Biomedical subjects

C M Brown

Publications and source records attributed to C M Brown.

At least 37 records · Page 2Linked to original sources

PubMed2001

Large harmonic softening of the phonon density of states of uranium.

Phonon density-of-states curves were obtained from inelastic neutron scattering spectra from the three crystalline phases of uranium at temperatures from 50 to 1213 K. The alpha-phase showed an unusually large thermal softening of phonon frequencies. Analysis of the vibrational power spectrum showed that this phonon softening originates with the softening of a harmonic solid, as opposed to vibrations in anharmonic potentials. It follows that thermal excitations of electronic states are more significant thermodynamically than are the classical volume effects. For the alpha-beta and beta-gamma phase transitions, vibrational and electronic entropies were comparable.

Journal Article↗

PubMed2001

Syntactic processing in left prefrontal cortex is independent of lexical meaning.

In language comprehension a syntactic representation is built up even when the input is semantically uninterpretable. We report data on brain activation during syntactic processing, from an experiment on the detection of grammatical errors in meaningless sentences. The experimental paradigm was such that the syntactic processing was distinguished from other cognitive and linguistic functions. The data reveal that in syntactic error detection an area of the left dorsolateral prefrontal cortex, adjacent to Broca's area, is specifically involved in the syntactic processing aspects, whereas other prefrontal areas subserve general error detection processes.

Adult↗

PubMed2001

Utility of intraoperative frozen section analysis of sentinel lymph nodes in breast cancer.

BACKGROUND: Intraoperative frozen section pathologic analysis of sentinel lymph node (SLN) may guide immediate (single-stage) completion axillary dissection for patients with nodal metastases. METHODS: The results of 203 consecutive patients undergoing SLN biopsy who had intraoperative pathology consultation between January 1998 and September 2000 were reviewed. SLN were analyzed by standard frozen section procedures. Final pathologic analysis included hematoxylin and eosin (H&E) staining of serial sections at 2-mm intervals. RESULTS: Frozen section analysis correctly identified a positive or negative result in 185 of 203 cases (overall accuracy 91%). In 17 of 53 cases, the SLNs were negative for tumor by frozen section, but positive on permanent section analysis (sensitivity 68%). The mean size of the nodal metastases was 6.2 mm and 1.5 mm in patients found to have true positive and false negative results, respectively (P <0.003). A single false positive SLN is reported. CONCLUSIONS: Two thirds of the patients were spared the need for reoperative axillary lymphadenectomy.

Aged↗

PubMed2001

Outbreak of Norwalk virus in a Caribbean island resort: application of molecular diagnostics to ascertain the vehicle of infection.

In 1998, an outbreak of gastroenteritis affected at least 448 persons including 122 staff at a resort hotel in Bermuda. A survey among staff indicated that gastroenteritis was associated with eating or drinking at the hotel (OR = 60, 95% CI = 2.4-15.1). Multiple specimens of drinking water had elevated faecal coliform levels and Escherichia coli present, suggestive of faecal contamination. Stools from 18 of the 19 persons with gastroenteritis that were tested were positive for genogroup-II Norwalk-like viruses (NLVs). RT-PCR analysis of a 31 specimen of water produced a genogroup-II NLV genome with a sequence identical to that of NLVs in the stools of three ill persons. This outbreak shows the value of new molecular diagnostics to link illness with a contaminated source through the use of sequence analysis. The risk of outbreaks such as these could be reduced in tourism dependent regions like Bermuda and the Caribbean by regular evaluation of data from the inspection and monitoring of drinking water supplies and waste water systems, by ensuring the chlorination of supplemental drinking water supplies and by establishing food-safety initiatives.

Base Sequence↗

PubMed2001

Dermal injection of radioactive colloid is superior to peritumoral injection for breast cancer sentinel lymph node biopsy: results of a multiinstitutional study.

