Transferable, plasmid-mediated vanB-type glycopeptide resistance in Enterococcus faecium

An approximately 60-kb transferable, vanB-carrying plasmid has been identified in a clinical Enterococcus faecium strain. A similar plasmid has been observed in an unrelated E. faecium strain, suggesting that plasmid transfer of vanB operons occurs in nature and plays a role in the dissemination of VanB-type resistance among strains of E. faecium.     

Congenital abnormalities in Brazilian children associated with misoprostol misuse in first trimester of pregnancy

BACKGROUND: Misoprostol is commonly used to induce abortion in Brazil, and in other countries in South and Central America where abortions are illegal. However, misoprostol is not very effective in inducing abortions, and exposure to the drug in utero can cause abnormalities in the fetus. We aimed to define the common phenotypical effects of exposure to the drug. METHODS: We studied 42 infants from S?o Paulo, Brazil, who were exposed to misoprostol during the first 3 months of gestation, and then born with congenital abnormalities. We interviewed each of the infants' mothers to find out about misoprostol exposure and dosage. Each infant was physically examined by a geneticist or a neuropaediatrician. FINDINGS: 17 of the infants had equinovarus with cranial-nerve defects. Ten children had equinovarus as part of more extensive arthrogryposis. The most distinctive phenotypes were arthrogryposis confined to the legs (five cases) and terminal transverse-limb defects (nine cases) with or without Mobius sequence. The most common dose of misoprostol taken was 800 microg (range 200-16000 microg). INTERPRETATION: Deformities attributed to vascular disruption were found in these children. We suggest that the uterine contractions induced by misoprostol cause vascular disruption in the fetus, including brain-stem ischaemia. Information on the effects of taking misoprostol during pregnancy should be made more widely available, to dissuade women from misusing the drug.     

Stability of fumonisins in thermally processed corn products

Little is known about the stability of fumonisins in corn-based foods during heating. This study investigated the effects of canning, baking, and roasting (dry heating) processes on the stability of fumonisins in artificially contaminated and naturally contaminated corn-based foods. All samples were analyzed for fumonisin levels by both a commercial enzyme-linked immunosorbent assay (ELISA) and a high-performance liquid chromatographic (HPLC) method. Canned whole-kernel corn showed a significant (P < or = 0.05) decrease in fumonisins by both ELISA (15%) and HPLC (11%) analyses. Canned cream-style corn and baked corn bread showed significant (P < or = 0.05) decreases in fumonisin levels at an average rate of 9% and 48%, respectively, as analyzed by ELISA. Corn-muffin mix artificially contaminated with 5 micrograms of fumonisin B1 (FB1) per g and naturally contaminated corn-muffin mix showed no significant (P < or = 0.05) losses of fumonisins upon baking. Roasting cornmeal samples artificially contaminated with 5 micrograms of FB1 per g and naturally contaminated cornmeal samples at 218 degrees C for 15 min resulted in almost complete loss of fumonisins.     

Transurethral cystotomy repair

We present a novel transurethral technique for cystotomy repair. This method can be used for immediate bladder repair following limited bladder injury and avoids the morbidity associated with laparotomy.     

Aorta transplantation in man: clinical and immunological studies

Aortic transplantation has progressively gained interest over the last few years and it is becoming a first choice indication in the substitution of infected prostheses. The most frequent complication in long-term vascular outcome (wall thickening, aneurysmatic dilation, stenosis), may occur through an immunological mechanism. In this study we investigated nine recipients, aged 48 to 65 years, of aorta segment replacement for anti-HLA antibody production (specificity and Ig class), CD3-CD4-CD8 T cell subpopulation dynamics and aorta wall thickness. Mismatch-specific IgG antibodies to HLA class I and HLA class II antigens were detected 1, 3 and 6 months after transplantation and persisted at a high concentration for at least 1 year. Furthermore, the absolute number of CD3, CD4 and CD8 positive lymphocytes increased progressively after aorta allograft. Tomography scanning showed a progressive thickness of the aorta wall. We can speculate that these anti-HLA antibodies in the recipients have the potential to harm the implant; therefore, aorta allograft should involve the induction of immunological tolerance by appropriate immunosuppressants.     

Estimating costs of programme services and products using information provided in standard financial statements

