Income differences in persons seeking outpatient treatment for mental disorders: a comparison of the United States with Ontario and The Netherlands

BACKGROUND: Variations in the relationships among income, use of mental health services, and sector of care are examined by comparing data from 3 countries that differ in the organization and financing of mental health services. METHODS: Data come from the 1990-1992 National Comorbidity Survey (n = 5,384), the 1990-1991 Mental Health Supplement to the Ontario Health Survey (n = 6,321), and the 1996 Netherlands Mental Health Survey and Incidence Study (n = 6031). Analysis of the association between income and use of mental health services was carried out for the population that was between ages 18 and 54 years. Differential use of mental health treatment was examined in 3 sectors: the general medical sector, the specialty sector, and the human services sector. RESULTS: No significant association between income and probability of any mental health treatment was observed for persons with psychiatric disorders in any of the 3 countries. However, there were significant differences among countries in the association between income and sector of mental health care treatment. In the United States, income is positively related to treatment being received in the specialty sector and negatively related to treatment being received in the human services sector. In the Netherlands, patients in the middle-income bracket are less likely to receive specialty care, while those in the high-income bracket are less likely to be seen in the human service sector. Income is unrelated to the sector of care for patients in Ontario. CONCLUSIONS: Future research should examine whether differential access to the specialty sector for low-income people in the United States is associated with worse mental health outcomes.     

Effects of propylene oxide exposure on rat nasal respiratory cell proliferation.

Long-term exposure of rodents to propylene oxide (PO) induced inflammation, respiratory cell hyperplasia, and nasal tumors at concentrations >/= 300 ppm, suggesting a possible role for cytotoxicity and compensatory cell proliferation in PO carcinogenesis. In this study, the effects of PO exposure on histopathology and cell proliferation in nasal and hepatic tissues were studied in male F344 rats exposed by inhalation for 3 or 20 days (0, 5, 25, 50, 300, and 500 ppm). Histopathology revealed an increase in mucous cell hyperplasia in the anterior nasal passages after 20 days of exposure (>/=300 ppm). This was associated with the formation of goblet cell nests. Cell proliferation was measured in the respiratory epithelium (NRE; mucociliary and transitional) lining the anterior nasal passages, the nasopharyngeal meatus (NPM), and the liver using BrdU administered with 3-day osmotic pumps. Significant increases in cell proliferation occurred (>3.6-fold) in the mucociliary epithelium lining the anterior nasal cavity at and above 300 ppm for both exposure periods. In the mucociliary epithelium, the 20-day labeling was commonly associated with nests of goblet cells. Significant increases in cell proliferation (>2.3-fold) were observed in the transitional epithelium at 500 ppm after 3 days of exposure and at 300 and 500 ppm after 20 days of exposure. Significant increases in cell proliferation in the NPM (>2.8-fold) were evident at 500 ppm PO after 3 days and at 300 and 500 ppm PO after 20 days of exposure. No exposure-related changes in cell proliferation were observed in the liver. These studies demonstrate a clear concordance between the site and exposure concentration for tumor induction and those causing significant increases in cell proliferation in the rat nose.     

Early increase of peripheral B cell levels in kidney transplant recipients with CMV infection or reactivation

BACKGROUND: Cytomegalovirus (CMV) infection or reactivation is a frequent complication of renal transplantation. Diagnosis of these conditions relies on the detection of circulating antigen, or of specific IgM and/or IgG, which develop over several weeks. Evocative clinical features may be detected earlier, but lack specificity. Rapid and early changes in the partition of lymphocyte subsets could be an additional indication of pending CMV infection. METHODS: A systematic follow-up of peripheral B lymphocytes identified immunophenotypically by the determination of surface immunoglobulins (sIg), performed in 97 kidney transplant recipients, allowed to identify transient increases apparently predictive of CMV primo-infection or reactivation over the next 3 months. To better define the nature of these B cells, an extended investigation was performed for 14 prospective patients. In addition to surface Ig, membrane CD19, HLA-DR, and CD80 expression were explored. The cytoplasmic presence of mu, kappa, and lambda chains was also examined. B cell function was investigated using the ELISPOT technique, which allows an enumeration of the populations of IgG, IgA, and IgM secreting B cells. RESULTS: Retrospective analysis of the clinical outcome of the cohort of 97 patients evidenced that early transient increases in B cell levels were significantly (P<0.0001) associated with CMV infection. The same trend was noted in the smaller series of patients who benefited from a more extensive investigation of B cells, 10 of whom presented clinical or biological signs of CMV infection. Mature B cells, expressing surface Ig, CD19, DR, and CD80 are those presenting transient increases. No significant variation of preB (cmu+/kappalambda-) or activated (spot-forming) cells was evidenced in these patients. CONCLUSION: Individual examination of each patient's immune reconstitution profile allows to detect transient peaks of mature B cell during the initial immunosuppressive therapy, that appear to be predictive of oncoming CMV infection or reactivation.     

