bluuebunny/crossref_metadata_2025 huggingface dataset:
Techniques, indications, and toxicity of therapeutic hemapheresis in children
Authors: Kasprisin Duke O.
Published: February 2007

Although therapeutic hemapheresis has grown dramatically in the past decade, its utilization and popularity in pediatrics remain limited. The lack of well‐defined indications for treatment and technical difficulties in the management of hemapheresis for small patients have prevented its widespread use. However, there have been more than 130 reports describing the use of hemapheresis in children less than 15 years of age, including more than 20 reports describing it in children less than 5 years. Only one controlled trial of hemapheresis in children has been published. It studied the use of plasma exchange for the treatment of diabetes mellitus.

In general, practitioners depend upon the accepted indications in adults to justify usage of this therapy in children. Unfortunately, major differences exist in the adult and pediatric presentation of certain diseases and there has not been universal acceptance of the indications for this therapy in children.

Numerous technical difficulties continue to plague the development of hemapheresis therapy in pediatrics and therefore continue to limit the number of studies undertaken. The major technical difficulties include vascular access and excessive extracorporeal volume. These problems are not insurmountable since several patients less than 1 year of age have been successfully treated by hemapheresis. The various techniques used in these cases will be discussed.

Additional problems unique to the pediatric population are the difficulty in getting approval for research studies that involve minors, the complexity of informed consent, the problem of patient cooperation and compliance, and the difficulty of explaining a complicated procedure to children of varying developmental levels. Although there are a few detailed studies, complications in the treatment of pediatric cases are usually a combination of technical problems and untoward reactions, and it is difficult to compare these studies with those published involving adult patients.
Thermofiltration in hypercholesterolemia treatment: Analysis of removal and posttreatment cholesterol recovery
Authors: Malchesky P. S. , Werynski A. , Nomura H. , Takeyama Y. , Yamashita M. , Nosè Y.
Published: February 2007

Thermofiltration, a system of membrane plasmapheresis for LDL apheresis, is used to treat patients with refractory hyperlipidemia. In this system, the separated plasma is warmed to or above physiologic temperature, filtered with a membrane filter, and returned to the patient on‐line. Plasma infusion products are not required.

In this study one calculated plasma volume was treated weekly, biweekly, or monthly in patients classified as type II hypercholesterolemic. Reduction and sieving of lipoproteins were evaluated. The reduction ratios of high‐density lipoprotein cholesterol (HDLc) and low‐density lipoprotein cholesterol (LDLc) were 0.30 ± 0.06 and 0.58 ± 0.05, respectively (mean ± S.D.). Sieving coefficients of the plasma filter for HDLc and LDLc were 0.62 ± 0.12 and 0.03 ± 0.02, respectively (mean ± S.D. of 31 treatments).

To evaluate the posttreatment recovery the apparent fractional catabolic rates (FCRa) for total cholesterol and LDLc were calculated. FCRa was 0.151 ± 0.06 and 0.148 ± 0.06 day−1 for total cholesterol and LDLc, respectively.

The ratio of the posttreatment concentration on the seventh day to the concentration immediately pretreatment was found to be significantly higher for HDLc than for LDLc, 0.92 ± 0.8 vs. 0.77 ± 0.1 (mean ± S.D.), due to faster HDLc recovery. The ratio of LDLc/HDLc was lowered for up to 2 weeks after the treatments.
Modified method of exchange transfusion in sickle cell disease
Authors: Talacki Carol A. , Ballas Samir K.
Published: February 2007

The treatment of various complications of sickle cell disease has included red cell exchange in the past, and the development of automated pheresis equipment has greatly simplified such exchanges. Traditionally, the patient's red cells have been exchanged while their plasma was returned to them. Recently, plasma factors have been thought to play a role in the pathogenesis of vasoocclusive events. Therefore, we performed whole blood exchange, which consisted of replacement of the patient's plasma with albumin and saline in addition to the usual replacement of erythrocytes. A total of 32 whole blood exchanges were performed on 12 patients with a variety of complications of their disease. The procedure was done using standard pheresis equipment and was relatively simple to perform. There were no serious complications and the clinical outcome was good with 10 out of 12 patients experiencing improvement.
Thrombotic complications of subclavian apheresis catheters in cancer patients: Prevention with heparin infusion
Authors: Haire William D. , Edney James A. , Landmark James D. , Kessinger Anne
Published: February 2007

Twenty‐two silicone rubber apheresis catheters were placed into the subclavian veins of 18 cancer patients to allow serial leukapheresis for collection of circulating hematopoietic stem cells. The tips of the catheters were placed in the innominate vein to avoid reinfusion of citrate into the right atrium and the resulting tendency to cardiac arrhythmias.

Sixteen catheters were placed without prophylactic anticoagulation. Anticoagulation was prematurely discontinued in one patient because of the inconvenience of the portable heparin infusion pump. Six of these 17 catheters developed venographically proven thrombotic complications and five others had presumed thrombosis‐related access failure or caused symptoms of venous obstruction, but confirmation of the presence of a thrombus with venography was not obtained. Three catheters spontaneously withdrew from the vein, one during urokinase infusion for thrombosis. Only three catheters had uncomplicated apheresis courses.

Prophylactic heparin infusions via portable infusion pumps were given after placement of six catheters. As long as the heparin infusions were continued all patients had uncomplicated apheresis courses. One patient's heparin was prematurely discontinued. Within 3 days of its discontinuance, radiographically proven thrombotic catheter occlusion occurred. Patients given heparin were less likely to develop complications (P lt; 0.001).