OBJECTIVE: To determine whether spectral analysis of unprocessed radiofrequency (RF) signal offers advantages over standard videodensitometric analysis in identifying the morphology of coronary atherosclerotic plaques. METHODS: 97 regions of interest (ROI) were imaged at 30 MHz from postmortem, pressure perfused (80 mm Hg) coronary arteries in saline baths. RF data were digitised at 250 MHz. Two different sizes of ROI were identified from scan converted images, and relative amplitudes of different frequency components were analysed from raw data. Normalised spectra was used to calculate spectral slope (dB/MHz), y-axis intercept (dB), mean power (dB), and maximum power (dB) over a given bandwidth (17-42 MHz). RF images were constructed and compared with comparative histology derived from microscopy and radiological techniques in three dimensions. RESULTS: Mean power was similar from dense fibrotic tissue and heavy calcium, but spectral slope was steeper in heavy calcium (-0.45 (0.1)) than in dense fibrotic tissue (-0.31 (0.1)), and maximum power was higher for heavy calcium (-7.7 (2.0)) than for dense fibrotic tissue (-10.2 (3.9)). Maximum power was significantly higher in heavy calcium (-7.7 (2.0) dB) and dense fibrotic tissue (-10.2 (3.9) dB) than in microcalcification (-13.9 (3.8) dB). Y-axis intercept was higher in microcalcification (-5.8 (1.1) dB) than in moderately fibrotic tissue (-11.9 (2.0) dB). Moderate and dense fibrotic tissue were discriminated with mean power: moderate -20.2 (1.1) dB, dense -14.7 (3.7) dB; and y-axis intercept: moderate -11.9 (2.0) dB, dense -5.5 (5.4) dB. Different densities of fibrosis, loose, moderate, and dense, were discriminated with both y-axis intercept, spectral slope, and mean power. Lipid could be differentiated from other types of plaque tissue on the basis of spectral slope, lipid -0.17 (0.08). Also y-axis intercept from lipid (-17.6 (3.9)) differed significantly from moderately fibrotic tissue, dense fibrotic tissue, microcalcification, and heavy calcium. No significant differences in any of the measured parameters were seen between the results obtained from small and large ROIs. CONCLUSION: Frequency based spectral analysis of unprocessed ultrasound signal may lead to accurate identification of atherosclerotic plaque morphology.     

Investigation of the N-substituent conformation governing potency and mu receptor subtype-selectivity in (+)-(3R, 4R)-dimethyl-4-(3-hydroxyphenyl)piperidine opioid antagonists

A study of the binding site requirements associated with the N-substituent of (+)-(3R,4R)-dimethyl-4-(3-hydroxyphenyl)piperidine (4) derivatives was undertaken using a set of rigid vs flexible N-substituents. The study showed that compounds 7-9 bearing the trans-cinnamyl N-substituent most closely reproduced the potency at the opioid receptor of the flexible N-propylphenyl or N-propylcyclohexyl analogues previously reported. Neither the N-substituted cis-cinnamyl nor the cis-phenylcyclopropylmethyl compounds 10 and 11, respectively, showed high affinity for the opioid receptor. However, the N-trans-phenylcyclopropylmethyl compound 12 closely approximated the affinity of compounds 7-9. Additionally, we found that free rotation of the phenyl ring is necessary for high affinity binding and mu receptor subtype selectivity as the planar N-substituted thianaphthylmethyl and benzofuranylmethyl compounds 13 and 14 had significantly lower binding affinities. Altogether, these findings suggest that the high binding affinity, selectivity, and antagonist potency of N-propylphenyl or N-propylcyclohexyl analogues of (+)-(3R, 4R)-dimethyl-4-(3-hydroxyphenyl)piperidine (4) are achieved via a conformation wherein the connecting chain of the N-substituents is extended away from piperidine nitrogen with the appended ring system rotated out-of-plane relative to the connecting chain atoms. This conformation is quite similar to that observed in the solid state for 5, as determined by single crystal X-ray analysis. Additionally, it was found that, unlike naltrexone, N-substituents bearing secondary carbons attached directly to the piperidine nitrogen of 4 suffer dramatic losses of potency vs analogues not substituted in this manner. Using a functional assay which measured stimulation or inhibition of [35S]GTP-gamma-S binding, we show that the trans-cinnamyl analogues of (+)-(3R, 4R)-dimethyl-4-(3-hydroxyphenyl)piperidine (4) retain opioid pure antagonist activity and possess picomolar antagonist potency at the mu receptor.     

Covalent modifications of aminophospholipids by 4-hydroxynonenal

Lipid oxidation is implicated in a wide range of pathophysiological disorders, which leads to reactive compounds such as aldehydes. Among them 4-hydroxynonenal (4-HNE) reacts strongly with the NH2 groups of amino acids and forms mainly Michael adducts and minor Schiff-base adducts. Such reactions occur also with compounds containing thiol groups. No data are available describing 4-HNE interactions with amino-phospholipids. To investigate such a possibility, 4-HNE was incubated with either phosphatidylethanolamine (PE) or phosphatidylserine (PS) in an aqueous-organic biphasic system and the resulting products were identified by liquid chromatography-mass spectrometry (LC-MS). Our study points out the potential capacity of 4-HNE to react with phospholipids containing amino groups and particularly PE. The main resulting compounds found were a Michael adduct plus a minor Schiff base adduct, which was partly cyclized as a pyrrole derivative via a loss of water. Its stabilization as a pyrrole derivative allows to differentiate 4-HNE from the other aldehydes generated via lipid oxidation (e.g., malondialdehyde, 2-nonenal) that lack the 4-hydroxyl group. Their formation seems not to be affected when the pH varies from 6.5 to 8.5. Surprisingly, PS reacted poorly producing only a small amount of Michael adduct, the Schiff-base adduct being nondetectable. We conclude that such adducts, if they are formed in cell membranes, could alter the phospholipase-dependent cell signaling.