EBV early lytic protein BFRF1 alters emerin distribution and post-translational modification.

The nuclear envelope (NE), a structural element of fundamental importance for the cell, is the first barrier that meets a virus in the early stages of viral maturation. Therefore, in order to allow the passage of nucleocapsids, viruses are known to modulate the architecture of the nuclear membrane to permit a proficient viral infection. Epstein-Barr Virus (EBV), a pathogen from Herpesvirus family, possesses two well conserved proteins, BFRF1 and BFLF2, which together form the heterodimeric nuclear egress complex (NEC) that is involved in the early steps of nuclear egress. Here we show that EBV replication causes the delocalization of emerin, a cellular LEM-domain protein normally distributed on the nuclear rim. We also demonstrate that the early lytic protein BFRF1 is responsible for emerin delocalization. Expression of BFRF1 alone or in combination with BFLF2 induces emerin hyperphosphorylation. Altogether, these results suggest a novel mechanism by which EBV exploits the cellular machinery for nucleocapsid egress.

Low-dose brain computer tomography sensitivity: a comparative study with a conventional technique.

A comparative study between brain conventional computed tomography (CT) examinations and low-dose examinations was performed. The aim of the work was to show if a low-dose technique can be used instead of a standard one. Forty patients with 51 brain lesions were studied with both techniques. The low-dose technique was optimized with mAs reduction to obtain a 25% dose reduction compared to standard acquisitions. Even if images have a poor signal-to-noise ratio, the low-dose technique visualized all the lesions disclosed by conventional examination except three chronic vascular lacunar infarcts. In conclusion, the low-dose technique can be adopted instead conventional CT scans in selected cases.

A survey of medical staff attitudes to an antibiotic approval and stewardship programme.

BACKGROUND: Antibiotic stewardship programmes (ASPs) are advocated to ensure appropriate antimicrobial use; with short-term evidence they may improve outcomes, limit adverse effects, encourage cost-effectiveness and reduce antibiotic resistance. At Concord Hospital, a 450-bed acute care hospital, we have used a telephone-based ASP for 15 years. There may be differences in attitudes to the ASP by prescribers, which may influence its long-term efficacy. METHOD: A 40-item self-administered questionnaire was sent to 190 junior and 250 specialist medical staff. We aimed to elicit medical staff attitudes to the ASP's utility, educational value, effect on patient care and ease of use. RESULTS: One hundred and sixty-four completed questionnaires were returned. Most (82%, 95% confidence interval (95%CI) 75-87%) clinicians had used the ASP, 98% of whom believed it to be a reasonable system. Most staff (85%, 95%CI 79-90%) believed that seeking approval made teams think carefully about antibiotic choice, agreed it provided helpful advice (91%, 95%CI 85-95%) and that the approval system provided useful advice and was educational (88%, 95%CI 81-92%). The ASP was felt time-consuming and detracting from clinical duties by 33% (95%CI 26-41%), while 10% (95%CI 5.8-15.7%) believed it undervalued intuition and experience. Few (19%, 95%CI 13-25%, P < 0.0001) clinicians believed it infringed their autonomy. The advice given through the ASP was believed by most (89%, 95%CI 81-92%) to improve patient outcomes. CONCLUSION: The ASP was surprisingly well supported by all levels of staff, and reinforced the benefits of maintaining an ASP policy.

Florid hyperplasia of mesonephric remnants involving prostate and periprostatic tissue. Possible confusion with adenocarcinoma.

Two cases of florid hyperplasia of mesonephric remnants occurring in the prostate are described. One case was originally interpreted as invasive adenocarcinoma on transurethral resection (TUR), resulting in radical prostatectomy. In the second case, a TUR specimen was diagnostic for adenocarcinoma, which was confirmed in the radical prostatectomy specimen. Florid mesonephric hyperplasia in the second case was an incidental finding. The TUR specimen in the first case and sections of the prostatectomy specimens in both cases contained a proliferation of tubules, which ranged from aggregates of microacini to dilated structures containing a characteristic colloid-like material. The location of these lesions in the base of the prostate gland and periprostatic soft tissue suggests that these may be mesonephric remnants that have become hyperplastic. This type of lesion shares many features with mesonephric hyperplasia occurring in the female genital tract, including the presence of eosinophilic intratubular material and a lobular arrangement of microacini lined by a single layer of epithelium with prominent nucleoli. However, the latter feature, along with the apparent permeation of the prostatic fibromuscular stroma, periprostatic soft tissue, and even neural spaces, closely mimicked prostatic adenocarcinoma. In both cases, the proliferating tubules reacted with keratin 903 and were negative for prostate-specific antigen and prostate acid phosphatase, thereby excluding the diagnosis of prostatic adenocarcinoma. We concluded that lobular hyperplasia of mesonephric remnants is a distinct histologic entity that may occur in the prostate and periprostatic soft tissues and closely mimic prostatic adenocarcinoma.

