51Cr-RBCs and 125I-albumin as markers to estimate lymph drainage of the peritoneal cavity in sheep

The purpose of this study was to compare the use of 125I-labeled human serum albumin (125I-HSA) and autologous 51Cr-labeled red blood cells (51Cr-RBCs) as lymph flow markers to estimate lymph drainage of the peritoneal cavity in conscious sheep. In one group, we assessed lymph drainage from the appearance of intraperitoneally administered tracer in the bloodstream. To determine distribution of drainage into discrete lymph compartments, in a second group of studies, lymph was collected from the caudal mediastinal lymph node and the thoracic duct, both of which are involved in lymphatic drainage of the ovine peritoneal cavity. Ringer lactate solution (50 ml/kg) containing 8-10 microCi each of 125I-HSA and 51Cr-RBCs was infused into the peritoneal cavity. Lymph drainage was calculated by dividing the change in mass of tracer in the blood or lymph compartments by the average intraperitoneal tracer concentration. In noncannulated animals, lymph drainage averaged over 6 h was higher with 125I-HSA as tracer (1.35 +/- 0.12 vs. 0.62 +/- 0.19 ml.h-1.kg-1 with 51Cr-RBCs). A similar pattern was noted in terms of drainage into the caudal lymphatic (0.89 +/- 0.23 and 0.52 +/- 0.19 ml.h-1.kg-1 with 125I-HSA and 51Cr-RBCs, respectively) and thoracic duct (0.16 +/- 0.06 and 0.05 +/- 0.02 ml.h-1.kg-1 with 125I-HSA and 51Cr-RBCs, respectively). Analysis of 125I-HSA and 51Cr-RBC concentrations in lymph and intraperitoneal fluid suggested sieving of RBCs at the diaphragmatic stomata or lymph nodes. Using 125I-HSA as tracer and combining data from noncannulated and cannulated sheep, we estimated peritoneal lymph drainage to be 1.35 ml.h-1.kg-1, with 66% of this flow drained by the caudal vessel, 22% by the parasternal pathway (right lymph duct), and 12% by the thoracic duct.     

Quantitation of lymphatic drainage of the peritoneal cavity in sheep: comparison of direct cannulation techniques with indirect methods to estimate lymph flow

OBJECTIVE: It has been suggested that lymphatics may contribute to ultrafiltration failure in patients on continuous ambulatory peritoneal dialysis (CAPD) by absorbing dialysate and ultrafiltrate from the peritoneal cavity. In most studies lymphatic drainage has been estimated from the disappearance of an instilled tracer from the peritoneal cavity or estimated from the appearance of an intraperitoneally administered tracer in the bloodstream. However, in sheep it is possible to cannulate several of the relevant lymphatics that drain the peritoneal cavity and assess lymph drainage parameters directly. The purpose of this study was to estimate lymph drainage from the peritoneal cavity in sheep using the disappearance of tracer from the cavity and the appearance of intraperitoneally instilled tracer in the bloodstream and to compare these results with those obtained from our previous studies using cannulation techniques. DESIGN: Experiments were performed in anesthetized and nonanesthetized animals. Volumes of 50 mL/kg of Dianeal 4.25% containing 25 microCi of 125I-albumin were infused into the peritoneal cavity. RESULTS: In anesthetized sheep the calculated peritoneal lymph drainage from monitoring the disappearance of tracer from the peritoneal cavity over 6 hours was 1.873 +/- 0.364 mL/kg/hour. Monitoring the appearance of tracer in the blood gave significantly lower peritoneal lymph flow rates of 1.094 +/- 0.241 mL/kg/hour. Directly measured lymph flow rates from our earlier publication were lower still and ranged from 0.156 +/- 0.028-0.265 +/- 0.049 mL/hour/kg, depending on how we estimated the right lymph duct contribution to peritoneal drainage, since we could not cannulate this vessel. We repeated these experiments in conscious sheep. The value for lymph flow estimated from the disappearance of tracer from the peritoneal cavity was 2.398 +/- 0.617 mL/hour/kg and from the appearance of tracer in the blood, 1.424 +/- 0.113 mL/hour/kg. The lymph flow rates monitored from indwelling lymphatic catheters ranged from 1.021 +/- 0.186-1.523 +/- 0.213 mL/hour/kg (again, depending on our estimates for the right lymph duct). CONCLUSIONS: Lymph flow rates measured from indwelling lymphatic catheters provided the most conservative values for lymphatic drainage of the peritoneal cavity under dialysis conditions. Estimates of lymphatic drainage based on the appearance of tracer in the blood gave values that were on average higher. The method using the disappearance of tracer from the cavity to estimate lymph flows overestimated peritoneal lymph drainage. Fluid was lost from the peritoneal cavity, and the estimated proportion of liquid lost through lymphatic drainage depended on the technique used to measure lymph flow rates.     

