Cystatin C and neutrophil gelatinase-associated lipocalin: biomarkers for acute kidney injury after congenital heart surgery.

QUESTIONS UNDER STUDY: To evaluate the diagnostic value of serum Cystatin C and urine neutrophil gelatinase-associated lipocalin (NGAL) for the detection of acute kidney injury in patients undergoing congenital heart surgery. METHODS: Serial samples of serum Cystatin C and urine NGAL were collected from 139 consecutive patients with congenital heart defects aged 3 days to 30 years after admission to the intensive care unit, 2 and 6 hours after the end of cardiopulmonary bypass. Biomarker levels were compared to perioperative data retrospectively. Acute kidney injury was defined according to the paediatric-modified RIFLE classification. RESULTS: According to the paediatric-modified RIFLE criteria 53% of patients developed evidence of acute kidney injury. Serum Cystatin C concentrations were strongly correlated with severity of acute kidney injury. Optimal sensitivity of 80% and specificity of 66% for the prediction of acute kidney injury occurred at a cut-off value of 0.995 mg/l, 2 hours after the end of cardiopulmonary bypass. The 2 hour urine NGAL concentration was significantly correlated to the duration of cardiopulmonary bypass, time of aortic cross clamping, and serum lactate concentration. Moreover a significant correlation was found between urine NGAL and both length of hospital stay and mechanical ventilation. CONCLUSIONS: In patients after congenital heart surgery, urine NGAL indicates the damaging force of cardiopulmonary bypass and serum Cystatin C is a valuable predictive biomarker for resulting acute kidney injury.

Functional null mutations in the gonosomal homologue gene TBL1Y are associated with non-syndromic coarctation of the aorta.

In patients with congenital heart defects, chromosomal anomalies are 100 times more frequent than in control subjects. Coarctation of the aorta can be detected in 15-20% of patients with Ullrich-Turner syndrome. By extensively reviewing literature involving breakpoint analysis of gonosomal deletions in Ullrich- Turner syndrome patients with and without coarctation of the aorta, we identified several gonosomal homolgous gene pairs of interest. Four of these homologous gene pairs were investigated by standard DNA sequencing in a cohort of 83 patients with non-syndromic coarctation of the aorta. Subsequently stability of mutant RNA and protein was analyzed to verify functional relevance of detected mutations. We identified two unreported missense mutations in Exon 8 (p.D69H) and 9 (p.R176W) of TBL1Y. Bioinformatic analysis and 3D modelling predicted that both mutations lead to TBL1Y loss of function. In RT-PCR and Western blot analyses of HEK293 cells transfected with a vector carrying the full-length TBL1Y (wild-type and mutant), we documented the predicted protein instability by showing protein decay for both mutant proteins. TBL1Y is similar to its gonosomal homologue, TBL1X, and its autosomal homologue, TBLR1, on chromosome 3. Both genes are part of co-repressor machineries and required for transcriptional activation by transcription factors that involve CtBP1/2, which contributes to Notch signaling. Several studies have shown that Notch signalling is important for proper development of the left ventricular outflow tract. Our findings suggest that TBL1Y is involved in the genesis of non-syndromic coarctation of the aorta.

Severe consequences of healthcare-associated infections among residents of nursing homes: a cohort study.

The aim of this study was to identify the consequences of healthcare-associated infections in Norwegian nursing homes, to include debilitation, hospital transfer and mortality. We followed the residents of six nursing homes in two major cities in Norway during the period October 2004 to March 2005. For each resident with infection we randomly selected two controls among residents who did not have an infection. Cases and the controls were followed for 30 days as a cohort in order to measure the incidence of complications and risk ratio (RR) in the two groups. The incidence of infection was 5.2 per 1000 resident-days. After 30 days follow-up 10.9% of residents who had acquired infection demonstrated a reduction in overall physical condition compared with 4.8% in the unexposed group (RR: 2.3). Altogether 13.0% of residents with infections were admitted to hospital compared with 1.4% in the unexposed group (RR 9.2), and 16.1% residents with infections died in the nursing home during follow-up compared with 2.4% in the unexposed group (RR: 6.6). Residents with lower respiratory tract infections demonstrated higher morbidity and mortality. In conclusion, healthcare-associated infections cause severe consequences for people living in nursing homes, including debilitation, hospital admission and death.

