bluuebunny/crossref_metadata_2025_split huggingface dataset:
COMPARISON OF FACTOR VIII CONCENTRATES IN NON‐BLEEDING PATIENTS
Authors: Schimpf KI. , Rothmann P. , Schumacher K. 
Published: August 2010

ABSTRACT: The comparison ofin vivorecovery of Factor VIII:C of 3 Factor VIII concentrates in two consecutive cross‐over studies on non‐bleeding patients suffering from a severe hemophilia A showed in both instances equally strong differences; values more than twice as high were obtained with product C than with product A. The cause for this was found to lie in the different declarations of the products. With calculations based on the results of thein vitrotesting of the concentrates, the recoveries of the 3 products largely converged. For this reason one should demand that declarations for all products be made in accordance with uniform rules.In both studies the mean values of the half elimination times (half‐lives) of Factor VIII:C were in each case the same for the 3 products; but in study a) the mean value of half‐lives was distinctly longer (14.1 hrs) than in study b) (10.5 hrs). The recovery, too, was higher in study a) (1.96 YO) per injected unit measured than in study b) (1.4%). This occurred despite identical conditions in both studies. An explanation for this was not found.There was a tendency towards a positive relationship between recovery and body weight.According to the applied cross‐over design, the rank order of the Factor VIII:C recoveries found between the various concentrates were not blurred by the individual differences from patient to patient; nor were they blurred by the strong varying hematocrit values and other unknown factors relating to deviations in recovery, distribution time and elimination time from patient to patient. There can be no doubt as to the advantages of the cross‐over methodoly when performing directin vivocomparisons.
FACTOR VIII RELATED ACTIVITIES IN CONCENTRATES
Authors: Nilsson Inga Marie , Borge Lise , Gunnarsson Margoth , Kristoffersson Ann‐Charlotte 
Published: August 2010

ABSTRACT: Factor VIII related activities were investigated in 3 low purity concentrates (fraction 1‐0 and freeze‐dried cryoprecipitates), 2 intermediate concentrates, and 8 high purity concentrates. The parameters studied were VIII:C by one‐stage assay and chromogenic assay, VIII clotting antigen (VIII:CAg), VIII related antigen (VIIIR:Ag) by electroimmunoassay, immunoradiometric assay (IRMA), crossed immuno‐electrophoresis (CIE) and SDS agarose gel electrophoresis followed by staining with radioactive antibody, ristocetin cofactor activity (R:RCF) and fibrinogen. The VIII:C values from the chromogenic assay method agreed well with those obtained by the one‐stage assay. The specific activity varied considerably between the different concentrates and even between different batches. DDAVP Octonativ and Factorate had the highest specific activity. With the exception of Factorate, all preparations had higher concentrations of VIII:CAg than of VIII:C — probably indicating inactivation of the biological activity of VIII:C during the manufacturing process.Studies of the Factor VIII/von Willebrand factor showed that all the concentrates contain considerable amounts of VIIIR:Ag as measured by electroimmunoassay. The intermediate and the high purity concentrates had much lower concentration of VIIIR:Ag as determined by IRMA than by electroimmunoassay, and the dose response curves were non‐parallel. On CIE they showed an abnormal migration. Multimeric sizing demonstrated that all the intermediate and high purity concentrates were lacking in the high molecular weight multimers. Fraction 1‐0 and the cryoprecipitates, the only preparations capable of correcting the bleeding defect in patients with von Willebrand's disease, showed about the same concentration of VIIIR:Ag as determined by electroimmunoassay and IRMA, normal migration in CIE, and the same multimeric pattern as normal plasma. The VIIIR:RCF values were much lower than those for VIIIR:Ag, as determined by electroimmunoassay.Thus, considerable differences were found of thein vitroproperties of Factor VIII related activities between low, intermediate and high purity Factor VIII concentrates. The action of proteases and the techniques used in purification probably have a crucial effect on the properties.
Extramedullary haemopoiesis after bone marrow transplantation
Authors: Arnold R. , Calvo W. , Heymer B. , Schmeiser T. , Heimpel H. , Kubanek B. 
Published: August 2010