Peritonitis: pathophysiology and local defense mechanisms

The peritoneal cavity can be divided in the supracolic infracolic and paracolic spaces, the lesser sack and the pelvis. The peritoneum is a semipermeable membrane which allows a flux of solutes into and from the peritoneal cavity. In addition, particles can be absorbed through the stomata of the diaphragmatic peritoneum. Secondary peritonitis is always a polymicrobial infection. The flora consists of aerobic enterobacteriaeceae and anaerobs mainly B. fragilis. These two groups of bacteria act synergistically. Besides unspecific defence mechanisms, i.e. the direct absorption of bacteria and the entrapment of bacteria in fibrin, the immunological defence mechanisms of the peritoneal cavity are triggered by endotoxin contained in the cell wall of the invading bacteria leading to the production of cytokines by macrophages, activation of complement and as a result the migration of granulocytes from the intervascular space into the peritoneal cavity.     

Differential inhibition of fluid accumulation and tumor growth in two mouse ascites tumors by an antivascular endothelial growth factor/permeability factor neutralizing antibody

In the accompanying paper (Luo et al., Cancer Res., 58: 2652-2660, 1998), we demonstrated that vascular endothelial growth factor (VEGF), also designated vascular permeability factor (VPF), significantly accumulated in all mouse malignant ascites tested, suggesting its fundamental role in ascites tumors. Removal of VEGF may inhibit the development of ascites tumors. In this study, using a goat antimouse VEGF-neutralizing antibody, we tested this hypothesis with two well-defined syngeneic mouse ascites tumors: MM2 breast adenocarcinoma and OG/Gardner lymphoma 6C3HED (expressing moderate and low levels of VEGF, respectively). This antibody significantly inhibited MM2 and OG cell-free ascites fluid-induced hyperpermeability of mouse peritoneal microvessels and in vitro endothelial cell growth. Mice bearing tumors were administered i.p. daily with the antibody or normal goat IgG as controls for 8 days, at doses of 20-fold (for MM2-bearing mice) or 40-fold (for OG-bearing mice) the estimated amounts of VEGF that kinetically accumulated in the ascites fluid after the tumor inoculation. The average volume of ascites fluid, number of tumor cells and leaked RBCs, and the peritoneal microvessel permeability in MM2-bearing mice that received the antibody treatment were significantly lower than those in the matched controls (P < 0.01). Unexpectedly, OG-bearing mice did not show satisfactory response to the anti-VEGF treatment. This discrepancy was not likely due to inadequate doses or different host immune responses, but it was quite possibly to the different characteristics of MM2 carcinoma and OG lymphoma tumors, the latter being strongly invasive, and/or the existence of an inflammatory mediator(s), such as bradykinin or cytokine(s) other than VEGF. In summary, our results directly demonstrated, for the first time, differential roles for VEGF in ascites tumors in vivo and suggest the potential of VEGF inhibition as a specific therapy for ascites tumors of carcinoma origin, which are the major cause of the malignant ascites in adult humans.     

