Fluorescence lifetime imaging distinguishes basal cell carcinoma from surrounding uninvolved skin

Background  Fluorescence lifetime imaging (FLIM) is a novel imaging technique that generates image contrast between different states of tissue due to differences in fluorescence decay rates.
Objectives  To establish whether FLIM of skin autofluorescence can provide useful contrast between basal cell carcinomas (BCCs) and surrounding uninvolved skin.
Methods  Unstained excision biopsies of 25 BCCs were imaged en face with FLIM following excitation of autofluorescence with a 355 nm pulsed ultraviolet laser.
Results  Using FLIM we were able to distinguish areas of BCC from surrounding skin in an ex vivo study. Significant reductions in mean fluorescence lifetimes between areas of BCC and areas of surrounding uninvolved skin were demonstrated ( P  <   0·0001). These differences were apparent irrespective of the decay model used to calculate the fluorescence lifetimes (single vs. stretched exponential) or the long-pass filter through which the emitted autofluorescence was collected (375 vs. 455 nm). Conversely, there was no significant difference between the BCC and uninvolved areas of each sample when mean autofluorescence intensities were examined. Moreover, wide-field false-colour images of fluorescence lifetimes clearly discriminated areas of BCC from the surrounding uninvolved skin.
Conclusions  We therefore believe that FLIM has a potential future clinical role in imaging BCCs for rapid and noninvasive tumour delineation and as an aid to determine adequate excision margins with best preservation of normal tissue.     

Pituitary adenomas in patients with Cushing disease: initial experience with Gd-DTPA-enhanced MR imaging

To assess the role of magnetic resonance imaging in the evaluation of adrenocorticotropic-hormone (ACTH)-producing pituitary adenomas, and the effect of intravenously administered gadolinium-diethylenetriaminepentaacetic acid (DTPA) on lesion/pituitary contrast, imaging was performed in 13 patients with clinical and chemical evidence of Cushing disease. Images were obtained at 0.5 T before and after the injection of Gd-DTPA (0.1 mmol/kg). Lesions were identified in eight of 12 precontrast and ten of 12 postcontrast studies. In these 12 patients adenomas were found at transsphenoidal surgery. The other patient, with normal images, was found to have an ectopic source of ACTH. Coronal images corresponded remarkably well with the neurosurgeon's intraoperative findings. Serial T1-weighted images disclosed early enhancement of the pituitary gland and delayed enhancement of the cystic adenomas. The discrepancy in times to peak enhancement accounted for improved lesion/pituitary contrast in some early images and for reversal or diminution of lesion/pituitary contrast in later images.     

Impact of bowel obstruction at the time of initial presentation in women with ovarian cancer

Objective  To determine whether the presence of bowel obstruction at the time of initial presentation has any prognostic significance in these women.
Design  Retrospective cohort study.
Setting  Dedicated gynaecological oncology service of a large tertiary institution.
Population  Women who had a bowel obstruction as part of their initial presentation of ovarian cancer were identified between 1995 and 2007. Each woman was matched with four control women (with disease but no obstruction).
Methods  Women with disease were compared with controls to determine the impact, if any, of bowel obstruction at presentation. Several prognostic variables including bowel obstruction were also evaluated in a Cox proportional hazard model.
Main outcome measures  Progression-free survival (PFS) and overall survival (OS).
Results  Forty-eight women with disease and 192 controls were identified during the study period. The median follow-up period was 19 months among women with disease versus 20 months in controls. No differences were seen in demographics and clinical characteristics of the women. Optimal cytoreduction rate was similar between the two groups (75% versus 78%, P  = 0.7). Patients with bowel obstruction had a shorter PFS and OS compared with controls [19 months versus 21 months ( P  = 0.01) and 22 versus 35 months ( P  = 0.008)], respectively. Bowel obstruction at presentation was an independent prognostic variable with a hazard ratio of 1.5 ( P  = 0.009). Other prognostic variables were age, stage and extent of surgical cytoreduction.
Conclusions  Bowel obstruction at the time of initial presentation is an adverse prognostic factor in women with ovarian cancer.     

泊沙康唑在健康志愿者肺组织中的药动学与药效学研究

泊沙康唑是一种具有广谱抗菌作用的三唑类抗真菌药,对曲霉、隐球菌、念珠菌、组织胞浆菌及酵母等有效。美国已批准泊沙康唑的适应证包括：在应用免疫抑制剂患者中的侵袭性曲霉病和念珠菌病的预防性用药,及难治性口咽部念珠菌病的治疗,而将泊沙康唑用于肺部及其他弥漫性真菌病的治疗尚处于临床研究阶段。作者以一项前瞻性、开放的临床试验进行了泊沙康唑在健康志愿者肺组织中的药动学／药效学（PK／PD）研究。     