Morphologic dysplasia in de novo acute myeloid leukemia (AML) is related to unfavorable cytogenetics but has no independent prognostic relevance under the conditions of intensive induction therapy: results of a multiparameter analysis from the German AML Cooperative Group studies.

PURPOSE: On the basis of cytomorphology according to the French-American-British (FAB) classification, we evaluated the prognostic impact of dysplastic features and other parameters in de novo acute myeloid leukemia (AML). We also assessed the clinical significance of the recently introduced World Health Organization (WHO) classification for AML, which proposed dysplasia as a new parameter for classification. PATIENTS AND METHODS: We analyzed prospectively 614 patients with de novo AML, all of whom were diagnosed by central morphologic analysis and treated within the German AML Cooperative Group (AMLCG)-92 or the AMLCG-acute promyalocytic leukemia study. RESULTS: Patients with AML M3, M3v, or M4eo demonstrated a better outcome compared with all other FAB subtypes (P <.001); no prognostic difference was observed among other FAB subtypes. The presence or absence of dysplasia failed to demonstrate prognostic relevance. Other prognostic markers, such as age, cytogenetics, presence of Auer rods, and lactate dehydrogenase (LDH) level at diagnosis, all showed significant impact on overall and event-free survival in univariate analyses (P <.001 for all parameters tested). However, in a multivariate analysis, only cytogenetics (unfavorable or favorable), age, and high LDH maintained their prognostic impact. Dysplasia was not found to be an independent prognostic parameter, but the detection of trilineage dysplasia correlated with unfavorable cytogenetics. CONCLUSION: Our results indicate that cytomorphology and classification according to FAB criteria are still necessary for the diagnosis of AML but have no relevance for prognosis in addition to cytogenetics. Our results suggest that the WHO classification should be further developed by using cytogenetics as the main determinant of biology. Dysplastic features, in particular, have no additional impact on predicting prognosis when cytogenetics are taken into account.     

Proteoglycans on bone marrow endothelial cells bind and present SDF-1 towards hematopoietic progenitor cells.

Recognition events between hematopoietic progenitor cells (HPC) and bone marrow endothelial cells (BMEC) initiate homing of HPC to the bone marrow. The chemokine SDF-1 is present on BMEC and plays a crucial role in bone marrow engraftment. We studied the role of proteoglycans (PGs) on BMEC in binding and presentation of SDF-1. SDF-1 mRNA was present in three human BMEC cell lines. Competition experiments showed that 125I-SDF-1 alpha binding to the BMEC cell line 4LHBMEC was inhibited by heparins, heparan sulfate (HS) intestinal mucosa, chondroitin and dermatan sulfate (CS/DS), but not by HS bovine kidney. Pretreatment of 4LHBMEC with glycosaminoglycan (GAG)-degrading enzymes or sodium chlorate demonstrated that SDF-1 bound to both HSPGs and CS/DSPGs in a sulfation-dependent manner, as determined with an SDF-1 antibody recognizing the CXCR4-binding site. 4LHBMEC bound four-fold more SDF-1 than HUVEC. Isolated endothelial PGs did not bind SDF-1 in a filter or microplate-binding assay, suggesting the necessity of membrane association. In flow adhesion experiments, endothelial arrest of CXCR4+ KG-1 and not of CXCR4- KG-1a cells increased significantly when SDF-1 was presented on 4LHBMEC. In conclusion, SDF-1 is produced by BMEC and binds to the BMEC cell surface via HS and CS/DS-GAGs, thereby presenting its CXCR4 binding site to HPC contributing to their arrest.     

Associations of substance use, abuse, and dependence with subsequent suicidal behavior

General population survey data are used to disaggregate the associations of substance use disorders with suicide attempts in order to evaluate a number of hypotheses about the processes leading to these associations. Data are from the US National Comorbidity Survey (1990-1992). Discrete-time survival analysis is used to study the effects of retrospectively reported temporally prior substance use, abuse, and dependence in predicting first onset of suicidal behavior. Alcohol and drug use predict subsequent suicide attempts after controlling for sociodemographics and comorbid mental disorders. Previous use is not a significant predictor among current nonusers. Abuse and dependence are significant predictors among users for three of the 10 substances considered (alcohol, inhalants, and heroin). The number of substances used is more important than the types of substances used in predicting suicidal behavior. Disaggregation shows that the effects of use are largely on suicidal ideation and nonplanned attempts among ideators. In comparison, the effects of use on suicide plans and planned attempts among ideators are not significant. Clinicians need to be aware that current substance use, even in the absence of abuse or dependence, is a significant risk factor for unplanned suicide attempts among ideators.     

