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Biomedical subjects

G Berlin

Publications and source records attributed to G Berlin.

At least 19 recordsLinked to original sources

Effect of photopheresis on lymphocyte population in children with newly diagnosed type 1 diabetes.

In recent years photopheresis has been claimed to be an effective form of immunomodulation. It has also been shown to have an effect on the disease process at the onset of type 1 diabetes. In a double-blind, placebo-controlled randomized study, we analyzed if the effect of photopheresis in children with newly diagnosed diabetes is related to changes in the balance of lymhocyte populations. We also analyzed if lymphocyte subsets were related to recent infection, mild or aggressive disease manifestations, heredity, or gender. Nineteen children received active treatment with photopheresis, while 21 children received sham pheresis (placebo group). No influence of a history of previous infection, heredity, or certain clinical parameters on lymphocyte subsets was found. At the onset of type 1 diabetes, girls showed a higher proportion and a larger number of T cells (CD3+) and T-helper cells (CD4+) and a higher proportion of naïve CD4+ CD45RA+ cells. In the placebo group, an increase in the number of subsets with the activated phenotype in both the CD4(CD29+) and the CD8 (CD11a+) compartments was noted during the course of the study. These changes did not occur in the photopheresis group. No relation between lymphocyte subsets and clinical outcome was found 1 year after the treatment with photopheresis. In conclusion, we found no major effect of photopheresis on lymphocyte populations in a group of children with newly diagnosed type 1 diabetes. However, in the placebo group the proportions of activated CD4 and CD8 cells increased over time. Since these changes did not occur in the actively treated group, our findings suggest that photopheresis may have some suppressive effects.

Adolescent↗

A rapid and reliable flow cytometric routine method for counting leucocytes in leucocyte-depleted platelet concentrates.

BACKGROUND AND OBJECTIVES: To ensure a proper quality control it is important to use a reliable method to count low numbers of leucocytes in leucocyte-reduced platelet concentrates (PCs). MATERIALS AND METHODS: A modified flow cytometric method for counting low numbers of leucocytes, based on a reference population contained in tubes with an exact number of fluorescent beads and staining with propidium iodide was used. To increase the number of events, the original sample volume was increased. RESULTS: There was a good correlation in the number of leucocytes (r = 0.99) between the modified flow cytometric method and microscopy of samples from unfiltered and expected numbers from serially diluted PCs. Samples from leucocyte-reduced PCs obtained by apheresis or filtered buffy coats showed no correlation between results from the modified flow cytometric method and microscopy (Nageotte). CONCLUSION: Counting by microscopy gave a lower number of leucocytes than the modified flow cytometric method when counting a low number of cells. However, analysis of the serially diluted PCs proved that the modified flow cytometric method was reliable and rapid, making it suitable for clinical routine use.

Blood Banking↗

The use of cell products for treatment of autoimmune neuroinflammatory diseases.

Cell products are live cells that are given to patients in order to replace or modify the function of missing or dysfunctional cells. Progress in technology and in the understanding of pathobiology may lead to the use of cell products in many areas. This review outlines the use of cell products in the treatment of autoimmune diseases, with focus on neuroinflammatory diseases like multiple sclerosis. Treatment of autoimmune diseases should be selective and specific in order to avoid serious side effects. To achieve this, T lymphocyte regulation has been in focus for several immunomodulatory regimens. One area of great interest is the use of T cell vaccination, when autologous attenuated auto-reactive T cells are given to patients in order to initiate a specific immune response to the pathogenic T cell populations. Phopheresis may be an immunomodulatory treatment related to T cell vaccination. Another promising area involves ex-vivo alteration of the cytokine profile of harmful auto-reactive T cells. This can be achieved by genetic manipulation or by certain cytokine stimulations. A subsequent adoptive cell transfer will, by homing mechanisms, lead to at site specific delivery of the cells, which will have a local down-regulatory effect on the inflammatory process. Although unsolved questions regarding doses, timing, optimal preparing conditions and mechanisms still remain, both T cell vaccination and adoptive transfer of ex-vivo manipulated cytokine secreting cells have proven successful for treatment of neuroinflammation in experimental models. T cell vaccination was shown to be feasible in patients with multiple sclerosis, however, otherwise the experience in humans so far is limited.

