bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Management of Haemophiliacs who have Antibodies to Factor VIII
Authors: Rizza C R 
Published: August 2010

The management of haemophiliacs with factor VIII antibodies is still one of the major problems in the treatment of haemophilia in spite of our greater understanding of the nature and mode of action of those antibodies.The approach to treatment varies from centre to centre and may consist of factor replacement with human or porcine factor VIII, administration of prothrombin complex concentrates, plasmapheresis, immunosuppressive drugs or different combinations of the above.At Oxford we have relied entirely on human factor VIII replacement for the management of acute bleeding. In twenty‐four patients receiving on demand therapy for 2–10 years we have details of amounts of factor VIII used, frequency of dosage and levels of factor VIII antibody. Eight patients with low levels of antibody have lost their antibody. In 7 patients with higher levels there has been a reduction in anamestic response and level of antibody in the blood. In the remaining patients some of whom are infrequently treated there has been little change in the antibody response.The above findings are described in the light of other regimens of therapy employing high or low dosage factor VIII replacement.
Overcoming Factor VIII Inhibitors: A Possible New Approach
Authors: Barrowcliffe T W , Kemball‐Cook G , Gray E 
Published: August 2010

Treatment of haemophiliacs with antibodies to Factor viii is still a major clinical problem, neither high‐dose Factor viii nor Factor ix concentrates being completely effective. An alternative approach was suggested by the finding that Factor viii, when complexed with phospholipid and Factor IXa, was protected from antibody attack, and that the major protective effect was provided by the phospholipid.The protective effects of various phospholipids were assessed by addition to Factor viii concentrates, incubation with human antibodies to VIII:C and measurement of residual clotting activity in three different assay systems. The most active material was a home‐made extract of bovine brain, prepared by a modified Folch method. Of three commercial lipid preparations manufactured for intravenous injection, one was inactive and the other two were only active at high concentration.Studies with purified phospholipids showed that phosphatidyl serine (PS) was the most active fraction. Phospholipid analyses showed that the three intravenous lipid preparations all contained less than 10% PS, whereas the bovine brain extract contained 20–25%.These studies show that Factor viii can be protected from antibody attack by addition of phospholipid extracts which are rich in PS, and suggest that a Factor viii product containing a suitable phospholipid could be of benefit to haemophiliacs with inhibitors.
Immunological Dysfunction and Persistent Lymphadenopathy in Patients with Classic Hemophilia
Authors: Tsoukas C , Gervais F , Fuks A , Guttmann R D , Strawczynski H , Shuster J , Gold P 
Published: August 2010

Thirty‐four asymptomatic heterosexual adults with severe classic hemophilia without inhibitors receiving more than 40,000 units of factor VIII concentrate per year were studied and compared to 10 heterosexuals receiving cryoprecipitate and to 22 age matched controls. Anergy was noted in 68 percent of the patients treated with factor VIII concentrates, 57 percent of those treated with cryoprecipitate and 5 percent of the controls. The lyophilized factor VIII treated group had a significant elevation of serum IgG, decreased mitogen responses, high nonstimulated background activity, and altered T cell subsets with an increase in total T lymphocytes, T suppressor cells and decreased Th/Ts ratios.Four of the patients with cellular immune dysfunction developed fatigue, night seats, dyspnea, weight loss, neuropathic pain and rashes. They had diffuse, peripheral, non‐tender lymphadenopathy. Two had splenomegaly. All four were anergic, had inverted Th/Ts ratios, with an increase in suppressor cells. Three had lymph node biopsies which demonstrated reactive follicular hyperplasia. All had elevated serial titers to EBV. The systemic symptoms resolved as these titers returned towards normal. The lymphadenopathy is persistent although all four patients have gained weight and feel well. The persistent lymphadenopathy syndrome in hemophilia is a distinct entity which occurs in a subset of hemophiliacs with severe cellular immune dysfunction.
Alternatives to Financing
Authors: Aledort L M 
Published: August 2010

Comprehensive care for hemophilia patients has clearly demonstrated that it is cost effective and offers the patient a better, more active life. However, the cost of underwriting the core personnel has not been adequately addressed or resolved.Alternatives are presented which include a) federal or state support, b) third party reimbursement mechanisms, c) liaisons with blood programs and, d) cost overrides on product.
Innovative Alternatives to Human Factor VIII
Authors: Tuddenham E.G.D. 
Published: August 2010

