In-vivo dosimetry for field sizes down to 6 × 6 mm2 in shaped beam radiosurgery with microMOSFET.

The aim of this study is to evaluate microMOSFET as in-vivo dosimeter in 6 MV shaped-beam radiosurgery for field sizes down to 6 × 6 mm2. A homemade build-up cap was developed and its use with microMOSFET was evaluated down to 6 × 6 mm2. The study with the homemade build-up cap was performed considering its influence on field size over-cover occurring at surface, achievement of the overall process of electronic equilibrium, dose deposition along beam axis and dose attenuation. An optimized calibration method has been validated using MOSFET in shaped-beam radiosurgery for field sizes from 98 × 98 down to 18 × 18 mm2. The method was detailed in a previous study and validated in irregular field shapes series measurements performed on a head phantom. The optimized calibration method was applied to microMOSFET equipped with homemade build-up cap down to 6 × 6 mm2. Using the same irregular field shapes, dose measurements were performed on head phantom. MicroMOSFET results were compared to previous MOSFET ones. Additional irregular field shapes down to 8.8 × 8.8 mm2 were studied with microMOSFET. Isocenter dose attenuation due to the homemade build-up cap over the microMOSFET was near 2% irrespective of field size. Our results suggested that microMOSFET equipped with homemade build-up cap is suitable for in-vivo dosimetry in shaped-beam radiosurgery for field sizes down to 6 × 6 mm2 and therefore that the required build-up cap dimensions to perform entrance in-vivo dosimetry in small-fields have to ensure only partial charge particle equilibrium.

An optimized calibration method for surface measurements with MOSFETs in shaped-beam radiosurgery.

Nowadays MOSFET dosimeters are widely used for dose verification in radiotherapy procedures. Although their sensitive area satisfies size requirements for small field dosimetry, their use in radiosurgery has rarely been reported. The aim of this study is to propose and optimize a calibration method to perform surface measurements in 6 MV shaped-beam radiosurgery for field sizes down to 18 × 18 mm(2). The effect of different parameters such as recovery time between 2 readings, batch uniformity and build-up cap attenuation was studied. Batch uniformity was found to be within 2% and isocenter dose attenuation due to the build-up cap over the MOSFET was near 2% irrespective of field size. Two sets of sensitivity coefficients (SC) were determined for TN-502RD MOSFET dosimeters using experimental and calculated calibration; the latter being developed using an inverse square law model. Validation measurements were performed on a realistic head phantom in irregular fields. MOSFET dose values obtained by applying either measured or calculated SC were compared. For calibration, optimal results were obtained for an inter-measurement time lapse of 5 min. We also found that fitting the SC values with the inverse square law reduced the number of measurements required for calibration. The study demonstrated that combining inverse square law and Sterling-Worthley formula resulted in an underestimation of up to 4% of the dose measured by MOSFETs for complex beam geometries. With the inverse square law, it is possible to reduce the number of measurements required for calibration for multiple field-SSD combinations. Our results suggested that MOSFETs are suitable sensors for dosimetry when used at the surface in shaped-beam radiosurgery down to 18 × 18 mm(2).

Peptide binding to ochratoxin A mycotoxin: a new approach in conception of biosensors.

Ochratoxin A (OTA) is a widespread and abundant natural carcinogenic mycotoxin produced by several species of Aspergillus and Penicillium fungi. Due to the ubiquitous presence of these fungi in food and potential risk for human health, a rapid and sensitive in vitro detection assay is required. Analytical methods for OTA detection/identification are generally based on liquid-liquid extraction, clean-up using an immunoaffinity column (IAC), and identification by reversed-phase high pressure liquid chromatography with fluorescence detection (HPLC-FLD). However, IACs are costly and have a short lifespan. Therefore, an interesting approach would appear to be the design and chemical synthesis of a mimotope peptide simulating mycotoxin-specific antibodies. We have developed a promising alternative method that is based on the use of peptides which are able to bind to specific chemical functions and/or molecular structures. Accordingly, a number of peptides (derived from the structures of major redox proteins) were selected and produced by chemical solid phase syntheses. The ability of such peptides to bind to ochratoxin A was evaluated by HPLC. The peptide NF04 (structurally derived from an oxidoreductase enzyme), which was found to be the sole potently reactive compound among tested molecules, was further evaluated in a peptide-based enzyme-linked immunosorbent assay (peptide-based ELISA), thus confirming its specific interaction with ochratoxin A.

