Synthesis and surface expression of ICAM-1 in polymorphonuclear neutrophilic leukocytes in normal subjects and during inflammatory disease.

During bacterial peritonitis of patients on continuous ambulatory peritoneal dialysis (CAPD) leukocytes, particularly polymorphonuclear neutrophilic granulocytes (PMNs), migrate into the peritoneal cavity. However, at the site of inflammation PMNs are not sufficiently able to protect the host against micro-organisms. Adhesion molecules, such as ICAM-1 (CD54), are involved in the interaction between endothelial cells and PMNs leading to the accumulation of PMNs at the site of inflammation. As PMNs are the predominant cell type in the peritoneal cavity in peritonitis, the aim of this study was to find out whether PMNs from CAPD peritonitis patients were able to express ICAM-1. Flow cytometric analyses with the anti-CD54 monoclonal antibody demonstrated that normal PMNs constitutively express slight amounts of ICAM-1. In contrast to normal PMNs, peritoneal PMNs from patients with CAPD peritonitis expressed high amounts of ICAM-1 (p = 0.003). Furthermore, ICAM-1 expression on peripheral blood PMNs of these patients significantly differed from PMNs from healthy donor (p = 0.01). Furthermore, Northern blot analysis revealed a weak signal of ICAM-1 mRNA in normal PMNs. However, peritoneal PMNs from CAPD peritonitis patients expressed a strong signal for ICAM-1 mRNA, suggesting that ICAM-1 is newly synthesized when PMNs invade the peritoneal cavity. In summary, this study clearly demonstrates that peritoneal PMNs of CAPD peritonitis express high amounts of ICAM-1 receptor on the level of mRNA and on the surface. Therefore, it is tempting to speculate that peritoneal PMNs interact amongst each other between ICAM-1 and its counter receptors CD11a,b/CD18 receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

Unified inflectional processing of regular and irregular verbs: a PET study.

Psycholinguistic theories propose different models of inflectional processing of regular and irregular verbs: dual mechanism models assume separate modules with lexical frequency sensitivity for irregular verbs. In contradistinction, connectionist models propose a unified process in a single module. We conducted a PET study using a 2 x 2 design with verb regularity and frequency. We found significantly shorter voice onset times for regular verbs and high frequency verbs irrespective of regularity. The PET data showed activations in inferior frontal gyrus (BA 45), nucleus lentiformis, thalamus, and superior medial cerebellum for both regular and irregular verbs but no dissociation for verb regularity. Our results support common processing components for regular and irregular verb inflection.

MCP-1 levels are elevated in peritonitis fluid from CAPD patients due to secretion by peritoneal macrophages.

The migration of leukocytes, including polymorphonuclear neutrophils and monocytes, into the peritoneal cavity is a key event of intraperitoneal inflammation. We investigated the levels of two members of the chemokine family, interleukin 8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1), in the dialysate effluent of 18 continuous ambulatory peritoneal dialysis (CAPD) patients with peritonitis and compared them with chemokine levels in noninfected CAPD effluent. Being a major source of inflammatory cytokines, we also isolated peritoneal macrophages from peritonitis effluent to determine the mRNA expression directly after isolation. The mean (SEM) concentrations of IL-8 and MCP-1 were significantly higher in the effluent of peritonitis patients than in noninfected effluents MCP-1: 22.5 +/- (6.27) versus 0.37 +/- (0.1) ng/mL and IL-8: 2.39 +/- (1.15) versus 0.04 +/- (0.01) ng/mL. Northern blot analysis of isolated effluent macrophages revealed strong signals for MCP-1 and IL-8. Our findings showed that CAPD effluent from patients with peritonitis contains markedly elevated MCP-1 and IL-8 levels, suggesting that these chemokines participate in leukocyte recruitment during CAPD peritonitis. Isolation of mRNA of peritonitis-derived peritoneal macrophages revealed strong signals for MCP-1 and IL-8, suggesting that macrophages are a major source of these inflammatory mediators.

Cost-effective on-site screening for anaemia in pregnancy in primary care clinics.

OBJECTIVE: To determine the feasibility, accuracy and cost of developing a system of on-site screening for anaemia in pregnancy in primary care clinics. SETTING: Mobile clinic team in Hlabisa health district, KwaZulu-Natal. METHODS: Four hundred and forty-nine consecutive women attending antenatal clinics were screened for anaemia (haemoglobin < 10 g/dl) using copper sulphate solution; the results were compared with true haemoglobin levels as determined by an automated analyser. Three hundred women had haemoglobin concentration estimated with a portable haemoglobinometer and results compared with those from the automated analyser. RESULTS: Screening with copper sulphate solution was highly sensitive (95.7%) but had low positive predictive value for anaemia (37.2%). Haemoglobin concentration estimated by haemoglobinometer correlated highly with results from the analyser (r = 0.82; P < 0.0001), and the mean difference in concentrations between the two methods was 1.1 g/dl. The average cost of screening all women with copper sulphate solution (6 cents/sample) and determining the true concentration in those screened as possibly anaemia (R2.64/sample) was 72 cents per woman. The cost of using an automated analyser was R6.20 per sample. CONCLUSION: Combined use of copper sulphate solution and a haemoglobinometer is a feasible, accurate and cost-effective way of screening for and diagnosing anaemia in pregnant women, on-site, in primary care clinics.

