Incomplete activation of peripheral blood dendritic cells during healthy human pregnancy.

Successful pregnancy relies on the adaptation of immune responses that allow the fetus to grow and develop in the uterus despite being recognized by maternal immune cells. Dendritic cells (DCs) are central to the control of immune tolerance, and their state of activation at the maternal-decidual interface is critical to the feto-maternal immunological equilibrium. So far, the involvement of circulating DCs has been investigated poorly. Therefore, in this study we investigated whether, during healthy human pregnancy, peripheral blood DCs (PBDCs) undergo changes that may be relevant to the adaptation of maternal immune responses that allow fetal tolerance. In a cross-sectional study, we analysed PBDCs by six-colour flow cytometry on whole blood samples from 47 women during healthy pregnancy progression and 24 non-pregnant controls. We demonstrated that both myeloid and plasmacytoid PBDCs undergo a state of incomplete activation, more evident in the third trimester, characterized by increased expression of co-stimulatory molecules and cytokine production but lacking human leucocyte antigen (HLA)-DR up-regulation. To investigate the contribution of soluble circulating factors to this phenomenon, we also performed culture experiments showing that sera from pregnant women added to control DCs conditioned a similar incomplete activation that was associated with reduced DC allostimulatory capacity, supporting the in vivo relevance of our findings. We also obtained evidence that the glycoprotein hormone activin-A may contribute to DC incomplete activation. We suggest that the changes of PBDCs occurring during late pregnancy may aid the comprehension of the immune mechanisms operated by the maternal immune system to maintain fetal tolerance.

HIV-specific mucosal and cellular immunity in HIV-seronegative partners of HIV-seropositive individuals.

HIV-specific mucosal and cellular immunity was analyzed in heterosexual couples discordant for HIV status in serum and in HIV-unexposed controls. HIV-specific IgA but not IgG was present in urine and vaginal wash samples from HIV-exposed seronegative individuals (ESN), whereas both IgA and IgG were observed in their HIV-seropositive partners; antibodies were not detected in low-risk controls. Envelope protein (Env) peptide-stimulated interleukin-2 (IL-2) production by peripheral blood mononuclear cells (PBMCs) was detected in 9 out of 16 ESNs, 5 out of 16 HIV-infected patients and 1 out of 50 controls. Env peptide-stimulated PBMCs of ESNs produced more IL-2 and less IL-10 compared with those of HIV-infected individuals; no differences were observed in chemokine production or in CCR5 expression. These data demonstrate that a compartmentalized immune response to pathogens is possible in humans and raise the possibility of protective roles for cell-mediated immunity and mucosal IgA in HIV-seronegative individuals exposed to HIV.

Cytokine production patterns in cervical intraepithelial neoplasia: association with human papillomavirus infection.

BACKGROUND: Genital infection with certain strains of human papillomavirus (HPV) is associated with a high risk of malignant transformation, and HPV-associated cervical intraepithelial neoplasia (CIN) can become invasive cancer. Host factors are critical in regulating tumor growth, and cytokines that modulate immunologic control may be of particular importance. The type 1 cytokines interleukin 2 (IL-2) and interferon gamma (IFN gamma) are immunostimulatory and are thus capable of limiting tumor growth. The type 2 cytokines interleukin 4 (IL-4) and interleukin 10 (IL-10) are immunoinhibitory and are thus capable of stimulating tumor growth. PURPOSE: We analyzed the production of cytokines by peripheral blood mononuclear cells (PBMCs) in women with CIN associated with localized or extensively spread HPV infection. METHODS: Thirty women diagnosed with CIN and 10 age- and sex-matched healthy control subjects were enrolled in the study conducted at Istituto Nazionale Tumori, Milan, Italy. The following parameters were analyzed: 1) HPV infection of the cervix and other sites of the lower genital tract by colposcopic, cytologic, and histologic examinations; 2) HPV typing; 3) in vitro production of IL-2 by PBMCs in response to stimulation with soluble antigen (influenza [FLU] antigen) or to cell-associated human leukocyte antigen (HLA) alloantigen; and 4) in vitro production of the type 1 cytokines IL-2 and IFN gamma and of the type 2 cytokines IL-4 and IL-10 by PBMCs in response to mitogen stimulation. Statistical significance was determined by nonparametric tests (two-sided). RESULTS: High-grade CIN associated with HPV infection was detected in all case patients, and HPV type 16 or 18 infection was detected in cervical tissue of 21 (70%) of 30 case patients. HPV infection that had spread to other sites of the lower genital tract, thus resulting in more extensive disease, was detected in 16 (53%) of the 30 individuals with CIN, whereas HPV infection was limited to the portio in 14 (47%). IL-2 production by PBMCs in response to stimulation with soluble antigen or HLA alloantigen was reduced in the group with extensive disease compared with that in the group with localized disease or with that in healthy control subjects. In contrast, IL-4 and IL-10 production in response to mitogen stimulation was elevated in the group with extensive disease compared with that in the group with localized disease or with that in healthy control subjects. The highest production of IL-4 and IL-10 was detected in patients with HPV infection that had extended beyond the genital tract. CONCLUSIONS: CIN is characterized by different immunologic profiles, in which HPV infection is or is not confined to the portio. Production of cytokines that mainly enhance potentially protective cell-mediated immunity is defective in the women in whom extended HPV infection was observed. A pronounced shift from type 1 to type 2 cytokine production is associated with more extensive HPV infection. IMPLICATIONS: These data reinforce the need for detailed analyses of immune dysregulation in CIN patients. They also suggest the potential usefulness of the cytokine assays for determining prognosis or deciding whether cytokine-based therapy is indicated.

