Drainage Of Thoracic Duct Lymph Research Articles

The role of lymph factors in lung injury, bone marrow suppression, and endothelial cell dysfunction in a primate model of trauma-hemorrhagic shock.

Studies in rodent models of trauma-hemorrhagic shock (T/HS) have shown that factors contained in the intestinal lymph are responsible for acute lung injury and bone marrow suppression, and that they contribute to a systemic inflammatory state. Because results observed in rodent T/HS models may not fully reflect the response of injured patients, it is necessary to determine if these results can be replicated in primates before the institution of invasive studies in humans. Thus, the three goals of this study were to determine if diversion of thoracic duct lymph reduced T/HS-induced lung injury; to compare the biologic activity of thoracic duct lymph from baboons subjected to T/HS or trauma sham-shock (T/SS); and to compare the biologic activity and composition of plasma from baboons subjected to T/SS, T/HS, and T/HS with thoracic duct lymph drainage. Three groups of baboons were studied: T/SS plus lymph diversion via a thoracic duct catheter, T/HS, and T/HS plus lymph diversion (T/HS-LD). The trauma component consisted of a neck dissection with resection of the proximal clavicle plus a laparotomy. HS was to a mean arterial pressure of 40 mmHg and was maintained at 40 mmHg until the base excess reached -5 mEq or the total shock period reached 3 h. Volume resuscitation was carried out by reinfusing the shed blood plus crystalloids. Before, during, and after the T/HS or T/SS period, blood and lymph samples were obtained for analysis, and lung samples were harvested for measurement of lung wet-to-dry ratio at 5 h after the end of the shock period. Diversion of thoracic duct lymph prevented T/HS-induced lung injury as reflected in lung wet-to-dry weight ratios (T/SS = 4.6 +/- 0.5; T/HS+LD = 4.8 +/- 0.7; T/HS = 5.4 +/- 0.6; P < 0.05). Lymph from the T/HS group collected during the early postshock period was cytotoxic for human endothelial cells (HUVECs; 16% vs. 100% survival in T/SS lymph) and increased HUVEC monolayer permeability almost 2-fold (P < 0.01). T/HS lymph and plasma also suppressed red blood cell (erythroid burst-forming unit) and white blood cell (granulocyte-monocyte colony-forming unit) progenitor cell growth of human bone marrow to approximately 50% of control, whereas T/SS lymph and plasma were not suppressive (P < 0.05). Plasma cytokine levels were increased to a similar degree in the two T/HS groups. Thus, in a primate model of T/HS, gut-derived factors carried in the lymph potentiates lung injury and endothelial dysfunction, and suppresses bone marrow progenitor cell growth.

Myasthenia Gravis: A Review

Myasthenia Gravis: A Review

Trichinella spiralis: Newborn larval migration route in rats reexamined

The route by which Trichinella spiralis newborn larvae migrate from the small intestine to striated muscle was studied in inbred AO and random-bred Sprague-Dawley rats. Newborn larvae were quantitatively recovered from the thoracic duct lymph, peritoneal cavity, and hepatic portal vein blood during the course of a primary infection with 4000 muscle larvae. The total recovery of newborn larvae assessed in this manner was compared with the number of muscle larvae in control rats receiving the same infection. In both strains of rats, most of the newborn larvae were recovered from hepatic portal vein blood, fewer than 3% of newborn larvae were recovered from the thoracic duct lymph and peritoneal cavity combined. Long-term drainage of thoracic duct lymph (>24 hr) significantly increased newborn larval recovery over short-term drainage (<24 hr). We conclude that there are several natural pathways of newborn larval migration that result in muscle larval establishment. These include direct invasion of capillaries and lymphatics in the intestine as well as migration through the intestinal serosa to the peritoneal cavity. In both AO and Sprague-Dawley rats. ⩾97% of newborn larvae migrate via the hepatic portal vein blood to the general circulation.

