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PubMed1991

Host defense mechanisms in the peritoneal cavity of continuous ambulatory peritoneal dialysis patients. 2. Humoral defenses.

This is the second of a 2-part series reviewing host defense mechanisms of the peritoneal cavity of continuous ambulatory peritoneal dialysis (CAPD) patients. This article discusses humoral aspects of host defenses and accompanies the first article that focused upon cellular defenses. The purpose of this review is to provide a critical analysis of studies that have investigated the importance of peritoneal humoral immunity of CAPD patients in the pathogenesis of peritonitis. Specific attention is given to how CAPD alters normal humoral defenses of the peritoneal cavity and the clinical significance of such alterations.

Antibody Formation↗
PubMed1990

The disappearance of macromolecules from the peritoneal cavity during continuous ambulatory peritoneal dialysis (CAPD) is not dependent on molecular size.

The transport of macromolecules from the circulation to the peritoneal cavity is a size-selective restricted process, while the transport of these solutes from the peritoneal cavity is probably mainly by lymphatic absorption. If so, it should be independent of molecular size. Therefore, we studied with a clearance technique the disappearance of intraperitoneally administered inulin and polydisperse dextran 70 in nine continuous ambulatory peritoneal dialysis (CAPD) patients and compared the results with the simultaneously measured appearance clearance of serum proteins. Using gel permeation chromatography 18 dextran fractions with different molecular radii could be analyzed. Inulin clearance (2.94 mL/min) was higher than total dextran clearance (1.30 mL/min). The maximal dextran concentration in all dialysate samples was found in the 50.4 A fraction. The clearances of the dextran fractions were the same of different molecular sizes. All disappearance clearances were higher than the appearance clearances: the protein/dextran clearance ratio ranged from 0.15 for albumin/36 A to 0.04 for alpha 2-macroglobulin/91 A. This confirms that the appearance of a macromolecule, but not its disappearance is dependent on molecular size. It is concluded that the disappearance of macromolecules from the peritoneal cavity is mainly a size independent convective process, possibly by lymphatic uptake. This implies that total dextran 70 clearance can be used for measurement of lymphatic absorption in CAPD patients.

Adult↗
PubMed1994

Cancer antigen 125 is locally produced in the peritoneal cavity during continuous ambulatory peritoneal dialysis.

The local production of cancer antigen (CA) 125 in the peritoneal cavity of 14 continuous ambulatory peritoneal dialysis patients was studied. In addition, the relationship between the concentration of mesothelial cells and CA 125 in the peritoneal dialysate effluent was examined. The median results and ranges were as follows: plasma CA 125 14 U/mL (range 10-23), dialysate CA 125 18 U/mL (range 5.2-76), dialysate/plasma ratio 1.9 (range 0.61-5.4), and number of mesothelial cells 400/mL (range 10-5000). Peritoneal concentrations of mesothelial cells and CA 125 were positively correlated (r = 0.50, p < 0.01). Using a monoclonal antibody, CA 125-positive cells were found in the cytospin preparations of the cells of dialysis effluents. All these CA 125 positive cells were also positive for cytokeratin used as a mesothelial cell marker. In vitro experiments using mesothelial cells in monolayers showed a linear increase in CA 125 concentration both in time and in relation to the number of mesothelial cells. From these experiments a production rate of 24 U/hour/10(6) cells could be calculated. It is therefore concluded that CA 125 is locally produced in the peritoneal cavity during CAPD and that the mesothelial cells are the major source of this CA 125.

Antigens, Tumor-Associated, Carbohydrate↗
PubMed1992

Lymphatic versus nonlymphatic fluid absorption from the peritoneal cavity as related to the peritoneal ultrafiltration capacity and sieving properties.