Immunological activation markers in the serum of African and European HIV-seropositive and seronegative individuals.

OBJECTIVE: The concentration of type 1 and type 2 cytokines and fibroblast-associated apoptosis-1 soluble receptor (sAPO-1/Fas) was analysed in the sera of Ugandan and Italian HIV-1-seropositive and seronegative individuals. The data were compared to determine whether the immunological status of these groups was different. METHODS: Sixty-seven Ugandan and 30 Italian HIV-positive patients were analysed and stratified according to CD4 counts (group 1, > 500 x 10(6)/l; group 2, 200-500 x 10(6)/l; group 3, < 200 x 10(6)/l). Sera from 15 Ugandan and 11 Italian HIV-negative blood donors were also analysed. Serum concentration of type 1 cytokines [interleukin (IL)-2, IL-12, and interferon (IFN)-gamma] and type 2 cytokines (IL-4 and IL-10), and sAPO-1/Fas were measured by enzyme-linked immunosorbent assay. RESULTS: Serum levels of IL-2, IFN-gamma and IL-10 but not of IL-4 and IL-12, were elevated in HIV-positive group 1 and 2 Africans compared with HIV-positive Italian individuals. IL-4 was mildly augmented in HIV-positive group 3 African patients. Serum concentration of sAPO-1/Fas was reduced in HIV-positive Africans compared with HIV-positive Italian individuals. Finally, serum levels of IL-2 and IL-10 were increased and sAPO-1/Fas reduced when sera of HIV-negative African healthy controls were compared with their Italian counterparts. The ratio of type 1/type 2 cytokines was roughly 1.0 in HIV-negative African controls, and much greater than 1.0 in HIV-negative Italian controls. CONCLUSIONS: These preliminary findings indicate that immune activation is present in African HIV infection. Furthermore, these data raise the possibility that abnormal immune activation and increased susceptibility to antigen-induced cell death is present even in HIV-negative African controls.

Factors contributing to skeletal health of postmenopausal Mexican-American women.

Incidence rates of hip fracture are lower in Hispanic (HC) than non-Hispanic Caucasians (NHC). To investigate factors that may affect skeletal health of Hispanics, we recruited 152 healthy community-dwelling Mexican-American Caucasian women into a 4-year longitudinal study that evaluates bone mass, nutritional status, muscle strength, mobility, falls, and other factors that may contribute to fracture risk. Results from the baseline component of the study are reported herein. Average bone mineral densities (BMD) evaluated by dual-energy X-ray absorptiometry (DXA) in this study group did not differ from BMDs in healthy, NHC women of similar age. Hip axis length (HAL), however, was significantly shorter than that reported for nonosteoporotic NHC. Factors independently associated with greater BMD and BMC at certain skeletal sites were lean body mass, fat mass, acculturation, years of estrogen use, sun exposure, hip adductor strength, grip strength, erythrocyte folate, and serum glucose concentrations. Factors independently associated with lower BMD and BMC at certain skeletal sites were age, parity, and vertebral deformities (all p < 0.05). Thus, the decreased risk of hip fracture in HC compared with NHC does not appear to be due to high bone mass. However, other factors such as HAL and body composition may play a role in maintenance of skeletal integrity.

