Measurement of short-term 11C-thymidine activity in human head and neck tumours using positron emission tomography (PET).

Tumour uptake of 11C-thymidine labeled in the methyl position was assessed after intravenous injection in 13 patients with head and neck tumours. This activity was compared to other tracers such as C15O, 13NH3 and C15O2. In every single case a 'positive' tumour image after injection of 11C-thymidine was obtained. Time-activity curves showed the initial activity to be followed by a rapid decrease over the first 10-15 min with an apparent plateau thereafter. A similar level of uptake was found in normal salivary gland regions and myocardium, while higher activities were noted in liver and kidney parenchyma. It is suggested that both blood flow and cellular metabolism can influence 11C-thymidine imaging in this class of human tumours.     

Differential Effect of Diarrhea on FK506 Versus Cyclosporine A Trough Levels and Resultant Prevention of Allograft Rejection in Renal Transplant Recipients

Diarrhea is the most frequently reported adverse event in patients treated with mycophenolate mofetil. Twenty-six renal transplant patients on a mycophenolate mofetil-based immunosuppressive regime with persistent afebrile diarrhea were examined. Diarrhea caused a significant rise in FK-506 trough levels despite intake of stable doses, necessitating FK-506 dose reductions of 30% to obtain pre-diarrhea trough levels. In contrast, trough levels of cyclosporine A remained stable without dose adjustments. This suggests that absorption and/or metabolism is differentially altered for FK506 compared with cyclosporine A in patients with diarrhea. In nine patients mycophenolate mofetil was reduced or stopped because of persistent diarrhea without identifiable cause. This resulted in end-stage renal disease because of chronic rejection in two patients, and in acute rejection in two patients, all taking FK506 and steroids. Therefore, dose adjustments of FK506 in patients with diarrhea must be carefully monitored, especially when doses of mycophenolate mofetil are also reduced.     

Clonal chromosomal changes in juxta-articular myxoma

 Cytogenetic analysis of a juxta-articular myxoma revealed two distinct cytogenetically abnormal cell populations: inv(2)(p15q36) and +7, t(8;22)(q11–12; q12–13). These clonal chromosomal changes, the first to be reported in this tumour type, suggest that at least some juxta-articular myxomas are neoplastic rather than reactive in nature. Received: 8 June 1998 / Accepted: 17 August 1998     

Monte Carlo simulations of a scintillation camera using GATE: validation and application modelling

Geant4 application for tomographic emission (GATE) is a recently developed simulation platform based on Geant4, specifically designed for PET and SPECT studies. In this paper we present validation results of GATE based on the comparison of simulations against experimental data, acquired with a standard SPECT camera. The most important components of the scintillation camera were modelled. The photoelectric effect. Compton and Rayleigh scatter are included in the gamma transport process. Special attention was paid to the processes involved in the collimator: scatter, penetration and lead fluorescence. A LEHR and a MEGP collimator were modelled as closely as possible to their shape and dimensions. In the validation study, we compared the simulated and measured energy spectra of different isotopes: 99mTc, 22Na, 57Co and 67Ga. The sensitivity was evaluated by using sources at varying distances from the detector surface. Scatter component analysis was performed in different energy windows at different distances from the detector and for different attenuation geometries. Spatial resolution was evaluated using a 99mTc source at various distances. Overall results showed very good agreement between the acquisitions and the simulations. The clinical usefulness of GATE depends on its ability to use voxelized datasets. Therefore, a clinical extension was written so that digital patient data can be read in by the simulator as a source distribution or as an attenuating geometry. Following this validation we modelled two additional camera designs: the Beacon transmission device for attenuation correction and the Solstice scanner prototype with a rotating collimator. For the first setup a scatter analysis was performed and for the latter design. the simulated sensitivity results were compared against theoretical predictions. Both case studies demonstrated the flexibility and accuracy of GATE and exemplified its potential benefits in protocol optimization and in system design.     

55Cobalt (Co) as a PET-tracer in stroke, compared with blood flow, oxygen metabolism, blood volume and gadolinium-MRI

Axonal degeneration plays an important role in the accumulation of disability in patients with multiple sclerosis (MS). Pathological studies have demonstrated axonal damage, particularly in areas of acute inflammation and demyelination, and in chronic lesions. Axonal loss and its progression, which is associated with neurological disability, has also been demonstrated by magnetic resonance imaging (MRI) studies. The mechanisms of axonal loss are uncertain, but may involve axonal degeneration secondary to demyelination, or damage to the axonal cytoskeleton. Inflammatory mediators, including cytokines and proteolytic enzymes may contribute to axonal damage, as may nitric oxide. Axonal destruction may also be due to immune attack directed at axonal components. The realisation that axonal degeneration is a fundamental component of MS that may occur early in the disease course should alter the approach to management and open avenues to a more targeted immunotherapy aimed at reducing the progression of disability.     

Human kallikrein 6 (hK6): a new potential serum biomarker for diagnosis and prognosis of ovarian carcinoma.