Lysozyme concentrations in synovial fluid, pleural fluid and thoracic duct lymph in rheumatoid arthritis.

Lysozyme (LZM) concentrations in synovial fluid were determined in patients with seropositive and seronegative rheumatoid arthritis (RA) and in patients whose arthritic exudates had been caused by Reiter's disease, a Yersinia enterocolitica infection, osteoarthritis, or trauma. Patients with rheumatoid disease had significantly higher levels of lysozyme in synovial fluid than patients with non-rheumatic diseases. The concentration of lysozyme correlated with the number of polymorphonuclear leukocytes in synovial fluid in seronegative--but not in seropositive--rheumatoid arthritis. In patients with rheumatic arthritis the lysozyme level correlated inversely with the concentration of glucose in synovial fluid. In patients with rheumatoid pleural effusion, lysozyme levels in pleural fluid were comparable to those in serum. The concentration of LZM in thoracic duct lymph was roughly the same as in serum. During drainage of thoracic duct lymph, the lysozyme level in serum decreased.

Endogenous endotoxin absorption and the role of intestinal lymphatics.

We investigated the absorption routes of endotoxin derived from the intestine of rabbits with or without thoracic duct lymph drainage (TDLD). The intestinal circulatory disorders induced were superior mesenteric artery occlusion (SMAO) and superior mesenteric vein occlusion (SMVO). Detection and quantitation of endotoxin in plasma and lymph were carried out using a synthetic chromogenic substrate (peptide-4-methyl-coumarin amide, MCA). In the SMAO group, endotoxin levels in portal plasma exceeded levels in lymph from the thoracic duct throughout the experiment, and in the SMVO group, the relationship was reversed. In peripheral arterial blood, endotoxin levels were significantly lower in rabbits with TDLD than in those with intact lymphatic system. Intestinal lymphatics probably play an important role in appearance of systemic endotoxemia in non-septic shock.

EFFECTS OF SOME IMMUNOSUPPRESSIVE PROCEDURES ON MYASTHENIA GRAVIS*

Clinical Observations. A total of 53 MG patients have been treated with different immunosuppressive methods (alone or combined) with the following effects: Thymectomy was performed in 38 patients. The improvement was excellent in 15, and moderate or uncertain in 20. In three patients severe long-lasting deterioration followed the operation. ACTH treatment (n=32): Initial deterioration during the 5-7 days of heavy ACTH treatment (1000 IU) was followed by an improvement lasting on an average 4 months. The improvement was good or moderate in 78% of the patients. Betamethazone treatment has been tried in six patients where ACTH and azathioprine was ineffective. In four of these patients the results were excellent. Azathioprine treatment has been given to 26 patients for periods up to 7 years. An improvement is measurable after 6-12 weeks and it seems maximal after about 1 year. Of the 26, 80% responded favorable with reduction in the need for cholinesterase inhibitors. Severe complications were seen in three patients with one death. Drainage of thoracic duct lymph was initiated in 14 patients up to 4 weeks with rapid improvement lasting as long as drainage was performed. Long-termed effects of the drainage may be present, however. Retransfusion of homologous cell-free lymph precipitated a return of the myasthenic symptoms. Biochemical Studies on Myasthenic Lymph. Using a membrane preparation from the electric organ from Torpedo marmorata and tritiated Naja naja siamensis neurotoxin we demonstrated a decreasing binding of toxin to the receptor in the presence of MG lymph gamma-globulin fraction. Gammaglobulins from controls showed almost no inhibition of the neurotoxin binding. Immunological Studies. An increased frequency of HL-A1 and 8 was found in female patients. LD typing was also performed. During a period of three weeks of thoracic duct drainage 130X10(9) or about 10% of total number of lymphocytes in the body were removed. In the lymph an initial decrease in the proportion of thymus-derived lymphocytes (T cells) occurred, which was accompanied by a sequent increase in the proportion of bone-marrow-derived lymphocytes (B cells). Towards the end of drainage this effect was reverted. Mitogenic stimulation using lymphocytes from thoracic duct drainage revealed no differences as compared to normal cells. The proportions of T and B cells was studied in the peripheral blood in nine patients treated with ACTH. During treatment there was an initial decrease in the proportion of T cells accompanied by a subsequent rise in the proportion of B cells, which was maximal after 3-10 days. These proportions were reverted to normal 1-5 days after the maximal change. The effect of azathioprine on T and B cells has also been studied.