The presence of a polymorphism at the translation initiation site of the vitamin D receptor gene is associated with low bone mineral density in postmenopausal Mexican-American women.

We examined the association of bone mineral density (BMD) with a polymorphism in the gene encoding the vitamin D receptor (VDR) that causes a change in the predicted protein sequence. The polymorphism results from a C-to-T transition and creates an initiation codon (ATG) three codons proximal to a downstream start site. The polymorphism can be defined by a restriction fragment length polymorphism (RFLP) using the restriction endonuclease FokI. The presence of a FokI site, designated f, allows protein translation to initiate from the first ATG. The allele lacking the site (designated F), initiates from a second ATG site. Thus, translation products from these alleles are predicted to differ by three amino acids with the f variant elongated. In a group of 100 postmenopausal Mexican-American Caucasian women, subjects with the ff genotype (15% of the study population) had a 12.8% lower BMD at the lumbar spine than FF subjects (37% of the population) (p = 0.01). Heterozygote (Ff) subjects (48% of the population) had an intermediate BMD. This association between BMD and genotype was not apparent at the femoral neck or forearm. Over a 2-year follow-up period, a decrease in BMD at the femoral neck was greater in ff compared with FF subjects (-4.7% vs. -0.5%, p = 0.005). This trend was not apparent at the lumbar spine or forearm. There were no differences between genotype groups in measurements of 25-hydroxyvitamin D (25(OH)D), calcitriol, parathyroid hormone (PTH), osteocalcin, or urinary pyridinolines. We conclude that the FokI polymorphism of the VDR gene correlates significantly with decreased BMD at the lumbar spine and with an increased rate of bone loss at the hip in ff subjects. We emphasize that these initial data should be interpreted with caution but that the utility of this polymorphism as a genetic marker to determine BMD and osteoporosis risk warrants further study in larger populations with subjects of diverse ethnic backgrounds.

Vitamin D receptor polymorphisms, bone mineral density, and bone metabolism in postmenopausal Mexican-American women.

Common polymorphisms in the vitamin D receptor (VDR) gene have been shown to correlate with bone mineral density (BMD). However, attempts to replicate the original findings in other populations have yielded variable results. These disparities may reflect ethnic or environmental differences in the expression of the VDR effect upon BMD. We examined a relatively ethnically homogeneous group of 103 healthy postmenopausal Caucasian women of Mexican descent living in Northern California. We determined the VDR genotype and measured the BMD at the lumbar spine and femoral neck by dual-energy X-ray absorptiometry, as well as several biochemical indices of mineral metabolism. The prevalence of the BB genotype, associated in previous studies with the lowest BMD, was 8% and highly linked to the tt genotype. Absolute and age-adjusted BMD at both hip and spine showed a trend toward lower BMD in the BB, AA, and tt genotypes, but this trend did not achieve statistical significance. There were no consistent intergroup differences in change in BMD over 2 years of follow-up, nor in mean serum concentrations of 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, osteocalcin, or total urinary pyridinolines. Intact parathyroid hormone concentrations were significantly higher in subjects with the AA genotype, with a trend toward higher values in those with the BB and tt genotypes as well. Our data suggest that there may be a decrease in BMD associated with the B, A, and t alleles, but the intergroup difference in BMD is 0.2-0.5 standard deviations (SD) at the lumbar spine and 0.3 SD at the femoral neck, decreases that are smaller than previously reported. Given the relatively low prevalence of the BB/tt genotype in Mexican-American Caucasians, a larger sample would be required to detect a significant association between VDR alleles and differences in BMD of the magnitude suggested by our data. We conclude that a genotype effect of this magnitude, if present, would be clinically relevant, but the impact on BMD is too small to detect with statistical significance in a study of this size.

Effects of aluminum hydroxide on the parathyroid-vitamin D axis of postmenopausal women.

