Frailty-Related Factors among Women Living with and without HIV Aged 40 Years and Older. The Women's Interagency HIV Study.

BACKGROUND: Frailty is a clinical, geriatric syndrome linked to disability and mortality; and may be associated with a variety of factors among underrepresented and underserved women living with HIV (WLWH) and without HIV (WLWOH) transitioning through the adult life course. OBJECTIVES: Determine whether a published set of factors associated cross-sectionally with frailty in WLWH and similar WLWOH at average age 39 years in 2005/2006 were associated with frailty in 2018/2019 among women who initiated frailty assessments at age ≥40 years, or whether a new set of factors were associated with frailty. DESIGN: Cross-sectional analyses within a longitudinal cohort study. SETTING: The multi-center Women's Interagency HIV Study (WIHS). PARTICIPANTS: 1285 participants (951 WLWH, 334 WLWOH), median age 53 years (interquartile range 47-58 years). MEASUREMENTS: The Fried Frailty Phenotype (FFP) in association with 23 factors representing HIV serostatus, other infections, sociodemographic factors, health behaviors, and chronic diseases. RESULTS: Frailty prevalence was 11.1% in 2018/2019 (12.6% among WLWOH, 9.6% among WLWH, p=0.121). The published 2005/2006 final multivariable stepwise regression model contained 9 predictors of frailty. When refit to women in 2018/2019, only age ≥50 years and annual income ≤$12,000 were independently positively associated with frailty; other significant 2005/2006 factors, HIV serostatus, CD4+ count <500 cells/mL among WLWH, smoking, drinking, FIB-4 and eGFR, were not. A newly-derived stepwise model considering all 23 predictors measured in 2018/2019, showed independent positive associations between frailty and age ≥50 years, annual income ≤$12,000, obesity (body mass index (BMI) ≥30kg/m2), and history of tuberculosis and cancer. CONCLUSION: Different chronic and infectious disease factors were associated with frailty among WLWH and WLWOH over the adult life course. Understanding factors associated with frailty by adult life stage, allows identification and implementation of novel, temporal interventions to alleviate frailty-associated outcomes and enhance quality of life among WLWH and WLWOH.

Longitudinal evaluation of markers of inflammation in HIV-positive and HIV-negative Rwandan women.

OBJECTIVES: African women are disproportionately affected by HIV infection and may experience non-AIDS-related complications associated with inflammation. High-sensitivity C-reactive protein (hsCRP), d-dimer and transthyretin have been examined as inflammatory markers elsewhere, but it is unclear how they change over time in HIV-negative or HIV-positive African women with or without antiretroviral therapy (ART) initiation. METHODS: We examined hsCRP, d-dimer and transthyretin levels at baseline and at follow-up of ≥2 years in 185 HIV-negative and 510 HIV-positive Rwandan women who were ART naïve at study entry. Generalized estimating equations for each marker were used to investigate the association with HIV infection/CD4 count, ART and follow-up time. RESULTS: Compared with HIV-negative women, HIV-positive women had higher hsCRP and d-dimer and lower transthyretin concentrations, with greater differences at lower CD4 counts. After adjusting for CD4 count and other factors, ART was not significantly associated with log hsCRP (P = 0.36) at follow-up, but was independently associated with lower log d-dimer (P = 0.03) and higher transthyretin (P = 0.0008) concentrations. At ≥ 2 years of follow-up, hsCRP had not significantly changed in any group but log d-dimer had decreased significantly in all groups. Transthyretin declined significantly over time in HIV-negative women and HIV-positive non-ART initiators, but increased significantly in HIV-positive ART initiators. CONCLUSIONS: HIV infection and advanced immune suppression were associated with higher hsCRP and d-dimer and lower transthyretin concentrations. ART (independently of CD4 changes) was significantly associated with decreases in d-dimer and increases in transthyretin, but, in contrast to other studies, was not associated with decreases in hsCRP. We found no change in hsCRP over time in any group.

Simple Power and Sample Size Estimation for Non-Randomized Longitudinal Difference in Differences Studies.

