bluuebunny/crossref_metadata_2025_split huggingface dataset:
β2‐Microglobulin, lysozyme and lactoferrin in cerebrospinal fluid in patients with lymphoma or leukaemia: relationship to CNS involvement and the effect of prophylactic intrathecal treatment with methotrexate
Authors: ÖBerg G. , Haullgren R. , Venge P. 
Published: March 2008

SummaryCentral nervous system (CNS) involvement in patients with leukaemia or lymphoma presents a diagnostic problem. This study was conducted to test whether combined measurements of various cellular markers such as β2‐microglobulin (β2m), lactoferrin (LF) and lysozyme (LYS) in the cerebrospinal fluid (CSF) might aid in the diagnosis of CNS involvement in such patients. Forty‐two patients were studied. Sixteen were considered to have CNS involvement and 26 showed no signs of such involvement. In the group with symptoms or signs of CNS involvement, nine patients out of 12 had increased total protein in CSF, 14 of 14 increased β2m, 14 of 16 increased LYS and five of 15 increased LF. In patients without CNS involvement total protein was increased in four of 25. β2min three of 21. LYS in four of 28 and LF in one of 28 patients. The differences were statistically significant (P<0.01, P<0.001, P<0.001 and P<0.05, respectively). Prophylactic intrathecal methotrexate treatment in patients with acute lymphoblastic leukaemia caused an increase in the CSF of β2m, LYS and LF but not of total protein, which may reflect a drug‐induced inflammatory reaction in the CNS.We conclude that combined measurements of the three cell markers add to our understanding of the cellular reaction to malignant cells in the CNS in leukaemia and lymphoma and may be valuable supplements in the diagnosis of this CNS involvement.
Incidence and mechanism of neutropenia and thrombocytopenia in patients with human immunodeficiency virus infection
Authors: Murphy M. F. , Metcalfe P. , Waters A. H. , Carne C. A. , Weller I. V. D. , Linch D. C. , Smith A. 
Published: March 2008

SummaryThe incidence of lymphopenia, thrombocytopenia and neutropenia was studied in 105 homosexual men with HIV infection. Lymphopenia was common in patients with AIDS (75%), but its incidence in PGL (24%) was not significantly different from that in asymptomatic anti‐HIV positive (15%) homosexual men. Neutropenia and thrombocytopenia were found in patients with AIDS or PGL. but not in asymptomatic anti‐HIV positive homosexuals. The study suggests that the neutropenia and thombocytopenia in these patients were due to autoimmune destruction of neutrophils and platelets.
Monoclonal antibodies to factor VIII: their application in immunoblotting for the visualization of factor VIII in therapeutic concentrates and plasma
Authors: Furlong R. A. , Welch A. N. , Peake I. R. 
Published: March 2008

SummaryTwo monoclonal antibodies (McAb) termed 12A4 and 19C1 have been raised against human factor VIII. In immunoassays 12A4 bound to factor VIII antigen (VIII:Ag) in plasma but not serum whilst 19C1 bound to VIII:Ag in both plasma and serum. Both McAb were shown by immunoblotting to react with the carboxy (C) terminal polypeptide of factor VIII which appeared as a doublet with a molecular weight (Mr) of 77000/75000.The C terminal factor VIII polypeptide was detectable by immunoblotting in each of 12 therapeutic factor VIII concentrates, from six different manufacturers, although its level was variable.Factor VIII was visualized in plasma by immunoblotting following its immunoadsorption and elution from agarose‐bound monoclonal antibodies. No Mr 77000/75000 bands were detectable in plasma obtained from 13 unrelated CRM‐ haemophiliacs whilst 11 CRM+ haemophilic plasmas from seven kindred were shown to have a C terminal factor VIII polypeptide of normal molecular size.
The calcium permeability of cold‐stored erythrocytes
Authors: McNamara M. K. , Wiley J. S. 
Published: March 2008

SummaryThe calcium permeability of erythrocytes was studied by a new technique in which cells were loaded with an intracellular calcium chelator, quin 2, followed by measurement of 45Ca influx. The erythrocyte calcium permeability did not change during cold storage of blood in citrate‐phosphate‐dextrose for 6 weeks. Previous reports of an increased Ca2+ permeability in cold‐stored erythrocytes have been based on an ATP‐depletion technique which yields values for Ca2+ influx which are influenced by erythrocyte 2.3DPG levels.
Factor VIII polypeptide specificity of monoclonal anti‐factor VIII antibodies
Authors: Shima M. , Yoshioka A. , Nakai H. , Tanaka I. , Fujiwara T. , Terada S. , Imai S. , Fukui H. 
Published: March 2008

