Diffuse alveolar hemorrhage as an early complication of alemtuzumab treatment: A case report of a multiple sclerosis patient and an overview of 14 cases.

Alemtuzumab is effective in relapsing remitting multiple sclerosis (RRMS). Serious adverse events have led to a renewed safety reassessment by the European Medicines Agency (EMA), leading to an approval under strict conditions. We report a RRMS patient experiencing diffuse alveolar hemorrhage (DAH) on day 4 of her first alemtuzumab cycle. In addition, we present an overview of the cases of alemtuzumab-induced DAH that were included in EMA's review procedure, additional well documented cases reported to the EMA and those cases reported in the literature. Combining these cases revealed striking similarities. Importantly, DAH was an early complication. All RRMS patients with known outcome showed complete recovery.

Caregiver strain among life partners of persons with mild disability due to relapsing-remitting multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is a chronic disorder of the central nervous system with an unpredictable disease course. Life partners often become caregivers, which can be both rewarding and challenging, as the caregiver's physical and mental health is often negatively affected. Previous studies on caregiver strain focused on caregivers of persons with MS with relatively high disability levels, while caregiver strain may already be experienced by life partners living with mildly disabled persons with MS. OBJECTIVE: The current study examines factors associated with caregiver strain in life partners of persons with mild disability due to relapsing-remitting MS. METHODS: We included 173 persons with relapsing-remitting MS (79% female; mean age 42.8 years; 90% employed; median EDSS 2.0) and their life partners. The life partners completed questionnaires on caregiver strain and neuropsychiatric and cognitive functioning of the person with MS. The persons with MS completed questionnaires about demographics, fatigue, personality, physical, cognitive and neuropsychiatric functioning, and underwent neuropsychological and neurological examinations. A linear regression analysis was conducted to examine predictors of caregiver strain. RESULTS: 24% of the life partners experienced above average levels of caregiver strain. A multivariate linear regression analysis revealed that a higher age of the person with MS (ß = 0.16, p = 0.04), more physical disability (ß = 0.17 p = 0.04), more cognitive and neuropsychiatric problems of the person with MS as reported by the life partner (ß = 0.33, p = 0.001) and higher severity of neuropsychiatric symptoms as reported by the life partner (ß = 0.32, p = 0.001) were associated with higher caregiver strain (R2 = 0.49). CONCLUSION: Higher caregiver strain in life partners of persons with mild disability due to relapsing-remitting MS was primarily associated with cognitive and neuropsychiatric problems of the person with MS.

The capability set for work - correlates of sustainable employability in workers with multiple sclerosis.

BACKGROUND: The aim of this study was to examine whether work capabilities differ between workers with Multiple Sclerosis (MS) and workers from the general population. The second aim was to investigate whether the capability set was related to work and health outcomes. METHODS: A total of 163 workers with MS from the MS@Work study and 163 workers from the general population were matched for gender, age, educational level and working hours. All participants completed online questionnaires on demographics, health and work functioning. The Capability Set for Work Questionnaire was used to explore whether a set of seven work values is considered valuable (A), is enabled in the work context (B), and can be achieved by the individual (C). When all three criteria are met a work value can be considered part of the individual's 'capability set'. RESULTS: Group differences and relationships with work and health outcomes were examined. Despite lower physical work functioning (U = 4250, p = 0.001), lower work ability (U = 10591, p = 0.006) and worse self-reported health (U = 9091, p ≤ 0.001) workers with MS had a larger capability set (U = 9649, p ≤ 0.001) than the general population. In workers with MS, a larger capability set was associated with better flexible work functioning (r = 0.30), work ability (r = 0.25), self-rated health (r = 0.25); and with less absenteeism (r = - 0.26), presenteeism (r = - 0.31), cognitive/neuropsychiatric impairment (r = - 0.35), depression (r = - 0.43), anxiety (r = - 0.31) and fatigue (r = - 0.34). CONCLUSIONS: Workers with MS have a larger capability set than workers from the general population. In workers with MS a larger capability set was associated with better work and health outcomes. TRIAL REGISTRATION: This observational study is registered under NL43098.008.12: 'Voorspellers van arbeidsparticipatie bij mensen met relapsing-remitting Multiple Sclerose'. The study is registered at the Dutch CCMO register ( https://www.toetsingonline.nl ). This study is approved by the METC Brabant, 12 February 2014. First participants are enrolled 1st of March 2014.

