Biomedical subjects

Andrew Webb

Publications and source records attributed to Andrew Webb.

At least 19 recordsLinked to original sources

PubMed2007

Nitrite-derived nitric oxide protects the rat kidney against ischemia/reperfusion injury in vivo: role for xanthine oxidoreductase.

In normal conditions, nitric oxide (NO) is oxidized to the anion nitrite, but in hypoxia, this nitrite may be reduced back to NO by the nitrite reductase action of deoxygenated hemoglobin, acidic disproportionation, or xanthine oxidoreductase (XOR). Herein, is investigated the effects of topical sodium nitrite administration in a rat model of renal ischemia/reperfusion (I/R) injury. Rats were subjected to 60 min of bilateral renal ischemia and 6 h of reperfusion in the absence or presence of sodium nitrite (30 nmol) administered topically 1 min before reperfusion. Serum creatinine, serum aspartate aminotransferase, creatinine clearance, fractional excretion of Na(+), and plasma nitrite/nitrate concentrations were measured. The nitrite-derived NO-generating capacity of renal tissue was determined under acidic and hypoxic conditions by ozone chemiluminescence in homogenates of kidneys that were subjected to sham, ischemia-only, and I/R conditions. Nitrite significantly attenuated renal dysfunction and injury, an effect that was abolished by previous treatment of rats with the NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazole-1-oxyl-3-oxide (2.5 mumol intravenously 5 min before ischemia and 50 nmol topically 6 min before reperfusion). Renal tissue homogenates produced significant amounts of NO from nitrite, an effect that was attenuated significantly by the xanthine oxidoreductase inhibitor allopurinol. Taken together, these findings demonstrate that topically administered sodium nitrite protects the rat kidney against I/R injury and dysfunction in vivo via the generation, in part, of xanthine oxidoreductase-catalyzed NO production. These observations suggest that nitrite therapy might prove beneficial in protecting kidney function and integrity during periods of I/R such as those encountered in renal transplantation.

Animals↗

PubMed2005

Selective sparing of brain tissue in postmenopausal women receiving hormone replacement therapy.

Determining the benefits and/or drawbacks of hormone replacement therapy (HRT) on women's health is an imperative public health goal. Research in rodents suggests benefits of estrogen on neuronal growth and function. However, little research has investigated the effects of HRT on brain tissue in humans. We used high-resolution magnetic resonance imaging and an optimized voxel-based morphometric technique to examine the effects of HRT on brain volume in postmenopausal women. We report two main results: (a) HRT is associated with the sparing of grey matter in prefrontal, parietal, and temporal brain regions and white matter in medial temporal lobe regions, and (b) longer durations of therapy are associated with greater sparing of grey matter tissue. HRT should be considered a possible mediator of age-related neural decline in both grey and white matter tissues.

Age Factors↗

PubMed2005

Parallel imaging for NMR microscopy at 14.1 Tesla.

Parallel imaging techniques using arrays of mutually decoupled coils have become standard on almost all clinical imaging systems. Such techniques also have great potential for high-field magnetic resonance (MR) microscopy, where measurement times are usually long and susceptibility artifacts can be severe. However, it is technically very challenging to design efficient high-frequency phased arrays for small-diameter, vertical-bore magnets, especially since standard decoupling methods, such as impedance mismatched preamplifiers, cannot be easily integrated. A four-coil phased array was constructed for microimaging at 600 MHz, and sensitivity encoding (SENSE) and generalized autocalibrating partially parallel acquisitions (GRAPPA) reconstructions of spin-echo and echo-planar images of the mouse brain were performed to reduce imaging time and susceptibility artifacts, respectively.

Algorithms↗

PubMed2005

Longitudinal quality of life and quality adjusted survival in a randomised controlled trial comparing six months of bolus fluorouracil/leucovorin vs. twelve weeks of protracted venous infusion fluorouracil as adjuvant chemotherapy for colorectal cancer.

Longitudinal quality of life (QOL) assessment is infrequently made in adjuvant therapy for colorectal cancer (CRC). This analysis aims to assess QOL and quality adjusted survival (QAS) in patients receiving adjuvant 5-FU for stage II and III CRC. We performed a multicentre study in which 801 patients were randomised to 6 months of bolus 5-FU/leucovorin (LV n = 404) or 12 weeks of protracted venous infusion (PVI) 5-FU (n = 397). There were significant differences in the deterioration of QOL scores at week 2 with bolus 5-FU/LV compared to PVI 5-FU (P < 0.001), coinciding with toxicity peak during the first cycle. Following week 12, global QOL recovered to baseline when PVI 5-FU was stopped but this was delayed with bolus 5-FU/LV until completion at week 24. QOL scores significantly improved in both arms during follow-up (P < 0.001) and reached a plateau by year 1 without incremental improvement between years 2 and 5. There was a trend towards better QAS with PVI 5-FU. Twelve weeks of adjuvant PVI 5-FU was associated with significantly better QOL during treatment and faster time to recovery compared to 6 months of bolus 5-FU/LV.