Animals↗

A randomized controlled trial oftransfusion-related acute lung injury: is plasma from multiparous blood donors dangerous?

BACKGROUND: Transfusion-related acute lung injury (TRALI) and other posttransfusion reactions may be caused by granulocyte and/or HLA antibodies, which are often present in blood from multiparous donors. The purpose of this study was to compare the effects of plasma from multiparous donors with those of plasma from donors with no history of transfusion or pregnancy (control plasma) in a prospective, randomized, double-blind, crossover study. STUDY DESIGN AND METHODS: Intensive care patients, judged to need at least 2 units of plasma, were randomly assigned to receive a unit of control plasma and, 4 hours later, a plasma unit from a multiparous donor (> or = 3 live births) or to receive the plasma units in opposite order. The patients were closely monitored, and body temperature, blood pressure, and heart rate were recorded. Blood samples for analysis of blood gases, TNFalpha, IL-1 receptor antagonist, soluble E selectin, and C3d complement factor were collected at least on four occasions (before and after the transfusion of each unit). RESULTS: Transfusion of plasma from multiparous donors was associated with significantly lower oxygen saturation and higher TNFalpha concentrations than transfusion of control plasma. The mean arterial pressure increased significantly after the transfusion of control plasma, whereas plasma from multiparous donors had no effect on it. Five posttransfusion reactions were observed in 100 patients, in four cases after the transfusion of plasma from multiparous donors. CONCLUSION: Plasma from multiparous blood donors may impair pulmonary function in intensive care unit patients.

Acute Disease↗

Photopheresis at onset of type 1 diabetes: a randomised, double blind, placebo controlled trial.

BACKGROUND: In recent years photopheresis, an extracorporeal form of photochemotherapy using psoralen and ultraviolet A irradiation of leucocytes, has been claimed to be an effective form of immunomodulation. AIM: To evaluate its effect in type 1 diabetes we performed a double blind, controlled study using placebo tablets and sham pheresis in the control group. METHODS: A total of 49 children, aged 10-18 years of age at diagnosis of type 1 diabetes were included; 40 fulfilled the study and were followed for three years (19 received active treatment with photopheresis and 21 placebo treatment). RESULTS: The actively treated children secreted significantly more C peptide in urine during follow up than control children. C peptide values in serum showed corresponding differences between the two groups. The insulin dose/kg body weight needed to achieve satisfactory HbA1c values was always lower in the photopheresis group; there was no difference between the groups regarding HbA1c values during follow up. The treatment was well accepted except for nausea (n = 3) and urticaria (n = 1) in the actively treated group. There were no differences regarding weight or height, or episodes of infection between the two groups during follow up. CONCLUSION: Photopheresis does have an effect in addition to its possible placebo effect, shown as a weak but significant effect on the disease process at the onset of type 1 diabetes, an effect still noted after three years of follow up.

Adolescent↗

White blood cell subsets in buffy coat-derived platelet concentrates: the effect of pre- and poststorage filtration.

BACKGROUND AND OBJECTIVES: Our objective was to study the effect of storage time on the filtration of platelet concentrates (PCs). We compared the total number of white blood cells (WBC), as well as the distribution of WBC subsets, in units filtered before and after storage. MATERIALS AND METHODS: Buffy coat-derived PCs were filtered either fresh or after 5 days of storage, and total WBC were enumerated by flow cytometry. WBC subsets were analyzed by flow cytometry with three-color fluorescence. RESULTS: The total number of white cells before filtration was significantly higher in fresh units compared with stored units, whereas in postfiltration samples the number of white cells was significantly lower in the fresh compared with the stored units. Although absolute numbers were significantly reduced, filtration also induced significant changes in the proportions of subsets in both fresh and stored units; the percentage of T cells was decreased, whereas the percentage of B cells and monocytes was increased after filtration. CONCLUSION: Our results suggest that prestorage WBC filtration of platelet concentrates is superior in reducing the absolute numbers of WBC. However, both pre- and poststorage WBC filtration significantly affect the proportions of WBC in the final product, decreasing the number of T cells while apparently increasing the proportion of MHC class II-positive cell populations.

Blood Platelets↗

Lack of significant treatment effect of plasma exchange in the treatment of drug-induced toxic epidermal necrolysis?

