Elevated serum levels of macrophage migration inhibitory factor and stem cell growth factor ß in patients with idiopathic and systemic sclerosis associated pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) can be idiopathic or secondary to autoimmune diseases, and it represents one of the most threatening complications of systemic sclerosis (SSc). Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine with proinflammatory functions that appears to be involved in the pathogenesis of hypoxia-induced PH. In SSc patients, high serum levels of MIF have been associated with the development of ulcers and PAH. Stem cell growth factor ß (SCGF ß) is a human growth factor that, together with MIF, is involved in the pathogenesis of chronic spinal cord injury. The aim of our study was to measure serum levels of MIF in patients with idiopathic and SSc-associated PAH. We enrolled 13 patients with idiopathic PAH and 15 with SSc-associated PAH. We also selected 14 SSc patients without PAH and 12 normal healthy controls, matched for sex and age. PAH was confirmed by right hearth catheterism (mPAP>25 mmHg). MIF and SCGF ß levels were measured by ELISA. We found significantly higher circulating levels of MIF and of SCGF ß in patients with idiopathic PAH (P=0.03 and P=0.004) and with PAH secondary to SSc (P=0.018 and P=0.023) compared to SSc patients without PAH. Higher levels of MIF were found in those patients with an higher New York Heart Association (NYHA) class (P=0.03). We can hypothesize that MIF and SCGF ß are able to play a role in PAH, both idiopathic or secondary, and in the future they may be evaluated as useful biomarkers and prognostic factors for this serious vascular disease.

[Nailfold capillaroscopy]. / Nagelfalzkapillarmikroskopie.

Capillaroscopy is performed to evaluate the morphology, frequency and blood flow of nailfold capillaries as well as relevant extracapillary changes in rheumatic conditions. The main indication is the differentiation between primary and secondary Raynaud's phenomenon. Various rheumatic conditions show different and partially typical pathognomonic alterations of the microcirculation or capillary patterns. This simple, noninvasive, inexpensive and effective technique is well suited for early diagnosis, especially of connective tissue diseases. The specific significance is highest for systemic sclerosis which is the most frequently evaluated entity. The corresponding microscopic alterations allow stage-adapted conclusions concerning the acuity of inflammation to be formed. That is not the only reason why capillaroscopy represents an important tool in follow-up controls and together with other techniques, such as flow measurement by laser Doppler, further conclusions can be drawn.

Investigation of a new approach for 36Cl determination in solid samples using plastic scintillators.

This work reports a new approach for the determination of 36Cl in radioactive waste samples from nuclear decommissioning, wherein novel plastic scintillator (PS) materials were used for the concentration of 36Cl prior to the detection with scintillation counting. Different plastic scintillator (PS) materials were tested for their selective absorption and detection of 36Cl activity in solid samples. PS microspheres (PSm), cross-linked PSm (CPSm) and PS resin have been investigated. PS resin was identified as the most suitable material for 36Cl analysis. Pyrolysis and subsequent trapping of the volatile elements in a bubbler was used. The trapping solution was finally loaded onto a cartridge of the PS resin. Scintillation counting and ion chromatography were used to determine the activity concentration and the chemical recovery, respectively.

A comparison of different approaches for the analysis of 36Cl in graphite samples.

This study compares different approaches for the quantification of the massic activity of 36Cl in graphite samples. All approaches consisted of a combustion step in combination with a trapping solution to collect the volatile elements. Two different resins were used to separate 36Cl from the matrix (CL resin and PS resin). Liquid scintillation counting (LSC), scintillation counting (SC) and tandem inductively coupled plasma mass spectrometry (ICP-MS/MS) were used to quantify 36Cl activity. The chemical yield in all approaches was determined by means of ion chromatography (IC). In addition, the methods were applied to a real activated graphite sample.

High prevalence of capillary abnormalities in patients with diabetes and association with retinopathy.

