Quantification of dispersion of Gd-DTPA from the initial area of enhancement into the peritumoral zone of edema in brain tumors

To evaluate Gd-DTPA contrast enhancement of brain tumors over time and to describe the dispersion of contrast into the zone of peritumoral edema. We performed MR imaging with a dose of 0.4 mmol Gd-DTPA/kg on eleven patients diagnosed with 5 different supratentorial tumors. MR imaging was done at five intervals between 5 min and 6 h. The change in zone of enhancement was measured for each time point, and a linear measurement was made of the furthest dispersion of contrast from the original volume of enhancement. An increase in the zone of enhancement over time was seen for all tumors; the average increase in volume of contrast was 14.76 ± 3.35 cm³ (mean ± standard deviation). The largest changes in the zone of contrast enhancement, 18.6 ± 4.63 cm³, were seen in glioblastoma multiforme. The expansion of contrast enhancement assumed the morphology of the surrounding edema. The dispersion of Gd-DTPA over time into the zone of peritumoral edema is a potential source of error in clinical settings when there is a delay between Gd-DTPA injection and scanning.     

Genetic contributions of the serotonin transporter to social learning of fear and economic decision making

Serotonin (5-HT) modulates emotional and cognitive functions such as fear conditioning (FC) and decision making. This study investigated the effects of a functional polymorphism in the regulatory region (5-HTTLPR) of the human 5-HT transporter (5-HTT) gene on observational FC, risk taking and susceptibility to framing in decision making under uncertainty, as well as multidimensional anxiety and autonomic control of the heart in healthy volunteers. The present results indicate that in comparison to the homozygotes for the long (l) version of 5-HTTLPR, the carriers of the short (s) version display enhanced observational FC, reduced financial risk taking and increased susceptibility to framing in economic decision making. We also found that s-carriers have increased trait anxiety due to threat in social evaluation, and ambiguous threat perception. In addition, s-carriers also show reduced autonomic control over the heart, and a pattern of reduced vagal tone and increased sympathetic activity in comparison to l-homozygotes. This is the first genetic study that identifies the association of a functional polymorphism in a key neurotransmitter-related gene with complex social–emotional and cognitive processes. The present set of results suggests an endophenotype of anxiety disorders, characterized by enhanced social learning of fear, impaired decision making and dysfunctional autonomic activity.     

Bicyclic nucleoside inhibitors of varicella-zoster virus (VZV): Pd-catalysed synthesis of 5-aryl derivatives and their biological evaluation

We have recently reported the discovery of an entirely new category of potent antiviral agents based on novel deoxynucleoside analogues with unusual fluorescent bicyclic furano base moieties. In order to probe structure activity relationships we prepared a series of 5-aryl derivatives of the lead structures. We herein report the synthesis, characterization, and antiviral evaluation of these novel compounds. 5-Aryl derivatives of the parent nucleosides were synthesized from the corresponding alkynyl deoxyuridines using a simple, versatile and efficient one-step conversion, based on a palladium-catalysed cyclization. As previously noted for the lead compounds, a long alkyl side-chain on the base moiety is essential for antiviral activity. Even with the optimal (C8-C10) side-chain, most of the present compounds are markedly less active than their parent structures. However, some of the synthesized compounds still retained antiviral activity at non-cytotoxic concentrations, being only two- to fivefold less active than the current clinical agent acyclovir. Possible reasons for this structure activity relationship are discussed.     

Successful management of a consecutive cervical pregnancy by sonographically guided transvaginal local injection: case report and review of the literature.

OBJECTIVE: The purpose of this study was to describe the successful management of a recurrent cervical pregnancy with local injection and to review similarly treated cases to determine adverse outcomes. METHODS: A case of a recurrent cervical pregnancy treated with transvaginal local injection was reported. A MEDLINE English language search identified 90 cases of cervical pregnancy treated with local therapy. This literature was analyzed with regard to the various demographic and outcome variables described. RESULTS: Successful use of the transvaginal local approach is described. A review of cases identified a mean maternal age of 33.6 years with a mean gestational age at diagnosis of 7.5 weeks. Bleeding was the most common presenting sign (79%). The mean beta-human chorionic gonadotropin level at the time of diagnosis was 27,798 IU with an average time to resolution of 7.5 weeks. The most common risk factor was a history of curettage (69%), followed by previous cesarean delivery (35%). An additional dose of methotrexate was needed in 6% of cases. Bleeding requiring alternate procedures was present in 5% of cases. There were no complications in 81% of cases. The need for transfusion and development of infection were seen in 3% of cases each. There was 1 case (1.1%) requiring hysterectomy, and no maternal deaths were reported. CONCLUSIONS: Conservative management of cervical pregnancy using local injection has been reported to have a low complication rate and a high efficacy for cure.     

Evidence for cortical hyperexcitability of the affected limb representation area in CRPS: a psychophysical and transcranial magnetic stimulation study

Functional alterations in noxious, sensory and motor circuits within the central nervous system may play an important role in the pathophysiology of complex regional pain syndrome (CRPS). The aim of the present study was to search for further evidence of hyperexcitability in the hemisphere contralateral to the affected limb in patients with CRPS by employing both psychophysical and transcranial magnetic stimulation (TMS) methods. Twelve patients with CRPS type I, confined to the distal part of a limb (six in an upper-limb and six in a lower-limb), were enrolled in the study. The quantitative thermal, mechanical and 'wind-up' like pain testing was performed at the most painful site in the affected limb and in the ipsilateral limb. Results were then compared to those found at mirror sites in the contralateral limbs. TMS was used to assess the inter-hemispheric difference in parameters of corticospinal excitability, intracortical inhibition, and intracortical facilitation. The quantitative thermal and mechanical testing showed significant differences in cold, heat and mechanical pain thresholds, as well as in the first and last 'wind-up' stimuli between the affected and the contralateral limbs of the CRPS patients. No significant differences between the ipsilateral unaffected limbs and their contralateral pair limbs were found. A significant reduction in the short intracortical inhibition associated with a significant increase of the I-wave facilitation was found in the hemisphere contralateral to the affected side in the upper-limb CRPS group. No significant inter-hemispheric asymmetry between the affected and the non-affected sides was revealed in the lower-limb CRPS group. Taken together, these results suggest that in patients with well-localized CRPS, there is evidence for sensory and motor CNS hyperexcitability, though it seems to involve only corresponding regions within the CNS rather than the entire hemisphere.