In previous studies we proposed that estrogen increases circulating calcitriol in postmenopausal women by reducing plasma phosphorus concentrations. For this model to be plausible, a reduction in plasma phosphorus must be itself be sufficient to increase circulating calcitriol in elderly women. To assess this question we studied the effects of Al(OH)3 on daylong circulating levels of phosphorus, calcium, PTH, and calcitriol in 14 postmenopausal women. Subjects were studied on two 7-day periods of dietary control, in which calculated intakes for phosphorus, calcium, and sodium were 950, 800, and 3000 mg/day, respectively. During one randomly assigned period, subjects were given Al(OH)3 with each meal. Al(OH)3 significantly lowered daylong plasma phosphorus concentrations by 17% (0.95 +/- 0.02 mmol/L vs. 1.15 +/- 0.02, P less than 0.0005) (2.94 +/- 0.06 mg/dL vs. 3.57 +/- 0.07), and this was associated with a 38% rise in circulating calcitriol from 61.8 +/- 10.3 pmol/L to 85.2 +/- 10.1 pmol/L (25.7 +/- 4.3 pg/ml to 35.5 +/- 4.2 pg/ml) (P less than 0.0001). The rise in calcitriol correlated significantly with the reduction in phosphorus (r = 0.51, P = 0.03). Al(OH)3 did not significantly alter average daily circulating total calcium (2.32 +/- 0.008 vs. 2.32 +/- 0.005 mmol/L) (9.31 +/- 0.03 vs. 9.29 +/- 0.02 mg/dL), ionized calcium (1.19 +/- 0.003 vs. 1.19 +/- .004 mmol/L), or intact PTH (24.6 +/- 0.6 vs. 24.2 +/- 0.8 ng/L). Moreover, neither the renal phosphorus reabsorption maximum (TmP/GFR), baseline excretion of cAMP, nor the phosphaturic, cAMP, or calcitriol responses to infused hPTH(1-34) were altered by Al(OH)3. We conclude that Al(OH)3 treatment of older women lowers plasma phosphorus concentrations by restricting intestinal phosphorus absorption, and that older women retain the capacity to increase calcitriol levels in response to phosphorus restriction.

Effects of conjugated estrogen on the calcitriol response to parathyroid hormone in postmenopausal women.

We evaluated the effects of estrogen on the calcitriol response to the active peptide, human PTH(1-34), in postmenopausal women. Fifteen women were studied before and again after at least 1 month of treatment with conjugated equine estrogens, 1.25 mg/day. Six women received two series of four graded peptide infusions, each with the sequence 200, 400, 800, and 1600 USP U hPTH(1-34). Nine women received only one dose of peptide, either 200 or 800 U, before and while taking estrogen. Baseline values and the incremental and percent changes in circulating calcitriol 24 h after the 20-min infusions were evaluated. Estrogen treatment resulted in significant reductions in blood levels of calcium (2.26 +/- 0.03 mmol/L vs. 2.16 +/- 0.02, P less than 0.05) and phosphorus (1.23 +/- .05 mmol/L vs. 1.14 +/- 0.03, P less than 0.005), a rise in serum calcitriol concentrations (42.2 +/- 3.9 pg/mL vs. 28.6 +/- 3.1, P less than 0.005), and no change in circulating PTH. The rise in calcitriol after 200 U hPTH(1-34) was significantly greater on estrogen (17.6 +/- 2.0 pg/mL vs. 9.5 +/- 1.8, P less than 0.01), but estrogen did not alter incremental responses to larger doses. When results were normalized for differences in baseline values, the estrogen-related change in response to 200 U was no longer significant. hPTH(1-34) acutely increased urinary clearance of cAMP and phosphorus, but estrogen did not affect this response. We conclude that exogenous estrogen does not increase renal sensitivity to PTH in postmenopausal women.

Restorative effect of total parenteral nutrition on natural killer cell activity in malnourished cancer patients.

Decreased natural killer cell activity (NKCA) is associated with malnutrition in both cancer and non-cancer patients. We have studied the effect of total parenteral nutrition (TPN) on NKCA in 9 malnourished cancer patients, candidates for surgery. TPN was administered for a median of 10 days (range 7-11), providing 1.5-fold the estimated resting energy expenditure, with 30% as fat. Calorie:nitrogen ratio was 150:1. Basal human recombinant interferon-alpha 2a (rIFN-alpha 2a) and human recombinant IL-2 rIL-2) activated NKCA were measured, as were the main nutritional parameters, prior to and after TPN. NKCA increased in all patients and reached the normal range in 5, 3 and 4 subjects, respectively, for basal, rIFN-alpha 2a and rIL-2 activated NKCA. As regards nutritional assessment, body weight and IgM levels significantly increased from 47.7 to 50.1 kg and from 174 to 237 mg/dl, respectively. This study demonstrates that a 10-day TPN course increases and sometimes restores normal NKCA. Such effect was constant and preceded nutritional changes.

