Cortical circumferential profile of SPECT cerebral perfusion in Alzheimer''s disease

We developed a semiautomatic method termed “cortical circumferential profiling” for objective analysis of cerebral cortex function in emission tomographic neuroimaging studies. This method treats cortex as a continuous ring near the outer brain edge. A computer algorithm samples the cortex at 60 contiguous, equiangular locations, using 1-cm² samples. These values are plotted as a function of cortical angle to produce the cortical circumferential profile. This method was used in a study of regional cerebral perfusion in 15 patients with Alzheimer's disease and 8 elderly control subjects using N-isopropyl [I-123]-iodoamphetamine. Cortical circumferential profiling decreases variability, examines the entire cortex within slices at preselected levels above the orbital-meatal line, and facilitates intrasubject and intersubject comparisons.     

Sarcoplasmic reticulum calcium load regulates rat arterial smooth muscle calcium sparks and transient KCa currents

Voltage-gated Na⁺ current is reduced by acid solution. Protons reduce peak Na⁺ conductance by lowering single channel conductance and shift the voltage range of gating by neutralizing surface charges. Structure-function studies identify six carboxyls and a lysine in the channel's outer vestibule. We examined the roles of the superficial ring of carboxyls in acid block of Na_v1.4 (the rat skeletal muscle Na⁺ channel isoform) by measuring the effects of their neutralization or their substitution by lysine on sensitivity to acid solutions, using the two-micropipette voltage clamp in Xenopus oocytes. Alteration of the outer ring of carboxylates had little effect on the voltage for half-activation of Na⁺ current, as if they are distant from the channels' voltage sensors. The mutations did not abolish proton block; rather, they all shifted the p K _a (-log of the dissociation constant) in the acid direction. Effects of neutralization on p K _a were not identical for different mutations, with E758Q > D1241A > D1532N > E403Q. E758K showed double the effect of E758Q, and the other lysine mutations all produced larger effects than the neutralizing mutations. Calculation of the electrostatic potential produced by these carboxylates using a pore model showed that the p K _a values of carboxylates of Glu-403, Glu-758, and Asp-1532 are shifted to values similar to the experimentally measured p K _a. Calculations also predict the experimentally observed changes in p K _a that result from mutational neutralization or introduction of a positive charge. We propose that proton block results from partial protonation of these outer ring carboxylates and that all of the carboxylates contribute to a composite Na⁺ site.     

Clerkship directors' perceptions of the impact of HCFA documentation guidelines.

PURPOSE: Chart notes are used to support billing codes under the evaluation and management guidelines of the Health Care Financing Administration (HCFA), in addition to serving as a record of the visit. To better understand the effect of the HCFA documentation guidelines, the authors collected data on how the guidelines affect participation by university- and community-based faculty in clinical education programs. METHOD: In 2000, the authors sent six copies of their questionnaire to the associate deans of the 125 U.S. medical schools and requested they distribute them to all core clerkship directors. The questionnaire consisted of multiple-choice and short-answer questions regarding documentation of medical visits, participation of community-based faculty, understanding of HCFA documentation guidelines, and effects on education programs. RESULTS: The response rate was about 50%. Most of the 379 clerkship directors who responded (77%) stated they were aware the HCFA documentation guidelines include specifications regarding the role medical students can play and documentation of medical visits, and 64% indicated they were concerned the guidelines would affect their educational programs. Concerns included the loss of student independence and active participation in the patient care environment (37), time constraints and the changing balance between education and service (16), loss of faculty and decreased morale (11), and decreased quality of care for patients (7). CONCLUSION: Leaders of medical education must work to modify these guidelines to protect the quality of patients' care, while maximizing students' educational opportunity and participation.     

Phase III study of interferon alfa-NL as adjuvant treatment for resectable renal cell carcinoma: an Eastern Cooperative Oncology Group/Intergroup trial.

PURPOSE: To evaluate the role of adjuvant interferon alfa after complete resection of locally extensive renal cell carcinoma. PATIENTS AND METHODS: A total of 283 eligible patients with pT3-4a and/or node-positive disease were randomly assigned after radical nephrectomy and lymphadenectomy to observation or to interferon alfa-NL (Wellferon, Burroughs-Wellcome, Research Park, NC) given daily for 5 days every 3 weeks for up to 12 cycles. Patients were stratified on the basis of pathologic stage. Patients remained on treatment until documented recurrence, excessive toxicity, or patient/physician preference deemed removal appropriate. RESULTS: At median follow-up of 10.4 years, median survival was 7.4 years in the observation arm and 5.1 year in the treatment arm (log-rank P =.09). Median recurrence-free survival was 3.0 years in the observation arm and 2.2 years in the interferon arm (P =.33). Performance status (P =.003), nodal status (N2 v N0, P <.0001), and tumor stage (P =.0002) were significant prognostic factors in multivariate analysis. A proportional hazards model examining the effects of treatment arm and time to recurrence on survival after recurrence among patients who recurred found that random assignment to interferon treatment (P =.009) and shorter time to recurrence (P <.0001) were independent predictors of shorter survival after recurrence. Although no lethal toxicities were observed, severe (grade 4) toxicities including neutropenia, myalgia, fatigue, depression, and other neurologic toxicities occurred in 11.4% of those randomly assigned to interferon treatment. CONCLUSION: Adjuvant treatment with interferon did not contribute to survival or relapse-free survival in this group of patients.     