AIMS: To investigate the presence of capillary abnormalities in patients with Type 1 and Type 2 diabetes using nailfold videocapillaroscopy and to evaluate the possible correlation with the typical diabetes mellitus microangiopathic lesions detectable in retinal blood vessels. METHODS: Forty-nine patients with diabetes mellitus (21 with Type 1 and 28 with Type 2 diabetes) and 39 subjects without diabetes were enrolled. Ophthalmoscopy was performed on all patients and was followed by retinal fluorangiography when indicated. Subjects underwent nailfold videocapillaroscopy to evaluate density, length, morphology and distribution of capillary loops, presence of ectasia, microbleedings and blood flow modifications. A score (0-3) was applied to quantify features of nailfold videocapillaroscopy. RESULTS: Subjects with diabetes showed a significantly increased (P = 0.0001) nailfold videocapillaroscopy score and significantly greater alterations of capillary length (P = 0.004), distribution (P = 0.02), morphology (P = 0.0001), density (P = 0.02) and flux (P = 0.004), as well as presence of ectasic loops (P = 0.009) and of oedema/exudates (P = 0.03) compared with control subjects. In addition, patients with Type 1 diabetes had a significantly higher score (P = 0.01) and greater morphologic alterations (P = 0.03) compared with subjects with Type 2 diabetes. Nailfold videocapillaroscopy score also showed a positive correlation with retinopathy, detected by both ophthalmoscopy (P = 0.0001) and fluorangiography (P = 0.02), independently from sex, age, type of diabetes and all potential confounders. Moreover, nailfold videocapillaroscopy was capable of identifying alterations in almost 50% of patients with diabetes without retinopathy. CONCLUSIONS: A high prevalence of nailfold capillary changes is detected in patients with diabetes using nailfold videocapillaroscopy. These abnormalities tightly correlate with retinal damage and may be expression of a generalized microvessel involvement in both Type 1 and Type 2 diabetes.

More severe nailfold capillaroscopy findings and anti-endothelial cell antibodies. Are they useful tools for prognostic use in systemic sclerosis?

OBJECTIVE: Anti-endothelial cell antibodies (AECA) have been described in systemic sclerosis (SSc) but their clinical relevance is unclear. METHODS: Aim of this study was to measure serum levels of AECA in 62 SSc patients, examining the main clinical and laboratory features, including nailfold capillaroscopy (NC) abnormalities and looking for any significant association. RESULTS: Fourteen patients (23%) were AECA positive. An "early" NC pattern was observed in 21 patients (34%), an "active" pattern in 24 (39%) and a "late" pattern in 17 cases (27%). In those patients with AECA, a "late" NC pattern was significantly more frequent respect to the "early" and "late" patterns (p<0.05); besides AECA serum levels were significantly higher in the "late" group of patients respect to the other two (p<0.04 and p<0.02 respectively), also showing a significantly more severe modified skin score (mSS) (> or =15) (p<0.04), while those cases with more aggressive NC patterns ("active" and "late") had a more frequent finding of arterial hypertension (p<0.05) and cardiac involvement (p<0.05) respect to those with "early" NC pattern. CONCLUSION: Thus, advanced NC findings were more frequently found in those patients with higher levels of AECA and their contemporary presence may consent to identify specific SSc subsets i.e., those with higher skin scores and cardiovascular involvement. These data suggest that AECA may have a role in the progression of the endothelial damage and their presence and titer should be considered as an adjunctive risk factor for a more severe disease. We also confirm the diagnostic and prognostic validity for NC in SSc, underlying the importance for an accurate capillaroscopic assessment. The contemporary assessment of these two diagnostic tools can be useful to better define different subset of SSc patients.

On the sequential separation and quantification of 237Np, 241Am, thorium, plutonium, and uranium isotopes in environmental and urine samples.

