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Clonal heterogeneity, distribution, and pathogenicity of methicillin-resistantStaphylococcus aureus

Four thousand eighty-eightStaphylococcus aureus isolates obtained from patients hospitalised in a university clinic and four community hospitals over a period of one year were screened for methicillin resistance. A resistance rate of 5% was detected among initial isolates. Distribution of methicillin-resistantStaphylococcus aureus (MRSA) and methicillin-sensitiveStaphylococcus aureus showed an increased prevalence of MRSA in clinically significant specimens such as blood, central venous catheter tips, bronchial secretions, and wound secretions. Typing of 110 MRSA strains (initial isolates) by macrorestriction analysis of chromosomal DNA revealed 26 different genotypes that could be divided into five epidemic and 21 sporadic strains. More than 50% of all isolates belonged to one type that was confirmed to be closely related to the southern-German epidemic strain. Production of virulence factors such as enterotoxin A-D and toxic shock syndrome-toxin 1 among MRSA strains (initial isolates) occurred in ten of 26 different MRSA types. A strong correlation between genotype and toxin production was demonstrated.     

Effects of drugs combining H1 and H2 receptor antagonist activity on histamine release and life threatening anaphylactoid reactions in pigs

Summary Two recently synthetized drugs combining H1- and H2-receptor antagonist activity in a single molecule (alitidine, clophetidine) were compaired for their potency in preventing histamine release and lifethreatening anaphylactoid reactionin vivo with the usually tested H1/H2-blocker combination dimetindene/cimetidine. Saline premedication in a fourth group served as control. Anaesthetized and ventilated pigs were administered H1/H2-blockers or placebo and 500 ml of blood were removed. Subsequently, 500 ml saline solution containing 1 mg/kg compound 48/80 for initiating histamine release were rapidly reinfused (n=15 pigs per group). The system proved reliable in creating hypotension and histamine release in the placebo group. The extent of histamine release did not differ between the placebo, alitidine and dimetindene/cimetidine groups. However, clophetidine was shown to be effective in preventing increases in plasma histamine after compound 48/80. Tachycardia was almost completely prevented by dimetindene/cimetidine, was diminished by clophetidine, but was not affected by alitidine. Hypotension following 48/80 was best reversed by clophetidine. This investigation suggests that clophetidine is a most promising drug in preventing histamine release and its circulatory effects in a pig anaphylactoid shock model. It requires, however, further quantitative confirmation in experiments with a two-group design only, since the analysis of variance is less suitable for the extreme variation of the plasma-histamine values after administration of compound 48/80.     

Prenatal detection of congenital renal malformations by fetal ultrasonographic examination: an analysis of 709,030 births in 12 European countries

The study was performed to evaluate the prevalence of prenatal ultrasound diagnoses for renal anomalies in 20 registries of 12 European countries, and to compare the different prenatal scanning policies. Standardized data were acquired from 709,030 livebirths, stillbirths, and induced abortions during the study period of 2.5 years and transmitted for central analysis. At least one renal malformation was diagnosed in 1130 infants and fetuses. Prenatal diagnosis (PD) was given in 81.8% of all cases, 29% of these pregnancies were terminated. The highest detection rate was reported for unilateral multicystic dysplastic kidneys with 97% (102/105). An early diagnosis was documented for exstrophy of bladder at a mean gestational age of 18.5 weeks. Dilatations of the upper urinary tract were seen late in pregnancy at 28.3 weeks. Terminations of pregnancies (TOP) were performed in 67% (58/86) of the detected bilateral renal agenesis/dysgenesis, but only 4% of the unilateral multicystic dysplastic renal malformations (4/102). In about 1/3 of the cases, renal malformations are within the category of associated malformations, which include multiple non-syndromal malformations, chromosomal aberrations, and non-chromosomal syndromes. Renal malformations were detected in 2/3 of the associated category by the first prenatal ultrasound scan. Detection rates vary in the different countries of the European community due to diverse policies, ethical, and religious background. Countries with no routine ultrasound show the lowest rates in detection, and termination of pregnancy. Prenatally detected renal malformations should result in a careful examination for further anomalies. Prenatal ultrasound fulfills the needs of screening examinations and is a good tool in detecting lethal and severe renal malformations.     