Four monoclonal antibodies against factor VIII, NMC‐VIII/1, NMC‐VIII/2, NMC‐VIII/3 and NMC‐VIII/4, were produced. The first three antibodies were of the IgG1 immunoglobulin subclass, while the fourth was IgM. The affinity of each antibody for factor VIII was high and antifactor VIII clotting activity was detected in NMC‐VIII/2, NMC‐VIII/3 and NMC‐VIII/4. NMC‐VIII/1 had no inhibitory effect on factor VIII clotting activity. Immunoblotting using purified intact and thrombin‐treated factor VIII identified the antibodies’factor VIII polypeptide specificities. With thrombin‐treated factor VIII the factor VIII fragments for NMC‐VIII/1 and NMC‐VIII/2 were 80 kDa and 54 kDa, respectively, while both NMC‐VIII/3 and NMC‐VIII/4 recognised a 44 kDa fragment. With intact factor VIII, antibodies NMC‐VIII/2‐4 bound to polypeptides larger than 90 kDa, especially NMC‐VIII/2, which reacted with a chain of 330 kDa thought to be a mature form of factor VIII protein. We also detected a mature form of factor VIII in hepatic sinusoidal endothelial cells by immunoperoxidase staining.Identification of the factor VIII polypeptides bearing these fragments enabled us to clarify the localization of the factor VIII thrombin cleavage site, and suggested the existence of factor VIII in hepatic sinusoidal endothelial cells.
Selective decrease in platelet dense granule adenine nucleotides during recovery from acute experimental thrombocytopenia and ensuing thrombocytosis in baboons
Authors: Savage Brian , Hanson Stephen R. , Harker Laurence A. 
Published: March 2008

Summary Serial measurements of platelet volume, platelet content of adenine nucleotides, β‐thromboglobulin (β‐TG), platelet factor 4 (PF4) and ex vivo platelet aggregation were made in baboons under basal, steady‐state conditions of normal platelet production, and during recovery from acute thrombocytopenia induced by the exposure of flowing blood to spherical glass microbeads. The mean basal platelet count of 509.107X109/l (±1 SD; n=4) fell acutely to 36.8±12.6X109/l after the insertion of glass bead columns and blood filters, placed distally, for 60 min into surgically implanted arteriovenous‐shunts in heparinized baboons. After the irreversible removal of up to 90% of the baseline circulating platelet population, recovery from thrombocytopenia was characterized by a constant rate of increase in circulating platelet counts (115±11X109/l/d) and a rebound thrombocytosis to 1.5 times the basal platelet count after 7 d. Steadystate thrombocytopoiesis was achieved by 3–4 weeks after the onset of thrombocytopenia.Platelet dense granule ADP and ATP decreased significantly from 3.89±0.20 and 2.33±0.25 μmol/1011 platelets respectively at baseline to 2.17±0.37 and 1.68±0.37 μmol/1011 platelets respectively after 7 d (P<0.001 in both cases) and normalization was achieved only after 4 weeks. By contrast, the mean platelet volume and platelet content of β‐TG and PF4 did not change significantly throughout the course of study (P>0.1 in both cases). Platelet function, assessed by platelet aggregation ex vivo, demonstrated that platelet function was not impaired despite the significant decrease in dense granule ADP. We conclude that a selective, temporal reduction in platelet dense granule adenine nucleotides reflects changes in the thrombocytopoietic control mechanism secondary to induction of acute thrombocytopenia.
Neutrophil function in patients on continuous ambulatory peritoneal dialysis
Authors: Harvey D. M. , Sheppard K. J. , Morgan A. G. , Fletcher J. 
Published: March 2008

Summary Frequent and recurrent episodes of peritonitis are a major cause of morbidity in patients on continuous ambulatory peritoneal dialysis (CAPD). One factor contributing to this problem may be an abnormality of neutrophil function in these patients. We have therefore quantified phagocytosis and killing by circulating and peritoneal neu‐trophils from patients on CAPD with and without peritonitis. Circulating neutrophils from uninfected patients showed reduced phagocytosis of both Staphylococcus epidermidis and Candida guilliermondii because of an opsonic defect in CAPD serum and because of a defect of the neutrophils themselves.In contrast, phagocytosis by circulating and peritoneal neutrophils from patients with peritonitis was normal. Intracellular killing of C. guilliermondii was normal in all groups of neutrophils but killing of S. epidermidis, the organism most commonly isolated in CAPD peritonitis, was reduced. The possible mechanisms for the enhanced neutrophil activity seen in peritonitis, and for the decreased killing of S. epidermidis in contrast to normal killing of C. guilliermondii are discussed. A defect in killing of S. epidermidis may explain why peritonitis caused by this organism can be difficult to erradicate.
Endogenous erythroid clones (EEC) in polycythaemia and their relationship to diagnosis and the response to treatment
Authors: Reid C. D. L. , Fidler J. , Kirk A. 
Published: March 2008