Accuracy of on-site screening for syphilis among women attending a rural mobile antenatal clinic.

OBJECTIVE: To determine the accuracy and cost of on-site antenatal clinic syphilis screening, compared with laboratory-based screening. SETTING: Mobile primary care clinic providing antenatal care in remote rural areas in Hlabisa health district; the prevalence of syphilis is 8.5%. METHODS: 528 consecutive women screened for syphilis by a rapid plasma reagin (RPR) test on plasma derived from whole blood by gravity. A battery-powered, solar-charging rotator mixed antigen with plasma. The RPR test was repeated on serum in a reference laboratory for comparison. RESULTS: The on-site test was highly sensitive (86.7%; 95% confidence interval (CI) 72.5-94.5%) and highly specific (88.2%; 95% CI 84.9-90.9). The positive predictive value (40.6%; 95% CI 30.9-51.1) was low owing to a large number of samples reported as 'slightly positive' on site being reported as 'negative' in the laboratory. There were very few false-negative results on site (negative predictive value 98.6%; 95% CI 96.8-99.4). The cost of the rotator is R3 521 and reagent costs are 81c per woman screened. CONCLUSIONS: On-site RPR screening for syphilis is highly accurate, cheap and easy to do. This strategy may reduce perinatal mortality by increasing the proportion of pregnant women with syphilis who are adequately treated.

Epidemiology of syphilis in pregnancy in rural South Africa: opportunities for control.

The paper describes the epidemiology, risk factors and impact on pregnancy outcome of syphilis in pregnant women in rural South Africa. Prevalence was determined from laboratory records. A case-control study of 200 women (50 cases with syphilis) was done to investigate possible risk factors. To determine the impact on pregnancy outcome, and to evaluate the effect of treatment, a retrospective cohort was constructed. Overall prevalence of syphilis was 6.5%; it was highest in the urban antenatal clinic (9%). The odds ratios for syphilis in women gravidity 3-5 compared to gravidity 6 was 3.2 and 2.3 compared to women with gravidity 2 or less. For women with a previous birth, those with a previous perinatal death were 3.2 times more likely to have syphilis after adjusting for other risk factors. Pregnancy outcome was available for 187 women. The adjusted odds ratio of an adverse pregnancy outcome in women with syphilis was 11.8. All still births occurred in women with syphilis. The prevalence of syphilis is high in this rural area and screening should be applied to all women. Although screening was comprehensive, less than half of the detected cases were fully treated and a poor perinatal outcome ensued. On-site testing for syphilis at the time of booking would allow treatment to start immediately.

Effect of removing user fees on attendance for curative and preventive primary health care services in rural South Africa.

User fees are used to recover costs and discourage unnecessary attendance at primary care clinics in many developing countries. In South Africa, user fees for children aged under 6 years and pregnant women were removed in 1994, and in 1997 all user fees at all primary health care clinics were abolished. The intention of these policy changes was to improve access to health services for previously disadvantaged communities. We investigated the impact of these changes on clinic attendance patterns in Hlabisa health district. Average quarterly new registrations and total attendances for preventive services (antenatal care, immunization, growth monitoring) and curative services (treatment of ailments) at a mobile primary health care unit were studied from 1992 to 1998. Regression analysis was undertaken to assess whether trends were statistically significant. There was a sustained increase in new registrations (P = 0.0001) and total attendances (P = 0.0001) for curative services, and a fall in new registrations (P = 0.01) and total attendances for immunization and growth monitoring (P = 0.0002) over the study period. The upturn in demand for curative services started at the time of the first policy change. The decreases in antenatal registrations (P = 0.07) and attendances (P = 0.09) were not statistically significant. The number of new registrations for immunization and growth monitoring increased following the first policy change but declined thereafter. We found no evidence that the second policy change influenced underlying trends. The removal of user fees improved access to curative services but this may have happened at the expense of some preventive services. Governments should remain vigilant about the effects of new health policies in order to ensure that objectives are being met.

White matter asymmetry in the human brain: a diffusion tensor MRI study.

