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Atrial natriuretic peptide augments forearm capillary filtration in humans.

Low-dose infusions of atrial natriuretic peptide (ANP) into humans reduce cardiac filling pressures without enhancing renal excretion or producing vasodilation. The present human study was undertaken to seek an effect of ANP on capillary filtration in humans and to determine its relationship to reductions in cardiac filling pressures. Heart rate (electrocardiogram), blood pressure (cuff method), and renal excretion of salt and water were determined, and central venous pressure (jugular vein cannulation, strain-gauge transducer) and forearm venous compliance and capillary filtration coefficient (strain-gauge plethysmography) were derived by computer. Forearm girth and venous pressure (peripheral vein catheter) measurements were obtained while the arm was elevated above heart level, and an upper arm blood pressure cuff was intermittently inflated to venous occluding pressures of 20, 30, and 40 mmHg. Forearm measurements, hematocrit, plasma proteins, albumin and plasma levels of ANP were determined from euvolemic volunteers before and during 60 min intravenous infusions of ANP (5 ng.kg-1.min-1, n = 9) or placebo (isotonic saline, n = 7). ANP infusions produced physiological increases (4- to 5-fold) in plasma ANP (from a base line 35 +/- 6 pg/ml) (P less than 0.05). Hemodynamic responses to ANP consisted of a reduction in central venous pressure (P less than 0.05) and no change in heart rate, mean arterial pressure, or renal excretory parameters. ANP increased forearm capillary filtration between 37 and 63% (P less than 0.05) from base line but did not significantly alter forearm compliance measurements.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Mechanisms underlying enhanced capillary filtration induced by platelet-activating factor.

Fluid filtration rate with respect to surface area (Jv/S) from rat mesenteric capillaries was measured before and after platelet-activating factor (PAF) superfusion, a model of acute inflammation. Jv/S increased from a baseline value of 0.015 +/- 0.003 to 0.033 +/- 0.003 micron/s (n = 7 rats, P < 0.01) during PAF superfusion. Measurements of arteriolar pressure with a servo-nulling pressure system suggest that the dominant factor causing the increase in Jv/S during PAF superfusion is increased capillary permeability, rather than an increase in pressure. Jv/S did not increase when PAF superfusion was preceded by administration of the radical-scavenging enzymes catalase and superoxide dismutase, implicating a role for oxygen radicals in the PAF-induced capillary filtration. In another series of studies, three experiments were performed, i.e., PAF superfusion alone or PAF superfusion plus treatment with either a soluble form of sialyl-Lewisx oligosaccharide (SLex) or a nonbinding form of SLex (SLN). These experiments revealed that the increased Jv/S normally elicited by PAF is significantly blunted by administration of soluble SLex but not by the control oligosaccharide SLN. The results of this study invoke a role for oxygen free radicals and selectins (ligands for SLex) in the enhanced capillary fluid filtration elicited by PAF.

Animals↗

Starling forces that oppose filtration after tissue oncotic pressure is increased.

We tested the hypothesis that the effective oncotic force that opposes fluid filtration across the microvessel wall is the local oncotic pressure difference across the endothelial surface glycocalyx and not the global difference between the plasma and tissue. In single frog mesenteric microvessels perfused and superfused with solutions containing 50 mg/ml albumin, the effective oncotic pressure exerted across the microvessel wall was not significantly different from that measured when the perfusate alone contained albumin at 50 mg/ml. Measurements were made during transient and steady-state filtration at capillary pressures between 10 and 35 cmH(2)O. A cellular-level model of coupled water and solute flows in the interendothelial cleft showed water flux through small breaks in the junctional strand limited back diffusion of albumin into the protected space on the tissue side of the glycocalyx. Thus oncotic forces opposing filtration are larger than those estimated from blood-to-tissue protein concentration differences, and transcapillary fluid flux is smaller than estimated from global differences in oncotic and hydrostatic pressures.

Animals↗

Effect of hypercapnia on net filtration of fluid in the lungs of awake newborn lambs.

