Radio-iodinated Human Serum Albumin Research Articles

Albumin and fibrinogen synthesis rates in advanced chronic liver disease.

Synthesis of plasma proteins is an important function of the liver that has sparsely been investigated by modern techniques in patients with advanced chronic liver disease (CLD). Twenty-eight well-characterized patients with CLD under evaluation for liver transplantation were included. Albumin and fibrinogen synthesis rates were measured by the flooding dose technique using stable isotope labelled phenylalanine. Transcapillary escape rate of albumin and plasma volume were assessed by radio-iodinated human serum albumin. The absolute albumin synthesis rates were low (65 mg/kg/day, range 32-203), and associated with impaired liver function, as reflected by the risk-scores Child-Pugh (p = 0.025) and Model for End-stage Liver Disease rs = -0.62, p=0.0005. The fibrinogen synthesis rate (12.8 mg/kg/day, range 2.4-52.9) was also negatively associated with liver function. The synthesis rates of albumin and fibrinogen were positively correlated. Plasma volume was high (51 ± 9 mL/kg body weight), which contributed to an almost normal intravascular albumin mass despite low plasma concentration. Autoimmune inflammatory etiologies to CLD were associated with higher fibrinogen synthesis. De novo synthesis rates of albumin and fibrinogen in advanced chronic liver failure were negatively correlated to prognostic scores of liver disease. Albumin synthesis rate was low and associated with both liver failure and autoimmune inflammation, while fibrinogen synthesis was often normal and positively associated with chronic inflammation. This is different from acute inflammatory states in which both albumin and fibrinogen synthesis rates are high.

Effects of Intraperitoneal Hyaluronan on Peritoneal Fluid and Solute Transport in Peritoneal Dialysis Patients

Hyaluronan (HA) is a glycosaminoglycan found in connective tissues and tissue spaces, including the peritoneal cavity. In vivo studies in a rat model of peritoneal dialysis (PD) have shown that addition of HA to PD solution during an intraperitoneal dwell can alter peritoneal fluid transport and protect the peritoneal membrane from the effects of inflammation and repeated infusions of dialysis solution. The current study sought to evaluate the safety of intraperitoneal HA and its effect on peritoneal fluid and solute transport when administered during a dialysis dwell in humans. 13 PD patients were enrolled in a prospective, randomized crossover study involving three dialysis treatments using the following PD solutions: (1) a commercially available PD solution (Dianeal PD-4, 1.36% glucose; Baxter Healthcare Corporation, Alliston, Ontario, Canada); (2) Dianeal PD-4 containing 0.1 g/L HA, and (3) Dianeal PD-4 containing 0.5 g/L HA. Each 6-hour dialysis exchange was separated from the other exchanges by a 2-week washout period. Radioiodinated human serum albumin (RISA) was administered with the dialysis solution to evaluate intraperitoneal volume, net ultrafiltration (UF), and fluid reabsorption. Peritoneal clearances, dialysate/plasma ratios (D/P), and mass transfer area coefficients (MTACs) were determined for sodium, urea, creatinine, albumin, and glucose. Safety was evaluated by monitoring adverse events and changes in serum chemistries. Ten patients completed all three dialysis exchanges and two additional patients completed at least one treatment exchange. There were no reported adverse events related to HA administration and no significant changes in serum chemistries. There were no significant differences in net UF or peritoneal volume profiles among the three treatments. Mean net UF calculated using residual volumes, estimated by RISA dilution, tended to be slightly higher during treatment with solution containing 0.1 g/L HA and 0.5 g/L HA [74 +/- 86 (SE) and 41 +/- 99 mL, respectively] compared to control treatment (-58 +/- 129 mL). Although not statistically significant, there was a trend toward decreased fluid reabsorption during treatment with HA. Solute clearances, D/P ratios, and MTACs were similar for the three treatments. Serum levels of HA were also unaffected by the two treatment solutions. These data support the acute safety of HA when administered intraperitoneally with the dialysis solution to PD patients. Due to the small sample size and variability in net UF and fluid reabsorption, statistically significant differences were not demonstrated for these parameters. However, a trend toward decreased fluid reabsorption was observed, suggesting that HA may act by a mechanism similar to that observed in animal studies. Further studies are necessary to evaluate whether the beneficial effects of HA observed in animal studies can be shown in humans.