Multiple defects of T helper cell function in newly diagnosed patients with Hodgkin's disease.

T helper cell (TH) function, as assessed by interleukin-2 (IL-2) production and [3H]thymidine incorporation, was studied in 47 newly diagnosed untreated patients with Hodgkin's disease (HD) and 34 healthy controls. Three different stimuli were used to stimulate in vitro peripheral blood mononuclear cells (PBMC): influenza A vaccine (FLU), HLA alloantigens (ALLO) and phytohaemagglutinin (PHA). Four different patterns of TH function were observed in HD patients: (1) IL-2 production in response to all of the stimuli (40%); (2) IL-2 production in response to ALLO and PHA but not to FLU (26%); (3) IL-2 production in response to PHA alone (19%); and (4) failure to respond by IL-2 production to any of the three of the stimuli (15%). Thus, defective in vitro TH function was detected in the majority of these patients (60%). Defective TH function was observed in none of the 34 controls. Severely compromised TH function (patterns 3 and 4) tended to be associated with more advanced clinical presentation and more compromised haematological parameters (P < 0.05). The IL-2 production assay was more sensitive than the proliferative assay as only 30% of the HD patients failed to proliferate in response to FLU, and none failed to proliferate in response to either ALLO or PHA; this assay can detect subtle, multiple patterns of immune dysregulation in untreated HD patients. Our results suggest that HD is associated with a fundamental dysregulation in TH function, illustrate the complexity of such dysregulation, and raise the possibility that HD progression will be associated with a type-1-type-2 switch in immunoregulatory cytokine production.

Antibody-forming foci in soft-agar cultures of human peripheral blood cells.

Human peripheral blood lymphocytes (PBL) from healthy blood donors were grown in soft-agar gel with sheep red blood cells (SRBC) and autologous plasma as a source of complement. After 4--6 days incubation, foci of proliferating hemolysin-forming cells, surrounded by a lytic area of 0.2--0.5 mm, were detected on the surface of the plates. The response was antigen specific, since new hemolytic areas were observed on pouring a fresh agar-SRBC mixture over the surface of primary cultures, but not on pouring a mixture containing rat or rabbit erythrocytes. The antibody response was significantly increased by addition to the cultures of polyethylene glycol 6000 (PEG), 8% final concentration. The mean number of foci was 8.4 +/- 2.2 in cultures without PEG and 36.2 +/- 2.3 in PEG+ cultures, both containing 9 X 10(6) lymphocytes. This finding is in agreement with observations on the frequency of precursors of antibody-forming cells among lymphoid populations. The explanation of the mechanism by which PEG 6000 modified the immune reactivity of PBL is not clear. However, we think, that this technique provides a reliable methodology for PBL antigenic stimulation in vitro.

Immune responses to antigens of human endogenous retroviruses in patients with acute or stable multiple sclerosis.

A possible role for human endogenous retroviruses (HERV) in the pathogenesis of MS was investigated by analyzing HERV peptides-stimulated proliferation and cytokine production in MS patients with acute (AMS) or stable (SMS) disease. HERV peptides specific-proliferation and type 1 cytokine production by peripheral blood mononuclear cells was observed in AMS but not in SMS individuals, in whom a type 2 cytokine profile dominates. HERV peptides-stimulated immune responses were modified by changes in disease expression; mediated by CD4+ T lymphocytes; and not related to HLA class II molecules. These data suggest the possibility of a pathogenic role for HERV and HERV-specific immune responses in MS.

Monocyte mediated modulation of the antibody response in vitro.