PURPOSE: The discovery of new ovarian cancer biomarkers that are suitable for early disease diagnosis and prognosis may ultimately lead to improved patient management and outcomes. PATIENTS AND METHODS: We measured, by immunoassay, human kallikrein 6 (hK6) concentration in serum of 97 apparently healthy women, 141 women with benign abdominal diseases, and 146 women with histologically proven primary ovarian carcinoma. We then calculated the diagnostic sensitivity and specificity of this test and examined the association of serum hK6 concentration with various clinicopathologic variables and patient survival. RESULTS: Serum hK6 concentration between normal and benign disease patients was not different (mean, 2.9 and 3.1 micro g/L, respectively). However, hK6 in presurgical serum of ovarian cancer patients was highly elevated (mean, 6.8 micro g/L; P <.001). Serum hK6 decreased after surgery (to a mean of 3.9 micro g/L) in 68% of patients. The diagnostic sensitivity of serum hK6 at 90% and 95% specificity is 52% and 47%, respectively, in the whole patient population. For early stage disease (stage I or II), sensitivity is approximately 21% to 26%. When combined with CA-125, at 90% specificity, sensitivity increases to 72% (for all patients) and to 42% in stage I or II disease. Serum hK6 concentration correlates moderately with CA-125 and is higher in patients with late-stage, higher-grade disease and in patients with serous histotype. Preoperative serum hK6 concentration is a powerful predictor of disease-free and overall survival in both univariate and multivariate analyses. CONCLUSIONS: Serum hK6 concentration seems to be a new biomarker for ovarian carcinoma and may have value for disease diagnosis and prognosis.     

The addition of 4% oxygen to the CO(2) pneumoperitoneum does not decrease dramatically port site metastases

Study ObjectivePort site metastases (PSM) after laparoscopic surgery for advanced-stage ovarian carcinoma are a cause of concern, but the pathophysiology is unknown. Because CO₂ pneumoperitoneum was recently demonstrated to be a cofactor in adhesion formation and tumor implantation in a laparoscopic mouse model, and because both could be prevented by the addition of 4% oxygen to the CO₂ pneumoperitoneum, we wanted to test the hypothesis that PSM could be related to tumor cell hypoxia during CO₂ pneumoperitoneum.DesignA randomized controlled pilot trial to compare the incidence of PSM in women undergoing laparoscopy with a pure CO₂ pneumoperitoneum in comparison with women with CO₂ pneumoperitoneum with the addition of 4% oxygen (Canadian Task Force classification C).SettingUniversity Hospital Gasthuisberg, Leuven, Belgium.PatientsSince January 1, 2007, 22 consecutive women undergoing laparoscopy for suspected ovarian cancer with subsequent debulking laparotomy were included.InterventionsDiagnostic laparoscopy with 100% CO₂ versus laparoscopy with addition of 4% oxygen.Measurements and Main ResultsIn the control group, 9 (47%) PSM found in 19 port sites were excised. In the CO₂+oxygen group, a similar incidence was found, that is, 8 (50%) PSM in 16 port sites. The incidence of PSM was higher in small women (p <.018) and in high-grade malignancies. The pathophysiology of PSM is unknown, but besides direct wound contamination, aerosolization of tumor cells and gas leaks have been suggested together with a causal relationship with the CO₂ pneumoperitoneum. Tumor cell hypoxia probably is not an important mechanism because PSM were not prevented by adding small amounts of oxygen to the CO₂ pneumoperitoneum.ConclusionThe hypothesis of tumor cell hypoxia by the CO₂ pneumoperitoneum as a mechanism for PSM could not be confirmed.     

One Health surveillance of West Nile and Usutu viruses: a repeated cross-sectional study exploring seroprevalence and endemicity in Southern France, 2016 to 2020

BackgroundWest Nile virus (WNV) and Usutu virus (USUV), two closely related flaviviruses, mainly follow an enzootic cycle involving mosquitoes and birds, but also infect humans and other mammals. Since 2010, their epidemiological situation may have shifted from irregular epidemics to endemicity in several European regions; this requires confirmation, as it could have implications for risk assessment and surveillance strategies.AimTo explore the seroprevalence in animals and humans and potential endemicity of WNV and USUV in Southern France, given a long history of WNV outbreaks and the only severe human USUV case in France in this region.MethodsWe evaluated the prevalence of WNV and USUV in a repeated cross-sectional study by serological and molecular analyses of human, dog, horse, bird and mosquito samples in the Camargue area, including the city of Montpellier, between 2016 and 2020.ResultsWe observed the active transmission of both viruses and higher USUV prevalence in humans, dogs, birds and mosquitoes, while WNV prevalence was higher in horses. In 500 human samples, 15 were positive for USUV and 6 for WNV. Genetic data showed that the same lineages, WNV lineage 1a and USUV lineage Africa 3, were found in mosquitoes in 2015, 2018 and 2020.ConclusionThese findings support existing literature suggesting endemisation in the study region and contribute to a better understanding of USUV and WNV circulation in Southern France. Our study underlines the importance of a One Health approach for the surveillance of these viruses.