Leukaemia and pregnancy

In summary, the management of women diagnosed with leukaemia in pregnancy needs an interdisciplinary approach, including a careful oncological work-up as well as close monitoring of the pregnancy until delivery and beyond. Patients with acute leukaemias normally must receive anti-leukaemic treatment at full dosage prior to delivery, except for selected women diagnosed very close to term. Treatment should be avoided in the first trimester. The prognosis of pregnant women with acute leukaemia corresponds to that of an age-matched and diagnosis-matched non-pregnant cohort of patients, provided appropriate treatment is given. If given as of the second trimester, the typical chemotherapy regimes used for acute leukaemias imply acceptable acute toxicities to the fetus, with a somewhat increased risk of premature birth or developmental retardation, but no clear evidence of late sequelae in children and adolescents who were exposed to cytostatic agents whilst in utero. In chronic leukaemias and MDS, treatment may often be delayed until after delivery. In CML targeted therapy with imatinib mesylate is safe as of the second trimester, and possibly even before. Obstetric care and monitoring of women with leukaemia are essential throughout the pregnancy to ensure the best possible outcome for mother and child.

Cardiovascular mortality and exposure to extremely low frequency magnetic fields: a cohort study of Swiss railway workers

BACKGROUND: Exposure to intermittent magnetic fields of 16 Hz has been shown to reduce heart rate variability, and decreased heart rate variability predicts cardiovascular mortality. We examined mortality from cardiovascular causes in railway workers exposed to varying degrees to intermittent 16.7 Hz magnetic fields. METHODS: We studied a cohort of 20,141 Swiss railway employees between 1972 and 2002, including highly exposed train drivers (median lifetime exposure 120.5 muT-years), and less or little exposed shunting yard engineers (42.1 muT-years), train attendants (13.3 muT-years) and station masters (5.7 muT-years). During 464,129 person-years of follow up, 5,413 deaths were recorded and 3,594 deaths were attributed to cardio-vascular diseases. We analyzed data using Cox proportional hazards models. RESULTS: For all cardiovascular mortality the hazard ratio compared to station masters was 0.99 (95%CI: 0.91, 1.08) in train drivers, 1.13 (95%CI: 0.98, 1.30) in shunting yard engineers, and 1.09 (95%CI: 1.00, 1.19) in train attendants. Corresponding hazard ratios for arrhythmia related deaths were 1.04 (95%CI: 0.68, 1.59), 0.58 (95%CI: 0.24, 1.37) and 10 (95%CI: 0.87, 1.93) and for acute myocardial infarction 1.00 (95%CI: 0.73, 1.36), 1.56 (95%CI: 1.04, 2.32), and 1.14 (95%CI: 0.85, 1.53). The hazard ratio for arrhythmia related deaths per 100 muT-years of cumulative exposure was 0.94 (95%CI: 0.71, 1.24) and 0.91 (95%CI: 0.75, 1.11) for acute myocardial infarction. CONCLUSION: This study provides evidence against an association between long-term occupational exposure to intermittent 16.7 Hz magnetic fields and cardiovascular mortality.

[Swiss Research Agenda for Nursing (SRAN): the development of an agenda for clinical nursing research in Switzerland]

In many Anglo-Saxon and North European countries nursing research agendas have been developed to address priorities in nursing research in accordance with a nationally defined health policy. In Switzerland, due to lack of a nationwide governmental health policy, co-ordination of nursing research so far was scarce. The "Swiss Research Agenda for Nursing (SRAN)" project developed an agenda for clinical nursing research between 2005 and 2007. Based on literature reviews, expert panels and a national survey a project team formulated an agenda which passed a consensus conference. The agenda recommends aspects that should lead research and defines seven research priorities for nursing in Switzerland for the time between 2007 and 2017. Nursing research should prioritize to investigate 1) the effectiveness of nursing interventions; 2) the influences of service adaptations in a changing health care system; 3) the phenomena in patients requiring nursing care; 4) the influence of the work environment on the quality of nursing care; 5) the functioning of family and social systems; 6) varieties of life circumstances and their integration; and 7) the implementation of ethical principles in nursing. Written in German and French, the Swiss Research Agenda for Nursing for the first time formulates priorities for nursing research in Switzerland and can be used for strategic discussions. As a next step, the development of an action plan to enhance nursing research will take place in Switzerland.

