Validated tools to identify common mental disorders in the perinatal period: A systematic review of systematic reviews.

BACKGROUND: Uncertainty remains regarding the validity of screening tools to detect common mental disorders (CMDs) during perinatal periods. This umbrella review aims to provide an up-to-date summary of psychometric properties of tools for the identification of perinatal CMDs. METHODS: Reviews were identified via Ovid MEDLINE, PsychINFO, EMBASE, Global Health and Cochrane Database of Systematic Reviews electronic databases with no date or language restriction. Pooled sensitivity and specificity estimates and ranges were extracted and summarised using forest plots. Quality assessment was conducted using Measurement Tool to Assess Systematic Reviews (AMSTAR-2). RESULTS: Of 7,891 papers identified, 31 reviews met inclusion criteria. 76 screening tools were identified; most frequently validated were Edinburgh Postnatal Depression Scale (EPDS) (n = 28 reviews), Beck's Depression Inventory (BDI) (n = 13 reviews) and Patient Health Questionnaire (PHQ) (n = 12 reviews). Forest plots demonstrated a pattern of decreasing sensitivity and increasing specificity with increasing cut-off scores. Sub-group analysis of data extracted from low quality reviews demonstrated wider 95% CIs and overall lower specificity. Validity also varied according to ethnicity, socio-economic background and age. LIMITATIONS: Despite a low Covered Corrected Area (CCA) score the primary studies included within reviews overlapped; therefore we were unable perform meta-analysis. CONCLUSIONS: The evidence suggests that the EPDS, PHQ and BDI are useful across a range of diverse settings but the context of tool application is a key factor determining validity. This review highlights that utilizing screening tools in clinical practice is complex and requires careful consideration of the population, context, and health system it will be used in.

Public-health impact of accelerated measles control in the WHO African Region 2000-03.

BACKGROUND: In 2000, the WHO African Region adopted a plan to accelerate efforts to lower measles mortality with the goal of decreasing the number of measles deaths to near zero. By June, 2003, 19 African countries had completed measles supplemental immunisation activities (SIA) in children aged 9 months to 14 years as part of a comprehensive measles-control strategy. We assessed the public-health impact of these control measures by use of available surveillance data. METHODS: We calculated percentage decline in reported measles cases during 1-2 years after SIA, compared with 6 years before SIA. On the basis of data from 13 of the 19 countries, we assumed that the percentage decline in measles deaths equalled that in measles cases. We also examined data on routine and SIA measles vaccine coverage, measles case-based surveillance, and suspected measles outbreaks. FINDINGS: Between 2000 and June, 2003, 82.1 million children were targeted for vaccination during initial SIA in 12 countries and follow-up SIA in seven countries. The average decline in the number of reported measles cases was 91%. In 17 of the 19 countries, measles case-based surveillance confirmed that transmission of measles virus, and therefore measles deaths, had been reduced to low or very low rates. The total estimated number of deaths averted in the year 2003 was 90,043. Between 2000 and 2003 in the African Region as a whole, we estimated that the percentage decline in annual measles deaths was around 20% (90,043 of 454,000). INTERPRETATION: The burden of measles in sub-Saharan Africa can be reduced to very low levels by means of appropriate strategies, resources, and personnel.

Intravenous immunoglobulin in acute rheumatic fever: a randomized controlled trial.