Human peripheral blood monocytes (PBMC) were isolated by Ficoll-Hypaque density gradient and then fractionated by differential adhesion to plastic surface. Adherent cell-depleted PBMC, non-readherent fraction and firmly adherent fraction so obtained from PBMC, PBMC themselves and a mixture of the above cells, were then sensitized in vitro with sheep erythrocytes (SRBC) so as to produce a primary antigen-dependent, antigen-specific antibody response. It appears that adherent cell-depleted PBMC produce about twice as many haemolytic areas as compared to total PBMC (from 43 to 85). If depleted PBMC are co-cultured with firmly adherent or non-readherent cells, the number of haemolytic areas goes down to 19 or up to 102, respectively. Functional, histochemical, immunochemical and morphological data suggest that the inhibiting firmly adherent fraction is composed of typical phagocytizing cells, while the enhancing cells of the non-readherent fraction are similar to the dendritic cells described in human blood and some lymphoid organs, which do not exhibit active pinocytic activity, but are the principal accessory cells needed to stimulate lymphocyte responses.

Purification of interleukin-2 antibodies from healthy individuals.

By covalent binding of recombinant interleukin-2 (rIL-2) to Sepharose, it was possible to immunopurify specific human anti-IL-2 antibodies from a pool of immunoglobulins obtained from healthy subjects. Since low quantities of the ligand released by the matrix could interfere with the evaluation of the biological activity of anti-IL-2 antibodies, the antibody preparation was subjected to pepsin digestion which is known to destroy the IL-2 molecule. Purified human anti-IL-2 antibodies were found to be mostly IgG1 and able to neutralize IL-2 induced peripheral blood lymphocytes (PBL) proliferation in vitro. The availability of purified anti-IL-2 antibodies, obtained from healthy individuals, able to modulate IL-2 activity, could be important in several therapeutic approaches.

A role for mucosal immunity in resistance to HIV infection.

In a recent, thought-provoking novel by Elizabeth McCracken (The Giant's House. Avon Books, New York, 1997), two characters discuss love and its impossibilities. One brashly claims to be "immune to love", explaining the concept to his perplexed interlocutor, "...people become immune to love like they become immune to any disease. Either they had it bad early in life, like chicken pox and that's that; or they keep getting exposed to it in little doses and build up an immunity; or somehow they just don't catch it, something in'em is born resistant. I'm the last type. I'm immune to love and poison ivy". (p. 275) (E. McCracken, The Giant's House. Avon Books, New York, 1997). Substitute the words 'HIV infection' for 'love' and this intriguing metaphor summarizes the state of the art working hypotheses for the phenomenon of resistance to HIV infection in HIV-exposed individuals who, against all odds, do not seroconvert. These hypotheses will be discussed hereafter and particular emphasis will be placed upon a possible role for mucosal immunity in this phenomenon.

A possible role for the cortisol/anticortisols imbalance in the progression of human immunodeficiency virus.

The progression of HIV infection is accompanied by complex alterations in the production of adrenal steroids. Cortisol levels are increased in HIV infection whereas those of dehydroepiandrosterone (DHEA), a physiologic antagonist of the immunoregulatory activities of cortisol, decrease. The progression of HIV infection to AIDS is also characterised by a shift from a type 1 to type 2 cytokine production. Thus, defective production of interferon gamma (IFN gamma), interleukin (IL)-2, and IL-12 as well as increased production of IL-4, IL-5, IL-6, and IL-10 are observed in HIV-seropositive individuals and are proposed to be in vitro immunologic marker of progression. Cortisol and pharmacological doses of glucocorticoids (GC) suppress IL-2 and IFN gamma production and favour the production of IL-4. Furthermore, GC and IL-4 stimulate the differentiation of B lymphocytes into IgE producing plasma cells, the concentration of which augments in HIV infection. Finally, GC induce programmed cell death (PCD) in a variety of different cells, including mature T lymphocytes, and type 2 cytokines were recently proposed to augment the susceptibility of T lymphocytes to PCD. It was suggested that the progressive shift from type 1 to type 2 cytokine production characteristic of HIV infection could be at least partially provoked by the increase in the production of cortisol and the reduction of DHEA. This hypothesis is discussed within the scenario of an endrocrinologic imbalance being responsible for HIV progression at least partially via increased susceptibility of HIV + CD4 lymphocyte to PCD.

Falls in older Mexican-American women.

