Hepatic Portal Area Research Articles

The influence of cold preservation on the microcirculation of intrahepatic bile duct after liver transplantation

To discuss the influence of cold preservation on intrahepatic biliary microcirculation. Male Sprague Dawley (SD) rats were divided into 3 groups:cold preserve 1 h group (CP 1 h group), cold preserve 24 h group (CP 24 h group) and sham operation group (SO group). Five time points were determined as 0 h, 1 h, 6 h, 24 h and 72 h postoperation. Morphology was observed under light microscope. Dark microspheres were injected into hepatic artery and the number of microspheres in liver portal areas was measured under light microscope. The expressions of eNOS, ET-1 and ICAM-1 in microvascular endothelial cells of hepatic portal area were measured by immunofluorescence double staining technique and in situ hybridization histochemistry. The histological changes of intrahepatic bile duct were more severe in CP 24 h group than in CP 1 h group. The number of microspheres in implanted liver portal areas was increased significantly in CP 24 h group than in CP 1 h group at the same time point. Compared with CP 1 h group, the expression of eNOS in CP 24 h group significantly reduced after liver transplantation, while the expressions of ET-1 and ICAM-1 in CP 24 h group were significantly increased after liver transplantation. The changes of their mRNA expressions were the approximately same as well as their proteins expressions. Cold preservation brings obvious changes of intrahepatic biliary microcirculation and function of vascular endothelial cell after liver transplantation. The obstruction of microcirculation might play an important role in the reperfusion injury after cold preserve of intrahepatic biliary during liver transplantation.

Granulocyte colony-stimulating factor-mobilized autologous bone marrow stem cells promote the liver regeneration of partial liver transplant: an experiment with rats

To investigate the effects of granulocyte colony-stimulating factor (G-CSF)-mobilized autologous bone marrow stem cells on the liver regeneration of partial liver transplant. A 50% partial liver transplantation model as established by transplanting parts of the liver of female rats to the male rats with the equal weights that had had parts of their livers resected. Then the transplanted male rats were randomly divided into 3 equal groups: G-CSF + PLTx group that was injected hypodermically with recombinant human G-CSF (rhG-CSF) daily for 5 days and then underwent liver resection and 50% partial liver transplantation (PLTx); PLTx + G-CSF group that underwent PLTx and 3 hours after the transplantation received injection of rhG-CSF daily for 5 days, and PLTx control group that underwent PLTx and 3 hours later received injection of normal saline daily for 5 days. One, 3, 5, 7, and 14 days after the PLTx blood samples and livers were collected from 6 rats from each group, and one hour before the liver was taken bromodeoxyuridine (BrdU) was injected intraperitoneally to be integrated into the synthesis of DNA in the liver cells. Immunohistochemistry was used to detect the CD34 and BrdU-positive cells. In situ hybridization was used to detect the sry (sex-determining region) gene so as to determine the origin of the proliferating cells in the transplanted liver. The 14-day survival rate of the G-CSF + PLTx group was 90%, significantly higher than those of the G-CSF + PLTx (60%) and PLTx group (50%) (both P < 0.05) with a significant difference between the latter 2 groups too (P < 0.05). The mitosis index of liver cells 3 days after the transplantation of the PLTx + G-CSF group was 30% +/- 5%, significantly higher than those of the G-CSF + PLTx group (24% +/- 7%) and PLTx group (24% +/- 6%) (both P < 0.05) without a significant difference between the latter 2 groups. The rate of BrdU-positive cells of the PLTx + G-CSF group was 42% +/- 6%, significantly higher than those of the G-CSF + PLTx group (38% +/- 4%) and PLTx group (34% +/- 8%) (both P < 0.05). The transplantation the mitosis index and rate of BrdU-positive cells decreased since the 7th days after transplantation in all 3 groups, however, with the same relationship among them. The numbers of CD34(+) cell around the portal area of the 2 G-CSF groups increased since the 3rd day after transplantation in comparison with the PLTx group, was the highest on the 3rd day for the G-CSF + PLTx group, and continued to increase in the PLTx + G-CSF group. Since the 3rd day after transplantation, sry-positive cells were seen in the hepatic sinusoid and portal area in the 2 G-CSF groups, and were rarely seen in the PLTx group. G-CSF treatment after 50% PLTx significantly promotes liver regeneration and ameliorates the liver damage, thus raising the survival rate.

