GMS syndrome: a new dominant condition with goniodysgenesis, mental retardation, and short stature.

We describe a mother and daughter with a distinct phenotype that is different from previous reports. This is likely to constitute a new syndrome for which we propose the mnemonic GMS for G goniodysgenesis, M mental deficiency, and S short stature. The pattern of occurrence is compatible with either autosomal dominant or X-linked inheritance.     

In Vivo Complementation of ureB Restores the Ability of Helicobacter pylori To Colonize

The objective of this study was to determine (i) if complementation of ureB-negative Helicobacter pylori restores colonization and (ii) if urease is a useful reporter for promoter activity in vivo. Strains used were M6, M6DeltaureB, and 10 recombinant derivatives of M6 or M6DeltaureB in which urease expression was under the control of different H. pylori promoters. Mice were orally inoculated with either the wild type or one of the mutant strains, and colonization, in vivo urease activity, and extent of gastritis were determined. Of eight M6DeltaureB recombinants tested, four colonized mice. Of those, three had the highest in vitro urease activity of any of the recombinants, significantly different from that of the noncolonizing mutants. The fourth colonizing recombinant, with ureB under control of the cag-15 promoter, had in vitro urease activity which did not differ significantly from the noncolonizing strains. In vivo, urease activities of the four colonizing transformants and the wild-type control were indistinguishable. There were no differences in gastritis or epithelial lesions between mice infected with M6 and those infected with the transformants. These results demonstrate that recovery of urease activity can restore colonizing ability to urease-negative H. pylori. They also suggest that cag-15 is upregulated in vivo, as was previously suggested by demonstrating that it is upregulated upon contact with epithelial cells. Finally, our results suggest that total urease activity and colonization density do not contribute to gastritis due to H. pylori.     

Evaluation of histological criteria for bullous pemphigoid. Correlation with antigens recognized by immunoblotting of anti-epidermal autoantibodies

The aim of this study was to evaluate the histological findings observed in patients with bullous pemphigoid in whom the diagnosis of bullous pemphigoid could be confirmed by direct immunofluorescence and immunoblot serum analysis. Seven histological criteria were considered for selection of skin biopsy specimens: 1) cleavage of dermal epidermal junction; 2) migration of eosinophils along dermal epidermal junction; 3) presence of intra epidermal eosinophils (with or without associated spongiosis); 4) absence of keratinocyte necrosis; 5) absence of acantholysis; 6) absence of dermal fibrosis; 7) absence of vasculitis. Depending on the number of criteria observed the histological picture was considered as: highly suggestive, suggestive or poorly suggestive of bullous pemphigoid. The histological picture was considered as highly suggestive in 50% of cases, suggestive or poorly suggestive in 37% and 13% of cases respectively. Migration of eosinophils along dermal epidermal junction was observed in 23 biopsy specimens (50%). Histological findings considered as poorly suggestive of bullous pemphigoid consisted of a prurigo-like or an eczematous-like or a drug induced-like picture or no specific cutaneous erosions. An histological picture highly suggestive of bullous pemphigoid was observed in 67% of patients whose serum contained anti-BPAG2 antibodies and in only 36% patients of without anti-BPAG2 antibodies (p=0,04). On the contrary, only one bullous pemphigoid patient (4%) with circulating anti-BPAG2 antibodies had a histological picture poorly suggestive of bullous pemphigoid. These findings are in accordance with the pathogenic properties of anti-BPAG2 antibodies demonstrated in animal models. This study showed that: 1) typical histological findings of bullous pemphigoid are only observed in 50% of skin biopsy specimens. 2) The diagnosis of bullous pemphigoid should be considered in elderly patients even when a poorly specific prurigo-like or eczematous-like histological picture is observed. Moreover, it underlines the usefulness of direct immunofluorescence of skin biopsy specimens and indirect immunofluorescence and immunoblot analysis of serum in such atypical cases of bullous pemphigoid.     

