The Neutrons for Science Facility at SPIRAL-2.

The neutrons for science (NFS) facility is a component of SPIRAL-2, the new superconducting linear accelerator built at GANIL in Caen (France). The proton and deuteron beams delivered by the accelerator will allow producing intense neutron fields in the 100 keV-40 MeV energy range. Continuous and quasi-mono-kinetic energy spectra, respectively, will be available at NFS, produced by the interaction of a deuteron beam on a thick Be converter and by the 7Li(p,n) reaction on thin converter. The pulsed neutron beam, with a flux up to two orders of magnitude higher than those of other existing time-of-flight facilities, will open new opportunities of experiments in fundamental research as well as in nuclear data measurements. In addition to the neutron beam, irradiation stations for neutron-, proton- and deuteron-induced reactions will be available for cross-sections measurements and for the irradiation of electronic devices or biological cells. NFS, whose first experiment is foreseen in 2018, will be a very powerful tool for physics, fundamental research as well as applications like the transmutation of nuclear waste, design of future fission and fusion reactors, nuclear medicine or test and development of new detectors.

Sickness certification at oncology clinics: perceived problems, support, need for education and reasons for certifying unnecessarily long sickness absences.

Physicians' work with sickness certifications is an understudied field. The aims of this study were to gain knowledge of experiences concerning the sickness certification process among physicians working at oncology clinics. In 2008, all physicians working in Sweden (n = 36 898) were sent a questionnaire concerning sick-listing practices. All respondents working at an oncology clinic (n = 428) were included in the current study. Most of the physicians had sickness certification consultations at least weekly (91.3%). More than one fifth (22.3%) reported that they worked at a clinic with a workplace policy regarding the handling of sickness certification and 61.1% reported receiving at least some support in such cases from their immediate manager. Issuing unnecessary long sickness certificates were related to experiencing delicate interactions with patients and to lack of time. To a moderate degree, further competence was requested regarding: different types of compensation in the social insurance system, responsibilities of the Social Insurance Agency and employers, and sickness insurance rules. The large majority of physicians working in oncology reported regularly having consultations involving sickness certification. Overall, they reported few problems, low level of need for more competence regarding sickness certification, and low frequency of issuing sickness absences for longer periods than necessary.

High frequency of contact allergy to gold in patients with endovascular coronary stents.

BACKGROUND: Stent implantation is an effective method for treatment of atherosclerotic disease. Factors predisposing to in-stent restenosis are still largely unknown. Contact allergy to metal ions eluted from the stent has been suggested to be a risk factor. OBJECTIVES: To explore whether there is a possible induction of contact allergy to metals used in stents among patients with a stainless steel stent containing nickel (Ni stent) and patients with a gold-plated stent (Au stent). METHODS: Adults (n = 484) treated with coronary stent implantation participated in the study with patch testing. The study design was retrospective and cross-sectional with no assessment of contact allergy before stenting. Age- and sex-matched patch-tested patients with dermatitis (n = 447) served as controls. RESULTS: Of Au-stented patients, 54 of 146 (37%) were allergic to gold compared with 85 of 447 (19%) controls (P < 0.001). Within the stented population there were no statistically significant differences in contact allergy to gold or nickel between Ni-stented and Au-stented patients. In multivariate models where other risk factors for contact allergy to gold were considered, the Au stent showed a trend towards statistical significance (odds ratio 1.43, 95% confidence interval 0.95-2.16; P = 0.09). CONCLUSIONS: As the frequency of contact allergy to gold is higher in stented patients independent of stent type it suggests a previous sensitization. However, several pieces of circumstantial evidence as well as statistical analysis indicate the possibility of sensitization in the coronary vessel by the Au stent. Ni stents and Au stents should not be ruled out as risk factors for induction of contact allergy to these metals.

No link between viral findings in the prostate and subsequent cancer development.

In an investigation of 201 prostate tissue samples from patients with benign prostate hyperplasia that later progressed to prostate cancer and 201 matched controls that did not, there were no differences in the prevalence of adenovirus, herpesvirus, papilloma virus, polyoma virus and Candida albicans DNA.

Contact allergy to gold in patients with gold-plated intracoronary stents.

