Sharon Lewis

Neutrophil and monocyte alterations in chronic dialysis patients

Chronic renal failure patients maintained on dialysis have an increased risk for infection. This article summarizes research that has been done on the function of neutrophils (PMNs) and monocytes from chronic hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD) patients. The studies involving the HD patients showed that there is a decreased PMN in vitro chemotactic response, decreased C5a receptors on both PMNs and monocytes, and decreased oxidative metabolic responses of PMNs and monocytes to the chemotactic stimuli C5a and formyl-met-leu-phe (fMLP), but not to nonchemotactic factors. The results of studies involving phagocytosis have been conflicting and are discussed in this paper. Due to the basic principles of peritoneal dialysis, this treatment approach depletes the peritoneum of phagocytic cells, adversely affects the function of peritoneal WBCs, dilutes the existing opsonins, and alters the physiologic environment of the peritoneal cavity. Studies of peripheral PMN and monocyte function in CAPD patients have shown that, similar to HD patients, they also have decreased C5a receptors and decreased oxidative metabolic responses to the chemotactic factors C5a and fMLP. Although the factors contributing to the risk of infection in chronic dialysis patients are multifaceted, there are definitely alterations in PMN and monocyte function.

Are there sex differences in emotional and biological responses in spousal caregivers of patients with Alzheimer's disease?

The purpose of this study was to compare emotional and biological responses of men and women who are spousal caregivers of patients with Alzheimer’s disease (AD). Quality-of-life measurements, bioinstrumentation data, and immunophenotype assessments were obtained from female and male spousal caregivers of patients with AD. Spousal caregivers (women, n = 45 with average age 69.7; men, n = 16 with average age 71.4 years) completed questionnaires that assessed psychosocial variables. Blood was drawn and lymphocyte subsets (including natural killer [NK] cell number) were determined using flow cytometry. The degree of relaxation was determined measuring muscle tension (EMG) in the frontalis and trapezius muscles, skin conductance, skin temperature, and heart rate. Male spousal caregivers, as compared to female spousal caregivers, had significantly lower levels of stress, depression, caregiver burden (subjective), anxiety, anger-hostility, and somatic symptoms and higher levels of mental health, sense of coherence, NK cell number, and social and physical functioning. There were no statistically significant differences between the 2 groups in social support, coping resources, or T, T suppressor, or activated T cells. Women had more T helper cells and fewer NK cells than men. Men had fewer manifestations of a physiological stress response, as indicated by bioinstrumentation parameters. Unique sex-specific issues need to be considered when strategies are implemented to assist the increasing number of caregivers as our society ages.

Demonstration of specific receptors for fluoresceinated casein on human neutrophils and monocytes using flow cytometry

Abstract-Casein is chemotactic for human neutrophils (PMNs) and monocytes. The binding of fluorescein (FITC) -conjugated casein (mixture ofα,β,and κ- casein) and purifiedα-casein to PMNs, monocytes, and lymphocytes was analyzed using flow cytometry. These studies demonstrate that 75–95% of PMNs and 46–85% of monocytes have membrane receptors for casein while lymphocytes lack these receptors. The binding of FITC-casein and FITC-α-casein was specific and was blocked only by unlabeled casein andα-casein, but not by ovalbumin, bovine or human serum albumin,β-casomorphin, C5a, or formyl-methionyl-leucylphenylalanine (fMLP). The binding of FITC-casein was reversible when PMNs were stained with this fluorescent agent and subsequently incubated with unlabeled casein. Double-labeling studies of mononuclear cells using FITC-casein and the OKM1 monoclonal antibody in conjunction with a rhodamine conjugated anti-Ig second antibody demonstrate that mononuclear cells binding FITC-casein also stain with the OKM1 monoclonal antibody, indicating a specificity for monocytes.

A Stress-Busting Program for family caregivers

&NA; Aging baby boomers, longer life spans, and rising levels of Alzheimers disease and related dementias (ADRD) will result in a caregiver crisis in the near future. The ways in which caregivers deal with stresses related to caregiving will be critical to both their own well‐being and their ability to care for others. The purpose of this article is to describe the Stress‐Busting Program (SBP) for family caregivers and its effectiveness. The essential components of the SBP are education, stress management, problem solving, and support delivered in a group setting for 9 weeks. Results of the SBP indicate that throughout the program, caregivers experienced significant improvements in general health, vitality, social function, and mental health scores and decreases in anxiety, anger/hostility, depression, perceived stress, and caregiver burden. The SBP is a cost‐effective health‐promotion strategy for caregivers who have substantial ongoing stress.

Recurrent Peritonitis: Evidence for Possible Viral Etiology

A 45-year-old woman who was treated with continuous ambulatory peritoneal dialysis (CAPD) developed recurrent peritonitis characterized by cloudy effluents, elevated white blood cell (WBC) counts (predominantly lymphocytes), and negative culture results. This case report suggests that she may have had viral peritonitis as indicated by a positive viral culture, the presence of viral antibodies in serum and peritoneal dialysis effluent (PDE), hematological findings, and cell surface receptor studies. The possibility of a viral cause should be considered in patients with culture-negative peritonitis, especially if they do not respond to antibiotics.