Coping strategies in relation to negative work events and accommodations in employed multiple sclerosis patients.

BACKGROUND: Job loss is common in multiple sclerosis (MS) and is known to exert a negative effect on quality of life. The process leading up to job loss typically includes negative work events, productivity losses and a need for accommodations. By using active coping strategies job loss may be prevented or delayed. OBJECTIVE: Our goal was to examine negative work events and accommodations in relation to coping strategies in employed relapsing-remitting MS patients. METHODS: Ninety-seven MS patients (77% females; 21-59 years old) completed questionnaires concerning the patient's work situation, coping strategies, demographics, physical, psychological and cognitive functioning. Forward binary logistic regression analyses were conducted to examine coping strategies and other (disease) characteristics predictive of reported negative work events and accommodations. RESULTS: Nineteen per cent of the employed MS patients reported one or more negative work events, associated with a higher use of emotion-oriented coping and more absenteeism. Seventy-three per cent reported using one or more work accommodations, associated with a higher educational level and more presenteeism. MS patients reporting physical changes to the workplace employed more emotion-oriented coping, while flexible scheduling was associated with task-oriented coping. CONCLUSION: Emotion-oriented and task-oriented coping strategies are associated with negative work events and the use of accommodations.

[Improvement of vision in nursing home patients through eyeglasses]. / Visusverbetering door brilcorrectie bij verpleeghuispatiënten.

Adequate refraction correction may contribute to the quality of life of elderly persons who will be less dependent on care in daily life and will be less prone to fall. In nearly 20% of 102 nursing home residents binocular visual acuity improved with at least one line on the Snellen Chart by adjustment of refractive correction.

Prostaglandin inhibition by intraperitoneal indomethacin has no effect on peritoneal permeability during stable CAPD.

BACKGROUND: Prostaglandins can affect the vascular response and are locally produced in the peritoneal cavity. Prostaglandin inhibition in continuous ambulatory peritoneal dialysis (CAPD) patients during peritonitis using indomethacin intraperitoneally was found to decrease the intrinsic permeability to macromolecules. METHODS: In the present study the effects of prostaglandin inhibition were studied during stable, uninfected CAPD. Two standard peritoneal permeability analyses (1.36% glucose) were performed in 10 stable CAPD patients within 1 week with and without addition of 12.5 mg/l indomethacin. Furthermore, possible effects on the parameters of nitric oxide synthesis were determined. In five other patients a high dose of indomethacin was tested. The night before the indomethacin test, 12.5 mg/l indomethacin was added to the nightdwell and the test was performed with 25 mg/l indomethacin. RESULTS: In the normal dose indomethacin group, the dialysate concentrations of prostaglandin (PG) 6-keto-PGF1alpha and thromboxane (Tx) TxB2 were significantly lower with indomethacin (IND) compared with the control dwell (C): 6-keto-PGF1alpha median 93 (C) vs 7.5 (IND) ng/l, P=0.006 and TxB2 12.3 (C) vs 9.0 (IND) ng/l, P=0.04. The dialysate concentration of PGE2 was not different during the control dwell (68.5 ng/l) compared with the indomethacin experiment (50.3 ng/l, P=0.5). The mass transfer area coefficients (MTAC) of nitrate and cGMP, and parameters of nitric oxide synthesis, were similar during both experiments. The MTAC of creatinine and urate were not different with indomethacin: creatinine median 9.5 (C) vs 10.2 ml/min (IND), P=0.2 and urate 7.2 (C) vs 7.3 ml/min (IND), P=0.3. Only the MTAC of urea was marginally higher with indomethacin: 16.0 (C) vs 16.6 ml/min (IND), P=0.04. No differences were found in the clearances of the macromolecules beta2-microglobulin, albumin, IgG and alpha2-microglobulin. With the high indomethacin dose no inhibition of PGE2 was found: 69 (C) vs 63 ng/l(IND), not significant. Furthermore, no differences were found in the transport rates of small solutes or proteins. This indicates no effect of indomethacin on the peritoneal surface area and the size-selective permeability to macromolecules. In both groups no effect was found on the transcapillary ultrafiltration and the effective lymphatic absorption rate during the 4-h dwell. Consequently, the net ultrafiltration, the difference between these, did not change. CONCLUSIONS: The indomethacin induced inhibition of the synthesis of 6-keto-PGF1alpha and TxB2 did not lead to alterations in functional parameters of the peritoneal surface area, the intrinsic permeability to macromolecules and fluid kinetics. Therefore, these prostaglandins are not likely to be involved in the regulation of peritoneal transport during stable CAPD.