An increasingly common and effective method for the treatment of atherosclerotic disease in the coronary arteries is percutaneous transluminal coronary angioplasty (PTCA) and stenting. The stents are made of different metals. An increased rate of restenosis when using gold-plated stents has been shown. Contact allergy to gold is common in many countries. Recently, a study has shown an increased rate of contact allergy to nickel among patients with restenosis and a nickel-containing stent. The aims of our study were to investigate whether there was an increased rate of contact allergy to gold among patients with gold-plated stents and if this increased the risk of restenosis. 22 patients who had received a gold-plated stent were patch tested. An age- and sex-matched population of 88 patients, previously patch tested because of a suspected contact dermatitis, served as controls. In the stent group, 10/22 (45.5%) had a contact allergy to gold, in the control group 18/88 (20.5%); the difference is statistically significant (P = 0.04). There was no significant difference regarding frequency of restenosis. Our study indicates that there is a risk of sensitizing the patient when implanting a gold-plated stent. Further studies are needed to confirm these results and to evaluate whether there is an increased risk of restenosis.

Pharmacokinetic evaluation of a case of massive sotalol intoxication.

OBJECTIVE: To describe serum concentrations and clearance of sotalol after a massive overdose. CASE SUMMARY: A 37-year-old white man took 11.2 g of sotalol hydrochloride tablets in a suicide attempt. The first serum d,l-sotalol concentration 3 hours after taking the first tablet was 20.6 mg/L and the last measured concentration 59 hours later was 1.8 mg/L. Logarithmic transformation of the concentration data indicated two separate monoexponential phases in the elimination curve, with half-lives of 30.1 and 11.6 hours. DISCUSSION: The shorter serum half-life in the later phase is comparable with that in four previously reported sotalol intoxications and within the normal range. The elimination rate increased in a temporal manner with an increase in systolic blood pressure about 30 hours after the patient was admitted. Since the sotalol elimination rate depends principally on renal function, we believe the initially slow elimination is due to a temporary reduction of the renal function caused by the systolic hypotension. CONCLUSIONS: An initial phase of slow sotalol elimination may occur after severe overdoses. In our patient this was probably due to hypotension. Thus, blood pressure should be monitored carefully.

Supplementary iron intake and risk of cancer: reversed causality?

Dietary iron intake and body iron stores have been suggested to increase cancer risk, especially colorectal cancer. Within a population-based case-control study in Stockholm county 1993-94, information on dietary and supplementary iron intake were collected through a food frequency questionnaire. An initially noted positive association between intake of supplementary iron and colorectal cancer risk was reversed when intake 5 years prior to cancer diagnosis was subtracted. Reversed causality due to early disease giving symptoms of iron shortage, resulting in iron supplementation, is an issue to consider when a possible association between intake of iron and cancer risk is investigated.

Association between pre-PTCA blood haemoglobin concentration and the risk of symptomatic restenosis after successful PTCA of primary coronary stenoses.

BACKGROUND: Thrombus formation at the dilation site has been suggested to initiate the restenosis process after percutaneous transluminal coronary angioplasty (PTCA). High haemoglobin concentrations may predispose to thrombus formation by increasing blood viscosity, slowing coronary blood flow and increasing thrombocyte adhesion. METHODS: Pre-PTCA blood haemoglobin concentrations (Hb) in 44 patients with symptomatic restenosis > or = 50% of the vessel diameter (Group A) were compared with Hb in the remaining 215 patients in a consecutive study population (Group B). RESULTS: Median Hb (range) was 149 (119-164) g/l in Group A and 142 (117-164) g/l in Group B, P = 0.004. Odds ratio (95% CI) for symptomatic restenosis was 3.22 (1.62-6.42) when Hb was dichotomised according to the median in the entire material. Hb, but not sex was a significant risk factor in multivariate analysis. CONCLUSION: Hb is a hitherto not recognized factor associated with the risk of symptomatic restenosis after PTCA and may be a link coupling male sex with increased risk of restenosis.

Structure-activity relationships of organic acid anhydrides as antigens in an animal model.

Relationships between chemical structure and immunogenicity have been studied in 13 dicarboxylic acid anhydrides. Guinea-pigs were immunized intradermally by a single dose of 0.3 M solutions of succinic anhydride (SA), maleic anhydride (MA), methylmaleic anhydride (MMA), cis-cyclohexane-1,2-dicarboxylic anhydride (cis-HHPA), trans-cyclohexane-1,2-dicarboxylic anhydride (trans-HHPA), 4-methylcyclohexane-1,2-dicarboxylic anhydride (MHHPA), cis-1,2,3,6-tetrahydrophthalic anhydride (THPA1236), cis-3,4,5,6-tetrahydrophthalic anhydride (THPA3456), cis-3-methylcyclohex-4-ene-1,2-dicarboxylic anhydride (MTHPA34), cis-4-methylcyclohex-4-ene-1,2-dicarboxylic anhydride (MTHPA44), phthalic anhydride (PA), 4-methylphthalic anhydride (MPA), and trimellitic anhydride (TMA) in olive oil. Specific IgE, IgG, IgG1, and IgG2 antibodies against guinea-pig serum albumin conjugates of the anhydrides were determined by passive cutaneous anaphylaxis (PCA) tests and enzyme-linked immunoabsorbant assay (ELISA). Specific IgG was significantly increased in all animals, except those immunized with THPA3456 and SA, which sensitized only 3/9 and 7/9 animals, respectively. Furthermore, the specific IgG values were very low in the SA group. The titers of specific IgG1 and IgG2 were increased in the IgG-positive animals. Specific IgE was positive in all animals immunized with MA, MHHPA, MTHPA (both isomers), and MPA, and in 6/9 and 5/9 guinea pigs immunized with TMA and MMA, respectively. The IgE titers were generally very low; PCA was negative after dilutions to 1:32, or less. The results indicate a considerable variation in the sensitizing potential between different organic acid anhydrides. The most marked general effect of the chemical structure on immunogenicity was the enhancement of antibody formation when a hydrogen atom in the anhydride was substituted with a methyl group.