Apoptosis in organs of rats in early stage after polytrauma combined with shock.

Apoptosis in organs of rats in early stage after polytrauma combined with shock was researched. Sixty Sprague-Dawley rats were divided into six groups: normal control (A, n = 6), sham-operation (N, n = 6), single hemorrhagic shock (S, n = 6), two-site trauma/shock (B, n = 6), four-site trauma/shock (C, n = 6), and six-site trauma/shock (D, n = 30). Shock was kept 60 min by blood withdrawal. Polytrauma was performed by clamping different sites of limbs to make fractures according to different groups: B at both femurs; C at femurs and tibias; and D at femurs, tibias, and humeri. The animals of A were totally normal without any operation. The rats of N, S, B, and C were killed at 6 hours after resuscitation, and the rats of D were killed at 1, 3, 6, 12, and 24 hours, respectively. Then, DNA agarose gel electrophoresis, in situ end-labeling (ISEL), and light and electron microscopy were performed and the percentage of DNA fragmentation was detected to assess apoptosis. In B, C, and D, the special ladder patterns for apoptosis were seen in thymus, spleen, liver, lung, and intestine, but not in heart, kidney, and brain. However, positive responses were observed in all these eight organs by ISEL. At 6 hours after resuscitation, the percentages of DNA fragmentation in thymus, spleen, liver, lung, and intestine all increased together with the severity of trauma. In D, the percentages of DNA fragmentation in these five organs all increased significantly at 1 hour after resuscitation. At 3 hours, the percentages in spleen, liver, lung, and intestine reached peak, and declined gradually afterward, whereas those in thymus continued increasing after 3 hours and kept stable from 6 hours to 24 hours. It was shown by morphologic examination that the majority of apoptotic cells lay in cortex of thymus, in growth center of white pulp of spleen, in border area of hepatic lobule and portal area of liver, and at the base of crypts of intestine. In lung, multiple kinds of cells, including alveolar epithelial cells, vascular endothelial cells, and polymorphonuclear neutrophils, induced apoptosis. Apoptosis was induced in thymus, spleen, liver, lung, and intestine in early stage after polytrauma combined with shock, which may play partial roles in the development of multiple organ failure.

Lymphoma diagnosed as a solitary pancreatic head lesion by fine needle aspiration with endoscopic ultrasound

Purpose: Prymary lymphoma of the pancreas is a rare entity. Non-Hodgkins lymphoma can present in an extranodal site in up to 25% OF Cases. Pancreas is the primary site of origin in less than 3% of all Non-Hodgkin's lymphomas. In recent history, transcutaneous needle aspiration of pancreatic lesions is avoided because of the high percentage of needle tract tumor seeding. We report a case of a pancreatic mass that by CT appeared to be involving the porta hepatis area. Fine needle aspiration (FNA) by endoscopic ultrasound, a method not known for tumor seeding of the needle tract, revealed a B-Cell lymphoma originating in the head of the pancreas.

Unexplained intraoperative hypotension, acute ischemic hepatitis, and pancreatitis associated with aortorenal bypass surgery