No unexpected complications of apheresis were encountered as a result of the use of these catheters.

Silicone rubber subclavian catheters can be used for peripheral stem cell collection but have a high frequency of thrombotic complications. Systemic anticoagulation with heparin can minimize the likelihood of these complications.
Computerization of plateletpheresis quality control records with a commercially available spreadsheet program
Authors: McLeod Bruce C. , Viernes Ann , Reed Susan , Sassetti Richard J.
Published: February 2007

Many apheresis units lack the resources to acquire customized computer software for record keeping. We have adapted a commercially available “spreadsheet” program (Lotus 1‐2‐3) to aid in quality control activities for plateletpheresis. Data are entered in a grid pattern wherein each donation occupies one row and successive columns contain numerical data derived from the donation. The last two columns contain formulas that calculate yield and collection efficiency from values entered in preceding columns. The program runs on an IBM PC or equivalent with 512 K RAM; the combined cost of a computer and software is currently under $2,000.00. Data entry requires fewer keystrokes per record than computation of yield and efficiency with a calculator, and creates an inclusive permanent record for future analysis. Data sorting and statistical functions allow rapid identification of incomplete records, and derivation of average platelet yield and/or collection efficiency for any time period of interest. The program also facilitates determining the proportion of donations that fall below any chosen cutoff. Performance characteristics of a particular instrument or operator can be assessed easily by isolating the pertinent records and analyzing them separately. The system will thus accomplish a variety of quality control activities, including those mandated by licensing agencies. It can be implemented by apheresis personnel with limited “computer literacy” and is superior to manual tabulation of quality control data in both ease of data entry and facility of analysis.
Collection and cryopreservation of human stem and progenitor cells for bone marrow transplantation
Authors: Jacobs Peter , Wood Lucille , Horak Sue
Published: February 2007

Bone marrow collection was undertaken from human organ donors (Group 1; n = 7) to develop a closed‐system single‐step technique for stem and progenitor cell enrichment, using the Cobe 2997 continuous‐flow blood‐cell separator. The effects of programmed freezing, storage in liquid nitrogen, and thawing were then defined using these grafts. Once standardised, this method was extended to autografting following cryopreservation of a comparable fraction (Group 2; n = 8) and then to allogeneic transplantation after ex vivo exposure to the lytic monoclonal antibody, Campath‐1 IgM and human complement, but without cryopreservation (Group 3; n = 9). The median number of mononuclear cells harvested was 5.0 × 106/mL (n = 24), and this was not significantly different in the three groups. The ex vivo graft, composing marrow rich anticoagulated whole blood, was recirculated in the separator at a flow rate of 60 mL/minute, with a centrifuge speed of 1,100 r.p.m., and the mononuclear cell fractions were collected at the rate of 1.5 mL/minute. The average procedure time from formation of the interface in the single disposable channel to achievement of the final volume was 90 minutes. The mean recovery of the mononuclear cells was 101.4% (SD 38.0) and the GM:CFUc was 91% (SD 43.86). These figures were not significantly influenced by subsequent cryopreservation (Group 1; n = 7 and Group 2; n = 8) or following exposure to the monoclonal antibody, Campath‐1 IgM (Group 3; n = 9). The Cobe Model 2997 continuous‐flow blood fraction separator is ideally suited for the ex vivo enrichment of human bone marrow stem and progenitor cells in a volume that makes handling practical by a technique that is rapid and readily applicable to both autografting and allogeneic transplantation programmes.
The fenwal CS3000 inline pack is acceptable for donor blood sampling
Authors: Dayton Paula J. , Randels M. Joleen , Strauss Ronald G.
Published: February 2007

A blood sampling pack is available on closed system apheresis kits for the Fenwal CS3000 blood cell separator to facilitate same day donor testing while maintaining the closed system. Conceivably, the accuracy of complete blood counts (CBC) performed using pack samples might be compromised by clotting in the pack, by adherence of blood cells to the inner surface of the pack, or by dilution of the sample with priming fluid—should it inadvertently contaminate the pack. We studied paired blood samples collected simultaneously via the pack and a separate venipuncture in 17 donors. When collected properly, CBC values from pack and vein were nearly identical. Even when purposely contaminated with saline, pack values were lowered only slightly. Thus, the inline pack permits accurate sampling of donor blood for CBC while maintaining a closed system.
Experimental models of plasma perfusion
Authors: Pusey Charles D. , Aslam Mohammed , Cohen Jon , Courtney James M. , Ryan Calvin J.
Published: February 2007

A system allowing repeated plasma perfusion in the unrestrained conscious rat was developed in order to examine the effects of plasma filtration with on‐line sorbent treatment of plasma in various models of disease. In experimental autoimmune glomerulonephritis, perfusion over a column coated with glomerular basement membrane (GBM) antigen lowered circulating levels of anti‐GBM antibodies. In experimental endotoxaemia, perfusion over a column coated with polymixin B (PB) lowered circulating endotoxin levels and protected animals from haematological abnormalities and death. In experimental acute hepatic failure, perfusion over a combination of charcoal, resin, and PB columns improved survival in grades II and III hepatic coma. This experimental system has allowed preclinical evaluation of the effectiveness of different sorbents in the treatment of a range of disorders.
Preparation and storage of “leukocyte‐depleted single donor” platelet concentrate: A step forward in effective haemotherapy
Authors: Elias Mona K. , de Wolf Joost Th. M. , Blom Nel , Rijskamp Luit , Halie Ruud M. , Sibinga Cees Th. Smit
Published: February 2007

