Adherence to surgical site infection guidelines in Italian cardiac surgery units.

BACKGROUND: Data on the adherence to surgical site infection (SSI) prevention guidelines in Italian cardiac surgery units are lacking. METHODS: A multiple-choice questionnaire, structured into eight sections following the Centers for Disease Control 1999 (CDC) guidelines, was prepared and sent to 24 surgical units participating in a national study group (GIS-InCard); this units perform over 20% of all cardiac surgical procedures in Italy. Answers were stratified based upon the evidence of the recommendations: grade IA (ten questions), grade IB (52 questions), grade II (11 questions), and no recommendation (seven questions). RESULTS: 17 of the 24 units (72%) returned the questionnaire. Adherence to grade IA recommendations was 69 +/- 34%, with five units (29%) showing a > or =80% adherence. Adherence to grade IB and II was 65 +/- 26% and 71 +/- 28%, respectively. Adherence did not vary significantly depending on the evidence of the recommendation, i.e., grade IA, IB or II (p = 0.72). Low adherence levels to grade I recommendations were observed on hair removal: (1) it was performed systematically in all male patients (0% adherence), (2) it was performed on the morning of the intervention in 29% of centers, and (3) the method of hair removal was adequate in 41% of cases. Despite 94% of units having written guidelines on antibiotic prophylaxis, only 65% administered antibiotic prophylaxis with the correct timing - i.e., on anesthesia induction. CONCLUSIONS: Adherence to CDC SSI guidelines in Italy is fair. The evidence of the recommendation does not influence adherence. Organizational improvements, especially those regarding hair removal and the timing of antibiotic prophylaxis, should be implemented in most hospitals.

Defective copper-induced trafficking and localization of the Menkes protein in patients with mild and copper-treated classical Menkes disease.

Menkes disease is an X-linked disorder of copper metabolism. An overall copper deficiency reduces the activity of copper-dependent enzymes accounting for the clinical presentation of affected individuals. The Menkes gene product (MNK) is a P-type ATPase and is considered to be the main copper efflux protein in most cells. The protein is located primarily at the trans -Golgi network (TGN), but relocalizes to the plasma membrane in elevated copper conditions to expel the excess copper from the cell. Here we report the first missense mutation which causes mild Menkes disease, a mutation in a successfully copper-treated classical Menkes patient and the effect of each mutation on the localization of MNK within the cell. Using western blot analysis, MNK was detectable in cells from both patients, but appeared to be mislocalized in the treated case. In the mild Menkes patient, the protein appeared to be located in the TGN but failed to redistribute towards the cell periphery in response to copper. This is the first description of a mutation in a Menkes patient which affects the trafficking of MNK, and the loss of this process is consistent with the clinical phenotype.

Molecular structure of the Menkes disease gene (ATP7A).

We report a detailed molecular analysis of the genomic structure of the Menkes disease gene (MNK; ATP7A). There are 23 exons in ATP7A covering a genomic region of approximately 140 kb. The size of the individual coding exons varies between 77 and 726 bp, and introns vary in size between 196 bp and approximately 60 kb. All of the splice sites obey the consensus GT-AG rule except the splice donor of intron 9, which is GC instead of GT. The exon following this rare splice donor variant is alternatively spliced. A PGAM pseudogene and two highly polymorphic CA repeats map to introns within the gene. The structure is very similar to that of the closely related Wilson disease gene (WND; ATP7B). From exon 5 (exon 3 in ATP7B) to the end, all of the splice sites occur at exactly the same nucleotide positions as in the WND gene, except for the boundary between exons 17 and 18 (exons 15 and 16 in ATP7B) and a single codon difference at the boundary between exons 4 and 5 of the MNK gene (exons 2 and 3 in ATP7B). In contrast to the WND gene, in which the first four of six metal binding domains are contained in 1 exon, metal binding domains 1 to 4 are divided over 3 exons. The striking similarity of the MNK and WND genes at the genomic level is consistent with their relatively recent divergence from a common ancestral gene.

Mutations in the murine homologue of the Menkes gene in dappled and blotchy mice.

The murine homologue of the Menkes disease gene (MNK) was isolated from cDNA libraries, using human cDNA clones as probes, and by PCR. The predicted amino acid sequence shows a high level of identity (89.9%) with the human protein, and the predicted functional domains in the human protein are present. Using probes to the mouse Mnk gene, we found that the mottled dappled mutation was caused by alteration in the Mnk locus and lack of expression of Mnk RNA. Tissues of the blotchy mouse contained two larger sizes of MNK mRNA demonstrating a likely defect in RNA splicing. Thus, the mottled locus is homologous to the human MNK locus and dappled and blotchy are allelic mutations in this gene.