[Radiosurgery for brain arteriovenous malformations]. / Radiochirurgie stéréotaxique des malformations artérioveineuses cérébrales.

Radiosurgery as treatment for arteriovenous malformations has shown a good efficacy in reducing intracranial bleeding due to rupture. The choice of therapeutic modalities is based on evolutive risk and arteriovenous malformations volume, patient profile and risks stratification following therapeutic techniques (microsurgery, radiosurgery, embolization). Nidus size, arteriovenous malformations anatomical localization, prior embolization or bleeding, distributed dose are predictive factors for radiosurgery's good results and tolerance. This review article will highlight arteriovenous malformations radiosurgery indications and discuss recent irradiation alternatives for large arteriovenous malformation volumes.

[Stereotactic radiotherapy for intracranial meningioma]. / Radiothérapie stéréotaxique des méningiomes intracrâniens.

Meningiomas are the most common non-malignant tumours of the brain. Gross-total resection remains the preferred treatment, if achievable without morbidity. Radiation therapy is advocated for inoperable, incompletely resected, or recurrent grade 1 tumours, if there is a progressive, symptomatic lesion, or in case of functional impairment. Postoperative radiation therapy is recommended for grade 2 or 3 lesions. Fractionated stereotactic radiotherapy and stereotactic radiosurgery are high precision techniques, allowing good sparing of surrounding tissues. Fractionated stereotactic radiotherapy and stereotactic radiosurgery give comparable results, with excellent 5-year tumour control rates of more than 90% for benign meningiomas. Toxicity is low and seems equivalent, despite a biased use of fractionated stereotactic radiotherapy for larger meningiomas, close to critical structures. Fractionated stereotactic radiotherapy seems to be of special interest in the treatment of cavernous sinus or optic pathways meningiomas. The different therapeutic modalities should be discussed by a multidisciplinary team.

pH optimization for a reliable quantification of brain tumor cell and tissue extracts with (1)H NMR: focus on choline-containing compounds and taurine.

The aim of this study was to define the optimal pH for (1)H nuclear magnetic resonance (NMR) spectroscopy analysis of perchloric acid or methanol-chloroform-water extracts from brain tumor cells and tissues. The systematic study of the proton chemical shift variations as a function of pH of 13 brain metabolites in model solutions demonstrated that recording (1)H NMR spectra at pH 10 allowed resolving resonances that are overlapped at pH 7, especially in the 3.2-3.3 ppm choline-containing-compounds region. (1)H NMR analysis of extracts at pH 7 or 10 showed that quantitative measurements of lactate, alanine, glutamate, glutamine (Gln), creatine + phosphocreatine and myo-inositol (m-Ino) can be readily performed at both pHs. The concentrations of glycerophosphocholine, phosphocholine and choline that are crucial metabolites for tumor brain malignancy grading were accurately measured at pH 10 only. Indeed, the resonances of their trimethylammonium moieties are cleared of any overlapping signal, especially those of taurine (Tau) and phosphoethanolamine. The four non-ionizable Tau protons resonating as a singlet in a non-congested spectral region permits an easier and more accurate quantitation of this apoptosis marker at pH 10 than at pH 7 where the triplet at 3.43 ppm can be overlapped with the signals of glucose or have an intensity too low to be measured. Glycine concentration was determined indirectly at both pHs after subtracting the contribution of the overlapped signals of m-Ino at pH 7 or Gln at pH 10.

[Dosimetric stereotactic radiosurgical accident: Study of 33 patients treated for brain metastases]. / Traitement des métastases cérébrales par radiochirurgie stéréotaxique : étude de 33 cas liés à un accident de "surexposition".