A 69-year-old male smoker who had severe atherosclerotic renovascular disease associated with progressive deterioration of kidney function, poorly controlled hypertension, and a 5-cm solid fight renal mass was scheduled for partial nephrectomy and hepatorenal bypass. He had no history of other cardiovascular disease or prior abdominal surgery. The physical examination was unremarkable except for a blood pressure of 170/90 mmHg. Laboratory studies included normal white blood cell count, hematocrit, platelet count, liver function tests, and clotting characteristics. The blood urea nitrogen concentration was 25 mg/dL (normal, 8 to 25 mg/dL); creatinine, 2.2 mg/dL (normal, 0.7 to 1.4 mg/dL); and creatinine clearance, 25 mL/min. Carbon dioxide arteriography was performed 1 month before the surgery and showed bilateral proximal 80% renal artery stenosis. A lateral aortogram showed a mild proximal celiac trunk stenosis with patent splenic, hepatic, and superior mesenteric arteries, and occluded inferior mesenteric artery. The right hepatic artery originated from the superior mesenteric artery and had a 50% to 60% osteal stenosis. The preoperative electrocardiogram and thallium stress test were normal; a carotid duplex ultrasound showed a 40% to 59% stenosis of the fight internal carotid artery. Under general endotracheal anesthesia (induction and endotracheal intubation with 150 mg of propofol and 10 mg of vecuronium, and maintenance with oxygen, nitrous oxide, and isoflurane), a bilateral subcostal incision was made, and a Bookwalter retractor was positioned. At exploration, a decreased pulse was noted in the porta hepatis area; therefore, an aortorenal rather than a hepatorenal bypass was performed. After resection of the kidney mass under cold ischemia (duration, 45 minutes), the anterolateral side of the aorta was clamped, and an aortorenal bypass with a reversed greater saphenous vein graft was performed with warm ischemia time of 25 minutes. The patient received no systemic heparinization and only regional arterial heparin flushes (up to 1,000 U) were used during the revascularization. The operation lasted about 4 hours. During the first 2 hours, the systolic blood pressure was between 100 and ll0 mmHg, and a continuous intravenous dopamine drip (dose, 1 to 3 ~tg/kg/min) was administered. The central venous pressure was 15 to 18 mmHg. During the last 2 hours of the surgery, the systolic blood pressure was maintained between 90 to 100 mmHg (despite relatively low blood loss and light anesthesia with 0.2% to 0.3% isoflurane) with increased fluid administration, and dopamine and epinephrine infusions at 12 ~g/kg/min and 0.03 to 0.07 pg/kg/min, respectively. The estimated blood loss during the entire operation was 1,500 mL, and the patient received 2 U of packed red blood cells. In

Hepatic fibrosis produced in guinea pigs by chronic ethanol administration and immunization with acetaldehyde adducts

Experimental hepatic fibrosis was produced in the guinea pig. We produced hepatic necrosis associated with inflammatory cell infiltration in guinea pigs immunized with acetaldehyde adducts and fed ethanol for 40 days. Extending the period of these treatments to 90 days resulted in producing hepatic fibrosis developing around individual hepatocytes in the terminal hepatic venule areas and portal areas, accompanied by an increase in hepatic hydroxyproline content. In contrast, no fibrosis was observed in the livers of the control groups that had been exposed to nothing, ethanol alone, or a combination of ethanol and immunization with unmodified human hemoglobin. Minimal fibrotic changes were observed in animals immunized with human hemoglobin acetaldehyde adducts but not fed ethanol. These results indicate that the formation of acetaldehyde adducts and the acquisition of immunity against them can produce hepatic fibrosis. Immune mechanisms against acetaldehyde adducts may, in part, be involved in the pathogenesis of hepatic fibrosis seen in alcoholics.

Hepatic fibrosis produced in guinea pigs by chronic ethanol administration and immunization with acetaldehyde adducts

Experimental hepatic fibrosis was produced in the guinea pig. We produced hepatic necrosis associated with inflammatory cell infiltration in guinea pigs immunized with acetaldehyde adducts and fed ethanol for 40 days. Extending the period of these treatments to 90 days resulted in producing hepatic fibrosis developing around individual hepatocytes in the terminal hepatic venule areas and portal areas, accompanied by an increase in hepatic hydroxyproline content. In contrast, no fibrosis was observed in the livers of the control groups that had been exposed to nothing, ethanol alone, or a combination of ethanol and immunization with unmodified human hemoglobin. Minimal fibrotic changes were observed in animals immunized with human hemoglobin acetaldehyde adducts but not fed ethanol. These results indicate that the formation of acetaldehyde adducts and the acquisition of immunity against them can produce hepatic fibrosis. Immune mechanisms against acetaldehyde adducts may, in part, be involved in the pathogenesis of hepatic fibrosis seen in alcoholics.