The implementation of the one-pass-through separation technique using two stacked chromatography columns of TEVA - TRU resins for the separation of 237Np, 241Am, thorium, plutonium and uranium from environmental and urine samples was investigated. The sequential separation technique proved to be successful and gave similar results to those obtained when using individual separations. The analysis time was considerably improved. The amount of chemical waste was also reduced by 50% and the use of HClO4 was avoided. The technique of ICP-MS was also investigated as a complementary technique to alpha-spectrometry.

Characterization of the natural radioactivity of the first deep geothermal doublet in Flanders, Belgium.

Deep geothermal energy is a local energy resource that is based on the heat generated by the Earth. As the heat is continuously regenerated, geothermal exploitation can be considered as a renewable and, depending on the techniques used, a sustainable energy production system. In September 2015, the Flemish Institute for Technological Research (VITO) started drilling an exploration well targeting a hot water reservoir at a depth of about 3km on the Balmatt site near Mol. Geothermal hot water contains naturally occurring gases, chemicals and radionuclides at variable concentrations. The actual concentrations and potentially related hazards strongly depend on local geological and hydrogeological conditions. This paper summarizes the radiological characterization of several rock samples obtained from different depths during the drilling, the formation water, the salt and the sediment fraction. The results of our analyses show low values for the activity concentration for uranium and thorium in the formation water and in the precipitate/sediment fraction. Also, the activity concentrations of 210Pb and 210Po are low in these samples and the activity concentration of 226Ra is dominant. From the analysis of the rock samples, it was found that the layer above the reservoir has a higher uranium and thorium concentration than the layer of the reservoir, which on the other hand contains more radium than the layer above it.

Total body irradiation prior to bone marrow transplantation--the experience of the Institute of Oncology Prof. Dr. Al. Trestioreanu Bucharest.

PURPOSE: To present the technique of total body irradiation (TBI), applied for the first time in Romania, at the Institute of Oncology Bucharest, as part of stem cell transplantation for hematological malignancies. PATIENTS AND METHODS: The total dose administered was 12 Gy at the reference point, 2 Gy/fraction, one fraction per day, 6 consecutive days, with a total dose of 8 - 11.4 Gy delivered to the lung, using Mevatron Primus linear accelerator (6 MV & 15 MV, 200-300 cGy/min in isocenter), in vivo dosimetry detectors and equipment for the reference dosimetry, personalized blocks for lung shielding sustained by polymethylmethaacrylate (PPMA) plate, Simulix HP simulator, and computer tomographic (CT) scans. Techniques used were: a) two parallel opposed anteroposterior / posteroanterior (AP/PA) fields with the patient in prone and supine position; b) two parallel opposed lateral fields with the patient placed on a lateral table, at 320 cm from the source. The percentage depth dose, tissue maximum ratio (TMR), off axis ratio (OAR) and the reference dose rate were measured for every patient's geometrical characteristics, with an uncertainty of +/- 2.2% and were used to calculate monitor units and to evaluate the dose in organs at risk (lungs, gonads, eyes etc). RESULTS: 5 patients (3 with the AP/PA technique and 2 with the lateral technique) were irradiated. All patients completed their irradiation in good clinical condition. The acute side effects were minimal (WHO grade 1: nausea/ vomiting--all patients; diarrhea--1 patient; headache--2 patients; photophobia and diplopia--1 patient; head and neck skin erythema--all patients). Because of the short follow-up period no safe evaluation of late side effects can be done. However, during this period one patient developed a non-aggressive form of chronic liver graft vs. host disease (GVHD) and one patient died due to acute GVHD. CONCLUSION: TBI as part of stem cell transplantation for hematological malignancies was successfully realized at our Institute, with favorable clinical results. This technique is easy to carry out and reproducible.

Determination of 210Pb, 210Po, 226Ra, 228Ra and uranium isotopes in drinking water in order to comply with the requirements of the EU 'Drinking Water Directive.

