A comprehensive framework for evaluating the environmental health and safety implications of engineered nanomaterials

Engineered nanomaterials (ENM) are a growing aspect of the global economy, and their safe and sustainable development, use, and eventual disposal requires the capability to forecast and avoid potential problems. This review provides a framework to evaluate the health and safety implications of ENM releases into the environment, including purposeful releases such as for antimicrobial sprays or nano-enabled pesticides, and inadvertent releases as a consequence of other intended applications. Considerations encompass product life cycles, environmental media, exposed populations, and possible adverse outcomes. This framework is presented as a series of compartmental flow diagrams that serve as a basis to help derive future quantitative predictive models, guide research, and support development of tools for making risk-based decisions. After use, ENM are not expected to remain in their original form due to reactivity and/or propensity for hetero-agglomeration in environmental media. Therefore, emphasis is placed on characterizing ENM as they occur in environmental or biological matrices. In addition, predicting the activity of ENM in the environment is difficult due to the multiple dynamic interactions between the physical/chemical aspects of ENM and similarly complex environmental conditions. Others have proposed the use of simple predictive functional assays as an intermediate step to address the challenge of using physical/chemical properties to predict environmental fate and behavior of ENM. The nodes and interactions of the framework presented here reflect phase transitions that could be targets for development of such assays to estimate kinetic reaction rates and simplify model predictions. Application, refinement, and demonstration of this framework, along with an associated knowledgebase that includes targeted functional assay data, will allow better de novo predictions of potential exposures and adverse outcomes.     

Analysis of junior doctor supervision in Australasian emergency departments

Background: Supervision of junior doctors in ED is vital but limited literature exists on how it is provided. Objective: To assess Australasian ED supervision and review regional legislature supervision requirements. Methods: Between December 2008 and June 2009 emails containing a link to a cross‐sectional survey were sent to Directors of Emergency Medicine Training in all Australasian ED accredited for advanced training. Non‐responding ED were subsequently contacted by telephone or email. Regional legislature supervision requirements were obtained from postgraduate medical councils. Results: A total of 103 (98.1%) of 105 ED participated. Senior review in person was mandatory in 43.2% of ED for patients of PGY1 (postgraduate year 1 doctors) and 6.1% of ED for patients of PGY2 (P < 0.001). Of ED without mandatory review, 13% had written guidelines detailing which patients required review. When ED consultants were on‐site, they most commonly provided supervision in 60.2% of ED and shared supervision equally with registrars in 35.7% of ED; when consultants were off‐site registrars most commonly provided supervision in 87.6% of ED. Fewer major regional/rural base hospitals had 24 h PGY3 or above supervision than major referral and urban district hospitals (82.6% vs 100% and 100%, P < 0.01). Regional legislature requirements varied with no universal guidelines. Conclusion: There are significant differences between supervision requirements for PGY1 and PGY2. A minority of ED in Australasia do not have 24 h supervision by PGY3 or higher. Few ED have written guidelines for supervising PGY1 and PGY2. The majority of registrar supervision occurs without consultant oversight. Legislature requirements for supervision in ED are variable between regions.     

Arginine vasopressin and oxytocin responses to insulin-induced hypoglycemia in type 1 (insulin-dependent) diabetes

In normal humans, arginine vasopressin and oxytocin are released acutely from the posterior pituitary gland in response to hypoglycemia, and their release may assist counterregulation. The responses of these hormones to insulin-induced hypoglycemia were measured in 16 insulin-dependent diabetic patients with no autonomic neuropathy (8 patients who had been diabetic less than 5 yr and 8 patients who had been diabetic greater than 15 yr) and in 6 normal subjects. The time of the onset of hypoglycemia and the mean blood glucose nadirs were similar in all groups, but the blood glucose recovery was delayed in the diabetic patients. In the normal subjects plasma arginine vasopressin rose from a mean basal value of 0.4 +/- 0.2 (+/- SE) pmol/L to a maximum of 1.3 +/- 0.6 pmol/L, and plasma oxytocin rose from 0.7 +/- 0.1 pmol/L to a maximum of 1.2 +/- 0.2 pmol/L 30 min after the onset of hypoglycemia. The plasma arginine vasopressin and oxytocin concentrations after hypoglycemia were significantly higher in both of the diabetic groups compared with those in the normal group. Arginine vasopressin and oxytocin rose in all control subjects after hypoglycemia. The individual hormonal profiles in the diabetic patients were variable, with an exaggerated rise of oxytocin in some diabetic patients and no rise in others. The arginine vasopressin responses were exaggerated in all of the diabetic patients. There was no correlation between the hormonal responses and the duration of diabetes. The exaggerated plasma arginine vasopressin and oxytocin responses to hypoglycemia in diabetic patients may indicate the failure of a normal inhibitory mechanism which modulates hormonal secretion or a compensatory response to impaired glucose recovery.     