In this article we discuss the role of capillary fluid absorption via Starling mechanisms (the transcapillary hydrostatic pressure gradient opposed by the colloid osmotic pressure gradient as multiplied by the capillary UF coefficient) vs. lymphatic fluid absorption as determinants of the total fluid loss from the peritoneal cavity during continuous ambulatory peritoneal dialysis (CAPD). We also mention that, under nonsteady state conditions, there is in addition some net absorption of fluid into the interstitium of tissues surrounding the peritoneal cavity. Support for the contention that nonlymphatic fluid absorption directly into the capillaries is the major mode of fluid transport from the peritoneal cavity to the blood is given by measurements of the peritoneal-to-blood clearance of tracer albumin (or other proteins). Such measurements yield clearance values of the order of 0.2-0.3 ml/min in CAPD. This represents only about 20% of the total peritoneal fluid loss rate (1.2-1.3 ml/min) in ordinary CAPD dwells. Indirect support for a relatively low lymph flow is also derived from capillary physiology. Like continuous capillary walls, the peritoneal membrane shows a bimodal selectivity towards molecules of graded molecular size. Thus, small solute transport can be described as occurring by diffusion through numerous 'small' (approximately 50 A radius) pores, whereas large solute transport is consistent with blood-peritoneal convection through smaller numbers of 'large' (radius approximately 250 A) pores. Furthermore, peritoneal sieving data are compatible with the notion that large crystalloid osmotic pressure gradients cause fluid flow through a water-exclusive ('ultra-small' pore) pathway. A three-pore model of peritoneal selectivity can explain why small solute sieving coefficients are only 0.5-0.6, even though small solute reflection coefficients are close to zero. Another important implication of the three-pore concept is that the peritoneal UF-coefficient is much higher than previously thought, emphasizing the role of capillary absorption in the fluid loss from the peritoneal cavity in CAPD. It is concluded that fluid loss from the peritoneal cavity is dominated by capillary fluid absorption. Hence, lymphatic absorption accounts for just a small fraction of the peritoneal-to-blood absorption of fluid in peritoneal dialysis.

Absorption↗
PubMedDate not supplied

[Direct administration of sorbent into the peritoneal cavity in diffuse purulent peritonitis].

The changes in the peritoneal cavity at different intervals after direct administration of the sorbent in purulent peritonitis are investigated. Great quantity of granular sorbent administered directly into the peritoneal cavity provides a stronger therapeutic effect than kanamycin. However, the probability of commissure formation and commissural ileus is greater too. The presence of separate granules of the sorbent in the peritoneal cavity does not produce pathologic changes for a long time.

Animals↗
PubMed1994

Lymph flow and lymphatic drainage of inflammatory cells from the peritoneal cavity in a casein-peritonitis model in sheep.

The purpose of this study was to characterize the cellular responses in the peritoneal cavity and draining lymph in a sterile peritonitis model in conscious sheep. Lymph was collected from lymphatics that drained the peritoneal space (caudal mediastinal and thoracic ducts) as well as from lymph vessels that drained peripheral tissues (prescapular). Casein was used as the inflammatory agent. Dialysis solution (Dianeal 4.25%) containing 1g% casein and 25 microCi 125I-human serum albumin was infused into the peritoneal cavity in 50 ml/kg volumes. Peritoneal volumes increased from a mean infused volume of 1572 +/- 51 ml to a maximum of 2119 +/- 77 ml at 3 hours. Over 6 hours, the number of macrophages and lymphocytes in the peritoneal cavity remained relatively constant but the number of neutrophils increased from 9.9 +/- 4.2 x 10(7) to 9.2 +/- 1.9 x 10(9) total cells. Caudal lymph which drains directly from the peritoneal cavity through diaphragmatic stomata, demonstrated a 5 fold increase in flow rate over 6 hours following the Dianeal-casein infusion. Thoracic duct and prescapular flows declined approximately 70% and 50% respectively in the same time period. the concentration of lymphocytes and the lymphocyte outputs (product of volume and concentration) declined in all lymph compartments. No elevations in neutrophil numbers in the thoracic and prescapular lymph compartments were observed but neutrophil output in the caudal lymph increased steadily from 3.1 +/- 1.5 x 10(6) to 4.6 +/- 1.3 x 10(7)/hr at the 6 hour mark. We conclude that the major route of removal of inflammatory cells and fluid from the peritoneal cavity is through diaphragmatic lymphatics.

