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To test the hypothesis that neuropsychiatric symptomatology is predictive of the success of seizure control in patients newly treated with antiepileptic drugs (AEDs), and that this predictive value adds to that provided by other clinical, imaging, and genomic factors in a multivariate model.

PurposeTo report 3 cases with focal lesional epilepsy that had non-convulsive status epilepticus (NCSE) induced by treatment with tiagabine (TGB) and review the previously published cases. Drugs that enhance GABAnergic transmission are recognised to promote absence seizures in patients with generalised epilepsy syndromes and may on occasions even induce NCSE. However, that TGB can also induce NCSE in focal lesional epilepsy is not widely recognised in clinical practice.MethodThe clinical history, EEG and MRI findings were reviewed in 3 patients with lesional focal epilepsy who presented to our epilepsy programs over a 12 month period with TGB-induced NCSE. All previously reported cases in the English medical literature were reviewed.ResultsThe three patients had longstanding complex partial and secondarily generalised seizures refractory to multiple different anti-epileptic drugs. In two cases, MRI demonstrated a focal malformation of cortical development in the left parieto-occipital region and in the third left mesial temporal sclerosis. Following commencement of TGB in one patient and dose escalation in two, prolonged episodes of confusion and poor responsiveness were noted. Prolonged EEG monitoring demonstrated continuous high amplitude, generalised, 2-4 Hz delta activity with intermingled spikes during the episodes of unresponsiveness, consistent with NCSE. The clinical and EEG activity normalised following the administration of IV clonazepam followed by dose reduction or withdrawal of the TGB. Eleven previously reported cases of patients with partial epilepsy and a focal underlying lesion on MRI were identified, all of whom had similar features to that seen in our cases.ConclusionsThese cases illustrate that TGB may induce generalised NCSE in patients with focal lesional epilepsy, in addition to those with generalised syndromes. We hypothesise that patients may have developed an acquired alteration in the sensitivity of their thalamocortical circuitry that renders them more sensitive to the effects of drugs that enhance GABAnergic activity.

The Defense Industrial Security Program is not the only industrial security responsibility of the Defense Investigative Service. The Defense Industrial Facilities Protection Program (DIFPP) develops and promotes industrial protection within the United States. The AA and E protects sensitive conventional arms, ammunition and explosives held by defense contractors. Changes in government policy will affect the administration of these two Defense Investigative Service programs. Industrial security representatives will now receive specialized training to ensure efficiency in emergency preparedness.

In 1997 CA 125 celebrated its 15th anniversary. Since the discovery of OC 125, an antibody that recognizes CA 125, by Bob Bast and his colleagues, considerable progress has been made toward the development of more sensitive and more precise assay systems. However, a great deal of mystery still remains about the CA 125 molecule and further enlightenment will probably not come until the gene for CA 125 is cloned and the complete open reading frame for the peptide core identified. In the meantime, we have learned some structural features of the CA 125 molecule as well as a little about its regulation and the requirements for its secretion or release from epithelial derived cells in cultures. The CA 125 molecule is almost certainly a glycoprotein with a predominance of O-linkages. It is heterogeneous with regard to both size and charge, most likely due to continuous deglycosylation of side chains during its life-span in bodily fluids. It exists as a very large complex (perhaps as much as 4 million daltons) under natural conditions. The core CA 125 subunit is in excess of 200,000 daltons and it retains the capacity to bind both OC 125 class antibodies and M 11 class antibodies. As a denatured purified subspecies the CA 125 molecule appears to autoproteolyse presumably due to an endogenous protease activity inherent to the molecule. Release or secretion of CA 125 appears directly linked to the epithelial growth factor receptor signal transduction pathway. Prior to its release from cultured cells, CA 125 is phosphorylated (at either/both serine and threonine) and dephosphorylated when released. To stimulate discussion on the regulation of CA 125 synthesis, its secretion and its structural configuration, we have presented a model of a theoretical CA 125 molecule. Perhaps it will provide a focus of attention until the CA 125 gene is cloned and the real molecule is described.