Activation of portal-hepatic osmoreceptors in rats: role of calcium, acetylcholine and cyclic AMP

Osmoreceptors are sensory organs of paramount importance in water and electrolyte balance, yet the mechanisms for their activation are virtually unknown. Peripheral osmoreceptors have been localised in the hepatic portal vein area of rats. We thus superfused the portal adventitia with 0.2 ml of 4% NaCl before and after various pharmacological pretreatments (0.4 ml of 1 mM solutions) of the portal area, while monitoring the neural activity of the hypothalamo-neurohypophysial system. Portal superfusion with verapamil, to reduce Ca-influx, reversibly inhibited the response to osmotic stimuli by up to 50% ( P < 0.0005). Such inhibition (58%; P < 0.0005) was also seen with portal superfusion by atropine. Atropine did not affect hypothalamo-neurohypophysial responses to stimulation of portal bradykinin receptors with 0.2 ml 1 μM bradykinin, and portal superfusion with acetylcholine activated the hypothalamo-neurohypophysial system. The results thus support the hypothesis of a cholinergic neurotransmission linking portal osmoreceptive structures and afferent nerve endings. Diamide, which inhibits water efflux in frog skin, also reversibly inhibited responses to osmotic stimuli by 38% ( P < 0.0005). Pretreatments with trifluoperazine, a calmodulin inhibitor, and cordycepine, an adenylate cyclase inhibitor, diminished responses to osmotic stimuli by 30–45% ( P < 0.005), while cAMP and theophilline potentiated them by 38% ( P < 0.0005). Responses to bradykinin superfusion were reduced 20–30% ( P < 0.05) by both cordycepin and cAMP. The results suggest that portal osmoreceptors release acetylcholine to excite afferent nerves when exposed to an osmotic gradient. The mechanism of this release may be mediated by an efflux of water and an increase of intracellular calcium activity and cAMP.

Electron microscopic examination of mast cells and nerve processes in hepatic portal areas of the rat

Neural mechanisms are important in the regulation of numerous hepatic functions including hepatic blood flow, carbohydrate metabolism and biliary flow. The innervation of the liver is species specific and in the rat, light microscopic data indicated that catecholamine and cholinergic nerves were present in portal areas. (1,2) Electron microscopic studies described the presence of nerve endings in the connective tissue adjacent to blood vessels and bile ducts as well as limiting plate hepatocytes. (2) A previous study in this laboratory reported unmyelinated nerve processes near mast cells. (3) The present study was undertaken to quantify the appearance of nerves and their relationship to mast cells in hepatic portal areas in rats.Hepatic tissue from 8 rats was removed and fixed in 2% glutaraldehyde and 2% paraformaldehyde in a 0.1M Na cacodylate buffer (pH 7.3), postfixed in 1% osmium tetroxide, and embedded in Epon. Sections stained with uranyl acetate and lead citrate were viewed on a Philips 301 electron microscope. A minimum of 3 sections per rat and a total of 30 portal areas were analyzed.

Spinal substance P transmits bradykinin but not osmotic stimuli from hepatic portal vein to hypothalamus in rat

