Mechanical ventilation in critically ill cancer patients.

Outcomes for cancer patients undergoing mechanical ventilation have improved in recent times, and the outlook for this patient group is no longer hopeless. Advances in ventilation techniques and increasingly sophisticated equipment have allowed oncologic intensivists to intervene more effectively in their patients' critical illness. In addition, many of these patients are now referred for intensive care much earlier. This article reviews the use of mechanical ventilation in critically ill cancer patients and includes discussion of the recently published outcome literature. We also discuss some recent advances in the broader field of mechanical ventilation and demonstrate how these advances can be applied to the oncology population.     

Parents' Reasons for Bringing Young Children to Hospital Emergency for Non-Urgent Reasons

The use of hospital emergency departments (EDs) has increased in recent years. Within children's hospitals, use for non-emergency reasons is dominated by young children, especially infants. A research team at the Hospital for Sick Children in Toronto, Canada sought to understand its ED use better with a view to determining the best strategic policy for dealing with its non-emergency patients. It undertook a 2-phase analysis of the use of its ED: the first phase (Brown & Shaw, 2000) analyzed patterns of use from the ED's database; the second phase, reported here, asked 158 parents and caregivers of patients age 0-7 their reasons for coming to the ED. Interview questions directly addressed 11 research questions. Users of ED for non-urgent reasons were mostly parents, fairly well educated, lived in various parts in a large urban area, and were likely to have very young and/or only children. About two-thirds had been to the ED previously, most had taken their children to more than one health care setting, 89.9% had family physicians, most had visited their own physicians recently, most made their own decisions to come to the ED, and half knew of another place they could have gone. A wide variety of health reasons were provided for coming to this ED and for not going elsewhere, but the most common were: this hospital provides the best care, and an emergency situation was perceived. Information from this study suggests that there are no simple solutions to providing information, alternate settings, or disincentives to non-urgent ED users for three reasons: (1) people come to EDs for a wide variety of reasons, (2) it is difficult to identify a subgroup that can be targeted for intervention, and (3) parents and caregivers may not use alternate settings or physicians. Two groups that might be targeted for intervention are parents of infants (especially first time parents), and parents of only children. Intervention should be at various levels of sophistication. High numbers of non-urgent ED users may be ongoing, and the price some children's hospitals pay for their high profile and prestige.     

Does the perception of downloading speed influence the evaluation of web-based lectures?

Medical schools put little emphasis upon education on public health, even though public health has played an important role in this century. One way to harness its benefit in order to improve global health in the 21st century is to globally share lectures on public health through the Internet. We have developed the Supercourse comprising of web-based learning modules on epidemiology in a standardized format with the size of each web page less than 10 kilobytes. A cross-sectional observational study was conducted to investigate the association of the perception of the access speed to Web-based lectures by teachers with their perception of lecture quality. There were 223 teachers who rated the lectures: 72% were from North America or Western Europe, 40% had taught epidemiology, and 14% reported that the speed of access was slow. Odds ratio of above-average rating among those who reported that the speed of access was fast relative to those who reported that the speed of access was slow was 4.25 (2.03-8.91; P = 0.001). The odds ratios were similar and significant after taking into account several other factors, including the variation of rating across lectures, region, and experiences in teaching epidemiology. The results indicate that the perception of the quality of Web-based lectures is related to the speed of access to a web page. The speed of access may be as important, if not more important, as the content itself. This suggests that, to share educational materials on the Web globally for teachers, one must consider not only the content, but also how people at local sites gain access to the Internet.     

Effect of mercury(II) on Nrf2, thioredoxin reductase-1 and thioredoxin-1 in human monocytes.

OBJECTIVES: Human blood levels of mercury are commonly 10nM, but may transiently reach 50-75nM after dental amalgam placement or removal. Controversy persists about the use of mercury because the effects of these 'trace' levels of mercury are not clear. Concentrations of mercury > or =5000nM unequivocally alter redox balance in blood cells including monocytes. In the current study, we tested a hypothesis that concentrations of mercury <100nM altered levels and activities of key proteins that maintain monocytic redox balance. METHODS: Human THP1 monocytes were exposed to 10-75nM of Hg(II) for 6-72h, with or without activation by lipopolysaccharide (LPS). The redox management proteins Nrf2 and thioredoxin-1 (Trx1) were separated by electrophoresis, then quantified by immunoblotting. The activity of the seleno-enzyme thioredoxin reductase (TrxR1), important in maintaining Trx1 redox balance, was measured by cell-free and cell-dependent assays. RESULTS: Concentrations of Hg(II) between 10-75nM increased Nrf2 levels (3.5-4.5 fold) and decreased Trx1 levels (2-3 fold), but these changes persisted <24h. Hg(II) potently inhibited (at concentrations of 5-50nM) TrxR1 activity in both cell-free and intracellular assays. Furthermore, Hg(II) transiently amplified LPS-induced Nrf2 levels by 2-3 fold and limited LPS-induced decreases in Trx1. All effects of Hg(II) were mitigated by pre-adding N-acetyl-cysteine (NAC) or sodium selenide (Na2SeO3), supplements of cellular thiols and selenols, respectively. SIGNIFICANCE: Our results suggest that nanomolar concentrations of Hg(II) transiently alter cellular redox balance in monocytes that trigger changes in Nrf2 and Trx1 levels. These changes indicate that monocytes have a capacity to adapt to trace concentrations of Hg(II) that are introduced into the bloodstream after dental amalgam procedures or fish consumption. The ability of monocytes to adapt suggests that low levels of mercury exposure from dental amalgam may not overtly compromise monocyte function.     

