AT base pairs are the main target for mutations at the hprt locus of rat skin fibroblasts exposed in vitro to the monofunctional alkylating agent N-ethyl-N-nitrosourea

Spectra of N-ethyl-N-nitrosourea (ENU)-induced mutations differwidely among various in vitro and in vivo mutational systems.To investigate possible reasons for these differences, a mutationalsystem is needed in which the same target gene is used for comparisonin the same type of cells in vitro and in vivo. In the presentstudy, this was achieved by analysing at the molecular level35 hprt mutant rat fibroblast clones obtained from cell populationsexposed in vitro to ENU and comparing the mutational spectrumwith the previously determined spectrum of ENU-induced hprtmutants in the same target cells exposed in vivo. Twenty-eightmutants contained a single base pair alteration in the hprtcoding sequence. Most of these changes were found at AT basepairs (19/28), the AT to TA transversion being the most frequentkind of mutation (12/19), which is probably caused by O²-ethylthymine.Transversions at AT base pairs showed all mutated T's to belocated in the nontranscribed strand of the hprt gene, suggestinga strand specific fixation of mutations induced by O²-ethylthymine,which appears to be a general feature of ENU- and ENNG-inducedhprt mutations in mammalian cells. GC to AT transitions, probablycaused by O⁶-ethylguanine, were detected at a lower frequency(7/28). This in vitro mutational spectrum was very similar tothat of the same target cells exposed in vivo to ENU. A comparisonof the mutational spectra in AGT-proficient and AGT-deficientrodent cells exposed to ethylating agents showed that in contrastto the situation in AGT-proficient rat fibroblasts, GC to ATbase pair changes (and not AT to TA) are the predominant mutationsin AGT-deficient hamster cells. ⁴To whom correspondence should be addressed     

Role of technetium-99m planar bone scanning in the evaluation of low back pain

The records of 1018 patients with low back pain in a tertiary spine referral practice were reviewed. One hundred thirty-nine out of 1018 (13.6%) underwent technetium-99m planar bone scanning as part of their investigation. Seventy-three out of 139 scans (52%) showed increased uptake in some area, but only 27 out of 139 (19.4%) showed increased uptake specifically in the low back. Scans consistently yielded no findings with reference to the back when the prescan diagnosis was spinal stenosis, lumbar pain syndrome, herniated nucleus pulposus, or postlaminectomy syndrome. Some scans gave positive findings in patients with a diagnosis of degenerative disc disease, pseudarthrosis, spondylolisthesis, fracture, infection, metabolic disorder, or tumor. Positive scans were generally obtained early after presentation (within 3 months) and negative scans obtained later (after 6 months), suggesting that clinical suspicion is still the main indication for early scanning. Planar bone scanning was helpful in both diagnosis and therapeutic decisionmaking in many conditions.     

Migration and chemical modification of silicone in women with breast prostheses

Studies using magnetic resonance spectroscopy in human volunteers to evaluate their livers in vivo and to analyze their blood in vitro suggest that there are measurable amounts of silicon compounds in the blood of some women with implants and that there is migration of silicone to other organs such as the liver.     

Dopamine transporters, D2 receptors, and glucose metabolism in corticobasal degeneration.

Alterations in presynaptic and postsynaptic dopaminergic system and cerebral glucose metabolism in corticobasal degeneration (CBD) were assessed to evaluate the potential usefulness of different imaging methods for CBD. (123)I-FP-CIT/(123)I-beta-CIT SPECT and (123)I-IBZM SPECT as well as (18)F-FDG PET were performed in eight CBD patients. Decreased presynaptic dopamine transporter binding was found in all CBD patients while D2 receptor binding was reduced in only one patient. (18)F-FDG PET displayed a contralateral hypometabolism in cortical and subcortical areas in seven out of eight patients. Our results demonstrate that glucose metabolism and DAT are reduced, while D2 receptors may be frequently preserved in CBD.     

European system for cardiac operative risk evaluation predicts long-term survival in patients with coronary artery bypass grafting.

