The Neurosteroid Allopregnanolone Is Reduced in Prefrontal Cortex in Alzheimer’s Disease

BACKGROUND: Few data are currently available investigating neurosteroids (NS) in Alzheimer's disease (AD). The NS allopregnanolone may be decreased in serum and plasma in patients with AD, but it is unclear if allopregnanolone is also reduced in brain. Because a number of NS exhibit neuroprotective effects and impact cognitive performance in rodent models, these molecules may be relevant to the pathophysiology of neurodegenerative disorders. We therefore investigated prefrontal cortex (PFC) NS levels in AD. METHODS: Neurosteroid levels (allopregnanolone, pregnenolone, dehydroepiandrosterone [DHEA]) were determined in postmortem PFC in 14 male subjects with AD and 15 cognitively intact male control subjects by gas chromatography/mass spectrometry preceded by high-performance liquid chromatography purification. RESULTS: Subjects with AD exhibit significant reductions in allopregnanolone compared with cognitively intact control subjects (median levels = 2.50 ng/g vs. 5.59 ng/g, respectively; p = .02). Allopregnanolone levels are inversely correlated with neuropathological disease stage (Braak), r = -.49, p = .007. Median DHEA levels are elevated in subjects with AD (p = .01). CONCLUSIONS: Subjects with AD demonstrate significant reductions in PFC allopregnanolone levels, a finding that may be relevant to neuropathological disease stage severity. Neurosteroids may have utility as candidate biomarkers in AD.     

Stability of transverse expansion in the mandibular arch.

This was a retrospective, longitudinal cephalometric and cast study of 29 white patients at pretreatment, posttreatment, and an average of 6 years 3 months postretention. The goal was to assess changes with treatment and retention with the expanding mandibular lingual arch appliance in conjunction with fixed edgewise treatment. Seven mandibular cast measurements were assessed, including arch crowding, arch perimeter, arch length, and arch width at the permanent canines, first premolars, second premolars, and first molars. Cephalometric radiographs were digitized, and 16 cephalometric measurements were made. Repeated-measures analysis of variance and 2-sample t tests were used to determine statistically significant changes. It was found that the expanding lingual arch used for less than 6 months with the mandibular fixed edgewise appliance caused an increase in both the transverse and sagittal dimensions of the mandibular dental arch. Transverse expansion was more stable in the posterior region of the mandibular dental arch than in the anterior region. Mandibular intercanine width increase could be maintained only by fixed retention. Although the maxillary and mandibular incisors were advanced and proclined, lip protrusion did not occur.     

Introducing dental students to clinical patient care: The complete denture prosthodontics transition clinic

Using complete denture treatment as an introduction to clinical patient care for dental students, the purposes of the Complete Denture Prosthodontics Transition Clinic at the University of Colorado School of Dentistry are to reduce the time lapse between the preclinical complete denture prosthodontics course and the first denture patient experience, and to encourage development of student self-confidence and skills. In the 2002 spring semester, faculty at the University of Colorado School of Dentistry initiated the Complete Denture Prosthodontics Transition Clinic for DS-II (second-year) dental students, as an introduction to clinical patient care. Each patient was assigned to a team of two dental students. Three Division of Prosthodontics faculty members staffed each clinic session, providing a student-to-faculty ratio of approximately 6.6:1 and a patient-to-faculty ratio of approximately 3.3:1. All DS-II students in the Class of 2004 delivered their first complete dentures no later than 8 months (average, 184 days) after the last day of the preclinical complete denture prosthodontics course. The time from the diagnostic appointment through the denture placement appointment averaged 39 days for patients treated in this program, compared with an average of 98 days or more for previous classes. The program was successful in achieving the goal of reducing the time lapse between the preclinical complete denture prosthodontics course and the first denture patient experience.     

Sexual function in patients presenting to a urogynecology practice

The purpose of this study was to evaluate sexual function in women referred to a urogynecology practice. All new patients were mailed an optional female sexual function index (FSFI) in conjunction with their history forms; other sexual function information was obtained during the physician interview. Over 6 months, four hundred fifty new patients were enrolled. Of these, 243 (54%) were not sexually active. Reasons listed for sexual inactivity included partner problems/no partner (32%), low desire (14%), prolapse (10%), and pain (10%). There were several differences between sexually active and non-sexually active participants; however, after a multivariate analysis, only age, marital status, and stage/grade 1–2 of prolapse remained significant. One hundred nine sexually active patients completed the FSFI; the majority was sexually active two to four times per month. Female sexual dysfunction was noted in 70 (64%) patients. Lowest scores were noted for the domain of desire, followed by arousal, orgasm, lubrication, satisfaction, and pain. Reduced frequency of intercourse was the only factor significantly associated with dysfunction. Ninety-four percent were not embarrassed by the survey. Overall, sexual inactivity is common in patients presenting for urogynecologic care. Those that are sexually active report low rates of sexual activity and high rates of sexual dysfunction. Most sexually active patients will accept a sexual function questionnaire as part of their routine assessment.This research was presented at the American College of Obstetricians and Gynecologists annual clinical meeting, May 10, 2005, San Francisco, CA, USA.     

