L-aspartic acid and urea supplementation of low-protein layer diets

The purpose of the present experiments was to study the effect of a rise in local venous pressure pressure (Pv) on interstitial fluid hydrostatic (Pi) and colloid osmotic pressure (COPi) in rats. The Pv of the hind limb was increased by ligating the iliac veins and the inferior caval vein. Interstitial fluid for protein and COP determination was sampled from subcutaneous tissue of the hind limbs by a wick technique, and the Pi was measured by a modified Scholander technique. When the Pv was increased from 3 to 12 mm Hg, the COPi fell from 9 to 4 mm Hg. The Pi averaged -1 mm Hg under control conditions and was unchanged when the Pv was elevated to 12 mm Hg. No edema was detected. Higher rises in venous pressures resulted in further but less pronounced falls in interstitial fluid COP. Edema developed and the Pi increased to +1 to 2mm Hg. The results show that the fall in COPi is an important edema-preventing factor during increased venous pressure, whereas a rise in Pi only seems to oppose further increase of an already existing edema.     

The wick catheter technique for measurement of intramuscular pressure. A new research and clinical tool

The wick catheter technique was developed in 1968 for measurement of subcutaneous pressure and has been modified for easy intramuscular insertion and continuous recording of interstitial fluid pressure in animals and humans. Studies in dogs of the anterolateral compartment of the leg in simulation of the compartment syndrome showed the technique to be accurate and reproducible. The wick catheter technique is capable of important clinical applications in the diagnosis and treatment of acute and chronic compartment syndromes.     

Enhancement of the anti-tumour effects of the antivascular agent 5,6-dimethylxanthenone-4-acetic acid (DMXAA) by combination with 5-hydroxytryptamine and bioreductive drugs

The wick method for sampling of interstitial fluid from subcutis was applied in fluid balance studies in young pigs. Colloid osmotic pressure was measured in serum (COPs) and interstitial fluid (COPi) using a membrane colloid osmometer. Our aims were to determine the 'true' COPi, and to find the optimal duration of wick implantation. In series I (n = 6) a 'crossover' experiment was performed using wicks soaked in different priming solutions (non-diluted and diluted serum protein solutions or isotonic salt solution). Circulatory arrest was induced just before wick insertion in order to eliminate the vascular part of the acute inflammation. In series II (n = 6) wicks were removed in sequence after 60, 90, 120 and 180 min sampling time in anaesthetized pigs in vivo. COPs, COPi and haematocrit (HCT) together with haemoglobin (Hgb), serum albumin and total protein concentrations were determined in the same animals. In series I average COPs and COPi were 13.7 (1.4) and 7.2 (1.4) mmHg respectively (SD). In series II the optimal wick implantation times were estimated to be 60-90 min for wicks soaked in diluted protein solution, and 90-120 min for dry and saline-soaked wicks. COPs averaged 13.0 (0.7) mmHg, HCT 30.0 (1.6)%, Hgb 8.3 (0.9) g/dl, s-albumin 22.7 (0.6) g/l and s-protein 47.3 (2.3) g/l. Compared to commonly reported reference values, we found surprisingly low values for most of the measured variables. This may be related to the fact that we used immature pigs. An analysis of the validity of the wick method based on our own results and published reports is presented. We conclude that sampling of interstitial fluid with subcutaneous wicks is easy to perform in young pigs. However, the COP-values measured in wick fluid have to be carefully evaluated especially when sampling is performed in vivo.     

Capillary protein leak syndrome appears to explain fluid retention in cancer patients who receive docetaxel treatment

PURPOSE: The aim of our study was to elucidate whether the fluid retention syndrome induced by docetaxel is caused by capillary protein leakage or by other mechanisms. PATIENTS AND METHODS: Twenty-four patients with advanced or metastatic non-small-cell lung cancer (NSCLC; 23 patients) or metastatic head and neck cancer (one patient) were included on this prospective, nonrandomized trial. Docetaxel 100 mg/m2 was administered every 3 weeks with 5 days of dexamethasone prophylaxis to avoid hypersensitivity reactions and edema formation. Transcapillary forces, ie, colloid osmotic pressure of plasma (COPpl) and interstitial fluid (COPint) and interstitial hydrostatic pressure (Pint), were measured before the start of treatment and after total docetaxel doses of 200 and 500 mg/m2 by means of the well-documented wick and wick-in-needle methods. Body weight, degree of edema, blood pressure, and heart rate and hemoglobin, hematocrit, albumin, and total protein values were registered in parallel. RESULTS: After a total docetaxel dose of 200 mg/m2, COPpl, COPint, and hemoglobin, hematocrit, albumin, and total protein values had decreased significantly; Pint and body weight were unchanged; and only mild edema was observed. These findings suggest a plasma volume increase followed by enhanced fluid filtration to the interstitium. After a cumulative docetaxel dose of 500 mg/m2, the COPpl continued to decrease significantly, but COPint remained unchanged despite a significant increase in mean body weight and edema formation. These observations support the theory of a capillary protein leakage. CONCLUSION: Docetaxel appears to induce an initial enhancement of fluid filtration followed by a capillary protein leakage that leads to edema formation.     