The Effects of Ouabain and Potassium on Peritoneal Fluid and Solute Transport Characteristics

We reported anomalous transport characteristics of potassium during experimental peritoneal dialysis in rats and suggested that mechanisms of peritoneal potassium transport could be other than simple passive transport. Intracellular transport of potassium in cultured human mesothelial cells was reported to be regulated by three different pathways, such as channels blocked by ouabain, channels blocked by furosemide, and other. To investigate the effect of ouabain on peritoneal potassium and water transport characteristics. A single 4-hour peritoneal dwell was performed in 28 Sprague-Dawley rats. To minimize the diffusive transport of potassium, 4.5 mmol/L of KCl was added into conventional dialysis solution with 3.86% glucose [acidic peritoneal dialysis solution (APD)]. To evaluate the effect of the pH of dialysis solution on the transport of potassium and water, 4 mmol/L of NaOH was added into the potassium-containing study solutions [neutral peritoneal dialysis solution (NPD)]. To evaluate the effect of a potassium channel blocker on peritoneal potassium transport ATPase sensitive Na+-K+-transport inhibitor, ouabain (10(-5) mmol/L) was added to dialysis solutions immediately before the dwell study in eight rats with APD (APD-O) and six rats with NPD (NPD-O). Ouabain was not added in eight and six rats with APD and NPD (APD-C and NPD-C, respectively). They were used as control. Infusion volume was 30 mL. The intraperitoneal volume (V(D)) was estimated by using a volume marker dilution method with corrections for the elimination of volume marker, radioiodinated human serum albumin (RISA), from the peritoneal cavity (K(E)). The diffusive mass transport coefficient (K(BD)) and sieving coefficient (S) were estimated using the modified Babb-Randerson-Farrell model. V(D) was significantly higher (p < 0.05 from 90 min to 240 min) and K(E) (0.027+/-0.018 mL/min for APD-O, 0.026+/-0.017 mL/min for NPD-O, and 0.030+/-0.022 mL/min for NPD-C, vs 0.058+/-0.030 mL/min for APD-C, p < 0.05 for each) significantly lower during dialysis with APD-O, NPD-O, and NPD-C than with APD-C. The intraperitoneal glucose expressed as a percentage of the initial amount was significantly higher with APD-O, NPD-C, and NPD-O than with APD-C (p < 0.05 from 90 min to 240 min). K(BD) for sodium was higher during dialysis with ouabain than without ouabain, while K(BD) for urea, glucose, and potassium, and S for urea, glucose, sodium, and potassium did not differ between the four groups. The physiologic potassium concentration in neutral dialysis solutions and the use of ouabain decreased the intraperitoneal fluid absorption. The diffusive transport coefficient and sieving coefficient for potassium did not differ, while the diffusive transport coefficient for sodium increased during use of ouabain.

Acute haemodynamic effects of perindoprilat in essential hypertension at rest and during exercise.

The acute haemodynamic effect of perindoprilat was examined at rest, supine and sitting, and during 100 W bicycle exercise in 12 patients (mean age 42 years) with essential hypertension. Intra-arterial blood pressure and the heart rate were recorded continuously. Cardiac output was measured by dye dilution (Cardiogreen) and blood volume was determined by radio-iodinated (125I) human serum albumin. Two hours after a slow (3 min) intravenous injection of perindoprilat, blood pressure was reduced in all patients (P less than 0.01)--at rest sitting from 175/108 to 153/97 mmHg (11%)--because of reduction in total peripheral resistance index (f = 2.63; P less than 0.05). Only minor changes were seen in the heart rate, stroke index and cardiac output. The fall in blood pressure was significantly (P less than 0.05) correlated with blood volume (r = 0.65) and pretreatment total peripheral resistance index (r = 0.59).

Extraplacental transfer of water in the sheep.