Adult↗

PubMed2005

Reduced data acquisition time in multi-dimensional NMR spectroscopy using multiple-coil probes.

A new hardware-based approach is presented to reduce data acquisition times in multi-dimensional NMR spectroscopy using a multiple-coil probe. Using a four-coil setup, two-dimensional COSY and TOCSY spectra were acquired in one-quarter the time of conventional spectra by simultaneous acquisition of different effective t1 evolution times for each coil. Data processing consists of simple phase-shifting and intensity normalization of the individual data sets, and results in spectra almost identical to those acquired in a conventional manner. This method can potentially be integrated with other new data acquisition and processing schemes for further increases in data acquisition speed.

Chloroquine↗

PubMed2004

In vivo detection limits of magnetically labeled embryonic stem cells in the rat brain using high-field (17.6 T) magnetic resonance imaging.

Stem cell transplantation is a promising therapeutic approach for several neurological disorders. However, it has yet to fulfill its high expectations, partially due to the lack of a reliable noninvasive method for monitoring the biodistribution of the grafted stem cells in vivo. We have used high-resolution magnetic resonance imaging (MRI) at 17.6 T, combined with efficient magnetic labeling of the stem cells with iron oxide nanoparticles, in order to assess the in vivo detection limit in small animal models. Injection of different concentrations of magnetically labeled stem cells in gel phantoms led to significant reductions in image intensity from small cellular clusters of less than 10 cells. To determine the detection limit in vivo, various numbers of both labeled and unlabeled cells were injected stereotactically into the striatum of rats. Significant hypointense signal changes were observed for 100 labeled cells. After injection of approximately 20 labeled cells, signal reduction at the injection site was observed but could not be assigned unambiguously to the cells. Our results show that high-field MRI allows tracking of a minimal number of cells in vivo, well below the number used in previous studies, opening the possibility of gaining new insights into cell migration and differentiation.

Animals↗

PubMed2004

Reduction of nitrite to nitric oxide during ischemia protects against myocardial ischemia-reperfusion damage.

Nitric oxide (NO.) is thought to protect against the damaging effects of myocardial ischemia-reperfusion injury, whereas xanthine oxidoreductase (XOR) normally causes damage through the generation of reactive oxygen species. In the heart, inorganic nitrite (NO(2)(-)) has the potential to act as an endogenous store of NO., liberated specifically during ischemia. Using a detection method that we developed, we report that under ischemic conditions both rat and human homogenized myocardium and the isolated perfused rat heart (Langendorff preparation) generate NO. from NO(2)(-) in a reaction that depends on XOR activity. Functional studies of rat hearts in the Langendorff apparatus showed that nitrite (10 and 100 microM) reduced infarct size from 47.3 +/- 2.8% (mean percent of control +/- SEM) to 17.9 +/- 4.2% and 17.4 +/- 1.0%, respectively (P < 0.001), and was associated with comparable improvements in recovery of left ventricular function. This protective effect was completely blocked by the NO. scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazole-1-oxyl 3-oxide (carboxy-PTIO). In summary, the generation of NO. from NO(2)(-), by XOR, protects the myocardium from ischemia-reperfusion injury. Hence, if XOR is presented with NO(2)(-) as an alternative substrate, the resultant effects of its activity may be protective, by means of its production of NO. , rather than damaging.

Animals↗

PubMed2004

Cardiovascular fitness, cortical plasticity, and aging.

Cardiovascular fitness is thought to offset declines in cognitive performance, but little is known about the cortical mechanisms that underlie these changes in humans. Research using animal models shows that aerobic training increases cortical capillary supplies, the number of synaptic connections, and the development of new neurons. The end result is a brain that is more efficient, plastic, and adaptive, which translates into better performance in aging animals. Here, in two separate experiments, we demonstrate for the first time to our knowledge, in humans that increases in cardiovascular fitness results in increased functioning of key aspects of the attentional network of the brain during a cognitively challenging task. Specifically, highly fit (Study 1) or aerobically trained (Study 2) persons show greater task-related activity in regions of the prefrontal and parietal cortices that are involved in spatial selection and inhibitory functioning, when compared with low-fit (Study 1) or nonaerobic control (Study 2) participants. Additionally, in both studies there exist groupwise differences in activation of the anterior cingulate cortex, which is thought to monitor for conflict in the attentional system, and signal the need for adaptation in the attentional network. These data suggest that increased cardiovascular fitness can affect improvements in the plasticity of the aging human brain, and may serve to reduce both biological and cognitive senescence in humans.

