Occupational exposure to ethylene oxide. Relation between in vivo dose and exposure dose

As a basis for risk estimations for ethylene oxide (EtO) exposure and for the establishment of occupational exposure limits in work environments it is important to know the ratio between the in vivo dose and the exposure dose of this compound. For an assessment of this ratio, data on hemoglobin adduct levels in occupationally exposed workers and exposure levels in the work environment have been collected. The in vivo dose is directly proportional to the product of the uptake and retention time (1/lambda) of EtO in the body. The rate of clearance (lambda) of EtO has been calculated for individual workers from adduct levels and estimated EtO uptake. The wide range of lambda values found (approximately 1-65 h-1) can only partly be ascribed to a true variation between individuals with respect to clearance rates. One uncertainty results from the difficulties to estimate EtO uptake. A better estimate of lambda (approximately 3 h-1) is probably derived from the measurements of environmental and instantaneous blood concentrations of EtO in exposed workers by Brugnone et al [Int Arch Occup Environ Health 58 (1986) 105-112].     

Oxidized phospholipids predict the presence and progression of carotid and femoral atherosclerosis and symptomatic cardiovascular disease: five-year prospective results from the Bruneck study.

OBJECTIVES: The purpose of this work was to determine the predictive value of oxidized phospholipids (OxPLs) present on apolipoprotein B-100 particles (apoB) in carotid and femoral atherosclerosis. BACKGROUND: The OxPLs are pro-inflammatory and pro-atherogenic and may be detected using the antibody E06 (OxPL/apoB). METHODS: The Bruneck study is a prospective population-based survey of 40- to 79-year-old men and women initiated in 1990. Plasma levels of OxPL/apoB and lipoprotein (a) [Lp(a)] were measured in 765 of 826 (92.6%) and 671 of 684 (98.1%) subjects alive in 1995 and 2000, respectively, and correlated with ultrasound measures of carotid and femoral atherosclerosis. RESULTS: The distribution of the OxPL/apoB levels was skewed to lower levels and nearly identical to Lp(a) levels. The OxPL/apoB and Lp(a) levels were highly correlated (r = 0.87, p < 0.001), and displayed long-term stability and lacked correlations with most cardiovascular risk factors and lifestyle variables. The number of apolipoprotein (a) kringle IV-2 repeats was inversely related to Lp(a) mass (r = -0.48, p < 0.001) and OxPL/apoB levels (r = -0.46, p < 0.001). In multivariable analysis, OxPL/apoB levels were strongly and significantly associated with the presence, extent, and development (1995 to 2000) of carotid and femoral atherosclerosis and predicted the presence of symptomatic cardiovascular disease. Both OxPL/apoB and Lp(a) levels showed similar associations with atherosclerosis severity and progression, suggesting a common biological influence on atherogenesis. CONCLUSIONS: This study suggests that pro-inflammatory oxidized phospholipids, present primarily on Lp(a), are significant predictors of the presence and extent of carotid and femoral atherosclerosis, development of new lesions, and increased risk of cardiovascular events. The OxPL biomarkers may provide valuable insights into diagnosing and monitoring cardiovascular disease.     

The snack is critical for the blood glucose profile during treatment with regular insulin preprandially

OBJECTIVES: To evaluate how a snack influences the blood glucose profile during treatment with preprandial regular human insulin. DESIGN: In a randomized study a mid-morning snack either was or was not served. Insulin was given 30 min before the usual breakfast of the patients. Plasma free insulin and blood glucose were repeatedly determined for 5 h. SETTING: Outpatient clinic at a university hospital. SUBJECTS: Twenty patients with type 1 diabetes treated with multiple injections of regular insulin (Actrapid) and eight non-diabetic subjects. INTERVENTIONS: A mid-morning snack either was or was not served 2 h after the usual morning insulin injection. MAIN OUTCOME MEASURES: A difference in the blood glucose profile after a mid-morning snack. RESULTS: With a snack there was no difference in blood glucose fasting and at 12.30 h, whilst without a snack there was a decrease of almost 4 mmol L-1, several patients experienced low blood glucose and three had hypoglycaemia. An extended peak of free insulin was reached 30 min after the insulin injection with a slow decrease to the fasting level after 5 h. After the insulin injection a significant decrease in blood glucose occurred within 30-45 min. CONCLUSIONS: A snack 2 h after the insulin injection results in a smoother blood glucose profile and reduces the risk of hypoglycaemia in patients with type 1 diabetes treated with preprandial regular human insulin. Furthermore, the recommended interval of 30 min between insulin injection and a meal may be too long.     