1. Ten pregnant ewes were operated on at 130 days of gestation. The fetal trachea was intubated with a double-lumen tube, an inflatable occluder was placed around the umbilical cord, vascular catheters were placed in the fetal carotid artery and jugular vein and in the maternal jugular vein, and multiple catheters were placed in the amniotic and allantoic sacs. 2. At 139 days gestation, the fetus was ventilated in utero, and the umbilical cord was occluded. The extrafetal fluids were circulated by means of roller pumps. Known activities of radio-iodinated human serum albumin, tritium-labelled water and 14C-labelled urea were injected into the amniotic and/or allantoic fluids. Samples were obtained at 30 min intervals for several hours. 3. Extrafetal fluid volumes were calculated from the albumin distribution volumes. The amounts of labelled water transferred to the maternal circulation were calculated from the changes in tracer concentrations in extrafetal fluids and fetal plasma. 4. No labelled albumin was detected in fetal or maternal plasma. The permeability-surface area product of labelled water at the combined amniotic and allantoic interfaces with the ewe was 28.2 +/- 2.8 ml/min (mean +/- S.E.M.). In five preparations the values could be separately calculated for amniotic and allantoic interfaces. The two mean values (19 +/- 4 and 12 +/- 1 ml/min) were not significantly different from each other. The permeability-surface area product at the combined interfaces with the fetus was 0.96 +/- 0.17 ml/min. Urea was so much less permeable than water that no reliable permeability-surface area products could be calculated in all of the preparations. 5. We calculated that the hydraulic conductivity of the combined extraplacental pathway is more than 0.5% of that of the placenta. Because the osmotic gradient across the extraplacental pathway is one to two orders of magnitude greater than that across the placenta, extraplacental transfer of water can significantly affect intrauterine water volume.

The etiology of “white bile” in the biliary tree

“White bile” is the colorless fluid occasionally found in occluded biliary systems. The absence of pigments in this “bile” was not satisfactorily explained. The objectives of this study were to assess its etiology. In dogs, “white bile” developed whenever both the common bile duct and the cystic duct were ligated. In comparison, dark green (“black”) bile occurred when only the common bile duct was ligated leaving the gallbladder in communication with the obstructed ducts. The pressure in extrahepatic ducts containing “white bile” was significantly higher than in those filled with “black bile.” Flow in the extrahepatic ducts was assessed by the aid of radioiodinated human serum albumin (RIHSA). When “black bile” was present, the direction of flow was from the extrahepatic ducts into the gallbladder. Whenever “white bile” developed, a reverse flow from the extrahepatic ducts into the liver was observed. Thus, the role of the gallbladder appears to be decompression of the biliary system allowing bile flow from the liver even in obstruction. In the absence of the gallbladder water absorption activity, the colorless secretion of the bile ducts seems to “back wash” into the liver and replace the bile present in the ducts at the time of occlusion.

Mathematical model to study fluid and protein transfer in pulmonary edema in man.

We developed a mathematical model that integrates the various processes that affect fluid and protein transport in the lung. The model is based on experimental data and current concepts of fluid and protein transfer in the lung, with particular attention to experimental studies of lymph flow and protein content. The model is exercised with data obtained from 5 patients with fulminant pulmonary edema who are studied prospectively. Tracheobronchial fluid (TBF) was sampled sequentially during the course of edema. In addition, radioiodinated human serum albumin (RIHSA) was injected iv and its appearance was measured in TBF as well as in plasma (P). The oncotic pressure of P and TBF, together with the measured pulmonary vascular hydrostatic pressure, and the appearance of RIHSA in TBF were used to exercise the model. Water flux across the microvascular wall was calculated using the Starling equation, and the equation for protein transport utilized terms for convection and diffusion. Transport coefficients were estimated which produced the closest fit between the mathematically calculated and measured values for TBF protein concentration and the rate of RIHSA appearance in TBF for each patient. For patients with permeability edema, our mathematical model estimated that bulk flow coefficients, Kf for water flux and (1 – σ) for convective flow of protein increased while the estimate of the coefficient for protein diffusion ω was increased to a lesser extent. In hemodynamic edema, the model predicted Kf and ω to be somewhat elevated, but because the estimated σ was unchanged, there was no massive loss of protein from the vascular space. The measured values and the values calculated by the model for TBF/P protein ratio averaged 0.66 for hemodynamic edema, and 0.94 for permeability edema. The model predicted that a maximal increase in lymph flow, consistent with experimentally measured values, would substantially reduce extravascular volume in hemodynamic edema within 24 h, but would have little effect in permeability edema. One explanation for the observed greater concentration of tagged protein in the TBF than in P in 1 patient is provided by the model. The time after RIHSA injection when this crossover is predicted by the model averaged 20 h in hemodynamic edema, but only 4 h in permeability edema. The duration of this time interval may be a useful variable to distinguish the 2 types of edema. We recognize the shortcomings of a model based on disparate experimental data. However, we believe that the model provides a method to help improve our understanding of edemagenesis. The model gives the clinical investigator a prediction of what may follow the manipulation of one or more of the multiple variables that influence edemagenesis. As additional clinical and experimental knowledge of edemagenesis accumulates, the model can be refined.

