Staphylococcus aureus carriage among GPs in the Netherlands

Background

The extent to which GPs serve as a reservoir for antibiotic-resistant Staphylococcus aureus is unknown and not well studied.

Aim

To determine the prevalence of nasal S. aureus carriage among GPs in the Netherlands, as well as the antimicrobial resistance and the genotypes of isolated S. aureus.

Design of study

Observational, point-prevalence, and cross-sectional study.

Setting

GPs attending the annual conference of the Dutch College of General Practitioners in 2006.

Method

Nasal swabs were randomly taken from 395 GPs and analysed for the presence of S. aureus. Antimicrobial susceptibility was determined by a microbroth dilution method and the genotypes by spa typing, which was associated with multilocus sequence typing.

Results

Of the GPs, 129/395 (33%; 95% confidence interval [CI] = 28 to 37%) were carriers of S. aureus. No meticillin-resistant S. aureus (MRSA) was found. Resistance was observed to penicillin (71%; 95% CI = 63 to 79%), fusidic acid (7%; 95% CI = 3 to 13%), and clarithromycin (6%; 95% CI = 3 to 12%). In 72% of the isolates, an MRSA-related genotype of S. aureus was found.

Conclusion

The low antibiotic resistance found among S. aureus of GPs suggests that GPs are not a reservoir of antibiotic-resistant S. aureus strains. The relatively high resistance to fusidic acid, which has not previously been described in the Netherlands and is mostly because of antibiotic use, suggests that patients infect GPs and not the other way round. GPs may be at risk for nasal carriage of S. aureus with an MRSA-related genotype.     

Another observation with VATER association and a complex IV respiratory chain deficiency

The VATER association of vertebral anomalies (V), anal atresia (A), esophageal atresia and/or tracheo-esophageal fistula (TE), radial and renal anomalies (R) is a common congenital association of unknown origin with probably heterogeneous causes. Here, we report on a girl presenting with pre- and postnatal growth retardation, esophageal atresia, vertebral and costal anomalies and a unilateral radial defect, consistent with the diagnosis of VATER association. In the first month of life, she presented with failure to thrive, severe episodes of hypoglycemia, liver dysfunction and high levels of lactate, which prompted us to perform metabolic screening. A complex IV respiratory chain deficiency (RCD) was diagnosed on a liver biopsy. The respiratory chain defect was not observed in skin fibroblasts. No mtDNA point mutation or deletion was identified. The girl is now 9 years old and has a normal mental development but persistent feeding difficulties and moderate hyperlactatemia. To our knowledge, this is the second report of VATER association with mitochondrial disorder. In a previous report, a VACTERL association was observed in a girl with the mitochondrial A3243G point mutation. The association of VATER phenotype with a mitochondrial disorder may be coincidental but could also suggest that the presence of multiple malformations is the result of the antenatal expression of RCD.     

Toward experimental assessment of receptor occupancy: TGN1412 revisited

In March 2006, 6 healthy volunteers experienced serious adverse reactions during a first-in-human clinical trial of the superagonistic anti-CD28 mAb TGN1412. A first investigation excluded contaminations of the drug product or protocol irregularities as the root cause. Later, an expert scientific group convened in the United Kingdom to develop recommendations pertinent to minimizing risks of first-in-human clinical trials. The expert scientific group concluded from in silico calculations that at the initial dose of 0.1 mg/kg, which was adjusted on the basis of the no observed adverse effect level, approximately 86.2% to 90.9% CD28 receptor occupancy was obtained. Here we developed a flow cytometric method that revealed receptor occupancy of approximately 45% to 80% under the above conditions. Thus we present a method to experimentally determine receptor occupancy that can be taken as one parameter to define the minimal anticipated biological effect level as the basis for calculating safer starting doses for first-in-human clinical trials for products in which a potential risk has been identified. Additional measures are being discussed that will help to significantly improve safety of first-in-human clinical trials.     

