bluuebunny/crossref_metadata_2025 huggingface dataset:
Short Bursts of Weak Pulses Break Postictal Inhibition in the Neocortex of Wistar Rats
Authors: Tůma Lukáš , Krýsl David , Mareš Jan
Published: May 2003

Summary: Purpose:Postictal inhibition (PI) is a decrease in excitability that follows an epileptic seizure and decreases probability of new seizure occurrence. PI may involve both increased inhibition and persisting elevated excitation. Our experiments tested whether shorter trains of weak stimuli are able to unmask this residual increase of excitability during the PI.

Methods:Four epileptic afterdischarges (ADs) were evoked by intense electrical stimulation (20 s, 8 Hz, current intensity at 5× threshold) of the neocortex in two groups (A, B) of Wistar rats. Before the first AD and during the 10‐min interictal period, 8‐Hz trains of four weak pulses (half of the intensity used for the AD triggering; 4P) were applied every 20 s in group B and a single pulse with similar parameters in group A.

Results:The number of interictal epileptiform events evoked by 4P in the group B was significantly higher than that in the group A (evoked by single pulses) except after the second AD. Epileptic events were triggered by 4P also immediately after the AD termination.

Conclusions:It is apparent that weak stimulation can trigger epileptic phenomena during PI. Our results indicate that it is no longer possible to perceive PI only as persisting extreme and active inhibition. An appropriate stimulation can reveal more subtle (but important) excitatory events contributing to the functional status during the postictal period.
Effect of Topiramate on the Anticonvulsant Activity of Conventional Antiepileptic Drugs in Two Models of Experimental Epilepsy
Authors: Borowicz Kinga K. , Luszczki Jarogniew J. , Duda Andrzej M. , Czuczwar Stanislaw J.
Published: May 2003

Summary:  Purpose: The objective of this study was to evaluate the interaction of the novel antiepileptic drug (AED), topiramate (TPM), with conventional AEDs against amygdala‐kindled seizures in rats and pentylenetetrazol‐induced convulsions in mice.

Methods: Experiments were performed on mice and fully kindled rats. In pentylenetetrazol test, the chemoconvulsant was used at its CD97 dose of 105 mg/kg, producing clonic seizures in 97% of mice. Adverse effects were evaluated with the chimney test and passive avoidance task. Plasma levels of AEDs were measured with immunofluorescence.

Results: TPM at 20 mg/kg exerted a significant anticonvulsant effect as regards seizure and afterdischarge durations in amygdala‐kindled seizures in rats, being ineffective at lower doses. Coadministration of TPM (10 mg/kg) with valproate (VPA; at a subtherapeutic dose of 50 mg/kg) resulted in essential reductions of seizure and afterdischarge durations. TPM (10 mg/kg) combined with carbamazepine (CBZ; at a subtherapeutic dose of 15 mg/kg) significantly increased afterdischarge threshold, simultaneously decreasing the remaining seizure parameters (duration or severity of seizures and afterdischarge duration). TPM (10 mg/kg) given with phenobarbital (PB; 15 mg/kg) markedly shortened seizure severity and seizure and afterdischarge durations. Combinations of TPM with diphenylhydantoin (PHT) were ineffective against kindled seizures in rats. TPM combined with VPA and PB did not alter their plasma levels, but its combination with CBZ resulted in an increased free plasma CBZ concentration. TPM (10 and 20 mg/kg) alone and its combinations with conventional AEDs affected neither motor coordination nor long‐term memory, evaluated in the chimney and passive avoidance tests, respectively, in rats. In pentylenetetrazol‐evoked convulsions in mice, TPM (175 and 200 mg/kg) showed anticonvulsant effects per se. Moreover, TPM (at its subtherapeutic dose of 150 mg/kg), significantly potentiated the anticonvulsant action of ethosuximide (ESM), but not that of VPA, PB, or clonazepam (CZP) against pentylenetetrazol‐induced seizures. Either TPM alone (150 mg/kg) or its combination with ESM did not result in significant undesired effects.

Conclusions: The experimental data indicate that except for PHT, the combinations of TPM with conventional AEDs are beneficial against amygdala‐kindled seizures in rats. In the pentylenetetrazol test, this novel AED potentiated only the protection offered by ESM.
Neuronal Cell Death in a Rat Model for Mesial Temporal Lobe Epilepsy Is Induced by the Initial Status Epilepticus and Not by Later Repeated Spontaneous Seizures
Authors: Gorter Jan A. , Pereira Pedro M. Gonçalves , Van Vliet Erwin A. , Aronica Eleonora , Da Silva Fernando H. Lopes , Lucassen Paul J.
Published: May 2003

Summary:  Purpose: To determine whether repeated seizures contribute to hippocampal sclerosis, we investigated whether cell loss in the (para) hippocampal region was related to the severity of chronic seizure activity in a rat model for temporal lobe epilepsy (TLE).

Methods: Chronic epilepsy developed after status epilepticus (SE) that was electrically induced 3–5 months before. The presence of neuronal damage was assessed by using Fluoro‐Jade and dUTP nick end‐labeling (TUNEL) of brain sections counterstained with Nissl.

Results: We found a negative correlation between the numbers of surviving hilar cells and the duration of the SE (r = –0.66; p < 0.01). In the chronic phase, we could discriminate between rats with occasional seizures (0.15 ± 0.05 seizures per day) without progression and rats with progressive seizure activity (8.9 ± 2.8 seizures/day). In both groups, the number of TUNEL‐positive cells in parahippocampal regions was similar and higher than in controls. In the hippocampal formation, this was not significantly different from controls. Fluoro‐Jade staining showed essentially the same pattern at 1 week and no positive neurons in chronic epileptic rats.

