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Comparison of lymphocyte depletion and clinical effectiveness on filtration leukocytapheresis in patients with rheumatoid arthritis.

We evaluated the relationship between the clinical benefit of filtration leukocytapheresis (LCP) and the number of removed leukocytes in patients with rheumatoid arthritis (RA). LCP was performed in 31 drug-resistant RA patients. LCP was carried out 3 times with 1 week separating each session. Assessment of RA before and after LCP showed a substantial and rapid improvement in tender joint counts, swollen joint counts, and patients' and physicians' assessments. Careful analysis indicated that 19 of 31 patients with RA showed > or = 20% improvement following LCP therapy. The number of leukocytes in the peripheral blood significantly decreased during each session of LCP. However, there was no significant decrease in the number of circulating blood cells during the study period. No adverse reactions or complications were noted. There was no significant difference in any indices of clinical activity and the removal rates of leukocytes between responders and nonresponders. The total numbers of removed lymphocytes in responders were significantly higher than those in nonresponders (responders 64.1 x 10(8) versus nonresponders 50.7 x10(8), p < 0.05). The relationship between clinical effectiveness and the number of removed granulocytes and monocytes was not statistically significant. Our results suggest that filtration LCP to remove leukocytes from the peripheral blood, especially lymphocytes, exerts an immunomodulatory effect in patients with RA.

Adult↗

From membrane differential filtration to lipidfiltration: technological progress in low-density lipoprotein apheresis.

Extracorporeal low-density lipoprotein (LDL) apheresis is an established and highly effective therapy for patients with familial hypercholesterolemia (FH) not adequately responding to diet and drug therapy alone. Based on different methodology, five treatment options of LDL apheresis are available and in widespread practical use in Germany. All methods are safe and demonstrate equivalent efficacy of reducing LDL cholesterol with respect to the single apheresis session as well as during long-term treatment. Owing to methodological properties all methods also exhibit characteristics of additional plasma protein elimination, which do not impair, but in part, increase the beneficial therapeutic effect of LDL apheresis. Fibrinogen reduction has to be mentioned as an example. The lipidfiltration system is based on plasmafiltration previously named membrane differential filtration (MDF), synonymous with double filtration plasmapheresis (DFPP). The new term lipidfiltration was the result of technological progress leading to a significant improvement of the efficiency. The system consists of a novel lipid filter with enhanced sieving characteristics and capacity, and is completed by an enhanced therapy machine with an optimized heating unit.

Adult↗

Viability of granulocytes obtained by filtration leukapheresis.

Nylon filtration alters the morphology of human granulocytes and slightly reduces their phagocytic ability as measured by activation of the hexose monophosphate shunt (HMS) pathway of glucose metabolism. In addition, the ability of rat granulocytes to circulate in granulocytopenic rats is reduced, and this is not attributed to HMS activation during filtration. The activation of the hexose monophosphate shunt is related to the size of the particles rather than to the nature of the material.

Animals↗

Filtration characteristics of the dual-mode (Johnson and Johnson) micropore blood transfusion filter.

Stored human whole blood and red blood cells of varying age were passed through dual mode microscope blood transfusion filters. Passage through the filters resulted in markedly decreased screen filtration pressure (SFP) of the blood and increased filter weights. Numerous microaggregates were removed and SFP returned to normal. Filtration resulted in reduced platelet and white cell counts but other blood components were not adversely affected. On the basis of this research, we conclude that this micropore blood transfusion filter is effective in removing microaggregates from stored whole blood and red blood cells. It has a high capacity and rapid flow rate and is reliable during pressure transfusion.

Blood Transfusion↗

Filtration of cryoprecipitate: a microscopic assessment of filter depostion.

A recent survey indicated that many Canadian hemophiliacs and physicians did not consider it necessary to filter cryoprecipitate prior to infusion. Experiments were performed to demonstrate that no loss of factor activity resulted from filtration of cryoprecipitate through standard blood filters. Furthermore, examination of the material retained on standard and ultrafiltration elements using scanning and transmission electron microscopy demonstrated the presence of amorphous and fibrillar proteins that proved to be largely composed of fibrin. This was accompanied by cellular material including intact and disintegrating leukocytes, erythrocytes, and platelets. Nonbiologic material was also discovered, including cellulose and plastic debris. This study emphasizes the need for effective filtration of cryoprecipitate.

Chemical Precipitation↗

Filtration leukapheresis: the influence of granulocyte counts upon the donors' yield.