Photochemotherapy in the treatment of carcinoma of the vocal cords of early stage (Tis, T1)

The purpose of this study was to evaluate whether treatment with interleukin-2 (IL-2) and alpha-interferon (IFN-alpha-2a) causes protein leakage from plasma to the interstitium, leading to the so called 'capillary leak syndrome'. This syndrome is supposed to cause dose-limiting side effects such as weight gain, edema and pleural effusions. Seven patients with disseminated malignant melanoma or renal carcinoma were studied before and after 5 and 12 days of treatment. Transcapillary forces were studied by measuring colloid osmotic pressures in plasma and interstitial fluid (on the thorax and ankle) with a 'wick' method. The colloid osmotic pressure in plasma was reduced by 30-35% during treatment, but with corresponding reductions in the interstitium. Hemoglobin, hematocrit, serum albumin and total protein decreased, whereas moderate edemas and weight gain were observed. These results demonstrate that during treatment with IL-2 and IFN-alpha-2a there are both fluid retention and augmented filtration of fluid from the vascular to the interstitial compartment, but no indication for a capillary leak syndrome. This may explain many of the cardiovascular side effects observed during such treatment.     

Determinants of isogravimetric capillary pressure in the isolated dog hindlimb

The hindlimb of the dog was rapidly isolated and carefully perfused in an attempt to prevent transcapillary fluid shifts into the interstitium which may occur during normal surgical isolation and perfusion. In the control preparation before weight was allowed to increase, isogravimetric capillary pressure (Pci) averaged 8 mmHg lower than colloid osmotic pressure of the plasma (IIp). As the weight of the leg was increased, Pci increased and IIp - Pci decreased. When weight was increased by 5.8%, IIp - Pci averaged 3 mmHg; with a 9.8% increase in weight, IIp - Pci averaged 1.3 mmHg. The calculated value of compliance of the interstitial space averaged 0.50 ml/mmHg per 100 g of tissue and increased approximately 10-fold as the weight of the leg was increased. Since IIp - Pci has always been reported to be approximately 2 mmHg when the hindleg was isolated with standard surgical techniques, these data suggest that the procedures normally used to isolate and perfuse the hindlimb caused the weight of the limb to increase by 6% or more before Pci was determined. Furthermore, it appears that most of the variation in the reported value of Pci is due to variation in the value of IIp since IIp - Pci has always been reported to be very close to 2 mmHg in the isolated hindlimb.     

Interaction of transcapillary Starling forces in the isolated dog forelimb

Three of the four Starling forces were measured in the intact dog forelimb after anesthetization and all four of the Starling forces were measured in the same forelimb which was surgically isolated yet innervated. In the isolated forelimb, isogravimetric capillary pressure (Pci) averaged 15.6 mmHg; colloid osmotic pressure of the plasma proteins (IIp) averaged 19.9 mmHg; mean interstitial fluid pressure (Pif) was +0.4 mmHg, and the average value of interstitial colloid osmotic pressure (IIif) was 4.9 mmHg. Thus the net imbalance in the Starling forces, i.e., (Pci - Pif) - (IIp - IIif), averaged 0.3 mmHg. Furthermore, the value of IIif was consistently decreased after isolation (average decrease of 1.2 mmHg) while Pif was always increased following isolation (average increase of 4.3 mmHg). In addition, it was found that if the forelimb was denervated during isolation, then Pif was increased by an average of 2 mmHg above Pif in the innervated, isolated forelimb. In summary, these studies show that the differences between the intact and isolated forelimb are that Pci averages 10-11 mmHg in the intact forelimb and 15-16 mmHg in the isolated innervated forelimb while interstitial fluid pressure is negative in the intact limb and positive in the isolated limb.     