Treatment of hypercholesterolemia in patients with primary biliary cirrhosis might be more beneficial than indicated

Cholesterol circulating levels are elevated in most of the patients with primary biliary cirrhosis. This review questions whether hypercholesterolaemia represents a cardiovascular risk in primary biliary cirrhosis and whether it should be treated. The published evidence indicates that hypercholesterolaemia in patients with primary biliary cirrhosis should be considered a cardiovascular risk factor only when other factors are present. Ursodeoxycholic acid the standard treatment of primary biliary cirrhosis improves the cholestasis and hereby lowers circulating levels of cholesterol. Primary biliary cirrhosis is not a contraindication to prescribe statins or fibrates to these patients. Interestingly, these two classes of drugs have been shown to improve not only the lipid profile but also the liver tests. In particular fibrates have been found to normalize liver tests in patients responding incompletely to ursodeoxycholic acid. Statins as well as fibrates possess specific anti-inflammatory properties which may be beneficial in primary biliary cirrhosis. In conclusion, hypercholesterolaemia in the absence of other cardiovascular risk factors does not require specific therapeutic intervention in patients with primary biliary cirrhosis. However, statins as well as fibrates seem to have beneficial effects on the primary biliary cirrhosis itself and deserve formal testing within clinical trials.

Measures of endothelial dysfunction in plasma of patients with posttraumatic stress disorder

Posttraumatic stress disorder (PTSD) confers an increased cardiovascular risk. In 14 otherwise healthy patients with PTSD and in 14 age- and gender-matched non-PTSD controls, we investigated whether the categorical diagnosis of PTSD and severity of PTSD symptom clusters (i.e. re-experiencing, avoidance, arousal, and overall score) would be associated with plasma concentrations of three markers of endothelial dysfunction [soluble tissue factor (sTF), von Willebrand factor (VWF), and soluble intercellular adhesion molecule (sICAM)-1]. Compared with controls, patients had significantly higher sTF; this difference became nonsignificant when controlling for psychological distress. VWF and sICAM-1 levels were not significantly different between patients and controls. In the entire sample virtually all PTSD symptom clusters correlated significantly and positively with sTF and VWF but not with sICAM-1. The correlation between symptoms of re-experiencing and sTF was significantly different between patients and controls. Controlling for symptoms of anxiety and depression (i.e. psychological distress) rendered most associations between PTSD symptom clusters and sTF nonsignificant, whereas controlling for age retained significance of associations with VWF. Posttraumatic stress showed a continuous relationship with sTF and VWF, with the former relationship being partly affected by psychological distress. This suggests one mechanism by which posttraumatic stress could contribute to atherosclerosis.

Circulating fibrinogen but not D-dimer level is associated with vital exhaustion in school teachers

Meta-analyses have established elevated fibrinogen and D-dimer levels in the circulation as biological risk factors for the development and progression of coronary artery disease (CAD). Here, we investigated whether vital exhaustion (VE), a known psychosocial risk factor for CAD, is associated with fibrinogen and D-dimer levels in a sample of apparently healthy school teachers. The teaching profession has been proposed as a potentially high stressful occupation due to enhanced psychosocial stress at the workplace. Plasma fibrinogen and D-dimer levels were measured in 150 middle-aged male and female teachers derived from the first year of the Trier-Teacher-Stress-Study. Log-transformed levels were analyzed using linear regression. Results yielded a significant association between VE and fibrinogen (p = 0.02) but not D-dimer controlling for relevant covariates. Further investigation of possible interaction effects resulted in a significant association between fibrinogen and the interaction term "VE x gender" (p = 0.05). In a secondary analysis, we reran linear regression models for males and females separately. Gender-specific results revealed that the association between fibrinogen and VE remained significant in males but not females. In sum, the present data support the notion that fibrinogen levels are positively related to VE. Elevated fibrinogen might be one biological pathway by which chronic work stress may impact on teachers' cardiovascular health in the long run.