BACKGROUND: Acute rheumatic fever (ARF) remains the leading cause of acquired heart disease in children worldwide. No therapeutic agent has been shown to alter the clinical outcome of the acute illness. Immunological mechanisms appear to be involved in the pathogenesis of ARF. Intravenous immunoglobulin (IVIG), a proven immunomodulator, may benefit cardiac conditions of an autoimmune nature. We investigated whether IVIG modified the natural history of ARF by reducing the extent and severity of carditis. METHODS AND RESULTS: This prospective, double-blind, randomized, placebo-controlled trial evaluated IVIG in patients with a first episode of rheumatic fever, stratifying patients by the presence and severity of carditis before randomization. Patients were randomly allocated to receive 1 g/kg IVIG on days 1 and 2 and 0.4 g/kg on days 14 and 28, or they received a placebo infusion. Clinical, laboratory, and echocardiographic evaluation was performed at 0, 2, 4, 6, 26, and 52 weeks. Fifty-nine patients were treated, of whom 39 had carditis (including 4 subclinical) and/or migratory polyarthritis (n=39). There was no difference between groups in the rate of normalization of the erythrocyte sedimentation rate or acute-phase proteins at the 6-week follow-up. On echocardiography, 59% in the IVIG group and 69% in the placebo group had carditis at baseline. There was no significant difference in the cardiac outcome, including the proportion of valves involved, or in the severity of valvar regurgitation at 1 year. At 1 year, 41% of the IVIG and 50% of the placebo group had carditis. CONCLUSIONS: IVIG did not alter the natural history of ARF, with no detectable difference in the clinical, laboratory, or echocardiographic parameters of the disease process during the subsequent 12 months.

Regulation of mouse p45 NF-E2 transcription by an erythroid-specific GATA-dependent intronic alternative promoter.

The erythroid-enriched transcription factor NF-E2 is composed of two subunits, p45 and p18, the former of which is mainly expressed in the hematopoietic system. We have isolated and characterized the mouse p45 NF-E2 gene; we show here that, similar to the human gene, the mouse gene has two alternative promoters, which are differentially active during development and in different hematopoietic cells. Transcripts from the distal promoter are present in both erythroid and myeloid cells; however, transcripts from an alternative proximal 1b promoter, lying in the first intron, are abundant in erythroid cells, but barely detectable in myeloid cells. During development, both transcripts are detectable in yolk sac, fetal liver, and bone marrow. Transfection experiments show that proximal promoter 1b has a strong activity in erythroid cells, which is completely dependent on the integrity of a palindromic GATA-1 binding site. In contrast, the distal promoter 1a is not active in this assay. When the promoter 1b is placed 3' to the promoter 1a and reporter gene, in an arrangement that resembles the natural one, it acts as an enhancer to stimulate the activity of the upstream promoter la.

Outbreak of coccidioidomycosis in Washington state residents returning from Mexico.

In July 1996 the Washington State Department of Health (Seattle) was notified of a cluster of a flulike, rash-associated illness in a 126-member church group, many of whom were adolescents. The group had recently returned from Tecate, Mexico, where members had assisted with construction projects at an orphanage. After 1 member was diagnosed with coccidioidomycosis, we initiated a study to identify further cases. We identified 21 serologically confirmed cases of coccidioidomycosis (minimum attack rate, 17%). Twenty cases (95%) occurred in adolescents, and 13 patients (62%) had rash. Sixteen symptomatic patients saw 19 health care providers; 1 health care provider correctly diagnosed coccidioidomycosis. Coccidioides immitis was isolated from soil samples from Tecate by use of the intraperitoneal mouse inoculation method. Trip organizers were unaware of the potential for C. immitis infection. Travelers visiting regions where C. immitis is endemic should be made aware of the risk of acquiring coccidioidomycosis, and health care providers should be familiar with coccidioidomycosis and its diagnosis.

Intermediate filament interactions can be altered by HSP27 and alphaB-crystallin.