A simplified method for detecting cytomegalovirus by polymerase chain reaction from histologic sections of small biopsies.

Using a simplified procedure, we have extracted DNA from unstained paraffin sections of needle biopsies of kidney and liver transplants and identified the presence of CMV using the polymerase chain reaction. This method utilizes oligonucleotide primers for two genes shown to be specific for cytomegalovirus (CMV) as well as an internal control gene (hemoglobin) in a single reaction. Utilizing nested PCR amplification with agarose gel electrophoresis, CMV can be detected without radioisotopes to a level of sensitivity equivalent to one one-hundredth of a cytomegalic virocyte per cm2 of a 3-microM paraffin section. This method is applicable to situations where only scarce paraffin-embedded tissue is available.

Prostate cancer: correlation of MR images with tissue optical density at pathologic examination.

To explain the variability in detection of prostate cancer with magnetic resonance (MR) imaging, the authors correlated preoperative MR findings in 28 patients with tissue optical density (TOD) measurements on whole-mount pathologic slides prepared from radical prostatectomy specimens. TOD was used as an indicator of the degree of tissue compactness or openness. TOD measurements from proved cancers and from pathologic regions corresponding to MR lesions (areas of low signal intensity seen at T2-weighted MR imaging) were compared with TOD measurements from adjacent, nonmalignant tissue. TOD measurements corresponding to MR lesions were higher than noncancerous tissue measurements in all cases (P less than .005). Although most of these lesions represented cancers (21 of 30), nine of 30 represented benign tissue that was composed mainly of densely packed fibromuscular stroma (30% false-positive results). Thus, signal intensity appeared to be related to TOD rather than to a specific histologic tissue type, and the finding of a peripheral zone lesion with low signal intensity did not necessarily indicate the presence of a cancer.

Carcinoma of the prostate: MR images obtained with body coils do not accurately reflect tumor volume.

MR imaging with a body coil is unreliable in directly demonstrating tumor spread through the prostatic capsule. However, the likelihood of extracapsular spread of prostatic cancer rises with increasing tumor volume. The aim of our study was to assess the accuracy of MR with a body coil in diagnosing capsular penetration indirectly via an estimation of prostatic tumor volumes. Twenty-six patients with proved prostatic cancer that was clinically confined to the gland underwent MR imaging before radical prostatectomy and whole-mount pathologic sectioning of the specimen. Twenty of 31 lesions prospectively outlined on the MR images corresponded to cancers outlined on the pathology slides, and tumor volumes were calculated by using a voxel summation technique. On MR, tumor volume was underestimated in 11 of 20 cases and overestimated in nine of 20 cases. Only two of 20 size estimates based on MR findings were within 10% of actual tumor volume. Overlap in MR tumor volumes was significant between lesions with and without capsular penetration at microscopy. Factors contributing to inaccuracies in measurements of tumor volume on MR images included the variable histologic make-up of the tumors. Our results show that, although knowledge of the size of a prostatic lesion is important in predicting the behavior of the tumor, MR imaging with a body coil is not reliable for accurate estimation of tumor volume.

Diagnostic usefulness of nasal biopsy in Wegener's granulomatosis.

Wegener's granulomatosis (WG) frequently involves the upper respiratory tract, and nasal mucosal biopsy is often initially used to establish the diagnosis. To evaluate the diagnostic efficacy of nasal biopsy in WG, we reviewed the pathologic features of 30 such biopsy specimens from 17 patients with well-documented WG. Active vasculitis (granulomatous or nongranulomatous) was identified in seven of the patients (41%). The presence of extravascular foci of necrosis in lung biopsy samples has recently received attention as a characteristic feature of WG. Similar foci were found in the nasal samples from six of our patients, although vasculitis was absent in the samples from two of them. If extravascular foci of necrosis are regarded as characteristic or even diagnostic of WG, two additional patients in our series could be regarded as having had diagnostic nasal biopsies (nine of 17 patients). Nasal biopsy could thus be considered as diagnostic in 53% of the patients. Samples larger than 5 mm in greatest dimension were more likely to contain diagnostic features than were smaller samples (P = 0.002).