The consequences of a dosimetric radiosurgery accident are not the same as a conventional radiotherapy accident. The objective of this study was to estimate the clinical and radiological outcome of patients treated by radiosurgery for metastasis during the period of the overexposure accident that occurred in the Toulouse Radiosurgery Unit. Between April 2006 and March 2007, 33 patients with 57 metastases were treated in the Toulouse Radiosurgery Unit (Novalis(®), BrainLab). An initial error in the estimation of the scatter factors led to an overexposure to radiation. The median age was 55 years [range, 35-85]. Twenty-one patients (64%) harbored a single metastasis. The primary tumor location was lung (16 cases), kidney (nine cases), breast (four cases), and others (four cases). The mean tumoral volume was 3.2cm(3) [0.04-14.07]. The mean prescribed dose at the isocenter was 20 Gy [range, 10-23], the mean delivered dose was 31.5 Gy [range, 13-52], and the mean overdose was 61.2% [range, 5.6-226.8]. In order to evaluate the consequences of the overdose, three parameters were analyzed: a risk index using dose and volume, the volume of parenchyma that received more than 12 Gy, and the mean dose in a sphere of 20cm(3) surrounding the target volume. Median actuarial survival was 14.1 months, the survival rate was 79.4 % at six months, 59.1% at 12 months, and 27.2% at 24 months. The rate of tumor control was 80.7%. No morbidity was observed. There was no correlation between death and the parameters studied. The survival rates and times observed in our study of the patients treated for brain metastases by radiosurgery and overexposed were among the good results of the international literature. Deaths were not related to the overdose and no side effect was noted. This dosimetric accident has not had worse consequences in this population.

Milk, rather than other foods, is associated with vertebral bone mass and circulating IGF-1 in female adolescents.

SUMMARY: Low calcium intake hampers bone mineral acquisition in adolescent girls. This study explores dietary calcium sources and nutrients possibly associated with vertebral mass. Milk intake is not influenced by genetic variants of the lactase gene and is positively associated with serum IGF-1 and with lumbar vertebrae mineral content and density. INTRODUCTION: Low calcium intake hampers bone mineral acquisition during adolescence. We identified calcium sources and nutrients possibly associated with lumbar bone mineralization and calcium metabolism in adolescent girls and evaluated the possible influence of a genetic polymorphic trait associated with adult-type hypolactasia. METHODS: Lumbar bone mineral content (BMC), bone mineral density (BMD), and area, circulating IGF-1, markers of bone metabolism, and -13910 LCT (lactase gene) polymorphism; and intakes of milk, dairy products, calcium, phosphorus, magnesium, proteins, and energy were evaluated in 192 healthy adolescent girls. RESULTS: After menarche, BMC, BMD, serum IGF-1, and serum PTH were tightly associated with milk consumption, but not with other calcium sources. All four parameters were also associated with phosphorus, magnesium, protein, and energy from milk, but not from other sources. Girls with milk intakes below 55 mL/day have significantly lower BMD, BMC, and IGF-1 and higher PTH compared to girls consuming over 260 mL/day. Neither BMC, BMD, calcium intakes, nor milk consumption were associated with -13910 LCT polymorphism. CONCLUSIONS: Milk consumption, preferably to other calcium sources, is associated with lumbar BMC and BMD in postmenarcheal girls. Aside from being a major source of calcium, milk provides phosphates, magnesium, proteins, and as yet unidentified nutrients likely to favor bone health.

Sympathetic B antagonist prevents bone mineral density decrease induced by labyrinthectomy.

We previously showed that bilateral vestibular lesion in rats induces a bone loss in weight bearing bones. To determine whether this effect is mediated by the sympathetic nervous system (SNS), bone mineral density (BMD) was measured in 4 groups of 10 female Wistar rats: bilateral labyrinthectomy (Bilab), Bilab with propranolol treatment, sham operated with or withoutpropranolol. In untreated rats, 30 days after lesion Bilab animals showed a reduced BMD in distal femoral metaphysis comparatively to intact rats (p < 0.001). In treated rats, there was no difference in BMD 30 days after lesion. This protective effect of propranolol against bone loss suggests that the vestibular system influence on bone remodeling is mediated by SNS. If this hypothesis is correct, this could have important consequences in devising countermeasures to spaceflight induced bone loss.

Effect of Cu2+ on the oxidative folding of synthetic maurotoxin in vitro.

Maurotoxin (MTX) is a 34-mer scorpion toxin cross-linked by four disulphide bridges that acts on various K+ channel types. It folds according to an alpha/beta scaffold, i.e., a helix connected to a two stranded beta-sheet by two disulphide bridges. In a former study, various parameters that affect the oxidation and folding of the reduced form of synthetic MTX were investigated in vitro. It was found that MTX achieves its final 3-D structure by evolving over time through a series of oxidation intermediates, from the least to the most oxidized species. MTX oxidative intermediates can be studied by iodoacetamide alkylation of free cysteine residues followed by mass spectrometry analysis. Here, we have analysed the effect of Cu2+ (0.1 to 50 mM) on the kinetics of MTX oxidative folding and found that it dramatically speeds up the formation of the four-disulphide bridged, native-like, MTX (maximal production within 30 minutes instead of > 60 hours). This catalysing effect of Cu2+ was found to be concentration-dependent, reaching a plateau at 10 mM copper ions. Cu2+ was also found to prevent the slow transition of a three disulphide-bridged MTX intermediate towards the final four disulphide-bridged product (12% of total MTX). The data are discussed in light of the potential effects of Cu2+ on MTX secondary structure formation, disulphide bridging and peptidyl prolyl cis-trans isomerization.