To study the effect of hypercapnia on net transvascular filtration of fluid in newborn lungs, we measured pulmonary arterial and left pressures and collected lung lymph from 11 awake 2-wk-old lambs as they spontaneously breathed a gas mixture rich in carbon dioxide. After a 2-h control period in air, the lambs breathed 8-11% carbon dioxide mixed with air and nitrogen for 2-6 h. Average pulmonary arterial pressure and blood flow to the lungs increased during hypercapnia, but pulmonary vascular resistance did not change. In all cases, hypercapnia led to an acute transient increase in lymph flow. During sustained hypercapnia, however, flow of lymph was not significantly different from flow measured during the control period. The concentration of protein in lymph decreased at the onset of hypercapnia and remained low during sustained hypercapnia. These results suggest that acute hypercapnia increases net filtration by increasing the transvascular gradient of hydraulic pressure, whereas, in a "steady-state," neither hypercapnia nor the tachypnea that accompanies it alters net transvascular filtration of fluid in the lungs of unanesthetized newborn animals.

Animals↗

Original waveform of lung sound crackles: a case study of the effect of high-pass filtration.

In lung sound research, low-frequency noise usually disturbs the sound signal being recorded. Some researchers therefore use high-pass filtration before the final analysis. In this study, the effect of digital and analog high-pass filtration on the morphology of the lung sound crackles is evaluated. The original nonprefiltered crackle waveform is presented, and the effect of the high-pass filtration on the crackle waveform characteristics is elucidated in one patient with silicoasbestosis.

Acoustics↗

Effect of interstitial edema on lung lymph flow in goats in the absence of filtration.

We tested the effect of interstitial edema on lung lymph flow when no filtration occurred. In 16 anesthetized open-thorax ventilated supine goats, we set pulmonary arterial and left atrial pressures to nearly zero and measured lymph flow for 3 h from six lungs without edema and ten with edema. Lymph flow decreased exponentially in all experiments as soon as filtration ceased. In the normal lungs the mean half time of the lymph flow decrease was 12.7 +/- 4.8 (SD) min, which was significantly shorter (P less than 0.05) than the 29.1 +/- 14.8 min half time in the edematous lungs. When ventilation was stopped, lymph flow in the edematous lungs decreased as rapidly as in the normal lungs. The total quantity of lymph after filtration ceased was 2.7 +/- 0.8 ml in normal lungs and 9.5 +/- 6.3 ml in edematous lungs, even though extravascular lung water was doubled in the latter (8.4 +/- 2.4 vs. 3.3 +/- 0.4 g/g dry lung, P less than 0.01). Thus the maximum possible clearance of the interstitial edema liquid by the lymphatics was 6.3 +/- 4.8%. When we restarted pulmonary blood flow after 1-2 h in four additional goats, lymph flow recovered within 30 min to the baseline level. These findings support the hypothesis that lung lymph flow originates mainly from alveolar wall perimicrovascular interstitial liquid and that the contribution of the lung lymphatic system to the clearance of interstitial edema (bronchovascular cuffs, interlobular septa) is small.

Animals↗

Familial homozygous hypercholesterolemia: effective long-term treatment with cascade double filtration plasmapheresis.

BACKGROUND: Homozygous familial hypercholesterolemia (FH) is a rare disease with an incidence of 1 in 1 million births. It is characterized by blood cholesterol levels over 600 mg/dl and the development of extensive cutaneous xanthomata before the age of 5. Severe premature coronary artery disease results in fatal myocardial infarctions within the first two decades of life. The absence of LDL receptors makes homozygous FH resistant to treatment with most HMG-CoA reductase inhibitors, and alternative methods of removing cholesterol have been employed. METHODS: We used the ASAHI plasauto-IQ double filtration cascade plasmapheresis to treat 2 young brothers aged 14 and 11 years and 6 months for 5 years and 1 month and 3 years and 10 months, respectively. The elder brother has received 136 double filtration treatments at 2-week intervals and the younger brother 100 such treatments without complications. RESULTS: During the period of treatment the average pretreatment total serum cholesterol level for patient 1 was 442 mg/dl. The average posttreatment value was 163 mg/dl. The average fall in total serum cholesterol with each treatment was 63.2%. The mean total serum cholesterol for all the periods of treatment was calculated at 303 mg/dl. For the 2nd patient, the average pretreatment value of total serum cholesterol was 435 mg/dl. The posttreatment value was 124 mg/dl and the average fall 71.5%. The calculated mean total serum cholesterol for all periods of treatment was 280 mg/dl. CONCLUSIONS: Double filtration cascade plasmapheresis at 2-week intervals provides an effective and safe long-term treatment for patients with homozygous FH. The achieved reduction in serum cholesterol allows complete resolution of cutaneous xanthomata, arrests previous atherosclerosis, and prolongs normal life.

Adolescent↗

Mathematical model to characterize internal filtration.