Cold and warm infusion of Ringer's acetate in healthy volunteers: the effects on haemodynamic parameters, transcapillary fluid balance, diuresis and atrial peptides

The effects of Ringer's acetate (RAc) infusion with different temperatures, 18 degrees C compared to 36 degrees C, were studied in 20 healthy volunteers. An infusion volume of 20% of the estimated extracellular volume was given over 45 min. Before and after the RAc infusion, interstitial colloid osmotic pressure and interstitial fluid hydrostatic pressure were measured on the lateral part of the thorax and in the lower leg. Blood sampling and pressure measurements were performed through a cannula placed in the left radial artery, and arterial oxygen saturation was measured by pulse oximetry. Atrial peptides ANF (99-126) and ANF (1-98) in plasma were measured as indicators of volume loading. Cold RAc infusion increased mean arterial pressure from 82 (s.d. +/- 7) to 96 (s.d. +/- 9) mmHg (10.9-12.8 kPa) at the end of the infusion with a simultaneous fall in heart rate. Warm RAc infusion gave no changes in blood pressure or heart rate. The arterial oxygen saturation during the infusion of cold RAc was higher than during warm RAc infusion. Cold infusion produced the expected haemodilution with a fall in erythrocyte volume fraction (EVF) from 0.39 (+/- 0.03) to 0.33 (+/- 0.03) and a fall in plasma colloid osmotic pressure (COPp) from 21.7 (+/- 1.1) mmHg to 15.0 (+/- 1.3) mmHg (2.9-2.0 kPa). Warm infusion induced a nearly identical haemodilution. Interstitial colloid osmotic pressure fell from 11.6 (+/- 2.3) mmHg to 8.9 (+/- 2.7) mmHg (1.5-1.2 kPa) after warm infusion while cold infusion gave no changes. The changes in interstitial fluid hydrostatic pressure were not significant.(ABSTRACT TRUNCATED AT 250 WORDS)     

Preliminary study of colloid osmotic pressure for cardiopulmonary bypass

The ideal colloid osmotic pressure is beneficial to decrease the fluid accumulated in the pulmonary and other tissue during cardiopulmonary bypass. Schupbach reported the proper colloidosmotic pressure for cardiopulmonary bypass was 2.1 kPa (16 mmHg). Colloid osmotic pressures of blood and priming fluid during cardiopulmonary bypass were measured in 28 patients with heart disease by using colloid osmotic pressure detection apparatus. The value of colloid osmotic pressure suitable for the designed standard was apparently different among the Gelofusine group and other groups. P value was 0.005. Priming fluid for cardiopulmonary bypass needs to satisfy the quality and the quantity of colloid osmotic pressure. Using Albumin isn't economical. Whole blood and plazma are not suitable for increasing colloid osmotic pressure. Hydroxyethyl starch or Gelofusine is best choice in priming to get designed standard of colloid osmotic pressure. The ratio of hydroxyethyl starch or Gelofusine in priming fluid should beyond 1/2.     

New systems for replicating DNA in vitro

In order to investigate whether soluble intercellular adhesion molecule-1 (sICAM-1) and soluble interleukin-2 receptors (sIL-2R) were present in scleroderma skin, and to compare their levels to concentrations measured in plasma and clinical parameters, we examined suction blister fluid and plasma from 13 patients with systemic sclerosis and 11 healthy volunteers. Suction blisters and biopsies were from the transition zone between normal skin and scleroderma, and uninvolved abdominal skin. The levels of sICAM-1 and sIL-2R were significantly increased in both plasma and suction blister fluid from systemic sclerosis patients compared with healthy volunteers. ICAM-1 was localized to vessels and perivascular mononuclear infiltrates by immunohistochemical methods. IL-2R was expressed by CD3-positive cells. The elevated levels of sICAM-1 and sIL-2R in suction blister fluid point towards activation of endothelial cells and T cells in both the transition zone and uninvolved skin of systemic sclerosis patients.     