The purpose of this investigation was to determine the influence of granulocyte count on the yield of granulocytes. Healthy adult volunteer donors underwent filtration leukapheresis without premedication. The granulocyte count was measured before and immediately after the procedure. In 73 donors, there was an increase and in 67 donors there was a decrease in the granulocyte counts. In this study of nonmedicated donors those with high initial granulocytes counts and those in which there was a large increase in the postleukapheresis granulocyte counts provided the best yield with the filtration leukapheresis technique.

Blood Cell Count↗

Filtration. A method to prepare white cell-poor platelet concentrates with optimal preservation of platelet viability.

HLA alloimmunization is a major problem for thrombocytopenic patients receiving long-term platelet support. It is caused by white cells (WBCs) that are present as contaminants in platelet concentrates (PCs). Recent data have shown that filtration is an effective means to reduce WBC contamination, but it has little effect on the recovery of platelets. The present report evaluates two filters, a cellulose acetate (CA) filter requiring the inactivation of platelets with prostacyclin and a cotton wool (CW) filter requiring no platelet inactivation. The results show that, using fresh pooled PCs from six random donors, both filters reduce WBC contamination below 10(7) per PC, the likely threshold below which alloimmunization does not develop. With platelets stored for 2 to 3 days the efficacy of the CW filter decreases. Neither filter inflicts important damage to the platelets, as there is no considerable platelet activation or cell disruption. Moreover, PCs prepared by both filters show normal survival and effectively reduce the bleeding times. Thus, filtration of PCs results in platelets with optimal responsiveness both in vitro and in vivo.

Animals↗

Low cytokine contamination in buffy coat-derived platelet concentrates without filtration.

BACKGROUND: Cytokines (interleukin [IL]-1 beta, IL-6, and tumor necrosis factor [TNF]) generated by white cells during the storage of platelet concentrates can cause febrile nonhemolytic transfusion reactions. The high rate of febrile reactions reported in other studies was not observed in the patients in the authors' center. This discrepancy prompted the determination of cytokine levels in buffy coat-derived platelet concentrates. STUDY DESIGN AND METHODS: Platelet concentrates were produced from buffy coats by a standard large-scale production process. Buffy coats were separated from the red cell and plasma components, and then platelets were recovered from the buffy coats by a soft-spin procedure. Levels of cytokines (IL-1 beta, IL-6, IL-8, and TNF) were determined with commercial enzyme-linked immunosorbent assays. RESULTS: In platelet concentrates produced by the buffy coat method, IL-1 beta, IL-6, IL-8, and TNF were observed at or below the detection limit of current enzyme-linked immunosorbent assays after 5 days' storage at 22 +/- 2 degrees C. Therefore, prestorage filtration had no measurable effect on cytokine levels. In controls, IL-1 beta, IL-6, IL-8, and TNF were quantitatively detected after exogenous addition of recombinant cytokines or exposure to lipopolysaccharide. CONCLUSION: Platelet concentrates prepared from buffy coats may be virtually free of cytokines (IL-1 beta, IL-6, IL-8, and TNF) during 5 days of storage. Filtration is not required to reduce the recipient's cytokine exposure via such platelet concentrates.

Blood Platelets↗

In vitro and in vivo effects of prestorage filtration of apheresis platelets.

BACKGROUND: The effect of prestorage filtration on the quality of apheresis platelet concentrates stored for transfusion is undetermined. STUDY DESIGN AND METHODS: Investigation of 11 plateletpheresis components used a concurrent paired-study design. On the day of collection, each component was equally divided into two suspensions; one half was filtered, and the other half was not. Each suspension was stored for 5 days. In vitro testing was performed on the day of collection (Day 0) for cell counts and on Day 5 for measurements of lactate, glucose, blood gases, pH, platelet ATP, hypotonic stress ratio, extent of shape change in response to ADP, tissue necrosis factor alpha, interleukin 8, interleukin 1 alpha, interleukin 1 beta, interleukin 6, and platelet surface glycoproteins by flow cytometry. At the end of the 5-day period, a sample was taken from each of the two suspensions, radiolabeled with either 51Cr or 111In, and transfused concurrently. Posttransfusion samples were drawn for measurements of recovery and platelet survival and for functional assessment of the ex vivo ability of the circulating radiolabeled platelets to aggregate in response to ADP. RESULTS: The apheresis component had a mean platelet yield of 3.2 +/- 0.4 x 10(11) and a white cell yield ranging from 1 x 10(5) to 1 x 10(8), with a median of 2 x 10(7). Filtration resulted in a platelet loss of approximately 10 percent and a variable 2 to 3 log10 reduction in white cell content. No significant differences between filtered and unfiltered suspensions in paired t tests that would likely have an impact on platelet quality were observed in the in vitro tests. The in vivo recovery and survival were highly similar and not statistically different in filtered and unfiltered paired suspensions: the mean difference was 1.2 +/- 4.0 percent for recovery and 7.0 +/- 15 hours for survival. The functional assessment by aggregation to ADP showed no difference between filtered and unfiltered suspensions. A small decrease in tumor necrosis factor alpha and interleukin 8 was evident in the filtered suspension as compared to levels in the unfiltered suspensions. CONCLUSION: Prestorage white cell reduction in apheresis components resulted in WBC reduction by several log10 with no evident adverse effect on platelet viability or function.