Animals↗
PubMed1983

Elimination patterns of Escherichia coli and bacteroides fragilis from the peritoneal cavity. Studies with experimental peritonitis in pigs.

An animal model for study of bacterial elimination from the peritoneal cavity is presented. Using Escherichia coli and Bacteroides fragilis as infecting agents, two elimination patterns emerged. The patterns were related to the surface properties of the micro-organisms. The concentration of both species was greatly reduced within 2 to 4 hours after peritoneal contamination with 10(10) CFU. The elimination of B. fragilis was contemporaneous with mobilization of granulocytes into the peritoneal cavity, and was probably attributable to bactericidal action of the granulocytes. Most of the E. coli inoculum, however, was cleared before the granulocyte mobilization. Cell-free peritoneal fluid was found to have a bactericidal effect against a rough strain of E. coli, but not against a smooth strain, as demonstrated in vitro. This effect was inhibited by pretreatment of the peritoneal fluid with EDTA, EGTA or heat, which suggested that the alternate pathway of the complement system was involved. In vivo the rough strain of E. coli was rapidly eliminated, while elimination of the smooth strain followed the B. fragilis pattern. It is concluded that bacterial surface properties are important in bacterial peritonitis.

Animals↗
PubMed1991

Host defense mechanisms in the peritoneal cavity of continuous ambulatory peritoneal dialysis patients. 1.

This article provides a review of studies on peritoneal white blood cells (WBC) in CAPD patients. To some extent these studies support the concept that the peritoneal cavity of these patients contains adequate-functioning WBC that can provide effective antimicrobial defenses when they are studied in dialysate-free media. Commercially available dialysis solutions significantly impair WBC function. In some patients with high incidences of peritonitis, there appears to be reduced bactericidal capacity of their peritoneal macrophages. CAPD seems to contribute to a state of both macrophage and lymphocyte activation in the peritoneal cavity. The clinical consequences of this chronic activation are not known.

Cytokines↗
PubMed1990

Vancomycin absorption from the peritoneal cavity during dialysis-related peritonitis.

The uptake of vancomycin from the peritoneal cavity during acute episodes of peritonitis was compared to noninfected patients in 14 patients, 7 of whom had dialysis-related peritonitis. Treatment consisted of 8 hourly dialysate exchanges, followed by 4-h dwells containing 37.5 mg/L of vancomycin. On day 4, serum vancomycin concentrations were 13.4 +/- 4.8 mg/L in the controls and 15.5 +/- 6.8 mg/L in the group with peritonitis. After 180 min in the peritoneal cavity, 61% +/- 13% of the infused vancomycin remained in controls and 30% +/- 15% in patients with peritonitis (p less than 0.05). Uptake of vancomycin from the peritoneal cavity is enhanced during episodes of peritonitis.

Absorption↗
PubMed1990

The immunoglobulin allotype contributed by peritoneal cavity B cells dominates in SCID mice reconstituted with allotype-disparate mixtures of splenic and peritoneal cavity B cells.