Conclusions: Cell death in this rat model is related to the initial SE rather than to the frequency of spontaneous seizures. These results emphasize that it is of crucial importance to stop the SE as soon as possible to prevent extended cell loss and further progression of the disease. They also suggest that neuroprotectants can be useful during the first week after SE, but will not be very useful in the chronic epileptic phase.
The Provision of Epilepsy Care across Europe
Authors: Malmgren Kristina , Flink Roland , Guekht Alla B. , Michelucci Roberto , Neville Brian , Pedersen Birthe , Pinto Francisco , Stephani Ulrich , Özkara Cigdem
Published: May 2003

Summary:  Purpose: To assess the needs and resources available in the provision of basic epilepsy care across Europe.

Methods: A mailed questionnaire was used, the European Epilepsy Services inventory (EESI). The EESI was distributed to all 36 European chapters of the International League Against Epilepsy (ILAE), and answers were obtained from 32, a response rate of 89%. For the purpose of studying trends across Europe, the chapters were divided into a Western, an Eastern, a Central, and a Southern group.

Results: The survey results showed that there was a wide range in the number of physicians and specialists involved in epilepsy care across Europe, with a trend toward higher numbers of neurologists, pediatricians, and pediatric neurologists in Eastern Europe. Many different specialities were involved in epilepsy care, and many chapters reported differences in the provision of care across their countries, with less possibility for patients to see a specialist in the least provided areas, where most epilepsy patients were cared for by general practitioners and internists. Problems with high costs of the newer antiepileptic drugs were most pronounced in Eastern Europe. Problems with lack of comprehensive care and of epilepsy specialists, with stigma and social problems, and with insufficient professional education and knowledge about epilepsy were reported all across Europe.

Conclusions: Knowledge about differences in the pattern of provision of epilepsy care and about the main problems encountered by the European ILAE chapters is of importance in the continuing efforts to improve management of epilepsy all over Europe.
High Body Mass Index Does Not Predict Mortality in Older People: Analysis of the Longitudinal Study of Aging
Authors: Grabowski David C. , Ellis John E.
Published: May 2003

OBJECTIVE: To determine the excess mortality associated with obesity (defined by body mass index (BMI)) in older people, with and without adjustment for other risk factors associated with mortality and for demographic factors.

DESIGN: Retrospective cohort analysis of the Longitudinal Study of Aging (LSOA).

SETTING: Nationally representative sample of community‐dwelling older people.

PARTICIPANTS: Seven thousand five hundred and twenty‐seven participants age 70 and older in 1984.

MEASUREMENTS: We used Cox regression to calculate proportional hazards ratios for mortality over 96 months. We tested the hypothesis that increased BMI (top 15%) increased mortality rates in older people.

RESULTS: Death occurred in 38% of the cohort: 54% of the thin (lowest 10% of the population, BMI <19.4 kg/m2), 33% of the obese (highest 15%, BMI> 28.5 kg/m2), and 37% of the remaining participants (normal) died. Adjustment for demographic factors, health services utilization, and functional status still demonstrated reduced mortality in obese older people (hazard ratio 0.86, 95% confidence interval (CI) = 0.77–0.97) compared with normal. After adjustment, thin older people remained more likely to die (hazard ratio 1.46, 95% CI = 1.30–1.64) than normal older people. Sensitivity analyses for income, mortality during the first two years of follow‐up, and medical comorbidities did not substantively alter the conclusions.

CONCLUSION: Obesity may be protective compared with thinness or normal weight in older community‐dwelling Americans.
Adsorption of autoantibodies in the presence of LISS to detect alloantibodies underlying warm autoantibodies
Authors: Chiaroni Jacques , Touinssi Mohammed , Mazet Magali , De Micco Philippe , Ferrera Virginie
Published: May 2003

BACKGROUND : The safe transfusion of patients with warm autoimmune hemolytic anemia requires an efficient and time‐saving assay to detect alloantibodies underlying autoantibodies. Methods used include RBCs treated with ZZAP reagent, proteolytic enzyme, or untreated RBCs in the presence of PEG. We propose a method using LISS, which presents some advantages over previous methods.

STUDY DESIGN AND METHODS : We evaluated the effectiveness of autoantibody adsorption with papain‐treated and untreated RBCs in the presence of LISS for removal of autoantibodies, without affecting alloantibodies.

RESULTS
: One‐hundred twenty sera containing autoantibodies were adsorbed with our routine method, which uses papain‐treated allogeneic RBCs. Seven‐hundred twenty adsorptions (mean, 6 per sample) and 21,600 minutes (mean, 180 min per sample) were required to remove autoantibodies. Fifty sera were adsorbed with our routine method that uses papain‐treated allogeneic RBCs in the presence of LISS. The number of adsorptions and the completion time were, respectively, 144 (mean, 2.9 per sample) and 2,880 minutes (mean, 57.6 min per sample). Twenty sera were evaluated with untreated autologous RBCs, in the presence of LISS; 58 adsorptions (mean, 2.9) and 1,160 minutes (mean, 58 min per sample) were required. Three adsorptions with antigen‐negative allogeneic RBCs were performed on 8 sera containing alloantibodies with weak reactivity (anti‐K [1], anti‐D [1], anti‐Fy
a
[2], anti‐S [2], anti‐E [1], and anti‐Jk
a
[1]). Alloantibodies were detected with the LISS procedure with papain‐treated and untreated RBCs and the routine papain method. Alloantibodies with weak reactivity, tested against the same antibody‐detection RBCs, remained unchanged following adsorption of 5 sera. An anti‐S, with very weak reactivity, was no longer detected, and an anti‐Jk
a became weaker (1+), regardless of the procedure used. One anti‐D became weaker only with the LISS adsorption method.