Transient release of lipid peroxidation products as a non-invasive marker of successful reperfusion after thrombolysis for myocardial infarction.

OBJECTIVES: To evaluate an increase in plasma concentration of thiobarbituric acid reactive substances as a non-invasive biochemical test of reperfusion after thrombolysis and to investigate the relation between the inflammatory response after acute myocardial infarction and the production of the substances. METHODS: Venous samples were taken from 19 patients receiving thrombolysis for acute myocardial infarction before the start of therapy and every hour afterwards up to 5 hours and then at 24 and 48 hours and the concentration of thiobarbituric acid reactive substances measured. These substances are markers of lipid peroxidation induced by free oxygen radicals. Early reperfusion was judged by regression of ST elevation and late coronary artery patency from the results of coronary angiography 24-72 hours after thrombolysis. RESULTS: The concentration of thiobarbituric acid reactive substances increased in only 6 out of 14 patients with signs of early reperfusion. In patients with late coronary artery patency the corresponding number was 6 out of 15. However, a significant increase in the concentration of thiobarbituric acid reactive substances was found for the whole group 24 and 48 hours after treatment. The change in concentration in serum correlated significantly with that of C reactive protein--an acute phase reactant (r = 0.62, P < 0.01)--but not to the serum activities of markers of infarct size such as creatine kinase B and lactate dehydrogenase. CONCLUSIONS: The fluorimetric assay used in this study to measure the concentration of thiobarbituric acid reactive substances seems to be an insensitive method of detecting reperfusion after thrombolysis for myocardial infarction. The increase in concentrations found 24 and 48 hours after treatment correlated with C reactive protein concentrations but not with those of markers of infarct size.

Exposure-response relationships in the formation of specific antibodies to hexahydrophthalic anhydride in exposed workers.

OBJECTIVES: Exposure-response relationships in the formation of specific antibodies to hexahydrophthalic anhydride (HHPA) was studied in exposed workers. METHODS: The relation between exposure to HHPA and the levels of specific immunoglobin E [(radioallergosorbent test (RAST)] and immunoglobin G (enzyme-linked immunosorbent assay) antibodies was investigated in a cross-sectional study on 95 workers from two plants using epoxy resin with HHPA as a hardener; the mean time of exposure was 7 (range 0.1-25) years. RESULTS: The specific immunoglobin E and immunoglobin G was significantly increased in exposed workers when they were compared with unexposed workers or external referents. There was no significant difference in the number of RAST positives [N = 23 (24%)] between the groups of workers exposed to < 10 micrograms.m-3, 10--< 50 micrograms.m-3, or > or = 50 micrograms.m-3. No effects were found of atopy or smoking habits on the prevalence of RAST positives. Five out of seven workers positive for immunoglobulin E in the group with the lowest exposures reported frequent short-time (minutes per day) exposures exceeding 50 micrograms.m-3. A correlation was seen between specific immunoglobulin E and G antibodies (rs = 0.5). CONCLUSIONS: The results indicate that HHPA is a sensitizing compound even at low exposure levels and that short-time peak exposures may have an impact on immunoglobulin E sensitization.

Changed blood rheology in patients with idiopathic dilated cardiomyopathy.

Rheologic properties of blood were studied in 8 patients with dilated cardiomyopathy (DCM) and in 10 healthy subjects. Whole-blood viscosity was measured at four different shear rates, by means of a computer-controlled rotational viscometer. The patients had significantly higher blood viscosity at all shear rates, both at their natural hematocrits and after an in vitro adjustment of sample hematocrits to 45%. Erythrocyte filterability (5 microns pore size) was significantly lower, fibrinogen concentration significantly higher, and HDL-cholesterol concentration significantly lower in the patient group. No significant differences were found regarding hematocrit, mean corpuscular volume, hemoglobin concentration, leukocyte count and filterability (8 microns pore size), plasma viscosity, and total cholesterol concentration. The measured hemorheologic abnormalities may contribute to the previously reported reduction of coronary blood flow reserve in DCM patients and to myocardial microcirculatory disturbances, which have been suggested as a cause for DCM.