“Leukocyte‐depleted” platelet concentrates (LD‐SDPC) were prepared by cotton‐wool and by polyester filtration of “leukocyte‐poor” PC collected by the elutriation technique. The storage characteristics of LD‐SDPC were comparable to those of the filtered pools of multiple donor platelet concentrates (LD‐MDPC). However, LD‐SDPC were less activated and less damaged than LD‐MDPC over a 7‐day storage period, as evidenced by β‐thromboglobin percent release and lactic dehydrogenase percent leakage in both products. LD‐SDPC were prophylactically transfused to 12 thrombocytopenic patients; the mean bleeding time was shortened from 12 min 20 sec to 4 min 39 sec. Corrected count increment (CCI) was 22.8 at 1 hr and 14.1 at 24 hr compared to 15.5 and 10.0, respectively, with standard PCs.
Use of continuous flow erythrocytapheresis in pregnant patients with sickle cell disease
Authors: Morrison John C. , Morrison Francis S. , Floyd Randall C. , Roberts William E. , Hess L. Wayne , Wiser Winfred L.
Published: February 2007

The role of partial prophylactic red cell exchange transfusion in the management of pregnant patients with major sickle hemoglobinopathies is unclear. Over a 10‐year period, 131 pregnant patients with major hemoglobinopathies (HbS 101, HbS‐C 30) were managed by the same group of physicians. Of these, 103 received partial prophylactic exchange transfusion early during prenatal care while 28 received blood only when serious complications developed (control group). Patients treated with exchange transfusion received continuous flow erythrocytapheresis on an outpatient basis. The results indicate that there were fewer crises (P = .0001), a reduction in other significant medical complications (P = .002), and a decrease in maternal hospital days (P = .05) in those receiving prophylactic transfusions compared to women in the control group. The number of preterm deliveries (P = .004), the prevalence of low birthweight infants (P = .01), and the perinatal death rate (P = .01) were significantly lower among those who were routinely transfused. Two patients developed hepatitis, five had transfusion reactions, and 11 were found to have alloantibodies among those receiving prophylactic transfusions versus one, two, and five patients, respectively, in the control group. The results indicate a benefit of this methodology in the treatment of pregnant sickle cell patients in our population. However, a national collaborative randomized study is needed to adequately address the controversy regarding the use of red cell exchange in the pregnant sickler.
Granulocyte collection
Authors: Strauss Ronald G. , Rohret Patricia A. , Randels M. Joleen , Winegarden Diane C.
Published: February 2007

Techniques for collecting granulocytes for transfusion either to neutropenic patients or to neonates are described. Currently, the best granulocyte concentrates are prepared using continuous‐flow centrifugation leukapheresis of steroid‐stimulated donors in the presence of pentastarch. Donor reactions are mild and are similar to those expected with automated plateletpheresis.
Donor reactions during DDAVP‐stimulated plasmapheresis
Authors: Randels M. Joleen , Strauss Ronald G. , Cordle Delores , Koerner Theodore A. W. , Floss Alice S.
Published: February 2007

Donor exposure can be strikingly reduced for patients with classical hemophilia A and von Willebrand's disease when large volumes of potent cryoprecipitated AHF are prepared from donors following DDAVP (1‐deamino‐8‐D‐arginine vasopressin) stimulation and automated plasmapheresis—a procedure called “plasma exchange donation.” Although this procedure has been reported to be relatively safe for donors, data are limited. Accordingly, we studied 20 donors during 48 procedures using DDAVP (0.3 μg/kg IV) followed by 2–3 L plasma collection. Replacement fluid for each initial plasma exchange donation was plasma protein fraction; autologous cryoprecipitate‐poor plasma was used for subsequent procedures. Mild reactions, particularly facial flushing, were noted in all 48 procedures. No procedure was discontinued, but four were modified due to either an increased pulse rate (≤20/min from baseline) or a fall in systolic or diastolic blood pressure (≤20 mm Hg from baseline). No donor was deferred or withdrew from the program. Based on our modest experience, DDAVP stimulated plasma exchange donation appears to be a safe and effective method for collecting large quantities of plasma from which potent cryoprecipitated AHF can be prepared. © 1992 Wiley‐Liss, Inc.
Selective removal of anti‐acetylcholine receptor antibody in the low temperature operation of membrane plasma fractionation
Authors: Sawada Koji , Malchesky Paul S. , Zborowski Maciej , Koo Anna P.
Published: February 2007

The removal of anti‐acetylcholine receptor antibody (anti‐AChR Ab) by the plasma fractionator, Kuraray EVAL 2A, was measured as a function of the filtration temperature (4 and 37°C). Plasmas procured from eight myasthenia gravis (MG) patients undergoing routine plasma exchanges (PE: membrane plasma filtration: n = 4, and centrifugation: n = 4) were used in the studies. Plasma flow rate was 20 ml/min, and plasma perfusion in single pass was terminated when the transmembrane pressure of the filter reached 300 mm Hg. Solute concentration data from before and after perfusion were used to assess the sieving coefficient (SC) of each solute. Results show that the SCs for anti‐AChR Ab and albumin were significantly (P < .0002) lower at 4°C (0.15 and 0.52, respectively) as compared to 37°C (0.44 and 0.72, respectively). The SC of anti‐AChR Ab (0.15) was significantly lower than the SC of IgG (0.42; P < .006) at 4°C, even though it also belongs to the IgG class. The ratio of the SC of anti‐AChR Ab to albumin at 4°C (0.29) was significantly lower than that at 37°C (0.57; P < .003). These data indicate that the selectivity of removal of anti‐AChR Ab from albumin is higher at 4°C than that at 37°C. The volume treated at 4°C was significantly lower than that treated at 37°C, and it was less than that required for a clinical treatment; however, it was shown that filter backwashing is possible without loss of solute removal selectivity. Membrane filtration at 4°C for the removal of anti‐AChR Abs in MG patients could provide an alternative to PE and reduce the demand on plasma replacement products. © 1992 Wiley‐Liss, Inc.
Hematopoietic stem cell processing and cryopreservation
Authors: Rowley Scott D.
Published: February 2007

