Serum concentrations of 17beta-estradiol and estrone after multiple-dose administration of percutaneous estradiol gel in symptomatic menopausal women.

In two multicenter phase III efficacy studies, blood samples were obtained to evaluate the serum concentrations of 17beta-estradiol (E2) and unconjugated estrone (E1) after administration of a percutaneous gel or transdermal patch containing estradiol. In postmenopausal women, normal laboratory E2 and E1 serum concentrations range from 10-30 pg/mL and 20-40 pg/mL, respectively. Study subjects were healthy postmenopausal women with moderate to severe hot flushes occurring at least seven times daily or 60 times per week. Study 1 was a randomized, double-blind, multicenter study of percutaneous E2 gel 1.25 or 2.5 g (0.75 and 1.5 mg E2, respectively) versus placebo gel. Study 2 was a double-blind (blinded to E2 gel dose), randomized, active-controlled, multicenter, 12-week phase 3 study of E2 gel 0.625, 1.25, or 2.5 g (0.375, 0.75, or 1.5 mg E2, respectively) versus a transdermal E2 patch delivering 0.05 mg E2 per day. Serum E2 and E1 concentrations were evaluated at baseline and at week 12 for study 1 and at baseline and weeks 4, 8, and 12 for study 2 using radioimmunoassay. Median serum concentrations of E2 after 1.25- and 2.5-g gel administration appeared to be dose-proportional throughout both studies. In study 1, the median serum concentrations of E2 at week 12 were 33.5 and 65.0 pg/mL for 1.25- and 2.5-g gel dose, respectively. The corresponding E1 values were 49.0 and 58.0 pg/mL. In study 2, both E2 and E1 concentrations were relatively stable at weeks 4, 8, and 12. E2 values at week 12 for 0.625-, 1.25-, and 2.5-g gel doses and E2 patch were 25.0, 32.0, 60.0, and 38.5 pg/mL, respectively. The corresponding E1 values were 39.0, 41.0, 62.5, and 40.0 pg/mL. Application of the 1.25-g gel dose and a transdermal patch delivering 50 microg per day of E2 resulted in comparable median E2 and E1 concentrations. However, the 0.625-g gel dose did not produce E2 levels in a range expected to be consistently therapeutic in most postmenopausal women.

Language before and after temporal lobectomy: specificity of acute changes and relation to early risk factors.

We evaluated language functions in 154 patients with left hemisphere speech dominance undergoing anterior temporal lobectomy (ATL). Measures of phonemic and semantic fluency, confrontation naming, repetition, comprehension, and reading were administered before and 3 weeks postoperatively. Patients were grouped by focus (left, LT; right, RT) and presence of early risk factors for development of seizures (ER, early risk, < or = 5 years; NER, no early risk): (LT-ER, n = 45; RT-ER, n = 49; LT-NER, n = 27; RT-NER, n = 33). Preoperatively, the LT group showed a selective naming deficit as compared with the RT group. Postoperatively only the LT-NER group showed significant overall decline in language. For this group, the change was attributable to a selective decline in naming as compared with other functions. These data indicate that there is a specific risk to naming after dominant ATL for adult temporal lobe epilepsy (TLE) patients with a left hemisphere focus and the absence of an early risk factor for the development of seizures.

Neuropsychological deficits in neuroleptic naive patients with first-episode schizophrenia.

BACKGROUND: Medication and chronicity have complicated past attempts to characterize the neuropsychological performance of patients with schizophrenia. There have been inconsistencies regarding the pattern, selectivity, and sources of observed deficits. Our objective was to comprehensively examine neuropsychological function in patients with schizophrenia who had never been exposed to neuroleptic medication, and who were experiencing their first episode (FE) of psychosis. METHODS: Subjects were consecutive recruitments that included 37 patients with FE schizophrenia who were never exposed to neuroleptics. These subjects were compared with 65 unmedicated, previously treated (PT) patients and 131 healthy controls. RESULTS: The patients groups had nearly identical profiles showing generalized impairment, particularly in verbal memory and learning, attention-vigilance, and speeded visual-motor processing and attention. Verbal memory and learning accounted for most of the variance between patients and controls and removing this effect substantially attenuated all other differences. By contrast, both the FE group and PT group continued to show highly significant deficits in verbal memory and learning after controlling for attention, abstraction, and all other functions. Some functions not typically implicated in schizophrenia (spatial cognition, fine motor speed, and visual memory) were more impaired in the PT group than in the FE group. CONCLUSIONS: Verbal memory, as a primary neuropsychological deficit present early in the course of schizophrenia, implicates the left temporal-hippocampal system. Neuropsychological evaluations before treatment permit differentiation of primary deficits from changes secondary to medication or chronicity. This is essential for developing a neurobehavioral perspective on schizophrenia.

Neuropsychological function in schizophrenia. Selective impairment in memory and learning.

Unmedicated schizophrenic patients (according to DSM-III-R criteria) (n = 36) and age-matched normal controls (n = 36), balanced for parental socioeconomic status, were administered a battery of standardized neuropsychological tests. Patients showed generalized impairment relative to controls and a selective deficit in memory and learning compared with other functions. Selective impairment was not found on tests related to frontal system function (abstraction, verbal fluency, and motor). The observed pattern is consistent with greater involvement of the temporal-hippocampal system, against the background of diffuse dysfunction. Although impairment in memory and learning has been reported, the selectivity and relative severity compared with other behavioral functions have not been recognized. The specificity of this profile merits further examination. These findings lend support to the hypothesized importance of the temporal-hippocampal region in understanding the pathophysiology of schizophrenia.

Acute naming deficits following dominant temporal lobectomy: prediction by age at 1st risk for seizures.

Age at 1st risk for seizures may predict anomia following dominant anterior temporal lobectomy. We assessed confrontation naming before and 2 to 3 weeks after surgery in 45 right-handed patients grouped by side of focus and presence or absence of early (less than or equal to 5 years) risk factors. After left lobectomy, 6 of 10 (60%) patients with no early risks demonstrated significant decline (greater than or equal to 25%) in naming, but none of the patients with early risks showed this decline. After right lobectomy, there was no change. Cerebral representation of naming may be atypical in patients with early risks.