Objectives Most studies that clinically validated peri-ictal SPECT in intractable partial epilepsy had used technetium-99m-hexamethylpropylene amine oxime ( ^99mTc-HMPAO or ^99mTc-exametazime) as the radiopharmaceutical. Because of some theoretical advantages, technetium-99m-ethyl cysteinate diethylester ( ^99mTc-ECD or ^99mTc-bicisate) is increasingly being used instead. This study compares unstabilised ^99mTc-HMPAO and ^99mTc-ECD in the performance of peri-ictal SPECT in partial epilepsy. Methods The injection timing and localisation rates in 49 consecutive patients with partial epilepsy who had peri-ictal injections with unstabilised ^99mTc-HMPAO were compared with 49 consecutive patients who had peri-ictal injections with ^99mTc-ECD. Quantitative cortical/subcortical and cortical/extracerebral uptake ratios were also compared. Subtraction SPECT coregistered to MRI (SISCOM) was performed in patients whose interictal SPECTS were available. Results In the ^99mTc-ECD patients, the latency from seizure commencement to injection was shorter (median 34 v 80 seconds, p<0.0001) and there was a lower rate of postictal injections (16.3% v 57.1%, p<0.0001). The cortical/extracerebral and cortical/subcortical uptake ratios were greater in the ^99mTc-ECD images (median 5.0 v 3.6, and 2.5 v 2.2 respectively; both p<0.005), but the relative peri-ictal increase in uptake in the cortical focus did not differ significantly (median 37.0% v 37.0%; p>0.05). Blinded review of the SISCOM images were localising in a higher proportion of the ^99mTc-ECD patients (40/45 (88.9%) v 25/37 (67.6%), p<0.05), and had a better concordance with EEG, MRI, and with the discharge diagnosis. Conclusion ^99mTc-ECD compares favourably with unstabilised ^99mTc-HMPAO as a radiopharmaceutical for peri-ictal SPECT studies. Its use results in earlier injections and less frequent postictal injections than unstabilised ^99mTc-HMPAO, thereby enhancing the sensitivity and the specificity of peri-ictal SPECT for the localisation of intractable partial epilepsy.

Protein maps of in vitro hormone-modulated adenocarcinoma cells from an endometrial tumor are described. It is noted that mapping of tumor tissues by means of the two-dimensional analysis described by O'Farrell and associates6of 35S-methionine-labeled proteins can provide a characteristic map for each tumor and that the methionine-containing proteins of tumor cells can be independently modulated by the in vitro additions of estradiol and progesterone. Such protein modulation could be indicative of hormonal therapeutic responsiveness of individual endometrial adenocarcinomas and other hormone receptor-positive tumors. Tumor maps may further provide data for the identification and isolation of new tumor markers which might be correlated with the radiotherapeutic and chemotherapeutic sensitivity of the malignancy.

Therassignaling protein requires a posttranslational modification to localize it to the inner surface of plasma membrane. In this state it can behave as a signal transduction mediator. Farnesyltransferase plays an important role in this posttranslational processing ofrasby attaching a farnesyl group to the cysteine of therasC-terminal tetrapeptide. In this study, we investigated the relationship of K-rasexpression and mutation with farnesyltransferase β-subunit expression in 20 ovarian tumors (17 carcinomas and 3 low malignant potential tumors) and 4 normal ovaries. The expression level of mRNA was determined by using quantitative PCR and mutation analysis was performed by direct cDNA sequencing. K-rasmutations were found in 1 of 3 low malignant potential tumors and in 4 of 17 carcinoma cases. K-rasmRNA overexpression was found in 1 of 3 low malignant potential tumors (one with mutatedras) and in only 1 of 17 carcinoma cases. Farnesyltransferase β-subunit mRNA overexpression was found in 2 of 3 low malignant potential tumors and in 7 of 17 carcinoma cases. Interestingly, all K-rasmutation cases showed farnesyltransferase β-subunit overexpression. These findings suggest that there may be a direct relationship between K-ras(rasdysfunction) mutation and expression of farnesyltransferase β-subunit gene.