Blood Platelets↗

[Serum level of digoxin and digitoxin and glomerular filtration rate in hyper- and hypothyroidism].

In a comparative prospective study the serum levels of digoxin and digitoxin and the glomerular filtration of the kidneys were determined radioimmunologically in thyroid function disorders using the endogenous creatinine clearance and the 51Cr-EDTA clearance. Compared to a euthyroid control group 17 patients with hyperthyroidism showed a decreased and 5 patients with hypothyroidism showed a largely toxic digoxin level, both groups being on a maintenance therapy of 0.25 mg digoxin b. i. d. During an oral maintenance therapy of daily 0.1 mg digitoxin unchanged therapeutic serum levels were found in 35 hyperthyroid and 18 hypothyroid patients when compared to a euthyroid control group. Assessment of clearances showed that glomerular filtration rates were clearly increased in the hyperthyroid and lowered in the hypothyroid patients. Renewed assessment of the clearance in four hyperthyroid patients and three with hypothyroidism after thyroid recompensation showed a marked decrease of clearance values in hyperthyroidism and an increase in hypothyroidism. Increased clearance values in hyperthyroidism were associated with lowered digoxin serum levels. In contrast, lowered clearance values in hypothyroidism were accompanied by increased serum digoxin levels. There was no such association detectable for digitoxin.

Adult↗

Filtration leukapheresis for granulocyte transfusion therapy. Clinical and laboratory studies.

To study the clinical efficacy of granulocytes obtained by filtration leukapheresis, patients with clinically evident infection and granulocyte counts of smaller than 500 per cubic millimeter were randomly assigned to receive conventional therapy alone or with a granulocyte transfusion obtained from a single donor each day for four days. Five of 19 control patients survived to day 20, and 15 of 17 in the transfused group survived. Comparison of the two populations for variables such as age, disease, and severity and type of infection revealed no other factor that could account for the difference in survival. Outcome was not demonstrated to be related to HL-A match, post-transfusion counts, or presence of leukocyte antibodies. Functional studies of granulocytes obtained by filtration leukapheresis showed only minor differences although appearance was altered. Granulocytes so obtained can be used safely and efficaciously as adjunctive therapy for infection associated with granulocytopenia.

Acute Disease↗

Increased glomerular filtration rate in patients with major burns and its effect on the pharmacokinetics of tobramycin.

The clearance of endogenous creatinine in 20 burned patients, measured between the fourth and the 35th post-burn day, was a mean (+/- S.D.) of 172.1 p 48.4 ml per minute per 1.73 m2; in eight normal subjects the mean value was 125.4 g- 10.4 (P less than 0.02). Thirteen patients had values more than 2 S.D. above the normal mean. We confirmed this rise in glomerular filtration rate by measuring inulin or iothalamate clearance in nine patients. The pharmacokinetics of tobramycin were studied in 11 of the 20 patients and in eight normal subjects receiving continuous intravenous infusions of the drug. An inverse correlation was found between plasma half-life of the drug and creatinine clearance (r = 0.68, P less than 0.01). Increased creatinine clearances and shortened half-life of tobramycin occurred mainly in younger patients. Glomerular filtration rates in burned patients may rise to very high values and can be validly measured by creatinine clearance. The plasma half-lives of drugs with predominantly urinary excretion may decrease in patients with burns.

Adult↗

Increased glomerular filtration rate after converting-enzyme inhibition in essential hypertension.