Intervention effects on continuous longitudinal normal outcomes are often estimated in two-arm pre-post interventional studies with b≥1 pre- and k≥1 post-intervention measures using "Difference-in-Differences" (DD) analysis. Although randomization is preferred, non-randomized designs are often necessary due to practical constraints. Power/sample size estimation methods for non-randomized DD designs that incorporate the correlation structure of repeated measures are needed. We derive Generalized Least Squares (GLS) variance estimate of the intervention effect. For the commonly assumed compound symmetry (CS) correlation structure (where the correlation between all repeated measures is a constantρ) this leads to simple power and sample size estimation formulas that can be implemented using pencil and paper. Given a constrained number of total timepoints (T), having as close to possible equal number of pre-and post-intervention timepoints (b=k) achieves greatest power. When planning a study with 7 or less timepoints, given large ρ(ρ≥0.6) in multiple baseline measures (b≥2) or ρ≥0.8 in a single baseline setting, the improvement in power from a randomized versus non-randomized DD design may be minor. Extensions to cluster study designs and incorporation of time invariant covariates are given. Applications to study planning are illustrated using three real examples with T=4 timepoints and ρ ranging from 0.55 to 0.75.

Bone quality assessed using quantitative ultrasound at the distal radius does not differ in antiretroviral therapy-naïve HIV-positive and HIV-negative Rwandan women.

OBJECTIVES: The incidence of fractures appears to be increased in HIV-infected individuals. METHODS: We assessed bone quality using quantitative ultrasound (QUS) in HIV-infected and uninfected Rwandan women. A Sunlight Omnisense 7000 QUS was used to measure the speed of ultrasound (SOS) at the distal radius in 646 antiretroviral therapy (ART)-naïve HIV-infected women and 211 HIV-uninfected women. The Z-scores for SOS were based on data for women of the same age from the manufacturer's reference material. RESULTS: The mean CD4 cell count was 285 (± 166) cells/µL in the HIV-positive women. SOS Z-scores adjusted and unadjusted for body mass index did not differ between the groups. SOS did not differ by CD4 count (< 200 vs. ≥ 200 cells/µL: 4016 (± 117) vs. 4028 (± 107) m/s, respectively; p=0.19. CONCLUSIONS: In HIV-positive ART-naïve Rwandan women with advanced HIV disease, bone quality at the distal radius was similar to that in HIV-negative controls.

Risk Factors for the Development of BK Virus Nephropathy in Renal Transplant Recipients.

The BK polyoma virus has, in recent years, become a significant cause of renal allograft dysfunction and failure. Among 260 adult kidney transplant recipients, those with biopsy-proven BK virus nephropathy (BKVN) were compared with those without BKVN with regard to gender, age, race, rejection episodes, time on dialysis, number of organs transplanted, HLA match, live donor versus deceased donor, cold ischemia time, delayed graft function, cytomegalovirus (CMV) serostatus of donor and recipient, induction therapy, and maintenance immunosuppression. Episodes of rejection (35.7% of patients with BKVN vs 8.5% of patients without BKVN; P = .01), transplantation of >1 organ (35.7% of patients with BKVN vs 9.0% of patients without BKVN; P = .01), positive CMV serology in both donor and recipient (71.4% of patients with BKVN vs 41.1% of patients without BKVN; P = .03), and a greater cumulative dose of daclizumab use at the time of induction (2.24 ± 0.05 mg/kg in patients with BKVN vs 2.03 ± 0.14 mg/kg in patients without BKVN; P = .04) were statistically significant risk factors for the development of BKVN. Those who developed BKVN received a higher mean cumulative dose of rabbit antithymoglobulin for induction therapy, but that difference failed to achieve statistical significance (P = .07).

Depression in the first year of stay for elderly long-term nursing home residents in the USA.

BACKGROUND: Understanding the prevalence, incidence and cofactors of depression among long-term elderly nursing home (LTNH) residents domiciled for eight months or more may help optimize depression treatment in this vulnerable group. We quantified first year depression in American LTNH residents and the associations between depression and resident/facility characteristics. METHODS: Data were obtained from the Minimum Data Set and Online Survey Certification and Reporting for 634,060 LTNH residents admitted from 1999 to 2005 in 4,216 facilities. Depression first diagnosed at admission and at subsequent quarterly intervals through the first year of stay was examined. Logistic regressions modeled correlates of newly identified depression in each time-period. RESULTS: Recorded depression at admission and during the first year increased from 1999 to 2005. By 2005, 54.4% of LTNH residents had depression diagnosed over the first year; 32.8% at admission and a further 21.6% later during the first year. Antidepressant use was reported prior to depression diagnosis for 48% of those first identified depressed after admission. Men, non-Hispanic blacks, never married, and severely-cognitively impaired LTNH residents were less often identified with depression, particularly at admission. Pain and physical comorbidity were positively associated with depression identified throughout the first year. Prior institutionalization was associated with depression at admission, but not new depression after admission. Facility characteristics had weaker associations with depression. CONCLUSIONS: High depression rates at admission and during the first year indicate a need to monitor and treat large numbers of American LTNH residents for depression. Reduced associations between demographics and depression as stays progress suggest other factors have increased roles in depression etiology.