Interstitial albumin mass and transcapillary extravasation rate of albumin in DMBA-induced rat mammary tumours

Transcapillary extravasation rate for radio-iodinated human serum albumin (I-HSA) from plasma to interstitial fluid, interstitial albumin mass and interstitial albumin concentration have been determined in dimethyl-benz-alpha-anthracene (DMBA)-induced mammary tumours in rats. The plasma radioactivity of tracer was kept constant in awake, freely moving rats by a continuous infusion of I-HSA from 1 to 72 h after an initial priming dose. Capillary leakiness for I-HSA was calculated as the plasma equivalent volume of I-HSA located extravascularly after 1 h infusion divided by the blood volume in the tissue, i.e. as the fractional extravasation rate (FER). The experiments showed that FER was highest in tumours while intestine and skin had FER of about 70% and 25% that of tumour respectively. Heart and skeletal muscle had similar FER about 1/8 that of tumour. Interstitial albumin concentration in tumour averaged 42% of plasma albumin concentration in tumour. Intestine, heart and skeletal muscle had interstitial albumin concentrations between 34 and 37% of plasma albumin concentration while skin had an albumin concentration averaging 20% that of plasma. Lymph flow was calculated as the product of the fractional turnover rate constant for interstitial albumin and interstitial volume (extravascular 51Cr-EDTA volume) and averaged 36.7 X 10(-3) mg/g X h in tumour while intestine and heart had lymph flows of 19.1 X 10(-3) and 14.1 X 10(-3) ml/g X h respectively. In muscle and skin lymph flow was 2.4 X 10(-3) and 18.3 X 10(-3) ml/g X h respectively. It is suggested that the high interstitial fluid pressure previously observed in these tumours will contribute in maintaining interstitial volume in a steady state by opposing fluid filtration into the interstitium and maintaining a lymph flow high enough to remove excess fluid and protein from the interstitium.

Effects of acute hypertension on the extravasation of macromolecule in the temporal bone--the possible involvement of the blood-inner ear barrier.

In guinea pigs the radioactivity in the vascular beds was washed out by a cardiac perfusion of saline 15 min after the injection of 50 microCi of radioiodinated human serum albumin (RISA). The brain and temporal bones were dissected and a blood sample was obtained. To examine the degree of extravasation of RISA, the extravascular radioactivity in the tissues was measured and expressed as a ratio to that of the blood. Intravenous injection of amphetamine sulfate increased the extravasation in the brain and the temporal bone of the rat but did not increase it in either tissue of the guinea pig. It was proposed that this was because amphetamine did not cause the blood pressure of the guinea pig to reach the "critical level" which would cause the opening of the blood-tissue barrier. In the rat the degrees of extravasation in both the brain and the temporal bone paralleled the maximal mean arterial pressure caused by amphetamine. It is proposed on the basis of these data that there may exist a blood-inner ear barrier and that this barrier has the same characteristics as the blood-brain barrier.