Changes in plasma lipids with psychosocial stress are related to hypertension status and the norepinephrine stress response

Hypertension is a known risk factor for cardiovascular disease. Hypertensive individuals show exaggerated norepinephrine (NE) reactivity to stress. Norepinephrine is a known lipolytic factor. It is unclear if, in hypertensive individuals, stress-induced increases in NE are linked with the elevations in stress-induced circulating lipid levels. Such a mechanism could have implications for atherosclerotic plaque formation. In a cross-sectional, quasi-experimentally controlled study, 22 hypertensive and 23 normotensive men (mean +/- SEM, 45 +/- 3 years) underwent an acute standardized psychosocial stress task combining public speaking and mental arithmetic in front of an audience. We measured plasma NE and the plasma lipid profile (total cholesterol [TC], low-density-lipoprotein cholesterol [LDL-C], high-density-lipoprotein cholesterol, and triglycerides) immediately before and after stress and at 20 and 60 minutes of recovery. All lipid levels were corrected for stress hemoconcentration. Compared with normotensives, hypertensives had greater TC (P = .030) and LDL-C (P = .037) stress responses. Independent of each other, mean arterial pressure (MAP) upon screening and immediate increase in NE predicted immediate stress change in TC (MAP: beta = .41, P = .003; NE: beta = .35, P = .010) and LDL-C (MAP: beta = .32, P = .024; NE: beta = .38, P = .008). Mean arterial pressure alone predicted triglycerides stress change (beta = .32, P = .043) independent of NE stress change, age, and BMI. The MAP-by-NE interaction independently predicted immediate stress change of high-density-lipoprotein cholesterol (beta = -.58, P < .001) and of LDL-C (beta = -.25, P < .08). We conclude that MAP and NE stress reactivity may elicit proatherogenic changes of plasma lipids in response to acute psychosocial stress, providing one mechanism by which stress might increase cardiovascular risk in hypertension.

Effect of IGF-I therapy on VLDL apolipoprotein B100 metabolism in type 1 diabetes mellitus

Abnormal lipid metabolism may be related to the increased cardiovascular risk in type 1 diabetes. Secretion and clearance rates of very low density lipoprotein (VLDL) apolipoprotein B100 (apoB) determine plasma lipid concentrations. Type 1 diabetes is characterized by increased growth hormone (GH) secretion and decreased insulin-like growth factor (IGF) I concentrations. High-dose IGF-I therapy improves the lipid profile in type 1 diabetes. This study examined the effect of low-dose (40 microg.kg(-1).day(-1)) IGF-I therapy on VLDL apoB metabolism, VLDL composition, and the GH-IGF-I axis during euglycemia in type 1 diabetes. Using a stable isotope technique, VLDL apoB kinetics were estimated before and after 1 wk of IGF-I therapy in 12 patients with type 1 diabetes in a double-blind, placebo-controlled trial. Fasting plasma triglyceride (P < 0.03), VLDL-triglyceride concentrations (P < 0.05), and the VLDL-triglyceride-to-VLDL apoB ratio (P < 0.002) significantly decreased after IGF-I therapy, whereas VLDL apoB kinetics were not significantly affected by IGF-I therapy. IGF-I therapy resulted in a significant increase in IGF-I and a significant reduction in GH concentrations. The mean overnight insulin concentrations during euglycemia decreased by 25% after IGF-I therapy. These results indicate that low-dose IGF-I therapy restores the GH-IGF-I axis in type 1 diabetes. IGF-I therapy changes fasting triglyceride concentrations and VLDL composition probably because of an increase in insulin sensitivity.

Growth hormone (GH) replacement therapy reduces serum sialic acid concentrations in adults with GH-deficiency: a double-blind placebo-controlled study

Patients with adult GH-deficiency are thought to have an increased risk of cardiovascular disease. Sialic acid (SA) concentrations have been proposed as a marker of atherosclerotic disease probably related to an inflammatory response of the arterial wall. SA as a marker of cardiovascular disease in adult GH-deficiency and its relation to changes in fasting lipid profile and hormone concentrations have not yet been investigated.

[Dyslipidemia - when are lipid lowering medications useful in clinical practice?]

Dyslipidemia is one of the main modifiable cardiovascular risk factors. There is strong evidence for the efficacy of lipid-lowering drugs in secondary prevention, as well as in primary prevention for patients at high cardiovascular risk. In primary prevention, indication for lipid-lowering interventions should be based on an individual assessment of the cardiovascular risk and on the LDL cholesterol level, despite less strong evidence for the efficacy of drug-based interventions in low risk patients. Treatment consists of statins, as well as lifestyle modifications such as body weight control and increased physical exercise. The latter constitute the primary intervention in patients at low cardiovascular risk. Secondary dyslipidemias due to an underlying medical condition and familial dyslipidemias such as Familial Hypercholesterolemia and Familial Combined Hyperlipidemia should be identified and treated accordingly, taking into account that the risk scoring systems are not appropriate in these situations.