Summary The growth in culture of circulating erythroid progenitors (BFU‐e) from 34 patients with erythrocytosis was evaluated together with the clinical and bone marrow features at presentation and the subsequent response to treatment. Clonal erythroid growth in vitro in the absence of added erythropoietin (EEC) was observed in 17/18 patients with clinically unequivocal polycythaemia vera and in these patients bone marrow morphology was also abnormal. EEC were also present in three out of five patients with only a single minor criterion of that disease but none of the 11 patients without major or minor criteria or evidence of secondary polycythaemia were EEC positive. This group had a very low incidence of bone marrow abnormalities, was probably heterogenous in nature and included two patients with elevated serum immunoreactive erythropoietin of unknown cause.The reduction in haematocrit following treatment was assessed in EEC positive and negative patients and was found to be inferior in those lacking EEC. Thus both the poor therapeutic response and the low incidence of bone marrow abnormalities in patients lacking any other clinical features of polycythaemia vera correlated closely with the absence of EEC in in vitro culture. Myeloproliferative disorder may therefore be an unlikely cause of the erythrocytosis in such individuals.
Refined chromosome study helps define prognostic subgroups in most patients with primary myelodysplastic syndrome and acute myelogenous leukaemia
Authors: Yunis Jorge J. , Lobell Michael , Arnesen Mark A. , Oken Martin M. , Mayer Mary G. , Rydell Robert E. , Brunning Richard D. 
Published: March 2008

SummaryBased on a 6·1/2‐year study of 284 consecutive adult patients with primary myelodysplastic syndrome (MDS) and and acute myelogenous leukaemia (AML), we have found that refined chromosome analysis can be used as an independent prognostic indicator in the great majority of patients with MDS and AML. In MDS, the FAB subtype was also found to have prognostic value and this was enhanced when the chromosomal findings were taken into consideration. In AML, the age of the patient correlated more closely with the chromosomal changes in predicting prognosis in most patients than did the FAB classification.Previously we reported that refined chromosome analysis of bone marrow specimens from 161 adult patients with primary or non‐therapy related MDS and AML identified three prognostic chromosomal categories in each disease, representing 40% of all patients (Yunis et al, 1984, 1986). By extending our study to 284 patients, as well as a longer follow‐up, it was possible to determine the prognostic implications of two additional chromosomal categories in MDS and five in AML. Since 73% of all patients are now represented in well‐defined chromosomal subgroups with prognostic significance, refined chromosome analysis emerges as a tool that could have considerable impact in clinical decision making and in the development of treatment protocols.
Use of minisatellite DNA probes for recognition and characterization of relapse after allogeneic bone marrow transplantation
Authors: Min Gao Ling , Hibbin Jill , Arthur Christopher , Apperley Jane , Jeffreys Alec , Goldman John 
Published: March 2008

SummaryRestriction fragment length polymorphisms can be used to distinguish blood and marrow cells from close relatives. We used two probes that recognize a series of dispersed and highly polymorphic tandem‐repetitive mini‐satellite regions in the human genome that can be detected via a shared 10–15 base pair core sequence similar to the generalized recombination sequence (χ) of E. coli. We have studied the resulting individual‐specific DNA fingerprints in 15 patients before and after allogeneic bone marrow transplantation performed for chronic myeloid leukaemia and in two patients transplanted for acute leukaemia. Early engraftment could be demonstrated at 3 weeks post‐transplant based on the recognition of cells of donor origin. One patient who failed to engraft had only recipient type marrow cells 3 months post‐transplant. Nine patients who relapsed after transplantation had only cells of recipient origin. In one patient who relapsed after transplantation with T‐cell depleted donor marrow, fractionation studies showed that his T‐cells at relapse were of recipient origin. We conclude that these minisatellite probes are valuable for characterizing the origin of different cell populations after marrow transplantation and could be useful for characterizing relapse when donor and recipient are of the same sex.
Childhood monosomy 7 revisited
Authors: Evans J. P. M. , Czepulkowski B. , Gibbons B. , Swansbury G. J. , Chessells J. M. 
Published: March 2008