An investigation of human and rat liver microsomal mycophenolic acid glucuronidation: evidence for a principal role of UGT1A enzymes and species differences in UGT1A specificity.

Mycophenolic acid (MPA; 1,3-dihydro-4-hydroxy-6-methoxy-7-methyl-3-oxo-5-isobenzylfuranyl)-4-methyl-4-hexenoate), the active metabolite of the immunosuppressant prodrug, mycophenolate mofetil, undergoes glucuronidation to its 7-O-glucuronide as a primary route of metabolism. Because differences in glucuronidation may influence the efficacy and/or toxicity of MPA, we investigated the MPA UDP-glucuronosyltransferase (UGT) activities of human liver microsomes (HLMs) and rat liver microsomes with the goal of identifying UGTs responsible for MPA catalysis. HLMs (n = 23) exhibited higher average MPA glucuronidation rates (14.7 versus 6.0 nmol/mg/min, respectively, p < 0.001) and higher apparent affinity for MPA (K(m) = 0.082 mM versus 0.20 mM, p < 0.001) compared with rat liver microsomes. MPA UGT activities were reduced >80% in liver microsomes from Gunn rats. To identify the active enzymes, human and rat UGT1A enzymes were screened for MPA-glucuronidating activity. UGT1A9 was the only human liver-expressed UGT1A enzyme with significant activity and exhibited both high affinity (K(m) = 0.077 mM) and high activity (V(max) = 28 nmol x min(-1) x mg(-1)). Spearman correlation analyses revealed a stronger relationship between HLM MPA UGT activities and 1A9-like content (r(2) = 0.79) relative to 1A1 (r(2) = 0.20), 1A4-like (r(2) = 0.22), and 1A6 (r(2) = 0.41) protein. A different profile was observed for rat with three active liver-expressed UGT1A enzymes: 1A1 (medium affinity/capacity), 1A6 (low affinity/medium capacity), and 1A7 (high affinity/capacity). Our data suggest that UGT1A enzymes are the major contributors to hepatic MPA metabolism in both species, but 1A9 is dominant in human, whereas 1A1 and 1A7 are likely the principal mediators in control rat liver. This information should be useful for interpretation of MPA pharmacokinetic and toxicity data in clinical and animal studies.     

Occupancy of striatal and extrastriatal dopamine D2/D3 receptors by olanzapine and haloperidol.

There have been conflicting reports as to whether olanzapine produces lower occupancy of striatal dopamine D(2)/D(3) receptor than typical antipsychotic drugs and preferential occupancy of extrastriatal dopamine D(2)/D(3) receptors. We performed [(18)F] fallypride PET studies in six schizophrenic subjects treated with olanzapine and six schizophrenic subjects treated with haloperidol to examine the occupancy of striatal and extrastriatal dopamine receptors by these antipsychotic drugs. [(18)F] setoperone PET studies were performed in seven olanzapine-treated subjects to determine 5-HT(2A) receptor occupancy. Occupancy of dopamine D(2)/D(3) receptors by olanzapine was not significantly different from that seen with haloperidol in the putamen, ventral striatum, medial thalamus, amygdala, or temporal cortex, that is, 67.5-78.2% occupancy; olanzapine produced no preferential occupancy of dopamine D(2)/D(3) receptors in the ventral striatum, medial thalamus, amygdala, or temporal cortex. There was, however, significantly lower occupancy of substantia nigra/VTA dopamine D(2)/D(3) receptors in olanzapine-treated compared to haloperidol-treated subjects, that is, 40.2 vs 59.3% (p=0.0014, corrected for multiple comparisons); in olanzapine-treated subjects, the substantia nigra/VTA was the only region with significantly lower dopamine D(2)/D(3) receptor occupancy than the putamen, that is, 40.2 vs 69.2% (p<0.001, corrected for multiple comparison). Occupancy of 5-HT(2A) receptors was 85-93% in the olanzapine- treated subjects. The results of this study demonstrated that olanzapine does not produce preferential occupancy of extrastriatal dopamine D(2)/D(3) receptors but does spare substantia nigra/VTA receptors. Sparing of substantia nigra/VTA dopamine D(2)/D(3) receptor occupancy may contribute to the low incidence of extrapyramidal side effects in olanzapine-treated patients.