Die Abschrift als Schreibszene. Der ›Nuwe Parzifal‹ in der Handschrift Rom, Biblioteca Casanatense, Mss. 1409

The Codex Biblioteca Casanatense 1409 which has for a long time been neg- lected in Parzival scholarship, transmits German translations of three continuations of Chre ́tien de Troyes‘ Roman de Perceval ou Le Conte du Graal together with the last two books (XV/XVI) of Wolfram von Eschenbach’s Parzival. This article supports the for- merly casually made assumption that the Casanatense manuscript is in fact a direct copy of Codex Donaueschingen 97, the so called Rappoltsteiner Parzifal. As is to be shown, marks in the Donaueschingen codex, as well as significant copying errors in the Casanatense text and its treatment of initials suggest a direct relationship of the two witnesses. The notion of ,writing scene‘ (Schreibszene) with its implications of linguistic semantics, instrumentality, gesture and self reflection, proposed in modern literary scholarship, can help to understand peculiarities of the copying process in the Casanatensis, such as the numerous conceptual abbreviations and the adaptations in the handling of headings. In the final part of the article, the hypothesis is corroborated, that the copy of the Casa- natensis might have been produced in the surroundings of Lamprecht von Brunn (ca. 1320–1399), bishop of Strasburg and Bamberg, and counsellor of the emperor Charles IV.

Relative Energy Balance, CKD, and Risk of Cardiovascular and All-Cause Mortality.

BACKGROUND Mortality risk for people with chronic kidney disease is substantially greater than that for the general population, increasing to a 7-fold greater risk for those on dialysis therapy. Higher body mass index, generally due to higher energy intake, appears protective for people on dialysis therapy, but the relationship between energy intake and survival in those with reduced kidney function is unknown. STUDY DESIGN Prospective cohort study with a median follow-up of 14.5 (IQR, 11.2-15.2) years. SETTING & PARTICIPANTS Blue Mountains Area, west of Sydney, Australia. Participants in the general community enrolled in the Blue Mountains Eye Study (n=2,664) who underwent a detailed interview, food frequency questionnaire, and physical examination including body weight, height, blood pressure, and laboratory tests. PREDICTORS Relative energy intake, food components (carbohydrates, total sugars, fat, protein, and water), and estimated glomerular filtration rate (eGFR). Relative energy intake was dichotomized at 100%, and eGFR, at 60mL/min/1.73m(2). OUTCOMES All-cause and cardiovascular mortality. MEASUREMENTS All-cause and cardiovascular mortality using unadjusted and adjusted Cox proportional regression models. RESULTS 949 people died during follow-up, 318 of cardiovascular events. In people with eGFR<60mL/min/1.73m(2) (n=852), there was an increased risk of all-cause mortality (HR, 1.48; P=0.03), but no increased risk of cardiovascular mortality (HR, 1.59; P=0.1) among those with higher relative energy intake compared with those with lower relative energy intake. Increasing intake of carbohydrates (HR per 100g/d, 1.50; P=0.04) and total sugars (HR per 100g/d, 1.62; P=0.03) was associated significantly with increased risk of cardiovascular mortality. LIMITATIONS Under-reporting of energy intake, baseline laboratory and food intake values only, white population. CONCLUSIONS Increasing relative energy intake was associated with increased all-cause mortality in patients with eGFR<60mL/min/1.73m(2). This effect may be mediated by increasing total sugars intake on subsequent cardiovascular events.

Living Renal Allograft Transplantation: Diffusion-weighted MR Imaging in Longitudinal Follow-up of the Donated and the Remaining Kidney.

Purpose To determine whether diffusion-weighted (DW) magnetic resonance (MR) imaging in living renal allograft donation allows monitoring of potential changes in the nontransplanted remaining kidney of the donor because of unilateral nephrectomy and changes in the transplanted kidney before and after transplantation in donor and recipient, respectively, and whether DW MR parameters are correlated in the same kidney before and after transplantation. Materials and Methods The study protocol was approved by the local ethics committee; written informed consent was obtained. Thirteen healthy kidney donors and their corresponding recipients prospectively underwent DW MR imaging (multiple b values) in donors before donation and in donors and recipients at day 8 and months 3 and 12 after donation. Total apparent diffusion coefficient (ADCT) values were determined; contribution of microcirculation was quantified in perfusion fraction (FP). Longitudinal changes of diffusion parameters were compared (repeated-measures one-way analysis of variance with post hoc pairwise comparisons). Correlations were tested (linear regression). Results ADCT values in nontransplanted kidney of donors increased from a preexplantation value of (188 ± 9 [standard deviation]) to (202 ± 11) × 10(-5) mm(2)/sec in medulla and from (199 ± 11) to (210 ± 13) × 10(-5) mm(2)/sec in cortex 1 week after donation (P < .004). Medullary, but not cortical, ADCT values stayed increased up to 1 year. ADCT values in allografts in recipients were stable. Compared with values obtained before transplantation in donors, the corticomedullary difference was reduced in allografts (P < .03). Cortical ADCT values correlated with estimated glomerular filtration rate in recipients (R = 0.56, P < .001) but not donors. Cortical ADCT values in the same kidney before transplantation in donors correlated with those in recipients on day 8 after transplantation (R = 0.77, P = .006). FP did not show significant changes. Conclusion DW MR imaging depicts early adaptations in the remaining nontransplanted kidney of donors after nephrectomy. All diffusion parameters remained constant in allograft recipients after transplantation. This method has potential monitoring utility, although assessment of clinical relevance is needed. © RSNA, 2013 Online supplemental material is available for this article.