Peripheral osmo- and bradykinin-sensitive receptors which have been previously localised within the hepatic portal vein area, activate the hypothalamo-neuro-hypophysial system through a neural pathway projecting to the lower thoracic spinal cord. In this paper we attempted to identify the spinal transmitter(s) involved and to answer the question whether osmoreceptors are in fact chemosensitive nociceptors. The portal vein of anesthetised rats was superfused with 0.2ml of 4% NaCl or 1μM bradykinin, and hypothalamo-neurohypophysial responses were measured either electrophysiologically or by radioimmunoassay of arginine vasopressin. Responses to bradykinin, but not to hypertonic saline, were abolished in rats pretreated 2 wks previously with capsaicin s.c., and immunocytochemistry for substance P in these animals showed that substance P was strongly depleted both in the dorsal thoracic spinal cord and in the portal vein. The spinal injection of 8μl 0.1 mM capsaicin at T8–T9 elicited a pronounced hypothalamo-neurohypophysial response, and diminished reversibly the response to bradykinin superfusion of the portal vein. Spinal capsaicin had no effect on responses to hypertonic saline. Similarly, the spinal (T8–T9) injection of 8 μg substance P antagonist, the [ d-Pro 4, d-Trp 7,9,10, Val 8] substance P (4–11), reduced reversibly the responses to bradykinin by about 50% without affecting those to hypertonic saline. The spinal injection of 8 μg substance P, at the same site where substance P antagonist was applied, elicited within 4s a prolonged response (several min). A slightly longer delay between stimulus and neurophysiological response was observed for spinal capsaicin and for bradykinin superfusion. Responses to hypertonic saline superfusion of the portal vein, however, occurred within 1–2 s. The results show that portal vein osmoreceptors are distinct from chemo-sensitive nociceptors, and suggest that substance P may be a spinal mediator for chemo-sensitive portal vein nociceptors. The spinal transmitter for osmosensitive afferents, and the physiological importance of the portal vein area in chemosensation remain to be established.

Polycystic kidney and liver disease in Springbok: I. Morphology of the lesions

Spontaneous polycystic kidney and liver disease in an inbred herd of Springbok (Antidorcas marsupialis) was studied by light microscopy, transmission electron microscopy, and microdissection. Springbok are a small species of gazelle of the family Bovidae native to South Africa. Since 1976, 18% of all live calves born have had nephromegaly and died within 2 weeks of birth. Examination of kidney and liver from ten calves which had died or were sacrifices since 1978 revealed bilateral, symmetrical nephromegaly due to moderate to marked focal dilatation of tubules predominately in the outer zone of the medulla. Microdissection of renal tissue from three affected calves indicated polycystic kidneys had cysts in all of the bends of Henle's loops, over half of the ascending limbs, and about one fourth of the collecting ducts. All of these calves had proliferation and cystic dilatation of bile ducts in most hepatic portal areas. The bile ducts were irregularly dilated and confluent with only a slight increase in periductular connective tissue. Ultrastructural studies revealed no consistent changes in the basement membranes of either the renal or hepatic cysts. This disease has several features similar to the autosomal recessive form of polycystic kidney disease in man and may prove a useful animal model.

Reoperation in the treatment of biliary atresia

Rehepatic-portoenterostomy and curettage were performed as reoperative procedures for treatment of biliary atresia. In cases of rehepatic-portoenterostomy, microsurgical technique is an important factor in order to obtain satisfactory operative results. The indication for rehepatic-portoenterostomy, the age of the patient, the size of the intrahepatic bile ducts at the porta hepatis area, the degree of liver fibrosis and liver cell change are closely related to the prognosis of rehepatic-portoenterostomy cases. Since 1977, all seven cases who underwent rehepatic-portoenterostomy showed bile excretion and at present, 3 out of 7 have no jaundice. Curettage is an effective treatment for cessation of bile flow in cases which underwent hepatic portoenterostomy and showed bile excretion for a certain period postoperatively. The timing of curettage is closely related to the results of the curettage. In 9 out of 17 cases which received curettage, we were able to obtain fairly good bile flow and at present, 4 out of 9 show no jaundice.

Osmosensitivity of the hepatic portal vein area and vasopressin release in rats.

