Gonadotropins induce higher active renin levels in the follicular fluid of normal and hyperstimulated cycles.

The objective of this study was to analyze follicular fluid active renin and its relationship to steroid hormones throughout the normal and gonadotropin-stimulated menstrual cycle. Active renin was measured in the follicular fluid of patients undergoing tubal sterilization (n = 16) and in vitro fertilization (IVF) (n = 25); IVF patients were either in a natural cycle (n = 7) or undergoing controlled ovarian hyperstimulation (n = 18). The largest visible follicle was aspirated at the time of laparoscopic tubal sterilization; ultrasound guided transvaginal follicular aspiration was used in the IVF group. Follicular fluid active renin, estradiol and progesterone levels were measured with immunoradiometric and fluoroimmunoassays. The cycle day was correlated with the spontaneous luteinizing hormone (LH) surge or human chorionic gonadotropin (hCG) administration, as well as active renin, estradiol, progesterone levels and the estradiol/progesterone ratio using simple and multiple regression and analysis of variance (ANOVA). Cycle day independently influenced active renin, progesterone and the estradiol/progesterone ratio in a statistically significant manner (p < 0.0001). The active renin and progesterone levels were highest during the periovulatory period (p < 0.0001 and p < 0.002, respectively) and the estradiol/progesterone ratio correlated inversely with cycle day (p < 0.003). Although the follicular fluid active renin, estradiol and progesterone levels were higher after controlled ovarian hyperstimulation when compared to natural cycles, this difference did not reach statistical significance. Our findings suggest that active renin levels in follicular fluid increase in the follicular phase of the menstrual cycle, reaching peak levels in the periovulatory period following the LH surge or hCG administration, providing indirect support for the hypothesis that the ovarian renin-angiotensin system (RAS) is under gonadotropin control.

Gonadotropins induce the release of interleukin-1 beta, interleukin-6 and tumor necrosis factor-alpha from the human preovulatory follicle.

PROBLEM: The effects of exogenous gonadotropin administration and steroid levels on the release of various cytokines into the human follicular fluid (FF) were studied. METHOD OF STUDY: Forty patients were included in two groups, those undergoing controlled ovarian hyperstimulation (COH) (n = 33) and natural cycles (n = 7). FF transvaginal aspirations were performed 36 hr after administration of human chorionic gonadotropin or a spontaneous surge of luteinizing hormone, respectively. FF cytokine measurements were performed with sensitive immunoassays. RESULTS: FF cytokine levels were higher after COH [interleukin (IL)-1 beta, 6.6 +/- 0.32 pg/ml; IL-6, 18.7 +/- 2.1 pg/ml; and tumor necrosis factor (TNF)-alpha, 32.5 +/- 4.9 pg/ml] than in natural unstimulated cycles (0.52 +/- 0.1 pg/ml, P < 0.001; 8.9 +/- 1.2 pg/ml, P < 0.01; and 13.2 +/- 2.6 pg/ml, P < 0.001, respectively). FF estradiol (E2) and progesterone levels were not statistically different between groups, despite the higher serum E2 levels observed in patients after COH. CONCLUSIONS: Gonadotropins might regulate ovarian secretion of cytokines, because FF IL-1 beta, IL-6, and TNF-alpha levels after COH were higher than during natural cycles.

Optimizing end-stage renal disease therapy for the patient with diabetes mellitus.