Longitudinal Relationship of Low Leisure Satisfaction but not Depressive Symptoms With Systemic Low-Grade Inflammation in Dementia Caregivers.

Objectives.This study aimed to further elucidate the biobehavioral mechanisms linking dementia caregiving with an increased cardiovascular disease risk. We hypothesized that both elevated depressive symptoms and a behavioral correlate of depression, low leisure satisfaction, are associated with systemic inflammation.Method.We studied 121 elderly Alzheimer's disease caregivers who underwent 4 annual assessments for depressive symptoms, leisure satisfaction, and circulating levels of inflammatory markers. We used mixed-regression analyses controlling for sociodemographic and health-relevant covariates to examine longitudinal relationships between constructs of interest. RESULTS: There were inverse relationships between total leisure satisfaction and tumor necrosis factor-α (TNF-α; p = .047), interleukin-8 (IL-8; p < .001), and interferon-γ (IFG; p = .020) but not with IL-6 (p = .21) and C-reactive protein (p = .65). Lower enjoyment from leisure activities was related to higher levels of TNF-α (p = .045), IL-8 (p < .001), and IFG (p = .002), whereas lower frequency of leisure activities was related only to higher IL-8 levels (p = .023). Depressive symptoms were not associated with any inflammatory marker (all p values > .17). Depressive symptoms did not mediate the relationship between leisure satisfaction and inflammation.Discussion.Lower satisfaction with leisure activities is related to higher low-grade systemic inflammation. This knowledge may provide a promising way of improving cardiovascular health in dementia caregivers through behavioral activation treatments targeting low leisure satisfaction.

Energy harvesting from the cardiovascular system, or how to get a little help from yourself

Human energy harvesting is envisioned as a remedy to the weight, the size, and the poor energy density of primary batteries in medical implants. The first implant to have necessarily raised the idea of a biological power supply was the pacemaker in the early 1960s. So far, review articles on human energy harvesting have been rather unspecific and no tribute has been given to the early role of the pacemaker and the cardiovascular system in triggering research in the field. The purpose of the present article is to provide an up-to-date review of research efforts targeting the cardiovascular system as an alternative energy source for active medical implants. To this end, a chronological survey of the last 14 most influential publications is proposed. They include experimental and/or theoretical studies based on electromagnetic, piezoelectric, or electrostatic transducers harnessing various forms of energy, such as heart motion, pressure gradients, and blood flow. Technical feasibility does not imply clinical applicability: although most of the reported devices were shown to harvest an interesting amount of energy from a physiological environment, none of them were tested in vivo for a longer period of time.Human energy harvesting is envisioned as a remedy to the weight, the size, and the poor energy density of primary batteries in medical implants. The first implant to have necessarily raised the idea of a biological power supply was the pacemaker in the early 1960s. So far, review articles on human energy harvesting have been rather unspecific and no tribute has been given to the early role of the pacemaker and the cardiovascular system in triggering research in the field. The purpose of the present article is to provide an up-to-date review of research efforts targeting the cardiovascular system as an alternative energy source for active medical implants. To this end, a chronological survey of the last 14 most influential publications is proposed. They include experimental and/or theoretical studies based on electromagnetic, piezoelectric, or electrostatic transducers harnessing various forms of energy, such as heart motion, pressure gradients, and blood flow. Technical feasibility does not imply clinical applicability: although most of the reported devices were shown to harvest an interesting amount of energy from a physiological environment, none of them were tested in vivo for a longer period of time.