Macromolecular sieving by glomerular basement membrane in vitro: effect of polycation or biochemical modifications

To evaluate the effect of biochemical modifications not possible in vivo, filters of dog glomerular basement membrane (GBM) were constructed in ultrafiltration cells in vitro. The sieving coefficients (SCs) of three protein markers of differing size and charge (native, anionic bovine albumin-BSA; cationized BSA-cBSA; and immunoglobulin G-IgG) were determined using filters of differing amounts of control GBM, and under varying transmembrane pressures (delta P). Flow rates did not increase proportionately with increasing delta P, indicating filter compressibility. Protein SCs did not change with changing delta P, but did decrease with increasing filter thickness. Control filters showed a small but definite charge selectivity (SCcBSA++ - SCBSA greater than 0); a much greater degree of size selectivity (SCcBSA - SCIgG) was observed. Hexadimethrine (HDM), a polycation which causes proteinuria in vivo, led to marked increases in protein SCs. In contrast, removal of the major population of intrinsic GBM negative charges by carboxyl group methylation only produced a small increase in the filtration of BSA, with no change in filtration of cBSA or IgG. Other biochemical modifications (heparinase or neuraminidase treatment) had no effect on filter permselectivity. Carboxyl group methylation essentially abolished filter binding of cationized ferritin, which showed substantial binding to control filters. These in vitro studies provide confirmatory evidence for a direct effect of HDM on the permselective properties of GBM. In addition, biochemical modification studies suggest a fundamental difference between the binding of an exogenous polycation to GBM anionic sites and the removal of intrinsic charges.     

Beneficial effects of intensive plasma exchange followed by immunosuppressive therapy in severe Graves' ophthalmopathy

Nine patients with severe Graves' ophthalmopathy were treated by intensive plasma exchange, followed by immunosuppression. Severity of ocular involvement and response to therapy were evaluated clinically by numerical scoring (ophthalmopathy index). Serum thyroid stimulating immunoglobulins (TSI) and urinary excretion of glycosaminoglycans (GAG) were measured immediately before and immediately after plasmapheresis. Plasma exchange was rapidly accompanied by marked clinical improvement in 8/9 patients. The most marked effects were on soft tissue involvement, proptosis, intraocular pressure, and visual acuity. The ophthalmopathy index decreased from 9.7 +/- 4.1 to 5.7 +/- 2.2 (P less than 0.001) after plasmapheresis. Serum TSI levels were initially elevated in 6 patients and remained positive in 3 patients after treatment. Urinary GAG excretion was initially 2- to 12-fold normal levels and was decreased by 60%. After plasmapheresis, patients received immunosuppressive drugs for 3-6 months. The follow-up period, after withdrawal of drugs, ranged from 5 to 38 months with a median of 17 months. The ocular condition remained stable in 6 patients. Three patients had a relapse 1 year after plasmapheresis: they were treated a second time by plasma exchange with subsequent improvement. In conclusion, intensive plasma exchange provided prompt and effective improvement in patients with severe progressive Graves' ophthalmopathy. This therapeutic procedure, followed by immunosuppression, gave long lasting results. Relapses were responsive to plasmapheresis therapy. The data suggest that plasma exchange may represent the best primary treatment for severe progressive Graves' ophthalmopathy.     

体外循环动脉微栓过滤器性能离体实验研究

目的:通过离体实验评价成人型动脉滤器(QUART)、米道斯动脉滤器(MEDOS)和宁波动脉微栓滤器的跨滤器压差和气泡去除能力。方法:分别选用QUART、MEDOS和宁波3种动脉过滤器各15个,依次为QG组、MG组和NG组,连接模拟体外循环管路,使用1 000 mL0.9%氯化钠预充环路,并在管路上连接Stockert气泡捕捉器。同时在动脉滤器的入口端、出口端和排气管处连接电子测压仪,使用管钳维持动脉滤器出口处压力为80 mmHg(1 mmHg=0.133 kPa),测定动脉滤器入口端、出口端和排气管处的压力。在流量为5.0 L/min时,于动脉滤器入口处每隔1 min加入10 mL空气,最多不超过80mL。结果:预充后NG组中9个(9/15,60.0%)动脉微栓滤器发出报警音,明显高于QG组和MG组,差异具有统计学意义(P<0.05);首次倒排时,QG、MG和NG组分别有1/15(6.7%)、13/15(86.7%)和15/15(100.0%)发出报警音,QG组明显低于MG组和NG组,差异具有统计学意义(P<0.05)。随着主泵流量的增加,3种动脉滤器入口端压力、出口端压力及压差均逐渐升高。相同流量下,3种动脉滤器入口端压力、出口端压力和压差差异均无统计学意义(P>0.05);流量为5 L/min,3组动脉滤器分别加入气体至80 mL时均未发出报警音。结论:使用动脉滤器时,排气需要2遍以上,才能安全使用。正常转机流量下,3种动脉滤器跨滤器压差基本相同。3种动脉滤器均有较强的气泡隔离能力。     