OBJECTIVE: Comparison of outcome in patients with toxic epidermal necrolysis (TEN) in patients who received plasma exchange (PE) compared with the results in two other centres that used almost identical treatment protocols but without PE. DESIGN: Retrospective comparative case series with two recently published case series serving as controls. SETTING: National burns intensive care unit (ICU) and Department of Transfusion Medicine at Linköping University Hospital, Sweden. PATIENTS: 8 consecutive patients admitted with TEN who received PE during 1987-1997. INTERVENTIONS: Neither prophylactic antibiotics nor cortisone were used. The patients were given a median of 5.5 PE treatments (range 1-8). RESULTS: Eight patients with a median (range) age of 45 years (5-89) and with a median skin involvement total body surface area (TBSA) of 38% (12-100) were treated. The length of stay in the burns ICU was 15 (13-25) days and the time from onset of the cutaneous signs until complete re-epithelialisation was 24 days (13-55) for the seven survivors. Five patients fulfilled the diagnostic criteria of sepsis. One patient with extensive ischaemic cardiac disease developed septic shock and died (mortality 12.5%). Two patients developed side effects from PE. CONCLUSIONS: To our knowledge, this is the largest series yet presented using PE in the treatment of TEN. Our results, in patients with less cutaneous involvement, similar causative agents, and similar demographic data as in the other two studies (controls), were no different as far as mortality, length of stay, or time to re-epithelialisation were concerned. This finding does not support the use of PE in the treatment of TEN.

Adolescent↗

Kinetics of peripheral blood stem cell harvests during a single apheresis.

BACKGROUND: The enumeration of CD34+ cells in the peripheral blood of patients before leukapheresis is commonly used to predict the outcome of stem cell harvests. The concept that an increased number of transplanted cells gives faster marrow reconstitution triggers an interest in investigating the kinetics of peripheral blood stem cells during leukapheresis. The aim of this study was to investigate the issue of recruitment of hematopoietic progenitor cells during a single leukapheresis. STUDY DESIGN AND METHODS: Nine leukapheresis procedures (in 8 patients) were investigated. In each case, 3 blood volumes were processed. Samples from peripheral blood, the collection line of apheresis equipment, and the collected component were obtained after each blood volume was processed. The enumeration of CD34+ cells was performed, and the total number of progenitors, as a sum of the number of cells in the peripheral blood and the number of cells in the collected component, was calculated. RESULTS: A mean of 13.3 L of blood was processed, and a component with a mean volume of 424 mL and a mean of 10.1 x 10(6) CD34+ cells per kg of body weight was collected. White cell and mononuclear cell counts in peripheral blood declined concomitantly during the procedures. The calculated total number of cells--that is, the sum of the number of cells in the collected component and the number of cells in the peripheral blood--showed a concomitant, but not equal, rise in polymorphonuclear cells, mononuclear cells, and CD34+ cells during the leukapheresis. This apparent mobilization of progenitors into the peripheral blood did not correlate with the slightly increased number of polymorphonuclear cells or with the more pronounced increase in mononuclear cells. CONCLUSION: There is a substantial recruitment of progenitor cells during a single leukapheresis.

Adult↗

Plasma exchange or immunoadsorption in patients with rapidly progressive crescentic glomerulonephritis. A Swedish multi-center study.

A therapeutic removal of antibodies may be achieved by immunoadsorption (IA) or by plasma exchange (PE). The aim of this prospective randomised study was to compare the efficacy of these different techniques with regard to treatment of patients with rapidly progressive glomerulonephritis (RPG) having at least 50% crescents. Forty-four patients with a RPG were included for treatment either by IA or PE (with albumin as substitution for removed plasma). All patients were additionally treated with immunosuppression. A median of 6 sessions of PEs were performed in 23 patients compared with 6 IAs in 21 patients. Goodpasture's syndrome (GP) was present in 6 patients (PE 3, IA 3). All of them started and ended in dialysis, two died. Among the remaining 38 patients (26 men, 12 women) 87% had antibodies to ANCA. Creatinine clearance for PE versus IA were at a median at start 17.1 and 19.8 ml/min, and at 6 months 49 and 49 ml/min, respectively. At 6 months 7 of 10 patients did not need dialysis (remaining: IA 0/5 and PE 2/5, n.s.). The extent of improvement did not differ between the groups. Three patients died during the observation period of 6 months (IA 2; PE 1, on HD). Although no difference was found between the IA or the PE group this study shows that the protocol used was associated with an improved renal function in most patients (except for Goodpasture's syndrome) whereas 70% of them could leave the dialysis program.