[Chemical synthesis of lactococcin B and functional evaluation of the N-terminal domain using a truncated synthetic analogue]. / Synthèse chimique de la lactococcine B et évaluation fonctionnelle de son extrémité N-terminale grâce à un analogue synthétique tronqué.

The lactococcin B (LnB) is a hydrophobic, positively charged bacteriocin, produced by Lactococcus lactis ssp. cremoris 9B4. It consists of a peptidic chain made up of 47 amino acid residues, and inhibits Lactococcus exclusively. In order to study its biological activity a synthetic lactococcin B (LnBs) was obtained by solid-phase chemical synthesis using a Fmoc strategy. LnBs was shown to be indistinguishable from the natural peptide. In addition, a synthetic (7-47) LnBst analogue was obtained by withdrawal of peptidyl-resin after the 41 cycle of LnBs peptide chain assembly. The synthetic N-terminal truncated (7-47) LnBst analogue was found to be inactive on indicator strains. Our results strongly suggest that the first six N-terminal amino acid residues are involved in the bactericidal activity of LnB.

[Treatment of pediatric obesity: effects on body composition and physical fitness]. / Prise en charge ambulatoire de l'obésité: effets sur la composition corporelle et la capacité aérobie.

AIMS: To assess the efficiency of an ambulatory weight management programme of pediatric obesity, including 1 gymnastic session per week, on body composition and physical fitness (max). SUBJECTS: Fifteen adolescents participated in the 9-month intervention. BMI and fitness and physical activity assessed by a questionnaire were evaluated at baseline, and after intervention. RESULTS: Prepubescent subjects (N=6): no significant change of BMI, body composition, nor max. Pubescent subjects: significant decrease of BMI, and z score BMI, and % fat mass, increase of fat free mass. Activity questionnaire: non-significant trend to decreased TV watching, significant increase in practice of physical activity during weekend. CONCLUSION: A modest increase in physical practice, included in the dietary-behavioural management of adolescent obesity, is able to improve overweight and physical fitness.

Delayed Medullar Syndrome after Aneurysmal Subarachnoid Haemorrhage. A Case report of Cystic Arachnoiditis!

SUMMARY: We described a case of chronic spinal cystic arachnoiditis after subarachnoid haemorrhage in a 54-year-old woman with a ruptured vertebral artery aneurysm treated by coils. At three months she complained of lumbar pain.At twelve months she presented lower limbs paresthesia then a rapidly bilateral motor deficit. MR showed a spinal arachnoiditis with two compressive cysts. Surgical decompression was inefficient and after three months spinal compression symptoms worsened and MR signs were unchanged.

The evolution of weight and body composition in renal transplant recipients: Two-year longitudinal study.

UNLABELLED: Previous series have reported weight gain after kidney transplantation. However few studies have investigated the body composition after kidney transplantation, particularly during longitudinal follow-up. In this prospective study, we assessed the changes in body composition after kidney transplantation. We also analyzed the effect of steroid withdrawal from the immunosuppressive regimen on weight gain and body composition. METHODS: Thirty-eight cadaveric kidney transplant recipients were followed for 2 years posttransplant. Total and segmental body composition were measured by dual energy X-ray absorptiometry (DEXA) at the time of transplantation as well as 3, 6, 12, and 24 months later. RESULTS: In 28 patients (group A), prednisone was stopped by month 6, whereas, in 10 patients (group B), it was continued throughout the study. In the overall patient group, there were no significant changes in body weight. However, a trend to increased weight was observed in group B. In this group, patients showed an early increase in total body fat with a central accumulation of fat mass that was maintained during the follow-up period. On the other hand, total lean mass increased significantly in group A but did not change significantly in group B. CONCLUSION: In summary, overall the group showed no major changes in body weight during the 2 years after transplantation. Steroid withdrawal in kidney transplant recipients may have a significant positive effect on body composition.