Informant ratings of cognitive decline of elderly people: relationship to longitudinal change on cognitive tests

Formal assessment of cognitive decline with cognitive tests can be difficult, requiring either two measurement points or a comparison of 'hold' with 'don't hold' tests. Informant-based assessment provides an alternative approach because informants can adopt a longitudinal perspective and directly rate cognitive change. A study was carried out to assess the validity of informant ratings collected by means of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). A community sample of 500 subjects aged 74 or over underwent four cognitive tests on two occasions 3½ years apart. On the second occasion, informants filled out the IQCODE. Subjects rated as having moderate or severe decline were found to have greater change on the cognitive tests. These findings support the validity of informant ratings of cognitive decline.     

Fatal potential of supraventricular tachycardia in hypertrophic cardiomyopathy

Aortocaval fistula (ACF) represents a rare complication of abdominal aortic aneurysm (AAA) that may lead to hyperdynamic heart failure. We briefly describe a 58-year-old man with an old myocardial infarction, who developed leg oedema and worsening exertional dyspnea due to ACF complicating an AAA. This uncommon case highlights that an appropriate investigation for AAA and ACF should be performed in high-risk patients presenting with a history of worsening leg oedema and dyspnea in the absence of an obvious precipitating factor.     

The effect of azathioprine (Imuran) on the kinetics of monocytes and macrophages during the normal steady state and an acute inflammatory reaction

The effect of azathioprine on the kinetics of peripheral blood monocytes and peritoneal macrophages was studied in normal mice and in mice in which an inflammatory reaction was provoked. Two dosage levels were used: a high dose of 200mg/kg which is the maximum tolerated daily dose in mice, and low dose of 3 mg/kg which is about equivalent to a nontoxic, immunosuppressive, anti-inflammatory dose in man. The number of peripheral blood monocytes decreases gradually during azathioprine treatment of normal mice, the extent and duration being dependent on the dose and duration of administered over a period of 9 days gives an almost complete reduction, and a low dose (3 mg/kg) given for the same period results in a reduction of about 50%. This effect seems to be reversible, because when treatment is stopped the number of monocytes starts to increase 24-48 hr later. The number of peritoneal macrophages is only affected when a high dose (200 mg/kg) is given over a long period; a low dose has virtually no effect. In mice in which an inflammatory reaction was prevoked in the peritoneal cavity, the normally occurring increase in the numbers of both peripheral blood monocytes and peritoneal macrophages was suppressed, the extent being dependent on the dose of azathioprine administered. Labeling studies with 3H-thymidine indicated that the reduction of peripheral blood monocytes and peritoneal macrophages in the inflammatory exudate is due to a diminished monocyte production.     

Granulocyte colony-stimulating factor administration to healthy volunteers: analysis of the immediate activating effects on circulating neutrophils

In four healthy volunteers, we analyzed in detail the immediate in vivo effects on circulating neutrophils of subcutaneous administration of 300 micrograms of granulocyte colony-stimulating factor (G-CSF). Neutrophil activation was assessed by measurement of degranulation. Mobilization of secretory vesicles was shown by a decrease in leukocyte alkaline phosphatase content of the circulating neutrophils. Furthermore, shortly postinjection, Fc gamma RIII was found to be upregulated from an intracellular pool that we identified by immunoelectron microscopy as secretory vesicles. Intravascular release of specific granules was shown by increased plasma levels of lactoferrin and by upregulation of the expression of CD66b and CD11b on circulating neutrophils. Moreover, measurement of fourfold elevated plasma levels of elastase, bound to its physiologic inhibitor alpha 1- antitrypsin, indicated mobilization of azurophil granules. However, no expression of CD63, a marker of azurophil granules, was observed on circulating neutrophils. G-CSF--induced mobilization of secretory vesicles and specific granules could be mimicked in whole blood cultures in vitro, in contrast to release of azurophil granules. Therefore, we postulate that the most activated neutrophils leave the circulation, as observed shortly postinjection, and undergo subsequent stimulation in the endothelial microenvironment, resulting in mobilization of azurophil granules. Our data demonstrate that G-CSF should be regarded as a potent immediate activator of neutrophils in vivo.     

