Trifluoromethanesulfonic acid,an alternative solvent medium for the direct electrophilic fluorination of DOPA: new syntheses of 6‐[18F]fluoro‐L‐DOPA and 6‐[18F]fluoro‐D‐DOPA

Previous work from this laboratory has shown that the direct fluorination of 3, 4‐dihydroxy‐phenyl‐L ‐alanine (L ‐DOPA) in anhydrous HF (aHF) or BF₃/HF with F₂ is an efficient method for the synthesis of 6‐fluoro‐L ‐DOPA. Since then, ¹⁸F‐labeled 6‐fluoro‐L ‐DOPA ([¹⁸F]6‐fluoro‐L ‐DOPA) has been used to study presynaptic dopaminergic function in the human brain and to monitor gastrointestinal carcinoid tumors. This work demonstrates that the reactivity and selectivity of F₂ toward L ‐DOPA in CF₃SO₃H is comparable with that in aHF. This new synthetic procedure has led to the production of [¹⁸F]fluoro‐L ‐DOPA and [¹⁸F]fluoro‐D‐DOPA isomers in 17±2% radiochemical yields (decay corrected with respect to [¹⁸F]F₂). The 2‐ and 6‐FDOPA isomers were separated by HPLC and subsequently characterized by ¹⁹F NMR spectroscopy. The corresponding [¹⁸F]‐FDOPA enantiomers have been obtained in clinically useful quantities by a synthetic approach that avoids the use of aHF. Copyright © 2007 John Wiley & Sons, Ltd.     

Intracisternal sodium nitroprusside fails to prevent vasospasm in nonhuman primates

OBJECTIVE: Hemoglobin contributes to vasospasm after subarachnoid hemorrhage. One mechanism may involve binding of nitric oxide, destruction of nitric oxide, or both. Support for this mechanism would be evidence that nitric oxide donors prevent vasospasm. This study attempted to provide such evidence. METHODS: A randomized, blinded study was conducted in which 13 monkeys underwent cerebral angiography and creation of a right subarachnoid hemorrhage. Subcutaneous osmotic pumps were implanted to deliver sodium nitroprusside (n = 7) or vehicle (n = 6) via catheters into the right basal cisterns. Seven days later, angiography was repeated, and the animals were humanely killed. Levels of cyclic nucleotides, hemoglobins, and thiocyanate were measured. RESULTS: Significant vasospasm of the right middle cerebral artery was present in animals treated with sodium nitroprusside (35 +/- 22% reduction in diameter, P < 0.05, paired t test) and placebo (28 +/- 20% reduction, P < 0.05, not significantly different from nitroprusside group by unpaired t test). Adequate delivery of sodium nitroprusside was supported by the finding of a significant increase in cyclic guanosine monophosphate levels in the cerebral arteries of treated animals compared with placebo (P < 0.05, unpaired t test). Thiocyanate was not present in significantly increased amounts in animals treated with nitroprusside, although this group did display elevated concentrations of nitrosyl hemoglobin (measured by electron paramagnetic resonance spectroscopy) and cyanomethemoglobin (measured by spectrophotometry) in the cerebrospinal fluid on Day 7. CONCLUSION: The lack of effect of sodium nitroprusside was not the result of inadequate drug delivery because cyclic guanosine monophosphate levels were significantly increased in vasospastic arteries. Vasospasm may not have been prevented because of a toxic effect of sodium nitroprusside metabolites, involvement of smooth muscle relaxation or contraction processes downstream of cyclic guanosine monophosphate, or both.     

Targeted mass treatment for syphilis with oral azithromycin

From mid 1997 to end of 1999, there was a sexually-transmitted infectious syphilis outbreak mainly in heterosexual people in British Columbia, Canada, that was concentrated in Vancouver. The rate across the province increased from less than 0.5 to 3.4 per 100000, and the rate in Vancouver reached 12.9 per 100000. We aimed to eliminate the syphillis outbreak by treating people at risk of infection. In 2000, a targeted mass treatment programme provided azithromycin (1.8 g orally) to 4384 at-risk residents in this city. After the programme, syphilis frequency fell significantly for 6 months (p=0.016), but rose again in 2001. Results from curve fitting analyses showed that the number of cases in 2001 (177) was higher than expected (0.0001相似文献   

Preliminary experiences with sentinel lymph node detection in cases of vulvar malignancy

Lymph node status is the most important prognostic factor in vulvar malignancy. The aim of this pilot study was to explore the clinical significance of radionuclide lymphoscintigraphy in the management of vulvar neoplasms. Eight patients with squamous cell carcinoma and two patients with malignant melanoma of the vulva were studied with 100 MBq technetium-99m nanocolloid (Sentiscint, OSSKI, Budapest) 1 day before surgery. The location of the sentinel lymph node was checked by a single-head gamma camera-computer system (MB 9200, Mediso, Budapest). Vulvectomy with bilateral inguinofemoral lymphadenectomy was performed in each case. At lymphadenectomy, the sentinel lymph node was separately removed and histologically studied. Three of the ten patients had positive sentinel lymph nodes (micrometastasis). Five months later one of them had local recurrence of the vulvar cancer, and another had inguinal recurrence of the tumour 6 months postoperatively; the third patient was operated on only recently. Our preliminary results are impressive and suggest that lymphoscintigraphy is an easy and reliable method for detection of the sentinel lymph node in vulvar malignancy.     