CONCLUSION : Autoantibodies can be adsorbed more efficiently in the presence of LISS.
Adverse effects in blood donors after whole‐blood donation: a study of 1000 blood donors interviewed 3 weeks after whole‐blood donation
Authors: Newman Bruce H. , Pichette Shawn , Pichette Dena , Dzaka Ema
Published: May 2003

BACKGROUND : There are no reports in the transfusion medicine literature that describe adverse reactions and donor arm injuries after whole‐blood donation based on solicited information.

STUDY DESIGN AND METHODS : The present study solicited adverse reaction and donor arm injury information from 1000 randomly selected whole‐blood donors approximately 3 weeks after the whole‐blood donation. Two 16‐gauge phlebotomy needles in use were also compared.

RESULTS : Thirty‐six percent of the donors had one or more adverse effects (AEs). The most common systemic AEs were fatigue (7.8%), vasovagal symptoms (5.3%), and nausea and vomiting (1.1%). The most common arm findings were bruise (22.7%), arm soreness (10.0%), and hematoma (1.7%). Men were half as likely as women to have an AE (23% AE vs. 48% AE, p < 0.0001). Repeat blood donors had fewer AEs than first‐time blood donors (36% AE vs. 47% AE, p < 0.007), and African‐American donors had numbers of AEs similar to those of Caucasian donors (31% AE vs. 38% AE, p = 0.30). The two phlebotomy needles did not differ in causing blood donor AEs.

CONCLUSION : AEs after donation and complaints may be more common than previously thought. The postdonation interview is a good tool for defining the blood donor's experience. It can also be used to evaluate and potentially improve blood donor safety and comfort.
Early neutrophil engraftment following autologous BMT provides a functional predictor of long‐term hematopoietic reconstitution
Authors: Zubair Abba , Zahrieh David , Daley Heather , Schott Daryls , Gribben John G. , Freedman Arnold , Ritz Jerome
Published: May 2003

BACKGROUND : Previous studies have demonstrated that the number of CD34+ progenitor cells in the stem cell graft is highly predictive of the rapidity of short‐term hematopoietic engraftment. The aim of this study was to identify factors that predict long‐term hematopoietic reconstitution (LHR) following autologous BMT.

STUDY DESIGN AND METHODS : To identify predictors of LHR, peripheral blood counts and marrow biopsies were evaluated at 1 year after transplant in 81 patients with B‐cell non‐Hodgkin's lymphoma (NHL) or chronic lymphocytic leukemia who underwent autologous BMT. Results were correlated with CD34+ cell dose, granulocyte‐monocyte colony‐forming units (CFU–GM) infused, and time to neutrophil engraftment (TNE).

RESULTS : Total MNC dose, CD34+ cell dose, and CFU–GM infused were significantly associated with TNE (p = 0.011, p < 0.0001, and p = 0.078, respectively). Patients with chronic lymphocytic leukemia were more likely to have received a low CD34+ cell dose than patients with B‐cell non‐Hodgkin's lymphoma (p = 0.01). Among the four principal predictors, only TNE showed consistent significant correlation with WBC, absolute neutrophil, and platelet count at 1 year after transplant. Logistic regression model showed that TNE was a more sensitive predictor of LHR than either CD34+ cell dose or CFU–GM infused.

CONCLUSION : TNE is an in vivo functional measure of LHR and is a more sensitive predictor of LHR at 1 year after BMT than either CD34+ cell dose or CFU–GM infused.
TRALI due to granulocyte‐agglutinating human neutrophil antigen‐3a (5b) alloantibodies in donor plasma: a report of 2 fatalities
Authors: Davoren A. , Curtis B.R. , Shulman I.A. , Mohrbacher A.F. , Bux J. , Kwiatkowska B.J. , McFarland J.G. , Aster R.H.
Published: May 2003

BACKGROUND : TRALI is usually an immunologic reaction to WBC antibodies in infused plasma and ranks second only to ABO mismatch as a cause of transfusion‐associated death. Implicated donors are usually multiparous women (≥3 pregnancies).

STUDY DESIGN AND METHODS : Two fatal cases of TRALI were evaluated by reviewing clinical and laboratory findings and characterizing alloantibodies present in donor plasma. Investigation for WBC antibodies was by lymphocytotoxicity (LCT), FlowPRA (FlowPRA, One Lambda, Inc.) and granulocyte immunofluorescence and agglutination assays. Patient 1 was a 62‐year‐old man with chronic T‐cell lymphocytic leukemia, and Patient 2 was a 54‐year‐old woman undergoing a cadaveric kidney transplant. Both patients developed acute respiratory distress and hypotension during (Patient 1) and approximately 30 minutes after (Patient 2) transfusion. Fulminant pulmonary edema ensued in both cases necessitating mechanical ventilation and both patients died within 24 hours of the onset of respiratory complications.

RESULTS : The donors of the implicated blood components were women with a history of two pregnancies but no blood transfusions. Weak apparently panreactive granulocyte antibodies were detected with flow cytometry. However, in the granulocyte agglutination test, strong antibodies specific for human neutrophil antigen (HNA)‐3a (5b) were identified in both donors.

CONCLUSION : It is concluded that female blood donors with only two previous pregnancies can form clinically important granulocyte‐reactive alloantibodies leading to fatal TRALI reactions in recipients. The sometimes devastating consequences of TRALI should prompt the development of strategies to prevent or reduce its incidence. Further research is warranted to investigate recipient and donor factors responsible for TRALI, including whether 5b (HNA‐3a) alloantibodies are especially prone to cause severe reactions, and to better characterize the HNA‐3a (5b) antigen, particularly at the molecular level.
Attitudes of Swiss mothers toward unrelated umbilical cord blood banking 6 months after donation
Authors: Danzer Enrico , Holzgreve Wolfgang , Troeger Carolyn , Kostka Ulrike , Steimann Sabine , Bitzer Johanes , Gratwohl Alois , Tichelli André , Seelmann Kurt , Surbek Daniel V.
Published: May 2003

BACKGROUND :During the past decade, the use of umbilical cord blood (CB) as a source of transplantable hematopoietic stem cells has been increasing. Little is known about the psychosocial consequences that later affect parents after unrelated CB donation. The objective of this study was to evaluate the attitudes of mothers toward unrelated donation of umbilical CB for transplantation 6 months after giving birth.