Intraperitoneal interleukin-8 and neutrophil influx in the initial phase of a CAPD peritonitis.

OBJECTIVE: To investigate whether or not a change in dialysate interleukin-8 (IL-8) concentration precedes the onset of clinically overt peritonitis and is significant in the recruitment of granulocytes during continuous ambulatory peritoneal dialysis (CAPD)-related peritonitis. DESIGN: CAPD patients stored their overnight effluent at 4 degrees C, which was routinely thrown away after 2 days. If peritonitis developed, patients delivered their effluent of the preceding two nights and the peritonitis effluent for analysis. A control study was performed 1 to 3 months after recovery. Dialysate samples were analyzed for number of cells, differential cell count, IL-8 and elastase concentrations, and their neutrophil chemoattractive capacity. In addition, serum samples during peritonitis were analyzed for IL-8 concentrations. RESULTS: Ten peritonitis episodes in 7 patients were analyzed. Numbers of neutrophils and levels of dialysate IL-8 and elastase started to increase 4 to 12 hours before the first peritonitis effluent. The dialysate/serum IL-8 ratio was 423.5 during peritonitis and 7.0 in the postperitonitis controls. There was a significant correlation between the number of neutrophils and IL-8 concentration in the dialysate. The in vitro neutrophil chemotaxis was increased toward the peritonitis effluents, as compared to control effluents. Incubation of the peritonitis effluents with anti-IL-8 monoclonal antibody blocked the increase in neutrophil chemotaxis above control levels by an average of 26.7%. CONCLUSION: IL-8 is produced in the peritoneal cavity during CAPD treatment and may mediate part of the neutrophil recruitment and degranulation in the initial phase of a CAPD peritonitis.

Cytokine patterns in the effluent of continuous ambulatory peritoneal dialysis: relationship to peritoneal permeability.

Cytokines are pluripotent pleiotropic agents that have received widespread attention over the last few years. Not surprisingly, the have also been studied in the context of continuous ambulatory peritoneal dialysis. Cytokines play a central role in this treatment modality for uremic patients, because these inflammatory mediators act upon the biological dialysis membrane, i.e. the peritoneum, while simultaneously they participate in host defense mechanisms. This review describes which cytokines are present in dialysate, whether there is support for intraperitoneal release, and under which circumstances. If focuses particularly on the relationship between cytokines in peritoneal effluent and peritoneal permeability to macromolecules. In addition, the presence of prostanoids in dialysate and their role in the local regulation of peritoneal permeability are discussed, because cyclooxygenase products are tightly linked to cytokine networks.

Impaired initial cell reaction in CAPD-related peritonitis.