Use-effectiveness of the female versus male condom in preventing sexually transmitted disease in women.

BACKGROUND: Data are limited on the female condom's effectiveness against STDs. GOAL: The goal was to compare STD rates between women given small-group education on, and free supplies of, either female or male condoms. STUDY DESIGN: Female patients at an STD clinic (n = 1442) were randomly assigned to condom type and followed via medical records for STDs (gonorrhea, chlamydia, early syphilis, or trichomoniasis). RESULTS: In an intention-to-treat analysis, the odds ratio for a comparison of STD occurrence between the female and male condom groups was 0.75 (95% confidence interval [CI], 0.56-1.01), and it did not change with adjustment. In a second analysis among women returning for subsequent screening, incidence rates for the first new postintervention STD per 100 woman-months of observation were 6.8 in the female condom group and 8.5 in the male condom group (rate ratio = 0.79 [CI, 0.59-1.06]). CONCLUSION: Compared with those provided with male condoms alone, women counseled on, and provided with, female condoms fared no worse and experienced a nonsignificant reduction in STDs.

Sociodemographic correlates of indoor allergen sensitivity among United States children.

BACKGROUND: Exposure to indoor allergens is associated with asthma morbidity. Nationally, asthma morbidity disproportionately affects socially disadvantaged populations, but it is unclear whether exposure to indoor allergens follows a similar pattern. OBJECTIVE: We sought to examine the national prevalences and demographic correlates of sensitivity to indoor allergens related to asthma. METHODS: Analysis of a cross-sectional survey of a representative sample of 4164 United States children aged 6 to 16 years who participated in allergen testing in the Third National Health and Nutrition Examination Survey from 1988 to 1994 was performed. The main outcome measures were sensitivity reactions to cockroach, dust mite, cat, and Alternaria alternata, as measured via skin prick testing. RESULTS: Multivariate models, including sex, age, race-ethnicity, education, poverty, family history, region of country, housing age, crowding, and urban residence, revealed significant racial-ethnic disparities in sensitivity. Compared with white children, African American children had higher odds ratios (ORs) of cockroach or dust mite sensitivity (cockroach OR, 2.5 [95% CI, 1.9-3.2]; dust mite OR, 1.3 [95% CI, 1.0-1.7]), as did Mexican American children (cockroach OR, 1.9 [95% CI, 1.3-2.8]; dust mite OR, 1.6 [95% CI, 1.2-2.2]). African American children also had significantly higher odds of sensitivity to A alternata (OR, 2.1 [95% CI, 1.5-2.8]). CONCLUSIONS: African American and Mexican American children are substantially more likely than white children to be sensitized to allergens important in asthma. Differences in indoor allergen sensitivity are consistent with racial differences in asthma morbidity. Along with other data, these findings suggest that racial disparities in housing, community, or both environmental factors play a role in determining national patterns of asthma morbidity.

Allocation of subjects to test null relative risks smaller than one.

Allocating a proportion k'=1/(1+ radicalr(0)) of subjects to an intervention is a practical approach to approximately maximize power for testing whether an intervention reduces relative risk of disease below a null ratio r(0)<1. Furthermore, allocating k'(s), a convenient fraction close to k', to intervention performs nearly as well; for example, allocating k'(s)=3/5 for 0.5> or =r(0)>0.33,2/3 for 0.33> or =r(0)>0.17 and 3/4 for 0.17> or =r(0)> or =0.10. Both k' and k'(s) are easily calculated and invariant to alterations in disease rate estimates under null and alternative hypotheses, when r(0) remains constant. In examples that we studied, allocating k' (or k'(s)) subjects to intervention achieved close to the minimum possible sample size, given test size and power (equivalently, maximum power, given test size and sample size), for likelihood score tests. Compared to equal allocation, k' and k'(s) reduced sample sizes by amounts ranging from approximately 5.5 per cent for r(0)=0.50 to approximately 24 per cent for r(0)=0.10. These sample size savings may be particularly important for large studies of prophylactic interventions such as vaccines. While k' was derived from variance minimization for an arcsine transformation, we do not recommend the arcsine test, since its true size exceeded the nominal value. In contrast, the true size for the uncorrected score test was less than the nominal size. A skewness correction made the size of the score test very close to the nominal level and slightly increased power. We recommend using the score test, or the skewness-corrected score test, for planing studies designed to show a ratio of proportions is less than a prespecified null ratio r(0)<1.