Intraperitoneal pressure: ascitic fluid and splanchnic vascular pressures, and their role in prevention and formation of ascites

Seventeen patients with ascites due to cirrhosis underwent hepatic venous catheterization and pressure measurement in the ascitic fluid. Intraperitoneal fluid hydrostatic pressure (IFP) ranged 3.5-22, mean 11.2 mm Hg, and correlated closely to the pressure in the inferior vena cava (r = 0.97, P < 0.001), which was on average 1.8 mmHg above that of ascitic fluid (P < 0.005). Wedged hepatic venous pressure (WHVP) (range 19-43, mean 32 mmHg) correlated directly to IFP (0.89, P < 0.001) and was significantly higher than that of ten cirrhotic patients without ascites (range 12-27, mean 20 mmHg, P < 0.005). After diuretic therapy WHVP decreased to an average of 20 mmHg. Mean plasma colloid osmotic pressures were 20 mmHg (range 18-24 mmHg)( and 23 mmHg (range 19-29 mmHg) in patients with and without ascites, the values being significantly different (P < 0.05). Colloid osmotic pressure of ascitic fluid ranged 1-14, mean 4.9 mmHg. Mean ratio between albumin concentration in ascitic fluid and plasma was 0.31 (range 0.12-0.77). In five pigs portal venous pressure (PVP) increased during infusion of fluid into the peritoneal cavity. The increase in PVP was smaller than that of IFP (P < 0.02), indicating that ascitic fluid stems the pressures in the splanchnic venous vascular bed up to a higher level, but that the transmural hydrostatic pressure difference decreases simultaneously. The results are discussed in relation to the local 'oedema-preventing' mechanisms: (a) increased interstitial hydrostatic fluid pressure, (b) decreased interstitial fluid colloid osmotic pressure, (c) increased lymph flow, and it is concluded that the peritoneal space can be considered as a special part of the interstitium in which IFP is considered to play an important role in regulation of ascitic fluid.     

Testosterone replacement increases fat-free mass and muscle size in hypogonadal men

To test the hypotheses that plasma volume (PV) expansion 24 h after intense exercise is associated with reduced transcapillary escape rate of albumin (TERalb) and that local changes in transcapillary forces in the previously active tissues favor retention of protein in the vascular space, we measured PV, TERalb, plasma colloid osmotic pressure (COPp), interstitial fluid hydrostatic pressure (Pi), and colloid osmotic pressure in leg muscle and skin and capillary filtration coefficient (CFC) in the arm and leg in seven men and women before and 24 h after intense upright cycle ergometer exercise. Exercise expanded PV by 6.4% at 24 h (43.9 +/- 0.8 to 46.8 +/- 1.2 ml/kg, P < 0.05) and decreased total protein concentration (6.5 +/- 0.1 to 6.3 +/- 0.1 g/dl, P < 0.05) and COPp (26.1 +/- 0.8 to 24.3 +/- 0.9 mmHg, P < 0.05), although plasma albumin concentration was unchanged. TERalb tended to decline (8.4 +/- 0.5 to 6.5 +/- 0.7%/h, P = 0.11) and was correlated with the increase in PV (r = -0.69, P < 0.05). CFC increased in the leg (3.2 +/- 0.2 to 4.3 +/- 0.5 microl . 100 g-1 . min-1 . mmHg-1, P < 0. 05), and Pi showed a trend to increase in the leg muscle (2.8 +/- 0. 7 to 3.8 +/- 0.3 mmHg, P = 0.08). These data demonstrate that TERalb is associated with PV regulation and that local transcapillary forces in the leg muscle may favor retention of albumin in the vascular space after exercise.     

Threshold values of colloid-osmotic pressure, serum albumin or protein during perioperative period

The water flux across the capillary membrane is directly related to a gradient of hydrostatic and colloid osmotic forces. The membrane is not an absolute barrier to proteins. Any change in the capillary permeability tends to decrease the plasmatic colloid osmotic pressure. The interstitial space includes a perimicrovascular space and a compliant connective tissue space, where oedema accumulates. The lymphatics may easily drain excess filtration, but cannot clear constituted oedema. Primarily, the risk of pulmonary oedema determines the lower limit of the colloid osmotic pressure. During the perioperative period, any extrapolation of the colloid, osmotic pressure from protidaemia or albuminaemia would be approximate. Two major conclusions can be drawn from the results of Guyton and Lindsey. First, in the absence of left ventricular failure, a 50% decrease in colloid osmotic pressure does not increase extravascular lung water. Second, in the case of left ventricular failure, when the left atrial pressure exceeds 10 mmHg, a 50% decrease in colloid osmotic pressure significantly increases the risk of pulmonary oedema. In these experiments, an impairment in capillary membrane permeability is likely. As a result, the threshold at which extravascular water starts to accumulate cannot be precisely defined. However, in the perioperative period, capillary membrane permeability is frequently altered by the acute phase reaction. Finally, in most perioperative clinical situations, a 50% decrease in colloid osmotic pressure may not require any treatment.     

