Lack of effect of a single dose of hydrocortisone on serotonin(1A) receptors in recovered depressed patients measured by positron emission tomography with [11C]WAY-100635.

BACKGROUND: Elevated cortisol levels might account for the reduction in central serotonin 1A (5-hydroxytryptamine [5-HT](1A)) receptor binding and function observed in patients with major depression. We tested this hypothesis by studying the effect of acute administration of hydrocortisone on 5-HT(1A) receptor binding potential (BP) in subjects recovered from depression. METHODS: We studied 14 subjects (8 male, 6 female) who had recovered from at least two episodes of major depression and had been euthymic and drug free for at least 6 months. Serotonin 1A receptor BP was measured by [(11)C]WAY-100635 in conjunction with positron emission tomography. Subjects were tested on two occasions in a double-blind, random-order, crossover design after administration of either hydrocortisone (100 mg orally) or placebo 12 hours previously. Positron emission tomography scans were analyzed with a region of interest analysis. RESULTS: Hydrocortisone treatment did not decrease 5-HT(1A) receptor BP either in the hippocampus, which was our a priori hypothesis, or in other cortical 5-HT(1A) regions; however, female subjects had a higher 5-HT(1A) receptor BP in certain brain areas compared with male subjects. CONCLUSIONS: These data are consistent with an earlier study in healthy volunteers and do not support the proposal that decreased 5-HT(1A) receptor BP in patients with acute major depression is a consequence of cortisol hypersecretion.     

Evaluation of variable line-shape models and prior information in automated 1H spectroscopic imaging analysis.

Analysis of in vivo short TE 1H spectra is complicated by broad baseline signal contributions and resonance line-shape distortions. Although the assumptions of ideal metabolite resonance line-shapes and slowly varying baseline signals can be used to separate these signals, the presence of broad or asymmetric line-shapes can invalidate this model. More complex line-shape models are computationally expensive or difficult to constrain, particularly for the low signal-to-noise commonly found for in vivo MR spectroscopic imaging applications. In this study, two time-domain models for fitting variable spectral line-shapes are examined, one using B-splines and another using summed sinusoids. The methods were verified using both phantom and human data, and Monte Carlo simulations were used to evaluate variations in calculated metabolite amplitudes due to interactions between the baseline and line-shape estimations. Additional studies investigated the use of prior line-shape information, obtained from either a water MRSI measurement or calculations from B(0) maps, to determine parameter starting values or optimization constraints. Both line-shape models showed the ability to fit the variety of line-shapes present in both the phantom and human MRSI data, with similar or improved accuracy over a Gaussian line-shape model; however, this improvement resulted in only minor improvement for the high-SNR phantom data and moderate improvements in regions with asymmetry for the fitted in vivo metabolite images. The use of prior line-shape information was of most benefit when applied toward setting optimization constraints but was of limited benefit when used to define initial starting values.     

Intensity-dependent regional cerebral blood flow during 1-Hz repetitive transcranial magnetic stimulation (rTMS) in healthy volunteers studied with H215O positron emission tomography: I. Effects of primary motor cortex rTMS.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) affects the excitability of the motor cortex and is thought to influence activity in other brain areas as well. We combined the administration of varying intensities of 1-Hz rTMS of the motor cortex with simultaneous positron emission tomography (PET) to delineate local and distant effects on brain activity. METHODS: Ten healthy subjects received 1-Hz rTMS to the optimal position over motor cortex (M1) for producing a twitch in the right hand at 80, 90, 100, 110, and 120% of the twitch threshold, while regional cerebral blood flow (rCBF) was measured using H(2)(15)O and PET. Repetitive transcranial magnetic stimulation (rTMS) was delivered in 75-pulse trains at each intensity every 10 min through a figure-eight coil. The regional relationship of stimulation intensity to normalized rCBF was assessed statistically. RESULTS: Intensity-dependent rCBF increases were produced under the M1 stimulation site in ipsilateral primary auditory cortex, contralateral cerebellum, and bilateral putamen, insula, and red nucleus. Intensity-dependent reductions in rCBF occurred in contralateral frontal and parietal cortices and bilateral anterior cingulate gyrus and occipital cortex. CONCLUSIONS: This study demonstrates that 1-Hz rTMS delivered to the primary motor cortex (M1) produces intensity-dependent increases in brain activity locally and has associated effects in distant sites with known connections to M1.     