OBJECTIVE: To determine the optimal radioactive colloid injection technique for sentinel lymph node (SLN) biopsy for breast cancer. SUMMARY BACKGROUND DATA: The optimal radioactive colloid injection technique for breast cancer SLN biopsy has not yet been defined. Peritumoral injection of radioactive colloid has been used in most studies. Although dermal injection of radioactive colloid has been proposed, no published data exist to establish the false-negative rate associated with this technique. METHODS: The University of Louisville Breast Cancer Sentinel Lymph Node Study is a multiinstitutional study involving 229 surgeons. Patients with clinical stage T1-2, N0 breast cancer were eligible for the study. All patients underwent SLN biopsy, followed by level I/II axillary dissection. Peritumoral, subdermal, or dermal injection of radioactive colloid was performed at the discretion of the operating surgeon. Peritumoral injection of isosulfan blue dye was performed concomitantly in most patients. The SLN identification rates and false-negative rates were compared. The ratios of the transcutaneous and ex vivo radioactive SLN count to the final background count were calculated as a measure of the relative degree of radioactivity of the nodes. One-way analysis of variance and chi-square tests were used for statistical analysis. RESULTS: A total of 2,206 patients were enrolled. Peritumoral, subdermal, or dermal injection of radioactive colloid was performed in 1,074, 297, and 511 patients, respectively. Most of the patients (94%) who underwent radioactive colloid injection also received peritumoral blue dye injection. The SLN identification rate was improved by the use of dermal injection compared with subdermal or peritumoral injection of radioactive colloid. The false-negative rates were 9.5%, 7.8%, and 6.5% (not significant) for peritumoral, subdermal, and dermal injection techniques, respectively. The relative degree of radioactivity of the SLN was five- to sevenfold higher with the dermal injection technique compared with peritumoral injection. CONCLUSIONS: Dermal injection of radioactive colloid significantly improves the SLN identification rate compared with peritumoral or subdermal injection. The false-negative rate is also minimized by the use of dermal injection. Dermal injection also is associated with SLNs that are five- to sevenfold more radioactive than with peritumoral injection, which simplifies SLN localization and may shorten the learning curve.

Breast Neoplasms↗

PubMed2001

Defining the optimal surgeon experience for breast cancer sentinel lymph node biopsy: a model for implementation of new surgical techniques.

OBJECTIVE: To determine the optimal experience required to minimize the false-negative rate of sentinel lymph node (SLN) biopsy for breast cancer. SUMMARY BACKGROUND DATA: Before abandoning routine axillary dissection in favor of SLN biopsy for breast cancer, each surgeon and institution must document acceptable SLN identification and false-negative rates. Although some studies have examined the impact of individual surgeon experience on the SLN identification rate, minimal data exist to determine the optimal experience required to minimize the more crucial false-negative rate. METHODS: Analysis was performed of a large prospective multiinstitutional study involving 226 surgeons. SLN biopsy was performed using blue dye, radioactive colloid, or both. SLN biopsy was performed with completion axillary LN dissection in all patients. The impact of surgeon experience on the SLN identification and false-negative rates was examined. Logistic regression analysis was performed to evaluate independent factors in addition to surgeon experience associated with these outcomes. RESULTS: A total of 2,148 patients were enrolled in the study. Improvement in the SLN identification and false-negative rates was found after 20 cases had been performed. Multivariate analysis revealed that patient age, nonpalpable tumors, and injection of blue dye alone for SLN biopsy were independently associated with decreased SLN identification rates, whereas upper outer quadrant tumor location was the only factor associated with an increased false-negative rate. CONCLUSIONS: Surgeons should perform at least 20 SLN cases with acceptable results before abandoning routine axillary dissection. This study provides a model for surgeon training and experience that may be applicable to the implementation of other new surgical technologies.

Breast Neoplasms↗

PubMed2001

Reducing community dyspepsia drug costs: a controlled trial.

BACKGROUND: Dyspepsia drug costs account for nearly 0.5% of the National Health Service budget. We hypothesised that improved management of dyspepsia would lead to reduced drug costs. AIM: To determine whether a multifaceted educational strategy for general practitioners aimed at improving quality of dyspepsia management can control dyspepsia costs without increasing demand for endoscopy. METHODS: A multifaceted educational intervention was delivered to general practitioners in West Gloucestershire but not to those in the east of the county. Dyspepsia drug costs, the primary outcome measure, were obtained from the Prescription Pricing Authority and compared between the two sides of the county. Referral rates for endoscopy, admission to the gastrointestinal bleed unit, and delayed diagnosis of gastric cancer were secondary measures recorded in West Gloucestershire only. RESULTS: Following the intervention, drug costs declined and then stabilised in West Gloucestershire. Drug costs peaked in the control group 15 months after those in the intervention group. Using an autoregressive integrated moving average model it was estimated the overall costs in the intervention group reduced by 57.9 pence per head of population per half year (95% confidence interval 45.8-69.9 pence/half year; p<0.0001) in comparison with the control group. This difference was maintained for three consecutive years resulting in a cumulative saving of pound1.13 million. Referral rates for upper gastrointestinal endoscopy remained stable during the study period. CONCLUSION: A multifaceted educational intervention for general practitioners designed to improve the quality of care of patients with dyspepsia is an effective means of controlling dyspepsia drug costs without increasing demand for endoscopy.