Immunodetection of SV40 large T antigen in human central nervous system tumours.

BACKGROUND/AIMS: DNA sequences from Simian virus 40 (SV40) have been previously isolated from various human tumours of the central nervous system (CNS). This study aimed to investigate a series of tumours of the CNS for the expression of the SV40 large T antigen (Tag), which is an oncogenic protein of the virus. METHODS: A French series of 82 CNS tumours was investigated for Tag expression using a monoclonal antibody and immunohistochemistry. A Tag positive hepatocellular carcinoma cell line from transgenic mice and a kidney biopsy from a patient infected by SV40 were used as positive controls. RESULTS: None of the tumours (20 ependymomas, 20 glioblastomas, 12 oligodendrogliomas, three plexus choroid adenomas, two plexus choroid carcinomas, 15 meningiomas, and 10 medulloblastomas) contained SV40 Tag positive cells. CONCLUSIONS: The lack of SV40 Tag in 82 CNS tumours of various types is at variance with previous studies from different countries, and suggests that the virus may not be an important factor in CNS tumorigenesis, at least in French cases.

Detection of human cytomegalovirus genome and gene products in central nervous system tumours.

Human cytomegalovirus (HCMV) genome and related proteins have been reported in a great proportion of malignant gliomas. However, these results are unexpected since HCMV is not known as an oncogenic virus. By immunohistochemistry (with an anti-IE1 monoclonal antibody) and in situ hybridisation (with biotinylated DNA probes) on tissue microarrays and frozen sections, we investigated a French series of central nervous system (CNS) tumours, including 97 glioblastomas. In 10 cases of glioblastoma, rare astrocyte-like cells, admixed with tumour cells, stained positively for HCMV and in one case a doubtful staining of rare cells was noticed. This may indicate a reactivation of the virus under local immunosuppression but none of the cases of CNS tumours (n=132) contained HCMV genomes and/or proteins in a significant proportion of tumour cells. Our results strongly suggest that HCMV is unlikely to be implicated in the development of human malignant gliomas, at least in French cases.

Small conductance calcium-activated K+ channels, SkCa, but not voltage-gated K+ (Kv) channels, are implicated in the antinociception induced by CGS21680, a A2A adenosine receptor agonist.

It has been shown that A2A adenosine receptors are implicated in pain modulation. The precise mechanism by which activation of A2A receptors produces analgesic effects, however, remains unclear. The aim of this study was to investigate the possible involvement of apamin-sensitive calcium-activated potassium channels (SKCa) and voltage-gated potassium (Kv) channels in A2A receptor activation-induced analgesic effects. Using mice, we evaluated the influence of apamin, a non specific blocker of SKCa channels, Lei-Dab7 (an analog of scorpion Leiurotoxin), a selective blocker of SKCa2 channels, and kaliotoxin (KTX) a Kv channel blocker, on the CGS 21680 (A2A adenosine receptor agonist)-induced increases in hot plate and tail pinch latencies. All drugs were injected in mice via the intracerebroventricular route. We found that apamin and Lei-Dab7, but not KTX, reduced antinociception produced by CGS21680 on the hot plate and tail pinch tests in a dose dependent manner. Lei-Dab 7 was more potent than apamin in this regard. We conclude that SKCa but not Kv channels are implicated in CGS 21680-induced antinociception.

[A patient with visceral leishmaniasis and acute renal failure in necrotizing glomerulonephritis]. / Leishmaniose viscérale autochtone avec insuffisance rénale aiguë par glomérulonéphrite infectieuse.

Renal involvement is an unusual complication of human visceral leishmaniasis (VL). The kidney lesions are characterized more by interstitial damage than glomerular or vascular damage. This case represents a 20 years-old man admitted with pancytopenia, purpura, acute renal failure, and nephrotic syndrome associated with heavy proteinuria. The diagnosis of VL was made on bone marrow smear cytology where Leishmania amastigotes were found. The renal biopsy revealed a segmental necrotising glomerulonephritis with 70% crescents. Treatment with liposomal amphotericine B alone has been ineffective on the course of renal failure, however, partial recovery was obtained after the administration of high dose corticosteroids. We present the various clinical, biological, and histological aspects of this case, from the south of France. It gave us the opportunity to discuss these unusual manifestations of immunomediated necrotising skin and renal lesions.