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S Fulton

Publications and source records attributed to S Fulton.

17 recordsLinked to original sources

National Institutes of Health Consensus Development Conference Statement: adjuvant therapy for breast cancer, November 1-3, 2000.

OBJECTIVE: Our goal was to provide health-care providers, patients, and the general public with an assessment of currently available data regarding the use of adjuvant therapy for breast cancer. PARTICIPANTS: The participants included a non-Federal, non-advocate, 14-member panel representing the fields of oncology, radiology, surgery, pathology, statistics, public health, and health policy as well as patient representatives. In addition, 30 experts in medical oncology, radiation oncology, biostatistics, epidemiology, surgical oncology, and clinical trials presented data to the panel and to a conference audience of 1000. EVIDENCE: The literature was searched with the use of MEDLINE(TM) for January 1995 through July 2000, and an extensive bibliography of 2230 references was provided to the panel. Experts prepared abstracts for their conference presentations with relevant citations from the literature. Evidence from randomized clinical trials and evidence from prospective studies were given precedence over clinical anecdotal experience. CONSENSUS PROCESS: The panel, answering predefined questions, developed its conclusions based on the evidence presented in open forum and the scientific literature. The panel composed a draft statement, which was read in its entirety and circulated to the experts and the audience for comment. Thereafter, the panel resolved conflicting recommendations and released a revised statement at the end of the conference. The panel finalized the revisions within a few weeks after the conference. The draft statement was made available on the World Wide Web immediately after its release at the conference and was updated with the panel's final revisions. The statement is available at http://consensus.nih.gov. CONCLUSIONS: The panel concludes that decisions regarding adjuvant hormonal therapy should be based on the presence of hormone receptor protein in tumor tissues. Adjuvant hormonal therapy should be offered only to women whose tumors express hormone receptor protein. Because adjuvant polychemotherapy improves survival, it should be recommended to the majority of women with localized breast cancer regardless of lymph node, menopausal, or hormone receptor status. The inclusion of anthracyclines in adjuvant chemotherapy regimens produces a small but statistically significant improvement in survival over non-anthracycline-containing regimens. Available data are currently inconclusive regarding the use of taxanes in adjuvant treatment of lymph node-positive breast cancer. The use of adjuvant dose-intensive chemotherapy regimens in high-risk breast cancer and of taxanes in lymph node-negative breast cancer should be restricted to randomized trials. Ongoing studies evaluating these treatment strategies should be supported to determine if such strategies have a role in adjuvant treatment. Studies to date have included few patients older than 70 years. There is a critical need for trials to evaluate the role of adjuvant chemotherapy in these women. There is evidence that women with a high risk of locoregional tumor recurrence after mastectomy benefit from postoperative radiotherapy. This high-risk group includes women with four or more positive lymph nodes or an advanced primary cancer. Currently, the role of postmastectomy radiotherapy for patients with one to three positive lymph nodes remains uncertain and should be tested in a randomized controlled trial. Individual patients differ in the importance they place on the risks and benefits of adjuvant treatments. Quality of life needs to be evaluated in selected randomized clinical trials to examine the impact of the major acute and long-term side effects of adjuvant treatments, particularly premature menopause, weight gain, mild memory loss, and fatigue. Methods to support shared decision-making between patients and their physicians have been successful in trials; they need to be tailored for diverse populations and should be tested for broader dissemination.

Adjuvants, Pharmaceutic↗

Brain reward circuitry and the regulation of energy balance.

Reward signals contribute to the regulation of energy balance by influencing switching between feeding and competing behaviors. Properties of natural rewards are mimicked by electrical stimulation of certain brain regions. The rewarding effect produced by stimulating the perifornical region of the hypothalamus is modulated by body weight and is attenuated both by leptin and insulin. Research is reviewed concerning the dependence of the rewarding effect of perifornical stimulation on long-term energy stores and the effects of two neuropeptides implicated in the regulation of energy balance, neuropeptide Y and corticotropin-releasing hormone. It is proposed that the potentiating effect of weight loss on perifornical self-stimulation is not tied to an increased propensity to eat or to an enhancement of food reward per se, but resembles the influence of long-term energy stores on non-ingestive behaviors that defend body weight, such as hoarding.

Animals↗

Modulation of brain reward circuitry by leptin.

Leptin, a hormone secreted by fat cells, suppresses food intake and promotes weight loss. To assess the action of this hormone on brain reward circuitry, changes in the rewarding effect of lateral hypothalamic stimulation were measured after leptin administration. At five stimulation sites near the fornix, the effectiveness of the rewarding electrical stimulation was enhanced by chronic food restriction and attenuated by intracerebroventricular infusion of leptin. In contrast, the rewarding effect of stimulating neighboring sites was insensitive to chronic food restriction and was enhanced by leptin in three of four cases. These opposing effects of leptin may mirror complementary changes in the rewarding effects of feeding and of competing behaviors.

