Using multi-country household surveys to understand who provides reproductive and maternal health services in low- and middle-income countries: a critical appraisal of the Demographic and Health Surveys.

OBJECTIVE: The Demographic and Health Surveys (DHS) are a vital data resource for cross-country comparative analyses. This study is part of a set of analyses assessing the types of providers being used for reproductive and maternal health care across 57 countries. Here, we examine some of the challenges encountered using DHS data for this purpose, present the provider classification we used, and provide recommendations to enable more detailed and accurate cross-country comparisons of healthcare provision. METHODS: We used the most recent DHS surveys between 2000 and 2012; 57 countries had data on family planning and delivery care providers and 47 countries had data on antenatal care. Every possible response option across the 57 countries was listed and categorised. We then developed a classification to group provider response options according to two key dimensions: clinical nature and profit motive. RESULTS: We classified the different types of maternal and reproductive healthcare providers, and the individuals providing care. Documented challenges encountered during this process were limitations inherent in household survey data based on respondents' self-report; conflation of response options in the questionnaire or at the data processing stage; category errors of the place vs. professional for delivery; inability to determine whether care received at home is from the public or private sector; a large number of negligible response options; inconsistencies in coding and analysis of data sets; and the use of inconsistent headings. CONCLUSIONS: To improve clarity, we recommend addressing issues such as conflation of response options, data on public vs. private provider, inconsistent coding and obtaining metadata. More systematic and standardised collection of data would aid international comparisons of progress towards improved financial protection, and allow us to better characterise the incentives and commercial nature of different providers.

A role for smad6 in development and homeostasis of the cardiovascular system.

Smad proteins are intracellular mediators of signalling initiated by Tgf-betasuperfamily ligands (Tgf-betas, activins and bone morphogenetic proteins (Bmps)). Smads 1, 2, 3, 5 and 8 are activated upon phosphorylation by specific type I receptors, and associate with the common partner Smad4 to trigger transcriptional responses. The inhibitory Smads (6 and 7) are transcriptionally induced in cultured cells treated with Tgf-beta superfamily ligands, and downregulate signalling in in vitro assays. Gene disruption in mice has begun to reveal specific developmental and physiological functions of the signal-transducing Smads. Here we explore the role of an inhibitory Smad in vivo by targeted mutation of Madh6 (which encodes the Smad6 protein). Targeted insertion of a LacZ reporter demonstrated that Smad6 expression is largely restricted to the heart and blood vessels, and that Madh6 mutants have multiple cardiovascular abnormalities. Hyperplasia of the cardiac valves and outflow tract septation defects indicate a function for Smad6 in the regulation of endocardial cushion transformation. The role of Smad6 in the homeostasis of the adult cardiovascular system is indicated by the development of aortic ossification and elevated blood pressure in viable mutants. These defects highlight the importance of Smad6 in the tissue-specific modulation of Tgf-beta superfamily signalling pathways in vivo.

Targeted deletion of the tub mouse obesity gene reveals that tubby is a loss-of-function mutation.

The mouse tubby phenotype is characterized by maturity-onset obesity accompanied by retinal and cochlear degeneration. A positional cloning effort to find the gene responsible for this phenotype led to the identification of tub, a member of a novel gene family of unknown function. A splice defect mutation in the 3' end of the tub gene, predicted to disrupt the C terminus of the Tub protein, has been implicated in the genesis of the tubby phenotype. It is not clear, however, whether the Tub mutant protein retains any biological activity, or perhaps has some dominant function, nor is it established that the tubby mutation is itself responsible for all of the observed tubby phenotypes. To address these questions, we generated tub-deficient mice and compared their phenotype to that of tubby mice. Our results demonstrate that tubby is a loss-of-function mutation of the tub gene and that loss of the tub gene is sufficient to give rise to the full spectrum of tubby phenotypes. We also demonstrate that loss of photoreceptors in the retina of tubby and tub-deficient mice occurs by apoptosis. In addition, we show that Tub protein expression is not significantly altered in the ob, db, or melanocortin 4 receptor-deficient mouse model of obesity.

Sleep disturbance in mild to moderate Alzheimer's disease.

BACKGROUND AND PURPOSE: To determine the prevalence of sleep disturbance in a memory clinic population of Alzheimer's disease (AD) patients and identify its clinical correlates. PATIENTS AND METHODS: Data from 215 attendees at a memory clinic, who were diagnosed with Alzheimer's disease, were examined. This included data from cognitive, functional and neuropsychological assessments. Sleep disturbance was determined using the question about diurnal rhythm disturbance on the BEHAVE-AD questionnaire. Two groups, with and without sleep disturbance, were compared. Group differences were analysed using univariate analysis and stepwise logistic regression analysis. RESULTS: The prevalence of sleep disturbance in this sample was 24.5%. The BEHAVE-AD 'aggressiveness' (P=0.009) and 'global rating' (P=0.029) (a measure of global impact of behavioural disturbance) were found to be significant predictors of sleep disturbance in AD. CONCLUSIONS: Sleep disturbance in AD is associated with other behavioural symptoms, notably aggressiveness. Sleep disturbance in AD has significant impact on the patient and/or caregiver. Consideration of co-morbid behavioural symptoms may aid the clinician in choosing a suitable treatment for sleep disturbance in AD.