Plasma separator Plasmaflo OP

In recent years, polyethylene and polysulfone membranes have been used for plasma separation in Japan. The polyethylene membrane, manufactured by melt spinning method, has a sponge-like symmetric structure. The plasma separator Plasmaflo OP (Asahi Medical, Tokyo, Japan) with a polyethylene membrane shows excellent performance and safety for plasma separation. More than 20 indications for therapeutic plasmapheresis are reimbursed in Japan. Future development is expected in new membrane designs for new indications or advanced plasmapheresis methodologies.     

Embolic protection filters for carotid stenting: differences in flow obstruction depending on filter construction.

PURPOSE: To investigate the pressure gradient and degree of flow reduction associated with embolus protection filters for carotid stenting in an in vitro experiment. METHODS: Three filter devices with a perforated membrane design and one wire mesh type filter were tested. At a pressure of 70 mmHg, the flow reduction and pressure gradient were measured in a 5-mm tube using blood-mimicking fluid. RESULTS: The pressure gradient in the wire mesh filter was 1.65+/-0.49 mmHg (95% CI 1.32 to 1.86). The mean pressure gradient in the perforated membrane filters was 6.88+/-2.62 mmHg (95% CI 6.22 to 7.55, p<0.0001). There was also a significant correlation between pressure gradient and flow reduction (r=-0.77, p<0.01). CONCLUSION: Embolic protection filters cause a pressure gradient and obstruct blood flow. This effect is marked in perforated membrane filters and almost absent in the wire mesh filter.     

Study of plasma levels of soluble CD40 ligand in systemic lupus erythematosus patients who have undergone plasmapheresis

We studied whether soluble CD40 ligands (sCD40L) are removed by means of double filtration plasmapheresis (DFPP), and the removal may help decrease activity of systemic lupus erythematosus (SLE). We studied 10 female patients with active SLE. Double filtration plasmapheresis was conducted one or two times per week. Plasma sCD40L levels were measured before and after each round of DFPP and throughout the treatment course. The plasma sCD40L level of SLE patients was significantly higher (14.09 +/- 18.88 ng/mL) than that of healthy individuals (0.19 +/- 0.20 ng/mL; P < 0.0001). In the SLE patients, plasma sCD40L levels were significantly lower following DFPP (P = 0.0251). The plasma waste from DFPP of an SLE patient was subjected to gel filtration, and the sCD40L concentration in each fraction was measured. We observed a peak in the fraction corresponding to > or =60 kDa. These results indicate that trimers and higher order complexes of sCD40L are removed during DFPP. Plasma sCD40L level and SLE disease activity index (SLEDAI) were decreased following the treatment course (mean 9.3 months). sCD40L exists as both a monomer and trimer in the plasma of SLE patients. The trimer as well as higher-order compounds can be removed via DFPP. It was thought that removal of sCD40L via DFPP may be useful for improving the overall condition of SLE.     