The European Union published in 2013 a new Drinking Water Directive with stricter requirements for measuring natural radioactivity. In order to adhere to this, a method for sequential separation of 210Pb, 210Po, 238U and 234U in drinking water was applied using UTEVA® and Sr resins. Polonium-210, 238U and 234U were quantified using alpha-particle spectrometry and 210Pb using liquid scintillation counting. Radium-226 and 228Ra were determined using 3M Empore Radium RAD Disks, and their quantification was done using a Quantulus™ 1220 liquid scintillation counter.

Liver iron overload assessment by MRI R2* relaxometry in highly transfused pediatric patients: an agreement and reproducibility study.

AIMS: Perform an agreement and reproducibility study of the estimation of iron overload in highly transfused pediatric patients comparing R2* relaxometry (R2*=1000/T2*) to the reference technique liver/muscle signal intensity ratio (SIR). PATIENTS AND METHODS: Ninety-two MRI were performed in 68 children who were mainly transfused for sickle cell disease, mean age 9.9 years old. The examination included six sequences for the SIR protocol and a single multiecho T2* sequence. R2* relaxometry was measured by two radiologists independently, either by a region of interest (ROI) in the right liver, or an outline of the whole liver. Hepatic iron load was determined by the Wood formula (Fe mg/g=R2*×0.0254+0.202). The validity of R2* relaxometry compared to SIR was evaluated by the coefficient of variation and the quadratic weighted Kappa value. RESULTS: The correlation between R2* relaxometry and SIR was very good with a Pearson coefficient of 0.89 and a coefficient of variation of 17.3%. The inter- and intraobserver reproducibility of the measurement of R2* relaxometry by ROI and whole liver mapping was excellent. However, we observed a common positive variation of one class between SIR and R2* relaxometry, with higher hepatic iron content values with SIR than with R2* relaxometry. CONCLUSION: Hepatic iron content can be rapidly and precisely estimated on MRI by multiecho gradient-echo sequences.

Microfabrication techniques using focused ion beams and emergent applications.

The application of focused ion beam (FIB) machining in several technologies aimed at microstructure fabrication is presented. These emergent applications include the production of micromilling tools for machining of metals and the production of microsurgical tools. An example of the use of microsurgical manipulators in a circulatory system measurement is presented. The steps needed to transform the laboratory fabrication of these tools and manipulators into a routine FIB production process are discussed. The ion milling of three-dimensional cavities by the exact solution of a mathematical model of the FIB deflection is demonstrated. A good agreement between the model calculation and the ion beam control has been obtained for parabolic and cosine cross-section features with planes of symmetry.

Unusual localisation of an ectopic pregnancy.

We present a case of ectopic pregnancy with a peculiar localisation: beneath the peritoneal serosa covering the anterior wall of the uterus, at the level of the uterovesical pouch. The case raised some diagnostic and management problems for the medical team. Considerations are made concerning the etiopathology of this unusual form of ectopic pregnancy.

[Colonic tubular adenoma following ureterosigmoidostomy: CT features]. / Adénome colique tubuleux après urétérosigmoïdostomie: aspect tomodensitométrique. à propos d'un cas.

We report a case of benign colonic tubular adenoma arising in a 36-year-old female at the site of ureterosigmoidostomy performed 25 years before. The tumor was revealed by recurrent episodes of pyelonephritis; hydronephrosis was present. On colonic enema, the tumor appeared lobulated, 4 cm in diameter. CT scan showed a multiloculated mass, which enhanced after injection. Pathology revealed a tubular adenoma of the colon with cystic dilatation of glandular structures. The role of imaging studies in the follow-up of patients after ureterosigmoidostomy is discussed.

Certification of the reference material IRMM-426 for radionuclides in dried bilberries.

A new reference material for the activity concentration of (137)Cs, (40)K and (90)Sr in a dried berry matrix was certified from a batch of bilberries collected in the vicinity of the Chernobyl nuclear power plant. Radionuclides in this material were metabolised by the plants, therefore no spiking had to be performed. The material was processed at IRMM and homogeneity and stability of the certified parameters were demonstrated. The certified property values for (137)Cs, (40)K and (90)Sr were determined in the course of a supplementary comparison, CCRI(II)-S8.