Aged↗

PubMed2004

Behavioral conflict, anterior cingulate cortex, and experiment duration: implications of diverging data.

We investigated the relationship between behavioral measures of conflict and the degree of activity in the anterior cingulate cortex (ACC). We reanalyzed an existing data set that employed the Stroop task using functional magnetic resonance imaging [Milham et al., Brain Cogn 2002;49:277-296]. Although we found no changes in the behavioral measures of conflict from the first to the second half of task performance, we found a reliable reduction in the activity of the anterior cingulate cortex. This result suggests the lack of a strong relationship between behavioral measurements of conflict and anterior cingulate activity. A concomitant increase in dorsolateral prefrontal cortex activity was also found, which may reflect a tradeoff in the neural substrates involved in supporting conflict resolution, detection, or monitoring processes. A second analysis of the data revealed that the duration of an experiment can dramatically affect interpretations of the results, including the roles in which particular regions are thought to play in cognition. These results are discussed in relation to current conceptions of ACC's role in attentional control. In addition, we discuss the implication of our results with current conceptions of conflict and of its instantiation in the brain. Hum. Brain Mapping 21:96-105, 2004.

Adult↗

PubMed2004

Design of a capacitively decoupled transmit/receive NMR phased array for high field microscopy at 14.1T.

A design is presented for a "phased array" of four transmit/receive saddle-geometry volume coils for microimaging at 600 MHz within a 45 mm clear-bore vertical magnet. The small size of the coils, approximately 10 mm in length, and high frequency of operation both present considerable challenges for the design of a phased array. The particular design consists of four saddle coils, stacked vertically, in order to produce an array suitable for imaging samples, typical of many microimaging studies, with a large length:diameter ratio. Optimal coil overlap is used to reduce the mutual inductance between adjacent coils, and capacitive networks are used to maximize the isolation between all of the coils. Standard 50 Omega input impedance preamplifiers are used so that the preamplifiers do not have to be integrated directly into the probe. Isolation between coils was better than 20 dB for all coil pairs. An increase in signal-to-noise of 70 +/- 3% was achieved, averaged over the whole array, compared to a single coil of the same dimensions. High resolution phased array images are shown for ex vivo tissue samples.

Animals↗

PubMed2004

A european, multicenter, observational study to assess the value of gastric-to-end tidal PCO2 difference in predicting postoperative complications.

Automated online tonometry displays a rapid, semicontinuous measurement of gastric-to-endtidal carbon dioxide (Pr-etCO2) as an index of gastrointestinal perfusion during surgery. Its use to predict postoperative outcome has not been studied in general surgery patients. We, therefore, studied ASA physical status III-IV patients operated on for elective surgery under general anesthesia and a planned duration of >2 h in a European, multicenter study. As each center was equipped with only 1 tonometric monitor, a randomization was performed if more than one patient was eligible the same day. Patients not monitored with tonometry were assessed only for follow-up. The main outcome measure was the assessment of postoperative functional recovery delay (FRD) on day 8. Among the 290 patients studied, 34% had FRD associated with a longer hospital stay. The most common FRDs were gastrointestinal (45%), infection (39%), and respiratory (35%). In those monitored with tonometry (n = 179), maximum Pr-etCO2 proved to be the best predictor increasing the probability of FRD from 34% for all patients to 65% at a cut-off of 21 mm Hg (2.8kPa) (sensitivity 0.27, specificity 0.92, positive predictive value 64%, negative predictive value 70%). We conclude that intraoperative Pr-etCO2 measurement may be a useful prognostic index of postoperative morbidity.

Adult↗

PubMed2004

Melorheostosis involving the craniofacial skeleton.

Melorheostosis is a rare bone disorder, usually affecting the long bones and adjacent soft tissue. It was originally described by Leri and Joanny in 1922, after its classic x-ray features of flowing hyperostosis resembling dripping candle wax. There have been fewer than 10 reported cases of craniofacial involvement, and in most instances these have also involved the appendicular skeleton. The authors report a case of melorheostosis with isolated craniofacial involvement, describe the clinical course and radiologic and histologic features, and review the pertinent literature.

Aged↗

PubMed2003

The roles of changes in deoxyhemoglobin concentration and regional cerebral blood volume in the fMRI BOLD signal.