Healthcare-associated infection among residents of long-term care facilities: a cohort and nested case-control study.

Knowledge of infection control measures in nursing homes is limited. This study aimed to assess the incidence of, and potential risk factors for, healthcare-associated infection in long-term care facilities in Norway. Incidence of healthcare-associated infection was recorded prospectively in six long-term care facilities located in two major cities in Norway between 1 October 2004 and 31 March 2005. For each resident with an infection we aimed for two controls in a nested case-control study to identify potential risk factors. Incidence of infection was 5.2 per 1000 resident-days. Urinary and lower respiratory tract infections were the most common. Patients confined to their beds [odds ratio (OR=2.7)], who stayed <28 days (OR=1.5), had chronic heart disease (OR=1.3), urinary incontinence (OR=1.5), an indwelling urinary catheter (OR=2.0) or skin ulcers (OR=1.8) were shown to have a greater risk for infection. Age, sex and accommodated in a two- versus single-bed room were not significant factors. Incidence of infection in nursing homes in Norway is within the range reported from other countries. This study identified several important risk factors for healthcare-associated infection. There is a need to prevent infection by implementing infection control programmes including surveillance in long-term care facilities.

Primary intraosseous carcinoma of the jaws arising from an odontogenic cyst--a case report.

BACKGROUND: Squamous cell carcinoma of the jaw located purely in the bone is extremely rare. Most of these intraosseous carcinomas, also called odontogenic carcinomas are thought to arise from the epithelial lining of an odontogenic cyst. CASE REPORT: A primary intraosseous carcinoma arising from an odontogenic cyst in a 64-year-old woman is reported. No subjective symptoms were noted by the patient. Multiple retained teeth with associated presumed cystic lesions were evident in the lower jaw on a routine radiograph. Histology revealed an intraosseous carcinoma after removal of the teeth and "cystectomy". No metastasis was detected. Segmental resection of the mandible, selective neck dissection and reconstruction with an iliac bone graft was performed. The patient is free of disease after 3 years. CONCLUSION: Although primary intraosseous carcinoma is rare, this case emphasizes the importance of careful histological examination of apparently innocuous odontogenic cysts. In addition, as malignant changes in their epithelial lining are always possible, "cystic" lesions should not only be removed but as completely as possible.

Uptake and metabolism of a dual fluorochrome Tat-nanoparticle in HeLa cells.

The ability to use magnetic nanoparticles for cell tracking, or for the delivery of nanoparticle-based therapeutic agents, requires a detailed understanding of probe metabolism and transport. Here we report on the development and metabolism of a dual fluorochrome version of our tat-CLIO nanoparticle termed Tat(FITC)-Cy3.5-CLIO. The nanoparticle features an FITC label on the tat peptide and a Cy3.5 dye directly attached to the cross-linked coating of dextran. This nanoparticle was rapidly internalized by HeLa cells, labeling 100% of cells in 45 min, with the amount of label per cell increasing linearly with time up to 3 h. Cells loaded with nanoparticles for 1 h retained 40-60% of their FITC and Cy3.5 labels over a period of 72 h in label-free media. Over a period of 144 h, or approximately 3.5 cell divisions, the T2 spin-spin relaxation time of cells was not significantly changed, indicating retention of the iron oxide among the dividing cell population. Using confocal microscopy and unfixed cells, both dyes were nuclear and perinuclear (broadly cytoplasmic) after Tat(FITC)-Cy3.5-CLIO labeling. Implications of the rapid labeling and slow excretion of the Tat(FITC)-Cy3.5-CLIO nanoparticle are discussed for cell tracking and drug delivery applications.