Plasma enzyme levels in the anaesthetised dog during drainage of thoracic duct lymph.

The effect of continuous removal of thoracic duct lymph on plasma activities of creatine phosphokinase (PCK), glutamic-oxaloacetic transaminase (PAST); and lactic dehydrogenase (PLDH), uas examined in pentobarbital-anaesthetised dogs over a 5.5-hour period. PCK and PAST declined relative to levels in control dogs while PLDH was unaltered. Lymph/plasma (L/P) ratios for AST and CPK were greater, and for LDH less, than the L/P ratio for total protein. It was concluded that PCK, and to some extent PAST, are normally maintained by introduction of enzyme, escaping from the intracellular compartment, into the circulating blood via the lymphatic system. PLDH and PAST appear to be maintained principally by introduction of enzyme directly from the intracellular to the plasma compartment.

Lymphopoiesis and lymphocyte recirculation in the sheep fetus.

The production and the circulation of lymphocytes has been examined in the sheep fetus where neither foreign antigen nor immunoglobulins occur. It was found that as the lymphoid organs increased in size during fetal life, the numbers and the output of lymphocytes in the thoracic duct lymph increased. The recirculating pool of lymphocytes was estimated to be 5.5 +/- 1.5 X 10(8) cells in fetal lambs 95-100 days of age, 5.7 +/- 1.2 X 10(9) cells in fetuses 130-135 days of age, and 1.2 +/0 9.3 X 10(10) cells in fetuses near to term. The rate of addition of lymphocytes to the recirculating pool was 3.2 +/- 1.9 X 10(6) cells/h in fetuses of 100 days and 3.4 +/- 0.9 X 10(7) cells/h in fetuses of 130 days of age. Lymphocytes recirculated from blood to lymph in fetuses; labeled cells injected into the blood stream reappeared in the thoracic duct lymph promptly and reached maximum levels around 12-18 h after they were injected. Labeled lymphocytes were detected subsequently in greatest numbers in the lymph nodes, particularly in the mesenteric lymph nodes and in the interfollicular areas of the Peyer's patches. Chronic drainage of thoracic duct lymph from fetuses in utero for periods of up to 36 days had no obvious effects on the growth or development of the fetus and only minimal effects on the content of lymphocytes in the various lymphoid tissues even though the number of cells in the blood and lymph were reduced to between 20-30% of normal levels. Thymectomy done in fetuses about 2 mo befor cannulation of the thoracic duct reduced the output of cells in the thoracic duct to about 25% of normal levels and caused a significant reduction in the content of lymphocytes in the various lymphoid tissues. Thymectomized fetal lambs subjected to thoracic duct drainage for periods up to 2 wk in utero had a similar complement of lymphocytes in their lymphoid tissues to intact thymectomized fetal lambs. Lymphocytes obtained from the thoracic duct lymph of lambs thymectomized 2 mo previously recirculated from blood to lymph when they were injected intravenously, although they did this at a significantly slower rate than did lymphocytes from normal lambs.

Study on the Thoracic duct lymph Drainage in Congestive Heart Failure.

Study on the Thoracic duct lymph Drainage in Congestive Heart Failure.

Hepatic portoenterostomy. Indicated or not in the treatment of biliary atresia?

