enterobacter cloacue (2), Streptococcus faecalis (2). Ent. adenocarboxylata (1). Clostridium septicum (1). Strept. B (1). alpha streptococcus (1) and P. fluorescens (1). In‐vitro testing showed that all Gram‐positive organisms were sensitive to teicoplanin, and Gram‐negative organisms to ciprofloxacin or ceftazidime. There were seven cases of superimposed infections with eight organisms isolated, all cases occurring in patients receiving ciprofloxacin alone: coagulase‐negative staphylococci (4). Strep. sangius (1). Strep. viridans (1), diphtheroids (1) and P. maltophilia (1). Both ciprofloxacin and ceftazidime are comparable in efficacy as empirical mono‐therapy for febrile neutropenic patients. There is, however, a significant increase in the incidence of superimposed infection in patients receiving only ciprofloxacin. In view of the very high incidence of Gram‐positive septicaemia, we suggest that teicoplanin should be added as part of the initial empiric antibiotic regimen in all febrile neutropenic patients.
In vitro growth pattern and differentiation predict for progression of myelodysplastic syndromes to acute nonlymphocytic leukaemia
Authors: Raymakers R. , Witte T. De , Joziasse J. , Van Der Lely N. , Boezeman J. , Haanen C. 
Published: March 2008

Summary. In 153 consecutive patients with myelodysplastic syndrome (MDS) the prognostic value of FAB‐classification, cytogenetics, Bournemouth score, a history of previous radio‐or chemotherapy and in vitro bone marrow growth were retrospectively analysed, for both acute nonlymphocytic leukaemia (ANLL) development and survival. Thirty‐eight of the 153 patients (25%) showed progression to ANLL, 63 (41%) died during the myelodysplastic phase due to infection or bleeding and three (2%) received allogeneic bone marrow transplantation (BMT). Univariate analysis showed that the FAB‐classification, in vitro growth pattern and differentiation, and cytogenetics had a predictive value for ANLL development and survival. The Bournemouth score was predictive only for survival. Most predictive for the development of ANNL were in vitro growth pattern and maturation. Patients with normal in vitro growth progressed to ANLL in 6% of the cases, in patients with hypoplastic or leukaemic growth 32.5% developed ANLL (P <0·0001). The ANLL incidence in patients with normally differentiated in vitro colonies was 14.5%, compared with a 52% incidence in cases showing no in vitro cell maturation (P=0·001). The combination of growth pattern and differentiation revealed an ANLL incidence of 4.2% in cases of normal growth and differentiation, and 60.4% if the in vitro growth and/or differentiation was abnormal (P=0·006). In vitro maturation was the only parameter predictive for ANLL development in multivariate analysis.From our data it is concluded that the predictive value of in vitro bone marrow culturing in patients with MDS can be increased by including in vitro maturation as a distinct parameter. The in vitro prognostic data can be important in selecting MDS patients for intensive chemotherapy or BMT.
AUTOTRANSPLANTS IN ACUTE LEUKAEMIA
Authors: Gale Robert Peter , Horowitz Mary M. , Butturini Anna 
Published: March 2008

Summary The data we review indicate that in adults with ALL in first remission intensive chemotherapy and radiation given before a transplant is more effective in eradicating leukaemia than current chemotherapy. This is not so in adults with AML in first remission where more intensive therapy does not reduce the likelihood of relapse. Furthermore, leukaemia relapse because of re‐infused leukaemia cells is an important issue in autotransplants for ALL. Whether re‐infusing leukaemia cells would be important in AML were more effective pretransplant therapy developed is unknown. Presently, there appears to be little sense to test in vitro approaches to remove leukaemia cells in autotransplants for AML because efficacy cannot be evaluated. (A randomized trial is an exception but would not be expected to show a difference.)Another conclusion is that attempts to induce GVHD in autotransplant recipients, such as by using cyclosporine post‐transplant (Jones et al, 1989), are more likely to succeed in AML than ALL since the impact of GVHD is substantially greater (Horowitz et al, 1990). However, the GVHD‐related antileukaemia effect in AML is associated with chronic GVHD whereas cyclosporine treatment of autotransplant recipients results in acute GVHD. Also, attempts to separate clinical and antileukaemia effects of GVHD were unsuccessful (Sullivan et al, 1989). Another caution is that in AML we detected an immune antileukaemia effect distinct from GVHD (termed GVL) only after HLA‐identical sibling transplants. Since GVL was absent in twins it is unlikely to operate after autotransplants.In summary, there is sense in studying autotransplants in adults with acute leukaemia in first remission. However, there are currently no convincing data that autotransplants are superior to current therapy. More intensive treatment seems effective in ALL; the focus should be on increasing the antileukaemia efficacy of pretransplant therapy and on attempts to remove leukaemia cells from the graft. In AML, there is no evidence that more intensive therapy is more effective. This problem needs resolution before evaluating attempts to remove leukaemia cells from the graft. The best place to test new pretransplant regimens is in twins and recipients of HLA‐identical sibling transplants without GVHD. The data and ideas we review and discuss should be useful in planning clinical trials.
Treatment of anti‐recombinant interferon‐alpha 2 antibody positive CML patients with natural interferon‐alpha
Authors: Wussow P. v. , Jakschies D. , Freund M. , Hehlmann R. , Brockhaus F. , Hochkeppel H. , Horisberger M. , Deicher H. 
Published: March 2008