STUDY DESIGN AND METHODS : A prospective study was performed with a standardized, anonymous questionnaire distributed to 131 women 6 months after CB donation. The questionnaire included topics concerning views about the ethical accuracy of having donated CB, emotional responses after donation, concerns about genetic testing and research with CB samples, attitude toward anonymity between her child and possible unrelated CB recipient, and willingness to repeatedly donate umbilical CB in a next pregnancy.

RESULTS : The vast majority (96.1%) stated that they would donate umbilical CB again, and all respondents were certain that their decision to have donated umbilical CB was ethical. With regard to the potential risks of genetic testing and “experimentation” of umbilical CB, a significant correlation (p = 0.01) was found between negative attitudes and the decision not to donate umbilical CB again. Additionally, it was observed that women who had a negative experience concerning the donation of CB would not donate again (p = 0.004).

CONCLUSIONS : This study shows a high degree of satisfaction of unrelated umbilical CB donation for banking in women 6 months after delivery. Despite a well‐performed and detailed informed consent procedure, one of the ongoing issues for the donators in CB banking involves the concern regarding of improper use of the cells, such as genetic testing or experimentation. Accurate and detailed counseling of pregnant women and their partners therefore maximizes the likelihood that they will donate CB for unrelated banking. These data provide a basis for the improvement of donor selection procedures and public education regarding the use of CB for banking and transplantation.
An evaluation of predictive factors for CD34+ cell harvest yields from patients mobilized with chemotherapy and growth factors
Authors: Ford C.D. , Chan K.J. , Reilly W.F. , Petersen F.B.
Published: May 2003

BACKGROUND : Accurately predicting the outcomes of peripheral blood stem cell harvests is important because unproductive collections are expensive and subject the donor to unnecessary toxicity.

STUDY DESIGN AND METHODS : Predictive factors for stem cell mobilization and collection by a retrospective review of 104 consecutive donors were evaluated.

RESULTS
: Of several previously suggested measures, the peripheral CD34+ cell concentration on the day of harvest (pCD34
DH
) correlated best with total numbers of CD34+ collected (r = 0.88). This was followed by the pCD34 on the day before harvest (pCD34
Day –1
) (r = 0.74). The peripheral WBC count on the day of harvest (pWBC) was inferior (r = 0.39). When ratios of potential predictive factors divided by the previous day's value were examined, pWBC ratio was found to be a significant independent predictive factor for cells collected (r = 0.45). Furthermore, the predictive value of both the pCD34
Day –1 and the pWBC can be improved by combining with the pWBC ratio. To examine whether the chosen collection starting days were optimal, serial pCD34 obtained daily during the harvest procedures was examined. Poorly mobilizing donors, who required several days of collection, did not reach maximal harvest yields until the fourth collection day.

CONCLUSIONS
: pCD34
DH
is the optimal predictive factor for harvest yields. If pCD34
DH
is not available, pCD34
Day –1 or pWBC combined with the pWBC ratio may offer the best prediction of harvest outcomes. The best harvest yields on poorly mobilizing donors occur 3 to 4 days after the usual collection starting times.
Changes in functional activities of plasma fibrinogen after treatment with methylene blue and red light
Authors: Suontaka Anna‐Maija , Blombäck Margareta , Chapman John
Published: May 2003

BACKGROUND : Methylene blue (MB) plus light treatment used for virus inactivation of human plasma units may lead to changes in the functional activities of fibrinogen.

STUDY DESIGN AND METHODS
: Single‐donor units of fresh plasma were treated with 1.0 μ
M
MB and a red light dose of 48 J per cm
2 . The effects of MB plus red light treatment on fibrinogen clottability, fibrin polymerization and gelation, clot stabilization, and fibrinolysis were studied.

RESULTS
: The concentration of clottable fibrinogen was unchanged during MB plus red light treatment, but a light‐dose‐dependent decrease of the concentration of functional fibrinogen was found. The initial release rate of fibrinopeptide A was slightly increased after MB plus red light treatment. Turbidity measurements of fibrin gel showed prolonged clotting time, lower fibrin fiber mass‐to‐length ratio, and slightly smaller fiber diameter. At a given clotting time, a gel with lower fibrin fiber mass‐to‐length ratio was produced. Clot stability and fibrinolysis remained normal.
l ‐Histidine added to plasma before MB plus red light treatment normalized the thrombin‐induced coagulation time in a dose‐dependent way.

CONCLUSION : MB plus red light treatment affected the polymerization and gelation phase of fibrin. A tighter fibrin gel structure was formed. No effect on stabilization of fibrin clot or fibrinolysis was found.
Low frequency of observed anti‐HLA among transfused preterm infants
Authors: Ishibashi Naohisa , Ohto Hitoshi , Ujiie Niro , Ariga Hiromichi , Ishii Tsutomu , Suzuki Hitoshi
Published: May 2003

BACKGROUND : Although low‐birth‐weight infants (LBWI) often receive multiple transfusions, there is controversial information on their development of antibodies against WBCs or platelets.

STUDY DESIGN AND METHODS : A total of 52 LBWI with birth weights less than 1500 g were randomly assigned to receive either RBCs that had been WBC‐ reduced (n = 25) or nonfiltered blood (n = 27). Serum samples collected from 37 infants at 3 months of age and from 30 children when they were 5 to 11 years old were tested. Anti‐HLA was assayed with an anti‐human globulin‐augmented lymphocytotoxicity test against a panel consisting of 13 lymphocytes and against parental cells.