Drainage of the biliary tree in infants with biliary atresia remains an unsolved problem, for more than 90% of such infants have an uncorrectable-type lesion, ie, no extra-hepatic bile duct is available for anastomosis to the intestine. The history of attempts to surgically circumvent this problem has been a most depressing one. Claims of success with procedures such as the use of artificial ducts to connect the liver and gastrointestinal tract 1 and the drainage of thoracic duct lymph 2,3 have all been short lived. Biliary atresia, for unknown reasons, is much more common in Japan than in the United States. This had led to great interest in the surgical treatment of the disease by Japanese investigators. Kasai and associates, in 1957, first reported the use of hepatic portoenterostomy in the surgical treatment of uncorrectable types of biliary atresia. 4 They originally claimed a cure rate of approximately 10%. More

Drainage of Thoracic Duct Lymph in Twelve Patients with Myasthenia gravis

The effect of thoracic duct lymph drainage (5-34 days) in 12 patients with myasthenia gravis on muscular function has been followed for 5-43 months. Among the results obtained were: (1) During the drainage the myasthenic symptoms decreased markedly after 1-4 days and remained so during the drainage. (2) The doses of cholinesterase inhibitors had to be markedly reduced during the lymph drainage in eight patients. (3) Discontinuation of the lymph drainage increased the myasthenic symptoms within a few days. However, after a median observation time of 14 months with conventional treatment all but one of the patients had improved. (4) Retransfusion of the patients own cell-free lymph caused a worsening of the myasthenic symptoms. This effect could also be obtained following infusion of IgG preparations from the patients lymph. Three retransfusions of cell suspensions obtained from the thoracic duct lymph from two patients had no effects on their myasthenic symptoms. (5) It is suggested that thoracic duct lymph drainage can be combined with other forms of treatment in severe cases of myasthenia gravis.

The effect of thoracic duct lymph drainage in myasthenia gravis.

The following effects were noticed when lymph was drained from the thoracic duct of four patients with severe myasthenia gravis. (1) A pronounced improvement in the myasthenic symptoms was seen after 1–4 days of drainage. In one patient (G. K.) an almost complete remission was seen and the dose of anticholinesterase could be markedly reduced. (2) When the lymph drainage was discontinued the myasthenic symptoms increased again to about the same level as before the drainage. (3) The myasthenic symptoms returned rapidly when the patients own cell-free lymph was retransfused. (4) The lymph drainage did not seem to affect the further course of myasthenia gravis.

Hypercalcaemia in acute leukaemia.

A thoracic duct lymph drainage was performed in ten patients, six of them suffered from a malignant disease of the lymphatic system. The daily output of lymph fluid and its total content of lymphocytes were determined in addition to the lymphocyte counts of simultaneously taken blood and lymph samples. In patients with malignant lymphomas, autologous blood lymphocytes were labeled in vitro with3H-cytidine and were then retransfused. Thereby the minimal recirculation time and the percentage of recirculating, labeled lymphocytes could be evaluated.

The presence of non-recirculating long-lived lymphocytes in rat blood.

An attempt has been made to find out if all the long‐lived lymphocytes in the rat are recirculating between blood and lymph.Selective labelling of long‐lived lymphocytes was obtained by daily injections of 3H‐thymidine for a period of 2–3 weeks, and by subsequently waiting at least 14 days after the last injection. The rats were then depleted of recirculating lymphocytes by continuous drainage of thoracic duct lymph for 2–4 days. The content of labelled cells in blood and thoracic duct lymph at various stages during the drainage period was evaluated by radioautographic and radiochemical techniques. The lymph depletion caused a reduction in the percentage of labelled cells in thoracic duct lymph, but not in blood, where actually an increase in the percentage of labelled lymphocytes was recorded.The results suggest that there is a group of long‐lived lymphocytes in rats which do not recirculate between blood and lymph.