44 patients underwent bone marrow transplantation (BMT) for treatment of severe aplastic anaemia or haematological malignancies. During their post‐transplant phase all patients had erythroblasts and granulocytic precursors in their peripheral blood. 15 patients died between day +6 and d +346 after BMT and autopsies were performed. The sections of all 15 patients revealed extramedullary haemopoiesis in the spleen. Extra‐medullary haemopoiesis in the liver was found only in those patients who died early (between d +6 and d +21 after BMT). Medullary haemopoiesis, normally only occurring in the vertebral body, was also observed in the shaft of the femur.The present data show that after BMT all tissues with a haemopoietic matrix in ontogenesis can be repopulated with haemopoiesis in the early phase of reconstitution, possibly to compensate for the haemopoietic insufficiency after conditioning therapy. The expansion of haemopoiesis in the later period of up to 1 year after BMT, remains to be explained.
Effect of sera from various vertebrate species on mouse erythroid progenitor proliferation
Authors: Butin Christophe , Blanchet Jean Paul 
Published: August 2010

Sera from different vertebrate species were tested for their stimulating activity upon mouse CFU‐E growth. Crude sera were either naturally stimulating or toxic. Absorption on mouse blood and spleen cells or decomplementation removes or neutralizes the toxicity, probably mediated through natural anti‐mouse antibodies. All but 2 sera tested (ox and sheep) were stimulatory. This stimulating activity was found to be either heat‐sensitive or ‐resistant according to the sera. Upon chromatography on DEAE cellulose, 2 fractions were obtained which were both stimulatory. Whether these two stimulating activities correspond to different molecules or to only 1 absorbed on different serum proteins remains to be determined.These results confirm previous results obtained for mouse and human sera and suggest that this cross‐reactive stimulating activity may have an important role in vertebrate erythropoiesis.
Prognostic value of the determination of serum lactic dehydrogenase and its isoenzymes in children with acute lymphoblastic leukaemia
Authors: Hi¸söUnme Gönül , Çag̈lar Kazim , Renda Nurten 
Published: August 2010

Serum total lactic dehydrogenase (LDH) levels have been found to be significantly higher in 21 children with acute lymphoblastic leukaemia (ALL) at initial diagnosis than the values of 12 children who achieved remission. The mean value of serum LDH levels in patients with high‐risk factors was 2347 ± 1490 U/ml (range 430–5460 U/ml), while in patients at standard risk it was 652 ± 385 U/ml (range 110–1320 U/ml). The serum LDH values were above 1320 U/ml in 70% of the 13 children with high‐risk factors.The serum isoenzyme patterns were analyzed in 17 of these children at the initial diagnosis. Although LDH‐3 and LDH‐2 were prominent at the time of diagnosis; LDH‐2 and LDH‐1 were the prodominant isoenzymes in remission. The highest concentrations of LDH‐3 were observed in the high‐risk group at diagnosis and the ratio of LDH‐3 to LDH‐2 exceeding 1.0 was found in children who had high‐risk factors, but not in any patients in the standard risk group.
Translocation (2;11) (p21;q23) in acute non‐lymphocytic leukaemia: A non‐random association
Authors: de LaChapelle Albert , Knuutila Sakari , Elonen Erkki 
Published: August 2010

A reciprocal apparently balanced translocation between chromosomes 2 and 11, t(2;11) (p21;q23), was the sole chromosome abnormality in mitoses studied from 2 patients because of suspected acute leukaemia. The first patient, a 66 year‐old male who had had no exposure to mutagenic agents, presented with a myelodysplastic preleukaemic syndrome lasting 17 months before ANLL‐M4 was diagnosed. The second patient, who had been irradiated after surgical removal of a mixed parotid gland tumour 36 years earlier, presented with ANLL‐M1. Both patients had prostatic cancer.We have found 4 patients with the same translocation described in the literature. All had a myelodysplastic syndrome at presentation. One of these patients died of ANLL‐M6; the others survived after different periods of observation.Comparison of the cytogenetic features of all 6 patients indicates that the translocation was apparently identical. The t(2;11) was the sole abnormality in 5 of the 6 patients. The clinical features were somewhat different. However, features common to all patients included male sex, age over 50, and involvement of the non‐lymphocytic series of haematopoietic cells in a preleukaemic or leukaemic condition. A previous history of exposure to irradiation occurred in 2 or, possibly, 3 patients. This translocation should presently be listed as a non‐randomly occurring one with clinical consequences affecting myeloid cells.
DOSE‐RELATED PHARMACOLOGIC EFFECTS OF HIGH DOSE ARA‐C AND ITS USE IN COMBINATION WITH ASPARAGINASE FOR THE TREATMENT OF PATIENTS WITH ACUTE NON‐LYHPHOCYTIC LEUKEMIA*
Authors: Capizzi Robert L. , Powell Bayard L. , Cooper M. Robert , Rathmell James P. , White J. Courtland , Muss Hyman B. , II Frederick Richards , Jackson Don V. , Stuart John J. , White Douglas R. , Zekan Patricia J. , Cruz Julia M. , Spurr Charles L. 
Published: August 2010