Either bone marrow or peripheral blood may be harvested to provide hematopoietic stem cells (HSC) for autologous transplantation. Both, however, comprise heterogeneous cell populations. The HSC necessary for successful engraftment constitute a very small fraction of the cells harvested. After collection, the harvested cells usually undergo several processing steps to reduce the product volume, remove cells (such as mature blood cells or tumor cells), or to cryopreserve the cells for later reinfusion. Granulocytes and red blood cells, for example, survive cryopreservation poorly using freezing techniques designed for HSC. Therefore, bone marrows being cryopreserved must be depleted of mature blood cells to avoid toxicity from infusion of damaged mature blood cells. Mature blood cells may also impede the variety of tumor cell purging techniques currently being studied. These processings are designed to minimize the loss of HSC while achieving an appropriate HSC product for the individual patient. A number of apheresis devices and cell washers simplify the enrichment of HSC in the harvested cell products. In contrast, tumor cell purging techniques are not standardized between the various transplant centers. © 1992 Wiley‐Liss, Inc.
Successful management of paraprotein‐associated peripheral polyneuropathies by immunoadsorption of plasma with staphylococcal protein A
Authors: Weinstein Robert , Sato P. T. Sachiko , Shelton Kimaada , Hartigan Nancy , Ropper Allan H. , Hayes Michael , Cardillo Kathleen
Published: February 2007

Two patients with paraprotein‐associated peripheral polyneuropathy were treated successfully using immunoadsorption of patient's plasma with staphylococcal protein A. Both had previously been treated with immunosuppressive agents or plasma exchange, and were rapidly relapsing at the time of their protein A immunoadsorption therapy. One patient was treated “on‐line” with a blood cell separator, and one was treated “off‐line.” Both responded well to therapy with minimal toxicity. Serum levels of circulating immune complexes were elevated in one patient and remained so during and after therapy. Immunoadsorption with protein A should be investigated as a therapeutic option for patients with paraprotein‐associated peripheral polyneuropathy. The therapy is relatively easy to administer, particularly “off‐line,” and was well tolerated by our patients. More experience, including formal clinical trials, will be required to properly define the indications for, and mechanism of response to, this therapy. © 1993 Wiley‐Liss, Inc.
HIV infection at home and in the workplace
Authors: Evatt Bruce
Published: February 2007

Major questions have been raised concerning an individual's risk for contracting HIV infection when they come into contact with a patient who has AIDS in the home and/or workplace. Specific concerns are addressed and guidelines are reviewed. © 1993 Wiley‐Liss, Inc.
Immunomodulation during treatment of polymyositis with plasmapheresis and immunosuppressive drugs
Authors: Dau Peter C.
Published: February 2007

Immunologic studies were carried out in a patient with polymyositis (PM), who showed increasing muscle strength and decreasing serum creatine phosphokinase levels during 20 weeks of treatment with plasmapheresis in conjunction with prednisone and cyclophosphamide. After an initial rise, serum IgG declined with treatment. Natural killer (NK) lymphocytes were reduced by 74%, B cells by 95%, and T cells by 38%. Spontaneous proliferation of peripheral blood mononuclear cells increased dramatically. Within the CD4+ T cell subset there was increasing maturation as shown by a rise in percent mature (CD29+) cells and reciprocal decline of immature (CD45RA+) cells. At the same time CD4+ T cells became increasingly activated as shown by HLA‐DR expression.

The percentage of CD8+ T cells increased strongly with treatment, and they showed increased activation and expression of the cytotoxic CD29+ and CD11b‐ phenotypes. CD8+ T cells exhibiting CD45RA or CD11b+ suppressor phenotypes were overall unchanged; however, on follow‐up a proportion of CD8+ cells expressed the activated suppressor effector (CD11b—CD28—) phenotype. In addition to control of PM by the possible deletion of activated autoreactive B and T lymphocyte clones with cyclophosphamide, the activation and maturation of CD4+ T cells during treatment may have downregulated the autoreactive disease process, either through direct antiidiotypic suppression or by induction of the observed increase in cytotoxic and suppressor CD8+ T cells. © 1994 Wiley‐Liss, Inc.
Protein a immunoadsorption treatment in hematology: An overview
Authors: Howe Robert B. , Christie Douglas J.
Published: February 2007