Despite massive expenditure of effort and money in fractionation of human blood plasma, it is clear that the end‐product factor VIII is deficient in quantity and its quality seriously compromised by infectious agents both known and unknown. These problems may not be soluble by ever greater blood collection drives and ever more stringent process controls. The average fractionation puts only 20 per cent of donated factor into the bottle of concentrate. Are radical new methods of purification needed?Meanwhile, the vast majority of our potential resources of factor VIII and IX, free of all known human pathogens are thrown away. In the United Kingdom last year, over 600,000 million units of sheep, pig and cow factor VIII were washed down the abbatoir gutters or consumed as black pudding. Already, some haemophiliacs with inhibitors are successfully treated with highly purified porcine factor VIII. Could new purification methods and chemical modifications make this natural abundance of animal factor VIII available to treat all haemophiliacs?Genetically engineered factor VIII made by cultured cells, pure and in unlimited quantities is a theoretical possibility which stands as a ‐ perhaps the ‐ supreme challenge to biotechnology today. Undaunted, several groups have taken up this quest. Huge obstacles bar the way but like Everest it attracts our highest endeavours because it is there.Finally, what thoughts should we entertain of gene therapy? “Ah, could we not seize this sorry scheme of things entire and mould it closer to the heart's desire?” There have been false dawns but recent progress on gene insertion and control raise more than a glimmer of fresh hope.
THE CONTROL AND STANDARDIZATION OF FACTOR VIII
Authors: Aronson David L. , Thomas Duncan P. 
Published: August 2010

ABSTRACT:  Factor VIII concentrates have been used increasingly over the past decade for the treatment of patients with classical haemophilia. To ensure broad comparability between the potency estimates of therapeutic concentrates prepared by different manufacturers, a Factor VIII standard is required.The principles of biological standardization are discussed, particularly as they apply to the standardization of Factor VIII, both in plasma and concentrates.The role of the WHO International Standards is considered, as well as the importance of secondary standards. The control of Factor VIII concentrates by the regulatory authorities in the U.S.A. and the U.K. is also discussed. It is concluded that optimal control of Factor VIII concentrates requires a continuing interchange between producers, regulators and users.
Immune phenotype heterogeneity in AML
Authors: Öst Å. , Christensson B. , Andreasen R. , Hast R. , Lagerlöf B. , Reizenstein P. , Trowbridge I. S. , Biberfeld P. 
Published: August 2010

Blood cells from 46 patients with acute myeloid leukaemia were studied for expression of various surface markers, defined by a panel of 12 monoclonal antibodies and the expression of Fcγ receptors. Corresponding studies were done on normal bone marrow cells. Antibodies which bound to leukaemic cells in high frequencies were those which most frequently also bound to normal bone marrow cells. Immunophenotypic analysis revealed a marked antigenic heterogeneity in AML, also evident within single FAB subclasses. However, leukaemic cells of FAB subclass M1 significantly more often expressed HLA class I antigen than those of FAB subclass M5a, whereas Fcγ receptors which were expressed only on a few cells in M5a, were increasingly frequent on leukaemic cells of M1‐M2, M4, and M5b leukaemias.The frequency of cells reacting with the monoclonal antibody T50/12,11,2 was related to the complete remission rate of the patients. Patients with high frequencies of cells reacting with this antibody had a better complete remission rate than patients with fewer cells binding to this antibody.The immunophenotypic heterogeneity an AML may reflect a great biological variability of this disease. This variability may be of importance for the classification and treatment of AML.
A method for quantitation of H+‐ion activity relating to packed erythrocytes
Authors: Torp. H. E. 
Published: August 2010

To try to contribute new information on the problem concerning red cell destruction in the spleen, a new method which makes it possible indirectly to quantitate H+‐ion activity relating to packed erythrocytes, has been devised.The method is based on the chemical reaction:5 I– + I O–3 + 6 H+ ⇄ 3 I2 + 3 H2OWhen blood is added to a solution of iodate and iodine in excess, the amount of iodine formed depends on the H+‐ion quantity offered by the blood. The erythrocytes primarily act as H+ donors, secondarily as iodine acceptors. Acetone added primarily liberates iodine from the erythrocytes and subsequently acts as a solvent. The amount of dissolved iodine was determined by photometry. The method makes it possible to quantitate the H+‐ion activity relating to packed erythrocytes in microvolumes of blood.
The dynamic morphology of the transferrin‐transferrin receptor system in human leukaemia/lymphoma cell lines and its relation to iron metabolism and cell proliferation
Authors: Forsbeck Klas , Nilsson Kenneth 
Published: August 2010

