Molecular epidemiology of Staphylococcus epidermidis in neonatal intensive care units

Late‐onset sepsis (LOS) in preterm neonates is increasingly reported to be associated with gut‐colonizing Staphylococcus epidermidis. We aimed to describe the molecular epidemiology of S. epidermidis colonizing the gut of neonates hospitalized in two neonatal intensive care units. S. epidermidis from rectal swabs were typed by multilocus variable‐number tandem‐repeat analysis (MLVA), randomly chosen isolates of predominant MLVA types additionally by multilocus sequence typing. Antimicrobial susceptibility, the presence of icaA, IS256, arginine catabolic mobile element (ACME), agr type, and SCCmec type were determined. Of 276 neonates (38.4%), 106 were colonized with S. epidermidis, yielding a total of 139 isolates (62 in one unit and 77 in another unit). Of the 55 MLVA types identified, the five predominant detected in both units corresponded to sequence type (ST) 2, ST5, and ST59 or its single locus variant ST81 and formed three major MLVA clonal complexes accounting for 74.8% of all isolates. Overall, the prevalence of mecA, icaA, IS256, and ACME was 91.4%, 28.1%, 64%, and 77%, respectively. Of the mecA‐positive isolates (n = 127), 43.9% carried SCCmec type IV. Of eight episodes of LOS, four were caused by ST2 and two by ST5. Preventing gut colonization with nosocomial epidemic S. epidermidis in hospitalized neonates could contribute to the prevention of LOS.     

Joint area constraint had no influence on bone loss in proximal tibia 5 years after total knee replacement.

After total knee replacement (TKR) the bone mineral density (BMD) decreases in the proximal tibia. Our aim was to evaluate if changes in constraint of the cemented AMK TKR (DePuy, Johnson & Johnson, Leeds, UK) had any effect on postoperative bone remodeling in the proximal tibia. We used dual-energy X-ray absorptiometry in 43-53 knees to record changes in BMD in three regions of interest around the tibial component up to 5 years after operation with the AMK (DePuy) TKR. The knees had been randomly allocated to receive a flat or a concave tibial insert with retention of the posterior cruciate ligament when preoperative deformity was less severe, and either a concave or a posterior-stabilized (PS) insert with resection of the posterior cruciate ligament when deformity was more pronounced. All designs were associated with loss of BMD in the proximal tibia. The mean bone loss varied from 5 to 23% depending on the region of interest. There were no statistically significant differences between the groups, and the alteration of tibial insert constraint did not influence the bone remodeling. However, low precision values may have impaired the detection of differences.     

Regulation of the cholesterol side-chain cleavage cytochrome P-450 and adrenodoxin mRNAs in cultured choriocarcinoma cells.

Cytochrome P-450scc (P-450scc) catalyzes the cholesterol side-chain cleavage reaction, a rate-limiting enzymatic step for progesterone synthesis in trophoblastic and other steroidogenic cells. Adrenodoxin is the iron/sulfur protein donating electrons to P-450scc during this reaction. We examined the effects of cholera toxin (CT), an activator of adenylate cyclase, and 12-O-tetradecanoylphorbol acetate (TPA), a phorbol ester protein kinase C activator, on the levels of mRNAs encoding P-450scc and adrenodoxin in JEG-3 choriocarcinoma cells. CT induced in a concentration- and time-dependent manner P-450scc and adrenodoxin mRNA levels to 8-fold and 1.5-fold above that of control, respectively. TPA also increased P-450scc and adrenodoxin mRNA levels about 3-fold and 1.5-fold above that of control, respectively. Epidermal growth factor (EGF) was found to weakly induce P-450scc mRNA accumulation with a maximal 20% stimulation above basal levels. The effects of CT and TPA were apparently additive on both mRNAs. The protein synthesis inhibitor cycloheximide diminished basal, CT-, TPA-, and EGF-stimulated P-450scc mRNA accumulation whereas the opposite was observed for the adrenodoxin mRNA. Insulin-like growth factor I (IGF-I) appeared to have no effect on either mRNA. These data indicate that: (1) the accumulation of P-450scc and adrenodoxin mRNAs is mainly controlled by the cyclic adenosine 3',5'-monophosphate (cAMP)-dependent pathway but their stimulation by TPA- and EGF-induced signals may also play a weaker synergistic role; (2) the protein synthesis inhibitor cycloheximide inhibits basal, CT-, TPA- and EGF-stimulated P-450scc mRNA levels while it increases the expression of adrenodoxin mRNA suggesting that in the malignant trophoblasts these two enzyme mRNAs are differentially controlled.     