Convective-diffusive dialysis techniques have recently gained considerable favor. Indeed, convective fluxes through dialyzer membranes have been demonstrated to play a role in enhancing the clearance of middle-molecular-weight solutes. An interesting opportunity is given by exploiting the internal filtration (IF)/back filtration mechanism that occurs spontaneously in high-flux dialyzers, but is difficult to quantify. In view of overcoming this drawback, a semi-empirical, lumped-parameter mathematical model for characterization of IF phenomena was developed. The model considers a dialyzer as composed by N adjacent axial blocks. For each block, hydrodynamics in the blood and dialysate compartments are determined considering hydraulic resistance and calculating local filtration. Blood viscosity and oncotic pressure are calculated locally based on hematocrit and protein concentration. Resistance parameters were determined experimentally for the BS-UL (Toray Industries Inc., Tokyo, Japan) dialyzers. The set of equations describing the model, implemented into a software program, is solved using a numerical method. Simulations allow highlighting the role of device-, treatment- and patient-dependent parameters in affecting IF. Provided an extensive validation is carried out, the use of a mathematical model could be the key to make IF more understandable and its use reliable in clinical practice.

Computer Simulation↗

Application of an automated plasma filtration device and a blood monitoring system for LDL apheresis.

This study describes the adaptation of a filtration separation device (AK 10 from Gambro, München, FRG) and a blood monitor system (BTS 100 from Diamed, Köln, FRG) to the automated adsorption/desorption device for LDL apheresis. Plasma separation by filtration was performed by a hollow-fiber filter (OP5, Asahi Corp., Japan). In order to evaluate the quality of the plasma obtained by filtration, the platelet contamination, the activity of factors V and VIII and the concentration of the immunoglobulins IgG and IgM were determined. The following results were found: Platelet contamination of the plasma was 2,740/microliters. As compared to the patient's pretreatment values, activity of factor V was 94%, activity of factor VIII was 104%, concentration of IgG was 96%, concentration of IgM was 94%. Ten LDL aphereses were evaluated: red cell counts, platelet counts, hemoglobin concentration and hematocrit were not changed significantly. Thus, this new combination system represents an improved alternative to previously performed centrifugation methods.

Blood Cell Count↗

Microvascular filtration is increased in postural tachycardia syndrome.

BACKGROUND: Postural tachycardia syndrome (POTS) is related to defective peripheral vasoconstriction of dependent extremities with redistributive hypovolemia. METHODS AND RESULTS: To test whether enhanced microvascular filtration produces leg enlargement, we studied 12 patients 13 to 19 years of age with POTS and defective leg vasoconstriction and 13 age-matched healthy control subjects, with strain-gauge plethysmography used to measure venous pressure (Pv), forearm and calf blood flow, vascular capacitance, and the microvascular filtration coefficient (Kf). Measurements were made while the patient was supine and at steady state during upright tilt to 35 degrees. Supine Pv was not different in POTS, but upright leg Pv tended to be increased above control. Arm and leg peripheral arterial resistance was decreased in the supine and upright positions in patients with POTS compared with control subjects (P=0.01, upright legs). Supine Kf was not significantly increased in the forearm in patients with POTS but was increased in the calf (9.3+/-2.2 versus 5.7+/-2.4 [10(-3)] mL/100 mL per minute per mm Hg, P=0.04), correlating with calf blood flow (rs=0.84, P=0.002). Kf was invariant with orthostasis. The hydraulic contribution to upright filtered flow at 35 degrees tilt, the product of Kf and Pv, was approximately twice that of control (0.41+/-0.09 versus 0.19+/-0.04 mL/100 mL per minute, P=0.04). CONCLUSIONS: Increased microvascular filtration accounts for enhanced leg swelling in patients with POTS with increased arterial blood flow.

Adolescent↗

Immunoelectrophoresis of Mycobacterium tuberculosis antigens. Comparative analysis of cell extract and culture filtrate antigens.

Immunoelectrophoretic analyses were performed on a cell extract and culture filtrate of Mycobacterium tuberculosis, H37Rv strain using homologous polyvalent goat antisera. General similarity between the cell extract and culture filtrate antigens was found. Significant variation between two anti-culture filtrate antisera was observed. These antigens and antisera also differed significantly from previously described reference reagents. These findings demonstrate the necessity of using reference materials for precise identification of mycobacterial antigens in comparative studies.

Animals↗

Decorin modulates wound healing in experimental glaucoma filtration surgery: a pilot study.