Prediagnostic serum glyceraldehyde-derived advanced glycation end products and mortality among colorectal cancer patients

Glyceraldehyde-derived advanced glycation end products (glycer-AGEs) could contribute to colorectal cancer development and progression due to their pro-oxidative and pro-inflammatory properties. However, the association of glycer-AGEs with mortality after colorectal cancer diagnosis has not been previously investigated. Circulating glycer-AGEs were measured by competitive ELISA. Multivariable Cox proportional hazards models were used to calculate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) for associations of circulating glycer-AGEs concentrations with CRC-specific and all-cause mortality among 1034 colorectal cancer (CRC) cases identified within the European Prospective Investigation into Cancer and Nutrition (EPIC) study between 1993 and 2013. During a mean of 48 months of follow-up, 529 participants died (409 from CRC). Glycer-AGEs were statistically significantly positively associated with CRC-specific (HR_{Q5 vs Q1} = 1.53, 95% CI: 1.04-2.25, P_trend = .002) and all-cause (HR_{Q5 vs Q1} = 1.62, 95% CI: 1.16-2.26, P_trend < .001) mortality among individuals with CRC. There was suggestion of a stronger association between glycer-AGEs and CRC-specific mortality among patients with distal colon cancer (per SD increment: HR_{proximal colon} = 1.02, 95% CI: 0.74-1.42; HR_{distal colon} = 1.51, 95% CI: 1.20-1.91; P_{effect modification} = .02). The highest HR was observed among CRC cases in the highest body mass index (BMI) and glycer-AGEs category relative to lowest BMI and glycer-AGEs category for both CRC-specific (HR = 1.78, 95% CI: 1.02-3.01) and all-cause mortality (HR = 2.15, 95% CI: 1.33-3.47), although no statistically significant effect modification was observed. Our study found that prediagnostic circulating glycer-AGEs are positively associated with CRC-specific and all-cause mortality among individuals with CRC. Further investigations in other populations and stratifying by tumor location and BMI are warranted.     

Plasma osteoprotegerin,its correlates,and risk of heart failure: a prospective cohort study

Heart failure (HF) is a disabling condition involving complex vascular, neurohormonal and immune systems’ interactions. Osteoprotegerin (OPG), a bone-regulatory cytokine, has been suggested to play a key role in skeletal, vascular, and immune biology, with elevated levels observed in both experimental and clinical HF. In the present study we aimed to identify clinical OPG correlates and investigated whether elevated OPG, as a marker of HF vascular and immune activation, may interact with N-terminal pro-brain natriuretic peptide (NT-proBNP), a marker of HF neurohormonal activation, thus synergistically increasing HF risk. We used a case-cohort study, nested within the European Prospective Investigation into Cancer and Nutrition-Potsdam, comprising 2647 participants including 252 incident HF cases identified during a mean follow-up of 8.2 ± 1.6 years. In both men and women significant positive associations were observed between OPG and age, smoking, prevalent diabetes, C-reactive protein, sex hormone-binding globulin, and additionally prevalent coronary heart disease and uric acid in men only. In women, OPG was furthermore positively related to hypertension and fetuin-A. After multivariable adjustment each doubling of OPG was associated with a 3.01-fold increased HF risk (95 % CI 1.49–6.06) in men. A significant interaction was observed between OPG and NT-proBNP. In men, a combination of high levels of both OPG and NT-proBNP, compared to a combination of low levels, was associated with an approximately fivefold increased HF risk. In women, no associations were observed. These findings suggest that, in men, the activation of different immune, neurohormonal, and vascular pathophysiological pathways may confer increased HF risk.