ABSTRACTClinical resistance to ara‐C is dose and schedule dependent. Patients refractory to or who have relapsed on combinations of drugs which include standard doses of ara‐C (100–200 mg/m2daily for 5 to 7 days) can be induced into clinical remissions with high dose ara‐C (HiDAC). The interaction between HiDAC and asparaginase is schedule‐dependent; pharmacologic synergy and an improvement in the therapeutic index occurring with sequential HiDAC→Asparaginase. This combination has been applied in clinical trial: ara‐C 3 g/m2as a 3 hr IV infusion was given every 12 hrs for 4 doses. At the end of the 4th infusion, 6000 IU/m2asparaginase was given IM. This therapy was given on days 1 and 8. Refractory/ relapsed patients had a 68% complete remission rate. Treatment of 49 patients with previously untreated ANLL was associated with an 80% and 40% complete remission rate in patients <60 and >60 years of age, respectively. Median time to complete remission for both age groups was 30 days. The lower complete remission rate in older patients reflects higher induction deaths (ID) (50%), not innate drug resistance. Laboratory investigations have focused on the biochemical pharmacology of HiDAC in an attempt to explain the unique therapeutic utility of this mode of drug administration. These data suggest that human leukemia cells transport ara‐C across the cell membrane relatively less efficiently than experimental leukemia cells. The systemic metabolite of ara‐C, ara‐U, may also influence the drug's effect. In the murine leukemia L5178Y, both in vitro and in vivo, high concentrations of ara‐U are cytostatic in S‐phase. the phase of the cell cycle wherein ara‐C cytotoxicity is increased. In vivo, high concentrations of ara‐U also retard systemic deamination of ara‐C as well as its renal excretion. These features increase the terminal half‐life of HiDAC in the plasma and thus prolong cellular exposure to the drug. The interactions between ara‐U and ara‐C thus invoke selfpotentiation of HiDAC.
PHARHACOKINETIC STUDIES ON ARA‐C
Authors: Liliemark Jan 
Published: August 2010

SUMMARYPharmacokinetic studies of ara‐C in plasma are reviewed. The value of monitoring ara‐C in plasma is limited, because ara‐C is an inactive prodrug, and has to be phosphorylated to ara‐CTP intracellularly to excert its activity. Therefore, the pharmacokinetics of ara‐CTP in leukemic cells was studied. The differences between the pharmacokinetics of ara‐C in plasma and ara‐CTP in leukemic cells in terms of elimination rates and heterogeneity are important and there seems to be only poor correlation between the two. This is the rational for attempts to correlate the pharmacokinetics of cellular ara‐CTP to clinical effect of ara‐C treatment. The accumulation of ara‐CTP seems to be saturated during high‐dose ara‐C treatment. As a consequence, the duration of infusion is a more important determinant of the efficacy than the dose in high‐dose ara‐C treatment. This should be considered in design of high‐dose ara‐C treatment protocols.
CELLULAR PHARMACOLOGY AND OPTIMAL THERAPEUTIC CONCENTRATIONS OF 1‐β‐D‐ARABINOFURANOSYLCYTOSINE 5‘‐TRIPHOSPHATE IN LEUKEMIC BLASTS DURING TREATMENT OF REFRACTORY LEUKEMIA WITH HIGH‐DOSE 1‐β‐D‐ARABINOFURANOSYLCYTOSINE
Authors: Plunkett William , Iacoboni Stephen , Keating Michael J. 
Published: August 2010