Application of intermaxillary fixation screws in maxillofacial trauma.

PURPOSE: The use of intermaxillary fixation (IMF) in the treatment of maxillofacial trauma represents the cornerstone of fracture reduction and immobilization. Many modalities of IMF have been described; recently IMF screws have been introduced into clinical practice, however, hardware failure can occur. We performed a retrospective study evaluating hardware-associated complications for self-drilling/tapping IMF screws. MATERIALS AND METHODS: A retrospective study on 49 patients requiring IMF was performed. The diagnosis, duration of IMF, screw site, use of elastic or wire fixation, and associated complications were recorded. IMF screws were used to adjunct open reduction techniques, for definitive closed reduction, or fracture prevention following dentoalveolar surgery. Follow-up examinations were performed until fracture healing was complete (6 to 8 weeks). RESULTS: A single adverse event occurred in 19 patients (39%) while 4 patients (8%) had more than 1 complication. The most common event was screw loosening; 29% of patients had at least 1 screw dislodged in the treatment period. Of the total number of screws placed (229), 15 (6.5%) became loose, and were equally distributed among the mandible and maxilla. The remaining complications noted were root fracture, 4% (2 of 49); loosened wires, 6% (3 of 49); screw shear, 2% (1 of 49); malocclusion, 2% (1 of 49); and ingested hardware, 2% (1 of 49). CONCLUSIONS: Overall the IMF self-drilling/tapping screws have been shown to be a useful modality to establish maxillomandibular fixation. It is a safe, and time-sparing technique; however, it is not without limitations or potential consequences which the surgeon must be aware of in order to provide safe and effective treatment.     

Neuroactive Properties of Reproductive Steroids

Migraine is 3 times more common in postpubertal women than in men. Migraine is frequently exacerbated perimenstrually and commonly occurs exclusively at that time. It is often benefited by pregnancy and menopause. Estrogen withdrawal has been implicated as a mechanism for triggering migraines. The mechanism, however, is not well understood. Reproductive steroids have neuroactive properties that can modulate neuronal morphology and physiology. Increasing evidence suggests that circulating reproductive steroid levels regulate the balance of neuroexcitatory and neuroinhibitory activities in some brain regions by influencing synaptic plasticity. Estrogen has neuroexcitatory, whereas progesterone has neuroinhibitory, effects in most preclinical and clinical models. Several neurotransmitter systems that are implicated in migraine vary with reproductive steroid levels during the reproductive cycle. Estrogen stabilization may provide effective treatment in susceptible women, especially for catamenially exacerbated migraine.     

Cleveland Clinic Lerner College of Medicine: an innovative approach to medical education and the training of physician investigators.

Cleveland Clinic Lerner College of Medicine (CCLCM) is an innovative, five-year medical education track within Case Western Reserve University School of Medicine (Case) with a focused mission to attract and educate a limited number of highly qualified persons who seek to become physician investigators. CCLCM curriculum governance, faculty appointments and promotions, and admissions committees are integrated with respective Case committees. The CCLCM curriculum is based on faculty-defined professional attributes that graduates are expected to develop. These attributes were used to create curricular and assessment principles that guided the development of an integrated basic science, clinical science, and research curriculum, conducted in an active learning environment. An organ-system approach is used to solidify an understanding of basic science discipline threads in the context of relevant clinical problems presented in PBL and case-based discussion formats. Clinical skills are introduced in the first year as part of the two-year longitudinal experience with a family practice or internal medicine physician. The research program provides all students with opportunities to learn and experience basic and translational research and clinical research before selecting a research topic for their 12- to 15-month master-level thesis project. All Case students participate in required and elective clinical curriculum after the second year, but CCLCM students return to the Cleveland Clinic on selected Friday afternoons for program-specific research and professionalism-learning activities. A unique portfolio-based assessment system is used to assess student achievements in nine competency areas, seven of which reflect the Accreditation Council for Graduate Medical Education competencies.