Summary. Monosomy 7 is found in acute myeloid leukaemia (AML) and myelodysplasia and is characteristic of a rare chronic myeloproliferative disease (MPD) of young children. We have seen 16 children with monosomy 7. Their clinical features and response to treatment are discussed.Monosomy 7 diseases appear to have a particularly poor prognosis. The AML is often resistant to treatment and relapse is common. Children with chronic MPD die of bone marrow failure or evolve to AML or myelofibrosis. We have treated these children intensively with combination chemotherapy and allogeneic bone marrow transplantation. Four children with MPD received supportive care and low dose chemotherapy alone. They all died, surviving between 4 months and 4 years. Six children with MPD received intensive chemotherapy: three remitted, one relapsing after 9 months, the others remaining in remission at 18 months and 3 years. One child with MPD has undergone successful BMT and survives 71/2 years after presentation.Remission was achieved in three of four cases of AML. They all relapsed within 9 months. Bone marrow transplantation was successful in one child with myelofibrosis.Intensive chemotherapy and early bone marrow transplantation is likely to offer these children their best chance of survival.
Biochemical markers in multiple myeloma: a multivariate analysis
Authors: Simonsson B. , Källander C. F. R. , Brenning G. , Killander A. , Gronowitz J. S. , Bergström R. , Åhre A. 
Published: March 2008

Summary.The analysis of individual biochemical and clinical variables in 121 patients with multiple myeloma showed that serum β2‐microglobulin (S‐β2m) had the most significant relation to survival. Other variables such as serum thymidine kinase (S‐TK), serum lactate dehydrogenase (S‐LDH), Screatinine, haemoglobin (Hb), ESR, S‐albumin, age and clinical stage were also significant. No such relationship was found with M‐component, presence of light chains in urine, type of secreted immunoglobulin or S‐calcium. The exclusion of clinical stage in the first multivariate analysis resulted in a model consisting of S‐β2m, age and S‐TK, none of the other variables gave additional information. When in the second multivariate analysis the basic variables involved in staging procedure were excluded and clinical stage included, stage III, but not stage II, was found to give additional information to the model described above.Individual analysis of the variables showed that Hb had the most significant relation to effect of initial therapy. Other significant variables were S‐TK, S‐β2m and age. When using the multivariate approach, Hb alone was found to contain all the relevant information.
Chimaerism following allogeneic bone marrow transplantation: detection of residual host cells using the polymerase chain reaction
Authors: Lawler M. , McCann S. R. , Conneally E. , Humphries P. 
Published: March 2008

SummaryChimaerism was assessed in five recipients following sex mismatched allogeneic bone marrow transplantation. Techniques included karyotyping of bone marrow cells, dot blot DNA analysis of blood and bone marrow suspensions, and in vitro amplification of DNA by the polymerase chain reaction (PCR) using blood and bone marrow suspensions and stored bone marrow slides. Results of karyotypic analysis suggested complete chimaerism in four patients, while in one patient mixed chimaerism was detected. Mixed chimaerism was also detected, however, in a second patient using PCR and confirmed by dot blot analysis on all tissues examined. PCR is a sensitive tool for investigation of chimaerism following bone marrow transplantation. Since this technique does not require radioactivity, it is an attractive method for use in a clinical laboratory. This technique represents a further development in the use of DNA methodologies in the assessment of haematological disease.
The effect of total body irradiation dose and chronic graft‐versus‐host disease on leukaemic relapse after allogeneic bone marrow transplantation
Authors: Frassoni Francesco , Scarpati Daniele , Bacigalupo Andrea , Vitale Vito , Corvo Renzo , Miceli Salvatore , Gualandi Francesca , Occhini Domenico , Clavio Marino , Van Lint Maria Teresa , Marmont Alberto 
Published: March 2008