Self-reported fertility in long-term survivors of acute myeloid leukemia

Acute myeloid leukemia (AML) survival rates in younger patients have improved considerably since the 1970s. In order to evaluate the impact of AML and its treatment on fertility and family situation in adult long-term survivors, we used the Swedish population-based registries to identify 161 adult patients diagnosed with AML within the Leukemia Group of Middle Sweden (LGMS) 1973–2003, who survived for more than 5 years and were alive in 2010. Ninety-eight patients (61 %) completed a questionnaire including items on reproductive concerns, family situation, and infertility-related distress. After excluding women >45 years and/or postmenopausal women and men >55 years, 22 women and 38 men were included in the final analysis. Nine of the women (41 %) tried to conceive after treatment, but only three succeeded. Five (83 %) of the unwillingly childless women reported “a moderate” or “a lot” of distress caused by this. Among men in the same age group, all six who wanted children after treatment succeeded. None of the men 46–55 years old cryopreserved their sperm or tried to father a child. Among patients who wanted children after AML treatment, 46 % of the women and 40 % of the younger men reported that they were not, or not fully, informed about fertility-related issues. In contrast, among men 46–55 years, none reported they would have wanted more information. Infertility among young female AML survivors thus remains an important clinical issue, and there is a need for improved clinical counseling and education in this area.     

Symptom documentation in cancer survivors as a basis for therapy modifications

In order to suggest therapy modifications with the aim of diminishing the risk of therapy-induced long-term distressful symptoms in cancer survivors, data are needed relating details of therapy to the long-term symptom situation. In this article, the concepts and means used to assess the latter while developing the Radiumhemmet scale for symptom assessment are described. The focus is on the subjective long-term situation, and symptoms as a perceived abnormality are defined. For conceptual clarity, one symptom at a time is considered, excluding scales in which items are summarized. Moreover, measures of disease occurrence in the population are translated (epidemiologically) into measures of symptom occurrence in an individual. Nature distinguishes one long-term symptom from another. Occurrence of a symptom in an individual is measured by an incidence (e.g. number of defecations per week) or prevalence rate (e.g. urinations with involuntary cessation divided by the total number of urinations). Any scale expressing symptom intensity is arbitrary, be it 'verbal' (no/little/moderate/much pain) or visual (analogue or with integers). A time period describes symptom duration. The relevance of a symptom to emotions and social activities, sometimes cited as the associated symptom-induced distress, is a separate issue from symptom occurrence, intensity, and duration.     

Clinical application of opioid equianalgesic data

Physicians and other healthcare professionals may often be faced with the need to change opioids during the course of a patient's opioid analgesic care due to a number of clinical reasons. The act of converting opioid analgesics, for many physicians, nurses, and pharmacists, who do not receive adequate training, remains a challenging and often uncomfortable aspect of pain treatment. Part of the challenge clinicians face is secondary to the relatively weak literature evidence base that exists to support the equianalgesic ratios provided in textbooks, journals, and other medical resources. Another aspect involves the lack of a widely recognized treatment algorithm or guideline to assist clinicians with opioid conversion. The final decision on which opioid dose to prescribe must involve a thorough clinical assessment to minimize the risk of prescribing inappropriate opioid doses over or under the patient's actual need. The purpose of this paper is to provide the clinician with an approach for dealing with the conversion between opioid analgesics that is standardized, yet allows for individualized results to meet unique patient needs. We present a 5-step process as a guide for clinicians faced with the need to change a patient's opioid regimen. This approach may help to build a comfort level when dealing with the clinical challenges of converting from one opioid to another.     

Distressful symptoms after radical cystectomy with urinary diversion for urinary bladder cancer: a Swedish population-based study

OBJECTIVE: To study the excess prevalence of distressful symptoms after radical surgery for urinary bladder cancer. METHODS: We included all patients who underwent cystectomy due to bladder cancer before 1996 in Stockholm County. A control group was randomly selected from the general population. Information was collected by means of an anonymous postal questionnaire. RESULTS: Completed questionnaires were returned by 310 (71%) controls and 251 (85%) cystectomized individuals. A 5-fold (reservoir) and 9-fold (conduit) increase in defecation urgency and a 4-fold (reservoir) and 6-fold (conduit) increase in faecal leakage were reported in individuals operated on. Urinary tract infection was increased 3-fold in cystectomized individuals compared with controls, during the previous year 26% of the patients reported a symptomatic infection. The perception of a reduced physical attractiveness due to disease was more than 5-fold increased in the men operated on compared to the controls. The majority, 135 out of 201 (67%), reported that they would have refused alternative bladder-sparing procedures if they decreased the prospects of survival by even as little as 1%. CONCLUSIONS: The patient's situation after cystectomy is considerably impaired due to changed bowel and sexual function, urinary tract infections and a sense of decreased attractiveness. However, most patients are in spite of this unwilling to compromise survival.     

The development of advanced drinking habits in adolescence--a longitudinal study

This paper aims at exploring the relations between early risk factors and the development of advanced drinking habits in adolescence. Data were derived from the longitudinal research program Individual Development and Adjustment. Results confirm earlier findings from longitudinal studies in this field. Three important factors have been identified: significant others, general sociability, and personality/conduct. More important, though, is that results indicate that knowledge about one or two background characteristics is not enough to make predictions of adolescent drinking habits. Rather, it is the ensemble of circumstances that together lead to an increased risk for advanced drinking habits in adolescence.