Effect of colchicine on carrageenin-induced granulomatous inflammation in rats.

The effect of colchicine on inflammatory responses in chronic, proliferative inflammation was investigated by using 8-day-old granuloma pouch induced with carrageenin in rats. Colchicine was injected directly into the granuloma pouch, and then vascular permeability of the granuloma pouch, blood volume in the granulation tissue and incorporation of 3H-proline into non-collagen protein of the granulation tissue were determined. Vascular permeability was assayed with the aid of radioiodinated human serum albumin as a tracer. The volume of the blood in the granulation tissue was also measured by using radioiodinated human serum albumin. In the early stage in the action of colchicine, it induced enhancement of the vascular permeability in the granulation tissue, and then, it induced suppression in the late stage in its action. The blood content of the granulation tissue did not change in the early stage but lowered in the late stage in advance to the suppression of the vascular permeability. Therefore, the most primary action of locally injected colchicine is to raise the vascular permeability in the local tissue, and then to decrease blood volume in the local tissues with resultant suppression of the vascular permeability. Incorporation of labeled proline into tissue protein was suppressed under the influence of colchicine regardless of its effect on the vascular permeability.

Apparent escape rate of RIHSA and 51Cr-labeled erythrocytes from the blood of volume-expanded rats

The disappearance rate constant of radioiodinated human serum albumin (RIHSA) and 51Cr-tagged erythrocytes was measured in rats before and after intravenous, isoncotic blood volume expansion (6% bovine albumin; 75 or 33% of blood volume). Before volume expansion the average slope of the semilogarithmically plotted plasma RIHSA activity was -2.068 X 10(-3) +/- 0.146 X 10(-3) (SE) min-1. The slope was not significantly changed when tested by subsequent tracer injections which were made immediately after and 1 h after volume expansion. Preinfusion plasma volume (PV) was constant, but total erythrocyte volume (RCV) increased at a significant rate from 0.0253 +/- 0.0030 to 0.0300 +/- 0.0038 ml/g body wt over the 2-h period. PV was elevated and RCV was unchanged by the infusion, but both decreased significantly thereafter. The observed erythrocyte loss could not be accounted for by sampling or bleeding. Arterial hematocrit remained constant while RCV and PV were decreasing, and it was identical to whole-body hematocrit throughout. It was concluded that 1) isoncotic albumin expansion did not change the rate constant of transcapillary albumin loss; 2) nonsteady state PV could be calculated from a single preinfusion RIHSA dose; and 3) sequestration of blood may be a part of the rat's response to volume expansion.

Changes in plasma volume and haematocrit in intact and splenectomized sheep during feeding.

Changes in jugular haematocrit during daily 2-h feeding periods in trained sheep with and without spleens were compared with changes in the concentration of the plasma tracer radio-iodinated human serum albumin. Jugular haematocrit was increased by 16% in intact sheep and 9% in splenectomized sheep 20 min after they started to eat dry rations. The dilution of tracer in plasma, studied after mixing in the vascular system had been completed, showed four phases. Phase 1 was the rate of removal of tracer in the period before eating began. Phase 2 was the sudden increase in plasma radioactivity that occurred in the first 20 min of eating, indicating a loss of plasma from the circulation. Phase 3 was the decrease in tracer concentration during the remaining feeding period and phase 4 was a post-feeding phase, characterized by a slower rate of decrease of tracer than during phase 3, implying that there was significant recycling of tracer during this phase. The sudden increase in plasma radioactivity, initiated by the onset of feeding, represented a reduction in plasma volume of 10-12%. Minimum plasma volume coincided with peak haematocrit values. The reduced plasma volume accounted for the increased haematocrit in splenectomized sheep, but only accounted for about half of the increase in intact sheep. The residual increase in haematocrit in intact sheep was most likely the result of splenic contraction.

Lamb fetal pulmonary fluid. I. Validation and significance of method for determination of volume and volume change.