Macrophage-derived nitric oxide induces apoptosis of rat hepatoma cells in vivo

Although nitric oxide (NO) has been postulated to play important roles in host defense mechanisms against tumor cells, a direct evidence supporting this hypothesis is lacking. To obtain molecular insights into the antitumor action of NO, its metabolism and effect on ascites hepatoma (AH-130) cells were investigated in tumor-bearing rats. Kinetic analysis revealed that substantial amounts of nitrite and nitrate, metabolites of NO, appeared in plasma and ascites of AH-130-inoculated rats. Western blot analysis revealed that a large number of macrophages that expressed inducible type of NO synthase (iNOS) appeared in cancerous ascites, particularly during 1 to 2 weeks after inoculation of AH-130 cells. When NO generation by peritoneal macrophages increased, a significant fraction of AH-130 in ascites fluid underwent apoptosis as judged from the fragmentation of their nuclear DNA. Kinetic analysis revealed that NO strongly inhibited mitochondrial electron transport and changed calcium status in AH-130 cells, particularly under low oxygen tensions such as in cancerous ascites. Intraperitoneal injection of NO donor strongly enhanced DNA fragmentation of AH-130 cells. Antimycin A, a specific inhibitor for mitochondrial electron transport, also induced DNA fragmentation of AH-130 cells by a mechanism that was inhibited by adding ascorbate and tetramethyl-p-phenylene diamine (TMPD) as electron donors. These results indicate that NO derived from peritoneal macrophages inhibits mitochondrial electron transport and disturbs calcium homeostasis in ascites hepatoma AH-130 cells, thereby inducing their apoptosis in vivo.     

Influence of diagnostic and treatment factors in the population pharmacokinetics of gentamicin

STUDY OBJECTIVES: To determine the feasibility of macroscopic visualization of small ovarian cancer metastases in vivo by fluorescence after intravenous administration of 5-aminolevulinic acid (ALA); to assess the time after drug injection when fluorescence of small metastases is maximum; and to correlate macroscopic in vivo fluorescence with both microscopic ex vivo fluorescence and histologic findings. DESIGN: Controlled animal study (Canadian Task Force classification I). SETTING: University-based facility. SUBJECTS: Twenty-four healthy, female Fischer rats. INTERVENTION: Diffuse peritoneal metastatic cancer was induced in Fischer 344 rats by intraperitoneal injection of 1 million syngeneic ovarian cancer cells (NuTu-19). Four weeks after induction ALA100 mg/kg was injected intravenously, and diagnostic laparotomy was performed 1, 3, 6, or 9 hours thereafter. MEASUREMENTS and MAIN RESULTS: The peritoneal cavity was illuminated with the Wood's lamp (ultraviolet light). Fluorescence was determined by direct visualization and compared with a calibrated fluorescent disk. Tissues were collected, sectioned, and examined by fluorescence and conventional light microscopy. Within 1 to 3 hours after intravenous injection of ALA, in vivo fluorescence of tumor nodules (diameter 0.4-5.0 mm) was macroscopically visible. Tumor-free peritoneum did not show fluorescence and was significantly distinguishable from cancer nodules. Fluorescence from intestinal tissues was comparable with tumor nodules. Microscopic fluorescence analysis showed similar values for tumor nodules and peritoneum. Stained histologic specimens of peritoneal surface revealed a superficial layer of cancer cells responsible for fluorescence. The time course of the fluorescence curve in the intestine peaked twice, at 1 and 6 hours after ALA injection. Macroscopically fluorescing nodules were histology confirmed as malignant. CONCLUSIONS: Fluorescence detection of small cancer nodules after intravenous injection of ALA is feasible for nodules smaller than 0.5 mm on the peritoneum. One to 3 hours after drug injection is optimal for diagnosis of metastases.     