Our objective was to determine the incidence of peritonitis episodes with an impaired initial cell reaction (IICR:neutrophil number < 100 x 10(6)/L) over a period of ten years, and to find possible explanations for this unusual presentation of peritonitis. A retrospective review of the files of continuous ambulatory peritoneal dialysis (CAPD) patients included in the CAPD program 1984 and 1993 was done. Analysis of cytokine and prostanoid patterns during four peritonitis episodes with an IICR was compared to 12 episodes with a normal initial cell reaction (NICR). Dialysate cell numbers and immunoeffector characteristics of peritoneal cells were compared in 7 IICR patients in a stable situation and a control group of 70 stable CAPD patients. The setting was a CAPD unit in the Academic Medical Center in Amsterdam. Thirty-five CAPD patients who had one or more peritonitis episodes with an IICR and a control group of 249 CAPD patients were included in the study. The incidence of peritonitis with an IICR was 6%. These episodes occurred more than once in 51% of the patients who presented with IICR. In 72% the cell reaction was only delayed: a cell number exceeding 100 x 10(6)/L was reached later. Staphylococcus aureus was significantly more frequently the causative microorganism compared to all peritonitis episodes (PE) that occurred during the study period. Patients with IICR had lower dialysate cell counts in a stable situation, compared to a control group (p < 0.01). This was caused by a lower number of macrophages and CD4 positive lymphocytes. The phagocytosis capacity of the macrophages appeared to be normal. In a comparison of four PE with an IICR and 12 episodes with an NICR, the tumor necrosis factor-alpha (TNF-alpha) response was similar and occurred on day 1, also pointing to normally functioning macrophages. However, the maximal appearance rates of interleukin-6 (IL-6) and IL-8 occurred later in the episodes with IICR compared to NICR (day 2 vs day 1, p < 0.05). No differences were found in vasodilating prostaglandins, mesothelial cell markers (cancer antigen 125, phospholipids, hyaluronan), and mesothelial cell numbers in the stable situation nor during peritonitis. Peritonitis can present as abdominal pain in the absence of a cloudy dialysate. In some of the patients this presentation occurred more than once. This impaired, most often delayed, cell reaction was associated with a delayed secondary cytokine response. As IL-6 and IL-8 can be synthesized by mesothelial cells, this suggests an impaired functioning mesothelium. This could not be confirmed, however, by a lower number of mesothelial cells in effluent or lower dialysate levels of mesothelial cell markers.

Effects of intraperitoneal cyclooxygenase inhibition on inflammatory mediators in dialysate and peritoneal membrane characteristics during peritonitis in continuous ambulatory peritoneal dialysis.

Peritonitis complicating continuous ambulatory peritoneal dialysis (CAPD) can be used as an in vivo model to study the contribution of mediators in dialysate to the regulation of peritoneal permeability. Previously we reported that changes in the peritoneal appearance rates of the cytokines interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF alpha) were related to alterations in the effective peritoneal surface area. Changes in the intrinsic peritoneal permeability were mainly related to those in the peritoneal appearance rate of the prostanoid prostaglandin E2 (PGE2) and partly also to that of IL-6. In this intervention study the role of these mediators was further analyzed. Eleven peritonitis episodes were followed on 8 consecutive days from the start of the infection and once after recovery. Indomethacin was given intraperitoneally during the first 3 days. beta 2-Microglobulin clearance was used as indicator of the effective peritoneal surface area. The intrinsic peritoneal permeability was characterized functionally by the restriction coefficient. The 15 peritonitis episodes studied previously served as the control group. This study supports the formerly obtained relationships in two ways. First, significant reductions were observed for peritoneal PGE2, 6-keto-PGF1 alpha, and TxB2 during cyclooxygenase inhibition to 6%, 0.6%, and 9% of the values on day 1, whereas simultaneously the intrinsic permeability was less increased. This indomethacin effect on intrinsic permeability was not entirely significant, probably because of the additional role of IL-6, which was not influenced by indomethacin. Also, the appearance rate of TNF alpha in the effluent was not affected by cyclooxygenase inhibition. Accordingly, the changes in the effective surface area were similar to those in the control group. Second, in 8 of the 11 cases, new rises both in peritoneal PGE2 and in intrinsic permeability occurred after discontinuation of indomethacin. Rebounds were not seen for TNF alpha or IL-6, and, consistently, not for the effective surface area. In conclusion, local cyclooxygenase inhibition results in a less-increased intrinsic permeability during peritonitis but has no effect on the effective surface area. These data support our previous finding that IL-6 and TNF alpha contribute to alterations in surface area, whereas PGE2 is more involved in intrinsic peritoneal permeability changes.

Dialysate markers of peritoneal tissue during peritonitis and in stable CAPD.