An indicator-dilution method is described for measuring fetal pulmonary fluid, FPF, volume (Ve), and volume change with time (Vs) in the lamb fetus in utero. The indicator, albumin, which is the predominant protein of normal FPF, was administered directly to FPF in the form of radio-iodinated human serum albumin (RISA). We have shown that (1) RISA is distributed homogeneously throughout the FPF compartment, (2) it is not altered within FPF, (3) it does not alter the functional characteristics of FPF, and (4) it remains within the FPF compartment throughout the period of measurement. Ve varies directly with the weight of the fetus so that Ve per kilogram was 31.6-35.6 ml/kg in four of five fetuses. The Ve per kilogram was lower in one fetus at the start of the experiment but increased rapidly to 29.0 ml/kg within 45 min. Thus the relaxation volume of the fetus in utero is in the range of functional residual capacity (FRC) and thoracic gas volume of the air-breathing neonate, which indicates that the pulmonary transformation at birth is, in essence, an isovolumic change in state wherein the fetal liquid-lung becomes the neonatal air-lung. The rate at which FPF is formed (Vs) is about 1.5 ml/hr-kg; however, the rate may change in so far as both rapid increases and rapid decreases of FPF volume were observed. When breathing movements were induced in the fetus by stimulation of the sciatic nerve, FPF volume decreased rapidly (Vs equals -3.0 ml/hr-kg), which indicates that negative intrathoracic pressures promote its resorption. When FPF volume fell transiently or was low initially, there was subsequent rapid restoration of volume to the range of anticipated FRC.

Lamb fetal pulmonary fluid. II. Fate of phosphatidylcholine.

Using the radio-iodinated human serum albumin ([131-I]-RISA) dilution method to measure lamb fetal pulmonary fluid (FPF) volume, we followed the disappearance of protein-complexed, 14-C-labeled phosphatidylcholine ([14-C]PC) during the first 90 min after its injection into FPF. The FPF samples were analyzed for total lipid 14-C activity and for distribution of 14-C in PC, other phospholipids (PL), fatty acids (FA), and neutral lipids (NL). For most sampling periods ascending aortic (AAo) and right atrial (RA) blood samples were obtained simultaneously with FPF and serum was analyzed for total lipid 14-C activity and for distribution of 14-C in total PL, FA, and NL. These studies indicate that (1) PC is cleared rapidly from FPF with an estimated half-time of 15-57 min; (2) FPF-PC may be metabolized to lyso-PC and FA within the fluid itself; and (3) FA derived from PFP-PC enter the pulmonary circulation, thus establishing a pulmonary arteriovenous FA gradient. The possible sites at which PC may be cleared from FPF are considered.

Creatinine, potassium, and calcium flux from chicken cerebrospinal fluid.

Brains of methoxyflurane-anesthetized chickens were perfused from a lateral cerebral ventricle to cisterna magna with an artificial cerebrospinal fluid (CSF) containing trace quantities of radioiodinated human serum albumin (RIHSA) or inulin (1.0 mg/ml) to measure CSF bulk absorption. In addition, it contained either trace quantities of 22Na, 42K, 45Ca or [14C]creatinine; the concentrations of the latter three were varied to determine permeability coefficients (K-D's) as a function of concentration. A mass balance for the tracer molecules was calculated to determine their movement into brain or blood. K-D's for 45Ca, 42K, 22Na, and creatinine (Cr) were unaffected by perfusion time and the latter two were larger than previously reported (3). The lack of effect of time on K-D and the large values for K-D22Na and K-D-Cr are attributed to anesthetic effects on brain blood flow. K-D-Cr and K-D42K were larger than K-D22Na or K-D45Ca and K-D's for 45Ca, Cr, and 42K were independent of their inflow concentrations. An active transport process is suggested for potassium and creatinine, but one that is located at sites other than the ependymal wall. Bulk flow clearance accounted for RIHSA movement from CSF, whereas nonbulk clearance accounted for 50% of 22Na and 45Ca movement and 90% of 42K clearance. Fifty percent of 42K and 25% of 22Na and 45Ca were found in brain. The large recovery of 42K in brain supports the hypothesis that intracellular potassium serves as an exchangeable pool for the tracer.