1. The role of intraperitoneal osmoreceptors in hypothalamo-neurohypophyseal control was studied in urethane- or nembutal-anaesthetized rats. Plasma samples were taken for radioimmunoassay of arginine vasopressin, and the electrical activity of single supraoptic endocrine neurones and of the hypothalamo-neurohypophyseal tract were monitored during superfusion of the hepatic portal vein with hypo-, iso- and hypertonic solutions. 2. Plasma arginine vasopressin increased within 1 min following superfusion with 0.3-0.9 osmolal NaCl solutions in a dose-related manner from basal levels of 30 pg/ml, to 170 pg/ml. Prior superfusion with xylocaine or intravenous infusions of 800 micrograms atropine-methyl bromate abolished this response, although vasopressin was still released to nicotine in atropine-blocked rats. 3. Portal vein superfusions had no significant effects on arterial blood pressure, plasma osmolality and plasma Na concentrations. 4. Forty supraoptic neurones were antidromically activated from the neural lobe/stalk region. Superfusions of the portal vein with NaCl solutions (0.33-1.20 osmole/kg, 37 degrees C, 5-120 sec) stimulated seven out of eight phasically firing and eight out of twenty-four continuously firing neurones. One phasically active, ten continuously firing and four silent cells were not affected, and six continuously firing neurones were inhibited by the superfusions. 5. The amplitude decreases of antidromic compound action potentials in the hypothalamo-neurohypophyseal tract, reflecting an increase of the orthodromic nerve impulse traffic, ranged from 17 to 22% for superfusions with 1.2 osmolal NaCl or LiCl solutions, from 8 to 11% for 1.2 osmolal Na isethionate or choline Cl and from 3 to 9% for 1.2 osmolal glucose; there was no effect when 1.2 osmolal urea and isotonic or hypotonic NaCl solutions were applied. 6. Responses of the amplitude of compound action potentials to superfusions with 1.2 osmolal NaCl solutions or with 0.1 mumole ACh, but not to electrical stimulation of the portal vein or its superfusion with 1.2 osmolal KCl, were abolished by prior application of 0.3 mumole atropine sulphate. Prior superfusions with xylocaine abolished the responses to all stimuli above. 7. These results suggest that within the hepatic portal vein area there are osmosensitive receptor cells and/or nerve terminals which activate the hypothalamoneurohypophyseal system through a peripheral cholinergic mechanism.

A histopathological study of the remnant of extrahepatic bile duct in so-called uncorrectable biliary atresia

Histopathological study of the remnant of extrahepatic bile ducts in 40 cases of so-called uncorrectable biliary atresia, upon which we operated the last three years, has been performed. The histological findings of the remnant were classified into three types. Only two cases were found to have type 1a ducts in the porta hepatis area, from which we can expect better prognosis postoperatively. We also found that as the patients become older, the size of the duct in the remnant becomes smaller and the hepatic fibrosis becomes more remarkable. Therefore the operation should be performed in the infant with this lesion as young as possible. As for the evaluation of operative results of hepatic portoenterostomy for this lesion, a proper evaluation can be made only in those cases in which a microscopic examination of the remnant of extrahepatic bile duct at the porta hepatis area has been adequately performed. Concerning the pathogenesis of biliary atresia, we presume that congenital abnormalities of bile ducts are a basic factor, and additional nonspecific inflammation and bile stasis complete its pathological condition.

Bovine viral diarrhea virus-induced abortion

History and Clinical Signs : There frequently is a history of a febrile disease with signs compatible with bovine viral diarrhea (BVD) in the herd just prior to the occurrence of abortions. Abortion during the first trimester is usually undetected and is recognized as repeat breeding. Gross Lesions : There are no gross lesions specific for BVD abortion, however, teratologic defects such as cerebellar hypoplasia and alopecia have been found in calves infected in utero . Microscopic Lesions : Mild, localized vasculitis, mild placentitis with mononuclear cell infiltration, and reticuloendothelial hyperplasia especially of the hepatic portal areas and the lymph nodes are common, though not specific lesions. Cultural Procedures : The BVD virus is not usually present in the fetus aborted due to BVD infection and the presence of the BVD virus in an aborted fetus does not necessarily indicate that BVD was the cause of the abortion. Serologic Procedures : The appearance of BVD neutralizing antibody in aborting cows and other animals in the herd previously negative for this antibody or a 2 to 4 fold increase in BVD antibody titer indicates BVD has occurred in the herd. This evidence indicates that the abortion(s) may have been caused by this infection. The presence of active specific BVD neutralizing antibody in the serum of newborn or aborted calves indicates that they were infected with BVD virus in utero . The presence of such antibodies along with lesions and other significant findings will aid in determining the role of the BVD virus in abortion cases. Preferred Diagnostic Methods : 1. 1. Establish through herd history and serologic means that BVD infection was active in the herd just prior to or during the occurrence of abortions. 2. 2. Demonstrate the presence of active, specific BVD neutralizing antibodies in serum from aborted fetuses. 3. 3. Demonstrate fetal lesions and/or teratologic defects compatible with in utero BVD infection. 4. 4. Isolate BVD virus from aborted fetuses and correlate its presence with other significant evidence of its presence.