Lymphatic drainage of hypertonic solution from peritoneal cavity of anesthetized and conscious sheep

Lymphatic drainage of the peritoneal cavity may reduce ultrafiltration in continuous ambulatory peritoneal dialysis. We assessed lymphatic drainage of the peritoneal cavity in sheep under dialysis conditions by cannulation of the relevant lymphatic vessels and compared lymphatic drainage in anesthetized and conscious animals. Lymph was collected from the caudal mediastinal lymph node and the thoracic duct, both of which are involved in the lymphatic drainage of the ovine peritoneal cavity. Volumes of a hypertonic dialysis solution (50 ml/kg 4.25% Dianeal) containing 25 microCi 125I-human serum albumin were instilled into the peritoneal cavity, and lymph flows and the appearance of labeled protein in the lymphatic and vascular compartments were monitored for 6 h. Intraperitoneal pressures increased 4-5 cmH2O above resting levels after infusion of dialysate. On the basis of the appearance of tracer in the lymph, drainage of peritoneal fluid into the caudal lymphatic was calculated to be 3.09 +/- 0.69 and 14.14 +/- 2.86 ml/h in anesthetized and conscious sheep, respectively. Drainage of peritoneal fluid into the thoracic duct preparations was calculated to be 1.32 +/- 0.33 and 14.69 +/- 5.73 ml/h in anesthetized and conscious sheep, respectively. Significant radioactivity was found in the bloodstream, and at least a portion of this was likely contributed by the right lymph duct, which was not cannulated in our experiments.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cellular and humoral immunity to leukemia cells in BCG-induced growth control of a murine leukemia

The antitumor effects of weekly iv injections of 1.0 mg BCG and/or sc injections of 10(7) irradiated leukemia cells were studied in an isogeneic, transplantable lymphoid leukemia in the C57BL/6 mouse. The injections were started at day 1 after ip inoculation of 10(5) leukemia cells. BCG prolonged the survival time of most animals and cured 22%. BCG plus irradiated cells cured only about 10% of the mice, and irradiated cells alone had no curative effect. Individual tumor-bearing mice in the various experimental groups were examined with respect to ascites tumor cell number; complement-dependent cytotoxic antibodies in sera; direct and antibody-dependent cytotoxicity to tumor cells of lymphoid cells from peritoneal fluid, the spleen, and peripheral lymph nodes; and the cytology of ascites, the spleen, and lymph nodes. Only the antibody-dependent lymphocyte-mediated cytotoxicity (ADLMC) was correlated with the ascites tumor cell number, since the ADLMC was high only in mice with a tumor cell number less than that of the controls. Furthermore, since mice with a low tumor cell number had predominantly only lymphocytes as the nonmalignant cell type in their peritoneal fluid, ADLMC may have had an important role in BCG-induced control of tumor growth.     

Utilization of intravenous dihydroxypropyl theophylline (dyphylline) in an aminophylline-sensitive patient, and its pharmacokinetic comparison with theophylline

1. The transport of zinc has been studied in normal human leucocytes incubated in both a tissue culture medium and Krebs buffer. 2. 65Zn influx is characterized by an initial rapid phase followed by a slower influx. 65Zn influx is directly dependent upon the extracellular zinc concentration. 3. Net zinc influx could only be demonstrated in Krebs buffer at zinc concentrations in excess of 4.3 mumol/l and in tissue culture fluid at zinc concentrations in excess of 43.1 mumol/l. 4. A 65Zn efflux rate constant of approximately 1.0 per h was observed in both 4.3 and 15.4 mumol of zinc/l of Krebs buffer or tissue culture fluid. 5. In a zero external zinc Krebs buffer the 65Zn efflux rate constant fell to 0.57 per h and was accompanied by a small net zinc efflux.     

Therapeutic effect of the matrix metalloproteinase inhibitor, batimastat, in a human colorectal cancer ascites model

The matrix metalloproteinase inhibitor batimastat was administered to a human colorectal cancer ascites model, which was initiated by injection of C170HM2 cells into the peritoneal cavity of SCID mice and resulted in solid tumour deposits and ascites formation. The cell line expressed both the 72 and 92 kDa forms of gelatinase by zymography. Batimastat administered from day 0 (40 mg kg-1) reduced the volume of ascites to 21% of control in mice treated from day 0 (P < 0.002) but not day 10. Formation of solid peritoneal deposits was significantly reduced to 77% of vehicle control when batimastat was administered from day 0 (P < 0.01) and 69% of control when administered from day 10 (P < 0.05). Thus, batimastat has the ability to reduce the volume of ascites forming in SCID mice injected intraperitoneally with the human colorectal cell line, C170HM2, when administered from day 0 but not from day 10. Solid peritoneal tumour deposits were significantly reduced in both treatment groups, highlighting the therapeutic potential of batimastat in this clinical condition.     