Staphylococcal protein A efficiently binds immunoglobulins and circulating immune complexes (CIC) and provides an effective medium to remove immunoglobulins and CICs from plasma while sparing albumin and most coagulation proteins. Although it activates the complement system its clinical use abrogates the need for plasma expanders necessitated by plasma exchange. Despite anecdotal reports of utility in several hematologic syndromes, publications of clinical trials are available only for autoimmune thrombocytopenic purpura (AITP) and refractoriness to platelet transfusions (RFT) associated with alloimmunization. In the former situation Snyder et al. (Blood 79:2237–2245, 1992) reported on 72 patients with AITP all of whom had failed at least two previous therapies including splenectomy in 68%. Forty‐six percent achieved improved platelet counts following treatment. The response was durable (8–26 mo) in all but 10%. Spleen‐intact patients could not be differentiated from those who had been splenectomized. Both responders and nonresponders showed significant decreases in CIC and platelet‐directed immunoglobulin (PDIG), but responders achieved near‐normal levels. The beneficial response of these factors, particularly in spleen‐intact patients, warrants a prospective study. In our studies at the University of Minnesota twelve patients with thrombocytopenia secondary to bone marrow failure who were refractory to platelet transfusion were treated with protein A immunoadsorption. Ten had demonstrable antiplatelet Abs (Anti‐HLA, HPA, ABO). Seven of 12 demonstrated improved platelet counts and post‐transfusion corrected count increments after treatment. This was associated with decreased platelet utilization and clinical bleeding. A prospective controlled clinical trial is justified. © 1994 Wiley‐Liss, Inc.
Synchronization of plasma exchange and cyclophosphamide in severe and refractory autoimmune hemolytic anemia
Authors: Silva Victor A. , Seder Richard H. , Weintraub Lewis R.
Published: February 2007

Two cases of severe autoimmune hemolytic anemia (AIHA) that failed multiple treatment modalities obtained complete and long‐lasting remissions with a combination of three one volume plasma exchange (PE) on succeeding days followed 6 hours later on the 3rd day by cyclophosphamide (cyc) 750 mg/m2 IV, and cyc/prednisone (pred) qd tapering to either no therapy or minimal therapy over a 6 month period. Both cases remain without evidence of AIHA after 43 and 19 months follow‐up. Possible non‐exclusive mechanisms that explain this favorable outcome are enhanced cytotoxic effect of cyc on proliferating lymphocytes participating in the antibody rebound phenomena, suppression of B lymphocytes with daily cyc/pred, and/or formation of anti‐idiotype antibodies.

We present two cases of severe and refractory AIHA, one warm and the other cold, that obtained complete and long‐lasting responses to a synchronized therapy of three daily one volume PE followed 6 hours later by cyc 750 mg/m2 IV and low doses of daily cyc and pred. In both cases the auto‐antibodies virtually disappeared. In one case, red cell allo‐antibodies disappeared as well.
Effects on donors of repeated leukocyte losses during plateletpheresis
Authors: Strauss Ronald G.
Published: February 2007

All blood components collected by automated cytapheresis contain donor leukocytes. The possibility that repeated cytapheresis donation might lead to clinically important leukocyte losses and immunodeficiency has been a longstanding concern. Although convincing data do not exist to substantiate this concern, it is common practice to limit the number of annual cytapheresis donations per donor and to monitor donors for developing lymphocytopenia. Clinically significant immunodeficiency is unlikely to occur unless donors lose >1 × 1011 lymphocytes within a few weeks period of time or unless donor lymphocyte counts fall persistently to <0.5 × 109/L. Each plateletpheresis procedure, when performed using modern cell separators that are designed to produce a relatively “pure” platelet concentrate, leads to the loss of 1.0 × 106 to 5.0 × 107 leukocytes. Thus, automated plateletpheresis as performed in 1994 is extremely unlikely to cause clinically significant lymphocyte depletion and consequent immunodeficiency.
Effects on recipients of exposure to allogeneic donor leukocytes
Authors: Dzik Walter H.
Published: February 2007

Blood transfusion recipients are exposed to allogeneic donor leukocytes at the time of transfusion. Exposure to allogeneic donor leukocytes has been linked to a variety of complications of transfusion including primary HLA alloimmunization and platelet refractoriness, febrile nonhemolytic transfusion reactions, transmission of leukotropic viruses, transfusion‐associated graft versus host disease, and transfusion‐induced immune suppression. The development of high‐performance leukodepletion blood filters and of low‐leukocyte plateletapheresis machines has provided the technology to reduce recipient exposure to allogeneic donor leukocytes. This article provides a brief review of current information on the utility and shortcomings of these technologies for the prevention of leukocyte‐mediated transfusion complications.
Plasma exchange for preeclampsia: II. Unsuccessful antepartum utilization for severe preeclampsia with or without hellp syndrome
Authors: Martin James N. , Perry Kenneth G. , Roberts William E. , Norman Patricia F. , Files Joe C. , Blake Pamela G. , Morrison John C. , Wiser Winfred L.
Published: February 2007