Adult↗

Treatment of psoriatic arthritis with extracorporeal photochemotherapy and conventional psoralen-ultraviolet A irradiation.

OBJECTIVE: To study the use of combined photopheresis and psoralen-ultraviolet A irradiation (PUVA) in the treatment of psoriatic arthritis. METHODS: Eight patients with psoriasis and sero-negative arthritis received photopheresis for 12 weeks, followed by photopheresis plus PUVA for another 12 weeks. Clinical and laboratory examinations were performed every 3 months for up to 1 year after therapy. RESULTS: Four patients experienced a marked improvement of joint symptoms that lasted for > or = 12 months post-therapy (74% decrease in the Ritchie articular index; P < 0.01). Prior to therapy, these patients had a higher CD4:CD8 ratio than the poor responders. Only minor laboratory changes occurred. CONCLUSION: A more extensive trial of photopheresis plus PUVA in psoriatic arthritis is warranted.

Adult↗

Factors influencing white cell removal from red cell concentrates by filtration.

BACKGROUND: The preparation of blood components by hard centrifugation results in red cell concentrates with a small amount of plasma. The influence of various plasma factors, temperature, and storage time on white cell reduction by filtration was studied. STUDY DESIGN AND METHODS: Red cell concentrates were suspended in 100 mL of saline-adenine-glucose-mannitol (SAGMAN) solution or in SAGMAN solution in which 5 or 10 mL had been replaced with an equal amount of fresh plasma, albumin (4%), or heat-inactivated plasma. After overnight storage at 4 degrees C, filtration at a slow flow rate (2 hours) was performed. The effect of temperature was studied by filtration at 4 degrees C and 37 degrees C. To study the influence of storage time, red cell concentrates were stored for 4 to 8 hours or 14 to 20 hours at 4 degrees C and filtered through another model of filter. The number of white cells was counted microscopically or by flow cytometry. RESULTS: When 5 or 10 mL of plasma was added, a significantly smaller number of white cells were found after filtration than were found in the SAGMAN control (the median difference between pairs: 23.6 x 10(6) for 5 mL [p = 0.006] and 14.9 x 10(6) for 10 mL [p = 0.003]). The number of white cells was significantly higher with 10 mL of albumin than with 10 mL of plasma (difference, 15.0 x 10(6); p = 0.006). When heat-inactivated plasma was used, the number of white cells was significantly lower than when fresh plasma was used (difference, 0.3 x 10(6); p = 0.009). Filtration at 37 degrees C resulted in a 64-percent reduction in white cells and that at 4 degrees C led to a 99.7-percent reduction (p = 0.006). When the second filter was used, a slight but significantly lower number of white cells was found in the red cell concentrate stored for 14 to 20 hours than in that stored for 4 to 8 hours (difference, 0.03 x 10(6); p < 0.001). CONCLUSION: The amount of plasma in the red cell concentrate and the storage time and temperature are important factors in the outcome of white cell reduction by filtration. The effect of plasma does not seem to be due to a general influence of protein or to the activity of complement or fibrinogen.

Blood Preservation↗

Transfusion of platelet concentrates--clinical evaluation of two preparations.

The aim of this study was to compare the clinical effect of transfusion of platelet concentrates (PC) prepared from pooled buffy coats (BC) and PCs collected from a single donor (SD) by an apheresis technique. The influence of storage time and various clinical conditions was also studied. Thirty-two patients suffering from haematological malignancies were given a total of 326 platelet concentrates; 180 BC-PCs and 146 SD-PCs, median 7 transfusions per patient. BC-PCs contained 312 +/- 52 x 10(9) and SD-PCs 383 +/- 133 x 10(9) platelets/unit (mean +/- SD). The mean storage time of BC-PC was 3 d and that of SD-PC 1 d. The mean platelet count of the patients before transfusion was 11 +/- 8 x 10(9)/L. Regression analysis showed a significant decrease of the post-transfusion platelet corrected count increment (CCI) during storage of PCs for 1-5 d (BC-PC: p < 0.01; SD-PC: p < 0.05). There was no difference in platelet increment between BC-PC and SD-PC. Human leukocyte antigen (HLA) alloimmunization was the major cause of clinical refractoriness to random donor platelet transfusions but splenomegaly also caused low CCI values.