Sonographic features of benign thyroid nodules: interobserver reliability and overlap with malignancy.

OBJECTIVE: To prospectively determine the sonographic findings of nodular hyperplasia of the thyroid, to compare these with reported findings associated with malignancy, and to assess interobserver reliability. METHODS: Seventy thyroid nodules were scanned, and then biopsies of the nodules were performed under sonographic guidance with fine-needle cytologic analysis; in all cases images were reviewed by 2 experienced radiologists without knowledge of clinical outcome. Findings reported associated with malignancy were specifically assessed. Interobserver agreement between the expert and secondary readers for each finding was calculated by the kappa or weighted kappa statistic and the Fisher exact test of independence. RESULTS: There were 68 benign and 2 malignant nodules in a population of 63 female and 7 male patients. The mean benign nodule size was 2.9 cm; 60% were solid; 54% were hypoechoic; 59% were microlobulated or macrolobulated; 47% had central vascularity; 24% contained calcifications; and 82% were elliptical in shape. There was very good interobserver reliability for the presence of calcium (kappa = 0.91) and good agreement for the presence and location of vascularity (kappa = 0.75) and the amount of cystic components (kappa = 0.62; all P < .01). CONCLUSIONS: Sixty-nine percent of benign nodules had at least 1 finding reported previously as associated with malignancy. The interobserver reliability of the sonographic findings was good to very good for 3 of the 5 findings assessed.     

Models,strategies, and tools

This paper presents a case for careful consideration of theory in planning to implement evidence-based practices into clinical care. As described, theory should be tightly linked to strategic planning through careful choice or creation of an implementation framework. Strategies should be linked to specific interventions and/or intervention components to be implemented, and the choice of tools should match the interventions and overall strategy, linking back to the original theory and framework. The thesis advanced is that in most studies where there is an attempt to implement planned change in clinical processes, theory is used loosely. An example of linking theory to intervention design is presented from a Mental Health Quality Enhancement Research Initiative effort to increase appropriate use of antipsychotic medication among patients with schizophrenia in the Veterans Health Administration.     

Mild traumatic brain injury in an insured population: subjective complaints and return to employment

The great majority of traumatic brain injury (TBI) is of mild severity, with Glasgow Coma Scores (GCS) of 13-15, post-traumatic amnesia of less than 48 hours and brief, if any, hospitalization. All mild TBI admissions to hospital were provided with education in the form of a brief interview and a brochure on minor head trauma from the National Head Injury Foundation. Seventy-seven insured individuals with mild TBI were contacted by phone between 1 and 3 months post-injury to determine the frequency and severity of post-traumatic symptoms and the rate of return to work (RTW). Twenty-six per cent of those contacted had subjective complaints; 88% had returned to work or school; 16% of those returning did so with some symptoms. Only 45% of symptomatic individuals sought medical consultation for their condition when offered. Education about post-traumatic symptoms from the onset may provide sufficient reassurance to most individuals that future use of medical services is seen as unnecessary. Rate of RTW is relatively higher than reported in previous studies of mild TBI.     

Effects of acute administration of d-amphetamine and haloperidol on procedural learning in man

The effects of an indirect dopamine-agonist, d-amphetamine, and a non-selective dopamine receptor antagonist, haloperidol, were investigated in normal male volunteers using a between-subjects double-blind design in a procedural learning task, thought mainly to involve unconscious/automatic learning. The results showed: (1) d-amphetamine facilitated response speed, whereas haloperidol inhibited it, in comparison to placebo; (2) the linear increase in procedural learning corresponded with pharmacological manipulation of degree of dopaminergic activity, i.e. subjects given haloperidol showed the least, and subjects given d-amphetamine the greatest, procedural learning. The implications of these findings are discussed in relation to investigation of abnormalities of procedural learning processes in schizophrenia. Received: 28 June 1996/Final version: 2 October 1996