Racial disparities in joint replacement use among older adults

BACKGROUND: Although joint replacement can restore function for arthritis patients with severe joint disease, this procedure has not been used equally across racial groups. Differences in joint replacement use are assessed from a national sample. OBJECTIVE: This study evaluates the role of health conditions and economic access to explain differences in joint replacement among older black and Hispanic minorities relative to white persons. DESIGN: Longitudinal (1993-1995) Asset and Health Dynamics Among the Oldest Old (AHEAD) study. SETTING: National probability sample of US community-dwelling older adults. PATIENT POPULATION: AHEAD participants (n = 6159) aged 69 to 103 years. MEASUREMENTS: The outcome is subject-reported 2-year use of any arthritis-related joint-replacement. Independent variables are demographics, health needs (arthritis, other medical conditions, functional health), and economic access (income, assets, education, and health insurance). RESULTS: Older minorities reported arthritis-related joint replacements (black: 0.98%; Hispanic: 0.97%, annually) less frequently compared with white persons (1.48% annually). Older minorities were significantly less likely to use joint replacement compared with white persons (OR, 0.37; 95% CI, 0.20, 0.71) controlling for demographics, and arthritis and other health needs. Disparities remained significant (OR, 0.46; 95% CI, 0.22, 0.98) after additionally controlling for economic medical access. Use was lower among people who depended solely on Medicare compared with those with supplemental health insurance (OR, 0.46; 95% CI, 0.22, 0.95). CONCLUSIONS: These national data document low rates of arthritis-related joint replacement among older Hispanic persons comparable to black persons. Less use among older minorities compared with white persons is not explained by differences in health needs or economic access. Other cultural and attitudinal factors merit investigation to explain disparities.     

Diagnostic testing by CFTR gene mutation analysis in a large group of Hispanics: novel mutations and assessment of a population-specific mutation spectrum

Characterization of CFTR mutations in the U.S. Hispanic population is vital to early diagnosis, genetic counseling, patient-specific treatment, and the understanding of cystic fibrosis (CF) pathogenesis. The mutation spectrum in Hispanics, however, remains poorly defined. A group of 257 self-identified Hispanics with clinical manifestations consistent with CF were studied by temporal temperature gradient electrophoresis and/or DNA sequencing. A total of 183 mutations were identified, including 14 different amino acid-changing novel variants. A significant proportion (78/85) of the different mutations identified would not have been detected by the ACMG/ACOG-recommended 25-mutation screening panel. Over one third of the mutations (27/85) occurred with a relative frequency >1%, which illustrates that the identified mutations are not all rare. This is supported by a comparison with other large CFTR studies. These results underscore the disparity in mutation identification between Caucasians and Hispanics and show utility for comprehensive diagnostic CFTR mutation analysis in this population.     

The resolution, enrichment, and organization of normal bone marrow high proliferative potential colony-forming cell subsets on the basis of rhodamine-123 fluorescence

Cell sorting on the basis of rhodamine-123 (Rh123) fluorescence has been used in conjunction with negative immunomagnetic selection to analyze the high proliferative potential colony-forming cell (HPP-CFC) compartment of normal murine bone marrow and to resolve and enrich HPP-CFC subpopulations responsive to different combinations of the hemopoietic growth factors interleukin 1 alpha (IL-1 alpha), interleukin-3 (IL-3), and colony-stimulating factor 1 (CSF-1). HPP-CFC with a specific requirement for IL-1 alpha plus IL-3 plus CSF-1 in order to proliferate were resolved and enriched on the basis of their low Rh123 retention (Rh-dull), whereas HPP-CFC that grew in the presence of IL-3 plus CSF-1, IL-3 alone, or CSF-1 alone were Rh-bright. Further addition of IL-1 alpha to IL-3 plus CSF-1 stimulated few additional HPP-CFC in the Rh-bright fraction. Our data confirm the value of Rh123 as a probe for the dissection and analysis of the primitive hemopoietic stem cell (PHSC) compartment. These data also show that the Rh123 staining characteristics of IL-1 alpha plus IL-3 plus CSF-1-responsive HPP-CFC are consistent with the hypothesis that these HPP-CFC are closely related to PHSC with long-term reconstituting capacity in vivo and that they are among the most primitive progenitors yet detected in clonal agar culture.     