Insulin glargine or neutral protamine Hagedorn in patients with severe insulin resistance: Is there a benefit?

OBJECTIVE: To determine the benefit of neutral protamine Hagedorn (NPH) insulin compared with insulin glargine in a patient with type 2 diabetes mellitus and severe insulin resistance. METHODS: We describe the patient's clinical findings and treatment course. RESULTS: A 52-year-old man with a 3-year history of type 2 diabetes mellitus did not achieve adequate glucose control despite escalation of his treatment regimen to insulin glargine, 80 units twice daily; insulin lispro, 60 units before each meal; and metformin. Dietary and lifestyle changes were emphasized and implemented while medication adherence with appropriate insulin technique was reviewed at each visit. Insulin glargine was replaced with the same dosage of NPH insulin. After 3 months, a significant drop in hemoglobin A1c was noted, from 9.5% to 6.1%, consistent with the improved capillary glucose measurements. The effect was maintained over the following year, without any major hypoglycemic events. CONCLUSION: NPH insulin might be superior to the long-acting analogue insulin glargine in cases of severe insulin resistance, but randomized studies are needed to confirm our finding and clarify the involved mechanisms.

Fanconi's syndrome and nephrogenic diabetes insipidus in an adult treated with ifosfamide.

Fanconi's syndrome is a serious condition characterized by type II proximal renal tubular dysfunction, with urinary loss of glucose, amino acids, phosphate, bicarbonate, and potassium. Ifosfamide-induced Fanconi's syndrome is reported in about 1.4-5% of children being treated for solid tumors, yet only a few cases have been reported in adults. We describe a 54-year-old man who came to the hospital with symptoms of neutropenic fever 4 days after his fourth cycle of ifosfamide and doxorubicin treatment for recurrent sarcoma with metastases to the lung. During admission, he was noted to have severe renal tubular dysfunction; ifosfamide-induced nephrogenic diabetes insipidus and Fanconi's syndrome were suspected. He received supportive therapy that resulted in incomplete resolution of signs and symptoms. The patient was discharged after a 5-day hospital stay when his white blood cell count increased from 0.1-2.5 × 10(3) /mm(3) and his fever had resolved. Use of the Naranjo adverse drug reaction probability scale indicated a probable relationship (score of 7) between the patient's development of diabetes insipidus and Fanconi's syndrome and his use of ifosfamide. This dual diagnosis of diabetes insipidus and Fanconi's syndrome in an adult makes this case unusual, as well as therapeutically challenging. We conducted a review of the existing literature regarding ifosfamide-induced Fanconi's syndrome and describe the proposed mechanisms and therapeutic options. This case suggests that patients treated with ifosfamide should be monitored closely for renal function to identify, and perhaps prevent, these rare adverse events. Preliminary animal models show promise for adding N-acetylcysteine to ifosfamide treatment, but more research is necessary before using this drug as a therapeutic option.

EC comparison on the determination of 226Ra, 228Ra, 234U and 238U in water among European monitoring laboratories.

In anticipation of new European requirements for monitoring radioactivity concentration in drinking water, IRMM organized an interlaboratory comparison on the determination of low levels of activity concentrations (about 10-100 mBq L(-1)) of the naturally occurring radionuclides (226)Ra, (228)Ra, (234)U and (238)U in three commercially available mineral waters. Using two or three different methods with traceability to the International System of Reference (SIR), the reference values of the water samples were determined prior to the proficiency test within combined standard uncertainties of the order of 3%-10%. An overview of radiochemical separation and measurement methods used by the 45 participating laboratories are given. The results of the participants are evaluated versus the reference values. Several of the participants' results deviate by more than a factor of two from the reference values, in particular for the radium isotopes. Such erroneous analysis results may lead to a crucial omission of remedial actions on drinking water supplies or to economic loss by an unjustified action.