SummaryOne‐hundred and five patients undergoing allogeneic bone marrow transplantation (BMT) for acute myeloid leukaemia (AML) (n = 61) and chronic myeloid leukaemia (n= 44) were analysed for risk factors associated with relapse. All patients received marrow from an HLA identical sibling after preparation with cyclophosphamide 120 mg/kg and total body irradiation (TBI) 330 cGy on each of the three days prior to transplantation. There was a difference of ±18% between the nominal total dose of 990 cGy and the actual dose received as indicated by dosimetric recordings. While interstitial pneumonitis had minimal impact on survival (4%) there was a considerable difference in the incidence of relapses. The incidence of relapse was 55% versus 11% in patients receiving less or more than 990 cGy respectively and this had a major impact on survival (38% v. 74% at 7 years) since transplant‐related mortality was comparable in the two groups. A multivariate Cox analysis indicated that a lower TBI dose (less than 990 cGy) was the most significant factor associated with relapse and the second most important factor associated with recurrence of leukaemia was the absence of chronic graft‐versus‐host‐disease (cGvHD). Actuarial relapse incidence was 62%, 28% and 18% for patients with no, limited or extensive chronic GvHD respectively. However, chronic GvHD had no significant impact on survival. Combined stratification for TBI dose and cGvHD showed that the dose effect of TBI on relapse was evident both in patients with and without cGvHD. Chronic GvHD influenced the risk of relapse only in patients receiving less than 990 cGy. These results suggest that a higher dose of TBI, within this schedule, produced long‐term disease‐free survival in the majority of AMLs and CMLs. Minor radiobiological side effects were experienced, but a small reduction of the dose may significantly increase the risk of relapse.
Bleeding time, blood groups and von Willebrand factor
Authors: Caekebeke‐Peerlinck Kathelijne M. J. , Koster Ted , Briët Ernest 
Published: March 2008

SummaryThe bleeding time in healthy volunteers was determined according to both the Ivy and the Simplate II techniques. A significantly longer bleeding time in people with blood group O than in people with non‐O blood groups was demonstrated with both techniques. This difference could not be attributed to a difference in sex ratio, platelet count or haematocrit. The mean level of von Willebrand factor in blood group O is lower than in non‐O blood groups, but we found no association between the level of von Willebrand factor and the bleeding time, despite the very broad range of von Willebrand factor levels in the subjects examined.
The natural history of human immunodeficiency virus infection in a haemophilic cohort
Authors: Lee Christine A. , Phillips Andrew , Elford Jonathan , Miller Elizabeth J. , Bofill Margarita , Griffiths Paul D. , Kernoff Peter B. A. 
Published: March 2008

Summary112 haemophilic patients infected with HIV were followed up with clinical and laboratory assessment between 1 December 1979 and 30 November 1988. Sixty‐six (59%) of the patients developed HIV‐related clinical symptoms and 22(20%) developed AIDS. Twenty (18%) of the patients developed p24 antigenaemia. Amongst the 59 patients whose date of seroconversion could be estimated the calculated 8‐year cumulative incidence of AIDS was 40% (symptoms 73%). For the whole cohort of 112 patients, the median slope of linear regression of the absolute T4 lymphocyte count was steeper for those with AIDS (‐0.113 × 109/1 per year) than for those without AIDS (‐0.054 × 109/1 per year) (P < 0.02). While 15 cases of AIDS developed during 58 patient‐years of follow up after falling below a T4 lymphocyte count of 0.2 × 109/1, only two cases occurred during 450 patient‐years before reaching this count. Thus the decline of the T4 lymphocyte count to 0.2 × 109/1 may be an appropriate additional end‐point for the assessment of new treatments for asymptomatic patients infected with HIV.
Heparin‐induced thrombocytopenia: mechanism of interaction of the heparin‐dependent antibody with platelets
Authors: Chong Beng H. , Fawaz Ismail , Chesterman Colin N. , Berndt Michael C. 
Published: March 2008

SummaryThe interaction of the heparin‐dependent antibody with heparin and platelets has been studied using the sera and purified IgG of four patients with heparin‐induced thrombocytopenia. Both normal platelets and Bernard‐Soulier syndrome (BSS) platelets which lack glycoprotein (GP) Ib, GPV and GPIX, aggregated in response to patient serum or IgG, but only in the presence of heparin. A monoclonal antibody (Mab) against platelet Fc II receptor (IV. 3) strongly inhibited the heparin‐dependent aggregation of both normal and BSS platelets induced by patient sera/IgG. Inhibition by the anti‐GPIb Mab (AK2) was variable and occurred only with normal platelets. Anti‐GPIX Mab (FMC 25) was not inhibitory with either normal or BSS platelets. Similar results were obtained using 14C‐serotonin release instead of platelet aggregation as a measure of platelet activation. These findings suggest that (1) the reaction of the heparin‐dependent antibody with platelets and heparin is mediated by a Fc‐dependent mechanism, (2) GPIb, GPV and GPIX are not involved in this reaction, and (3) the inhibitory effect of anti‐GPIb Mab on normal platelets is due to steric interference consistent with the platelet Fc receptor being in close proximity to GPIb.