Animals↗

Antidysrhythmics. Emergent.

The emergent treatment of dysrhythmias in the ED continues to evolve. Classic medications such as bretylium and lidocaine are given with newer drugs like amiodarone, ibutilide, and sotalol. Studies in progress will examine their efficacy in the ED. The emergency physician must keep abreast of the growing body of literature.

Anti-Arrhythmia Agents↗

Multifrequency tympanometry and histopathology in chinchillas with experimentally produced middle ear pathologies.

Middle ear lesions were produced in chinchillas by introducing fascia, Gelfoam, silastic or a combination of these materials into the labyrinthine and mastoid bullae. After 1-2 months, conventional 226 Hz and multifrequency tympanometry (MFT) were performed and the animals were sacrificed for histopathological analysis of the middle ear. Specific middle ear lesions were created including abnormal tympanic membrane thickness, tympanic membrane mass, tympanic membrane adhesion, mastoid bulla obstruction, ossicular adhesions and reduced middle ear volume. Several potentially strong associations emerged between tympanometric measures and pathological conditions. The strongest were the combinations of thick tympanic membrane and irregular multifrequency tympanograms, tympanic membrane mass and notched 226 Hz admittance tympanograms, tympanic membrane adhesions and low 226 Hz admittance, and tympanic membrane adhesions and low resonant frequency. 226 Hz static admittance had a sensitivity of 0.73 and a specificity of 0.75 for detecting significant middle ear pathology. Tympanometric width was not an effective diagnostic test, separately or in combination with static admittance. The most effective test based on 226 Hz measures was the combination of low admittance or admittance notch. MFT was superior to 226 Hz tympanometry. The combination of low resonance or double resonance or irregular patterns had a sensitivity and specificity of 0.91 and 1.0, respectively. Combining 226 Hz tympanometry with MFT improved the performance relative to 226 Hz tympanometry alone but not relative to MFT alone. The results support clinical reports that multifrequency tympanometry detects some middle ear pathologies that are not detected by conventional 226 Hz tympanometry.

Acoustic Impedance Tests↗

Computers and medical information: an elective for fourth-year medical students.

The Computers and Medical Information elective is a collaborative effort to expose students to a variety of computer applications for medical information management. The course has a modular format so that students can work with a variety of people who are enthusiastic users of computer-based information systems. The elective emphasizes learning by doing. Faculty introduce concepts and systems and serve as guides in the use of systems. Students have rated the course positively and, after four years as an elective, some of the course's content has been integrated into the required curriculum.

Computer Communication Networks↗

Preparative peptide purification by cation-exchange and reversed-phase perfusion chromatography.

Cation exchange was compared to reversed-phase chromatography for the preparative purification of a 28-residue peptide (vasoactive intestinal polypeptide) on the 100-mg scale. Optimized high-speed, high-resolution methods were developed for both chromatographic modes on POROS Perfusion Chromatography flow-through particle chromatography columns. While both methods appeared to provide similar purity, the cation exchange column had approximately ten times the loading capacity per unit column volume as the reversed-phase column. Five-minute methods for desalting the cation exchange-purified peptide and analysis of fractions were developed using small reversed-phase columns. The cation-exchange method was scaled up to process 95 mg of crude peptide in a 12-min run.

Amino Acid Sequence↗

Turn-taking and speech act patterns in the discourse of senile dementia of the Alzheimer's type patients.

Conversational discourse patterns of 11 normal elderly and 11 senile dementia of the Alzheimer's type (SDAT) patients engaged in dyadic interaction with an examiner were examined. Differences in word usage, turn taking, and speech act production were investigated both for the two-subject groups and for the examiner's conversations with each group. Compensatory shifts in discourse by participants are identified. For the subject, differences were shown on words per turn with SDAT subjects speaking in shorter turns and in nonverbal responses with SDAT subjects using this strategy more frequently. Speech act categories of Requestives and Assertives also differed with SDAT subjects using more Requestives and fewer Assertives. The SDAT subjects had significantly more occurrences of unintelligible utterances. For the examiner, words per turn differed with the examiner using shorter turns with SDAT subjects. No differences were shown in the examiner's patterns of speech act usage, nonverbal responses, or intelligibility. In general, these results indicate significant discourse differences in the words per turn level for all participants and speech act levels of conversation for SDAT subjects. They also indicate generally maintained interaction patterns by speakers so that the discourse genre of conversation is sustained. The pattern of compensatory shifts in discourse suggests retained flexibility in the communication system of early and mid stage SDAT patients.

Aged↗

31P NMR measurements of the ADP concentration in yeast cells genetically modified to express creatine kinase.