Laboratory routines cause animal stress.

Eighty published studies were appraised to document the potential stress associated with three routine laboratory procedures commonly performed on animals: handling, blood collection, and orogastric gavage. We defined handling as any non-invasive manipulation occurring as part of routine husbandry, including lifting an animal and cleaning or moving an animal's cage. Significant changes in physiologic parameters correlated with stress (e.g., serum or plasma concentrations of corticosterone, glucose, growth hormone or prolactin, heart rate, blood pressure, and behavior) were associated with all three procedures in multiple species in the studies we examined. The results of these studies demonstrated that animals responded with rapid, pronounced, and statistically significant elevations in stress-related responses for each of the procedures, although handling elicited variable alterations in immune system responses. Changes from baseline or control measures typically ranged from 20% to 100% or more and lasted at least 30 min or longer. We interpret these findings to indicate that laboratory routines are associated with stress, and that animals do not readily habituate to them. The data suggest that significant fear, stress, and possibly distress are predictable consequences of routine laboratory procedures, and that these phenomena have substantial scientific and humane implications for the use of animals in laboratory research.     

Design and use of a prefabricated fiber-reinforced composite substructure for the chairside replacement of missing premolars.

Fiber-reinforced resin composites (FRCs) have been used to make frameworks to support particulate resin composite veneers in the replacement of missing teeth. Both prosthetic laboratory-fabricated and chairside-fabricated approaches have been used with varying degrees of success. The chairside FRC fixed partial denture has been mainly used for anterior tooth replacement where the emphasis is on esthetics rather than withstanding occlusal load. This article focuses on the use of this technology in the chairside replacement of premolars. The concept of using a prefabricated framework is described in detail. This approach allows for the efficient delivery of a consistently made chairside prosthesis. This is in contrast with the time-consuming and less consistent result of FRC framework fabrication directly in the mouth. The goal for this concept is to use a premade framework finalized by the provider at chairside to provide medium- to long-term posterior tooth replacement, with minimal abutment tooth reduction.     

Comparison of 180° and 360° acquisition for myocardial perfusion SPECT with compensation for attenuation, detector response, and scatter: Monte Carlo and mathematical observer results

BACKGROUND: The optimal projection data acquisition strategy for myocardial perfusion (MP) single photon emission computed tomography (SPECT) remains controversial. METHODS: We compared MP SPECT using 180 degrees and 360 degrees projection data obtained with the same acquisition time, reconstructed either with filtered back projection (FBP) or the iterative ordered-subsets expectation maximization (OS-EM) algorithm with various combinations of attenuation, detector response, and scatter compensation using mathematical observers and a myocardial defect detection task. We used Monte Carlo-simulated projection data from a population of 3-dimensional nurbs-based cardiac-torso (NCAT) phantoms with ranges of variability in patient anatomy, organ uptake, defect location, defect size, and noise level based on clinical data. Projection data from 180 degrees and 360 degrees acquisitions were generated by assuming the same acquisition time. After iterative or FBP reconstruction, standard postprocessing methods were applied. For each acquisition and reconstruction method, we optimized the number of iterations and cut-off frequency of the Butterworth filter using the Channelized Hotelling Observer methodology. The optimum set of parameters was that which gave the maximum area under the curve. RESULTS: For both acquisition protocols, OS-EM with compensations provided better performance than FBP or OS-EM without compensation. For FBP, the optimized 180 degrees acquisition provided a statistically significant increase in AUC as compared with optimized 360 degrees acquisition. For OS-EM, the AUCs for 180 degrees were slightly larger than for 360 degrees acquisitions when comparing images reconstructed with the same compensations. However, the differences were smaller and not statistically significant. CONCLUSION: With optimized reconstruction and filtering parameters, 180 degrees acquisition provided a statistically significant improvement over 360 degrees acquisition for FBP reconstruction. However, for OS-EM the differences were small and not statistically significant.