A 31P-NMR study of the effects of reflow on the ischaemic rat heart

The movement of neutral amino acids across the blood-brain barrier is bidirectional, however, blood to brain transport is much better characterized than brain to blood transport. Available evidence points to the existence of a single transport system (system L) at the luminal capillary surface. The properties of this system place constraints on possible mechanisms of regulating blood-brain neutral amino acid transport activity. One property, mediation of exchange transport, suggests that amino acid influx is coupled to efflux, particularly efflux of glutamine, synthesized in glial astrocytes from ammonia and glutamic acid. Such a coupling could account for increased blood-brain neutral amino acid transport in liver disease and decreased transport activity after treatment with methionine sulfoximine, a glutamine synthetase inhibitor.     

Cerebral angioseriotomography (author''s transl)]

K transport has been investigated during progression of cultured Ehrlich ascites tumor cells through the cell cycle. Using a double thymidine block technique, Ehrlich cells carried in continuous culture have been synchronized, as verified by simultaneous monitoring of cell number, cell volume, 3H-thymidine incorporation and mitotic index. Unidirectional influx, efflux and cell content of K have been monitored throughout the cell cycle. The nature of the pump mediated, ouabain-sensitive K flux and the furosemide-sensitive component of K flux, presumably representing K-K exchange, have also been evaluated. In early S period the ouabain sensitive component, representing the Na-K pump, comprises 52% of the total unidirectional K influx and subsequently declines during G2 period to a minimum of 40% in mid G2. During M and early S the activity again rises. As the ouabain sensitive component becomes maximal in late S period, the furosemide sensitive component diminishes from approximately 30% of the total influx to approximately 10%. The same pattern is observed in the G2 period. As the pump component diminishes, the furosemide sensitive component increases. Furosemide sensitive K efflux has also been monitored and the pattern is equivalent to that observed in the invlux studies. No change in net K flux is observed in the presence of furosemide. This indicates that the furosemide sensitive component represents an exchange component for K. These results are consistent with the conclusion that the alterations in exchange and pump fluxes are physiological events associated with progression of the cell cycle.     

The regulation of membrane 125I- and 86Rb+ permeability in a virally transformed cell line (NCL-SG3) derived from the human sweat gland epithelium

We have explored the factors that may regulate membrane permeability in a cell line (NCL-SG3) derived from the human sweat gland epithelium. Ionomycin increased the rate of 125I-efflux from preloaded cells and this action appeared to be due to an increase in intracellular free calcium ([Ca2+]i). The ionomycin-evoked increase in 125I- efflux was reduced in cells that were exposed either to barium or to valinomycin in the presence of a high concentration of external potassium. It thus appears that a fraction of the ionomycin-evoked increase in 125I- efflux is due to the activation of potassium channels and experiments using 86Rb+ also suggested that ionomycin increased the rate of potassium efflux, an effect which was totally abolished by barium. Blockade of Na(+)-K(+)-2Cl- cotransport and of Cl- -HCO3- exchange reduced the basal rate of 125I- efflux and the ionomycin-evoked increase in 125I-efflux from control cells and from cells depolarized by valinomycin. These transport systems thus contribute to anion efflux, although [Ca2+]i-dependent chloride channels also appear to be present. Acetylcholine increases [Ca2+]i in the secretory cells of human sweat glands, but this neurotransmitter did not increase [Ca2+]i in NCL-SG3 cells and so membrane permeability was not under cholinergic control. Adrenaline did not increase [Ca2+]i, but this hormone did evoke cyclic-3',5'-adenosine monophosphate (cyclic AMP) production. However, membrane permeability was not under adrenergic control, as the cells did not appear to express functional, cyclic AMP-dependent anion channels. This may be because they were not fully differentiated under the culture conditions. ATP consistently evoked a dose-dependent increase in anion efflux that appeared to be mediated by [Ca2+]i. The increase in [Ca2+]i was initiated by the release of calcium from a limited internal store and was subsequently sustained by calcium influx. UTP and ADP also increased [Ca2+]i, whereas adenosine, AMP and alpha,beta-methylene ATP were without effect. These data thus suggest that a subclass of type 2 purine receptor, which is functionally coupled to phosphoinositidase C, is present in these cells.     