Rabbit muscle creatine kinase has been introduced into the yeast Saccharomyces cerevisiae by transforming cells with a multicopy plasmid containing the coding sequence for the enzyme under the control of the yeast phosphoglycerate kinase promoter. The transformed cells showed creatine kinase activities similar to those found in mammalian heart muscle. 31P NMR measurements of the near-equilibrium concentrations of phosphocreatine and cellular pH together with measurements of the total extractable concentrations of phosphocreatine and creatine allowed calculation of the free ADP/ATP ratio in the cell. The calculated ratio of approximately 2 was considerably higher than the ratio of between 0.06 and 0.1 measured directly in cell extracts.

Adenosine Diphosphate↗

Influence of pore and particle size on the frontal uptake of proteins. Implications for preparative anion-exchange chromatography.

Several silica-based anion-exchange packings were synthesized with nominal pore sizes of 250, 500 and 1000 A in 10-, 20- and 50-micron particles. The static ("equilibrium") adsorption capacities for bovene serum albumin (mol. wt. 69,000), alpha-lactalbumin (17,500) and ferritin (440,000) were first measured using bulk material. The media were then packed into columns for frontal uptake experiments to measure adsorption from a flowing mobile phase. In general, frontal uptake was inversely related to both flow-rate and particle size. However, the magnitude of these relationships was strongly dependent on the pore to protein diameter ratio. More specifically, the uptake of bovine serum albumin was significantly more sensitive to linear velocity and particle size than alpha-lactalbumin. A mathematical model of the chromatographic process was used to calculate radial adsorption profiles across the chromatographic particle during frontal uptake. It was shown that restricted intraparticle diffusion due to insufficient pore size causes incomplete utilization of internal surface area. Under such conditions, protein is only bound within a finite shell on the outermost side of the particle; therefore, the effective loadability of the packing is greatly reduced. These data suggest that a pore size of at least 500 A will be required for the preparative chromatography of proteins with a molecular weight higher than ca. 100,000. This observation is especially evident when using particle sizes greater than 10 micron.

Adsorption↗

Ultrafiltration vs equilibrium dialysis for determination of free fraction.

The analytical basis of membrane separation in determining plasma free drug concentrations is developed from consideration of the generalised ideal mass action and conservation laws applied to thermodynamic states of differing component volumes. The intuitively surprising theoretical independence of free drug concentration with changing fractional volume of protein predicts the equivalence of final free drug concentration after uniform pre-dilution with that after equilibrium dialysis against the same volume of buffer. Similarly, the ultrafiltrate free concentration of drugs in ideal plasma binding equilibrium is theoretically constant, regardless of the extent of reduction in fractional volume of binding protein during filtration. The pitfalls in calculating free and bound fraction and concentration from equilibrium dialysis are reviewed and expressions presented to correct the major artefacts. The dilution behaviour of drugs is predicted from the normalised mass action model. Practical aspects of validating ultrafiltration free drug levels using equilibrium dialysis are outlined.

Blood Proteins↗

Congenital malformations of middle and inner ears of parabiotic twins.

We describe herein the congenital malformations of the middle and inner ears in temporal bones of parabiotic, monozygotic twins. Temporal bones were removed from twin B, who had no fetal cardiac activity and was born dead at 23-4/7 weeks, and twin A, the donor or "pump" twin in intrauterine life, who died shortly after birth at 20-6/7 weeks. The temporal bones were processed routinely in celoidin, stained with hematoxylin and eosin, and examined by light microscopy. We found that twin B had Mondini's dysplasia with associated deformities of the middle ear and in general showed more developmental anomalies than twin A, and we conclude that Mondini's dysplasia with anomalies of the middle ear may occur in the parabiotic twin syndrome, and the abnormalities may be explainable as the result of vascular disturbance, which also causes other lesions in these unusual cases.

Ear, Inner↗

Outgrowing schwannomas arising from tympanic segments of the facial nerve.

PURPOSE: Although there have been numerous reports of clinical cases of facial nerve schwannoma, histopathologic studies of its early stages of development are rare. The purpose of this study was to describe the incidence, origin, and pathology of small, asymptomatic schwannomas of the facial nerve. MATERIALS AND METHODS: Fifteen hundred twenty-six ears from the human temporal bone collection of the Otitis Media Research Center Otopathology Laboratory at the University of Minnesota were studied under light microscopy. RESULTS: Twelve bones with morphologic indications of type A Antoni tissue that mimics facial schwannoma in the tympanic cavity were selected. The 12 ears were from nine individuals with asymptomatic histories. The twelve schwannomas developed from perineurium at dehiscences in the facial canal near the oval window, forming defects in the epineurium by growth of Schwann cells downward and outward toward the stapes. No obvious compressions or lesions within fibers in the facial nerve were observed. CONCLUSION: Because these tumors grow slowly without hearing loss or facial nerve symptoms, they may be mistaken for granulation tissue during surgery for chronic otitis media.

Adult↗