Patients with diabetes represent the fastest growing segment of the end-stage renal disease (ESRD) population, which itself is growing at a rate of approximately 10% per year. The most recent report of the United States Renal Data System (USRDS) shows a prevalence of diabetes among patients with ESRD of 27.3% (59,403 of 217,479) and an incidence of 33.6% (19,013 of the 56,610). The majority of patients with ESRD secondary to diabetes (67.7%) are treated by hemodialysis, 13.2% by peritoneal dialysis, and 19.1% have functioning renal transplants. The number of patients over 60 years of age has increased steadily. Parallel with this increase, the percentage of patients with one or more comorbid conditions increased from 66% to 85% in patients with diabetes and from 57% to 66% in patients without diabetes. The relative risk of death in patients with diabetes is markedly increased and is further exacerbated in patients with poor nutritional status. Although diabetes is the most common primary disease associated with death in the ESRD population, the mortality for patients with ESRD secondary to diabetes has decreased from 46% in 1982 to 29% in 1993. Patients with ESRD from diabetes challenge the nephrologist because they have the greatest number of comorbid conditions, the highest levels of physical dysfunction, and the greatest dependency in activities of daily living. The goal of therapy is to improve quality of life, as well as reduce mortality. Patients with diabetes experience improved survival after either kidney transplant or enhanced Kt/V on dialysis. Therefore, the most important therapeutic intervention is to maximize renal replacement therapy (either by transplantation or by providing levels of dialysis adequacy higher than previously recommended). In addition, attention to several basic principles helps to guide therapy; control of hypertension, control of hyperglycemia, control of lipid abnormalities, treatment of malnutrition, and attention to the effects of erythropoietin. Advanced glycation and products (AGEs) have been proposed as new "uremic toxins", because of their pathogenetic association with a variety of vascular and morbid complications. There is sound experimental evidence to suggest that reducing the accumulation of these products to normal levels may prevent diabetic complications. Better understanding of the nature of the relationship between formation and removal is needed to direct therapeutic interventions towards adequate control of the accumulation of AGEs in patients with renal failure, with or without diabetes.

Markedly elevated cytokines in pleural effusion during the ovarian hyperstimulation syndrome: transudate or ascites?

OBJECTIVE: To study levels of proinflammatory cytokines in pleural fluid during the severe ovarian hyperstimulation syndrome (OHSS). DESIGN: Case report. SETTING: Tertiary academic medical center. PATIENT(S): A 35-year-old female with a 6-year history of unexplained infertility on menotropin therapy and 28 healthy normal controls. INTERVENTION(S): Thoracentesis for severe pleural effusion and venipunctures. MAIN OUTCOME MEASURE(S): Interleukin-1 beta (IL-beta), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) levels were measured by ELISA and compared between pleural effusion and serum from normal controls. RESULT(S): Pleural effusion IL-1 beta and IL-6 levels were higher than serum. Interleukin-6 levels were elevated particularly in pleural effusion (1,961.89 pg/mL) compared with serum (3.9 +/- 0.41 pg/mL). CONCLUSION(S): Our results confirm the high cytokine levels observed in OHSS. Cytokines have been implicated in capillary permeability, extravasation of fluid, oliguria, and shock. We have postulated that these mediators are released from the corpora lutea into the peritoneum and systemic circulation. Alternatively, the presence of high cytokine levels in pleural fluid maybe the result of diaphragmatic defects, which allow for the migration of ascites into the pleural space.

Abdominal catastrophe: visceral injury as a cause of peritonitis in patients treated by peritoneal dialysis.

OBJECTIVE: Peritonitis is considered an acceptable and controllable risk in patients undergoing chronic peritoneal dialysis (PD). In contrast, peritonitis due to visceral leakage represents a true "abdominal catastrophe" because of striking morbidity and mortality. To delineate the incidence, causes, and outcomes of catastrophic peritonitis, we compared patients who developed peritonitis due to documented visceral leakage with patients who developed peritonitis due to enteric organisms without evidence of visceral leakage. DESIGN: Retrospective chart review. SETTING: PD Unit located in tertiary care referral center. PATIENTS: 230 patients treated by PD between January 1988 and June 1996. MAIN OUTCOME MEASURES: All episodes of PD-related peritonitis occurring over an 8-year period. Hospital course of all patients with or without renal failure who were treated at University Hospitals of Cleveland for ischemic bowel disease, cholecystitis, viscus perforation, or diverticulitis. RESULTS: Anatomically documented visceral injury caused 32.5% of episodes of enteric bacterial peritonitis in 72 patients between January 1988 and June 1996. The overall incidence of this "abdominal catastrophe" was 11.3%, or 26 of a total of 230 patients treated by PD. Of the 26 patients, 50% died, 30.7% survived but switched permanently to hemodialysis, and only 19.2% remained on, or returned to, PD. Compared to renal failure patients treated by hemodialysis or transplantation and to non-renal failure patients, the incidence of abdominal catastrophe was 20-60 times greater in patients treated by PD. CONCLUSIONS: Evidence for injury of an abdominal organ should be sought in all patients treated by PD who develop peritonitis with enteric organisms. Surgical intervention is definitive for diagnosis, and if performed early may reduce morbidity and mortality.