ABSTRACTThe pharmacology of 1‐β‐D‐arabinofuranosylcytosine 5′‐triphosphate (ara‐CTP) has been studied in the circulating leukemic blasts of patients with refractory leukemia during therapy with high doses of single‐agent ara‐C. Cellular ara‐CTP was analyzed by high‐pressure liquid chromatography. The median trough concentrations of ara‐CTP in blasts of patients who responded to intermittent high‐dose ara‐C (3 g/m2× 4–12 doses) was 196 μM, whereas 75 μM was the lowest trough ara‐CTP concentration that discriminated between complete remission and treatment failure (p=0.03). The median steady state ara‐CTP concentrations in the blasts of patients who responded to a high dose continuous infusion protocol (2 doses of 3 g/m2every 12 hr followed by a continuous infusion of 330–3000 mg/m2× 4 d) were clustered between 79 and 206 μM. The values of treatment failures were predominantly outside this range (p<0.005). These results suggest that the optimal concentration range for intracellular ara‐CTP in the treatment of refractory leukemia may be 75 to 200 μM.
Dental unit water: bacterial decontamination of old and new dental units by flushing water
Authors: Watanabe E , Agostinho AM , Matsumoto W , Ito IY 
Published: August 2010

Abstract:  Objective: To evaluate by means of Petrifilm™ system (3M, St Paul, MN, USA) the level of bacterial contamination in water from old and new dental units (air–water syringes and high‐speed turbines) before and after flushing water through waterlines. The old dental units had been used for 13 years and the new dental units for 1 year. A fast method named Petrifilm™ AC (3M) was employed to evaluate the level of water contamination with total aerobic bacteria and Petrifilm™ EC for Escherichia coli and coliforms.Methods: Dental unit water were collected before and after flushing of 4 (air–water syringes) and 2 min (high‐speed turbines) from 24 old and new dental units. Thereafter, samples were diluted, inoculated onto Petrifilm™ plates and incubated.Results: The filtered tap water that filled up dental unit reservoirs showed a low level of bacterial contamination (4 and 15 CFU ml−1). However, all water samples from old and new dental units were highly contaminated. The flushing of dental unit waterlines reduced the bacterial count in all dental unit water, but the reduction was better in water from new dental units than from old dental units. E. coli and coliforms were not detected in any water samples analysed.Conclusion: Flushing water is a simple measure that should do part of dental routine, because it was able to reduce the level of total aerobic bacteria in water from old and new dental units.
Acoustic Startle Response in the Study of Developmental Toxicity
Authors: HIRONAKA Naoyuki 
Published: August 2010

AbstractAcoustic startle response (ASR) is a defensive reflex that occurs shortly after presentation of a brief intense acoustic stimulus. It consists of a sudden contraction of facial and skeletal muscle. ASR in rodents is a gross vibration‐like movement of the body that is easy to elicit, record, and analyze quantitatively. It can also be used as a reliable and sensitive measure of physiological mechanism of developmental toxicity. The basic neural mechanisms of ASR have been elucidated. The cochlear nucleus and the reticular nucleus of pons are essential to the induction and regulation of ASR amplitude. Fear or anxiety augments ASR (fear potentiation) and functionally involves amygdala. A brief presentation of a weak acoustic stimulus shortly before the presentation of a startling stimulus suppresses ASR (prepulse inhibition). Prepulse inhibition is thought to be regulated by the dopaminergic mesolimbic system. Taken together, these phenomena suggest the use of ASR as a means of modeling anxiety/fear and the sensorymotor abnormalities that may present themselves in a condition such as schizophrenia. In this review, the fundamental behavioral and neural features of ASR are described and major findings in connection with the toxicology of ASR are reviewed. Finally, the significance of ASR in the study of developmental toxicology including behavioral teratology is discussed. Key words: acoustic startle response, fear potentiation, prepulse inhibition, developmental toxicology, behavioral teratology
3‐Chloro‐4‐(dichloromethyl)‐5‐hydroxy‐2(5H)‐furanone (MX) as a Direct‐Acting Teratogen in Micromass in vitro Tests
Authors: TERAMOTO Shoji , TAKAHASHI Ken L. , KIKUTA Masayuki , KOBAYASHI Hiroko 
Published: August 2010