Comparative evaluation of two fixed doses of 185 and 370 MBq 131I, for the treatment of Graves' disease resistant to antithyroid drugs

Radioiodine (131I) treatment is often applied for the treatment of Graves' disease (GD). The optimal dose of 131I for Graves' hyperthyroidism is debated. Various techniques suggest either fixed doses or varying doses based on elaborate calculations of the gland size, 131I uptake, and 131I turnover. Fixed dose regimens avoid dose calculations but there is no consensus on the actual dose to be administered. We compared two routinely recommended fixed 131I doses of 185 and 370 MBq for this purpose. Fifty nine patients with GD who had not been previously treated with 131I were randomized in two groups. Group A consisted of 33 patients who were treated with 185 MBq of 131I. Group B consisted of 26 patients who were treated with 370 MBq of 131I. Group A patients were 21% male and 78% female, mean age 38.1+/-14.4, range 15 to 77 y. Group B patients were 27% male and 73% female, mean age 40.7+/-11.7, range 27 to 72 y. All patients were reexamined every six months for two years. The following clinical outcomes were noticed: a) Persistent hyperthyroidism, which was considered as failure to treatment, requiring further 131I treatment. b) Hypothyroidism; requiring life-long replacement treatment. c) Euthyroid state. Euthyroid and hypothyroid states were considered as a response to treatment of hyperthyroidism. In Group A, 10 patients (30.3%) became euthyroid and 6 (18.2%) hypothyroid (an overall response of 48.5%), while 17 (51.5%) remained hyperthyroid by the end of the follow-up period. In Group B, 10 patients (38%) became euthyroid and 13 (50%) hypothyroid, an overall response of 88.5%. Non responders were 3 patients (11.5%). No correlation was noted between the outcome of treatment and age, sex, size of the thyroid gland or thyroid uptake in each Group of patients, while a significant correlation was noted between the disease outcome and the amount of administered 131I (P<0.003). The incidence of hypothyroidism by the end of two years of follow up was less in Group A than in Group B and the incidence of non responders to treatment was lower in Group A. In view of the higher cost of treatment, the longer time elapsing to treatment, the number of office visits by the patients and the higher number of patients with persistent hyperthyroidism in Group A, we conclude that a fixed dose of 131I of 370 MBq is more useful and effective for the treatment of GD as compared to 185 MBq of 131I.     

The neural correlate of very-long-term picture priming

Repetition priming denotes a behavioural change caused by prior exposure to a stimulus. The effect is known to last for weeks. This study addresses the underlying neural mechanisms for very-long-term picture priming by using event-related functional magnetic resonance imaging complemented by a behavioural paradigm. Previous functional imaging studies with shorter retention intervals have shown that priming is associated with changes in the activity of both the occipital and posterior temporal cortex. In this study we compared retention intervals of 1 day and 6 weeks after initial exposure to a picture stimulus. Priming-related decreases in cortical activity in posterior extrastriate and dorsal left inferior frontal areas were found only for the shorter retention interval. In contrast, fMRI activation in the inferior posterior temporal and anterior left inferior frontal cortex was reduced following priming for both retention intervals. In the behavioural paradigm, the priming effect was stable over time. We conclude that the left inferior frontal and inferior posterior temporal cortex play a key role in the very-long-term priming effect.     

Brain morphometry using diffusion-weighted magnetic resonance imaging: application to schizophrenia

Loss of cortical gray matter is accompanied by a commensurate increase in the sulcal and intraventricular cerebrospinal fluid volume. On diffusion-weighted magnetic resonance imaging, this would be reflected as a higher apparent diffusion coefficient in affected brain regions. On the basis of the above premise, we suggest that the apparent diffusion coefficient may be used as a surrogate marker for the assessment of regional brain volume deficits. We demonstrate this approach by voxelwise analysis of registered apparent diffusion coefficient images from a group of 15 patients with schizophrenia and 15 age-matched healthy controls. We found widespread regional apparent diffusion coefficient increases in patients. Affected areas included the bilateral insular cortex, hippocampus, temporal lobe, and occipital areas. These results largely concur with previous findings of cortical volume deficits in schizophrenia.