Effect of moderate physical exercise on serum lipoproteins. A controlled clinical trial with special reference to serum high-density lipoproteins.

A controlled trial is reported on the effects of mild-to-moderate physical activity on serum lipoproteins. After two baseline examinations 100 asymptomatic middle-aged men were randomly assigned to exercise and control groups. The exercise group participated in a 4-month exercise program that consisted of 3-4 weekly sessions. The control group was advised to maintain their previous exercise habits. The success of the program was corroborated by the increase in VO2 in the training group, but not in the control group. Serum triglycerides decreased from 1.54 +/- 0.10 to 1.27 +/- 0.08 mmol/1 (p less than 0.001) and high-density lipoprotein (HDL) cholesterol increased from 1.27 +/- 0.04 to 1.41 +/- 0.04 mmol/1 (p less than 0.01) in the exercise group during the trial. No change was seen in the control group. As the concentration of apolipoprotein AI stayed constant in both groups, the ratio HDL cholesterol/apolipoprotein AI increased only in the exercise group. The level of low-density lipoprotein (LDL) cholesterol and apolipoprotein AII decreased in both groups during the trial. The alterations in serum triglycerides and HDL cholesterol in the exercise group were not dependent on weight reduction; similar changes were also seen in subjects with constant body weight during the intervention.     

Insulin sensitivity after a reduced-fat diet and a monoene-enriched diet in subjects with elevated serum cholesterol and triglyceride concentrations

BACKGROUND AND AIMS: To investigate the effect of a reduced-fat diet and a monoene-enriched diet (MUFA diet) on serum lipids, glucose and insulin metabolism in subjects with elevated cholesterol and triglyceride concentrations. METHODS AND RESULTS: Eighteen subjects with elevated serum cholesterol and triglyceride concentrations consumed the MUFA diet (39% of energy (E%) as fat and 21 E% monoenes) and the reduced-fat diet (34 E% fat, 16 E% monoenes) for 4 weeks according to a randomized cross-over design. Both periods were preceded by consumption of a standardized baseline diet for 2 weeks. Serum lipid and lipoprotein concentrations were determined at the beginning and end of each diet period. A frequently sampled intravenous glucose tolerance test was performed after the MUFA diet and the reduced-fat diet. Insulin sensitivity index (SI) was 40% higher after the reduced-fat diet than after the MUFA diet (2.42 +/- 0.42 vs 1.73 +/- 0.24 10(-4) min-1 U-1 ml-1, p = 0.018). This change in insulin sensitivity was seen in 13 subjects and was most evident in those who began with the MUFA diet. Compared to the baseline diet (high in saturated fat), both experimental diets lowered serum total and LDL cholesterol concentrations (6.6-6.9%, p < 0.05 and 7.4-8.0%, p < 0.05 respectively). CONCLUSIONS: Both diets were equally effective in lowering serum lipid concentrations, but the reduced-fat diet resulted in better insulin sensitivity.     

Inhibin/activin betaB-subunit expression in pheochromocytomas favors benign diagnosis

Malignancy of pheochromocytomas is difficult to estimate on the basis of histopathological features. Good prognostic markers are not available. In our search for new markers to differentiate malignant pheochromocytomas from benign ones we tested the value of inhibin/activin subunit expression. Inhibins are heterodimeric glycoproteins consisting of an alpha-subunit and either a betaA- or a betaB-subunit. Activins are composed of beta-subunits only. Immunohistochemically inhibin/activin betaB-subunit was strongly positive in the normal adrenal medulla, but the cortex was negative. A striking difference was found in inhibin/activin betaB expression between benign and malignant pheochromocytomas. The majority of benign adrenal tumors (27 of 30) showed strong or moderate immunoreactivity, whereas all seven malignant tumors were negative or only weakly positive for inhibin/activin betaB-subunit. The percentage of positively staining cells varied greatly in extraadrenal pheochromocytomas and in those benign tumors that showed over 5 mitoses/10 high power fields, necrosis, or capsular or vascular invasion, here called borderline tumors. Inhibin/activin betaB messenger ribonucleic acid was also found in pheochromocytomas. However, no significant differences in messenger ribonucleic acid levels were found in various types of tumors. Weak immunohistochemical positivity for inhibin/activin betaA-subunit was detected in the adrenal cortex, but the medulla and most of the pheochromocytomas were negative. Our data show that inhibin/activin betaB-subunit is expressed in normal adrenal medullary cells. Strong staining is found in most benign adrenal pheochromocytomas, whereas malignant tumors are almost negative. This suggests that loss of inhibin/activin betaB-subunit expression in pheochromocytomas may be used as an indicator of malignant potential.