Novel target sites for estrogen action in the dorsal hippocampus: an examination of synaptic proteins

Structural studies have shown that estrogens increase dendritic spine number in the dorsal CA1 field of rat hippocampus using Golgi impregnation as well as the number of dorsal CA1 synapses visualized via electron microscopy. The present study was carried out to further these findings by examining changes in the levels of pre- and postsynaptic proteins using radioimmunocytochemistry (RICC). In this study, 2 days of estradiol-benzoate treatment produced significant and comparable increases in synaptophysin, syntaxin, and spinophilin immunoreactivity (IR) in the CA1 region of the dorsal hippocampus of ovariectomized female rats. For spinophilin, IR was also increased in the hilar region of the dentate gyrus as well as CA3. In all cases, the nonsteroidal estrogen antagonist CI628, which has been previously shown to block spine formation, inhibited the effects of estrogen. However, these protein differences were not detected in whole hippocampus using Western blots. These findings add to a growing body of evidence that estrogens increase synapses in the CA1 region of hippocampus along with changes in previously unidentified sites. These results also suggest that RICC is a rapid and sensitive method for examining molecular changes in synaptic profiles in anatomically distinct brain regions.     

Relative importance of enterochromaffin cell hyperplasia, anxiety, and depression in postinfectious IBS

BACKGROUND & AIMS: Both psychological and mucosal changes (increased enterochromaffin [EC] cells and T lymphocytes) have been associated with postinfectious irritable bowel syndrome (PI-IBS). However, previous studies have been underpowered to determine the relative importance of these changes in predicting the development of PI-IBS. Our aim was to prospectively determine the relative importance of both psychological and histologic factors in the development of PI-IBS after Campylobacter infection. METHODS: Questionnaires detailing psychological and bowel symptoms were sent to 1977 patients 3 months after infection. Twenty-eight patients with new-onset PI-IBS, 28 age- and sex-matched patient controls who were asymptomatic after infection, and 34 healthy volunteers underwent rectal biopsy, which was assessed for serotonin-containing EC cells, mast cells, and lamina propria T lymphocytes. RESULTS: PI-IBS, predominantly of the diarrhea-predominant subtype, occurred in 103 of 747 (13.8%) of those infected. EC cell counts per high-power field (hpf) were higher in patients with PI-IBS (35.8 +/- 1.2) compared with patient controls (30.6 +/- 1.9; P = 0.022) and volunteers (29.1 +/- 1.8; P = 0.006). Lamina propria T lymphocytes per hpf were higher in patients with PI-IBS (127.1 +/- 8.7) and patient controls (113.4 +/- 6.2) in contrast to healthy volunteers (97.1 +/- 5.7) (P = 0.006 and P = 0.058, respectively). Anxiety, depression, and fatigue were significantly increased in patients with PI-IBS compared with patient controls. Multivariate analysis indicated that increased EC cell counts and depression were equally important predictors of developing PI-IBS (relative risk, 3.8 and 3.2 for each standard deviation increase in respective values). CONCLUSIONS: Both increased EC cells and depression are important independent predictors of developing PI-IBS.     

Full‐limb and knee radiography assessments of varus‐valgus alignment and their relationship to osteoarthritis disease features by magnetic resonance imaging

Objective

To examine the correlation between hip‐knee‐ankle and femur‐tibia radiograph angles, calculate the offset of the femur‐tibia angle with respect to the hip‐knee‐ankle angle, calculate the sensitivity and specificity and area under the receiver operating characteristic (ROC) curve of the femur‐tibia angle, and examine the relationship of malalignment by each approach with osteoarthritis (OA) tissue pathology in the mechanically stressed compartment using magnetic resonance imaging (MRI).

Methods

Individuals with knee OA underwent full‐limb and knee radiographs and knee MRI. Linear regression was used to determine if the 2 angles differed systematically and to identify the cutoff. Alignment means for MRI grades were compared using Dunnett's t‐test.

Results

In the 146 participants (109 women, mean age 70 years, body mass index 30.6 kg/m²), femur‐tibia and hip‐knee‐ankle angles correlated (r = 0.86; 95% confidence interval [95% CI] 0.81, 0.90). On average, the femur‐tibia angle was 3.4° more valgus (3.0° in women and 4.7° in men); after correction, its sensitivity and specificity (to predict the hip‐knee‐ankle angle) were 0.84 and 0.84 for identifying varus and 0.98 and 0.73 for valgus, respectively. The area under the ROC curve (95% CI) was 0.91 (0.86, 0.96) for varus and 0.94 (0.89, 0.99) for valgus. Varus severity worsened comparably with each alignment measure as medial lesion score on MRI worsened. Laterally, as lesion score worsened, comparably worse valgus was seen with either assessment approach.