OBJECTIVE: To investigate whether dialysate concentrations of substances that are locally produced within the peritoneal cavity can be used to study the effects of inflammation on peritoneal tissue. DESIGN: We followed the appearance rates (AR) of concentrations of cancer antigen (CA) 125, phospholipids (PHL), hyaluronan (HA), and the procollagen peptides PICP (procollagen 1 C-terminal) and PIIINP (procollagen 3 N-terminal) in dialysate during peritonitis (8 consecutive days) and after recovery. Data were compared with the stable situation. SETTING: CAPD (continuous ambulatory peritoneal dialysis) unit in the Academic Medical Center in Amsterdam. PATIENTS: Twelve CAPD patients with a total of 16 episodes of peritonitis and 10 clinically stable CAPD patients were studied. RESULTS: All substances showed temporal increments in dialysate during peritonitis compared to control. No difference was found between the control day of peritonitis and the stable patients. Maximum AR were reached in the acute phase of peritonitis for CA125, PHL, and HA and on day 4 for both PICP and PIIINP. A second increment in CA125 occurred on days 4 to 6. These findings indicate acute damage to the mesothelium (CA125) and other cells (PHL) by the infection. HA may reflect stromal changes. Subsequently, peritoneal healing (PICP,PIIINP) and remesothelialization (second peak CA125) are likely to occur. CONCLUSIONS: Dialysate concentrations of these substances can be used as markers for the effects of peritonitis on the peritoneum of CAPD patients in vivo. The similarity between the marker concentrations in the effluent after recovery from peritonitis and those in stable CAPD patients implies that complete peritoneal healing is likely to occur after uncomplicated peritonitis.

Nitrate in stable CAPD patients and during peritonitis.

During continuous ambulatory peritoneal dialysis (CAPD) peritoneal vessels are dilated. Nitric oxide (NO) causes vasodilation in many organs. Nitrate, a stable metabolite of NO, was measured in plasma and dialysate. In 6 stable CAPD patients standard peritoneal analyses were performed. The mass transfer area coefficient (MTAC) of nitrate was 11.5 mL/min (10.0-17.0 mL/min) (median and range). The MTAC of creatinine was of the same order of magnitude: 10.7 mL/min (8.0-14.2 mL/min), although the molecular weight of nitrate is lower (62 vs 113 dalton). The correlation between the MTAC of nitrate and the MTAC of creatinine indicated diffusion from the circulation and not local production of NO (r = 0.71; p = 0.11). Peritoneal permeability is increased in the acute phase of peritonitis, partly caused by extensive vasodilation. The potential role of NO during peritonitis was investigated in 8 CAPD patients with 11 peritonitis episodes in the acute phase and after recovery. The median dialysate/plasma (D/P) ratio of nitrate in the acute phase was 1.47 (range 0.96-2.55), which was higher than after recovery: 1.07 (0.99-1.75), p < 0.05. No relation was found between the D/P ratio of nitrate and the D/P ratio of TNF alpha (tumor necrosis factor). In conclusion, dialysate nitrate levels in stable CAPD patients are likely to be determined by diffusion from the circulation. D/P ratios exceeding 1.0 during the acute phase of peritonitis are probably the result of local NO production. This may contribute to the marked vasodilation during peritonitis.

Analysis of inflammatory mediators and peritoneal permeability to macromolecules shortly before the onset of overt peritonitis in patients treated with CAPD.

OBJECTIVE: To investigate whether changes in peritoneal membrane characteristics and inflammatory mediators in dialysate precede the onset of overt infection during continuous ambulatory peritoneal dialysis (CAPD)-related peritonitis. DESIGN: CAPD patients with a high peritonitis incidence stored every night bag at 4 degrees C. Routinely, each bag was thrown away after two days. Only if patients developed peritonitis, all bags were delivered for study. Thus, two night bags immediately prior to the first peritonitis bag were available for analysis. A control study was done 14 days after recovery. Dialysate samples were measured for TNF alpha, IL-6, PGE2, 6-keto-PGF1 alpha, TxB2, and serum proteins. The clearance of beta 2-microglobulin was used as an indicator of the effective peritoneal surface area. The intrinsic peritoneal permeability was characterized by the restriction coefficient. RESULTS: Eight episodes occurred in 5 patients. The night dwells available prior to the first peritonitis effluent were drained maximally nine dwells and minimally one dwell before the first peritonitis bag. Dialysate leukocyte counts exceeded 100 x 10(6)/L only on the day of manifest infection. However, bacterial cultures were already positive at least one day before overt infection in four episodes and in three of these cases two days before. No changes were observed prior to peritonitis for the clearance of beta 2-microglobulin or the restriction coefficient. In contrast to these permeability characteristics, the cytokines, TNF alpha and, though less significant, also IL-6, were increased in dialysate one day prior to overt infection, when compared to the values obtained at the control investigation. This was especially evident in effluents drained no longer than two dwells before the first peritonitis bag. Prostaglandin concentrations in dialysate were not different before the onset of manifest peritonitis from the values measured after recovery. CONCLUSION: In this study, the increased effective peritoneal surface area and intrinsic peritoneal permeability during acute infection appeared to be preceded by elevations in the cytokines TNF alpha and, to a lesser extent, IL-6. These increments occurred only very shortly before the onset of clinical symptoms.