Summary Of 38 patients with a Philadelphia‐chromosome positive chronic myeloid leukaemia treated with recombinant interferon alpha (rIFN‐α) 2a or 2b and monitored for emergence of IFN‐antibodies in their sera 11 patients developed rIFN‐α2 binding and 10 rIFN‐α2 neutralizing antibodies. rIFN‐α neutralizing antibody positive patients experienced significantly (P<0·025) more clinical relapses (6/10) than IFN‐antibody negative patients (6/28) during continuous IFN‐therapy. Furthermore, IFN‐antibody‐positive patients with titre above 400 INU/ml were more likely to relapse under rIFN‐α‐therapy than IFN‐antibody‐negative patients with titre below 400 INU/ml (P<0·05).Seven rIFN‐antibody‐positive patients experiencing a clinical relapse or a primary non‐responsiveness were treated with two‐ to three‐fold increased doses of rIFN‐α2. Only one of these seven patients developed a partial haematological remission upon intensification of the rIFN‐α2 therapy. Consecutively, the six patients failing high dose rIFN‐α treatment were switched to a natural IFN‐α preparation (3 × 9 × 106 I.U. weekly s.c.). Under such treatment two of the six patients achieved a long‐lasting complete, one a partial haematological remission.In high‐titred IFN‐antibody positive patients significantly altered serum‐IFN‐titre and minimal IFN‐inducible Mxhomologue concentrations were measured; in contrast, nIFN‐α induced normal IFN‐titre and dose‐equivalent Mxhomologue amounts in these patients. The data prove that high‐titred rIFN‐α neutralizing antibodies abrogate the biological action of rIFN‐α, but not of nIFN‐αin vivo and explains why nIFN‐α can be effective in the anti rIFN‐α2 positive patients.
Proteolysis of factor VIII heavy chain polypeptides in plasma and concentrates
Authors: Kemball‐Cook G. , Edwards S. J. , Barrowcliffe T. W. 
Published: March 2008

Summary Factor VIII heavy chain (FVIII HC) polypeptides have been studied in both normal plasma and FVIII concentrates on exposure to three coagulation proteases.FVIII samples were incubated with labelled affinity‐purified anti‐FVIII Fab’fragments, immunocomplexes formed were visualized by autoradiography after sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS‐PAGE), and apparent relative molecular masses (Mr) of each band assigned. FVIII HC polypeptides were detected in all types of samples, including plasma, without further purification.Normal plasma contained a range of polypeptides with the largest dominant band at a net apparent Mr of 250–300 kD, and the smallest at 80–90 kD: the bands visualized correspond to the 90–210 kD HC species seen on conventional analysis of purified FVIII. No bands were produced from samples of haemophilic plasma.Treatment of plasma or FVIII concentrate with low concentrations (1 IU/ml) of thrombin removed the 250–300 kD and other intermediate bands, intensified then removed the 80–90 kD polypeptide and produced a band at 40–50 kD. Thrombin‐associated rise and fall in FVIII clotting activity by one‐stage assay correlated with intensity of the 80–90 kD polypeptide. A polypeptide of Mr 40–50 kD was also produced after incubation with activated factor X: activated factor VII plus thromboplastin had no effect on HC structure.FVIII polypeptides were visualized in prothrombin complex concentrates, with a more degraded profile seen in a deliberately ‘activated’product.
A new dual‐label technique for platelet survival studies with the use of 111indium and 114mindium tropolonate
Authors: De Vries R. A. , De Bruin M. , Oldenburg S. J. , Zwiers A. , Marx J. J. M. , Poortman J. , Hart H. Ch. , Van De Wiel A. 
Published: March 2008

Summary A dual‐label technique to study the survival of two different populations of platelets within one individual was developed using 111indium and 114mindium. The validity of the technique was demonstrated in seven individuals with an expected equal survival time of two platelet populations and in two persons with an expected difference in platelet survival time.Since the energy spectra of the two indium isotopes are very close, a well‐type germanium semiconductor detector was applied. By adaptation of the counting time the effective dose equivalent of the dual‐label procedure could be restricted to 1·6 mSv.The dual‐label technique provides an instrument for studying the survival of two different populations of platelets simultaneously within one individual.
Molecular basis for hereditary antithrombin III quantitative deficiencies: a stop codon in exon IIIa and a frameshift in exon VI
Authors: Gandrille S. , Vidaud D. , Emmerich J. , Clauser E. , Sié P. , Fiessinger J. N. , Alhenc‐Gelas M. , Priollett P. , Aiach M. 
Published: March 2008

Summary. Antithrombin III (AT III) is an inhibitor of serine protease (serpin) comprising 432 amino acids. Quantitative AT III deficiencies are associated with a high risk of thrombotic disease. Although this risk is smaller in patients with qualitative AT III deficiencies, the molecular defects characterizing the latter have been the subject of many studies. However, in quantitative AT III deficiencies, only three mutations have been described: Pro 407 to Leu and Ala 404 to Thr (both located in the C‐terminal part of the AT III molecule) and also a frameshift in exon IIIa.Using the asymmetric polymerase chain reaction (PCR) and genomic DNA analysis by direct sequencing, we detected two mutations in three unrelated families: (i) a C→T transition in exon IIIa in two families, leading to the replacement of the codon corresponding to Arg 129 by a stop codon, and (ii) in the third family, insertion of an adenine in the codon corresponding to Phe 408, a highly conserved serpin amino acid. This insertion altered the reading frame and led to the appearance of a premature stop signal. Patients of all three families were heterozygous for their abnormality.These results show that asymmetric PCR and genomic DNA analysis by direct sequencing permit fast identification of the molecular basis of quantitative AT III deficiencies. It is concluded that in many cases the absence of AT III gene product probably results from point mutation, as previously observed for another serpin, alpha‐1‐antitrypsin.