Massive ascites due to abdominal pregnancy

We describe a case of an abdominal pregnancy which presented in the first trimester with rapid accumulation of blood stained ascites. The ascites resolved completely following surgical removal of a gestational sac from the peritoneal cavity. The pathophysiology of ascites in this case may be similar to that in cases of ascites in other non-malignant gynaecological conditions.     

Aging-related changes in calcium oscillations in fertilized mouse oocytes

In vivo studies of lymphocyte biology have used intravenous (i.v.) injection as the primary mode of cell transfer, a protocol consistent with the anatomic distribution of most lymphocytes. However, for study of peritoneal cavity B cells, i.v. injection does not correlate with anatomical localization. This report describes the restoration of B-cell function in B lymphocyte-defective X-chromosome-linked immune-defective (XID) mice after intraperitoneal transfer of immunoglobulin heavy chain (Igh)-disparate peritoneal cavity (PerC) cells. In contrast to i.v. transfer, intraperitoneal (i.p.) transfer restored B-cell function in young, but not adult (> 8 weeks), XID mice. When host and donor Igh allotype matched, PerC B-cell engraftment was noted in older recipients; this reconstitution however, was also age-dependent. Migration from the peritoneum to systemic circulation was necessary for serum IgM production as shown by the presence of donor antibody-secreting cells in the host spleen. Host lymphocytes also influenced the success of i.p. transplantation as severe combined immune-deficient mice, regardless of age, exhibited donor serum IgM production. Recipient age, Igh allotype, and immune-deficiency were found to have an impact on the ability of i.p.-transferred PerC B cells to restore B-cell function in XID mice.     

Albumin exchange and polymorphonuclear vascular transit in hyperoxic pulmonary oedema in awake rats

Vascular inflammatory response to hyperoxia (FIO2 greater than 0.98) was studied in awake jugular and carotid catheterized rats. Simultaneous i.v. injection of 125I albumin (125I A), 99mTc polymorphonuclear cells (99mTc PMN) and 51Cr red blood cells (51Cr RBC) allowed to study both the macromolecule exchange through vascular endothelium and the leukocyte uptake by several organs (liver, lungs, spleen) with respect to radiolabelled red blood cells, as an intravascular reference. Rats were exposed to O2 for 24, 38 and 45 h. They were anesthetized and killed by exanguination 15 to 120 min following the tracer injection. After 45 h exposure, the plasmatic 125I A half-life decreased significantly (158 +/- 42 min for the control; 106 +/- 34 min for the exposed animals). The ratio 125I A/51Cr RBC varied significantly in the lung. The iodinated albumin exchange through lung vascular endothelium was altered at the 24th h, with a significant difference reached by the 45th h. At the same time, the pulmonary decreasing curve of 99mTc/51Cr RBC ratio versus time was not not modified. In our experimental conditions, there was no detectable variation in the lung uptake and vascular transit of PMN cells. The discussion of the results must be related with the technics used in the present work when the albumin exchange increased.     

