Village health-workers and GOBI-FFF. An evaluation of a rural programme

Growth monitoring, oral rehydration, breast-feeding and immunisation--female education, family spacing and food supplementation (GOBI-FFF) are a selective package of World Health Organisation primary health care strategies recommended by UNICEF. Changes over a 1-year period in the implementation of the components of GOBI-FFF were investigated in a rural village in Ciskei to detect any changes associated with a newly modified village health-worker (VHW) programme. A baseline survey was conducted before the introduction of a modified VHW programme and a second survey took place a year later. The principles of GOBI-FFF were already familiar to and have since been increasingly practised by the community and health personnel. Breast-feeding is widespread, most carers know how to make oral rehydration solution and most children have a 'Road to Health' card and are being weighed regularly. However, malnutrition remains a major problem and the food supplementation programme is operating poorly. The high coverage of the community by the village health-workers and the clinic suggest that these two channels should be used more intensively to strengthen the GOBI-FFF programme in the area.     

Prenatal diagnosis of the fragile X syndrome: loss of mutation owing to a double recombinant or gene conversion event at the FMR1 locus.

The fragile X syndrome, an X linked mental retardation syndrome, is caused by an expanded CGG repeat in the first exon of the FMR1 gene. In patients with an expanded repeat the FMR1 promoter is methylated and, consequently, the gene is silenced and no FMR1 protein (FMRP) is produced, thus leading to the clinical phenotype. Here we describe a prenatal diagnosis performed in a female from a fragile X family carrying a large premutation. In chorionic villus DNA of the male fetus the normal maternal CGG allele and a normal pattern on Southern blot analysis were found in combination with the FRAXAC2 and DXS297 allele of the maternal at risk haplotype. A second chorionic villus sampling was performed giving identical results on DNA analysis and, in addition, expression of FMRP was shown by immunohistochemistry. We concluded that the male fetus was not affected with the fragile X syndrome. Subsequent detailed haplotype analysis showed a complex recombination pattern resembling either gene conversion or a double crossover within a 20 kb genomic region.     

IgA rheumatoid factor in mucosal fluids and serum of patients with rheumatoid arthritis: immunological aspects and clinical significance.

In order to gain insight into the production and clinical significance of IgA rheumatoid factor (IgA-RF) in mucosal fluids of patients with rheumatoid arthritis (RA), we examined tear fluid, saliva and serum from 80 patients with RA. Significant correlations were found between IgA-RF levels in tear fluid and saliva (P=0.002, r=0.57), saliva and serum (P<0.001, r= 0.79), and serum and tear fluid (P<0.001, r=0.31). No significant correlations were found between total IgA levels in these fluids. Comparison between circulating and mucosal IgA-RF levels after correction for total IgA, revealed that mucosal IgA-RF levels are on average 2.5 times higher than circulating IgA-RF levels. Analysis of IgA-RF specificity showed that lacrimal and salivary IgA-RF reactivity with various IgG subclasses is similar and differs from serum IgA-RF specificity. These results indicate local production of IgA-RF in salivary and lacrimal glands and support the view of a common origin of IgA-RF producing B cells present in mucosal tissues. Mucosal and circulating levels of IgA and IgA-RF were not associated with tests that quantify tear fluid production. This indicates that mucosal and circulating levels of IgA and IgA-RF in patients with RA cannot be regarded as markers for the development of secondary Sjögren's syndrome.     

Experimental analysis of the annotation of promoters in the public database

The ability to identify and examine promoter elements is important to researchers who wish to understand how gene expression is regulated in normal and pathological states. Unfortunately, the number of human promoters that have been directly experimentally defined is small. In order to determine if promoter sequences can be identified by simply aligning mRNA and genomic sequences, we have used a reporter gene assay to assess the promoter activity of the immediate 5' region flanking 38 mRNAs mapping to chromosome 21. For comparison, we have measured the activities of 19 sequences not thought to be promoters and 39 sequences taken from the Eukaryotic Promoter Database. Our results suggest that alignment of reference mRNAs to genomic sequence allows promoters to be identified for at least 75% of genes. These data provide the first empirical evidence that the current state of annotation of the genome is sufficient to allow molecular geneticists to correctly identify promoter sequences for most genes for which reference mRNA and genomic sequences are available.     

Structural brain abnormalities in patients with schizophrenia and their healthy siblings

OBJECTIVE: The authors sought to investigate the contribution of genotype on structural brain abnormalities in schizophrenia. METHOD: Intracranial volumes and volumes of the cerebrum, white and gray matter, lateral and third ventricles, frontal lobes, caudate nucleus, amygdala, hippocampus, parahippocampal gyrus, and the cerebellum were measured in 32 same-sex siblings discordant for schizophrenia and 32 matched comparison subjects by means of magnetic resonance imaging. RESULTS: Third ventricle volumes did not differ between the schizophrenic patients and their healthy siblings. However, both had higher third ventricle volumes than did the comparison subjects. The schizophrenic patients had lower cerebrum volumes than did the comparison subjects, whereas the cerebrum volume of the healthy siblings did not significantly differ from the patients or comparison subjects. Additionally, patients with schizophrenia displayed a volume reduction of the frontal lobe gray matter and a volume increase of the caudate nuclei and lateral ventricles compared to both their healthy siblings and comparison subjects. Intracranial volume, CSF volume, or volumes of the cerebellum, amygdala, hippocampus, or the parahippocampal gyrus did not significantly differ among the patients, siblings, and comparison subjects. CONCLUSIONS: Healthy siblings share third ventricle enlargement with their affected relatives and may partially display a reduction in cerebral volume. These findings suggest that third ventricular enlargement, and to some extent cerebral volume decrease, may be related to genetic defects that produce a susceptibility to schizophrenia.