Abstract3‐Chloro‐4‐(dichloromethyl)‐5‐hydroxy‐2(5H)‐furanone (MX) causes complete inhibition of rat embryonic midbrain (CNS) cell differentiation in the micromass in vitro test when applied at a concentration of 5 μg/ml under conditions where MX is rapidly degraded in culture medium with a half‐life of 56 min. This study investigated whether or not degradation products of MX have inhibitory effects on CNS cell differentiation following pre‐incubation of MX in culture medium for 0.5, 1 or 2 hr. When MX was pre‐incubated for 0.5 hr, the mean number of differentiated foci was 0.2 against 62.5 for the control. However, the number increased to 44.7 when pre‐incubation time was extended to 2 hr. These results suggest that MX, but not its degradation products, is a teratogen in vitro. MX manifested almost complete inhibitory effects on CNS cell differentiation by 0.5 hr of exposure.
Alopecia Universalis, Cleft Palate and Lip, Hypohydrosis, Hypodontia, Nail Dysplasia and Syndactyly: New Ectodermal Dysplasia Syndrome?
Authors: ABDEL‐SALAM Ghada M.E. , BUCSEK M. , CZEIZEL A.E. 
Published: August 2010

AbstractThe 3 year old girl has hypohydrotic ectodermal dysplasia, cleft lip and palate, striking alopecia with total absence of eye brows and body hair (alopecia universalis), epicanthic folds, strabismus, malpositioned small square‐shaped teeth with absent one in the upper jaw, small fingers with dysplastic nails and toes, pilonidal sinus, partial syndactyly between the 2nd and 3rd toes, and slight developmental delay.
Inherited Skin Diseases: DNA‐Based Diagnoses and Prenatal Diagnoses
Authors: SHIMIZU Hiroshi 
Published: August 2010

AbstractAmong a range of inherited skin disorders, some of markedly severe phenotypes have been widely considered as indications for prenatal diagnoses. Recent studies have achieved significant progress in understanding the molecular basis of these heritable skin diseases. These include epidermolysis bullosa (EB), a group of mechanobullous genodermatoses, ichthyosis, a heterogeneous condition of generalized hyperkeratosis, and oculocutaneous albinism, in which an abnormal melanin synthesis in the skin and eyes is a hallmark. The responsible gene for the dystrophic forms of EB has been identified as a gene encoding type VII collagen, for lethal Herlitz EB the genes encoding the α3, β3, or γ2 chain of laminin 5, for pyloric‐atresia junctional EB syndrome the genes encoding the α6 or β4 integrins, and for tyrosinase negative oculocutaneous albinism the tyrosinase gene. Specific mutations in the responsible gene or genes have implications for understanding the structure‐function relationship and phenotype/genotype correlation of each disorder, and also provide the basis for DNA‐based diagnoses as well as prenatal diagnoses for families at risk of a recurrence of the disease. Furthermore, understanding the genetic basis of each inherited skin disease sets the stage for gene therapy approaches for the treatment of the respective condition.
Radio‐Frequency Radiation and Birth Defects: Is There a Risk to Human Health?
Authors: BARNETT Stanley B. 
Published: August 2010

AbstractThis paper reviews studies in the radiofrequency spectrum which includes radiation from cellular telephones and other wireless networks. Modern mobile communications technology uses pulsed digital systems operating at frequencies of 900–1, 800 MHz. Although there are some reports that pulsed exposures may be more likely to produce biological effects than an equivalent energy deposition from continuous wave, there are relatively few data relevant to the frequency or the pulsing conditions used in telecommunications. Most of the literature on teratological studies on animals reports results of continuous wave transmission, 2,450 MHz (microwave oven frequency), at substantial levels of exposure; exceeding internationally prescribed safety levels for radio‐frequency radiation (RFR). Gross developmental anomalies were associated with significant increases above normal in embryonic or fetal temperature. The issue of possible athermal effects has not been properly resolved. Although it is now largely accepted that some biological responses to RFR occur at levels below which thermal mechanisms may be implicated, the absence of relevant directed research programs prevents sensible scientific conclusions on the consistency of data and their relevance to human health. Considering these limitations, there is no convincing independently verified evidence that exposures to RFR from current mobile telecommunications technology presents a serious health risk to human prenatal development.