Some functional and morphological aspects of the transferrin‐transferrin‐receptor (Tf‐TfR) system were investigated in 12 human haematopoietic tumour cell lines. The iron uptake ability, studied by 59Fe labelling, varied considerably between individual tumour cell lines. The studies of the morphology of the Tf‐TfR system by fluorescence based methods using labelling by FITC‐Tf, and by indirect immunofluorescence (OKT9 anti‐TfR monoclonal antibody) demonstrated that the iron uptake was the result of receptor‐mediated endocytosis (RME) of the Tf‐TfR complex. The RME was better developed in the haemoglobin synthesizing K‐562 cells than in the monocytic U‐937 cells, suggesting that the intracellular iron processing capacity differs from cell type to cell type.The efficiency of iron‐uptake, transport and storage was related to cell growth. Inhibition of growth by increasing cell densities or by drug treatments (phorbol ester TPA and difluoromethylornithine DFMO) was thus accompanied by a decrease in surface Tf binding, in cellular Tf handling capacity and in iron accumulation. TPA induced a redistribution of the TfR‐pool to the intracellular space as demonstrated by morphology.
Aseptic bone/bone marrow necrosis in leukaemia
Authors: Vesterby Annie , Jensen O. Myhre 
Published: August 2010

Aseptic (avascular) bone/bone marrow necrosis (ABN) was found in 21 leukaemic patients during a period of 14 yr, with a frequency of 6.5% in autopsied leukaemic patients, and with the highest frequency in ALL. 8 patients (38%) complained of bone pain. X‐ray examination was carried out in 7 of these with a positive result in 3 (43%). Only 1 patient had elevated S‐Alkaline phosphatase. Leucocytosis was found in 12 patients. Only 1 patient (ALL) received steroid in a rather high dose during 6 weeks. At autopsy ABN was found localized to the femur in all patients and 2 patients also had ABN in other bones. Post‐mortem X‐ray examination demonstrated changes in 8 of 15 cases (53%), with osteolysis in 6 and sclerosis in 2. 19 patients had had recent ABN with some fibroblast proliferation. In 4 of these, appositional bone formation had started. 2 patients had sclerosis as the only change.The pathogenesis of ABN is not known; an important factor, however, may be ischaemia due to vascular obstruction.
Coproporphyrinogen oxidase activity and porphyrin concentrations in peripheral red blood cells in hereditary sideroblastic anaemia
Authors: Pasanen A.V.O. , EklöUf M. , Tenhunen R. 
Published: August 2010

The activity of coproporphyrinogen oxidase and the concentrations of coproporphyrin and protoporphyrin (measured by HPLC) in peripheral red blood cells were established in 2 families with different types of hereditary sideroblastic anaemia. 2 males and 4 females were members of a family with an X‐chromosome‐linked and pyridoxine‐responsive HSA, and 3 females were members of another family where the mode of inheritance is not clear and where pyridoxine did not produce a haemotological response. Coproporphyrinogen oxidase activity was normal in 8 of 9 patients and slightly decreased only in 1 patient. All patients had normal red cell coproporphyrin concentrations, but red cell protoporphyrin concentration was decreased in 4 patients.These findings indicate that in vivo haem synthesis was not impaired at the step of coproporphyrinogen oxidase, hence enzymatic defects in earlier steps of haem synthesis are more evident. Earlier suggestions of impaired haem synthesis at this level, based on observed increased concentrations of coproporphyrin in peripheral red blood cells might be explained by the use of unspecific methods.
Evaluation of neutrophil alkaline phosphatase (NAP) activity: Untreated myeloid leukaemia, lymphoid leukaemia and normal humans
Authors: Bendix‐Hansen Knud , Helleberg‐Rasmussen Inge 
Published: August 2010