Appearance of tumor necrosis factor-alpha and soluble TNF-receptors I and II in peritoneal effluent of CAPD.

Dialysate and serum concentrations of tumor necrosis factor-alpha (TNF-alpha), soluble TNF-receptor I (sTNFRI) and soluble TNF-receptor II (sTNFRII) were measured during stable and infectious CAPD to determine whether these mediators are released intraperitoneally or derived from the circulation. Dialysate/serum ratios were compared to those of various marker proteins for peritoneal transport and to interleukin-6 (IL-6), which is locally produced. Peritoneal immunoreactive TNF-alpha could be detected in 19 of 20 stable CAPD patients after a night dwell, but only occasionally and in lower concentrations during and after a standard four-hour peritoneal permeability test. Both sTNFRs highly exceeded TNF-alpha dialysate concentrations. In case of peritonitis a median 16-fold increase in dialysate TNF-alpha occurred on the first day, which declined towards control values during a longitudinal follow-up of eight consecutive days. sTNFRI and sTNFRII in dialysate increased three- to fourfold. Their peaks, however, appeared on the second peritonitis day. Bioactive TNF-alpha was only detected when immunoreactive levels exceeded 1000 pg/ml. Serum values of all variables were not altered during infection; sTNFRs exceeded TNF-alpha 300- to 400-fold. During stable CAPD indirect evidence was obtained for transperitoneal transport from plasma to dialysate of TNF-alpha (molecular wt 17 kD), sTNFRI (55 kD) and sTNFRII (75 kD). Dialysate/serum (D/S) ratios were higher, the lower the molecular weight; they were related to D/S ratios of those marker proteins with the nearest molecular weight; D/S ratios were unrelated to the intraperitoneally produced IL-6. Furthermore, the observed D/S ratios were as expected theoretically for their molecular weights.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical significance and detection of individual differences and changes in transperitoneal transport.

A review is given on the pathophysiology of the transport of solutes and fluid during continuous ambulatory peritoneal dialysis. Special attention is paid to the assessment of peritoneal permeability in individual patients, its inter- and intraindividual variability, the effect of systemic disease, some regulatory mechanisms, and alterations observed during long-term continuous ambulatory peritoneal dialysis.

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.

Analysis of the peritoneal cellular immune system during CAPD shortly before a clinical peritonitis.

We analysed the peritoneal cellular immune system 24-48 h before the onset of a clinical peritonitis. Peritoneal cells were obtained from the overnight dialysis effluents 1 or 2 days (day-1 and day-2) preceding the day of peritonitis, the last overnight effluent before the peritonitis effluent (day P), and the first peritonitis effluent. Nine peritonitis episodes of six patients were studied. The number of Fc receptor positive cells, the chemotactic activity, and immunophenotype of the peritoneal cell population at day-2 and day-1 were similar to the postperitonitis control effluent. However, immunophagocytosis and phagocytosis capacity of the peritoneal macrophages was decreased in five of six episodes at day-2 and -1 compared to control peritoneal macrophages. The overnight effluents of day P revealed a moderate influx of neutrophilic granulocytes and an increase of bacterial killing capacity and chemotactic activity. Activation of the peritoneal T cells at day P was shown by the increase in MHC class II positive T cells and an increase in the CD4/CD8 ratio. Bacterial cell cultures of the effluents were positive in three episodes 24-48 h before peritonitis, and of all overnight effluents at day P. These results indicate that malfunctioning of phagocytosis by peritoneal macrophages may contribute to the development of a CAPD peritonitis.