Disparate changes in plasma and tissue pentosidine levels after kidney and kidney-pancreas transplantation.

The advanced glycation end-product, pentosidine, was measured in plasma proteins and skin collagen before and after kidney and kidney-pancreas transplantation in order to determine the relationship between plasma and tissue levels and to characterize the pattern of change in pentosidine levels after correction of hyperglycemia and/or renal failure. The content of pentosidine in skin collagen was higher than that in plasma proteins both before and after transplantation. However, there was no correlation between plasma and skin pentosidine levels. Prior to transplantation, the content of pentosidine in skin collagen was related to the duration of dialytic therapy, presence of diabetes mellitus, age, and female gender. Following transplantation, plasma pentosidine levels were inversely correlated with glomerular filtration rate (r = 0.64; p < 0.01). While plasma pentosidine levels consistently decreased after transplantation, levels in skin collagen increased in 10 of 13 patients, including 5 of 6 recipients of kidney-pancreas transplants. Our results indicate that tissue levels of pentosidine persist for long periods of time after kidney or kidney-pancreas transplantation, despite consistent decreases in levels measured in plasma proteins. The observed increase in tissue pentosidine levels in a majority of patients suggests that formation of advanced glycation end-products may continue after otherwise successful kidney or kidney-pancreas transplantation.

Ovarian hyperstimulation syndrome: pre-ovulatory serum concentrations of interleukin-6, interleukin-1 receptor antagonist and tumour necrosis factor-alpha cannot predict its occurrence.

The pathogenesis of the ovarian hyperstimulation syndrome (OHSS) is poorly understood. Since significant elevations in cytokines are found in OHSS, our objective was to conduct a prospective case-controlled study to assess if pre-ovulatory cytokine serum concentrations can predict its occurrence. The study group was selected from in-vitro fertilization patients who subsequently developed severe OHSS, along with a matched group who did not develop this complication (n = 20), and a healthy normal control group (n = 10). Interleukin-6 (IL-6), interleukin-1 receptor antagonist (IL-1RA) and tumour necrosis factor-alpha (TNFalpha) measurements were performed with sensitive immunoassays and confirmed with bioassays. Serum IL-6 (mean concentrations +/- SEM: 4. 38 +/- 0.36 pg/ml), IL-1RA (829 +/- 292 pg/ml) and TNFalpha (15.5 +/- 1.32 pg/ml) concentrations did not show differences throughout the normal menstrual cycle group. Cytokine variability and pre-ovulatory values were similar in OHSS compared to controlled ovarian hyperstimulation (COH) patients. However, average follicular phase serum IL-6 concentrations were higher in OHSS (8.71 +/- 0.41 pg/ml) and COH (7.66 +/- 0.38 pg/ml) patients than in normally menstruating women (4.34 +/- 0.99 pg/ml) (P < 0.0001). Pre-ovulatory serum IL-6 concentrations were also higher in OHSS (9 +/- 0.94 pg/ml) and COH (7.3 +/- 0.97 pg/ml) patients than in controls (4.57 +/- 1.1 pg/ml) (P < 0.01 and P < 0.04 respectively). All IL-1RA and TNFalpha concentrations were comparable in all the groups. This study suggests that cytokine measurements cannot be used to predict the occurrence of OHSS prior to the administration of human chorionic gonadotrophin.

The advanced glycation endproduct pentosidine and monocyte activation in uremia.

RATIONALE: Advanced glycation endproducts (AGEs) contribute to the pathogenesis of vascular complications in diabetes, aging and end-stage renal disease (ESRD). Immune abnormalities in patients with chronic renal failure and those treated by dialysis contribute to high rates of morbidity and mortality. We therefore sought a relationship between a circulating marker of immune dysfunction and plasma levels of the AGE pentosidine. METHOD: We studied non-diabetic patients with mild to advanced renal failure (n = 60), and with ESRD treated by hemodialysis (HD) (n = 44) and peritoneal dialysis (PD) (n = 19). The plasma protein content of the well characterized AGE, pentosidine was measured using HPLC. In the same samples the monocyte activation product neopterin was measured by RIA. RESULTS: Plasma levels of pentosidine and neopterin increased in parallel with the progression of renal failure. Pentosidine and neopterin were highly correlated in all patients even after adjustment for Ccr. This correlation was also present in patients with ESRD. CONCLUSION: These data suggest that the AGE pentosidine is associated with monocyte activation in renal failure, an interaction which may contribute to accelerated rates of complication and death by as yet unknown mechanisms.