Aged↗

PubMed2001

Accuracy of sentinel lymph node biopsy for patients with T2 and T3 breast cancers.

Although numerous studies have demonstrated that sentinel lymph node (SLN) biopsy can accurately determine the axillary nodal status for early breast cancer some studies have suggested that SLN biopsy may be less reliable for tumors >2 cm in size. This analysis was performed to determine whether tumor size affects the accuracy of SLN biopsy. The University of Louisville Breast Cancer Sentinel Lymph Node Study is a prospective multi-institutional study involving 226 surgeons. The study was approved by the Institutional Review Board of each institution, and informed consent was obtained from all patients. Patients with clinical stage T1-2 N0 breast cancer were eligible for the study. Some patients with T3 tumors were included because they were clinically staged as T2 but on final pathology were found to have tumors >5 cm. This analysis includes 2148 patients who were enrolled from August 1997 through October 2000. All patients underwent SLN biopsy using a combination of radioactive colloid and blue dye injection followed by completion Level I/II axillary dissection. Statistical comparison was performed by chi-square analysis. The SLN identification rate, false negative rate, and overall accuracy of SLN biopsy were not significantly different among tumor stages T1, T2, and T3. We conclude that SLN biopsy is no less accurate for T2-3 breast cancers compared with T1 tumors.

Breast Neoplasms↗

PubMed2000

A view of dynamics changes in the molten globule-native folding step by quasielastic neutron scattering.

In order to understand the changes in protein dynamics that occur in the final stages of protein folding, we have used neutron scattering to probe the differences between a protein in its folded state and the molten globule states. The internal dynamics of bovine alpha-lactalbumin (BLA) and its molten globules (MBLA) have been examined using incoherent, quasielastic neutron scattering (IQNS). The IQNS results show length scale dependent, pico-second dynamics changes on length scales from 3.3 to 60 A studied. On shorter-length scales, the non-exchangeable protons undergo jump motions over potential barriers, as those involved in side-chain rotamer changes. The mean potential barrier to local jump motions is higher in BLA than in MBLA, as might be expected. On longer length scales, the protons undergo spatially restricted diffusive motions with the diffusive motions being more restricted in BLA than in MBLA. Both BLA and MBLA have similar mean square amplitudes of high frequency motions comparable to the chemical bond vibrational motions. Bond vibrational motions thus do not change significantly upon folding. Interestingly, the quasielastic scattering intensities show pronounced maxima for both BLA and MBLA, suggesting that "clusters" of atoms are moving collectively within the proteins on picosecond time scales. The correlation length, or "the cluster size", of such atom clusters moving collectively is dramatically reduced in the molten globules with the correlation length being 6.9 A in MBLA shorter than that of 18 A in BLA. Such collective motions may be important for the stability of the folded state, and may influence the protein folding pathways from the molten globules.

Animals↗

PubMed2000

Transterm: a database of messenger RNA components and signals.

Transterm facilitates studies of messenger RNAs and translational control signals. Each messenger RNA (mRNA) from GenBank is extracted and broken into its functional components, its coding sequence, initiation context, termination context, flanking sequence representing its 5' UTR (untranslated region), 3' UTR and translational signals. In addition, numerical parameters characterising each coding region in Transterm, including codon and GC bias, are available. For each species in Transterm, the initiation and termination regions are aligned by their start or stop codons and presented as base frequency matrices and tables of the information content of the bases in the alignments. Users can obtain summaries of characteristics of the mRNAs for species of their choice and search for translational signals both in the Transterm database and in their own sequence. The current release contains data from over 10 000 species, including the complete genomes of 20 prokaryotes and three eukaryotes. Both flat-file and relational database forms of Transterm are accessible via the WWW at http://biochem.otago.ac.nz/Transterm/

Codon, Initiator↗

PubMed2000

An event-related brain potential analysis of visual word priming effects.