HSP27 and alphaB-crystallin are both members of the small heat shock protein family. alphaB-crystalllin has been proposed to modulate intermediate filaments and recently a mutation in alphaB-crystallin has been identified as the genetic basis of desmin related myopathy. This disease is characterised in its pathology by aggregates of intermediate filaments associated with alphaB-crystallin. Here we report that HSP27 like alphaB-crystallin is associated with glial fibrillary acidic protein and vimentin intermediate filament networks in unstressed U373MG astrocytoma cells. HSP27 is also associated with keratin filaments in MCF7 cells, indicating that this association is not restricted to a particular intermediate filament type. The association of sHSPs with both the soluble and filamentous intermediate filament fractions of U373 cells was demonstrated biochemically. Heat shock or drug treatments induced a co-collapse of intermediate filaments and associated small heat shock proteins. These data show that the presence of HSP27 or alphaB-crystallin could not prevent filament collapse and suggest that the purpose of this association is more than just filament binding. Indeed, in U373MG cells the intermediate filament association with small heat shock proteins is similar to that observed for another protein chaperone, HSC70. In order to discern the effect of different chaperone classes on intermediate filament network formation and maintenance, several in vitro assays were assessed. Of these, falling ball viscometry revealed a specific activity of small heat shock proteins compared to HSC70 that was apparently inactive in this assay. Intermediate filaments form a gel in the absence of small heat shock proteins. In contrast, inclusion of alphaB-crystallin or HSP27 prevented gel formation but not filament assembly. The transient transfection of GFAP into MCF7 cells was used to show that the induction of a completely separate network of intermediate filaments resulted in the specific association of the endogenous HSP27 with these new GFAP filaments. These data lead us to propose that one of the major functions of the association of small heat shock proteins with intermediate filaments is to help manage the interactions that occur between filaments in their cellular networks. This is achieved by protecting filaments against those non-covalent interactions that result when they come into very close proximity as seen from the viscosity experiments and which have the potential to induce intermediate filament aggregation as seen in some disease pathologies.

Immortalization of neuro-endocrine cells from adrenal tumors arising in SV40 T-transgenic mice.

Pheochromocytomas are adrenal medullary tumors which arise from the transformation of neural crest-derived cells. In the course of studies of mice transgenic for an SV40 T-gene ectopically expressed in the adrenal medulla, we observed the occurrence of large, mainly bilateral tumors in a high proportion of transgenic animals. From these tumors we established immortalized cell lines which grow in vitro at 32 degrees C (the permissive temperature for the tsA58 T-protein encoded by the transgene), but not at 38 C. These cells demonstrate characteristics of both neuronal (160 kd neurofilament) and endocrine (chromogranins) cells. The expression of Mash-1 and ret supports their initial characterization as early bipotential neuro-endocrine progenitors.

Expression in hematopoietic cells of GATA-1 transcripts from the alternative "testis" promoter during development and cell differentiation.

GATA-1 is a transcription factor expressed both in the hematopoietic system and in the Sertoli cells of the testis, and is essential for correct erythropoiesis. Hematopoietic and Sertoli cells transcribe GATA-1 from two different promoters: the proximal (erythroid) is active in hematopoietic cells; the distal (testis) is active in Sertoli cells. We investigated by RT-PCR the possibility that GATA-1 might be transcribed from the testis promoter also in hematopoietic cells. Testis promoter-derived transcripts are present at low levels in vivo at all stages of hematopoietic development. Purified multipotent progenitors, fractionated into populations expressing low or high levels of GATA-1, do not contain any "testis" transcripts. However, when grown in vitro, they rapidly express GATA-1 from the testis promoter in the presence of Erythropoietin (Epo) but not in that of other growth factors. This result reflects an Epo-dependent differentiation event, rather than a direct effect of Epo. Indeed, immortalized progenitor cell lines which respond to both Epo and SCF, continue to express testis-derived transcripts when switched from Epo to SCF.

Molecular heterogeneity of regulatory elements of the mouse GATA-1 gene.

The GATA-1 gene encodes a transcription factor expressed in early multipotent haemopoietic progenitors, in more mature cells of the erythroid, megakaryocytic and other lineages, but not in late myeloid precursors; its function is essential for the normal development of the erythroid and megakaryocytic system. To define regulatory elements of the mouse GATA-1 gene, we mapped DNaseI-hypersensitive sites in nuclei of erythroid and haemopoietic progenitor cells. Five sites were detected. The two upstream sites, site 1 and site 2, represent a new and a previously defined erythroid enhancer respectively. The site 1 enhancer activity depends both on a GATA-binding site (also footprinted in vivo) and on several sites capable of binding relatively ubiquitous factors. A DNA fragment encompassing site 1, placed upstream of a GATA-1 minimal promoter, is able to drive expression of a simian virus 40 (SV40) T-antigen in the yolk sac, but not bone-marrow cells, obtained from mice transgenic for this construct, allowing in vitro establishment of immortalized yolk-sac cells. A similar construct including site 2, instead of site 1, and previously shown to be able to immortalize adult marrow cells is not significantly active in yolk-sac cells. Sites 4 and 5, located in the first large intron, have no enhancer activity; they include a long array of potential Ets-binding sites. MnlI restriction sites, overlapping some of the Ets sites, are highly accessible, in intact nuclei, to MnlI. Although these sites are present in all GATA-1-expressing cells studied, they are the only strong sites detectable in FDCP-mix multipotent progenitor cells, most of which do not yet express GATA-1. The data indicate that appropriate GATA-1 regulation may require the co-operation of different regulatory elements acting at different stages of development and cell differentiation.