Decreased production of TGF-beta 1 by human alveolar macrophages compared with blood monocytes.

As the main immunocytes lining pulmonary alveoli, alveolar macrophages (AM) are critical to the maintenance of immune hemostasis of the lung. This study examined the capacity of AM obtained from healthy individuals in comparison with autologous blood monocytes (MN) to produce transforming growth factor-beta 1 (TGF-beta), a pivotal molecule in regulation of immune responses and in promotion of fibrosis. AM produced negligible TGF-beta in response to LPS at both 24 and 72 h of culture. In contrast, LPS induced significant levels of TGF-beta in MN cultures (79.5 +/- 35 pg/ml in AM vs 890 +/- 162 pg/ml in MN, p less than 0.001, at 24 h). AM also produced significantly less TGF-beta than MN in response to phorbol ester and Con A. By northern blot analysis, constitutive expression of TGF-beta mRNA was lower in AM than MN at the time of isolation and after 24 h of culture. Lower expression of steady state TGF-beta message was not due to a more rapid decay of its mRNA in AM. Furthermore, TGF-beta mRNA expression was up-regulated by rTGF-beta in MN but was not induced in AM. In contrast to TGF-beta, LPS-stimulated AM produced sixfold higher levels of TGF-alpha at 24 h than MN (p less than 0.01). Production of IL-10 by LPS-stimulated AM was sixfold lower than MN (p less than 0.005) at 24 h of culture, but was comparable with MN at 72 h. Both 10-day cultured monocytes and peritoneal macrophages also had reduced capacity to produce TGF-beta. Therefore, the inability to produce TGF-beta may be a feature of more differentiated mononuclear phagocytes. In health, the reduced expression of TGF-beta by AM and the intact ability to produce TGF-alpha and IL-10 may favor a timely and regulated host response to inhaled pathogens while limiting potentially deleterious inflammatory responses.

Elevated interleukin-6 levels in the ovarian hyperstimulation syndrome: ovarian immunohistochemical localization of interleukin-6 signal.

OBJECTIVE: To examine the production and immunolocalization of interleukin-6 (IL-6) in patients with the ovarian hyperstimulation syndrome. METHODS: The study group consisted of patients with ovarian hyperstimulation syndrome (n = 9) from whom serum and ascites samples were obtained. The control samples used were serum (n = 10) and peritoneal (n = 16) and follicular fluids (n = 8) from healthy individuals. Follicular fluid (n = 40) and serial serum samples were also obtained from patients undergoing menotropin stimulation for in vitro fertilization (IVF) before (n = 10) and after ovulation (n = 34). Interleukin-6 measurements were performed with a sensitive immunoassay and confirmed with a bioassay. Immunohistochemical localization of IL-6 was performed with a mouse monoclonal antibody in normal premenopausal (n = 5) and postmenopausal ovaries (n = 5), as well as with cells from stimulated follicular fluid aspirates (n = 3). RESULTS: We found significantly higher serum and ascites IL-6 levels in ovarian hyperstimulation syndrome (mean 18.8 +/- 1.1 and 810.8 +/- 60.7 pg/mL, respectively) compared with postovulatory serum and peritoneal fluid from normal controls (mean 4.4 +/- .69 and 44.7 +/- 7.5 pg/mL, respectively) (P < .001) or serum after menotropin stimulation (13.1 +/- 1.1 pg/mL) (P < .001). At the time of ovulation, follicular fluid IL-6 levels (normal controls, mean 9 +/- 2.1 pg/mL; menotropin stimulation, mean 10.1 +/- 4 pg/mL) were higher than in preovulatory serum (normal controls, mean 4.5 +/- .8 pg/mL; menotropin stimulation, mean 6.3 +/- 1.4 pg/mL) (P < .001). Immunohistochemical localization of IL-6 revealed intense staining in corpora lutea and theca cells from large antral follicles and luteinized granulosa cells in follicular aspirates after menotropin stimulation. CONCLUSION: Interleukin-6 levels are markedly elevated in the ovarian hyperstimulation syndrome when compared with controls. The higher follicular fluid IL-6 levels seen suggest local secretion of this cytokine. Immunohistochemical correlation demonstrated IL-6 within ovarian theca cells. These findings suggest a local role for IL-6 both in normal and stimulated ovarian function. Whether IL-6 is directly responsible for the clinical manifestations of this syndrome is unclear. However, when produced in massive amounts, the pro-inflammatory effects of IL-6 may contribute to its pathogenesis and perhaps serve as a marker for the disease.