Two experiments are reported that provide evidence on task-induced effects during visual lexical processing in a prime-target semantic priming paradigm. The research focuses on target expectancy effects by manipulating the proportion of semantically related and unrelated word pairs. In Experiment 1, a lexical decision task was used and reaction times (RTs) and event-related brain potentials (ERPs) were obtained. In Experiment 2, subjects silently read the stimuli, without any additional task demands, and ERPs were recorded. The RT and ERP results of Experiment 1 demonstrate that an expectancy mechanism contributed to the priming effect when a high proportion of related word pairs was presented. The ERP results of Experiment 2 show that in the absence of extraneous task requirements, an expectancy mechanism is not active. However, a standard ERP semantic priming effect was obtained in Experiment 2. The combined results show that priming effects due to relatedness proportion are induced by task demands and are not a standard aspect of online lexical processing.

Adult↗

PubMed2000

Forearm vascular responses during orthostatic stress in control subjects and patients with posturally related syncope.

The aim of this study was to compare the changes in forearm vascular resistance that occurred during orthostatic stress in asymptomatic volunteer subjects with those in patients with posturally related syncope. The authors hoped firstly that it would indicate the importance of vasoconstriction in the maintenance of blood pressure, and secondly that it might have diagnostic value if there were differences between symptomatic patients and asymptomatic volunteers. Twelve volunteers and 67 patients with unexplained syncope were classified as early or late fainters, based on their endurance of a test of combined head-up tilting and lower-body suction. Responses of vascular resistance were assessed from the ratio of arterial blood pressure (Finapres) to brachial artery blood velocity (Doppler). Changes in vascular resistance were greater in volunteers at all stages of the procedure than in patients. There was, however, no significant difference between the responses of early and late-fainting volunteers. These results demonstrate the importance of vasoconstriction in the resistance to posturally related syncope, and they indicate that assessments of responses of vascular resistance may improve the accuracy of the diagnosis.

Adult↗

PubMed2000

Vascular responses to orthostatic stress in patients with postural tachycardia syndrome (POTS), in patients with low orthostatic tolerance, and in asymptomatic controls.

Patients with postural tachycardia syndrome (POTS) are characterized by development of symptoms of orthostatic intolerance during standing that are not because of hypotension but are associated with tachycardia. The goal of this study was to compare the cardiac and vascular responses to orthostatic stress for patients with POTS (n = 8) with those for patients with low orthostatic tolerance (n = 29) and for healthy control subjects (n = 12). Responses of heart rate (ECG), arterial blood pressure, and brachial artery blood velocity (Doppler) were determined during a progressive orthostatic stress test of head-up tilt and lower body suction. Changes in forearm vascular resistance (mean arterial pressure/brachial velocity) were less for patients with POTS than for healthy persons, and also less than for most of the patients with low orthostatic tolerance. However, patients with POTS did not have a low tolerance to orthostatic stress (measured as time to discontinuation of the test). For the patients with POTS, the test was discontinued often because of symptoms associated with tachycardia but not hypotension, whereas for the other two groups, the test was discontinued because of hypotension. This study shows that for patients with POTS, abnormal sympathetic responses exist, with an increased sympathetic drive to the heart but deficient peripheral vascular responses, as measured in the forearm. This supports the hypothesis that patients with POTS may have a selective peripheral neuropathy, with small responses in some regions being compensated by overactivity in other regions.

Adolescent↗

PubMed2000

ERP effects of listening to speech: semantic ERP effects.

In this study, event-related brain potential effects of speech processing are obtained and compared to similar effects in sentence reading. In two experiments spoken sentences were presented with semantic violations in sentence-final or mid-sentence positions. For these violations N400 effects were obtained that were very similar to N400 effects obtained in reading. However, the N400 effects in speech were preceded by an earlier negativity (N250). This negativity is not commonly observed with written input. The early effect is explained as a manifestation of a mismatch between the word forms expected on the basis of the context, and the actual cohort of activated word candidates that is generated on the basis of the speech signal.

Adult↗

PubMed2000

ERP effects of listening to speech compared to reading: the P600/SPS to syntactic violations in spoken sentences and rapid serial visual presentation.

In this study, event-related brain potential effects of speech processing are obtained and compared to similar effects in sentence reading. In two experiments sentences were presented that contained three different types of grammatical violations. In one experiment sentences were presented word by word at a rate of four words per second. The grammatical violations elicited a Syntactic Positive Shift (P600/SPS), 500 ms after the onset of the word that rendered the sentence ungrammatical. The P600/SPS consisted of two phases, an early phase with a relatively equal anterior-posterior distribution and a later phase with a strong posterior distribution. We interpret the first phase as an indication of structural integration complexity, and the second phase as an indication of failing parsing operations and/or an attempt at reanalysis. In the second experiment the same syntactic violations were presented in sentences spoken at a normal rate and with normal intonation. These violations elicited a P600/SPS with the same onset as was observed for the reading of these sentences. In addition two of the three violations showed a preceding frontal negativity, most clearly over the left hemisphere.

