Sternal surgical-site infection following coronary artery bypass graft: prevalence, microbiology, and complications during a 42-month period.

OBJECTIVE: Surgical-site infection (SSI) is a serious and costly complication following coronary artery bypass graft (CABG). We analyzed surgical factors, microbiology, and complications at a 608-bed community teaching hospital to identify opportunities for prevention. METHODS: All patients undergoing CABG procedures from June 1997 through December 2000 were analyzed. Hospital records and postdischarge surveillance data were reviewed for demographics, surgical information, timing and classification of infection, microbiology, and bacteremic events. RESULTS: Of 3,443 patients undergoing CABG, sternal SSI developed in 122 (3.5%); 71 (58.2%) were classified as superficial SSI and 51 (41.8%) as deep SSI. Surgical antimicrobial prophylaxis was employed in all cases. On average, infection occurred 21.5 days (range, 4 to 315) after CABG. Most cases were diagnosed on readmission (59%); 20 cases (16%) were identified by postdischarge surveillance. Microbiological data were positive in 109 (89.3%), with a single pathogen implicated in most (86.2%). Gram-positive cocci were most frequently recovered (81%); gram-negative bacilli (17%), gram-positive bacilli (1%), and yeast (1%) were less common. Staphylococcus aureus was the most frequently isolated pathogen (49%). Bacteremia was noted in 22 instances (18%). It was significantly associated with deep SSI (P =. 002) and identified only in S. aureus cases. CONCLUSIONS: SSI complicated 3.5% of the procedures. S. aureus was implicated in most of the cases and was significantly associated with deep SSI. It was the only pathogen associated with secondary bacteremia. In addition to standard guidelines, targeted methods against S. aureus should help reduce the overall rate of SSI.     

1 alpha,25-dihydroxyvitamin D3-induced increments in hepatocyte cytosolic calcium and lysophosphatidylinositol: inhibition by pertussis toxin and 1 beta,25-dihydroxyvitamin D3

1 alpha,25-Dihydroxyvitamin D3 rapidly increases cytosolic calcium and alters membrane phospholipid metabolism in hepatocytes. To define the causal relationship between these events, we examined the effects of 1 alpha,25-dihydroxyvitamin D3 on 32P-labeled lysophosphatidylinositol levels and cytosolic calcium as affected by pertussis toxin and 1 beta,25-dihydroxyvitamin D3, the biologically inactive analog. 32P-labeled lysophosphatidylinositol was determined by two-dimensional thin-layer chromatography. Cytosolic calcium was measured in cells loaded with quin-2AM. Within 5 min, 1 alpha,25-dihydroxyvitamin D3 increased hepatocyte cytosolic calcium by 31% (p less than 0.05) and 32P-labeled lysophosphatidylinositol by 38% (p less than 0.05). Pertussis toxin inhibited the hormone-induced rise in cytosolic calcium but not the increase in 32P-labeled lysophosphatidylinositol. Exposure to exogenous lysophosphatidylinositol for 5 min increased cytosolic calcium by 40% (p less than 0.05), an effect that was also inhibited by pertussis toxin. 1 beta,25-Dihydroxyvitamin D3 had no effect on either hepatocyte cytosolic calcium or 32P-labeled lysophosphatidylinositol but prevented the 1 alpha,25-dihydroxyvitamin D3-induced increments. The results suggest that a G protein sensitive to pertussis toxin is required for the transduction of the lysophosphatidylinositol signal but not the generation of the signal. The ability of 1 beta,25-dihydroxyvitamin D3 to inhibit the 1 alpha,25-dihydroxyvitamin D3-induced changes in phospholipids suggests that the epimer may compete with 1 alpha,25-dihydroxyvitamin D3 for an initiating receptor.     

Effects of vitamin D3 and cyclosporin A on HgCl2-induced autoimmunity in Brown Norway rats

BACKGROUND.: Mercuric chloride (HgCl₂ induces a lymphoproliferative disorderand autoimmune glomerulonephritis in Brown Norway (BN) rats.This syndrome is the consequence of T cell-dependent polyclonalB cell activation and autoantibody production. We have previouslyshown that HgCl₂-induced autoimmune perturbations can be preventedin BN rats by the administration of cyclosporin A (CsA). Themost potent vitamin D₃ metabolite 1,25(OH)₂ D₃ (Vit D₃) sharescertain immunomodulatory properties with CsA. We therefore choseto compare the effects of Vit D₃ to those of CsA in BN ratstreated with HgCl₂ in order to establish whether Vit D₃ eitheralone or in combination with CsA can attenuate an autoimmunesyndrome in vivo. METHODS.: BN rats were treated with HgCl₂ according to a standard protocol.Subgroups of rats were also given CsA alone, Vit D₃ or syntheticanalogues of Vit D₃ alone, or combinations of both agents. Differentdoses and routes of administration were compared. The followingmarkers of disease activity were evaluated: mortality, peakproteinuria, serum IgE concentrations, and renal immunoglobulindeposition. RESULTS.: Disease activity was markedly attenuated in all rats treatedwith CsA alone. Vit D₃ and certain of its synthetic analoguesadministered alone also tempered the autoimmune process, butto a lesser extent than did CsA. The effect of CsA alone wasso potent, that no additive or synergistic effects could bedemonstrated when CsA was administered in combination with VitD₃. CONCLUSIONS.: Despite similar described immunomodulatory effects in vitro,CsA is clearly more effective than Vit D₃ in preventing HgCl₂autoimmune disease in BN rats. This suggests that there is adifference in the cellular targets of these two agents in vivo,and/or a difference in the potency with which HgCl2-triggeredimmune activation is suppressed.     