Early and advanced glycosylation end products. Kinetics of formation and clearance in peritoneal dialysis.

The chronic contact of glucose-containing dialysate and proteins results in the deposition of advanced glycation end products (AGEs) on peritoneal tissues in patients treated by peritoneal dialysis (PD), yet plasma levels of the AGE pentosidine are significantly lower in PD than in hemodialysis (HD). We measured glycation of peritoneal proteins in patients on PD over the time course of intraperitoneal equilibration of fresh peritoneal dialysate. The glycated content of peritoneal proteins (furosine method) was initially identical to plasma but increased 200% within 4 h due to in situ glycation as also demonstrated in vitro. In contrast, peritoneal proteins contained a 2-4 x greater content of the AGE pentosidine at all equilibrium time points. Plasma protein furosine content was identical in patients on PD and on HD. Fractionation by gel filtration of serum from patients on PD and HD revealed that > 95% of the pentosidine was linked to proteins > 10,000 mol wt; < 1% to proteins < 10,000 mol wt; and < 1%, free. Neither HD nor PD affected protein-bound pentosidine. The HD treatment decreased free and < 10,000 mol wt bound pentosidine. However clearance of protein-associated pentosidine by the peritoneal membrane may explain lower steady state levels in patients treated by PD.

Structure of advanced Maillard reaction products and their pathological role.

In this article we review recent progress and controversies relating to three areas of the field of advanced glycosylation end-products (AGE). A controversy exists as to whether pyrraline, an AGE detectable by immunohistochemistry in kidneys from patients with renal failure, exists in vivo. Recent data from the authors' laboratory revealed that pyrraline is present in alkaline or protease digests from human skin and plasma. However, the amounts are very low and pyrraline was found to undergo further reactions to form an ether with itself (dipyrraline) as well as a thioether with cysteine. This high reactivity of pyrraline may explain the difficulty of quantitating it accurately in biological material. In contrast, the glycoxidation products carboxymethyllysine (CML) and pentosidine are stable, very resistant to acid hydrolysis and easy to quantitate. They are present in elevated concentrations in the extracellular matrix in diabetes mellitus and ageing. In the diabetic human lens, CML is not elevated, in contrast to pentosidine, suggesting a different mechanism of formation. Recent data in diabetic dogs have shown that pentosidine is elevated only in lenses from poorly controlled dogs, in contrast to LM-1, a fluorophore thought to arise from ascorbate. Further studies are needed to clarify the intracellular mechanism of glycoxidation. The greatest concentrations of AGEs and glycoxidation products are found in patients with end-stage renal disease, and they are almost completely normalized by renal transplantation. Comparison of peritoneal dialysis (PD) with haemodialysis (HD) showed that PD is associated with lower plasma protein pentosidine, possibly due to selective transport of pentosidine-rich protein across the peritoneal wall. Fractionation of plasma proteins from ESRD patients by size showed that 90% of pentosidine is linked to HMW protein and 1-2% is in free form. The mechanism of accelerated glycoxidation in ESRD is still not understood.

Influence of dialysis modality on plasma and tissue concentrations of pentosidine in patients with end-stage renal disease.

Plasma and tissue concentrations of pentose-derived glycation end-products ("pentosidine") are elevated in diabetic patients with normal renal function and in both diabetic and nondiabetic patients with end-stage renal disease. To determine the influence of dialysis modality and other clinical variables on the accumulation of pentosidine, we used high-performance liquid chromatography to measure this advanced glycation end-product in plasma, skin, and peritoneal samples obtained from 65 hemodialysis and 45 peritoneal dialysis patients. Plasma pentosidine levels were significantly lower in peritoneal dialysis patients. Concentrations of pentosidine in skin were similar in the two groups. In contrast, peritoneal concentrations of pentosidine were significantly higher in the patients maintained on peritoneal dialysis. Our results demonstrate that dialysis modality influences the plasma and tissue distribution of pentosidine. Compared with hemodialysis, peritoneal dialysis is associated with lower levels of this glycation end-product in plasma, but with higher levels in the peritoneum. The mechanisms accounting for lower circulating levels of pentosidine in peritoneal dialysis patients remain to be determined. Higher levels in peritoneal tissues may reflect chronic exposure to the high concentrations of glucose in peritoneal dialysate.