RESULTS : None of 52 transfused LBWI of either group developed anti‐HLA (95% CI, 0%‐6.8% for overall, 0%‐13.7% for the WBC‐reduced group, and 0%‐12.7% for the nonfiltered group).

CONCLUSION : Multiply transfused LBWI rarely produced antibodies to HLA of blood donors and to noninherited maternal antigens. The benefits of WBC reduction to prevent HLA alloimmunization during infancy were not supported by this study and need further investigation.
A lack of serologic evidence of transmission of Chlamydia pneumoniae by transfusion of buffy coat‐depleted RBCs
Authors: Hedin Göran , Eriksson Iréne , Kumlin Urban , Boman Jens
Published: May 2003

BACKGROUND
: Recent studies have shown that a high percentage of blood donors harbor
Chlamydia pneumoniae
DNA and antigens within their PBMNCs. The aim of the present study was to investigate whether recipients of RBC transfusions who were seronegative for
C. pneumoniae before transfusion showed any evidence of seroconversion after transfusion.

STUDY DESIGN AND METHODS
: Patients who were possible recipients of RBC transfusion and negative in a screen test for IgG antibodies against
C. pneumoniae at the time of blood group determination were candidates to be included in the study. The patients were contacted 3.0 to 3.5 months after the blood group determination, and those who accepted to participate agreed that another venous blood sample could be taken.

RESULTS
: Among the patients who participated, 53 had become recipients of RBC transfusion (transfused group), and 51 later did not receive any RBC transfusion (control group). No significant change was found in IgG titer against
C. pneumoniae between the first and the second sample from the same patient, in either the transfused group or the control group.

CONCLUSION
: In our study, which was limited to 53 seronegative recipients of RBC units from seropositive donors, we found no serologic evidence that
C. pneumoniae could be transmitted by RBC transfusion.
The effect of exposing murine splenocytes to UVB light, psoralen plus UVA light, or γ‐irradiation on in vitro and in vivo immune responses
Authors: Fast Loren D.
Published: May 2003

BACKGROUND : WBCs in blood components are a major factor contributing to immune responses such as GVHD and alloimmunization that follow transfusion. Irradiation of blood components has been used to regulate the contribution of donor WBCs to these immune responses. A systematic comparison of how the exposure of lymphoid cells to γ‐irradiation, UVB light, or psoralen + UVA light (PUVA) effects immune response was conducted to better define the best type of irradiation to be used in different clinical settings.

STUDY DESIGN AND METHODS : Murine spleen cells were irradiated with varying doses and tested for their in vitro ability to be activated, to proliferate in response to mitogen or allogeneic stimulator cells, or to serve as stimulator cells. Irradiated donor cells were also tested for in vivo generation of GVHD, induction of alloantibody production, induction of restricted cytolytic T lymphocytes, and persistence of irradiated cells.

RESULTS : In general, increasing amounts of irradiation resulted in increased inhibition of in vitro and in vivo responses, although the doses required for inhibition differed from assay to assay. In contrast, irradiation of donor cells did not always result in inhibition of recipient alloantibody responses but was dependent on the donor‐recipient combination that was studied.

CONCLUSION : Control of the in vivo outcomes of transfusing allogeneic cells is regulated by the type and dose of irradiation used and by the genotype of the donor and/or recipient.
Transcription starting from an alternative promoter leads to the expression of the human ABO histo‐blood group antigen
Authors: Hata Yukiko , Kominato Yoshihiko , Takizawa Hisao , Tabata Sachiyo , Michino Junko , Nishino Kazuma , Yasumura Satoshi , Yamamoto Fumiichiro
Published: May 2003

BACKGROUND
: Using the 5′‐rapid amplification of cDNA ends technique with the ex vivo culture of AC133
–CD34+ cells, a transcription start site was recently identified approximately 0.7 kb upstream from the transcription start sites previously determined. The transcripts from the alternative starting exon 1a were demonstrated in the cells of both erythroid and epithelial lineages. Because the nucleotide sequence of exon 1a does not contain an ATG codon, we examined whether transcription starting from exon 1a leads to production of a functional glycosyltransferase.

STUDY DESIGN AND METHODS : Stable transfection experiments into the human gastric cancer MKN28 cells were performed using the various A transferase expression plasmids.

RESULTS : Large amounts of A antigens were demonstrated on the cells transfected with the A transferase expression plasmid containing the entire cDNA from exon 1a or the 5′‐truncated cDNA leading to the production of the N‐truncated protein with deletion of the cytoplasmic tail and a portion of the transmembrane domain. However, negligible amounts of A antigens were observed on the cells transfected with the A transferase expression plasmids containing the 5′‐truncated cDNA leading to the production of the N‐truncated proteins without the cytoplasmic tail and the transmembrane domain.

CONCLUSION : This study suggests that a functional A transferase could be produced by the transcription from exon 1a.
Short‐term liquid storage of umbilical cord blood
Authors: Hubel Allison , Carlquist Dale , Clay Mary , McCullough Jeffrey
Published: May 2003

BACKGROUND : Processing and banking of umbilical cord blood requires the development of methods for short‐term liquid storage. This study examines the conditions (temperature, time, and storage solution) for optimal storage of cord blood.

STUDY DESIGN AND METHODS : Cord blood obtained from normal donors was collected and divided into aliquots. Some of the aliquots were supplemented with a storage solution and undiluted cord blood was used as a control. MNC counts, percentage of cells that are CD34+45+, frequency of CFU‐GM, and solution pH were monitored for up to 72 hours in storage at 4°C and room temperature.