Immortalization of multipotent growth-factor dependent hemopoietic progenitors from mice transgenic for GATA-1 driven SV40 tsA58 gene.

The transcription factor GATA-1 is required for the normal development of erythroid cells. GATA-1 is also expressed in other hemopoietic cells, suggesting that it might be initially activated in a multipotent progenitor. To immortalize GATA-1-expressing progenitors, we generated mice transgenic for a thermosensitive SV40 T gene, driven by the GATA-1 promoter-enhancer. Immortalized marrow cells grow in culture at 32 degrees C but not at 38 degrees C, and are dependent on erythropoietin (Epo) or interleukin 3 (IL-3). Epo dependent cells express hemoglobin, high levels of GATA-1, GATA-2 and NF-E2 p45 mRNAs, and are positive for stem cell antigen 2 (Sca-2) and the early myeloid marker ER-MP12. IL-3 dependent cells can be derived from Epo dependent lines, and are hemoglobin-, Sca-2- and ER-MP12-negative, have low GATA-1 and NF-E2 p45 mRNA levels, and express myeloid markers Mac-1, F4/80 and Gr-1. Brief treatment of Epo dependent cells with myeloid growth factors (plus Epo) leads to the induction of Mac-1, F4/80 and Gr-1, concomitant with the disappearance from most cells of Sca-2, ER-MP12 and GATA-1 driven T antigen nuclear expression. Thus, the immortalized Epo dependent cells have the property of a progenitor capable of differentiation towards either the erythroid or myeloid lineages. These cells initiate transcription of a proportion of GATA-1 RNA molecules at an upstream promoter, previously known to be expressed only in testis cells.

Retroviral immortalization of phagocytic and dendritic cell clones as a tool to investigate functional heterogeneity.

We have developed a method to generate immortalized phagocytic and dendritic cell clones from various mouse tissues such as spleen, thymus, brain and bone marrow. The clones were phenotypically characterized and shown to retain the ability to respond to immune or inflammatory signals, e.g., IFN-gamma. Functional cytokine activity and nitric oxide production were maintained in activated macrophages, microglial and dendritic cell clones. Immune functions, such as antigen presentation was exhibited by all clones whereas tissue-specific properties such as the ability to respond to corticotropin-releasing hormone and produce beta-endorphin was shown in microglial cell clones but not in macrophage cell clones, indicating that heterogeneity of cells of the mononuclear-phagocytic lineage can be maintained in vitro after the immortalization procedure. Moreover, the continuous proliferation of the clones could be inhibited by various stimuli and further differentiation of the cells could be achieved in vitro.

The regulation of IgG4. 1. An immunoassay to detect bee venom specific IgG4 subclass levels.

Serum IgG consists of 4 subclasses designated IgG1-4. IgG subclasses have differing structures and different functions. The levels of antigen specific immunoglobulin in each of the subclasses is difficult to quantitate accurately but may be of significant diagnostic and therapeutic value. IgG4 constitutes approximately 4% of total IgG level in the serum. We describe an immunoassay which is highly sensitive and specific for IgG4 directed against bee venom. The assay can be performed in a routine diagnostic laboratory enhancing its value as a clinical tool. It is potentially useful in identifying patients who fail to respond to standard immunotherapy with bee venom. This immunoassay format can also be adapted to other antigens.

T cell receptor alpha-chain polymorphic allele frequencies in Caucasians and Polynesians.