The optimal use of allopurinol: an audit of allopurinol use in South Auckland

Background : Gout is a common and challenging problem in South Auckland, New Zealand. Allopurinol is widely used but urate reduction remains unsatisfactory. Allopurinol dosing guidelines and a therapeutic range for plasma oxypurinol levels have been published.
Aims : We aimed to determine the appropriateness of allopurinol dosing according to current guidelines and to assess the relationship between plasma creatinine, oxypurinol and urate. In addition, we assessed the clinical usefulness of the oxypurinol level.
Methods : Thirty-one patients, on a stable dose of allopurinol for at least three weeks, had plasma creatinine, urate and oxypurinol measured as part of routine clinical assessment. Relationships between the various methods were examined using regression analysis. Fisher's exact test was used to test associations with categorical variables.
Results : Fifty-five per cent of patients were on higher than recommended doses of allopurinol. There was a statistically significant relationship between calculated creatinine clearance and plasma oxypurinol level. Only 50% of patients with a plasma oxypurinol within the therapeutic range (30–100 μmol/L) had a plasma urate <0.42 mmol/L and this did not increase significantly in the patients with an oxypurinol level <100 μmol/L.
Conclusions : There is poor adherence to the current recommended dosing guidelines for allopurinol. Creatinine clearance rather than plasma creatinine needs to be used to predict the dose of allopurinol. The current role of the oxypurinol level is to identify non-compliers with allopurinol therapy. We need further research to clarify whether increasing the dose of allopurinol outside the recommended dose range to reach an oxypurinol level of close to 100 μmol/L may be of benefit in those who have not had sufficient urate reduction.     

Vancomycin-resistant enterococcus in end-stage renal disease

The percentage of nosocomial vancomycin-resistant enterococci (VRE) has been increasing rapidly in the United States. This has recently resulted in recommendations to reserve vancomycin use for cases with proven resistance to other antimicrobials. We prospectively investigated the incidence of VRE in our dialysis population and compared it with a control group of 40 clinic patients with chronic renal insufficiency (CRI) who had a serum creatinine level greater than 1.5 mg/dL, but were not undergoing dialysis. The incidence of VRE on our campus is almost 10%, which is similar to US data. We studied 50 chronic hemodialysis (HD) patients and 50 peritoneal dialysis (PD) patients. Each patient had a rectal swab test performed and cultured for the presence of enterococci. Antimicrobial exposures over the 6 months before the initial swab test were reviewed in each patient. At least one repeated swab test was performed in 30 CRI, 45 HD, and 37 PD patients. From the initial swab culture, vancomycin-sensitive enterococci (VSE) were isolated in 65% of CRI, 54% of HD, and 70% of PD patients. No CRI or HD patients had VRE isolated and 2% (1 of 50) of PD patients had VRE isolated. The remaining patients had no enterococci isolated. Review of antimicrobial exposures in the 6 months before the initial swab test showed 0% of CRI, 32% of HD, and 36% of PD patients received vancomycin. Other antimicrobials were administered to 40% of CRI, 46% of HD, and 78% of PD patients in the same time period. In the month immediately preceding the initial swab test, 0% of CRI, 12% of HD, and 22% of PD patients received vancomycin and 18% of CRI, 20% of HD, and 36% of PD patients received other antimicrobials. Results from repeated cultures showed that 57% of CRI, 40% of HD, and 38% of PD patients changed their culture status related to VSE, VRE, or no enterococci present. Cultures of 342 swabs from 140 patients yielded three VRE isolates in two patients. We conclude that despite the frequent use of vancomycin and other antimicrobials, the incidence of VRE in our renal population is less than the reported incidence. Given this lack of VRE isolates, we recommend the continued judicious use of vancomycin in treating renal patients and continued enterococcal sensitivity surveillance.     

Haemodiafiltration with sorbent-regenerated ultrafiltrate as replacement fluid: a multicenter study

BACKGROUND: Uncoated adsorbent charcoal may regenerate the ultrafiltrate suggesting its use as an endogenous substitution fluid. The objective of this study was to assess the safety and the long-term clinical results. METHODS: Thirty-three chronic uraemic patients were dialysed for 1 year using two haemodialysers in series in order to separate convection from diffusion. At the outflow of the convective haemofilter, a cartridge containing 130 g of uncoated charcoal was inserted. The regenerated ultrafiltrate was then infused at the entrance of the diffusive dialyser. Ex vivo and in vitro studies were performed to analyse the adsorption characteristics and the release of aluminium, other trace elements, and microparticles. RESULTS: Passage through the charcoal left urea, phosphate, potassium, calcium, and bicarbonate concentrations unchanged. Creatinine, uric acid and beta 2- microglobulin were almost completely absorbed by the charcoal. Aluminium release was dependent upon time of storage, as inferred from studies on inter-lot variability. Washing with bicarbonate buffer (pH 7.0) allowed reduction of aluminium levels to within the pharmacopoeia requirements for intravenous fluids. No significant pre- or post- charcoal differences were observed for several trace elements such as manganese, selenium, arsenic, cadmium, mercury, lead, chromium and zinc. Copper was completely retained in the charcoal. Regenerated ultrafiltrate infused at the entrance of the diffusive dialyser was free of microparticles, bacteria, and endotoxin. Clinical tolerance was excellent and blood pressure control satisfactory. A significant decrease in serum values of beta 2-microglobulin was observed at 6 and 12 months of treatment. CONCLUSIONS: Reinfusion of ultrafiltrate through an uncoated charcoal cartridge proved to be a safe, well- tolerated and simple technique. Further potential benefits of regenerated ultrafiltrate may also include the maintenance of acid-base balance with reinfusion of endogenous bicarbonate.