Variability in calculations of dialysis adequacy in patients using nightly intermittent peritoneal dialysis compared to CAPD.

Increasing numbers of patients receive peritoneal dialysis using noncontinuous methods such as nightly intermittent peritoneal dialysis (NIPD) rather than continuous ambulatory peritoneal dialysis (CAPD). We hypothesized that blood solute levels before and after NIPD would be large enough to produce significant variability in formulas based on the continuous peritoneal dialysis (PD) model. We found no diurnal differences in serum creatinine in NIPD or CAPD. However, our data demonstrate a 7.9% difference in serum urea measurements from evening to morning in patients treated by NIPD. This mathematical difference contributes to a 6.3% difference in the calculated value of KT/V and a 9.4% difference in the calculation of total urea clearance (liters per week) in these patients. By contrast, no difference in serum values or in calculated values of adequacy could be shown in patients on CAPD. These observations support the premise that CAPD represents a steady-state condition. NIPD patients demonstrate variability in serum levels of urea which may result in inaccurate calculations of dialysis adequacy. When blood samples are obtained in the morning soon after completing a cycle of NIPD, dialysis adequacy as measured by KT/V or total urea clearance (but not by total creatinine clearance) may be systematically overestimated.

Disparate cytochemical characteristics and production of cytokines and prostaglandin E2 by human mononuclear phagocytes from the blood, lung, and peritoneal cavity.

The cytochemical characteristics and the production of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and prostaglandin E2 (PGE2) by peritoneal macrophages were compared with those of blood monocytes and alveolar macrophages. The comparative percentages of mononuclear phagocytes positive for peroxidase were as follows: blood monocytes > peritoneal macrophages > alveolar macrophages. The comparative percentages of cells positive for nonspecific esterase were as follows: alveolar macrophages > peritoneal macrophages = blood monocytes. The intensity of staining for nonspecific esterase was highest in alveolar macrophages and lowest in blood monocytes. Constitutive release of TNF, IL-1 beta, and PGE2 was minimal by each cell type. Lipopolysaccharide-stimulated TNF production by alveolar macrophages was approximately five times greater than that of monocytes and 10 times greater than that of peritoneal macrophages. By contrast, lipopolysaccharide-stimulated blood monocytes produced significantly more IL-1 beta than did peritoneal or alveolar macrophages. Lipopolysaccharide-stimulated production of PGE2 by peritoneal macrophages was significantly less than that of alveolar macrophages or blood monocytes. Thus peritoneal macrophages release relatively low levels of IL-1 beta, TNF, and PGE2 in response to lipopolysaccharide. Peritoneal and alveolar macrophages differ with respect to both cytochemical characteristics and lipopolysaccharide-stimulated production of TNF and PGE2 but are similar in their limited capacity to produce IL-1 beta.

Lack of correlation between nasal cultures positive for Staphylococcus aureus and the development of S. aureus exit-site infections: results unaffected by routine mupirocin treatment of nasal S. aureus carriage.

Whether nasal carriage of Staphylococcus aureus is associated with an increased risk of S. aureus exit-site infection remains controversial. We performed nasal cultures prior to peritoneal dialysis catheter placement in all of our patients beginning in September 1990. We also performed nasal cultures on a cohort of patients already on peritoneal dialysis. Patients with positive cultures received a prescription for a ten-day course of intranasal mupirocin. Exit-site and nasal cultures were performed on every subsequent office visit until the end of the study in April 1993. The initial visit and three widely-spaced subsequent visits were chosen for data analysis. There were 68 patients entered into the study. Data from a total of 272 visits were analyzed. The patients ranged in age from 18-80 years. There were 27 diabetics. We found no correlation between initial positive nasal cultures and the subsequent development of a S. aureus exit-site infection. All identified nasal carriers were treated with mupirocin. However, the subsequent development of a S. aureus exit-site infection could not be correlated to a prior S. aureus carrier state or lack thereof.