Longitudinal predictors of depressive symptoms among low income injection drug users.

Effects of changes in physical health status and drug use, and prior social support on depressive symptoms were assessed in low income injection drug users. Data are from participants (n = 503) enrolled at baseline (1994-1995) who remained at one-year follow-up (79%), of whom 37% were HIV-positive and 36% female. Physical health was measured by HIV symptoms, AIDS, CD4 count and functional limitation (IADLs). One-third scored high on depressive symptoms (CES-D > or = 16) at one-year follow-up, representing no statistically significant change from baseline (38%). In multiple logistic regression, after controlling for baseline depression scores (OR = 6.11, p < 0.001) and drug use (OR = 1.20, p = 0.192), baseline functional limitation (OR = 3.28, p < 0.001) and declining functioning (OR = 3.60, p < 0.001) were positively, and quitting drug use was negatively, associated with depressive symptoms at follow-up. Low social support at baseline (OR = 0.58, p < 0.10) was marginally predictive of depressive symptoms. Depressive symptoms did not differ by gender. For HIV-positive respondents, functional limitation was predictive of depressive symptoms, but HIV illness and drug use were not. Facilitating drug treatment and preventive medical care may aid in reducing depression in this population. For HIV-positive drug users, drug treatment prior to AIDS may help reduce depressive symptoms, with potential implications for HIV service utilization and medical adherence.

The relation of type 2 diabetes and cancer.

Increasing evidence indicates that individuals with type 2 diabetes (diabetes) are at elevated risk for several common human malignancies, including cancers of the colon, breast, endometrium, pancreas, and liver. In particular, the consistent positive results reported by prospective investigations make it unlikely that methodologic issues, occult tumors, or chance results could explain the findings. Since diabetes and impaired fasting glucose together affect >25% of Americans above age 50, even a moderate etiologic association (e.g., relative risk = 1.5) would explain >10% of involved malignancies. Laboratory studies have suggested biologically plausible mechanisms. Insulin, for example, is typically at high levels during the development and early stages of diabetes. Activation of the insulin receptor by its ligand, or cross-activation of the insulin-like growth factor-I receptor, has been shown to be mitogenic and promote tumorigenesis in various model systems. A "unifying concept," in fact, holds that hyperinsulinemia may underlie the cancer associations of several additional risk factors, including high waist circumference, visceral fat, waist-to-hip ratio, body mass index, sedentary lifestyle, and energy intake. In this review, we assess current evidence regarding the relation of type 2 diabetes with cancer, and evaluate the findings in terms of well-accepted criteria for establishing causality.

Access to medical care and service utilization among injection drug users with HIV/AIDS.

Access to care and optimal service utilization among 287 low income African American former and current drug injectors was examined. Results indicated suboptimal outpatient care, and no evidence of alternative use of hospital services. Participation in drug treatment and case management were associated with greater access to care and use of outpatient services, even after controlling for current drug use, gender, and insurance. AIDS and physical functioning limitation were associated with emergency room (ER) use and hospitalization. Participation in drug treatment and case management and an AIDS diagnosis were associated with optimal outpatient service use. Daily alcohol use was associated with ER as the usual facility for care. Integration of substance abuse treatment, case management, and medical services delivery may contribute to improved HIV care for this population.

Illicit drug use in one's social network and in one's neighborhood predicts individual heroin and cocaine use.

PURPOSE: The nature of competing social environmental factors' influence on substance abuse is unclear. A longitudinal study was undertaken to determine the relative power of social network and neighborhood characteristics to predict continuing illicit drug use. METHODS: Three hundred forty-two inner-city adults with a history of injection drug use were followed for 1 year; their heroin and cocaine use were assessed semiannually. Multiple logistic regression models were fit to determine the degree to which social network and neighborhood characteristics, assessed at baseline, predicted continuing heroin and/or cocaine use throughout the study period. RESULTS: Two hundred thirty-six (69%) participants reported continuing heroin and/or cocaine use. Drug use by members of the social network was a stronger predictor of participants' continuing drug use (OR = 4.31, 95% CI 2.51 to 7.40) than was a high level of drug-related arrests in the participant's neighborhood (OR = 2.41, 95% CI 1.24 to 4.71), after adjusting for drug treatment and demographic variables. Both seemed to have independent effects on study participants' drug use. CONCLUSIONS: These findings reiterate the importance of breaking ties with drug-using associates, even for those who reside in high-risk environments. Further work is needed to develop interventions that increase drug users' success in altering social network composition or also treat drug-using network members.