OBJECTIVE: To determine the frequency of falls and identify risk factors for falls among older Mexican-American women. DESIGN: A prospective cohort study with an average follow-up of 2.7 years. SETTING: A clinical center at the Palo Alto Veterans Affairs Medical Center, California. PARTICIPANTS: 152 community-dwelling Mexican-American Caucasian women aged 59 years or older. OUTCOME MEASURES: Falls and injurious falls, as determined by monthly telephone interviews. RESULTS: The rate of falls was 508 per 1000 person-years (95% confidence interval (CI), 440-577). Injurious falls requiring medical attention occurred at a rate of 79 per 1000 person-years (95% CI, 52-107). Factors that were associated independently with an increased risk of falling were older age, a history of arthritis or rheumatism, a history of high thyroid, having fainted at least once in the year before baseline, current use of psychotropic medications, and walking fewer than 5 blocks a day. Those persons with an average time for the chair stand test had a lower risk of falling than those with the slowest times or the fastest times. CONCLUSIONS: The frequency of falls and injurious falls in this cohort of 152 relatively acculturated, healthy, older Mexican-American women was similar or slightly higher than previously reported rates for non-Hispanic Caucasian(s). Many of the factors associated with falls in this study were similar to those reported for non-Hispanic Caucasian women, suggesting that fall prevention measures tested mainly among non-Hispanic Caucasian women would also be appropriate for Mexican-American women.

Ethnic differences in insulin resistance and its consequences in older Mexican American and non-Hispanic white women.

BACKGROUND: This study was initiated to test the hypothesis that older, healthy, nondiabetic Mexican American women would be relatively resistant to insulin-mediated glucose disposal, hyperinsulinemic, and dyslipidemic as compared to a matched group of non-Hispanic White (NHW) women. METHODS: The study, cross-sectional in nature, involved 14 Mexican American and 19 NHW healthy, normotensive nondiabetic, postmenopausal women of similar age and body mass index. It took place in the General Clinical Research Center at Stanford Medical Center. Measurements were made of fasting plasma glucose, insulin and lipid concentrations, and plasma glucose and insulin concentrations following a 75 gram oral glucose challenge. Resistance to insulin-mediated glucose disposal was estimated by the steady-state plasma glucose (SSPG) concentration achieved at the end of a 3-hour constant infusion of glucose, insulin, and somatostatin. RESULTS: Mexican American women had significantly greater glucose (p < .001) and insulin (p < .001) responses to the oral glucose challenge than did the NHW women. Resistance to insulin-mediated glucose disposal was increased in Mexican American women (SSPG 195 +/- 25 mg/dl compared to 137 +/- 18 mg/dl in NHW; p < .001). While total cholesterol, low density lipoprotein (LDL)-cholesterol, and triglyceride concentrations were not significantly different in the two ethnic groups, high density lipoprotein (HDL)-cholesterol was significantly lower in the Mexican American women (51 mg/dl vs 61 mg/dl; p = .04). CONCLUSION: Older Mexican American women are more insulin resistant, glucose intolerant, and hyperinsulinemic, and have a lower HDL-cholesterol than a matched group of non-Hispanic White peers. These results were observed despite the exclusion of individuals with non-insulin dependent diabetes mellitus (NIDDM).

Bacillary disease and health seeking behavior among Filipinos with symptoms of tuberculosis: implications for control.

SETTING: Urban and rural communities and urban poor settlements in the Philippines. OBJECTIVE: To determine bacillary disease and action taking among individuals with symptoms of tuberculosis (TB), and to analyze their implications for TB control. STUDY DESIGN AND METHOD: Subjects aged 20 years and older were interviewed in the 1997 nationwide stratified multi-cluster survey. Sputum acid-fast smears and cultures were done in subjects with abnormal screening chest radiographs. RESULTS: Individuals with TB symptoms comprised 18.1% of the population studied. The prevalence of bacillary disease was 39/1000 in symptomatic subjects compared to 13/1000 in asymptomatic subjects. Symptom screening had a 14.3% positive predictive value and a 91.4% negative predictive value for bacillary disease. Significantly more symptomatic than asymptomatic subjects attended chest radiographic screening during the survey. However, in response to their symptoms, the majority (43.0%) took no action or self medicated (31.6%), while 11.8% consulted a private practitioner, 7.5% a public health center, 4.4% a hospital, and 1.7% a traditional healer. CONCLUSION: Sputum smear examination after symptom screening was acceptable for case finding. The health seeking behavior of subjects with TB symptoms was inappropriate. A health education program and public-private collaboration in directly observed therapy, short course (DOTS) are essential for TB control in the Philippines.