Selective plasma filtration for treatment of fulminant hepatic failure induced by D-galactosamine in a pig model

BACKGROUND: Plasma exchange may be useful for treating patients with fulminant hepatic failure but during the procedure growth factors that are important for hepatic regeneration are discarded. Addition of a selective plasma filter to the plasmapheresis circuit could eliminate protein bound toxic substances and retain growth factors for hepatic regeneration. This process is called selective plasma filtration. AIMS: To determine if selective plasma filtration could be a useful treatment modality for fulminant hepatic failure. METHODS: The system was tested in five groups of pigs with fulminant hepatic failure induced by galactosamine: group I, diseased control group (n=5); group II, sham control, (n=6); group III, plasma exchange (n=6); group IV, treatment with AC-1770 selective plasma filter (n=7); and group V, treatment with AC-1730 selective plasma filter which had a smaller pore size than AC-1770 (n=7). Fresh pig plasma was given to replace filtered plasma in pigs of groups III, IV, and V. Treatment was initiated 48 hours after administration of 0.75 g/kg galactosamine. The efficacy of selective plasma filtration was assessed by survival rate and improvement in haematological, biochemical, and immunohistological parameters. RESULTS: Pigs treated with AC-1770 or AC-1730 selective plasma filters survived longer than the other groups (group I: 55 (10) hours; group II: 68 (7) hours; group III: 91 (10) hours; group IV: 269 (156) hours; group V: 950 (555) hours). One pig in group IV survived for 50 days; one pig in group V survived for 77 days and another pig in group V is still alive (>150 days). After treatment, plasma levels of aspartate aminotransferase, bilirubin, bile acid, ammonia, lactate dehydrogenase, and alpha-glutathione-S-transferase decreased. Substantial amounts of tumour necrosis factor alpha (TNF-alpha) and endotoxin were found in the filtrate. The selective plasma filtration groups retained significantly higher amounts of hepatocyte growth factor than plasma exchange alone. Similar TNF-alpha clearance was observed in the selective plasma filtration groups and the plasma exchange group. On day 4, significant improvement in liver function, as measured by the indocyanine green clearance test, was observed in groups IV and V but not in the other groups. A higher regeneration index of hepatocytes was also observed in the groups treated with AC-1770 and AC-1730 selective plasma filters. CONCLUSION: Selective plasma filtration improved survival time and expedited liver regeneration in pigs with fulminant hepatic failure.     

Plasmapheresis--an international determination of status

The development of the therapeutic plasmapheresis reaches from the beginnings of the centrifugation technique in the early fifties and the appearance of membrane plasma filters in the late seventies up to numbers of treatment of about a quarter of a million a year all over the world. Instead of the former uncritical euphoria in the selection of patients nowadays a strict indication occupied the position. Efforts all over the world to confirm scientifically the efficacy of the plasmapheresis have not been finished up to now. Geographical differences in the diagnosis are in most cases the sequels of subjective factors of locally dominating working teams, which is demonstrated on the basis of international statistics. Specific modifications such as cascade filtration and plasma absorption are described.     

Ability to Remove Immunoglobulins and Antiganglioside Antibodies by Double Filtration Plasmapheresis in Guillain-Barré Syndrome: Is It Equivalent to Plasma Exchange?

Abstract: The value of plasma exchange (PE) in Guillain-Barré syndrome (GBS) is well established. In Japan, patients with GBS and related diseases often receive double filtration plasmapheresis (DFPP) as well as PE. No comparative trials between PE and DFPP, however, have been conducted. We compared their abilities to remove immunoglobulins and antiganglioside antibodies to find out whether DFPP is equivalent to PE. The ability to remove immunoglobulins and antiganglioside antibodies was compared between PE and DFPP using plasma samples from 41 patients with GBS and related diseases before and after each treatment session. The ability of DFPP to remove both IgGs and antiganglioside IgG antibodies were significantly inferior to those of PE. There is a less theoretical basis for selecting DFPP as the first choice of plasmapheresis for GBS and related disorders.—     

Comparison of Five Different Filters for the Removal of Leukocytes from Red Cell Concentrates