Osteonecrosis in patients infected with human immunodeficiency virus: a case-control study.

To evaluate risk factors for osteonecrosis in human immunodeficiency virus (HIV)-infected patients, demographic and clinical characteristics of case patients (n=17) and control patients (n=34) matched on initial clinic visit date, length of follow-up, and baseline CD4 cell count were compared. Case patients were more likely to have received corticosteroids (47.1% vs. 8.8%; matched odds ratio [OR], 13.1; 95% confidence interval [CI], 1.6-106), to have had an increase in CD4 cell count from nadir >0.050 x 10(9) cells/L (64.7% vs. 35.3%; OR, 4.9; 95% CI, 1.0-24), and to have had Pneumocystis carinii pneumonia (52.9% vs. 11.8%; OR, 7.6; 95% CI, 1.6-36). Use of protease inhibitors and history of other opportunistic infections did not significantly differ. In multivariate analysis, use of corticosteroids remained significantly associated with osteonecrosis, independently of HIV disease stage and protease inhibitor therapy. Corticosteroid use is an important risk factor for osteonecrosis, but its pathogenesis is likely multifactorial.

Children of injection drug users: impact of parental HIV status, AIDS, and depression.

We investigated the association between parental factors (including infection with human immunodeficiency virus [HIV], acquired immunodeficiency syndrome [AIDS] diagnosis, parental medical illness, and depression) and children's behavioral and emotional problems among children of injection drug users (IDUs). IDUs were recruited through community outreach. The sample included 73 parents of 73 children, aged 4 to 12 years. Parental depression (odds ratio [OR] = 4.61) and medical illness (OR = 4.70) were found to be significantly associated with internalizing (depressive and anxiety-related symptoms), but not with externalizing (aggressive and disruptive behaviors) symptoms in the children of IDUs. The clinical implications are that children of IDUs are known to be at high risk for psychiatric symptoms and disorders; these data suggest that children of depressed and/or medically ill IDU parents may be at even higher risk of internalizing symptoms (depression and anxiety symptoms) than children of IDUs who do not suffer from these conditions.

HIV-1 incidence among male workers at a sugar estate in rural Malawi.

OBJECTIVES: To determine incidence of HIV and associated risk factors in two cohorts of men working at a sugar estate in rural Malawi. DESIGN: Prospective studies. METHODS: After counseling and obtaining informed consent, male workers were tested for HIV-1 and syphilis. Baseline HIV-seronegative men were enrolled in two follow-up studies in 1994 and 1998, and were retested for HIV and syphilis at 6-month follow-up visits. Demographic, behavioral, and medical history was collected at baseline. Cumulative HIV incidence based on Kaplan-Meier methods was estimated. HIV incidence was also estimated per 100 person-years (p-y). Crude and adjusted rate ratios for the association of risk factors with incident HIV infection were obtained using Cox proportional hazards models. RESULTS: HIV prevalence was 24.3% among 1692 men screened in 1994 and 21.0% among 1349 men screened in 1998 (p <.03). HIV incidence was extremely high during 1994 to 1995 (17.1% for that 1-year period). Incidence dramatically declined in 1996, averaging about 3.5% per year from 1996 through 1999. Among men enrolled in the 1998 cohort, HIV incidence during 1998 to 1999 was 3.8%. After controlling for potential confounders reactive syphilis was associated with a twofold risk of HIV acquisition in each cohort. CONCLUSIONS: Urgent preventive measures are needed to control the spread of HIV in this economically important occupational cohort. In addition to conventional educational messages to reduce risky sexual behavior, treatment of other sexually transmitted diseases should be considered.

Initial plasma HIV-1 RNA levels and progression to AIDS in women and men.