Electrical correlates of brain injury resulting from severe hypotension and hemodilution in monkeys

The effects of hypotension, hemodilution, and their combination on the relationship between concurrent brain electrical activity and resulting brain injury were studied in anesthetized monkeys. The authors compared changes in the electroencephalogram and somatosensory and auditory evoked potentials with eventual neuropathologic outcome. Our goals were: 1) to define the margin of safety for the monkey brain during hemodilution and hypotension under several simulated clinical conditions; and 2) to determine whether noninvasive measurements of brain electrical activity can predict ischemic brain cell damage. Forty-one monkeys were anesthetized with halothane (0.8 vol % inspired) and ventilated mechanically. Arterial hypotension was induced with trimethaphan (25 +/- 8 mmHg mean arterial blood pressure [MABP] for 30 min). Hemodilution was induced by replacing blood with lactated Ringer's solution (14 +/- 2% hematocrit for 1 h). Combined hemodilution and hypotension consisted of 30 min of hemodilution alone followed by superimposing hypotension for 30 min (16 +/- 3% hematocrit and 29 +/- 5 mmHg MABP). Ten monkeys died following severe hypotension alone or combined hemodilution and hypertension as a consequence of cardiac arrest or undetermined (possibly neurologic) causes. No histologic evidence of ischemic brain cell injury was found in surviving monkeys subjected to hemodilution or hypotension alone. Neuropathologic alterations in the cerebral cortex, cerebellum, hippocampus and globus pallidus as well as neurologic and behavioral deficits were found in seven of 16 surviving monkeys subjected to both hemodilution and hypotension. These findings resulted from combinations of hematocrit less than 20% and MABP below 40 mmHg.(ABSTRACT TRUNCATED AT 250 WORDS)     

Early intellectual dysfunction following coronary bypass surgery

As part of a major prospective study of neurological and psychological complications of coronary artery bypass graft surgery, involving 312 patients, detailed psychometric testing was carried out before and after operation on 298 patients using a battery of 10 standard tests of intellectual function. This report is concerned with the early neuropsychological dysfunction detectable one week after operation. Two hundred and thirty-five patients (79 per cent of the cohort) showed impairment in some aspect of cognitive function at the seventh day after operation. Only 63 patients (21 per cent) showed no deterioration from levels before operation in any of the 10 test scores. One hundred and twenty-three of the patients whose scores deteriorated had no symptoms while in hospital. Eighty-nine patients complained of cognitive impairment, and 23 patients were considered to be overtly disabled by their intellectual dysfunction, during the period soon after operation. There is therefore a high incidence of early cerebral dysfunction detectable by psychometric testing following coronary artery bypass graft surgery. Often this was not of sufficient severity to cause serious concern to the patients or to interfere with their everyday activities in the hospital environment.     

Neocortical transplants grafted into the newborn rat brain demonstrate a blood-brain barrier to macromolecules

Vascular permeability was examined in fetal neocortical transplants grafted into the cerebral cortex of newborn rats. Methods based on the histochemical labeling of intravenously administered horseradish peroxidase or on the immunocytochemical demonstration of endogenous immunoglobulin showed the presence of a blood barrier within the transplants.     

Isolated post-challenge hyperglycaemia confirmed as a risk factor for mortality

Abstract Aims/hypothesis. The aim of this study was to examine the possible link between isolated post-challenge hyperglycaemia (2-h post-challenge plasma glucose ≥ 11.1 mmol/l, and fasting plasma glucose < 7.0 mmol/l) and mortality. Methods. The data from three population based longitudinal studies (in Mauritius, Fiji and Nauru) were pooled and mortality rates were determined in 9179 people who were followed for between 5 and 12 years. Results. There were 595 people with previously diagnosed diabetes, and 799 with newly diagnosed diabetes, of whom 243 (31) had isolated post-challenge hyperglycaemia. In comparison with people without diabetes, people with isolated post-challenge hyperglycaemia had an increased risk of all-cause mortality [Cox proportional hazards ratio (95 % CI): 2.7 (1.8–3.9) – men; 2.0 (1.3–3.3) – women], and of cardiovascular mortality [2.3 (1.2–4.2) – men; 2.6 (1.3–5.1) – women]. In addition, men with isolated post-challenge hyperglycaemia had a high risk of cancer death [8.0 (3.6–17.9)]. Conclusion/interpretation. These data show that isolated post-challenge hyperglycaemia, which can only be identified by the 2-h glucose, is common, and at least doubles the mortality risk. This should be considered in the design of screening programmes that use only fasting glucose [Diabetologia (1999) 42: 1050–1054] Received: 18 March 1999 and in revised form: 27 May 1999