Naphthalimido derivatives as antifolate thymidylate synthase inhibitors

A new series of N-(substituted)benzyl-1,8-naphthalimides 4, structurally related to the previously reported thymidylate synthase (TS) inhibitor naphthaleins 3, were synthesized and compounds tested for their inhibition of several species of TS. Moreover, their in vitro cytotoxicity together with antimycotic and antibacterial properties were assayed. While no activity was detected in the antibacterial tests, the m-nitro (4ae) and the p-nitro (4af) derivatives were found able to partially inhibit TS at low micromolar concentrations. Introduction of nitro or (substituted)-amino groups in position 4 of the naphthalic ring always led to less active compounds.     

Critical ovarian hyperstimulation syndrome in a coasted in-vitro fertilization patient

We report an instance of critical ovarian hyperstimulation syndrome in a highly responsive in-vitro fertilization patient despite the preventive measure of a 4 day 'coast' interval during which no gonadotrophins were administered while gonadotrophin-releasing hormone agonist therapy continued until serum oestradiol concentrations fell below 3000 pg/ml.      

Stability of Late Event-Related Potentials: Topographical Descriptors of Motor Control Compared with the P300 Amplitude

The P300-amplitude evoked with an acoustic oddball-paradigm is considered the most stable late event-related potential (ERP). This amplitude-index has become a standard parameter in electrophysiology. Recently, a robust ERP-parameter (NoGo-anteriorization, NGA) has been introduced, which reflects spatial brain electrical changes in relation to execution and inhibition of a motor response elicited with a Continuous Performance Test (CPT). The current study refers to the stability of this new topographical ERP-parameter compared to the stability of the classical P300-amplitude. For that purpose, 12 healthy subjects were investigated with both paradigms during recording of a 21-channel EEG. Analysis of the resulting ERPs revealed a very high stability for both, topographical and amplitude index: In every single subject, the brain electrical fields were characterized by a more anterior location in the NoGo- compared to the Go-condition (=NGA) and by higher amplitudes after target compared to distractor condition. T-tests, analyses of the effect size and of the power revealed equivalent differences between the two contrasting conditions for the topographical compared to the amplitude index. These results indicate that the stability of the topographical ERP-parameters elicited with the CPT is sufficient for an electrophysiological standard-index. The possibility to elicit a robust and specific spatial brain activation with the CPT is an ideal completion to the classical P300 amplitude effect and, therefore, hopefully will be a useful expansion of the standard paradigms in electrophysiological laboratories.     

METHYLATION STATUS OF BCL6 DISTINGUISHES DNA SAMPLES FROM BENIGN AND MALIGNANT LYMPHOPROLIFERATIVE DISORDERS

INTRODUCTION: Core biopsy of the breast has become the method of choice for tissue diagnosis of screen detected microcalcifications and some mass lesions in many breast assessment centres. Biopsy results are not available until the following day. Imprint cytology of fresh breast core samples allows same-day reporting and patient counselling.
AIM: To determine the accuracy of core imprint cytology when compared with core biopsy diagnosis when used in a breast assessment centre setting.
METHODS: Core imprints (CI) were prepared and reported on all fresh core biopsies (CB) performed at the Sir Charles Gairdner Hospital Breast Centre from May to December 2000. Fresh core samples were placed on a glass microscope slide. Core radiographs were taken for microcalcification lesions (MC). A laboratory technician gently and quickly rolled the cores on the slide with fine forceps. The cores were fixed in formalin, processed and reported next day. The imprint slide was air dried and stained with DiffQuik. CI were reported using four categories: Insufficient, Benign, Indeterminate and Malignant. Counselling and planning for management were possible on the same day in women with malignant diagnoses. Clinicians were advised not to discuss negative or indeterminate CI results with women and to defer to the final CB report.
RESULTS: Cores were performed on 381 lesions. There were 83 carcinomas (38 in MC and 45 in masses) and 56 were called malignant on CI (absolute sensitivity 67.5%; 78.9% for MC and 57.8% for masses). 3 malignancies on CB were negative on CI giving a false negative rate of 3.6%. There were no false positive diagnoses. The predictive value of a benign diagnosis was 95.3%. There were no adverse effects in the histology of CB.
CONCLUSION: CI was an accurate method of providing an immediate diagnosis of malignancy in two thirds of malignancies confirmed on CB.