The leukocyte depletion capacity and performance of 5 filters designed for filtration of red cell concentrates (RCC) were compared by counting leukocytes, measuring red cell volumes and by histological examination of the filters after use. To eliminate interdonor differences, 5 buffy-coat-poor RCC were pooled (in each of 10 experiments) and subsequently split up into the original bags. The RCC were passed over the Cellselect filter, a column filled with cellulose acetate, and over flat-bed polyester filters: the Cellselect Optima, the Pall RC 50, the Leukostop and the Sepacell R-500. The filtration was shortest with the Pall RC 50 (p less than 0.001 compared to the other 4 filters). Leukocyte removal was most effective with the cellulose acetate filter (p less than 0.01 compared to the other 4 filters) followed by the Cellselect Optima polyester filter (p less than 0.02 compared to the remaining 3 filters). Residual leukocytes did not exceed 50 x 10(6) for any brand of filter. Red cell recovery was similar for all 5 filters with mean values from 86.1 to 89.2%. The leukocyte numbers, counted in Türk's solution or in propidium iodide, gave comparable values in hemocytometers applying light microscopy or fluorescent microscopy, respectively. Histological examination showed that lymphocytes were mainly removed by trapping, whereas granulocytes showed a variable pattern: adhesion in presence of platelets or trapping.     

Systemic, splanchnic and renal hemodynamic effects of a dopaminergic dose of dopamine in patients with cirrhosis

The effects of dopamine on kidney function have not been elucidated in patients with cirrhosis. Moreover, although increased portal pressure has been observed with supradopaminergic doses of dopamine in these patients, the splanchnic hemodynamic effects of low doses of dopamine have not been previously studied. Thus we studied the acute systemic, splanchnic and renal hemodynamic effects of a dopaminergic dose of dopamine (1.5 micrograms/kg body wt min) in nine cirrhotic patients. Plasma dopamine levels increased markedly from 35 +/- 20 pg/ml to 31,400 +/- 4,900 pg/ml during dopamine administration. A significant diastolic pressure decrease of 10% was associated with a 15% increase in heart rate. Cardiac output was not altered. Although dopamine significantly increased azygos blood flow by 16%, wedged and free hepatic venous pressures were not altered. Dopamine significantly increased renal blood flow by 31%, but did not change the glomerular filtration rate. We conclude that a dopaminergic dose of dopamine increases azygos blood flow but not the hepatic venous pressure gradient. Finally, although it increases renal blood flow, dopamine does not seem to have any beneficial effects on glomerular filtration rate in cirrhotic patients.     

Acute effects of a somatostatin analogue on kidney function in type 1 diabetic patients

Suppression of growth hormone by means of somatostatin has been suggested as a possible adjunct therapy in Type 1 diabetes. To assess the acute effect of the somatostatin analogue SMS 201-995 on kidney function in uncomplicated Type 1 diabetes, 13 normoalbuminuric, normotensive diabetic patients were investigated before and during IV infusion of SMS 201-995 (8 micrograms h-1). A control experiment with infusion of carrier only was also performed. The SMS infusion induced a reduction in the glomerular filtration rate (clearance of 125I-iothalamate) and renal plasma flow (131I-hippuran) from 140 +/- 15 (mean +/- SD) and 550 +/- 69 to 131 +/- 14 (2p less than 0.005) and 492 +/- 73 ml min-1 1.73-m-2 (2p less than 0.001), while filtration fraction and total renal resistance rose (both 2p less than 0.001). Urinary albumin excretion rate, blood pressure, and blood glucose concentration were unchanged. Plasma growth hormone and glucagon were significantly suppressed. The reduction in glomerular filtration rate and renal plasma flow correlated with the fall in glucagon concentration (r = 0.57, 2p = 0.04, and r = 0.63, 2p = 0.02). The urinary flow rate was markedly reduced, urine osmolality increased, and fractional excretion of sodium, calcium, and phosphate were reduced. Arginine vasopressin, atrial natriuretic peptide, angiotensin II, and aldosterone were unchanged by the SMS infusion. Thus SMS 201-995 acutely reduces glomerular filtration rate and renal plasma flow in uncomplicated Type 1 diabetes and has an antidiuretic effect. The effects may be related to suppression of glucagon secretion.     