Comparison of Peritoneal White Blood Cell Parameters From Continuous Ambulatory Peritoneal Dialysis Patients With a High or Low Incidence of Peritonitis

The purpose of this study was to determine if there were differences in selected dialysate white blood cells (WBC) parameters between continuous ambulatory peritoneal dialysis (CAPD) patient groups identified as having a high or low incidence of peritonitis. Parameters studied were total peritoneal WBC yield, percentage and absolute number of various WBC types, and expression of WBC receptors known to be involved in normal host defense mechanisms. WBCs were obtained from peritoneal dialysis effluents (overnight dwell), which were collected at monthly intervals for 6 to 8 months from eight CAPD patients--four with a history of high peritonitis incidence (HPI) (more than two episodes in 12 months) and four with a history of low peritonitis incidence (LPI) (no episodes in more than 24 months). Our results demonstrated that there was no significant difference in the overall mean total cell yields or absolute cell counts between the two patient groups. WBC differentials, although differing somewhat among patients, stayed quite stable over time for an individual patient and there was no significant difference between the two patient groups. Analysis of receptors on the peritoneal WBC was performed using flow cytometry and fluorescein-conjugated chemotactic factors (C5a and fMet-Leu-Phe-Lys), as well as monoclonal antibodies specific for Fc receptors and complement receptors, CR1 (CD35) and CR3 (CD11b). Although there was a trend toward increased expression of all these receptors in the HPI patients, there was no significant difference in the fluorescence intensity of peritoneal neutrophils or macrophages that expressed these receptors between the two patient groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma proteins and lymphocyte phenotypes in long-term plasma donors

BACKGROUND: The possible effects of long‐term plasma donation remain unknown, but it is important to investigate them so that donor safety is ensured. The purpose of this study was to determine if long‐term plasma donation alters plasma proteins or lymphocyte phenotypes.

Investigation of the effect of long‐term whole blood donation on immunologic parameters

Few studies addressing possible immune sequelae of long‐term whole blood donation have been published. The purpose of this study was to determine if there were any differences in lymphocyte subsets, monocyte and neutrophil receptors, and antigens important to host defense in committed whole blood donors and in nondonor controls. Blood samples were obtained from 27 whole blood donors who had been donating on a regular basis for at least 4 years and from 21 nondonor controls. A panel of single‐ and dual‐labeled monoclonal antibodies was used to characterize peripheral white cells, and then the cells were analyzed by flow cytometry. Lymphocyte subsets included T (CD3) cells, helper T (CD4) cells, suppressor T (CD8) cells, B (CD19) cells, natural killer (NK) (CD56) cells, and subpopulations of T cells defined by the coexpression of markers for CD3/HLA‐DR, CD3/CD56, and CD8/CD11b. Monocyte and neutrophil analysis included quantitation of receptors for C5a, formyl‐met‐leu‐phe, and C3bi (CR3). Monocytes were also analyzed for expression of HLA‐DR and CD14 antigens. No significant differences were observed in the whole blood donors and nondonor controls for any of these factors used to assess immunologic status, except for an increase in C3bi receptors on both neutrophils and monocytes from whole blood donors. These findings indicate that the lymphocyte parameters analyzed in this study are unaltered by long‐term whole blood donation. Further research is necessary to determine the significance of complement receptor upregulation in whole blood donors and to identify any changes in the functional characteristics of peripheral white cells from whole blood donors.

Periodic elevation of complement activation products in peritoneal dialysis effluent

Peripheral white blood cells (WBCs) of chronic ambulatory peritoneal dialysis (CAPD) patients show a reduced expression of chemotactic receptors and a desensitization to chemotactic factor induced events. Chronic complement activation has been suggested as a cause of such phenomena, resulting from either uremia, the indwelling peritoneal catheter, and/or dialysis fluid stimulation. The presence of complement activation products in peritoneal dialysis effluent was assessed by longitudinal measurement of C3bi in eight patients over a 6 to 8 month period, while peritoneal polymorphonuclear leukocyte (PMN) and monocyte CR3 and C5a receptor expression was quantitated by flow cytometry. In six of eight patients, C3bi levels were stable over time and usually measured less than 5 micrograms/ml. Two other patients showed periodic elevation of C3bi, which was not associated temporally with peritonitis. Further study is required to identify the origin of such activated complement components within the peritoneal cavity. However, no correlation was found between dialysate C3bi levels and peritoneal PMN or monocyte expression of CR3 or C5a receptors. Furthermore, the incidence of peritonitis for the two individuals with elevated C3bi was discordant (1 episode/8 patient months vs. 0 episodes/32 patient months), suggesting little or no relationship between these parameters.

C5a receptors on neutrophils and monocytes from chronic dialysis patients.

C5a is generated by the activation of the complement system with the cleavage of complement component C5 into C5a and C5b. C5a, an important in vivo chemotactic factor and anaphylatoxin, was first identified as having an important role in dialysis patients by Craddock et al (1,2,3) in the 1970’s. Previously various investigators had observed that leukopenia occurred during the first 30 minutes of hemodialysis (HD) with cellulose dialysis membranes (4,5,6,7). Craddock et al demonstrated that this leukopenia resulted from pulmonary sequestration of neutrophils (PMN) which was provoked by a complement component generated from contact of the patient’s blood with the cellophane dialyzer (1,2,3). C5a became the likely suspect because it was known to induce neutrophil aggregation in vivo and it was logically reasoned that PMN and monocytes would accumulate in the lungs, the first large capillary network encountered in circulation, following passage of blood through the dialyzer.