Language ability and handedness are likely to be associated with asymmetry of the cerebral cortex (grey matter) and connectivity (white matter). Grey matter asymmetry, most likely linked to language has been identified with voxel-based morphometry (VBM) using T(1)-weighted images. Differences in white matter obtained with this technique are less consistent, probably due to the relative insensitivity of the T(1) contrast to the ultrastructure of white matter. Furthermore, previous VBM studies failed to find differences related to handedness in either grey or white matter. We revisited these issues and investigated two independent groups of subjects with diffusion-tensor imaging (DTI) for asymmetries in white matter composition. Using voxel-based statistical analyses an asymmetry of the arcuate fascicle was observed, with higher fractional anisotropy in the left hemisphere. In addition, we show differences related to handedness in the white matter underneath the precentral gyrus contralateral to the dominant hand. Remarkably, these findings were very robust, even when investigating small groups of subjects. This highlights the sensitivity of DTI for white matter tissue differences, making it an ideal tool to study small patient populations.

Effects of peritonitis exudates on chemotaxis and phagocytosis of human neutrophils.

OBJECTIVE: To elucidate the in vitro effects of peritoneal exudate in patients with peritonitis on the functions of normal neutrophils (chemotaxis and phagocytosis) and to correlate these findings with constituents of the exudate, severity of disease, and clinical course. DESIGN: Open study. SETTING: University hospital, Germany. SUBJECTS: Fifty consecutive patients with secondary peritonitis and healthy volunteers. INTERVENTIONS: Samples of peritoneal exudate were taken during operation and tested for their ability to stimulate or inhibit chemotaxis and phagocytosis of polymorphonuclear neutrophils (PMN). MAIN OUTCOME MEASURES: Correlation between chemotaxis and phagocytosis and concentrations of constituents of peritoneal exudate. RESULTS: Mean (SD) exudate-induced chemotaxis was 102.5 (22.8) microns compared with 62.3 (4) in the buffer control and 116 (17) in the 1 ng/ml C5a buffer control. The mean (SD) phagocytic index (uptake of zymosan and Candida albicans) was 68.8 (28.1) % of the respective serum control. There were correlations between chemotaxis and concentrations of C3a, endotoxin, and white cell count in the exudates; between phagocytosis and concentrations of C3a, IgG, IgM, protein and granulocyte elastase activity (GE and GE-alpha 1 proteinase inhibitor complex) in the peritoneal exudate; concentrations of endotoxin, and tumour necrosis factor alpha (TNF alpha), and granulocyte elastase activity in the exudate; and concentrations of C3a, IgG, IgM, and fibrinopeptide A in the exudate. There were no differences in chemotaxis and phagocytosis between patients who survived and those who died, and only the APACHE II score, the Sepsis Severity Score and the Mannheim Peritonitis Index correlated with mortality. CONCLUSION: It is still not clear whether other constituents of the exudate, variable conditions of resorption, inflammatory conditions within the peritoneal lining, or the individual patient's capacity to limit the systemic response, may have a critical role.

Inverse MCP-1/IL-8 ratio in effluents of CAPD patients with peritonitis and in isolated cultured human peritoneal macrophages.

An important event in intraperitoneal inflammation is the influx of leukocytes into the peritoneal cavity. Chemokines such as interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) play a major role in the recruitment of immune cells to the site of inflammation. We determined the concentrations of two members of the chemokine family, IL-8 and MCP-1, in the dialysate effluents of 18 continuous ambulatory peritoneal dialysis (CAPD) patients with peritonitis and of 18 non-infected CAPD patients by specific enzyme-linked immunosorbent assays (ELISA). Isolated peritoneal macrophages (PMs) from CAPD peritonitis patients were cultured and IL-8 and MCP-1 production was determined on protein (ELISA) and mRNA level (Northern blot) at designated timepoints over a 72-h culture period. PMs from non-infected patients served as controls. Much higher concentrations of IL-8 and MCP-1 were found in dialysate effluents of peritonitis patients than in effluents of non-infected patients: IL-8 2.39 +/- 1.15 vs 0.05 +/- 0.01 ng/ml and MCP-1 22.5 +/- 6.27 vs 0.42 +/- 0.07 ng/ml. IL-8 and MCP-1 release by cultured PMs from peritonitis patients and non-infected patients revealed significant differences: IL-8 40.3 +/- 2.2 ng/ml after 3 h and 194.2 +/- 34.9 ng/ml after 12 h compared to 21.02 +/- 6.15 ng/ml after 3 h and 89.64 +/- 30.28 ng/ml after 12 h, respectively; MCP-1 3.3 +/- 0.9 ng/ml after 3 h and 25.7 +/- 7.4 ng/ml after 12 h compared to 1.1 +/- 0.2 ng/ml and 1.8 +/- 0.2 ng/ml, respectively. Interestingly, the ratio of IL-8 to MCP-1 concentrations in the dialysate effluents (1:9.4) is reversed in the supernatants of cultured PMs. In the effluents and in the culture supernatants of PMs from CAPD peritonitis patients high amounts of IL-8 and MCP-1 are detectable, suggesting that PMs are an important source for these chemokines during peritonitis. Because of the inverse ratio of IL-8 and MCP-1 in the effluents and culture supernatants it can be assumed that PMs are responsible for the MCP-1 concentration to a lesser extent than for the IL-8 concentration in the effluents.