PURPOSE: To analyze the effect of perioperative decorin in an experimental setting of glaucoma filtration surgery. METHODS: Glaucoma filtration surgery, similar to that performed in clinical practice, was performed on 35 chinchilla rabbits (ChBB:CH). The animals received a unilateral subconjunctival injection of decorin (40-100 microg) or the vehicle alone before surgery and at different time intervals thereafter. Antifibrotic efficacy was established by clinical response and histologic examination. The animals were killed on day 14, and the eyes processed for histology. RESULTS: Both the vehicle and the decorin solution were well tolerated. No adverse effects such as inflammation or blurring of the optical media were observed. Conjunctival scarification occurred within 1 week in the control groups but was suppressed in the experimental groups. The intraocular pressure correlated with the fibrotic process and reached normal levels within 7 days after surgery in control animals, but remained significantly (P <0.001) reduced in the experimental groups. Histologic examination of the surgical area 14 days after surgery disclosed massive fibrosis in the control animals, but little deposition of extracellular matrix in the experimental groups. CONCLUSIONS: The data of this pilot study suggest that perioperative subconjunctival decorin applications significantly affect conjunctival scarring and surgical outcome of glaucoma filtration treatments in rabbits.

Animals↗

Studies on the purification of antihemophilic factor (factor VIII). II. Separation of partially purified antihemophilic factor by gel filtration of plasma.

A high degree of purification of antihemophilic factor was achieved by filtration of chylomicronpoor human plasma through columns of agarose. The final product contained, on the average, 67 units of antihemophilic activity per mg of protein, and was 3360-fold purified compared with the filtered plasma. The molecular weight of antihemophilic factor appeared to be at least two million. Preparations separated by gel filtration were contaminated with appreciable amounts of plasma thromboplastin antecedent (PTA), and traces of Christmas factor and Hageman factor, but no detectable fibrinogen was present. Similar fractions of plasma prepared from the blood of patients with classic hemophilia, von Willebrand's disease, or a circulating anticoagulant directed against antihemophilic factor contained, on the average, somewhat less protein than normal plasma; whether this difference was significant is not yet known. The purified fractions were partially stabilized by the addition of 1% gelatin. Adaptation of the technique of gel filtration to purification of antihemophilic factor for clinical use remains to be explored.

Anticoagulants↗

The influence of HES on the filtration properties of capillary membrane plasmaseparation.

Plasmaseparation is a treatment under discussion for critically ill patients, especially in sepsis and multiorgan failure. These patients receive a variety of different fluid substitutes, including hydroxyethylstarch (HES). HES is known to influence rheological properties, but nothing is known about the possible interactions between HES and the plamaseparation procedure. We used an in vitro plasmaseparation circuit with heparinized porcine blood. Before priming the system, 2 liters of blood were supplemented by adding 100 ml of either NaCl 0.9% or HES (n=6 in each group). We monitored the transmembrane (TMP) and the filtration pressure (PF) and measured free plasma hemoglobin (free Hb) and platelet counts before and after the two hours plasmaseparation procedure. The final transmembrane pressure was significantly higher with HES substitution. In the HES group we found negative filtration pressures from the very beginning with a significant further decrease toward the end of the experiments. A significant increase in free Hb and decrease in platelet counts were noted only in the HES group. Volume substitution with HES leads to impaired filtration properties and deteriorated hemocompatibility in in vitro plasmaseparation. Further studies have yet to evaluate whether or not the effects described also occur under clinical conditions.

Animals↗

Plasma filtration adsorption dialysis (PFAD): a new technology for blood purification.

Severe sepsis is one of the most significant challenges in critical care. Despite all the developments achieved in infectious diseases and critical care, along with numerous attempts to develop treatments, the mortality rate of severe sepsis and septic shock remains unacceptably high. The pathophysiology of severe sepsis and septic shock is only partially understood. Circulating pro- inflammatory and anti-inflammatory mediators appear to participate in the complex cascade of events which leads to deranged microcirculatory function, as we know from the peak concentration hypothesis. Therapeutic trials targeting single pro-inflammatory and anti-inflammatory mediators failed to demonstrate any benefit, suggesting that the unselective removal of different mediators may be a more appropriate approach. In severe sepsis several blood purification techniques, such as continuous hemofiltration (CVVH), high volume hemofiltration (HVHF), pulse high volume hemofiltration (HVHF), plasma filtration, plasma dsorption, coupled plasma filtration adsorption (CPFA), have been proposed but such techniques appear to have both theorical as well as practical limitations. Plasma Filtration Adsorption Dialysis (PFAD) is a new extracorporeal treatment which combines different principles of blood purification in a single device. The core of this technique is a new dialyzer composed by three suitable compartments that provide specific functions. The association of multiple principles permits specific removal of molecules implicated in the pathophysiology of patient's disease and re-establishment of hydro-electrolyte, acid-base equilibrium, if renal dysfunction-failure is present. The final target of PFAD is to obtain complete purification by combining principles of physics and chemistry to remove hydrophilic and hydrophobic molecules with a very wide range of weights.