Gammopathy in hamsters with xenogeneic tumours.

A PREVIOUS communication described the heterotransplantation of human heteroploid cells derived from a prostatic adenoma (MA 160) into nonimmunosuppressed 2-d-old hamsters1. Most animals receiving subcutaneous implants of 107 cells rejected them after 14 d (regressors). In some (27%), however, there was progressive tumour growth (persistors). This was associated with morphological signs of immunological stimulation as evidenced by a pronounced proliferation of plasma cells in lymph nodes, hepatic portal areas, spleen and kidneys. One biological expression of this proliferation was the presence of antibody directed against membrane antigens of living MA160 cells. At the time of peak tumour growth, fluorescent antibody titres as large as 1:1,280 were demonstrated in sera from animals with large tumours.

WaldenstrÖm's Macroglobulinemia with Increased Serum IgG Levels Treated with Low Doses of Cyclophosphamide

A patient had Waldenström's macroglobulinemia with increased serum levels of heterogeneous or "polyclonal" IgG in addition to elevated homogeneous or "monoclonal" IgM levels. A low dosage of cyclophosphamide was begun and has been continued to the present. Serum IgM levels fell promptly followed by a fall in IgG levels. After both the IgM and IgG levels had returned to normal no further fall occurred. Normal serum IgA levels were unaffected by the treatment. The fall in serum IgM and IgG values was accompanied by a disappearance of lymphocytes from the hepatic portal areas and a slight decrease in the lymphocytic infiltration of the bone marrow. A complete clinical remission began 6 months after therapy was begun and has continued to the present, 3 years later.

Graft-versus-host disease. Liver involvement in splenectomized rats.

Graft-versus-host disease was induced in adult hybrid rats by injection of spleen cells from either or both parental strains. Under the conditions of these experiments, GVH disease infiltrates appeared in the hepatic portal areas in all rats splenectomized before injection, but rarely in intact or sham-operated animals. Although other explanations are possible, it is likely that removal of the splenic sites of lymphocyte fixation (3) allowed more opportunity for the injected parental cells to settle in the liver.

Hodgkinʼs Disease Following Administration of Thorotrast

A case of Hodgkin's disease developing 12 yr following administration of ThO/sub 2/ is reported, representing the only known example of this disease associated with Th. Radiography of the abdomen showed increased density of the liver and spleen, as well as radiopaque densities in the abdomen presumably representing nodes which were heavily infiltrated with ThO/sub 2/. The densities in the liver and spleen were also ascribable to ThO/sub 2/ deposits. The tumor consisted of pleomorphic round and polyhedral cells and Reed-Sternberg cells, along with areas of fibrosis, necrosis, hemorrhage, and mononuclear cell reaction. Pleomorphic cellular changes were frequentiy found adjacent to deposits of ThO/ sub 2/. ThO/sub 2/ was also found throughout the reticuloendothelial system, as in the reticulum cells of the liver, spleen, and lymph nodes. Using a gas-flow counter, significant counts of radiation were detected in the spleen and periaortic lymphoid tissues, sites histologically demonstrated to contain Th and tumor Proliferated bile ducts in hepatic portal areas were of interest because of reported bile duct carcinoma of the liver in patients previously receiving Thorotrast. The presence of tumor cells in the reticuloendothelial system surrounding granules of ThO/sub 2/ suggests that Th induced or inttiated the development of Hodgkin'smore » disease with spread to the kidneys and other organs containirg little or no Th. A table is given listing anatomic sites where tumors associated with Thorotrast have been found in the commonly recognized types of tumors in rough order of incidence. It is suggested that there is ample evidence to incriminate Thorotrast as a definite oncogenic agent. (H.H.D.)« less