The MDR1 polymorphisms at exons 21 and 26 predict steroid weaning in pediatric heart transplant patients

Various polymorphisms of the MDR1 gene that encodes for P-glycoprotein (P-gp), a transmembrane pump, have been identified. A silent mutation C3435T in exon 26 and a G2677T mutation in exon 21 have been correlated with P-gp expression and function in humans. The objectives of this study were (a) to determine whether the MDR1 exon 21 and exon 26 polymorphisms were related to steroid weaning in a pediatric heart transplant (HTx) population, and (b) to determine whether an association exist between the MDR1 exon 21 and exon 26 polymorphisms in these patients. Sixty-nine pediatric HTx patients were studied. MDR1 genotyping was determined by polymerase chain reaction amplification, sequencing the DNA, and sequence evaluation using Polyphred software (University of Washington) to identify genotypes. The steroid dose at 1 year post-transplantation was recorded. For steroid weaning at one year post-HTx for MDR1 C3435T, 12 of 18 (67%) patients in the CC genotype were still on prednisone, whereas only 18 of 47 (38%) of the CT/TT group were still receiving prednisone (p = 0.04). Similar results were observed for the MDR1 G2677T genotyping and steroid weaning. Forty-three of 46 patients (93.5%) who have MDR1 C3435T allele also have a mutant G2677T allele (p < 0.001). We conclude that (a) a significantly larger number of MDR1 3435 CC HTx patients remain on steroids at 1 year after transplantation, and (b) the MDR1 C3435T genotype is associated with the G2677 genotype in pediatric HTx patients.     

Quinupristin-dalfopristin-resistant Enterococcus faecium on chicken and in human stool specimens

BACKGROUND: The combination of the streptogramins quinupristin and dalfopristin was approved in the United States in late 1999 for the treatment of vancomycin-resistant Enterococcus faecium infections. Since 1974, another streptogramin, virginiamycin, has been used at subtherapeutic concentrations to promote the growth of farm animals, including chickens. METHODS: To determine the frequency of quinupristin-dalfopristin-resistant E. faecium, we used selective medium to culture samples from chickens purchased in supermarkets in Georgia, Maryland, Minnesota, and Oregon and stool samples from outpatients. RESULTS: Between July 1998 and June 1999, samples from 407 chickens from 26 stores in four states were cultured, as were 334 stool samples from outpatients. Quinupristin-dalfopristin-resistant E. faecium was isolated from 237 chicken carcasses and 3 stool specimens. The resistant isolates from stool had low-level resistance (minimal inhibitory concentration [MIC], 4 microg per milliliter; resistance was defined as a MIC of at least 4 microg per milliliter). The resistant isolates from chickens in general had higher levels of resistance (MICs ranging from 4 to 32 microg per milliliter; MIC required to inhibit 50 percent of isolates, 8 microg per milliliter). CONCLUSIONS: Quinupristin-dalfopristin-resistant E. faecium contaminates a large proportion of chickens sold in U.S. supermarkets. However, the low prevalence and low level of resistance of these strains in human stool specimens suggest that the use of virginiamycin in animals has not yet had a substantial influence. Foodborne dissemination of resistance may increase, however, as the clinical use of quinupristin-dalfopristin increases.     

Correlation of amylase and lecithin sphingomyelin ratios in amniotic fluid samples

The use of amniotic fluid amylase (AF amylase) has been proposed as a screening test to determine fetal maturity. We reviewed data from 944 amniotic fluid samples analyzed by our laboratory for amylase and lecithin sphingomyelin (L/S) ratio between 1975 and 1980. AF amylase shows poor overall correlation with L/S ratios (r = 0.256). Retrospective analysis of AF amylase as a screen to determine the need for L/S ratios showed an overall sensitivity of 57%, and an overall specificity of 86% for AF amylase. Three groups were studied: a low amylase group (amylase less than 200 U/L), a middle group (amylase 200-300 U/L), and a high amylase group (amylase greater than 300 U/L). Only 55% of the low amylase group had an immature L/S ratio. The high amylase group had the best correlation between AF amylase and L/S ratio, but 13% of these samples had an immature or borderline L/S ratio. We conclude that AF amylase cannot be used as a screening test to determine the need to perform L/S ratios.     

Multipoint linkage mapping of the Xq25-q26 region in a family affected by the X-linked lymphoproliferative syndrome

We have performed, in a large Swiss family, a study of linkage between various DNA markers in the Xq24-27 region and the locus for the X-linked lymphoproliferative syndrome (XLP). Our results indicated that the marker DXS37 in Xq25-q26 is genetically linked to the XLP syndrome. The multipoint linkage analysis showed that the disease locus is distal to DXS11, but proximal to the hypoxanthine phosphoribosyl-transferase gene (HPRT).