To test the influence of an inhibitor of angiotensin-converting enzyme, teprotide (SQ 20881), we administered it to seven patients with essential hypertension and normal renal function and nine with an unequivocal reduction in creatinine clearance, caused by bilateral renal-artery stenosis in two and by essential hypertension in seven. Despite the fall in blood pressure (112.7 +/- 4.5 to 100.3 +/- 3.9 mm Hg, mean +/- S.E.M., P less than 0.01), there were prompt increases in both creatinine clearance (95.9 +/- 10.5 to 109.9 +/- 9.5 ml per minute per 1.73 m2 of body-surface area, P less than 0.01) and sodium excretion (17.0 +/- 5.9 to 31.7 +/- 7.2 mumol per minute, P less than 0.01) in patients with essential hypertension. The increase in glomerular filtration rate was most striking, averaging 33 per cent (66.0 +/- 10.3 to 88.0 +/- 9.2 ml per minute per 1.73 m2, P less than 0.001) in patients in whom an initial reduction was evident and hypertension was more severe. These observations suggest that a functional element, perhaps involving angiotensin-mediated renal vasoconstriction, frequently has a role in the reduction in glomerular filtration rate that occurs in essential hypertension. This class of agent may improve renal excretory function as it controls hypertension.

Angiotensin-Converting Enzyme Inhibitors↗

Increase in glomerular filtration rate in patients with insulin-dependent diabetes and elevated erythrocyte sodium-lithium countertransport.

Increased sodium-lithium countertransport in erythrocytes is found in patients with insulin-dependent diabetes mellitus (IDDM) and nephropathy. To determine whether such an increase precedes the onset of nephropathy and, if so, whether it is associated with changes in renal function, we measured erythrocyte sodium-lithium countertransport in 52 patients with IDDM but not nephropathy or hypertension and in 32 control subjects. Seventeen of the 52 patients with IDDM (33 percent) had sodium-lithium countertransport activity that exceeded the maximal activity in the control subjects (0.39 mmol of lithium per hour per liter of cells). Eighteen of the 52 patients with IDDM were studied in more detail. The 7 patients with raised sodium-lithium countertransport values had glomerular filtration rates (median, 159 ml per minute per 1.73 m2 of body-surface area; range, 134 to 197) that were significantly higher (P less than 0.01) than those in the remaining 11 patients with IDDM and normal sodium-lithium countertransport (median, 126 ml per minute per 1.73 m2; range, 110 to 176) or in the 10 control subjects (median, 128 ml per minute per 1.73 m2; range, 93 to 151). In the seven patients with elevated sodium-lithium countertransport, the filtration fraction (median, 0.27; range, 0.22 to 0.37) was also greater (P less than 0.01) than that in control subjects (median, 0.22; range, 0.18 to 0.28). There were no differences in renal function between the patients with IDDM and normal sodium-lithium countertransport and the control subjects. We conclude that sodium-lithium countertransport is increased in patients with IDDM before the onset of nephropathy and is associated with hyperfiltration. Thus, elevated sodium-lithium countertransport activity may be an early marker of diabetic nephropathy.

Adult↗

Reduction of cholera in Bangladeshi villages by simple filtration.

Based on results of ecological studies demonstrating that Vibrio cholerae, the etiological agent of epidemic cholera, is commensal to zooplankton, notably copepods, a simple filtration procedure was developed whereby zooplankton, most phytoplankton, and particulates >20 microm were removed from water before use. Effective deployment of this filtration procedure, from September 1999 through July 2002 in 65 villages of rural Bangladesh, of which the total population for the entire study comprised approximately 133,000 individuals, yielded a 48% reduction in cholera (P < 0.005) compared with the control.

Animals↗

A field-evolved differential filtration method for recovery of schistosome cercariae.

Modifications to Theron 's (1979) differential filtration technique are described which improve both sensitivity and reliability. Following pre-filtration to remove larger debris and some plankton, the sample is formalized; constant stirring prevents losses due to the cercarial stickiness normally caused by the fixation process. Once fixed, Schistosoma mansoni cercariae are reliably retained and well displayed on nylon monofilament cloth of 50 micrometers pore size. Such a coarse recovery filter permits very large samples to be processed and results in filters which are easy to read. Field comparison showed the method improved sensitivity by a factor of more than 20 times and laboratory evaluation indicated a recovery rate of over 80%.

Animals↗

Rapid delipidation of and particulate removal from human serum by membrane filtration in a tangential flow system.

Approximately 50% of the total lipids and virtually all of the colloids and particulates which impart turbidity to human serum are removed by filtration through 0.1 micrometer-poresize membrane filters in a high-volume tangential flow device. The advantages of the method over solvent extraction are: (a) no organic solvent(s) is added to the serum at any time, (b) filtrations can be performed rapidly at room temperature, (c) unstable lipoproteins and particulates are removed in 1 step, (d) scaleup from hundreds of ml to hundreds of liters is readily achievable, and(e) process time is markedly reduced.

Blood Chemical Analysis↗