EMS1 gene expression in primary breast cancer: relationship to cyclin D1 and oestrogen receptor expression and patient survival

The EMS1 and CCND1 genes at chromosome 11q13 are amplified in about 15% of primary breast cancers but appear to confer different phenotypes in ER positive and ER negative tumours. Since there are no published data on EMS1 expression in large series of breast cancers we examined the relationship of EMS1 expression with EMS1 gene copy number and expression of mRNAs for cyclin D1 and ER. In a subset of 129 patients, where matched tumour RNA and DNA was available, EMS1 mRNA overexpression was associated predominantly with gene amplification (P = 0.0061), whereas cyclin D1 mRNA overexpression was not (P = 0.3142). In a more extensive series of 351 breast cancers, there was no correlation between cyclin D1 and EMS1 expression in the EMS1 and cyclin D1 overexpressors (P = 0.3503). Although an association between EMS1 mRNA expression and ER positivity was evident (P = 0.0232), when the samples were divided into quartiles of EMS1 or cyclin D1 mRNA expression, the increase in the proportion of ER positive tumours in the ascending EMS1 mRNA quartiles was not statistically significant (P = 0.0951). In marked contrast there was a significant stepwise increase in ER positivity in ascending quartiles of cyclin D1 mRNA (P = 0.030). A potential explanation for this difference was provided by the observation that in ER positive breast cancer cells oestradiol treatment resulted in increased cyclin D1 gene expression but was without effect on EMS1. The relationship between EMS1 expression and clinical outcome was examined in a subset of 234 patients with median follow-up of 74 months. High EMS1 expression was associated with age > 50 years (P = 0.0001), postmenopausal status (P = 0.0008), lymph node negativity (P = 0.019) and an apparent trend for worse prognosis in the ER negative subgroup. These data demonstrate that overexpression of EMS1 mRNA is largely due to EMS1 gene amplification, is independent of cyclin D1 and ER expression and, in contrast to cyclin D1, is not regulated by oestrogen. Independent overexpression of these genes may confer different phenotypes and disease outcomes in breast cancer as has been inferred from recent studies of EMS1 and CCND1 gene amplification.     

Esophagitis in Sprague-Dawley rats is mediated by free radicals

Free radical-mediated esophagitis was studied during duodenogastroesophageal reflux (mixed reflux) or acid reflux in rats. The influence of reflux on esophageal glutathione levels was also examined. Mixed reflux caused more gross mucosal injury than acid reflux. Gross mucosal injury occurred in the mid-esophagus. Total glutathione (GSH) in the esophageal mucosa of control rats was highest in the distal esophagus. The time course of esophageal GSH in rats treated by mixed reflux showed a significant decrease 4 hr after initiation of reflux, followed by a significant increase from the 12th hour on. Mucosal GSH was increased in both reflux groups after 24 hr but significantly more so in the mixed than in the acid reflux group. The free radical scavenger superoxide dismutase (SOD) prevented esophagitis and was associated with decreased GSH levels. GSH depletion by buthionine sulfoximine (BSO) prevented esophagitis and stimulated SOD production in the esophageal mucosa. It is concluded that gastroesophageal reflux is associated with oxidative stress in the esophageal mucosa. The lower GSH levels in the mid-esophagus may predispose to damage in this area. Duodenogastroesophageal reflux causes more damage than pure acid reflux. Oxidative stress leads to GSH depletion of the esophageal mucosa in the first few hours following damage but then stimulates GSH production. GSH depletion by BSO does not worsen esophagitis since it increases the esophageal SOD concentration.     

Comparison of gastric mucosal pH and clinical judgement in critically ill patients

OBJECTIVES: To compare gastric tonometry (pHi) with estimates of pHi in ill injured patients, and to correlate pHi with haemodynamic variables. DESIGN: Prospective, non-interventional study. SETTING: ICU of Level I trauma centre, USA. MAIN OUTCOME MEASURES: 154 gastric tonometry measurements were compared with physicians' estimates of adequacy of resuscitation. Resuscitation was categorised as inadequate (pHi < 7.35) or adequate (pHi> or = 7.35). Measured and estimated pHi were also compared with oxygen delivery, oxygen consumption, cardiac index, mixed venous O2 saturation, and critical illness scores. RESULTS: Estimated pHi was often higher than measured pHi in the judgement of all four surgical intensive care physicians. Measured pHi correlated positively with mixed venous O2 tension (r = 0.21). There were significant negative correlations between measured pHi and both oxygen delivery (r = -0.25) and oxygen consumption (r = 0.28). Estimated pHi correlated positively with mean arterial pressure (r = 0.21) and hospital day (r = 0.26); it correlated negatively with pulmonary arterial elastance (r = -0.35). CONCLUSION: Experienced intensive care physicians tended to overestimate visceral perfusion, which suggests that gastric tonometry adds useful information over and above routine haemodynamic indices. Arterial blood pressure and mixed venous oxygen saturation correlated better with measured pHi than with other indices of perfusion.     

Interpretation time of serial chest CT examinations with stacked-metaphor workstation versus film alternator

PURPOSE: Interpretation time of serial staging chest CT cases, which each contained current and previous examinations, with a simple prototype workstation called filmstack was experimentally compared with interpretation time with a film alternator. MATERIALS AND METHODS: The filmstack displayed a "stack" of sections for each examination; user controls allowed rapid selection of preset attenuation windows and both synchronized and unsynchronized scrolling. Eight radiologists were timed as they used the filmstack and the film alternator to interpret four ergonomically complex serial CT cases. RESULTS: All reports dictated on the basis of findings with filmstack and film were of acceptable clinical accuracy. The time to examine a case with filmstack was significantly faster than the time with film, including the time to load and unload the alternator (99% confidence [P = .01]). There was no statistically significant difference in interpretation time between filmstack and prehung film. CONCLUSION: Use of a low-cost stacked CT workstation with a single 1,024 x 1,024 monitor is an effective means of interpreting cases that require comparison of multiple CT examinations.     

Predictability of healing of ischemic leg ulcers by radioisotopic and Doppler ultrasonic examination

In a prospective study of twenty-six patients with ischemic ulcerations of the lower extremity, the predictive reliability with regard to spontaneous wound healing of diabetes, pedal pulses, ankle blood pressure (ABP) as measured by doppler ultrasound, and "leg ulcer scan" as performed by the intra-arterial injection of radioactive albumin was evaluated. The results suggest that only the leg ulcer scan is significantly reliable in predicting the likelihood of spontaneous healing. The following format for the evaluation of the ischemic leg ulcer is therefore suggested: (1) If pedal pulses are present, a three week trial of conservative therapy is indicated before further evaluation. (2) If the doppler ABP is 50 mm Hg or less, the ulcer will not heal spontaneously. (3) Leg ulcer scan is indicated: (a) in the absence of pedal pulses if ABP is less than 50 mm Hg; (b) in the presence of pedal pulses if there is no evidence of spontaneous healing after three weeks of conservative therapy.