Estimation of the filtration variables in the rat lung

The filtration variables, filtration coefficient (K), perimicrovascular pressure (Ppmv) and reflection coefficient (sigma) were estimated independently in previous reports using the Starling Equation or the micropuncture method. We estimated these variables simultaneously. We measured filtration rate by a gravimetric method in isolated rat lung lobes in zone 1 conditions (alveolar pressure = 20 cmH2O) at two vascular pressures, Pvasc = 15 or 8 cmH2O and perfused the lobes with plasma containing a low or high concentration of protein. By extrapolating the log of the rate of weight gain to time = 0, we obtain the initial filtration rate. Assuming that protein filtered into perimicrovascular space only by convection, we substituted into the Starling Equation as follows: Q = K[(Pmv-Ppmv)-sigma 2 pi mv], where Pmv and pi mv are hydrostatic and plasma protein osmotic pressures in microvascular space. pi mv was estimated by Yamada's equation. We obtained K = 26.3 +/- 8.7 mg/(min.cmH2O.g), PPMV = 6.2 +/- 0.7 cmH2O, sigma = 0.46 +/- 0.07. The chief advantages of this method are that it does not require a separate estimation of isogravimetric pressure or a direct measurement of interstitial pressure, and that all variables are obtained simultaneously.     

Transfusion Results of Filtered and Subsequently Stored Random Platelet Suspensions Prepared from Buffy Coats

There is almost general agreement that removal of leukocytes from blood components reduces the incidence of HLA-antibody formation and refractoriness to random platelet transfusions. Recently filters have become available, which are able to reduce leukocyte contamination in platelet suspensions with acceptable platelet loss. We evaluated a cellulose acetate (CA) and a polyester (PE) filter, and stored buffy coat-derived platelet suspensions after filtration. Both filters are effective for the removal of leukocytes to levels below 5 x 10(6) per transfusate. For the CA filter, platelet recovery was 73 +/- 13% yielding 256 +/- 53 x 10(9) platelets per transfusate from 6 donors. For the PE filter, platelet recovery was 90 +/- 9% and 327 +/- 51 x 10(9) platelets per transfusate. When a loading dose of less than 5 x 10(8) leukocytes was applied, 98% of the CA-filtered suspensions and 100% of the PE-filtered suspensions contained less than 5 x 10(6) residual leucocytes. In 123 patients transfusion results of CA-filtered platelet suspensions stored for 72 h, were compared with those obtained by non-stored, non filtered, random platelet suspensions which had been leukocyte depleted by differential centrifugation. Platelet increments 1 and 20 h after transfusion showed no statistical difference between CA-filtered platelet transfusions stored for 72 h and non-stored, non-filtered platelet transfusions. In a new cohort of 117 patients, two filters and various postfiltration storage times were compared. Using both filters, the 1-hour posttransfusion increments decreased to approximately 60% after 96 h of storage compared to results of storage periods of 72 h or less.(ABSTRACT TRUNCATED AT 250 WORDS)     

Atrial natriuretic factor in hypertension: bioactivity at normal plasma levels

To ascertain whether small shifts in plasma atrial natriuretic factor (ANF) exerted biological effects in hypertension, we studied the renal, hemodynamic, and hormonal effects of ANF [human ANF-(99-126)] infused at a dose (0.75 pmol/kg/min for 3 hours) that would induce changes in plasma ANF confined to the normal, resting range, in a group of six young men with uncomplicated, mild essential hypertension. During ANF infusions, the patients excreted 11.8 +/- 2.0 mmol (mean +/- SEM) sodium more than during the time-matched placebo phase natriuresis (p less than 0.001, mean increase of 53% above placebo values). Urinary excretion of cyclic guanosine monophosphate rose to more than double (212%, p less than 0.001) placebo values. Plasma renin activity (0.4 +/- 0.05 vs. 0.9 +/- 0.12 nmol/l/hr, p less than 0.0001) and aldosterone concentrations (102 +/- 4 vs. 184 +/- 47 pmol/l, p less than 0.05) were clearly suppressed during administration of ANF. Plasma norepinephrine also fell significantly below placebo values (268 +/- 17 vs. 439 +/- 35 pg/ml, p less than 0.05). Urine volume, the excretion of electrolytes other than sodium, hematocrit, effective renal plasma flow, glomerular filtration rate, and filtration fraction were unaffected by ANF. Similarly, plasma concentrations of epinephrine, arginine vasopressin, adrenocorticotropic hormone, and cortisol were unchanged. Blood pressure and heart rate were unchanged. Minor perturbations in plasma ANF concentrations exert clear biological effects in patients with mild essential hypertension. These data suggest that such minor shifts in plasma ANF are of physiological relevance in mild hypertension and probably contribute to volume homeostasis in this condition.     