Methyltetrahydrophthalic anhydride in air--sampling and analysis.

Methyltetrahydrophthalic anhydride (MTHPA), an organic anhydride, is a sensitizing agent even at low air concentrations: no methods for its sampling and analysis have previously been reported. This paper outlines the use of Amberlite XAD-2 for sampling MTHPA vapour in air, followed by analysis using gas chromatography with flame ionization detection. The level of detection corresponds to a concentration in air of 10 micrograms m-3 for a 20 l. sampling volume. Up to 200 l. air has been sampled, at a sampling rate of 1 l. min-1, without detectable losses. The adsorption efficiency and the stability of the anhydride in the XAD-2 tubes were not influenced by a relative air humidity (RH) of 40%, but at RH 80% there was a loss of 18% at 50 l. air-sample volume. Results from sampling in XAD-2 tubes were 8% lower than those from parallel sampling in midget bubblers containing 10 ml 0.01 M sodium hydroxide.

A case of right coronary artery occlusion, caused by blunt chest trauma and treated with acute coronary artery bypass surgery.

A 37-year-old man sustained occlusion of the right coronary artery after a bicycle accident with blunt chest trauma over the left scapula. Acute coronary angiography was performed because of chest pain and ST-segment elevation. Despite surgically successful acute revascularization the patient developed a transmural inferior wall infarction. Coronary artery occlusion after blunt chest trauma is rare, especially occlusion of the right coronary artery. When it occurs, the impact is usually frontal (car accidents), and not dorsal as in this case. Coronary artery bypass surgery has been reported in a few cases but to the best of our knowledge this is the first report of bypass surgery at the stage of acute transmural ischaemia.

Studies on blood rheology in patients with primary pulmonary hypertension.

The rheologic properties of blood were studied in 6 patients with primary pulmonary hypertension (PPH) and compared with those of a control group of 10 healthy subjects. Blood viscosity was studied with a rotational viscometer and blood cell deformability with a filtrometer giving values for clogging particles (CP) and red cell transit time (RCTT). Blood viscosity at varying shear rates was found to be increased both at natural (p less than 0.025-0.005) and standardized hematocrit, 45% (p less than 0.05 at 40 s-1) in patients with PPH. Red cell deformability was reduced as indicated by a significant increase of RCTT (p less than 0.01). Increased values for hematocrit (p less than 0.001), hemoglobin concentration (p less than 0.001), and erythrocyte count (p less than 0.005) were found and decreased values for mean corpuscular hemoglobin concentration (MCHC) (p less than 0.025) and HDL cholesterol (p less than 0.005). Plasma viscosity, white cell deformability, white cell count, mean corpuscular volume (MCV), and plasma fibrinogen concentration did not significantly differ from the values found in the control group. It is concluded that patients with PPH have impaired blood rheology. The hemorheologic abnormalities in these patients may be of hemodynamic significance.

Specific antibodies to methyltetrahydrophthalic anhydride in exposed workers.

A group of 145 workers exposed to methyltetrahydrophthalic anhydride (MTHPA) was investigated. They were working in a plant which, since 1983, handled an epoxy resin with MTHPA as a hardener. Specific IgE antibodies (RAST) to a conjugate between MTHPA and human serum albumin (HSA) were statistically significantly increased (P = 0.001; 26 subjects = 18% positive) in the exposed group, compared to a non-exposed control group (n = 33). One positive worker was only exposed for 2 months. Twenty-three exposed subjects were also skin-prick test positive to MTHPA-HSA. The exposed group was divided into three different exposure categories, according to their contact with the epoxy resin. The average exposure levels at the time of the investigation were, in zone I 0.085 mg/m3, in zone II 0.014 mg/m3, and in zone III 0.010 mg/m3, though the exposure probably had been higher earlier. There was an association between exposure intensity and RAST-positive persons (P = 0.0025, chi-square trend test). Forty-four persons (30%) were smokers, and 16 (11%) atopics. No association between sensitization and either atopy or smoking was found. There was an association between exposure intensity and specific IgG antibodies (P = 0.0003, chi-square trend test). Specific IgG4 antibodies were closely related to specific total IgG antibodies (P = 0.0001). These findings demonstrate that MTHPA is a sensitizing agent at low levels of exposure.