RESULTS : MNC counts, CD34+45+ cell recovery, and frequency of CFU‐GM were all improved in samples diluted with a storage medium when compared to undiluted controls. MNC counts were higher when cells were stored at 4°C. MNC counts and the frequency of CFU‐GM were reduced at 72 hours when compared with 24 hours.

CONCLUSIONS : These results indicate that the recovery of cells from cord blood can be improved if samples are stored using a storage solution for 24 hours without significant cell losses. Some of the solutions determined to be effective in maintaining viability are approved for human applications, although not specifically cord blood preservation.
G‐CSF‐induced spleen size changes in peripheral blood progenitor cell donors
Authors: Stroncek David , Shawker Thomas , Follmann Dean , Leitman Susan F.
Published: May 2003

BACKGROUND : PBPC donors given G‐CSF experience splenic enlargement and, rarely, spontaneous rupture of the spleen. This study evaluated the incidence and time course of splenic enlargement in PBPC concentrate donors and assessed factors affecting size changes.

STUDY DESIGN AND METHODS : Twenty healthy adults were given G‐CSF (10 μg/kg/day) for 5 days and a PBPC concentrate was collected by apheresis. Ultrasound was used to assess craniocaudal spleen length before giving G‐CSF, on the day of apheresis and 3 or 4 days after apheresis. The effects of donor age, gender, race, and changes in blood chemistries, blood counts, and CD34+ cell counts on spleen length change were assessed.

RESULTS : Spleen length increased in 19 of 20 donors. Mean length changed from 10.9 ± 2.0 cm before G‐CSF to 12.3 ± 2.1 cm on the day of apheresis (p < 0.001). The mean increase in length was 1.5 ± 0.9 cm or 13.8 ± 9.1 percent. Spleen length increased 20 percent or more in six subjects. The spleen length fell to 11.3 ± 1.8 cm (p < 0.001) 3 or 4 days after apheresis, but it remained greater than baseline levels (p = 0.03). Spleen length change was not affected by donor gender, race, or age. There was no relationship between changes in spleen length and 1) baseline and apheresis‐day blood counts and chemistries, or 2) changes in blood counts and chemistries.

CONCLUSIONS : Spleen size increases in almost all PBPC donors. Enlargement is transient but may be marked in some donors and may place them at risk for splenic rupture.
Plasma and lipids from stored platelets cause acute lung injury in an animal model
Authors: Silliman Christopher C. , Bjornsen A. Jason , Wyman Travis H. , Kelher Marguerite , Allard Jenny , Bieber Sarah , Voelkel Norbert F.
Published: May 2003

BACKGROUND : Transfusion of PLT concentrates may cause TRALI, a life‐threatening reaction that has been linked to the infusion of anti‐WBC immunoglobulins or older, stored PLTs that contain bioactive lipids. We hypothesize that lipids generated during storage of PLTs cause TRALI in a two‐event animal model.

STUDY DESIGN AND METHODS
: Plasma from both whole‐blood PLTs (WB‐PLTs) and apheresis PLTs (A‐PLTs) was isolated on Day 0 (D.0) and Day 5 (D.5) of storage and heat‐treated before use. Rats were pretreated with saline or 2 mg per kg endotoxin (LPS), anesthetized, and the lungs were ventilated, isolated, and perfused with saline or 5‐percent PLT plasma. Pulmonary artery pressure, pulmonary edema, and leukotriene B
4 levels (perfusate) were measured.

RESULTS
: Plasma from D.5, but not D.0, of the identical WB‐PLT and A‐PLT units caused injury in lungs from LPS‐pretreated rats (LPS/D.5) evidenced by increases in pulmonary edema and leukotriene B
4 (p < 0.05). Lipid extracts and purified lipids from D.5 PLT plasma also elicited injury in lungs from LPS‐pretreated rats (p < 0.05). Saline/D.5 plasma or lipids or LPS/D.0 did not cause pulmonary edema. Prestorage WBC reduction was ineffective in inhibiting TRALI.

CONCLUSION : PLT‐induced TRALI may be the result of two events: 1) the clinical condition of the patient and 2) the infusion of lipids in stored PLTs.
Analysis of voluntary blood donors with biologic false reactivity on chemiluminescent immunoassays and implications for donor management
Authors: Kiely Philip , Stewart Yvonne , Castro Lea
Published: May 2003

BACKGROUND : Biologic false‐reactive (BFR) results in blood donors are problematic due to both component loss and donor‐management issues. This report analyzes the results of a longitudinal study of BFR donors and the implications for donor management.

STUDY DESIGN AND METHODS : Donors who gave BFR results on HBsAg, HIV‐1/HIV‐2, HCV, or HTLV‐I/HTLV/II chemiluminescent immunoassays (ChLIAs) (PRISM, Abbott) between May 1997 to March 1999 were analyzed. Donors were followed up for up to three donations after an index BFR episode. In addition, results of any negative donations before the index BFR result but within the study period were included in the analysis.

RESULTS : For donors who gave an index BFR result on the HBsAg ChLIA, 14.3 percent remained BFR at subsequent donations, whereas for the anti‐HIV‐1/HIV‐2, anti‐HCV, and anti‐HTLV‐I/HTLV‐II ChLIAs, the figures were 66.0, 77.4, and 71.6 percent, respectively. For donors who gave a second BFR result, the percentage who remained BFR at subsequent donations was 75.0, 80.6, 84.6, and 74.5 percent for the four assays, respectively. The rate at which negative repeat donors became BFR during the study period was 0.02, 0.07, 0.12, and 0.02 percent for the HBsAg, anti‐HIV‐1/HIV‐2, anti‐HCV, and anti‐HTLV‐I/HTLV‐II assays, respectively.