BACKGROUND: It is unclear whether there are differences between men and women with human immunodeficiency virus type 1 (HIV-1) infection in the plasma level of viral RNA (the viral load). In men, the initial viral load after seroconversion predicts the likelihood of progression to the acquired immunodeficiency syndrome (AIDS), but the relation between the two has not been assessed in women. Currently, the guidelines for initiating antiretroviral therapy are applied uniformly to women and men. METHODS: From 1988 through 1998, the viral load and the CD4+ lymphocyte count were measured approximately every six months in 156 male and 46 female injection-drug users who were followed prospectively after HIV-1 seroconversion. RESULTS: The median initial viral load was 50,766 copies of HIV-1 RNA per milliliter in the men but only 15,103 copies per milliliter in the women (P<0.001). The median initial CD4+ count did not differ significantly according to sex (659 and 672 cells per cubic millimeter, respectively). HIV-1 infection progressed to AIDS in 29 men and 15 women, and the risk of progression did not differ significantly according to sex. For each increase of 1 log in the viral load (on a base 10 scale), the hazard ratio for progression to AIDS was 1.55 (95 percent confidence interval, 0.97 to 2.47) among the men and 1.43 (95 percent confidence interval, 0.76 to 2.69) among the women. The median initial viral load was 77,822 HIV-1 RNA copies per milliliter in the men in whom AIDS developed and 40,634 copies per milliliter in the men in whom it did not; the corresponding values in the women were 17,149 and 12,043 copies per milliliter. Given the recommendation that treatment should be initiated when the viral load reaches 20,000 copies per milliliter, 74 percent of the men but only 37 percent of the women in our study would have been eligible for therapy at the first visit after seroconversion (P<0.001). CONCLUSIONS: Although the initial level of HIV-1 RNA was lower in women than in men, the rates of progression to AIDS were similar. Treatment guidelines that are based on the viral load, rather than the CD4+ lymphocyte count, will lead to differences in eligibility for antiretroviral treatment according to sex.

Competing risk adjustment reduces overestimation of opportunistic infection rates in AIDS.

To illustrate the importance of adjusting the estimates of cumulative incidence of acquired immunodeficiency syndrome (AIDS) related illnesses for competing risk of other causes of death, we compared unadjusted and adjusted (for competing events) incidence estimates for four AIDS illnesses: pneumocystis cavinii pneumonia (PCP), mycobacterium avium complex (MAC), cytomegalovirus (CMV), and esophageal candidiases. The study population was patients followed by the Johns Hopkins Hospital AIDS Service between 1989 to 1995. Ratios of 4 year unadjusted incidence estimates to 4 year adjusted incidence estimates for the four diseases ranged from 1.38 to 1.86, corresponding to cumulative death rates of 61% to 69%. For CMV, the ratios of 4 year unadjusted to adjusted incidence estimates for five groups of patients ranged from 1.5 to 2.33, corresponding to cumulative death rates of 48% to 78%. We conclude that ignoring the competing risk of death can result in substantial overestimation of disease occurrence, which may give misleading results in estimating and comparing the occurrence of a disease of interest.

Evaluation of plasma retinol-binding protein as a surrogate measure for plasma retinol concentrations.

Plasma retinol-binding protein (RBP) concentrations have been suggested as surrogate indicators for plasma retinol concentrations in the assessment of vitamin A status in less technologically developed settings. Plasma RBP was measured by radial immunodiffusion and plasma retinol by high performance liquid chromatography in a cross-sectional study of 900 pregnant women at the Queen Elizabeth Central Hospital, Blantyre, Malawi. The Spearman correlation coefficient between plasma RBP and retinol concentrations was 0.95 (p<0.0001). By linear regression, 0.70 micromol l(-1) retinol was equivalent to 21.1 mg l(-1) RBP. With these cut-off points for defining vitamin A deficiency, there was high concordance between categorical descriptions of deficiency using retinol and RBP by chi-square analysis (p<0.001). Measurement of plasma RBP by radial immunodiffusion is simple, inexpensive, and does not require expensive instrumentation. Plasma RBP concentrations measured by radial immunodiffusion are highly correlated with plasma retinol and can be used as a simple surrogate measure for vitamin A concentrations in large field studies.

Immunologic parameters of multiple chemical sensitivity.

Immunologic abnormalities have long been advanced as a potential mechanism for multiple chemical sensitivity (MCS). An immunologic mechanism is supported in part by the systemic nature of the symptoms reported, the complex interactions known to exist between the immune system and other systems, and limited experimental evidence. However, there are both theoretical grounds for doubting an immunologic mechanism in MCS and methodological constraints in many of the studies that have been conducted in humans. The authors discuss the structure and function of the immune system as it potentially applies to MCS, the uses and limitations of immunologic testing, and the evidence for immunologic theories of MCS. They describe recent work to validate some of the immunologic tests used in MCS and consider opportunities for further research.