On the methods for studying the mechanisms and bioavailability of iron

Bullous pemphigoid (BP) blisters contain several molecules, some of which spread into the blisters from the interstitial fluid, while others are produced locally and migrate into the circulation. The calculation of the ratios between blister/serum concentrations may help to distinguish between these two types of molecules. The rules regulating the diffusion of the molecules have been described only in suction blisters, where the theoretical molecular weight (MW) represents one of the principal influencing factors. The aim of the present study was to analyse the relationship between theoretical MWs and the ratios of concentrations of several molecules evaluated both in sera and in blister fluids. Eight cytokines (interleukin-2, interleukin-3, interleukin-4, interleukin-5, interleukin-10, tumor necrosis factor-alpha, oncostatin-M and vascular endothelial growth factor), two acute phase reactants (alpha-1 acid glycoprotein, haptoglobin), albumin, one soluble membrane molecule with adhesion functions (sICAM-1) and the eosinophil cathionic protein (ECP) were measured in samples from 15 patients affected with BP by means of commercially available tests. The data suggest that the MW may influence the rate of diffusion throughout the blister, both in input and output directions, despite the discontinuity observed at the basement membrane level on the BP blister floor.     

Effect of plasma colloid osmotic pressure on intraocular pressure during haemodialysis

BACKGROUND: In a previous case report, it was shown that an increase in plasma colloid osmotic pressure induced by the removal of fluid during haemodialysis was instrumental in decreasing intraocular pressure. The relation between changes in intraocular pressure, plasma osmolarity, plasma colloid osmotic pressure, and body weight before and after haemodialysis is evaluated. METHODS: Intraocular pressure, plasma osmolarity, plasma colloid osmotic pressure, and body weight were evaluated before and after haemodialysis in 36 patients. RESULTS: Intraocular pressure and plasma osmolarity both decreased significantly after haemodialysis (p < 0.0001). Plasma colloid osmotic pressure increased significantly after haemodialysis (p < 0.0001). Body weight decreased significantly because of the removal of fluid during haemodialysis (p < 0.0001). No significant correlation was found between the change in intraocular pressure and that in plasma osmolarity (r = -0.206, p = 0.2297), whereas the change in intraocular pressure was correlated with the change in plasma colloid osmotic pressure (r = -0.510, p = 0.0012) and the change in body weight (r = 0.534, p = 0.0006). A significant correlation was found between the change in plasma colloid osmotic pressure and that in body weight (r = -0.756, p < 0.0001). CONCLUSION: The change in intraocular pressure was inversely correlated with the increase in plasma colloid osmotic pressure caused by the removal of fluid during haemodialysis.     

Interstitial fluid oncotic pressures in rabbit subcutaneous tissue

Interstitial fluid oncotic pressures in rabbit subcutaneous tissues were measured by chronically implanted membrane osmometers. Pairs of osmometers were used, one using a membrane permeable and one impermeable to plasma proteins. Measurements from the small-pore membranes averaged 10.2 mmHg while pressures measured from the large-pore membrane osmometers averaged -1.2 mmHg, indicating that the measured pressures were osmotic rather than hydrostatic in nature. These values are in agreement with previously published values from this laboratory on oncotic pressures of excised rabbit skin and with a computer-simulation study of capillary fluid balance. The oncotic pressures described in this study are of the s-me general magnitude as those of lymph from most organs in the body.     

Time sequence and site of fluid accumulation in experimental neurogenic pulmonary edema

The initial phase of pulmonary edema development following intracranial pressure elevation was studied by means of transmission electron microscopy. Using perfusion fixation and application of a blood tracer (HRP horseradish peroxidase) the time sequence and site of fluid leakage out of pulmonary vessels was demonstrated: - passage of edema fluid through intercellular clefts of alveolar capillary endothelium - edema accumulation in alveolar interstitial tissue - draining of edema fluid from the alveolar septum to the interstitium of terminal bronchioli and to lymphatic vessels. An early interepithelial fluid leakage out of the alveolar wall remains questionable.     