Control of arterial pressure and renal function during chronic renin inhibition

The aim of this study was to determine whether the renin inhibitor CP-71362 (Pfizer Central Research, Groton, Connecticut, USA) is capable of inducing sustained reductions in arterial pressure in sodium-depleted dogs and to examine the changes in renal function associated with chronic renin inhibition. In addition, we also examined the chronic effects on renal function and blood pressure of the angiotensin converting enzyme (ACE) inhibitor enalaprilat. Infusion of CP-71362 (1.1 micrograms/kg per min, intravenously) for 7 days decreased mean arterial pressure from 87 +/- 3 to 75 +/- 2 mmHg, while causing no significant changes in sodium excretion, the glomerular filtration rate, or effective renal plasma flow. Plasma renin activity was suppressed to undetectable levels throughout the 7 days of CP-71362 infusion. Infusion of enalaprilat (4 mg/kg per day) for 7 days in sodium-depleted dogs decreased mean arterial pressure (from 85 +/- 2 to 64 +/- 3 mmHg) and renal vascular resistance, and increased effective renal plasma flow and sodium excretion, but caused no significant changes in the glomerular filtration rate. Thus CP-71362 is a potent inhibitor of dog plasma renin, and we observed no waning of this inhibitory effect of CP-71362's hypotensive actions over 7 days. The mechanisms responsible for the differences in the blood pressure and renal responses to CP-71362 and ACE inhibition are not clear, but may be dose-related or due to differences in the distribution of these compounds to various tissues, including the kidney.     

Comparison of selectivity of LDL removal by double filtration and dextran-sulfate cellulose column plasmapheresis, and changes of subfractionated plasma lipoproteins after plasmapheresis in heterozygous familial hypercholesterolemia

The possibility of selective removal of low density lipoprotein (LDL) by double filtration (DF) and dextran-sulfate cellulose (DSC) column plasmapheresis in hypercholesterolemia and the acute recovery process of the subfractionated plasma lipoproteins after plasmapheresis in heterozygous familial hypercholesterolemia were investigated. Sixty-six percent of the LDL cholesterol and 42% of the HDL cholesterol were removed by 2.5 L DF plasmapheresis with the second filters having average pore diameters of 30 nm and 40 nm. Fifty-nine percent of the LDL cholesterol was removed by 2.5 L DSC column plasmapheresis, while HDL cholesterol did not change. Therefore, DSC column plasmapheresis could remove LDL much more specifically than DF plasmapheresis. VLDL increased rapidly and reached the preplasmapheresis level within four days after plasmapheresis. IDL returned to the preplasmapheresis level in 2 weeks. The LDL1 level was approximately 80% of the preplasmapheresis level on the 14th day. LDL2 reached the peak at the seventh day. HDL2 and HDL3 moved in the same manner and reached the peak on the seventh day after DF plasmapheresis.     

Effect of pentoxifylline on hemodynamics, alveolar fluid reabsorption, and pulmonary edema in a model of acute lung injury

We investigated the effect of pentoxifylline (PTX) on the development of pulmonary edema in a model of adult respiratory distress syndrome in rabbits. Lung injury was induced by repeated saline lavages in adult rabbits weighing 2.5 to 3.5 kg. Rabbits pretreated with PTX (20 mg/kg bolus followed by 20 mg/kg/h infusion) developed significantly lower amounts of lung edema 4 h after saline lavage (extravascular lung water to dry weight ratio [W/D], 6.9 +/- 0.6 SD versus 8.9 +/- 0.5 in control animals). PTX produced a 25% increase in cardiac output, but there were no differences between treated and untreated groups in calculated pulmonary vascular resistance or microvascular pressure. To determine whether PTX could have lowered pulmonary venous resistance and thus lowered effective microvascular pressure for fluid filtration, we directly measured pulmonary artery and left atrial pressures, and measured by micropuncture the pressure in 20 to 40 microns subpleural venules in four open-chested rabbits 3 to 4 h after lavage. Venous resistance was low (venous pressure drop 0.9 +/- 0.1 mm Hg) and was unchanged by PTX infusion. To determine if PTX decreased lung water by accelerating active alveolar fluid reabsorption, a single 60-ml aliquot of saline was instilled into the lungs of normal rabbits treated with saline or PTX. Both groups had a similar decrease in lung water content 1 and 4 h later. Our data indicate that PTX reduces edema formation in rabbits after saline lavage, not by lowering microvascular pressures for fluid filtration or by acceleration alveolar fluid reabsorption, but possibly by its anti-inflammatory effect on neutrophil function.     