Induction of neuropeptide Y gene expression in the dorsal medial hypothalamic nucleus in two models of the agouti obesity syndrome.

Dominant mutations at the agouti locus induce several phenotypic changes in the mouse including yellow pigmentation (phaeomelanization) of the coat and adult-onset obesity. Nonpigmentary phenotypic changes associated with the agouti locus are due to ectopic expression of the agouti-signaling protein (ASP), and the pheomelanizing effects on coat color are due to ASP antagonism of alpha-MSH binding to the melanocyte MC1 receptor. Recently it has been demonstrated that pharmacological antagonism of hypothalamic melanocortin receptors or genetic deletion of the melanocortin 4 receptor (MC4-R) recapitulates aspects of the agouti obesity syndrome, thus establishing that chronic disruption of central melanocortinergic signaling is the cause of agouti-induced obesity. To learn more about potential downstream effectors involved in these melanocortinergic obesity syndromes, we have examined expression of the orexigenic peptides galanin and neuropeptide Y (NPY), as well as the anorexigenic POMC in lethal yellow (A(y)), MC4-R knockout (MC4-RKO), and leptin-deficient (ob/ob) mice. No significant changes in galanin or POMC gene expression were seen in any of the obese models. In situ hybridizations using an antisense NPY probe demonstrated that in obese A(y) mice, arcuate nucleus NPY mRNA levels were equivalent to that of their C57BL/6J littermates. However, NPY was expressed at high levels in a new site, the dorsal medial hypothalamic nucleus (DMH). Expression of NPY in the DMH was also seen in obese MC4-RKO homozygous (-/-) mice, but not in lean heterozygous (+/-) or wild type (+/+) control mice. This identifies the DMH as a brain region that is functionally altered by the disruption of melanocortinergic signaling and suggests that this nucleus, possibly via elevated NPY expression, may have an etiological role in the melanocortinergic obesity syndrome.

The use of a wild-type dihydrofolate reductase-encoding cDNA as a dominant selectable marker and induction of expression by methotrexate.

The cDNA (DHFR) encoding the wild-type (wt) dihydrofolate reductase (DHFR) was used as a dominant selectable marker in the transfection of murine hybridoma Sp2/0-Ag14 cells by protoplast fusion. The initial clones contained 100-400 copies of integrated plasmid DNA, and the high level of wt DHFR protein produced enabled the cells to survive the drug selection at 100 nM methotrexate (MTX). The expression of the gene of interest was several fold higher than when the mutant DHFR with decreased MTX binding was used as the selection marker, presumably because the clones were more sensitive to the stress induced by MTX. When the clones were propagated at higher concentrations of MTX, expression of both DHFR and the gene of interest increased. This induction is freely reversible, and we have shown that it is controlled at the transcriptional level, by nuclear run-off transcription assays.

Case reports: pseudomelanosis duodeni: association with systemic hypertension.

Two male patients with mild gastrointestinal bleeding had peculiar dark pigmentation of their duodenum on upper endoscopy. These pigmented lesions were still present 3 months after the original endoscopy and after resolution of all other mucosal lesions. Both patients had other medical problems, including hypertension. They have been on multiple antihypertensive medications for many years. Biopsies of these duodenal lesions showed the pigment to be present inside the macrophages found in the lamina propria and in between the epithelial cells. Electron microscopy revealed a lysosomal localization of this pigment. This melanin-like pigment proved to contain varying amounts of iron, sulfur, and calcium. This pigmentation is closely associated with systemic hypertension, even in the pediatric population.

Bilateral electrocochleographic findings in unilateral Menière's disease.

At present, electrocochleography is the only proven investigation that can demonstrate objectively the presence of endolymphatic hydrops. The electrophysiologic recordings in response to sound stimuli show an enhancement of the negative summating potential in these cases. It is well established that patients with unilateral Meniere's disease have a high likelihood of development of the disease bilaterally in the fullness of time. Using transtympanic electrocochleography in 40 patients who manifested unilateral clinical Meniere's disease, we have recorded bilateral abnormalities indicative of endolymphatic hydrops in 35% of cases. The early recognition of incipient Meniere's disease in the asymptomatic contralateral ear of a patient with known unilateral disease has obvious profound implications for patient management.