OBJECTIVE: To explore the efficacy of plasmapheresis/plasma exchange as the primary therapy to arrest and reverse the progression of severe preeclampsia with or without HELLP syndrome in order to postpone delivery and improve perinatal outcome in very preterm pregnancies. STUDY DESIGN: In this case series of patients managed over a 4‐year period from 1984 to 1987, seven gravidas with severe preterm preeclampsia underwent 1‐2 plasmaphereses/plasma exchange procedures using the IBM 2997 Cell Separator with continuous electronic fetal heart rate monitoring (n = 7 patients) and central cardiovascular monitoring (n = 3 patients). RESULTS: The seven patients (one with HELLP syndrome, six without HELLP) presented between 24 and 30 weeks gestation and, despite plasmapheresis/plasma exchange, the severity of each study subject's preeclampsia persisted without clinically significant improvement. Maternal‐fetal deterioration required cesarean delivery in all cases within 48 (in four patients within <36) hours of therapy. No clinically significant adverse effect of plasma exchange therapy was recorded during cardiovascular and laboratory monitoring; two fetuses developed repetitive late decelerations during exchange despite adequate maternal fluid preload. The only patient with HELLP syndrome developed eclampsia as her third plasma exchange within 25 hours was being initiated. Significant problems with fluid retention and displacement (variable amounts of pulmonary edema, pleural effusions, large volume ascites) were encountered in all patients. Four neonates died (24‐27 weeks/438‐820 g) and three survived intact (740, 950, and 1,280 g). One mother (case 5) developed end‐stage renal disease 21 months postpartum. CONCLUSIONS: The application of plasmapheresis/plasma exchange therapy as described in order to prolong very preterm pregnancies in the undelivered patient with severe preeclampsia/eclampsia with or without HELLP syndrome did not produced encouraging results. Patients in general were exposed to additional medical and surgical risk without a corresponding improvement in perinatal outcome.
Treatment of severe cardiac allograft rejection with extracorporeal photochemotherapy
Authors: Wieland M. , Thiede V. L. , Strauss R. G. , Piette W. W. , Kapelanski D. P. , Landas S. K. , Hunsicker L. G. , Vance S. J. , Randels M. J.
Published: February 2007

Two patients were treated with photopheresis for marked cardiac allograft rejection with hemodynamic compromise that had become unresponsive to standard therapy. Multiple episodes of rejection had occurred, and initial response to standard therapy was favorable. However, progressive deterioration was documented by serial endomyocardial biopsies, fever, congestive heart failure, and abnormal cardiac catheterization findings. In the absence of retransplantation, death seemed imminent. Photopheresis was begun. Both patients received oral 8‐methoxypsoralen and ⩾5 × 109 mononuclear cells were collected, treated with ultraviolet light A for 1.5 hours, and were reinfused. One procedure was performed weekly X4 and then monthly X5. Responses were striking with rapid loss of fever, improvement in exercise tolerance, normalization of cardiac hemodynamics, and improvement in endomyocardial biopsies. Although our experience with these two patients is anecdotal, photopheresis merits further study as treatment for severe cardiac allograft rejection.
Pyrogen reactions to human serum albumin during plasma exchange
Authors: Pool Mark , McLeod Bruce C.
Published: February 2007

Reactions to human serum albumin (HSA) in therapeutic plasma exchange (TPE) are rare. Nevertheless, older literature describes possible adverse effects, including specific immune responses to albumin or other proteins, and reactions due to contaminating organisms or pyrogen. During an eight day period three patients in our unit had unusual reactions after infusion of 1.5–2 L of HSA. Patient 1 had trembling that persisted for 20 min. Patient 2 had shaking for 40 min despite calcium gluconate infusion, and fever to 100.8° F. Patient 3 had severe rigors that subsided after 90 min when meperidine was finally given, and fever to 103.5°F. Record reviews revealed that all three patients had received HSA from the same lot, and that only one other TPE patient had received HSA from that lot. Neither our pharmacy nor the manufacturer was aware of other reactions associated with that lot. Material from a bottle only partially infused to patient 3 was negative in culture and was negative for pyrogen when retested by the manufacturer. Nevertheless, because patients 1 and 2 had each had multiple previous uneventful TPEs and because all three patients tolerated subsequent TPEs without incident when another brand of HSA was used, we conclude that these patients had pyrogen reactions to the implicated HSA lot. This experience illustrates the value of cluster recognition in arousing suspicion of unusual reactions to HSA and the value of recorded lot numbers in pursuing such suspicions. Apheresis personnel should be aware of the potential for pyrogen reactions with HSA and should record lot numbers of all fluids infused during TPE.
International Forum. Evaluation of the single needle procedure in plateletpheresis with the fresenius as 104 blood cell separator
Authors: Moog Rainer , Müller Norbert
Published: February 2007

The aim of the present study was to evaluate the single needle (SN) procedure for plateletpheresis with the AS 104 blood cell separator. One hundred fifty‐seven platelet collections with different protocols were carried out and analysed with respect to platelet yield, separation efficiency, leukocyte contamination, anticoagulant infused, and donation time. SN plateletpheresis resulted in a mean platelet yield of 2.6–3.1 × 1011 with separation efficiencies of 49.2–57.4%. The mean leukocyte contamination ranged from 2.8 to 40.5 × 106.

Parameters of product quality were investigated in 14 platelet concentrates (PC). Determination of glucose, lactate, lactate dehydrogenase (LDH), and morphology score showed good quality of the PC.
Immunomodulatory effects of donor lymphocyte infusions following allogeneic bone marrow transplantation
Authors: Soiffer Robert J. , Alyea Edwin P. , Ritz Jerome
Published: February 2007

Recently, donor lymphocyte infusions have been successfully used to treat patients with CML who have relapsed following allogeneic bone marrow transplantation (BMT). Responses can be achieved in more than 60–70% of patients with stable phase CML without the need for the additional high dose cytotoxic chemotherapy that would accompany a second transplant procedure. The clinical and molecular remissions induced by this approach are a clear demonstration of graft‐versus‐leukemia (GVL) activity. Although undoubtedly donor lymphocyte infusions are safer than a second BMT, they are associated with toxicities stemming from graft‐versus‐host disease (GVHD) and pancytopenia. In this review, the immunomodulatory mechanisms underlying the GVL activity of donor allogeneic lymphocytes infusions are presented. Unresolved issues regarding lymphocyte administration are discussed as well as potential ways to limit complications due to GVHD and pancytopenia. New potential applications of this immunotherapeutic approach for treatment of infectious disease and non‐hematologic malignancies will be presented.
Meta‐analysis of clinical studies of the efficacy of plasma exchange in the treatment of chronic progressive multiple sclerosis
Authors: Vamvakas Eleftherios C. , Pineda Alvaro A. , Weinshenker Brian G.
Published: February 2007