Adult↗

PubMed2000

The rewarding properties of neuropeptide Y in perifornical hypothalamus vs. nucleus accumbens.

There is a high coexistence of substance abuse in humans with eating disorders. One theory offered to account for this fact is that a common biochemical substrate may exist that mediates both processes. Brain neuropeptide Y (NPY) is one neurochemical system that might contribute to these separate, yet related, problems. To clarify the role of NPY in mediating reward processes and the possible interaction between reward and feeding, the present study examined the effects of injecting NPY bilaterally into the perifornical hypothalamus (PFH) vs. the nucleus accumbens (NAC) on intake of preferred vs. non-preferred food types, as well as on conditioned place preference (CPP) learning. NPY (24, 78, 156 and 235 pmol/side) stimulated intake of both regular powdered chow and sucrose when injected into the PFH, but not the NAC. A CPP that was negatively correlated with food intake occurred with the low (24 pmol/side) dose of NPY in the PFH, while a CPP that was not correlated with food intake was produced with the same dose in the NAC. The extent of the CPPs produced by NPY injection in both brain sites mirrored that produced by peripheral injection of amphetamine (2.5 mg/kg). These results indicate that NPY elicits reward-related behavior, but not feeding, from the NAC, and both behaviors from the PFH. However, the feeding effect derived from the PFH appears to overshadow a rewarding effect derived from this site. Considered together, these findings suggest that altered NPY functioning in both brain regions may contribute to some of the pathophysiological processes observed in eating disordered patients who have additional proclivities for substance abuse.

Amphetamine↗

PubMed2000

Discourse before gender: an event-related brain potential study on the interplay of semantic and syntactic information during spoken language understanding.

A study is presented on the effects of discourse-semantic and lexical-syntactic information during spoken sentence processing. Event-related brain potentials (ERPs) were registered while subjects listened to discourses that ended in a sentence with a temporary syntactic ambiguity. The prior discourse-semantic information biased toward one analysis of the temporary ambiguity, whereas the lexical-syntactic information allowed only for the alternative analysis. The ERP results show that discourse-semantic information can momentarily take precedence over syntactic information, even if this violates grammatical gender agreement rules.

Adult↗

PubMed2000

Practical guidelines for optimal gamma probe detection of sentinel lymph nodes in breast cancer: results of a multi-institutional study. For the University of Louisville Breast Cancer Study Group.

INTRODUCTION: Multiple radioactive lymph nodes are often removed during the course of sentinel lymph node (SLN) biopsy for breast cancer when both blue dye and radioactive colloid injection are used. Some of the less radioactive lymph nodes are second echelon nodes, not true SLNs. The purpose of this analysis was to determine whether harvesting these less radioactive nodes, in addition to the "hottest" SLNs, reduces the false-negative rate. METHODS: Patients were enrolled in this multicenter (121 surgeons) prospective, institutional review board-approved study after informed consent was obtained. Patients with clinical stage T1-2, N0, M0 invasive breast cancer were eligible. This analysis includes all patients who underwent axillary SLN biopsy with the use of an injection of both isosulfan blue dye and radioactive colloid. The protocol specified that all blue nodes and all nodes with 10% or more of the ex vivo count of the hottest node should be removed and designated SLNs. All patients underwent completion level I/II axillary dissection. RESULTS: SLNs were identified in 672 of 758 patients (89%). Of the patients with SLNs identified, 403 patients (60%) had more than 1 SLN removed (mean, 1.96 SLN/patient) and 207 patients (31%) had nodal metastases. The use of filtered or unfiltered technetium sulfur colloid had no impact on the number of SLNs identified. Overall, 33% of histologically positive SLNs had no evidence of blue dye staining. Of those patients with multiple SLNs removed, histologically positive SLNs were found in 130 patients. In 15 of these 130 patients (11.5%), the hottest SLN was negative when a less radioactive node was positive for tumor. If only the hottest node had been removed, the false-negative rate would have been 13.0% versus 5.8% when all nodes with 10% or more of the ex vivo count of the hottest node were removed (P =.01). CONCLUSIONS: These data support the policy that all blue nodes and all nodes with 10% or more of the ex vivo count of the hottest SLN should be harvested for optimal nodal staging.

Biopsy↗