Hearing loss fluctuating with blood sugar levels in Ménière's disease.

An unusual case of a patient with bilateral Ménière's disease is described whose disease presented in the second ear as a sensorineural hearing loss which fluctuated with the patient's level of blood glucose. The literature concerning the role of abnormal glucose metabolism in Ménière's disease is reviewed and the investigation and management of this patient's condition is discussed.

Apolipoprotein E promoter polymorphisms (-491A/T and -427T/C) and Alzheimer's disease: no evidence of association in the Irish population.

BACKGROUND: Alzheimer's Disease (AD) is a progressive neurodegenerative disorder with as yet poorly understood aetiology. Both environmental and genetic factors have been implicated as predisposing factors. The APOE e4 allele is an established genetic susceptibility factor for AD for several populations including the Irish. Polymorphisms (-491A/T and -427T/C) at the promoter region of the APOE gene are postulated to affect the expression of the gene through differential binding of transcription factors. AIMS: Two APOE promoter polymorphisms (-491A/T and -427T/C) are examined for possible association with AD. METHODS: Using a case-control study design, a sample of 112 Irish late onset Alzheimer's (LOAD) patients and 107 ethnically matched controls were investigated for association with the above polymorphisms. CONCLUSIONS: No evidence of association between any of the examined markers and AD was observed. Haplotype analysis using markers -491A/T and -427T/C in conjunction with the APOE (Hha I) polymorphism revealed significant associations of three haplotypes with AD. However, this association was mainly due to the highly significant association of the APOE e4 allele with AD and not of the promoter variants.

NGO management and health care financing approaches in the Eastern Democratic Republic of the Congo.

The role of cost-sharing in health care is a crucial, yet contentious issue. In conflict situations, cost-sharing becomes even more controversial as health and other institutions are failing. In such situations, NGOs manage health programmes which aim to aid populations in crisis and improve or at least sustain a deteriorating health system. This study looks at the issue of cost-sharing in the wider context of utilization rates and management approaches of three NGOs in the chronic, high-mortality crisis of the eastern DRC. Approaches to increase access to health care were found to exist, yet cost-recovery, even on the basis of maximum utilization rates, would only partially sustain the health system in the eastern DRC. Factors external to the direct management of NGO health programs, such as the wider economic and security situation, local management structures, and international donor policies, need to be taken into account for establishing more integrated management and financing approaches.

The clinical dementia rating sum of box score in mild dementia.

BACKGROUND: Making an early diagnosis of dementia is becoming increasingly important, but is difficult in practice. The Clinical Dementia Rating (CDR) scale is a widely used dementia staging instrument, yielding a global score and a summated score (sum of box score). This study examines the utility of the CDR sum of box score, rather than the CDR global score, in making a diagnosis of early dementia. OBJECTIVE: To determine whether the CDR sum of box score is predictive of an ICD-10 diagnosis of dementia in cases with mild cognitive deficits. METHODS: Clinical data recorded on our Memory Clinic database were examined for all patients seen over a 6-year period. Data were extracted from 276 first visits in which patients had scored 0.5 using the CDR global score. We examined the relationship between CDR sum of box score and consensus diagnosis of dementia using logistic regression. RESULTS: We found that increased CDR sum of box score was significantly associated with a higher probability of being assigned an ICD-10 diagnosis of dementia (p < 0.001). The odds ratio for the coefficient of CDR sum of box was 2.3 (95% CI 1.7-3.1), indicating that the likelihood of being diagnosed as having dementia increased by a factor of 2.3 for every point increase on the CDR sum of box score. CONCLUSION: These findings indicate that the CDR sum of box score provides additional information to the CDR global score in mild cases. The CDR sum of box score is a helpful indicator in making/excluding a diagnosis of dementia in people with mild cognitive deficits.

Colonic ganglioneuroma presenting as filiform polyposis.

A 74-year-old man had an isolated colonic ganglioneuroma presenting endoscopically as filiform polyposis coli. Extensive workup failed to show either von Recklinghausen's neurofibromatosis or multiple endocrine neoplasia (MEN) 2b. We discuss the clinical implications of this and review the literature.

Targeted disruption of the melanocortin-4 receptor results in obesity in mice.

The melanocortin-4 receptor (MC4-R) is a G protein-coupled, seven-transmembrane receptor expressed in the brain. Inactivation of this receptor by gene targeting results in mice that develop a maturity onset obesity syndrome associated with hyperphagia, hyperinsulinemia, and hyperglycemia. This syndrome recapitulates several of the characteristic features of the agouti obesity syndrome, which results from ectopic expression of agouti protein, a pigmentation factor normally expressed in the skin. Our data identify a novel signaling pathway in the mouse for body weight regulation and support a model in which the primary mechanism by which agouti induces obesity is chronic antagonism of the MC4-R.