OBJECTIVE: To evaluate the accuracy of predicting long-term mortality in patients with coronary artery bypass grafting (CABG) by using the European system for cardiac operative risk evaluation (EuroSCORE). METHODS: Medical records of patients with CABG (n=3760) between January 1992 and March 2002 were retrospectively reviewed and their predicted surgical risk was calculated according to the standard (study A) and logistic (study B) EuroSCORE. In study A the patients were divided into six groups: 0-2 (n=610), 3-5 (n=1479), 6-8 (n=1099), 9-11 (n=452), 12-14 (n=103) and >14 (n=17). In study B the patients were divided into seven groups: 0.00-2.00 (n=447), 2.01-5.00 (n=1190), 5.01-10.00 (n=890), 10.01-20.00 (n=686), 20.01-30.00 (n=234), 30.01-60.00 (n=254) and >60.00 (n=59). Long-term survival was obtained by the National Death Index and Kaplan-Meier curves were constructed and compared employing the log-rank test. Multivariate Cox regression analysis was performed in order to control for pre, intra and postoperative factors and adjusted hazard ratios were calculated for standard and logistic EuroSCORE groups. The receiver operating characteristic (ROC) curves were plotted to assess the discrimination ability of the EuroSCORE. RESULTS: In study A there were differences among the six groups in 30-day mortality (0.7%, 1.0%, 3.1%, 4.6%, 13.6% and 23.5%; P<0.001), in major complications (8.5%, 10.4%, 16.2%, 20.4%, 31.1% and 35.3%; P<0.001) as well as in actuarial long-term survival (86.2%, 79.6%, 53.6%, 37.9%, 24.9% and 0% from EuroSCORE 0-2 to >14; P<0.001). In study B there were differences among the seven groups in 30-day mortality (0.9%, 1.1%, 1.2%, 3.6%, 3.4%, 8.7% and 15.3%; P<0.001), major complications (8.5%, 10.1%, 12.1%, 18.4%, 16.2%, 26.0% and 30.5%; P<0.001) as well as in actuarial long-term survival (89.5%, 79.9%, 66.9%, 51.0%, 40.3%, 38.4% and 13.7% from EuroSCORE 0.00-2.00 to >60.00; P<0.001). Multivariate Cox regression analysis confirmed that EuroSCORE (standard or logistic) was a statistically significant predictor for long-term mortality, while the area under the ROC curve was 0.72 for either standard or logistic EuroSCORE. CONCLUSION: The predicted surgical risk in CABG patients as calculated by standard or logistic EuroSCORE is a strong predictor for long-term survival in addition to predicting operative survival for which it was originally designed.     

Use of stereotactic PET images in dosimetry planning of radiosurgery for brain tumors: clinical experience and proposed classification.

We developed a technique that allows the routine integration of PET in stereotactic neurosurgery, including radiosurgery. We report our clinical experience with the combined use of metabolic (i.e., PET) and anatomic (i.e., MRI and CT) images for the radiosurgical treatment of brain tumors. We propose a classification describing the relative role of the information provided by PET in this multimodality image-guided approach. METHODS: Between December 1999 and March 2003, 57 patients had stereotactic PET as part of their image acquisition for the planning of gamma knife radiosurgery. Together with stereotactic MRI and CT, stereotactic PET images were acquired on the same day using either (18)F-FDG or (11)C-methionine. PET images were imported in the planning software for the radiosurgery dosimetry, and the target volume was defined using the combined information of PET and MRI or CT. To analyze the specific contribution of the PET findings, we propose a classification that reflects the strategy used to define the target volume. RESULTS: The patients were offered radiosurgery with PET guidance when their tumor was ill-defined and we anticipated some limitation of target definition on MRI alone. This represents 10% of the radiosurgery procedures performed in our center during the same period of time. There were 40 primary brain lesions, 7 metastases, and 10 pituitary adenomas. Abnormal PET uptake was found in 62 of 72 targets (86%), and this information altered significantly the MRI-defined tumor in 43 targets (69%). CONCLUSION: The integration of PET in radiosurgery provides additional information that opens new perspectives for the optimization of the treatment of brain tumors.