Adsorption↗

Effects of membrane adhesion barriers on wound healing reaction after glaucoma filtration surgery: a comparative study with Interceed and Seprafilm.

PURPOSE: To evaluate and compare the effectiveness of two adhesion barriers, Interceed and Seprafilm, on wound heal ing reaction after glaucoma filtration surgery. MATERIALS AND METHODS: Full-thickness filtration surgery was carried out on three groups, each containing four rabbits. Interceed and Seprafilm prepared in 3 x 4 mm dimensions was put on and around scleral opening in Groups 1 and 2, respectively. All groups received tobramycin and dexamethasone drops tid for 14 days. Intraocular pressure (IOP), anterior chamber depth, and bleb appearance were checked on the first, third, seventh, and 14th days. The rabbits were killed on the 14th day and the trabeculectomy area with overlying conjunctiva was excised. The samples were fixed wi th 10% formalin, buried in paraffin, and stained with hematoxylin and eosin. The surgical site and surrounding subconjunctival area were evaluated histopathologically for cell counts (fibroblast, lymphocyte, eosinophil, and macrophage), presence of edema and foreign body reaction, and potency of the fistula tract. RESULTS: Mean IOP at the first and third day examinations was significantly different between groups, but there was no statistically significant difference among the groups with respect to IOP, anterior chamber depth, or bleb appearance at the seventh and 14th days. The groups were similar with respect to number of fibroblasts, eosinophils, and neutrophils. Number of macrophages was significantly increased in Groups 1 and 2 and number of vessels was significantly decreased in Group 1. CONCLUSIONS: Neither of these two adhesion-preventing substances seems to suppress wound healing reaction after glaucoma filtration surgery. However, a diminished wound healing reaction was expected wi th a decreased number of vessels, such as in Group 1. Increased number of macrophages in both groups may result in a decreased level of some inflammatory mediators.

Animals↗

Results of trabeculotomy and guarded filtration procedure for glaucoma associated with Sturge-Weber syndrome.

PURPOSE: To assess the efficacy of trabeculotomy and guarded filtration procedure in the management of glaucoma associated with the Sturge-Weber syndrome. METHODS: Six patients (seven eyes) with Sturge-Weber syndrome who underwent glaucoma surgery were retrospectively reviewed. One patient had bilateral glaucoma. Age at the time of operation ranged between 23 days and 9 years. The mean preoperative intraocular pressure was 30.6 mmHg (range 25-38 mmHg). Trabeculotomy and guarded filtration procedure were performed in three eyes each and both techniques were used in one eye. RESULTS: The mean follow-up was 6.3 (range 2-11) years. A single procedure lowered the intraocular pressure and arrested the progression of the disease in five eyes. Two patients required topical antiglaucoma medication. No patient needed reoperation. Two eyes suffered intra- and post-operative temporary choroidal effusions. CONCLUSIONS: Trabeculotomy in infancy and guarded filtration procedure in older children effectively stabilized the eyes and prevented further glaucomatous damage in our patients with Sturge-Weber syndrome.

Child↗

Antibody levels to whole culture filtrate antigens and to purified P32 during treatment of smear-positive tuberculosis.

Antimycobacterial IgG levels were measured repeatedly during treatment in 12 patients with moderate or severe pulmonary tuberculous disease using a dot immunobinding assay. We used reflectance densitometry equipment to quantify the immunoperoxidase staining and a Mycobacterium bovis BCG culture filtrate and the purified P32 protein as antigens. Antibody response against whole culture filtrate and P32 antigen increased after a three-month period of treatment. After this antibiotherapy was completed, the estimated amount of antibodies directed against the P32 decreased while those against the whole culture filtrate remained at the same level. A serologic test using P32 as the antigen seems to allow a better discrimination between active and healed tuberculosis.

Antibodies, Bacterial↗