Alterations during medical interpretation of ICU family conferences that interfere with or enhance communication

RATIONALE: Many conferences in the ICU occur with the families of patients with limited English proficiency, requiring a medical interpreter. Despite the importance of medical interpretation, little is known about the alterations that occur and their effect on communication. OBJECTIVES: This study characterizes the types, prevalence, and potential effects of alterations in interpretation during ICU family conferences involving end-of-life discussions. METHODS: We identified ICU family conferences in two hospitals in which a medical interpreter was used. Ten conferences were audiotaped; 9 physicians led these conferences, and 70 family members participated. Research interpreters different from those attending the conference translated the non-English language portions of the audiotaped conferences. We identified interpretation alterations, grouped them into four types, and categorized their potential effects on communication. RESULTS: For each interpreted exchange between clinicians and family, there was a 55% chance that an alteration would occur. These alterations included additions, omissions, substitutions, and editorializations. Over three quarters of alterations were judged to have potentially clinically significant consequences on the goals of the conference. Of the potentially significant alterations, 93% were likely to have a negative effect on communication; the remainder, a positive effect. The alterations with potentially negative effects included interference with the transfer of information, reduced emotional support, and reduced rapport. Those with potential positive effects included improvements in conveying information and emotional support. CONCLUSIONS: Alterations in medical interpretation seem to occur frequently and often have the potential for negative consequences on the common goals of the family conference. Further studies examining and addressing these alterations may help clinicians and interpreters to improve communication with family members during ICU family conferences.     

Effect of estrogens on skin aging and the potential role of SERMs

In humans, structural and functional changes attributable to aging are more visibly evident in the skin than in any other organ. Estrogens have significant effects on skin physiology and modulate epidermal keratinocytes, dermal fibroblasts and melanocytes, in addition to skin appendages including the hair follicle and the sebaceous gland. Importantly, skin aging can be significantly delayed by the administration of estrogen. This paper reviews the effects of estrogens on skin and the mechanisms by which estrogens can alleviate the changes due to aging that occur in human skin. The relevance of estrogen replacement therapy (HRT) in post-menopausal women and the potential value of selective estrogen receptor modulators (SERMs) as a therapy for diminishing skin aging are also highlighted.     

Asbestosis, pulmonary symptoms and functional impairment in shipyard workers

A group of 339 male shipyard workers responded to an invitation via shipyards, unions, and news media to be studied for the presence of asbestosis and its functional effects. Of these, 288 were white or black, had begun working in shipyards at least 20 years earlier, and had satisfactory chest x-ray film findings; 257 underwent spirometric testing, and 199 had single-breath diffusing capacities for carbon monoxide (Dsb) determined. There were radiographic signs of asbestosis in 64 percent. Of these, 28 percent had parenchymal disease only, 37 percent had pleural disease only, and 35 percent had both. There was pleural calcification in 9 percent. In only 14 (8 percent) was the profusion of opacities greater than 1/1 by the International Labour Organization's criteria. Age was closely related to the duration of exposure to asbestos. Thus, 87 percent of the workers who had asbestosis were born from before 1900 to 1910, 70 percent of those born in 1911 to 1920 had asbestosis, 62 percent of those born in 1921 to 1930 had the disease, and 31 percent of those born in 1931 to 1940 had signs of asbestosis. Function in nonsmokers was not significantly different from the reference population except for alveolar volume; ex-smokers had significantly reduced forced expiratory volume in one second, flow rates, Dsb, and alveolar volume. The forced vital capacity and thoracic gas volume were normal. Shipyard workers who smoked resembled reference smokers except for significantly reduced alveolar volume. These shipyard workers had minimal to moderate asbestosis with much pleural disease and little functional impairment when compared to a smoking-specific reference population.