CONCLUSIONS : Our results indicate that donors who give an index BFR result on the ChLIAs (PRISM, Abbott) should be allowed to continue donating because most donors with a HBsAg BFR result were negative at subsequent donations, and between 22.6 and 34.0 percent of those with BFR results on the HIV‐1/HIV‐2, HCV, or HTLV‐I/HTLV‐II assays gave subsequent negative donations. However, donors who give a second BFR result should be counseled and deferred because they were very unlikely to give subsequent negative results.
Developing a tracking system for coagulation factor concentrates in southern Ontario
Authors: Walker Irwin R. , Sek Julia T. , Almonte Theresa M. , Carruthers Julie B. , Chan Anthony K.C. , Pai Mohan K. , Thibault Alain A. , Heddle Nancy M.
Published: May 2003

BACKGROUND : In response to the transfusion‐ transmitted AIDS epidemic, Canadian authorities rec‐ ommended the development of tracking systems and improved reporting of adverse events. This study describes the development of a verifiable and comprehensive regional tracking system for coagulation factor concentrates.

STUDY DESIGN AND METHODS : The Hamilton‐ Niagara Regional Hemophilia Program received distribution and utilization data from Canadian Blood Services, 26 regional hospitals, and 70 individuals with bleeding disorders on home‐based therapy. Purpose‐specific software, the Canadian Hemophilia Assessment and Resource Management System (CHARMS), was used to store, monitor, analyze, and validate data.

RESULTS : During a 1‐year period (2001), all factor concentrates distributed in this region were accounted for. A higher proportion of FVIII and FIX concentrates (88 vs. 12%) was infused at home than in hospitals, and a higher proportion (63 vs. 28%) was used to prevent than to treat bleeds. During a period of shortage, a 5‐percent reduction in utilization of both FVIII and FIX concentrates was documented. One recall was managed swiftly and efficiently. Two patients reported allergic skin reactions.

CONCLUSION : A verifiable tracking system has been developed that can provide ongoing data for both clinical and administrative purposes. Data collection from patients needs to be made more efficient and real‐time recording is an important future objective. Such a system can be instituted locally for less than 1.5 percent of the cost of the factor concentrate used.
Increasing blood availability by changing donation patterns
Authors: Schreiber George B. , Sanchez Ana M. , Glynn Simone A. , Wright David J. ,   Retrovirus Epidemiology Donor Study
Published: May 2003

BACKGROUND : There is a declining margin between US blood collections and transfusions. Donation patterns were examined to characterize returning first‐time donors and predict the impact on blood availability of decreasing the number of nonreturning donors.

STUDY DESIGN AND METHODS : First‐time donors giving between 1991 and 1994 were followed for 3 to 6 years. The impact of decreasing the number of nonreturning donors in a 12‐month period was projected using the Poisson distribution to model the donation patterns of 539,063 donors who gave in 1995. Repeat donors were classified as “returning first‐time” (gave a first‐time donation within 12 months of their index donation), “established” (gave a repeat donation), and “inactive” (didn't donate in the 12 months before their index donation).

RESULTS : A total of 49 percent of first‐time donors did not return within 6 years. Returning first‐time donors tended to be US born, white, and had more than a high school education. In 1995, 30 percent of donors were first time, 31 percent were established, 7 percent were returning first time, and 32 percent were inactive, giving 1.5, 2.4, 1.9, and 1.7 donations in 12 months, respectively. Reducing nonreturning donors by 5 percent could increase blood collections by 2.7 percent. Similarly, 15 or 25 percent reductions in nonreturns could increase collections by 8.6 or 16.0 percent, respectively.

CONCLUSIONS : Most donors are not giving near the donation limit. A substantial increase in donations could be achieved by a relatively small decrease in donor nonreturn. Research is needed to understand why approximately half of first‐time donors donate only once.
DDAVP normalized the bleeding time in patients with congenital platelet TxA2 receptor abnormality
Authors: Fuse Ichiro , Higuchi Wataru , Mito Masao , Aizawa Yoshifusa
Published: May 2003

BACKGROUND
: An Arg
60
‐to‐Leu mutation was found in the first cytoplasmic loop of the PLT TxA
2
receptor as a new congenital PLT disorder characterized by impaired responsiveness to TxA
2 . However, it has not been clarified whether DDAVP is effective in correcting the bleeding time (BT) in this PLT disorder.

STUDY DESIGN AND METHODS
: DDAVP (0.4 μg/kg) was intravenously administered over 20 minutes in five patients with this PLT disorder, and template BT, PLT retention to glass beads, PLT aggregation, and a coagulation study were performed before and after the infusion of DDAVP. PLT TxA
2 synthesis defects (cyclo‐oxygenase deficiency, volunteers taking aspirin), thrombasthenia, and Bernard–Soulier syndrome were also included in this study.

RESULTS
: The normalization of BT was found in all patients with this PLT disorder, and one of the patients successfully underwent oral surgical procedures with DDAVP as the only hemostatic agent. DDAVP was also efficacious in the TxA
2 synthesis defect but not in other disorders. FVIII coagulation activity, vWF antigen, and ristocetin cofactor significantly increased in all patients after DDAVP, but no changes were seen in the PLT retention rate and PLT aggregation study after DDAVP infusion.

CONCLUSION
: DDAVP was effective in correcting BT in patients with impaired responsiveness to TxA
2
as well as impaired production of TxA
2.
Monitoring the Efficacy of Iodine‐131‐MIBG Therapy using Fluorine‐18‐FDG‐PET
Authors: Menzel C. , Graichen S. , Berner U. , Risse J. H. , Diehl M. , Döbert N. , Hamscho N. , Grünwald F.
Published: May 2003

Summary: Background: The purpose of this study was to assess the potential of fluorine‐18 fluoro‐2‐deoxy‐d‐glucose positron emission tomography (18F‐FDG‐PET) for monitoring the efficacy of iodine‐131 metaiodobenzylguanidine (131I‐MIBG) therapy in neuroendocrine tumours.

