Salivary levels of Epstein-Barr virus DNA correlate with subgingival levels, not severity of periodontitis

Objective:  The aim of this study was to determine the presence and quantity of human cytomegalovirus (CMV) and Epstein-Barr virus (EBV) DNA in the saliva of patients with periodontitis, and investigate the correlation between these factors.
Methods:  Presence and amounts of viral DNA in saliva and subgingival plaque samples, from healthy and disease sites, of 65 adults diagnosed with chronic periodontitis were determined using quantitative real-time polymerase chain reaction.
Results:  Epstein-Barr virus DNA was detected in saliva of 81.5% (53/65) of patients at a median concentration of 4325 copies ml⁻¹. CMV DNA was detected in saliva of one individual (1.5%) at low copy number. Patients who had EBV in saliva were 10 times more likely to have EBV in subgingival plaque than patients lacking EBV in saliva (odds ratio = 10.1, 95% confidence interval = 2.6–39.5; P  = 0.0009). EBV DNA burden in saliva positively correlated with the amounts detected in plaque and with amounts detected in increasing number of affected sites ( P  < 0.0001). EBV DNA presence and quantity in saliva did not correlate with increasing severity of disease as measured by periodontal indices.
Conclusions:  Epstein-Barr virus DNA presence and burden in saliva are associated with its presence and burden in subgingival plaque, but presence and burden in saliva does not correlate with periodontal disease severity.     

Sequencing a mouse acute promyelocytic leukemia genome reveals genetic events relevant for disease progression

Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia (AML). It is characterized by the t(15;17)(q22;q11.2) chromosomal translocation that creates the promyelocytic leukemia-retinoic acid receptor α (PML-RARA) fusion oncogene. Although this fusion oncogene is known to initiate APL in mice, other cooperating mutations, as yet ill defined, are important for disease pathogenesis. To identify these, we used a mouse model of APL, whereby PML-RARA expressed in myeloid cells leads to a myeloproliferative disease that ultimately evolves into APL. Sequencing of a mouse APL genome revealed 3 somatic, nonsynonymous mutations relevant to APL pathogenesis, of which 1 (Jak1 V657F) was found to be recurrent in other affected mice. This mutation was identical to the JAK1 V658F mutation previously found in human APL and acute lymphoblastic leukemia samples. Further analysis showed that JAK1 V658F cooperated in vivo with PML-RARA, causing a rapidly fatal leukemia in mice. We also discovered a somatic 150-kb deletion involving the lysine (K)-specific demethylase 6A (Kdm6a, also known as Utx) gene, in the mouse APL genome. Similar deletions were observed in 3 out of 14 additional mouse APL samples and 1 out of 150 human AML samples. In conclusion, whole genome sequencing of mouse cancer genomes can provide an unbiased and comprehensive approach for discovering functionally relevant mutations that are also present in human leukemias.     

Two-stage method to remove population- and individual-level outliers from longitudinal data in a primary care database

PURPOSE: In the UK, primary care databases include repeated measurements of health indicators at the individual level. As these databases encompass a large population, some individuals have extreme values, but some values may also be recorded incorrectly. The challenge for researchers is to distinguish between records that are due to incorrect recording and those which represent true but extreme values. This study evaluated different methods to identify outliers. METHODS: Ten percent of practices were selected at random to evaluate the recording of 513,367 height measurements. Population-level outliers were identified using boundaries defined using Health Survey for England data. Individual-level outliers were identified by fitting a random-effects model with subject-specific slopes for height measurements adjusted for age and sex. Any height measurements with a patient-level standardised residual more extreme than ±10 were identified as an outlier and excluded. The model was subsequently refitted twice after removing outliers at each stage. This method was compared with existing methods of removing outliers. RESULTS: Most outliers were identified at the population level using the boundaries defined using Health Survey for England (1550 of 1643). Once these were removed from the database, fitting the random-effects model to the remaining data successfully identified only 75 further outliers. This method was more efficient at identifying true outliers compared with existing methods. CONCLUSIONS: We propose a new, two-stage approach in identifying outliers in longitudinal data and show that it can successfully identify outliers at both population and individual level. Copyright ? 2011 John Wiley & Sons, Ltd.     

Blood patch treatment of chylothorax following transthoracic oesophagogastrectomy: a novel technique to aid surgical management

Chylothorax is a well-recognised complication of oesophagectomy, occurring in around 3% of cases. If managed conservatively, the mortality rate can be over 50%. We describe our experience of managing a patient with a chylothorax following oesophagectomy, and the use of a blood patch (a novel technique) to overcome persistent leakage following re-operation. The authors feel that this technique has the potential for a wider application in the treatment of chyle leak, especially if combined with minimally invasive or radiological techniques.     

Computed tomography overestimation of esophageal tumor length: Implications for radiotherapy planning

AIM: To assess the relationship between preoperative computed tomography (CT) and postoperative pathological measurements of esophageal tumor length and the prognostic significance of CT tumor length data.METHODS: A retrospective study was carried out in 56 patients who underwent curative esophagogastrectomy. Tumor lengths were measured on the immediate preoperative CT and on the post-operative resection specimens. Inter- and intra-observer variations in CT measurements were assessed. Survival data were collected.RESULTS: There was a weak correlation between CT and pathological tumor length (r = 0.30, P = 0.025). CT lengths were longer than pathological lengths in 68% (38/56) of patients with a mean difference of 1.67 cm (95% CI: 1.18-2.97). The mean difference in measurements by two radiologists was 0.39 cm (95% CI: -0.59-1.44). The mean difference between repeat CT measured tumor length (intra-observer variation) were 0.04 cm (95% CI: -0.59-0.66) and 0.47 cm (95% CI: -0.53-1.47). When stratified, patients not receiving neoadjuvant chemotherapy showed a strong correlation between CT and pathological tumor length (r = 0.69, P = 0.0014, n = 37) than patients that did (r = 0.13, P = 0.43, n = 19). Median survival with CT tumor length > 5.6 cm was poorer than with smaller tumors, but the difference was not statistically significant.CONCLUSION: Esophageal tumor length assessed using CT does not reflect pathological tumor extent and should not be the only modality used for management decisions, particularly for planning radiotherapy.