Controlled rate of drainage of thoracic duct lymph

Controlled rate of drainage of thoracic duct lymph can effect advantageous decreases in portal, systemic, and pulmonary venous hypertension. Anticonstrictor drugs complement this action. Serial renal function tests can corroborate the functional effectiveness of these plateaus of lowered pressure, achieved by limited favorable alterations in effective plasma volume.

Albumin to ascites: demonstration of a direct pathway bypassing the systemic circulation.

The transport of plasma albumin and newly made albumin into ascitic fluid was studied in eight patients with cirrhosis and ascites. The thoracic duct was cannulated in two patients and lymph collected over a period of 2 hr. Simultaneously albumin-(131)I and carbonate-(14)C were injected intravenously. The albumin-(131)I measured the transfer of plasma albumin into ascites and into thoracic duct lymph. The carbonate-(14)C, by labeling newly formed albumin, permitted the estimation of the transfer of newly formed albumin into plasma, ascites, and lymph. If the newly synthesized albumin entering ascites and thoracic duct lymph is delivered initially into the plasma, then the ratios of the albumin-(14)C and -(131)I in ascites and lymph compared with the content of albumin-(14)C and -(131)I in plasma would be identical. However, if some newly formed albumin is delivered directly into ascites or lymph, the ratio for albumin-(14)C would be higher than that for albumin-(131)I in lymph or ascites. The ratios of both labeled albumins found in ascites or lymph are expressed as per cent of the total plasma pool. In the eight patients studied 4.2-11.7% of the albumin-(14)C in plasma was found in ascites in 2 hr whereas only 0.4-2.2% of plasma albumin-(131)I entered in this same period. In the two patients studied during thoracic duct lymph drainage 6.1 and 13.5% of newly made albumin-(14)C appeared in lymph in 2 hr whereas only 2.8 and 3.8% of plasma albumin-(131)I was found in the lymph. In cirrhosis with ascites some newly formed albumin entered ascites and thoracic duct lymph by a direct pathway from the liver bypassing the systemic circulation.

Retrograde flow of portal vein blood in patients with cirrhosis.

In 1907, Herrick demonstrated that hepatic arterial flow could reflux into the portal vein (1). Spontaneous reversal of portal vein flow in patients with cirrhosis can occur only when the hepatic outflow resistence exceeds the resistance through portal venous collaterals and probably represents an advanced stage of portal hypertension. This report confirms the occasional existence of hepatofugal flow of portal venous blood in patients with cirrhosis and describes the radiographic characteristics of umbilical vein portograms demonstrating this phenomenon. Angiograms obtained from 2 of 150 patients with cirrhosis of the liver who had umbilical vein portography form the basis of this communication. Method The technic of umbilical vein catheterization has been previously reported (2, 3). This approach to the portal venous system is used whenever splenic puncture fails to demonstrate a portal vein or cannot be carried out because of contraindications, technical difficulties, or prior splenectomy. Umbilical vein catheterization has also been performed in patients with bleeding esophageal varices who were too ill to withstand a major surgical procedure, in order to monitor the response of the portal pressure to conservative modalities, such as thoracic duct lymph drainage (4), vasopressin (5), and extracorporeal umbilicosystemic shunts (6). Results The injection of a radiopaque substance, under pressure, through an umbilical vein catheter results in dispersion of the agent throughout the intrahepatic portal venous system. In patients without cirrhosis, the contrast medium rarely refluxes caudad in the portal vein but progresses cephalad through the liver. In patients with cirrhosis and portal hypertension, the contrast material refluxes caudad in the portal vein and into splenic, mesenteric, and coronary collaterals (Fig. 1, A). Angiograms obtained several seconds after completion of the injection show opacification of the liver as the medium passes through hepatic sinusoids (Fig. 1, B). Figure 2 illustrates a portogram series obtained from a patient with cirrhosis of the liver and bleeding esophageal varices, who had an umbilical vein catheter inserted to monitor the response of the portal pressure to vasopressin. This patient had ascites, muscle wasting, encephalopathy, prothrombin time of twenty-one seconds, serum bilirubin of 16.4 mg/100 ml and serum albumin of 2.0 g/100 ml. The vasopressin reduced the portal pressure 10 cm and controlled the bleeding. The patient was eventually discharged from the hospital and is alive twelve months later. Figure 2, A demonstrates the beginning of the portogram as 40 ml of 75 per cent Hypaque is injected at a pressure of 125 p.s.i. The right branch of the portal vein is not visualized, and the contrast material has begun to reflux into the splenic, mesenteric, and coronary veins. Figure 2, B is the portogram obtained at one second.