Elevated levels of interleukin-6 in ascites and serum from women with ovarian hyperstimulation syndrome.

OBJECTIVE: To examine the role of pro-inflammatory cytokines in ovarian hyperstimulation syndrome (OHSS). DESIGN: In vitro laboratory study of serum, peritoneal cells isolated and fluid obtained from ascites removed in the therapeutic management of four patients with OHSS. SETTING: Tertiary care referral teaching hospital. PATIENTS: Four patients with OHSS comprised the study population. Five healthy women at the time of elective laparoscopic tubal ligation served as controls. Control serum was also obtained from healthy adult volunteers, and control peritoneal fluid (PF) was obtained from patients on peritoneal dialysis. INTERVENTIONS: Therapeutic paracentesis was performed on four patients with OHSS. RESULTS: Peritoneal cells were isolated and fluid obtained from ascites removed in the therapeutic management of the women with OHSS. Peritoneal cells were obtained by intraoperative lavage from the control women. The cells were incubated with various concentrations of Escherichia coli lipopolysaccharide (LPS) for 20 and 48 hours. Interleukin-1 beta (IL-1 beta), tumor necrosis factor (TNF), interleukin-6 (IL-6), and prostaglandin E2 (PGE2) were assayed in the incubation supernatants. The release of the three cytokines and PGE2 in response to LPS by peritoneal cells from women with OHSS was not different from the controls. However, both serum and ascitic fluid from women with OHSS contained significantly greater levels of IL-6 than control serum and PF. No significant differences in TNF levels in serum, ascitic fluid, or PF could be found by ELISA or bioassay. CONCLUSIONS: Increased production of IL-6, released into the peritoneal cavity and the circulation, may mediate OHSS.

Role of dialysis modality in responses of blood monocytes and peritoneal macrophages to endotoxin stimulation.

Constitutive and endotoxin (lipopolysaccharide [LPS])-stimulated release of interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and prostaglandin E2 (PGE2) by blood monocytes and peritoneal cell preparations from patients on various forms of dialysis was measured. Monocytes were obtained from healthy controls (n = 20), and from patients on peritoneal dialysis (n = 8), on hemodialysis with cellulose ester membranes (n = 9), and on hemodialysis with polysulfone membranes (n = 8). Peritoneal macrophages were recovered by lavage during laparoscopic surgery from 11 healthy controls, from dialysate in 37 patients on peritoneal dialysis, and at catheter placement for transfer to peritoneal dialysis from eight patients on hemodialysis with polysulfone membranes. Peak LPS-induced production of TNF-alpha, IL-1 beta, and IL-6 by monocytes from patients on peritoneal dialysis and cellulose ester hemodialysis was less than that by monocytes from healthy controls. In contrast, monocytes from patients treated with polysulfone hemodialysis produced amounts of cytokine not different from controls. Lipopolysaccharide-stimulated PGE2 production by monocytes was the same in both patient and control groups. Peritoneal cell preparations from patients on peritoneal dialysis showed decreased release of IL-1 beta and TNF-alpha as compared with control peritoneal cells and with their own blood monocytes. To determine whether the decreased response to LPS by peritoneal cells compared with their own blood monocytes could be attributed to lower numbers of macrophages in the peritoneal cell preparations, adherence of peritoneal cells to plastic was performed. Adherence increased the percentage of macrophages from 70% to more than 90%. In monocytes and adherence purified peritoneal macrophages from peritoneal dialysis patients, no significant difference between monocytes and adherent peritoneal macrophages could be found for TNF-alpha and PGE2. Interleukin-1 beta production by the adherent peritoneal macrophages, as by total peritoneal cells, was significantly lower than that by monocytes. Constitutive production of PGE2 and IL-6 by peritoneal cells from patients on peritoneal dialysis was significantly increased. In contrast, LPS-stimulated production of TNF-alpha, IL-1 beta, and IL-6 by blood monocytes and peritoneal cells from patients receiving hemodialysis with polysulfone membranes was comparable to that produced by monocytes and peritoneal cells obtained from healthy controls. Thus, blood monocytes and peritoneal cells from patients on peritoneal dialysis and from patients on hemodialysis with cellulose-ester membranes demonstrate a decreased cytokine response to LPS, suggesting a state similar to endotoxin tolerance.(ABSTRACT TRUNCATED AT 250 WORDS)