Neutrophil alkaline phosphatase (NAP) activity was estimated in 50 healthy humans and 89 patients with leukaemia; 41 cases of acute myeloid leukaemia (AML), 22 cases of chronic myeloid leukaemia (CML), and 26 cases of lymphoid leukaemia (LL). The groups proved to be separate entities (p < 0.000 25) and the differences between the groups were statistically significant (p < 0.001) except for the difference between AML and LL.The 95% confidence limits for normal NAP scores were 15.0–132.6. Decreased scores were demonstrated in 73% of CML, 7% of AML but never in LL patients. Increased scores were found in 37% of AML, 31% of LL but never in CML patients. Evaluation of the distribution of the single cell NAP acivity (negative, weak positive, strong positive) showed decreased activity in 77% of CML, 15% of AML but never in LL patients. Increased activity was demonstrated in 63% of AML, 54% of LL and 9% of CML patients. The evaluation of single cell activity is a time‐saving method, which furthermore proved superior to the scoring method in discriminating between the types of leukaemia investigated.
Adaptation of the May‐Grünwald‐Giemsa staining method for automated differential counting of blood leucocytes by a Hematrak analyzer
Authors: Penttilä I.M. , Mahlamäki E. , Mononen I. , Kärkkäinen P. 
Published: August 2010

The selection of exact pH (6.85/6.90) concentrations of the stains and staining times made it possible to use the May‐Grünwald‐Giemsa (MGG) staining method for smears studied with a Hematrak model 240 automated differential leucocyte counter. The differences between the smears stained by the method of Wright according to the recommendations of the manufacturer and the present MGG‐modification resulted in non‐significant differences in the recognition of various types of leucocytes.The differences between the manual method and those obtained by Hematrak for the MGG‐stained samples with normal total leucocyte counts were nonsignificant with all types of leucocytes except basophils, which were underestimated by the instrument. The present staining procedure was adequate in studying of neutrophilias. When samples with lymphocytosis or with immature cells were examined, too few lymphocytes and immature cells and too many monocytes were obtained by the instrument, as compared to the manual method.
RESULTS OF INDUCTION AND CONSOLIDATION TREATMENT WITH INTERMEDIATE AND HIGH‐DOSE ARA‐C AND m‐AMSA CONTAINING REGIMENS IN PATIENTS WITH PRIMARILY FAILED OR RELAPSED ACUTE LEUKEMIA AND NON‐HODGKIN'S LYMPHOMA
Authors: Peters W.G. , Willemze R. , Colly L.P. 
Published: August 2010

SUMMARYFifty two patients (aged 15–57 years) with primarily failed and relapsed acute myelogenous (AML) or lymphoblastic leukemia (ALL) and with high‐grade non‐Hodgkin's lymphoma (NHL) have been treated with intermediate dose cytosine arabinoside. Ara‐C (1 g/m2 q 12 h × 12) with 3 d of m‐AMSA, 115 mg/m2 daily was given to 18 patients, with daunorubicin (3 patients) 45 mg/m2 daily for 3 days to 3 patients and in 14 patients 1 day of m‐AMSA (115 mg/m2) was administered.In 17 patients ara‐C was combined with VP16.213 120 mg/m2 i v. on day 1 and 7, m‐AMSA 115 mg/m2 i.v. on day 1 and 7 and prednisone 60 mg/m2 orally on days 1–7, these patients received methotrexate 10 mg/m2 intrathecally on day 1. Thirty three patients obtained a complete remission (AML 18/24, ALL 7/9, NHL 8/18).17 patients received consolidation treatment with 1–3 courses comprising 4 d of ara‐C (3 g/m2 q 12 h × 8). in 9 patients combined with m‐AMSA 115 mg/m2 i.v. on day 5 and in 8 patients with VP16.213 120 mg/m2 on day 1 and 5, m‐AMSA 115 mg/m2 on day 1 and 5 and prednisone 60 mg/m2 orally days 1–5 and methotrexate 10 mg/m2 intrathecally on day 1. Three patients underwent allogeneic bone marrow transplantation, all other patients received no further treatment.Median remission duration was 3 months for those patients who received no treatment after remission induction. Five patients who received consolidation treatment relapsed after 4 months (2 ALL), 6 months (NHL), 9 months (AML) and 16 months (AML). Thirteen patients still are in remission at 2+ ‐ 21+ months.In addition to vomiting, fever, skin rashes, conjunctivitis and myalgia toxicity included diarrhoea in 35.8 per cent of patients and 10 patients developed diffuse interstitial pneumonia without clear cause and probably due to ara‐C administration. Fifty‐eight septicemic episodes were observed, in 65% caused by Streptococcus viridans. The pancytopenic period ranged from 16–25 days (median 21 days) after the remission induction and 14–21 days (median 19 days) after the consolidation course.Intermediate dose ara‐C is active in primary refractory and relapsed acute leukemia and lymphoblastic non‐Hodgkin's lymphoma. Side effects are acceptable although interstitial lung‐involvement remains to be further investigated.
Enzyme markers in acute myeloid leukaemia
Authors: Skoog Lambert , Hagerstrom Torsten , Reizenstein Peter , Ost Åke 
Published: August 2010