Conclusion

In knee OA, the knee radiograph femur‐tibia and full‐limb radiograph hip‐knee‐ankle angles were correlated. The femur‐tibia angle, corrected for mean offset, was sensitive, specific, and had excellent discriminative ability for identifying varus and valgus alignment evidenced by area under the ROC curve. The relationship between alignment and specific OA MRI features was comparable with the 2 approaches. Use of the femur‐tibia angle, corrected for offset, should be considered in research and clinical settings.     

Estrogen alters hippocampal dendritic spine shape and enhances synaptic protein immunoreactivity and spatial memory in female mice

Estrogen (E) treatment induces axospinous synapses in rat hippocampus in vivo and in cultured hippocampal neurons in vitro. To better explore the molecular mechanisms underlying this phenomenon, we have established a mouse model for E action in the hippocampus by using Golgi impregnation to examine hippocampal dendritic spine morphology, radioimmunocytochemistry (RICC) and silver-enhanced immunocytochemistry to examine expression levels of synaptic protein markers, and hippocampal-dependent object-placement memory as a behavioral readout for the actions of E. In ovariectomized mice of several strains and F(1) hybrids, the total dendritic spine density on neurons in the CA1 region was not enhanced by E treatment, a finding that differs from that in the female rat. E treatment of ovariectomized C57BL/6J mice, however, caused an increase in the number of spines with mushroom shapes. By RICC and silver-enhanced immunocytochemistry, we found that the immunoreactivity of postsynaptic markers (PSD95 and spinophilin) and a presynaptic marker (syntaxin) were enhanced by E treatment throughout all fields of the dorsal hippocampus. In the object-placement tests, E treatment enhanced performance of object placement, a spatial episodic memory task. Taken together, the morphology and RICC results suggest a previously uncharacterized role of E in synaptic structural plasticity that may be interpreted as a facilitation of the spine-maturation process and may be associated with enhancement of hippocampal-dependent memory.     

Activation of phospholipase D by glyceraldehyde in isolated islet cells follows protein kinase C activation.

Our recent studies have demonstrated the presence in neonatal islet cells and intact adult islets of a phosphatidylcholine-directed phospholipase D (PLD) which is activated after phorbol ester stimulation. The present study describes PLD activation in the presence of a carbohydrate insulin secretagogue. At the highest concentration tested (20 mM) the triose, glyceraldehyde, induced formation of phosphatidic acid in cells prelabeled with [14C]arachidonic acid or [3H]myristic acid (164 +/- 7 and 210 +/- 9% of basal phosphatidic acid values, respectively). Experimental confirmation of a concentration-dependent specific activation of PLD was provided by the formation of a transphosphatidylation product, phosphatidylethanol, after stimulation with glyceraldehyde in the presence of added ethanol (1.5%). Additionally, there was an early (within 5 min) rise in [14C]arachidonate-labeled diacylglycerol (139 +/- 7% of basal) accompanied by an increase in intracellular diacylglycerol mass (51 +/- 2 pmol/mg protein) and an increase in membrane-associated protein kinase C activity (183 +/- 5% of basal) which preceded the activation of PLD, as indicated by the time course of glyceraldehyde-stimulated phosphatidylethanol formation in the presence of ethanol. Pretreatment of islet cells with 2 microM 12-O-tetradecanoylphorbol-13-acetate for 18 h, to down-regulate protein kinase C, was without effect on diacylglycerol and phosphatidic acid production after 5 min but inhibited completely the production of phosphatidylethanol at 30 min. The phosphohydrolase inhibitor propranolol (100 microM) potentiated the accumulation of phosphatidic acid and phosphatidylethanol incubation following incubation with glyceraldehyde. These findings demonstrate for the first time that a physiological nutrient activates a phospholipase directed against endogenous phosphatidylcholine in intact islet cells; furthermore, they indicate a role for PLD in a delayed formation of phosphatidic acid in the islet cell. The finding of an early rise in glyceraldehyde-stimulated diacylglycerol (which may be formed de novo or by the action of phospholipase C), suggests that PLD is recruited by the activation of protein kinase C by this nutrient.