To examine the hypothesis that addition of therapeutic plasma exchange (TPEX) to an immunosuppressive drug regimen increases that regimen's efficacy to halt the progression of chronic progressive multiple sclerosis (CPMS). METHODS: The literature was searched for prospective controlled clinical trials evaluating the efficacy of TPEX in CPMS. Six studies were eligible for meta‐analysis. Their results were combined, using Cochran's and Peto's methods. Three outcome measures were studied: 1) the change in Kurtzke's disability status scale (DSS) scores, 2) the relative odds of neurologic decline by 1 or more DSS grades, and 3) the relative odds of neurologic improvement by 1 or more DSS grades, in the treatment versus the comparison group of patients. Reported results of neurologic evaluations at 6, 12, 24, and 36 months of follow‐up were analyzed separately. RESULTS: TPEX significantly (P lt; .05) reduced the proportion of patients who experienced neurologic decline (by 1 or more DSS grades) at 12 months of follow‐up (relative odds of decline = 0.441, 95% confidence interval = 0.210–0.929). CONCLUSIONS: There is a need for further clinical research into the possibility of a beneficial effect of TPEX in patients with CPMS likely to experience neurologic decline over the ensuring 12 months. Targeting treatment to a particular subgroup of CPMS patients may be necessary for TPEX to prove effective.
Intensive blood and plasma exchange for treatment of coagulopathy in meningococcemia
Authors: Churchwell Kevin B. , McManus Michael L. , Kent Patricia , Gorlin Jed , Galacki Dolores , Humphreys Donald , Kevy Sherwin V.
Published: February 2007

Eight pediatric patients with fulminant meningococcemia, purpura, and disseminated intravascular coagulation who by multiple prognostic scoring systems were anticipated to have a poor outcome underwent intensive plasma exchange (IPE) or whole blood exchange (WBE) in addition to standard medical therapy. IPE/WBE was initiated shortly after admission with a mixture of both fresh frozen plasma and cryoprecipitate as the replacement solution. All IPE procedures were performed using a continuous flow system and a red cell prime. The mean fibrinogen level increased from 62 to 192 mg/dl, the prothrombin time (PT) decreased from a mean of 32.4 seconds to 15.1 seconds, and the mean activated partial thromboplastin time (APTT) decreased from 89.5 seconds to 40.1 seconds following completion of the initial IPE/WBE. There was a corresponding improvement in all coagulation factor levels but only slight improvement in antithrombin III (ATIII) and protein C levels. Seven of eight patients survived (87.5%) their initial presentation with the sole early death attributed to meningitis with cerebral edema. Mean fluid balance after the procedure was + 10.8 ± 5.87 cc/kg. There were no significant bleeding or cardiovascular complications during the procedure. There was no clinical or radiographic evidence of fluid overload after the procedure.

This experience demonstrates that IPE/WBE may be conducted safely in critically ill, unstable pediatric patients and is effective in rapidly improving coagulopathy without fluid overload.
Modifications to increase accuracy and consistency of anticoagulant delivery using the fenwal CS3000 plus
Authors: Burgstaler E. A. , Pineda A. A. , Geissler U. C.
Published: February 2007

Consistent and accurate delivery of anticoagulant (AC) with the Fenwal CS3000 Plus has been difficult to maintain. We have modified and evaluated methods to deliver AC more accurately and consistently at a 11:1 ratio on the Fenwal CS 3000 Plus. Two modifications (shortened AC tubing, shortened AC tubing with modified drip chamber) and two unmodified methods (unmodified right‐hand string, unmodified double string) were compared (n = 20 platelet apheresis procedures each), resulting in average AC ratios of 11.4 ± 0.5, 11.2 ± 0.4, 11.6 ± 1.3, and 12.1 ± 0.7:1, respectively. There was a significantly higher incidence of ratios within ±10% of 11:1 using the modified methods, 90% and 100%, versus the unmodified methods, 50% and 55%, respectively. Comparison of 36 plateletapheresis (each) using 15‐, 30‐, and 90‐minute intervals in AC drip rate monitoring revealed no significant difference. However, the 30‐minute interval had a better ratio, 11,4 ± 1.0 versus 11.6 ± 0.8 or 11.7 ± 1.1, and higher frequency of 11 ± 10%:1 at 81% versus 75% and 72% and was more practical to use than 15‐minute interval; the 90‐minute interval did require adjustments in 8% of the procedures. The use of a spring scale versus AC bag graduations (n = 75 plateletapheresis) to measure AC volume was significantly superior in measuring volume (343 ± 64 versus 373 ± 72 ml), ratio (11.2 ± 1.5 versus 10.2 ± 1.6), and ratios 11 ± 10%:1 (71% versus 52%). For more accurate and consistent AC delivery with the Fenwal CS 3000 Plus, we recommend three courses of action: 1) Shorten the AC line and modify the AC drip chamber, 2) use a 30‐minute interval to monitor AC drip rate and adjust only if off by more than 3 drops/15 sec, 3) use a spring scale rather than AC bag graduations to obtain more accurate measurement of AC volume used.
Masticatory motor patterns in ungulates: a quantitative assessment of jaw‐muscle coordination in goats, alpacas and horses
Authors: Williams Susan H. , Vinyard Christopher J. , Wall Christine E. , Hylander William L.
Published: February 2007