Ultrastructure, distribution, and density of lamellar bodies in human peritoneum

OBJECTIVE: To determine the ultrastructure, relative density, and location of lamellar bodies in the various regions, structures, cells, and intercellular matrix in normal human peritoneum; to carry out engineering analysis of the role of lamellar structures in serosal lubricancy and deduce what effect this system may have on the process of peritoneal dialysis. DESIGN: Five samples of normal human parietal peritoneum obtained at elective operation were fixed in a tannic acid-glutaraldehyde mixture and submitted to examination by transmission electron microscopy. Detailed analysis using reconstruction of serial electron micrographs and tracings of montages were employed in determining location, disposition, density, and geometric patterns of lamellar bodies in all levels of the peritoneal membrane. RESULTS: Lamellar profiles were found in greatest density enmeshed in surface microvilli and in mesothelial cytoplasm. Lamellar bodies were frequently observed capping the external portion of mesothelial junctional complexes, and within intercellular junctions. Lamellar bodies were also encountered in macrophages, both in the peritoneal cavity and submesothelial tissue, and also in fibroblasts. Lamellar bodies were present in low density in the matrix ground substance of submesothelial connective tissue, in blood vessel walls between smooth muscle, in endothelial cell cytoplasm, and in vascular lumina. CONCLUSION: Three-dimensional analysis of lamellae on mesothelial surfaces indicates that an arrangement of constantly changing microscopic spheres and cylinders would act as "ball and roller bearings" among the microvilli for the lubrication of opposing surfaces. The entrapment of fluid in lamellar bubbles, which in normal peritoneum fill the microvillous layer, would, if maintained in peritoneal dialysis, constitute a stagnant layer of considerable stability and inertia.     

Ascites, hydrothorax and ovarian tumor: Meigs' syndrome in a patient with small ovaries and increased CA 125 level

In a 51-year-old woman with bilateral Brenner tumours of the ovaries and with intermittent hydrothorax and ascites, Meigs' syndrome was diagnosed. The serum CA 125 level was 620 U/ml (normal: 5-35). Bilateral ovariectomy, hysterectomy and omentectomy were carried out. The ovaries were not enlarged. Postoperatively, the pleural effusion and ascites resolved and the CA 125 level decreased to 8.4 U/ml. The pathogenesis of hydrothorax probably involves passage through the diaphragm, and the CA 125 may be produced by the peritoneal lining or by the Brenner tumours.     

Kinetic correlates of methotrexate transport and therapeutic responsiveness in murine tumors

Net accumulation of methotrexate by carrier-mediated transport in different murine tumor cells in vitro exhibits a positive correlation with the relative drug pharmacokinetics and therapeutic responsiveness in these tumors in vivo. The transport of methotrexate by Sarcoma 180, Ehrlich carcinoma, P388, P288, and L1210 leukemia cells is qualitatively similar. Influx of drug exhibits saturation kinetics and is highly temperature dependent (Q10, 6.1 to 9.4). Efflux of exchangeable methotrexate from all of the different tumor cells exhibited first-order kinetics and the same high temperature dependence seen for influx (Q10, 6.1 to 8.0). The major kinetic determinant of responsiveness is the Km for influx. Values vary from 3.1 to 11.2 X 10(-6) M and are highest in cells from a nonresponsive Sarcoma 180 tumor, somewhat lower in the poorly responsive Ehrlich tumor, lower in moderately responsive P388 and P288 leukemias, and lowest in the highly responsive L1210 leukemia. Values for the influx Vmax differ to some extent, but in a manner not correlatable with responsiveness. The level of responsiveness of the P388 leukemia in vivo can also be partially attributed to an efflux rate that is lower than that measured for the other tumor cells. Steady-state levels of drug accumulation in vitro reflected influx and efflux rates and were consistently correlatable with therapeutic responsiveness. There was no significant difference in the extent to which folate and reduced 5-substituted folate derivatives compete with methotrexate for uptake in cells from all five tumors. The average value for Ki measured with folate for each tumor cell type was 50- and 80-fold higher than for 5-formyltetrahydrofolate and 5-methyltetrahydrofolate.     

Peritoneal tuberculosis: evaluation of the response to treatment by analysing the CA 125 levels

A case of a 32 years old woman with fever and exudative ascites is described. Tuberculous peritonitis was confirmed by abdominal laparoscopy, peritoneal biopsy and Low?nstein culture. A serum CA 125 level was 861 U/ml before therapy. The CA 125 level decreased a 30% after three weeks of antituberculous treatment. This tumor marker may be used to follow disease activity in tuberculous ascites.