Plasmapheresis and Paraproteinemia: Cryoprotein-Induced Diseases,Monoclonal Gammopathy,Waldenström's Macroglobulinemia,Hyperviscosity Syndrome,Multiple Myeloma,Light Chain Disease,and Amyloidosis

Therapeutic plasmapheresis has been in widespread use as either a primary or adjunctive therapy in the United States since the 1960s. There are several types of plasmapheresis procedures used to treat various diseases. Plasma exchange with a centrifugal plasma separator using replacement fluid such as human albumin solution is the most widely used method in the United States. Other forms of plasmapheresis include membrane plasma separation, membrane fractionation, cryofiltration apheresis, immunoadsorption, and chemical affinity column pheresis. Therapeutic plasmapheresis has been used for the treatment of paraproteinemia to remove harmful paraproteins. Paraproteinemia is a disease classification in which abnormal or large amounts of plasma proteins such as cryoproteins or immunoglobulins are produced. In most cases, plasmapheresis is used in combination with corticosteroids and immunosuppressive drugs to prevent production of abnormal proteins or to treat the underlying disease. Cryoprotein-induced diseases, which include cryoglobulinemia, cryofibrinogenemia, and cold IgM antibody agglutinin with cryoglobulin properties, are a subclass of paraproteinemia. Other categories of paraproteinemia include monoclonal gammopathy, Waldenström's macroglobulinemia, hyperviscosity syndrome, multiple myeloma, light chain disease, and amyloidosis. Some of these diseases may be interrelated, and they may be associated with one another. In this review paper, we discuss the role of plasmapheresis in the specific classes of paraproteinemia in the United States, including our own experience.     

Prospective evaluation of a method for estimating ascending aortic pressure from the radial artery pressure waveform

Pressure wave reflection in the upper limb causes amplification of the arterial pulse so that radial systolic and pulse pressures are greater than in the ascending aorta. Wave transmission properties in the upper limbs (in contrast to the descending aorta and lower limbs) change little with age, disease, and drug therapy in adult humans. Such consistency has led to use of a generalized transfer function to synthesize the ascending aortic pressure pulse from the radial pulse. Validity of this approach was tested for estimation of aortic systolic, diastolic, pulse, and mean pressures from the radial pressure waveform. Ascending aortic and radial pressure waveforms were recorded simultaneously at cardiac surgery, before initiation of cardiopulmonary bypass, with matched, fluid-filled manometer systems in 62 patients under control conditions and during nitroglycerin infusion. Aortic pressure pulse waves, generated from the radial pulse, showed agreement with the measured aortic pulse waves with respect to systolic, diastolic, pulse, and mean pressures, with mean differences <1 mm Hg. Control differences in Bland-Altman plots for mean+/-SD in mm Hg were systolic, 0.0+/-4.4; diastolic, 0.6+/-1.7; pulse, -0.7+/-4.2; and mean pressure, -0.5+/-2.0. For nitroglycerin infusion, differences respectively were systolic, -0.2+/-4.3; diastolic, 0.6+/-1.7; pulse, -0.8+/-4.1; and mean pressure, -0.4+/-1.8. Differences were within specified limits of the Association for the Advancement of Medical Instrumentation SP10 criteria. In contrast, differences between recorded radial and aortic systolic and pulse pressures were well outside the criteria (respectively, 15.7+/-8.4 and 16.3+/-8.5 for control and 14.5+/-7.3 and 15.1+/-7.3 mm Hg for nitroglycerin). Use of a generalized transfer function to synthesize radial artery pressure waveforms can provide substantially equivalent values of aortic systolic, pulse, mean, and diastolic pressures.