We investigated patterns of jaw‐muscle coordination during rhythmic mastication in three species of ungulates displaying the marked transverse jaw movements typical of many large mammalian herbivores. In order to quantify consistent motor patterns during chewing, electromyograms were recorded from the superficial masseter, deep masseter, posterior temporalis and medial pterygoid muscles of goats, alpacas and horses. Timing differences between muscle pairs were evaluated in the context of an evolutionary model of jaw‐muscle function. In this model, the closing and food reduction phases of mastication are primarily controlled by two distinct muscle groups, triplet I (balancing‐side superficial masseter and medial pterygoid and working‐side posterior temporalis) and triplet II (working‐side superficial masseter and medial pterygoid and balancing‐side posterior temporalis), and the asynchronous activity of the working‐ and balancing‐side deep masseters. The three species differ in the extent to which the jaw muscles are coordinated as triplet I and triplet II. Alpacas, and to a lesser extent, goats, exhibit the triplet pattern whereas horses do not. In contrast, all three species show marked asynchrony of the working‐side and balancing‐side deep masseters, with jaw closing initiated by the working‐side muscle and the balancing‐side muscle firing much later during closing. However, goats differ from alpacas and horses in the timing of the balancing‐side deep masseter relative to the triplet II muscles. This study highlights interspecific differences in the coordination of jaw muscles to influence transverse jaw movements and the production of bite force in herbivorous ungulates. J. Exp. Zool. 307A:226–240, 2007. © 2007. Wiley‐Liss, Inc.
The circulatory system in Mysidacea—Implications for the phylogenetic position of Lophogastrida and Mysida (Malacostraca, Crustacea)
Authors: Wirkner Christian S. , Richter Stefan
Published: February 2007

The morphology of the circulatory organs in Mysida and Lophogastrida (traditionally combined as Mysidacea) is revisited investigating species so far unstudied. In addition to classical morphological methods, a newly developed combination of corrosion casting with micro computer tomography (MicroCT) and computer aided 3D reconstructions is used. Lophogastrida and Mysida show a highly developed arterial system. The tubular heart extends through the greater part of the thorax and is connected with the ventral vessel via an unpaired descending artery. It is suggested that a distinct ostia pattern supports the monophyly of Mysidacea. The cardiac artery system is more complex in Lophogastrida than in Mysida, consisting of up to 10 pairs of arteries that supply the viscera. In both taxa, an anterior and posterior aorta leads off the heart. In the anterior part of the cephalothorax the anterior aorta forms dilations into which muscles are internalized; these structures are called myoarterial formations. One of these myoarterial formations can also be found in all the other peracarid taxa but not in other Malacostraca. J Morphol., 2007. © 2007 Wiley‐Liss, Inc.
Dating Quaternary volcanism and incision by the River Tigris at Diyarbakır, southeast Turkey
Authors: Bridgland David R. , Demi̇r Tuncer , Seyrek Ali̇ , Pringle Malcolm , Westaway Rob , Beck Anthony R. , Rowbotham George , Yurtmen Sema
Published: February 2007

New high‐precision Ar‐Ar dating of basalt underlying the city of Diyarbakır, southeast Turkey, constrains the Quaternary incision history of the River Tigris, strengthening the pre‐existing chronology based on magnetostratigraphy and K‐Ar dates. The basalt, which overlies Tigris terrace gravel 70 m above the river, is part of the Karacadağ shield volcano complex centred ca. 60 km to the southwest. The reverse‐magnetised Diyarbakır basalt, one of relatively few flow units to reach the Tigris valley axis, has been dated to 1196 ± 19 ka (±2σ). Two lower terraces have been recognised in the Diyarbakır area, 46 and 32 m above the present river, with at least one other further downstream. From this evidence the rate of Middle‐Late Pleistocene incision by the Tigris can be estimated; it probably reached ca. 0.07 mm a−1, reflecting the characteristic global increase in uplift rates observed at that time. Copyright © 2007 John Wiley & Sons, Ltd.
Kinetic Investigation into the Non‐Thermal Microwave Effect on the Ring‐Opening Polymerization of ε‐Caprolactone
Authors: Li Hao , Liao Liqiong , Liu Lijian
Published: February 2007

Rate constants of the ring‐opening polymerization (ROP) of ε‐caprolactone (ε‐CL) by microwave heating (MH) and flash conventional heating (FCH) have been measured. The reaction is catalyzed by stannous octanoate (Sn(Oct)2). With a microwave power level of 400, 500, 600, 700 and 800 W, the equilibrium temperature of the polymerization mixture increases from 165 to 180, 197, 213 and 228 °C. However, the rate constant does not continuously increase with the observed increase in temperature. Instead it abruptly increases at 180 °C (500 W), and the increase does not fit Arrhenius' law which, however, is followed by the polymerization under FCH conditions with an increase of the equilibrium temperature from 108 to 135, 151, 189 and 213 °C. The initiation time of the ROP by MH varies anomalistically with temperature and is not related to the rate constant, which is in contrast to that by FCH, which reduces exponentially from 127.5 to 36.40, 8.63, 1.22, and 0.579 min with the increase in polymerization temperature and rate constant. Based on the divergences it is reasonable to deduce that the acceleration of the ROP of ε‐CL by microwaves is induced not only by thermal conditions (the thermal microwave effect) but also by the non‐thermal microwave effect.

magnified image