Cerebrospinal fluid formation and bulk absorption in the freshwater turtle

Turtle brains were perfused from the lateral cerebral to the fourth ventricle with an artificial cerebrospinal fluid (CSF) containing a trace amount of radioiodinated human serum albumin (RIHSA); both inflow and outflow rates and RIHSA concentrations were measured. Steady-state clearances of RIHSA (C RIHSA) from the perfusate were measured at different intraventricular hydrostatic pressures. Both C RIHSA increased and outflow rate decreased linearly with increasing hydrostatic pressure. The CSF formation ( V ̇ f ) was 1.4 μl/min and was independent of hydrostatic pressure. Resistance to bulk absorption of CSF was 1790 cm·min/ml. The large resistance to bulk absorption in the turtle may be due to lack of an arachnoid membrane with associated valves.

The distribution of radio-iodinated serum albumin and low-density lipoprotein in tissues and the arterial wall

Plasma low-density lipoprotein labelled in the peptide component with radioiodine (RI-LDL) was injected into 11 patients in coma, in whom death was considered inevitable. Injected material was primarily Sf 0–9 LDL. The serum turnover of RI-LDL was followed until death of the patient. Parallel studies were carried out in another 11 subjects using radioiodinated human serum albumin (RI-HSA). Various tissues were recovered at necropsy and their radioactivity measured. The temporal pattern of radioactivity distribution in tissues was studied by comparing results from the individual patients in ascending order of the time elapsing between administration of labelled proteins and recovery of tissue. Results for RI-LDL and RI-HSA tissue to plasma radioactivity ratios were qualitatively similar.Equilibration between plasma and tissue radioactivity was most rapid in liver and spleen. Intima and inner media of aorta and coronary arteries showed rising ratios of tissue to plasma radioactivity over the 14–16-day maximum duration of these studies, and higher levels of radioactivity were reached in the arch and abdominal segments than in the thoracic aorta. Outer medial tissue/plasma ratios were lower and appeared to reach equilibrium earlier. The results show that plasma LDL peptide does enter the inner arterial wall, presumably across the intima, and that the intima may be the site of a slowly exchanging LDL pool.

Studies on phagocytosis: I. Uptake of radio-iodinated ( 131I) human serum albumin as a measure of the degree of phagocytosis in vitro

A new method is described for measuring the phagocytic activity of polymorphonuclear leukocytes (PMN) from rabbit peritoneal exudate based on the uptake of external fluid during phagocytosis. The advantages of the method are discussed.

A Comparison of Pulmonary Angiography and Intravenous Radioactive Albumin Lung Scanning in Chronic Obstructive Pulmonary Emphysema

SUMMARY Twelve patients with chronic obstructive pulmonary emphysema were studied with both pulmonary angiograms and intravenous R 131 IHSA (radio-iodinated human serum albumin) lung scans, in an attempt to localize the more severely affected areas of the lung. There was a good correlation between the two studies, particularly where the abnormalities were marked. Discrepancies between the distribution of the vasculature, as shown by the angiogram, and the degree of radioactivity on the lung scan were usually minor. It is suggested that lung scanning is a reasonably reliable method for defining the poorly vascularized areas in patients with emphysema.

Cross circulation in normal and intoxicated parabionts.

SummaryErythrocyte and plasma transfer times determined simultaneously with Cr51 tagged cells and radio-iodinated human serum albumin (RISA) in normal parabionts at less than 30 days after union were statistically similar to each other, but plasma half-time transfer was as long or longer than that for erythrocytes in all but one of 33 pairs. Normal pairs reinvestigated 10 and 15 months after surgical union showed some slowing of cross circulation. Pairs in a state of intoxication, as determined by clinical appearance corroborated by differentials in peripheral blood values, showed a great slowing of cross-circulation time. In addition to this slowing of cross-circulation time the intoxicated pairs exhibited plasma transfer faster than that for erythrocytes which was opposite to the pattern for normal parabionts. When injected into the anemic animal, the majority of tagged erythrocytes crossed to the hyperemic rat demonstrating unequal exchange; when injected into the hyperemic animal, the erythrocytes ten...