Effect of Lymph Drainage on Portal Pressure and Bleeding Esophageal Varices

The effect of thoracic duct lymph drainage on portal pressure and bleeding esophageal varices in 7 patients with cirrhosis has been evaluated. Four control patients with cirrhosis and bleeding varices were monitored in similar fashion without lymph drainage. Significant reductions in portal pressure were associated with hypovolemia from inadequate lymph replacement or recurrent hemorrhage from esophageal varices. The portal, central venous, and arterial pressures, urine output, and body weight remain unchanged when lymph was reinfused at the same rate as withdrawal. The functional thoracic duct pressure approached the central venous pressure. lymph drainage did not appear to control hemorrhage from varices since bleeding continued or recurred in 4 patients while lymph was being drained.

Experimental studies of thoracic duct anastomoses with the esophagus in dogs

Following the drainage of thoracic duct lymph into the esophagus in dogs, the protein loss caused by liver cirrhosis increases. Total cholesterol, total lipids and phospho-lipids decrease to normal levels. The elevated serum bilirubin falls to normal or slightly increased values. An increase of total protein and fat suggests an obliteration of the anastomosis, a frequent complication of the surgery. The cirrhotic changes cannot be halted by draining the lymph in spite of normal bilirubin levels. Following the drainage of thoracic duct lymph into the esophagus in dogs, the protein loss caused by liver cirrhosis increases. Total cholesterol, total lipids and phospho-lipids decrease to normal levels. The elevated serum bilirubin falls to normal or slightly increased values. An increase of total protein and fat suggests an obliteration of the anastomosis, a frequent complication of the surgery. The cirrhotic changes cannot be halted by draining the lymph in spite of normal bilirubin levels. Le commun ducto biliari esseva ligate in 14 canes. In 9 de illos, un secunde intervention esseva addite, consistente in le diversion del ducto thoracic ad in le esophago con le utilisation del vena jugular. Le resultato esseva reductiones del nivellos de proteina total e de albumina, sed le alterationes cirrhotic in le hepate non esseva afficite per iste typo de drainage lymphatic. le nivello de bilirubina deveniva normal o remaneva levemente elevate. Le nivello de cholesterol deveniva normal, e le mesmo valeva pro le phospholipido e le grassia total. Le commun ducto biliari esseva ligate in 14 canes. In 9 de illos, un secunde intervention esseva addite, consistente in le diversion del ducto thoracic ad in le esophago con le utilisation del vena jugular. Le resultato esseva reductiones del nivellos de proteina total e de albumina, sed le alterationes cirrhotic in le hepate non esseva afficite per iste typo de drainage lymphatic. le nivello de bilirubina deveniva normal o remaneva levemente elevate. Le nivello de cholesterol deveniva normal, e le mesmo valeva pro le phospholipido e le grassia total.

A clinical and pathological study of congenital biliary atresia

<h2>Summary</h2> In infants under 2 months of age with biliary atresia and absent extrahepatic bile ducts, thoracic duct lymph drainage should be performed as an initial procedure in order to prevent progressive cirrhotic changes, according to our histological studies. If ultrasonic echo examination shows the presence of a microcystic pattern and liver biopsy shows the presence of intraphepatic ducts, intrahepatic cholangio-jejunostomy should be performed as a second operation after the patients have reached the age of 6 months.