Adolescent↗

Growth factor release during preparation and storage of platelet concentrates.

The platelet content of platelet-derived growth factor (PDGF), a mitogen stored in the alpha-granules, was studied during preparation and storage of platelet concentrates (PC) and compared to the growth-promoting activity of platelets, beta-thromboglobulin (beta-TG) and lactate dehydrogenase (LD). We compared PC prepared from platelet-rich plasma (PRP-PC; n = 10) and from buffy coat. Two different pre-preparation storage periods of the buffy coat were used: 4 h (BC-PC:4h; n = 10) and 24 h (BC-PC:24h; n = 5). The platelet content of PDGF and beta-TG was measured by a RIA technique and the growth-promoting activity by incorporation of 3H-thymidine in stimulated fibroblasts. The platelet content of PDGF, beta-TG and the growth-promoting activity of the platelets decreased in a similar way during preparation and storage of PRP-PC (31 +/- 2, 35 +/- 2 and 33 +/- 7%, respectively, at day 5 of storage; mean +/- SEM). The release of LD was minor (3.9 +/- 0.5% at day 5). At day 1 of storage the platelet content of PDGF was significantly better preserved in BC-PC:4h than in BD-PC:24h (88 +/- 2 and 81 +/- 3%, respectively; p = 0.03). Comparing BC-PC:4h and PRP-PC we found a significantly better preservation of PDGF in BC-PC:4h until day 3 of storage (80 +/- 2 and 75 +/- 1%, respectively at day 3; p = 0.046). In conclusion the preparation of PC according to the PRP method initially induces a higher loss of PDGF, and hence of the growth-promoting activity, than the BC method.

Blood Platelets↗

Inadequate white cell reduction by bedside filtration of red cell concentrates.

BACKGROUND: White cell filtration of red cell concentrates is often performed at the bedside, in the ward, with the filter inserted in the blood administration line. The aim of this study was to evaluate the efficiency of this filtration method and compare it to filtration in the blood bank. STUDY DESIGN AND METHODS: One-day-old, buffy coat-reduced, hard-packed red cell concentrates in saline-adenine-glucose-mannitol solution were filtered through different filters designed for bedside or laboratory use. With filters designed for bedside use, filtration of red cells was performed under laboratory conditions at fast flow (10 min) or under bedside conditions at slow flow (2 hours). The remaining white cells were counted microscopically. Filters designed for laboratory use were evaluated at fast flow, and the number of contaminating white cells was counted by flow cytometry. RESULTS: With bedside filters, a significantly higher contamination of white cells was found in the units filtered at slow flow than at fast flow, regardless of the filter used. The number of units with > 5 x 10(6) white cells was 52 (78%) of 67 filtered at slow flow compared to 11 (23%) of 47 at fast flow, all filters taken together. This difference in white cell contamination was mainly due to an increase of polymorphonuclear cells in the red cell concentrates filtered at slow flow. With filters designed for laboratory use, 0 to 2 percent of units (n = 1448) were contaminated with > 5 x 10(6) white cells. CONCLUSION: Bedside filtration for white cell reduction at slow flow is inefficient for 1-day-old, buffy coat-reduced red cell concentrates.

Cell Separation↗

Immunochemical and clinical effects of immunosuppressive treatment in monoclonal IgM neuropathy.

A pathogenic role of the M protein in monoclonal IgM neuropathy has been suggested. This is based among other things on a close relation between immunosuppressive treatment, lowered concentration of M protein, and clinical effect. We studied five patients with monoclonal IgM and antibodies to peripheral nerve myelin. The immunosuppressive treatment was beneficial in three of the patients. In three patients there was a relationship between antibody concentration and clinical effect (in one there was no change in antibody concentrations and correspondingly no change in clinical status, and in two patients clinical improvement corresponded to decreased antibody concentrations). In two patients, however, there was no clear correlation, since one patient improved despite increasing antibody concentrations and one patient did not improve despite a lowered antibody concentration. It is therefore possible that other mechanisms may contribute to the effect of treatment.

Adult↗