The levels of TdT, AdA, 5′‐N, 20 a‐SDH and TK1 were analyzed in different FAB subgroups of AML. AdA, 5′‐N, 20 a‐SDH and TK1 showed large variations both within and between the different subgroups. It therefore seems unlikely that measurements of these enzymes will be able to aid morphological subclassification of AML. Neither could analysis of these enzymes give prognostic information.TdT was detectable in 46% of AML but the levels were only 1/10‐1/100 of those found in ALL. The enzyme was detected in leukaemic granulocytopoietic cells while leukaemic cells of monocytic origin were negative in all but 1 case. In addition, increased TdT activity was positively correlated to the length of survival.
Microbiological evaluation and antibiotic susceptibility of dental unit water systems in general dental practice
Authors: Uzel A , Cogulu D , Oncag O 
Published: August 2010

Abstract:  Objective:  The microbial quality of water in a dental unit water systems (DUWS) is of considerable importance because patients and dental staff are regularly exposed to water and aerosol generated from the dental units. The objective of this study was to evaluate the 20 DUWS in general dental practices and to determine the antibiotic susceptibility of the colonizing bacteria.Methods: Three water and one biofilm samples from each DUWS were investigated for total viable count (TVC), oral streptococci, Pseudomonas spp., Enterobacteria, Candida albicans and Legionella pneumophila.Results: A total of 44 morphologically different colonies were obtained from water samples and 20 types of colonies (45.5%) could be identified using API test strips. The mean TVC values were 4.36 log CFU ml−1 for source waters, 4.95 log CFU ml−1 for 3‐in‐1 syringe samples, 4.91 log CFU ml−1 for air rotor samples and 3.66 log CFU cm−2 for biofilm samples. Susceptibilities of the isolates were tested against piperacillin, ampicillin, ceftazidime, meropenem, gentamicin, tetracycline, ofloxacin and chloramphenicol by using microdilution method according to NCCLS. The meropenem and ofloxacin have shown the broadest spectrum against to the tested isolates.Conclusion: The study emphasizes the need for effective mechanisms to reduce the microbial contamination in DUWS, and highlights the risk for cross‐infection in general dental practice.
A survey on misunderstanding of dental scaling in Hong Kong
Authors: Young Cecilia 
Published: August 2010

Abstract:  There is no information on the misunderstanding of dental scaling; on whether the misunderstanding affects the general public to go for scaling or not; on complaints about dental scaling and suggestion of who should educate the public in the existing literature. This study gives the information from the general public in Hong Kong.Methods:  A cross‐sectional survey by telephone interview on a random sample of 1412 subjects aged 13 years and above in Hong Kong was conducted from 3rd January to 15th February 2006.Results:  More females had received scaling (adjusted OR = 1.73, 95%CI 1.31–2.29 P < 0.001), 51–60 years age group had the highest scaling experience (adjusted OR = 2.69, 95% CI 1.55–4.68, P < 0.001). Higher education was related to scaling experience (P < 0.001). Of the subjects with complete data, 22.5% (307/1364) had never received dental scaling, 17.9% (55/307) did not understand the purpose, 12.1% (37/307) replied that it would make the teeth thinner, 11.4% (35/307) replied that the gum space would become wider, and 11.4% (35/307) stated that scaling would damage the gum. In all, 45.9% (298/649) of the subject reported bleeding, 33.7% (139/413) sensitivity, 40.5% (62/153) smaller teeth and 23.9% (84/351) widened gum space because of mistakes made during the procedure; 8.6% (56/649) of those who experienced bleeding, 17.8% (27/152) of those who reported the teeth became smaller and 12% (42/350) of those who stated that the gum space became wider intended to reduce the frequency, delay or not go for scaling. A total of 79.6% (841/1057) experienced one of the perceived problems; 27.8% (234/841) had complained about scaling.Conclusion:  This study shows a common lack of knowledge of dental scaling in the Hong Kong population. Patients should be better informed about the aim before the procedure.