Anionic polymerization of exo-3,4,5-trithiatetracyclo[5.5.1.O2,6.O8,12]tridec-10-ene (dicyclopentadiene trisulfide)

The anionic polymerization of exo-3,4,5-trithiatetracyclo[5.5.1.O^2,6.O^8,12]tridec-10-ene ( 1 ) in bulk and/or in aromatic solvents (benzene, toluene) was studied. The polymerization was initiated with sodium benzenethiolate (sodium cation complexed with dibenzo-18-crown-6). Polymers with high-molecular weights were obtained (M _n ≈ 10⁵, osmometrically). The polymerization was found to be living and reversible; the equilibrium monomer concentration increases with the temperature. The ceilling temperature was estimated as 167°C. The thermodynamic data of the polymerization in toluene was determined and compared with those of the polymerization of exo-3,4,5-trithiatricyclo[5.2.O^2,6]decane. The standard enthalpy ΔH = ?(6,6 ± 0,6)kJ · mol ¹ and entropy ΔS = ?(29,3 ± 2,1)J · mol ¹ · K ¹ of the polymerization of 1 were evaluated from the temperature dependence of the equilibrium monomer concentration, determined dilatometrically.     

Strong association of HLA-Cw6 allele with juvenile psoriasis in Polish patients

Association of psoriasis vulgaris with HLA-C is not equally strong in different human populations. It has not yet been studied in Polish patients at DNA level, but only by serology that is inadequate for HLA-C. Therefore, we examined the distribution of HLA-C alleles by means of low resolution PCR-SSP in 102 Polish psoriatics and 123 healthy controls. We have found significantly higher representation of HLA-Cw*06 (odds ratio, 18.73; P(cor)<0.001) and significantly lower representation of HLA-Cw*07 (odds ratio, 0.41; P(cor)<0.038) in patients than in controls. Association of HLA-Cw*06 with psoriasis was even stronger in early age at onset (0-20 years) group: odds ratio, 77.71; P(cor)<0.001. Therefore, our population seems to belong to those with strong association of psoriasis with HLA-Cw*06.     

Germline mutations of the CDKN2 gene in UK melanoma families

Germline mutations in CDKN2 on chromosome 9p21, which codes for the cyclin D kinase inhibitor p16, and more rarely, mutations in the gene coding for CDK4, the protein to which p16 binds, underlie susceptibility in some melanoma families. We have sequenced all exons of CDKN2 and analysed the CDK4 gene for mutations in 27 UK families showing evidence of predisposition to melanoma. Five different germline mutations in CDKN2 were found in six families. Three of the mutations (Met53Ile, Arg24Pro and 23ins24) have been reported previously. We have identified two novel CDKN2 mutations (88delG and Ala118Thr) which are likely to be associated with the development of melanoma, because of their co-segregation with the disease and their likely functional effect on the CDKN2 protein. In binding assays the protein expressed from the previously described mutation, Met53Ile, did not bind to CDK4/CDK6, confirming its role as a causal mutation in the development of melanoma. Ala118Thr appeared to be functional in this assay. Arg24Pro appeared to bind to CDK6, but not to CDK4. No mutations were detected in exon 2 of CDK4, suggesting that causal mutations in this gene are uncommon. The penetrance of these mutant CDKN2 genes is not yet established, nor is the risk of non-melanoma cancer to gene carriers.      

Release from central auditory competition in the split-brain patient

We used dichotic digits (DD), staggered spondaic words (SSW), and frequency patterns (PATT) to study central auditory function before and after two-stage callosotomy. Preoperatively, the patient demonstrated reduced scores bilaterally on all these tests, consistent with documented bilateral hemisphere lesions. After the first operation (sectioning the posterior half of the corpus callosum), the dichotic tests (DD and SSW) revealed the expected decrease in left-ear scores, but there was improvement on the right, perhaps because there was release from central auditory competition. Our findings also suggest that the "auditory" portion of the corpus callosum may be in the posterior half of this structure.