Treatment of lymphedema of the arms and legs with 5,6-benzo-[alpha]-pyrone

BACKGROUND: Benzopyrones can reduce the volume of high-protein edema fluid by stimulating proteolysis. These compounds provide a method for removing excess protein and its consequent edema and reduce its clinical sequelae, such as chronic inflammation and secondary infections. METHODS: We conducted a randomized, double-blind, placebo-controlled, crossover trial of 5,6-benzo-[alpha]-pyrone in 31 patients with postmastectomy lymphedema of the arm and 21 patients with lymphedema of the leg of various causes (this agent, also known as 56 BaP, 1,2-benzopyrone, or coumarin, is not an anticoagulant). The patients received 400 mg of the active drug or placebo, each for six months. RESULTS: During the placebo period, lymphedema often worsened, especially in the arms. Measurements of limb volume showed that the active drug reduced the mean amount of edema fluid in the arms from 46 percent above normal to 26 percent above normal (P < 0.001) and the amount in the legs from 25 percent to 17 percent above normal (P < 0.001). The circumference of the arms was reduced from 17 percent to 13 percent above normal, and the circumference of the legs from 11 percent to 7 percent above normal (P < 0.001). The softness of the limb tissue was increased (P < 0.001), and elevated skin temperatures were reduced (P < 0.001). There were fewer attacks of secondary acute inflammation (P = 0.01). Bursting pains and feelings of hardness were decreased, as were feelings of tightness, tension, swelling, and heaviness; limb mobility also improved. The active drug was preferred to the placebo by 93 percent of the patients (P < 0.001). Side effects--mild nausea or diarrhea--occurred in seven patients taking the active drug. None withdrew from the trial, and the side effects disappeared after the first month of therapy. CONCLUSIONS: 5,6-Benzo-[alpha]-pyrone results in slow but safe reduction of lymphedema of the extremities.     

Chloroquine phosphate: a long-term follow-up of drug concentrations in skin suction blister fluid and plasma

Chloroquine is known to bind strongly to melanin and is accumulated in the skin. In dermatology, the drug is mainly used to treat photosensitivity disorders, but it has also been reported to cause sun sensitivity, especially in patients with rheumatoid arthritis. In the present study the concentrations of chloroquine phosphate in plasma and skin suction blister fluid (interstitial fluid in the skin) from 16 patients were studied by HPLC at steady-state (after 2 months' ingestion of 250 mg of the drug daily) and 2, 4 and 6-7 months after cessation of therapy. At steady-state the concentrations were similar in the two compartments, whereas after discontinuation the drug remained much longer in the skin than in the plasma. In tests using cow's eye melanin in vitro, UV irradiation failed to interact with the binding of chloroquine to melanin. It is speculated that the prolonged storage of the drug in the skin could be of importance for its therapeutic as well as adverse effects.     

Long-term effects of ventilation tubes for persistent otitis media with effusion in children

OBJECTIVE: To analyze the clinical and scintigraphic features in four postoperative patients with lower limb edema. DESIGN: Four case reports are presented, and causes of increased lymphatic flow are discussed. MATERIAL AND METHODS: Filtered 99mTc-sulfur colloid (0.1 mL; 20 MBq) was administered by subcutaneous injection into the second web space of each foot. Sequential local (inguinal) and whole-body imaging was performed periodically up to 24 hours after the injections. The patients were three women who were 40, 51, and 86 years of age and an 81-year-old man. RESULTS: Each patient had unilateral lower extremity swelling and had recently undergone an ipsilateral lower limb operation. One female patient had previously undergone proximal femoral vein ligation, and another female patient had venous insufficiency demonstrated by Doppler ultrasonography. The male patient had a history of severe arterial insufficiency, and the remaining female patient had no venous or arterial abnormalities. On lymphoscintigraphy, all patients showed increased lymphatic flow in the edematous lower limb. Only the male patient also demonstrated abnormal dermal backflow pattern. CONCLUSION: Increased lymphatic flow most likely is a normal response to lower limb edema in the presence of normal peripheral lymphatic structures. In the four described cases, a recent lower limb surgical procedure may have resulted in disturbance of normal proximal lymphatic channels. The role of sympathetic innervation of the peripheral lymphatic system is a potential factor determining lymphatic response to trauma or surgical intervention. Increased flow on lymphoscintigraphy may not necessarily represent normal flow, especially if other scintigraphic features of abnormal lymphatic function-such as dermal backflow pattern-are present.