Early cleavage predicts the viability of human embryos in elective single embryo transfer procedures

BACKGROUND: The reduction of multiple pregnancies by using elective single embryo transfers (eSET) requires critical and careful selection of the embryo for transfer. The current study was undertaken to assess whether early cleavage could be used as a marker of embryo competence in eSET procedures. METHODS: The study included analysis of 178 eSET procedures. All embryos were checked for early cleavage at 25-27 h post insemination or ICSI. The embryos that possessed two cells at 25-27 h post insemination or ICSI were designated as 'early cleavage' (EC) embryos and those that had not yet cleaved were classified as 'no early cleavage' (NEC) embryos. Selection of the embryo for transfer was based on embryo morphology and growth rate on day 2 and not early cleavage. Clinical parameters were compared between 72 EC and 106 NEC single embryo transfers. RESULTS: A significantly higher clinical pregnancy rate was observed after transfer of EC (50%) than NEC (26.4%) embryos. CONCLUSIONS: The current study provides compelling evidence that EC embryos possess significantly higher developmental competence than NEC embryos.     

Impact of micronutrient deficiency & malnutrition in systemic sclerosis: Cohort study and literature review

Objectives

The purpose of our study was to determine the prevalence and risk factors associated with malnutrition, and selenium (Se) and vitamin C (vitC) deficiencies in systemic sclerosis (SSc) patients.

Delineation of EFTUD2 Haploinsufficiency‐Related Phenotypes Through a Series of 36 Patients

Mandibulofacial dysostosis, Guion‐Almeida type (MFDGA) is a recently delineated multiple congenital anomalies/mental retardation syndrome characterized by the association of mandibulofacial dysostosis (MFD) with external ear malformations, hearing loss, cleft palate, choanal atresia, microcephaly, intellectual disability, oesophageal atresia (OA), congenital heart defects (CHDs), and radial ray defects. MFDGA emerges as a clinically recognizable entity, long underdiagnosed due to highly variable presentations. The main differential diagnoses are CHARGE and Feingold syndromes, oculoauriculovertebral spectrum, and other MFDs. EFTUD2, located on 17q21.31, encodes a component of the major spliceosome and is disease causing in MFDGA, due to heterozygous loss‐of‐function (LoF) mutations. Here, we describe a series of 36 cases of MFDGA, including 24 previously unreported cases, and we review the literature in order to delineate the clinical spectrum ascribed to EFTUD2 LoF. MFD, external ear anomalies, and intellectual deficiency occur at a higher frequency than microcephaly. We characterize the evolution of the facial gestalt at different ages and describe novel renal and cerebral malformations. The most frequent extracranial malformation in this series is OA, followed by CHDs and skeletal abnormalities. MFDGA is probably more frequent than other syndromic MFDs such as Nager or Miller syndromes. Although the wide spectrum of malformations complicates diagnosis, characteristic facial features provide a useful handle.     

The effect of RGD density on osteoblast and endothelial cell behavior on RGD-grafted polyethylene terephthalate surfaces

Hybrid materials combining polyethylene terephthalate and different types of cells (endothelial and osteoblastic cells) have been developed thanks to the covalent grafting of different densities of RGD containing peptides onto the polymer surface. Biomimetic modifications were performed by means of a three-step reaction procedure: creation of COOH functions, coupling agent grafting and the immobilization of the RGDC peptides. High resolution μ-imager was used to evaluate RGD densities (varying between 0.6 and 2.4 pmol/mm²) and has exhibited the stability of the surface grafted peptides when treated in harsh conditions. The efficiency of this route for biomimetic modification of a PET surface was demonstrated by measuring the adhesion of MC3T3 and HSVEC cells and by focal adhesion observation. Results obtained prove that a minimal RGDC density of 1 pmol/mm² is required to improve MC3T3 and HSVEC cells responses. Indeed, cells seeded onto a RGDC-modified PET with a density higher than 1 pmol/mm² were able to establish focal adhesion as visualized by fluorescence microscope compared to cells immobilized onto unmodified PET and RGDC-modified PET with densities lower than 1 pmol/mm². Moreover, the number of focal contacts was enhanced by the increase of RGDC peptide densities grafted onto the material surface. With this study we proved that the density of peptides immobilized on the surface is a very important parameter influencing osteoblast or endothelial cell adhesion and focal contact formation.