We have studied potential regulatory interactions between mature B lymphocyte populations by analysis of C.B-17 severe combined immunodeficient (SCID) mice reconstituted simultaneously with immunoglobulin allotype-congenic mixtures of spleen (SP) and peritoneal cavity (PerC) B cells. We have previously shown that the independent transfer of B cells from these sources leads to the long-term survival of donor B cells and reconstitution of immunoglobulin levels in SCID mice (Riggs, J.E., D.L. Robertson, R.S. Stowers, and D.E. Mosier, manuscript submitted for publication). SP and PerC B cells differ in numerous respects, with the PerC having higher proportions of large, activated B cells that express the IgM greater than IgD phenotype and greater numbers of CD5 B cells. The injection of equal numbers of B cells from SP and PerC into SCID recipients (e.g., BALB/c SP + C.B-17 Per C----SCID) has led to the following observations: (a) serum IgM allotypes in B cell chimeras revealed strict dominance by the allotype contributed by the PerC B cells; (b) this dominance was not due to regulatory T cells; (c) B cells of the unexpressed (i.e., SP) allotype were present in the chimera in the spleen but not the peritoneal cavity; and (d) immunization with TI and TD antigens failed to elicit the SP IgM allotype, whereas secondary TD antigen immunization elicited low levels of the SP IgG2a allotype. Additional experiments demonstrated concurrent expression of IgM allotypes derived from both SP and PerC B cells in recipients that: (a) received a 10-fold excess of SP B cells; (b) received SP B cells before PerC B cell transfer; or (c) received SP B cells intravenously and PerC B cells intraperitoneally. We conclude that the establishment of IgM synthesis by PerC B cells leads to a feedback inhibition of subsequent IgM synthesis by SP B cells, and that the frequency of B cells that can lead to this effect is substantially higher in peritoneal cavity than in spleen. These data provide further confirmation of regulatory interactions between B cells in the absence of T lymphocytes, but confound the interpretation of experiments supporting the existence of a separate CD5+ B cell lineage.

Animals↗
PubMed1996

[Anatomic and physiologic characteristics of the peritoneal cavity with reference to peritoneal dialysis].

Most common complications of peritoneal dialysis are those related to anatomic defect of the abdominal wall and peritoneum. The aim of this investigation was to examine the frequency of congenital and acquired wall defects in patients on CAPD treatment causing complications. Fifty patients, 32 women and 18 men, on CAPD treatment for more than two years, were investigated. Most common was a defect in the anterior-lateral abdominal wall predisposing to hernias in 14% of patients. Umbilical and pericatheteral hernias were more common than other, with a mean time of 21 months for the appearance. Persistence of vaginal process of peritoneum related to scrotal oedema was documented in 4% of patients. Communication of peritoneal cavity with the abdominal ostium of tuba uterina was found not to be an important factor for peritonitis.

Adult↗
PubMed1990

Surface phagocytosis and host defence in the peritoneal cavity during continuous ambulatory peritoneal dialysis.

Since patients on continuous ambulatory peritoneal dialysis are at high risk for peritonitis, the opsonins in peritoneal dialysis effluent responsible for phagocytosis and a neutrophil chemiluminescence response to surface-adherent Staphylococcus epidermidis were examined. In surface phagocytosis assays uninfected dialysate was as opsonic as 1% serum. The opsonic activity was heat stable and equal to that of purified IgG at the same concentration (0.1 mg/ml). In contrast, optimal chemiluminescence to surface-adherent Staphylococcus epidermidis was dependent on complement. C3 deposition on Staphylococcus epidermidis opsonized in dialysate was quantitated by an enzyme immunoassay (EIA) and represented 13% of control C3 deposited with opsonization in 10% serum. Unused dialysate was found to be inhibitory to neutrophil phagocytosis and complement deposition. A combination of the low pH and high dextrose concentration of dialysate was responsible, but restoration of the pH to 7.4 largely restored both indices. During peritonitis there was a parallel increase in IgG levels and C3 deposition (r = 0.8), and surface phagocytosis was also enhanced. On further analysis, subjects with a single episode of peritonitis had a significantly more opsonic peritoneal effluent than those who had two infections during the study. This latter group had a poor IgG response to infection. This study demonstrates the relative deficiencies of host defence in the peritoneal cavity and indicates that measures to improve opsonin delivery and reduce the inhibitory effects of dialysate would be beneficial.

Aged↗
PubMed2001

Polyethylenimine-mediated gene transfer into pancreatic tumor dissemination in the murine peritoneal cavity.