Methods: A total of seven 131I‐MIBG therapies with 3.7 to 10.2 GBq were carried out in three patients suffering respectively from a phaeochromocytoma, a paraganglioma and a metastatic neuroendocrine tumour of an unknown primary. The post‐therapeutic whole‐body scintigrams were compared with the results of six 18F‐FDG‐PET studies performed at the time of the therapies. One patient received three PET scans prior to each one of the MIBG therapies, and one patient was studied twice.

Results: 18F‐FDG uptake in tumour sites seemed to correlate well with tumour differentiation, showing no uptake in one patient with a highly differentiated neuroendocrine tumour, and moderate‐to‐intense uptake in the two other patients with metastatic disease. Those tumour sites that had a simultaneous positive uptake in both the MIBG scintigram and the PET scan showed response to therapy as a continuous reduction in MIBG uptake over time. They also showed a qualitative decrease in FDG accumulation during the follow‐up. This was associated with a decrease in the mean and maximum standard uptake values of more than 50 % in some metastases, while the X‐ray computed tomography showed no decrease in tumour volume. Two patients revealed additional metastases that were unknown on the basis of prior diagnostic or therapeutic PET scans and radiological follow‐up.

Conclusions: It may be concluded from these cases that 18F‐FDG‐PET is a valuable tool for an initial metabolic staging of neuroendocrine tumours prior to 131I‐MIBG therapy, as it can reveal tumour sites beyond the reach of radioisotope therapy. It may also be of importance in assessing therapeutic potential in those tumour sites that do show positive MIBG uptake.
Accuracy of Whole‐Body18F‐FDP‐PET for Restaging Malignant Lymphoma
Authors: Mikosch P. , Gallowitsch H. J. , Zinke‐Cerwenka W. , Heinisch M. , Pipam W. , Eibl M. , Kresnik E. , Unterweger O. , Linkesch W. , Lind P.
Published: May 2003

Summary:Background:The aim of this retrospective study was to evaluate the accuracy of fluorine‐18 fluorodeoxyglucose positron emission tomography (18F‐FDG‐PET) images, which were interpreted under daily routine conditions, in patients with Hodgkin's disease (HD) or non‐Hodgkin lymphoma (NHL) for restaging after chemotherapy and/or radiotherapy. For this purpose,18F‐FDG‐PET results were compared with morphological imaging methods and the patients’ clinical background.

Methods:121 PET images of 93 lymphoma patients (44 HD, 49 NHL) were investigated after chemotherapy/radiotherapy. For PET imaging, 160–200 MBq18F‐FDG was administered intravenously, followed by an infusion of 20 mg Furosemid in 250 mL saline. Whole‐body18F‐FDG‐PET images were obtained using a partial‐ring PET scanner without attenuation correction. The morphological imaging consisted in computed tomography and ultrasound (CT/US) in all patients, additional MRI in some patients, and iliac crest biopsy in cases of suspicious bone marrow involvement. The standard of reference was composed of biopsy data, clinical status at the time of investigation, and follow‐up of at least 12 months. The PET images were evaluated for their sensitivity, specificity and accuracy based on written reports, which were compiled from other imaging data and the clinical history of the patients.

Results:Sensitivity, specificity, and accuracy of18F‐FDG‐PET was 91 %, 81 %, and 85 %; of CT/US, 88 %, 35 %, 56 %, respectively. Major sources of error in18F‐FDG‐PET were due to asymmetric muscular hypermetabolism and inflammatory lesions misinterpreted as persistent viable lymphoma tissue. Furthermore, secondary malignancies other than lymphomas were another reason for misinterpretations of18F‐FDG‐PET studies.

Conclusions:18F‐FDG‐PET showed a comparable sensitivity but a higher specificity and accuracy compared with CT/US. To achieve a high accuracy in18F‐FDG‐PET, the nuclear medicine specialist needs imaging and clinical data as background information, which can only be acquired through close co‐operation with the referring clinicians. Pharmacological muscular relaxation in the course of18F‐FDG‐PET imaging may be advisable, as nonspecific muscular hypermetabolism was one of the problems at the image readings and a source of incorrect18F‐FDG‐PET interpretations.
Marathonlaufen läßt intrazelluläre Proteine aus Muskelzellen selektiv in das Plasma austreten
Authors: Ziegler Sophie , Niessner A. , Slany J. , Müller M. M. , Heinschink Angelika , Billensteiner Elke , Woloszczuk W. , Geyer G.
Published: May 2003

Zusammenfassung: Bei 19 Marathonläufern (2F, 17M) wurde vor und unmittelbar nach dem Lauf die Plasmakonzentration der Parameter Gesamt‐CK‐Aktivität, CK‐MB‐Masse, Myoglobin und Troponin I bestimmt. Unter dem Einfluß der Laufbelastung sind bei allen Probanden Gesamt‐CK und Myoglobin im Plasma signifikant angestiegen, wobei keine Korrelation mit dem Alter der Läufer und deren Laufzeit feststellbar war. Bei einigen der Läufer ist auch CK‐MB auf Werte angestiegen, die sonst für das Bestehen myokardialer Nekrosen sprechen. Es gibt jedoch keinen überzeugenden Hinweis dafür, daß diese Befunde wirklich durch Nekrosen im Myokard verursacht werden. Sie könnten auch Folgen einer zellulären Permeabilitätsstörung durch die Laufbelastung sein, die bei gesunden Läufern durch die Belastung der Muskulatur, etwa so wie das ,,stunning‘‘ des Myokards, lokal auftreten und – so eindrucksvoll die Befunde auch sein mögen – keine gesundheitlich nachteiligen Folgen zeitigen. Ihre Bedeutung für einen Trainingseffekt der Muskulatur erscheint gegenwärtig nicht beurteilbar.