Restriction length polymorphisms in the variable and constant regions of the T cell receptor alpha-chain were examined in 42 Caucasians, 29 Maoris and 27 Pacific Islanders. Southern blots of Taq I digested DNA were hybridized with the T cell receptor alpha-chain probe pY14. Our results confirm that a 1.4 kb T cell receptor alpha chain-Taq 1 band is allelic to a 0.5 kb band. A significant difference in the frequency of the 1.4 and 0.5 kb alleles of the variable region of the alpha-chain was detected in Caucasians when compared with Maoris or Pacific Islanders (P < 0.0001). No differences in the frequency of the 2.0 and 7.0 kb alleles of the constant region gene were detected between any of the racial groups. These data may be relevant to ethnic differences in susceptibility to immune disorders.

Distribution of cells bearing "rheumatic" antigens in peripheral blood of patients with rheumatic fever/rheumatic heart disease.

Cell surfaces of some peripheral blood cells from individuals with a history of rheumatic fever/rheumatic heart disease (RHD) have been demonstrated by the use of monoclonal antibodies to be antigenically distinct from the majority of the population. Our study examines the distribution of cells bearing these "rheumatic" antigens in 23 subjects with rheumatic fever/RHD of Maori, Polynesian and Caucasian ancestry and 182 members of their families (rheumatic fever/RHD families) as well as in 46 members of families in which no member had been demonstrated to have had rheumatic fever/RHD (control families). Mononuclear cells from the blood of all cooperating family members were prepared and non-T cells isolated by sheep red blood cell rosette depletion. The binding of monoclonal antibodies 83S19.23 and D8103 to non-T cells was measured using an immunoperoxidase technique. Subjects with rheumatic fever/RHD had a significantly higher proportion of cells binding the antibodies than the unaffected members of all families. Unaffected members of rheumatic fever/RHD families had significantly higher levels of such rheumatic cells than control families. An increase in the proportion of rheumatic cells with age was noted in unaffected members of rheumatic fever/RHD families but not in rheumatic fever/RHD subjects of control families. A level of 13% 83S19.23 positive non-T cells optimally discriminated between rheumatic and nonrheumatic individuals. The relative risk for rheumatic fever/RHD with 13% or greater positive cells was 9.48. The negative predictive value of having less than 13% positive cells was 98.3%. In the population studied, 83S19.23 seems especially capable of identifying those with low risk for rheumatic fever/RHD.

Cell surface markers and cellular immune response associated with rheumatic heart disease: complex segregation analysis.

A series of functional and cell surface markers associated with a significantly increased risk of rheumatic heart disease were analyzed for the contribution of genetic factors in their presence. Peripheral blood lymphocytes from nine large kindreds from the New Zealand Maori, Polynesian, and Caucasian populations were isolated, purified, and evaluated with lymphocyte surface markers (monoclonals 83S.19.23 and D8103), as well as studied for blastogenic response to a purified group A streptococcal extracellular product, blastogen A. Segregation analysis of blastogenic response and percent of cells positive for these cell surface markers was consistent with genetic control by single major genes; however, the contribution by polygenes varied by marker, indicating heterogeneity of genetic control of identification of cell surface glycoproteins and blastogenic response to streptococcal products.

Morphological abnormalities in the lymphocytes of patients with the Wiskott-Aldrich syndrome.

Lymphocytes from 18 patients with the Wiskott-Aldrich Syndrome (WAS) were examined by scanning electron microscopy (SEM). Most peripheral blood lymphocytes from normal individuals are covered with slender microvillus projections, but a large proportion of lymphocytes from WAS patients were found to be relatively devoid of microvilli. A lymphocyte morphology scoring system was developed to quantify the density of microvilli: Grade 4 classified those lymphocytes with greater than 75% of the surface covered with microvilli with progressive decrements to grade 1, which were those without microvilli. The mean lymphocyte morphology score of eight normal individuals was 3.62 +/- .22. The mean lymphocyte score of WAS patients was substantially lower (2.89 +/- .27, P less than .001). In addition, WAS lymphocytes often were qualitatively abnormal, with short, blunted microvilli. These morphological criteria were used to diagnose WAS from the cord blood lymphocytes of one "at-risk" patient. Thus, WAS is the first primary immunodeficiency in which morphological abnormalities have been identified that can aid in diagnosis.