Although peritoneal dissemination of cancer cells often occurs at the advanced stages of pancreatic, gastric or ovarian cancers, no effective therapy has been established. Cationic lipid-mediated gene transfer into peritoneal dissemination may offer a prospect of safe therapies, but vector improvements are needed with regard to the efficiency and specificity of the gene transfer. In this study, the intraperitoneal injection of plasmid DNA:polyethylenimine (PEI) complexes into mice was evaluated as a gene delivery system for the peritoneal disseminations. The luciferase and beta-galactosidase genes were used as marker genes. PEI was more efficient than the cationic lipids examined in this study in vivo, and the transgene was preferentially expressed in the tumors. Although PCR analysis showed that the injected DNA was delivered to various organs, the distributed DNA became undetectable by 6 months after the gene transfer. Blood chemistry and histological analysis showed no significant toxicity in the injected mice. This study demonstrated that the intraperitoneal injection of DNA:PEI is a promising delivery method to transduce a gene into disseminated cancer nodules in the peritoneal cavity.

Animals↗
PubMed1996

Acute bacterial peritonitis: permeability of cephalosporins in the peritoneal cavity.

Acute bacterial peritonitis is a common surgical disease treated with fluid resuscitation, surgery and antibiotics. The choice and use of antibiotics is an important supplement of therapy. Cephalosporins are among the most frequently used drugs for this condition. Although there is evidence that these agents reach the peritoneal cavity under normal conditions, no data are available regarding their delivery and concentration during acute secondary bacterial peritonitis. In order to determine the effectiveness of these agents in such cases, we studied the diffusion of three generations of cephalosporins--cefazolin, cefonicid and cefotaxime--into the peritoneal cavity during controlled bacterial peritonitis in rats. Our results show that all three drugs reached therapeutic concentrations in the peritoneal fluid; the highest concentration was obtained by the third-generation cefotaxime.

Acute Disease↗
PubMed2006

Disproportionally low clearance of macromolecules from the plasma to the peritoneal cavity in a mouse model of peritoneal dialysis.

BACKGROUND: This study was performed to establish a model for quantitative measurements of a number of basic peritoneal transport parameters, particularly transperitoneal clearances (Cl) of macromolecules, during mouse peritoneal dialysis. METHODS: Mice were anaesthetized using 3% isofluorane inhalation anaesthesia. The right jugular vein and the left femoral artery were cannulated for infusion and sampling purposes and for registration of (mean) arterial blood pressure. Access to the peritoneal cavity occurred via a thin abdominal catheter (Ø 0.7 mm). About 2.5 ml of either 4% (n = 9) or 1.5% (n = 5) glucose containing PD-fluid were instilled intraperitoneally (i.p.). Dialysate volume was followed vs time using i.p. RISA ((125)I human serum albumin) as a volume marker, after correcting for RISA mass disappearance from the peritoneum, assessed separately (n = 11). Microsampling (10 microl) of plasma and dialysate was performed for determinations of glucose, haematocrit, radioactivity (RISA and (51)Cr-EDTA) and Ficoll. RESULTS: The i.p. volume vs time curves [V(D)(t)] were, after scaling, similar to those observed in humans (and in rats). Clearance of RISA out of the peritoneal cavity (Cl(out)) was 9.33 +/- 0.83 microl/min and the clearance of RISA to plasma (Cl-->P) and the RISA clearance to the peritoneal cavity (Cl-->D) were 1.49 +/- 0.13 and 0.084 +/- 0.008 microl/min, respectively. The peritoneal transport coefficients for (51)Cr-EDTA and glucose, as well as Cl(out) and Cl-->P, were 13-17% of those previously assessed in 300 g rats, whereas Cl-->D was only approximately 2% of that in rat. CONCLUSIONS: All peritoneal transport parameters measured, except Cl-->D, scaled very well to the corresponding human data. The mechanisms of the disproportionally low clearance of macromolecules from the plasma to the peritoneal cavity in mice remain elusive and warrant further study.

Animals↗