To study the behavior of cerebral physiological parameters and to further the understanding of the functional magnetic resonance imaging (fMRI) blood-oxygen-level-dependent (BOLD) effect, multisource frequency-domain near-infrared and BOLD fMRI signals were recorded simultaneously during motor functional activation in humans. From the near-infrared data information was obtained on the changes in cerebral blood volume and oxygenation. To relate our observations to changes in cerebral blood flow the well-known "balloon" model was employed. Our data showed that the deoxyhemoglobin concentration is the major factor determining the time course of the BOLD signal. The increase in cerebral blood oxygenation during functional activation is due to an increase in the velocity of blood flow, and occurs without significant swelling of the blood vessels.

Adolescent↗

PubMed2003

Design of small volume HX and triple-resonance probes for improved limits of detection in protein NMR experiments.

Three- and four-frequency nuclear magnetic-resonance probes have been designed for the study of small amounts of protein. Both "HX" (1H, X, and 2H channels) and "triple-resonance" (1H, 15N, 13C, and 2H) probes were implemented using a single transmit/receive coil and multiple-frequency impedance matching circuits. The coil used was a six-turn solenoid with an observe volume of 15 microl. A variable pitch design was used to improve the B1 homogeneity of the coil. Two-dimensional HSQC spectra of approximately 1mM single labeled 15N- and double labeled 15N/13C-proteins were acquired in experimental times of approximately 2h. Triple-resonance capability of the small-volume triple-resonance probe was demonstrated by acquiring three-dimensional HNCO spectra from the same protein samples. In addition to enabling very small quantities of protein to be used, the extremely short pulse widths (1H = 4, 15N = 4, and 13C = 2 micros) of this particular design result in low power decoupling and wide-bandwidth coverage, an important factor for the ever-higher operating frequencies used for protein NMR studies.

Carbon Isotopes↗

PubMed2003

Paying attention to emotion: an fMRI investigation of cognitive and emotional stroop tasks.

In this research, we investigated the degree to which brain systems involved in ignoring emotionally salient information differ from those involved in ignoring nonemotional information. The design allowed examination of regional brain activity, using fMRI during color-word and emotional Stroop tasks. Twelve participants indicated the color of words while ignoring word meaning in conditions in which neutral words were contrasted to emotionally negative, emotionally positive, and incongruent color words. Dorsolateral frontal lobe activity was increased by both negative and incongruent color words, indicating a common system for maintaining an attentional set in the presence of salient distractors. In posterior regions of the brain, activity depended on the nature of the information to be ignored. Ignoring color-incongruent words increased left parietal activity and decreased parahippocampal gyrus activity, whereas ignoring negative emotional words increased bilateral occipito-temporal activity and decreased amygdala activity. The results indicate that emotion and attention are intimately related via a network of regions that monitor for salient information, maintain attention on the task, suppress irrelevant information, and select appropriate responses.

Adult↗

PubMed2002

Anemia and blood transfusion in critically ill patients.

CONTEXT: Anemia is a common problem in critically ill patients admitted to intensive care units (ICUs), but the consequences of anemia on morbidity and mortality in the critically ill is poorly defined. OBJECTIVES: To prospectively define the incidence of anemia and use of red blood cell (RBC) transfusions in critically ill patients and to explore the potential benefits and risks associated with transfusion in the ICU. DESIGN: Prospective observational study conducted November 1999, with 2 components: a blood sampling study and an anemia and blood transfusion study. SETTING AND PATIENTS: The blood sampling study included 1136 patients from 145 western European ICUs, and the anemia and blood transfusion study included 3534 patients from 146 western European ICUs. Patients were followed up for 28 days or until hospital discharge, interinstitutional transfer, or death. MAIN OUTCOME MEASURES: Frequency of blood drawing and associated volume of blood drawn, collected over a 24-hour period; hemoglobin levels, transfusion rate, organ dysfunction (assessed using the Sequential Organ Failure Assessment score), and mortality, collected throughout a 2-week period. RESULTS: The mean (SD) volume per blood draw was 10.3 (6.6) mL, with an average total volume of 41.1 (39.7) mL during the 24-hour period. There was a positive correlation between organ dysfunction and the number of blood draws (r = 0.34; P<.001) and total volume drawn (r = 0.28; P<.001). The mean hemoglobin concentration at ICU admission was 11.3 (2.3) g/dL, with 29% (963/3295) having a concentration of less than 10 g/dL. The transfusion rate during the ICU period was 37.0% (1307/3534). Older patients and those with a longer ICU length of stay were more commonly transfused. Both ICU and overall mortality rates were significantly higher in patients who had vs had not received a transfusion (ICU rates: 18.5% vs 10.1%, respectively; chi(2) = 50.1; P<.001; overall rates: 29.0% vs 14.9%, respectively; chi(2) = 88.1; P<.001). For similar degrees of organ dysfunction, patients who had a transfusion had a higher mortality rate. For matched patients in the propensity analysis, the 28-day mortality was 22.7% among patients with transfusions and 17.1% among those without (P =.02); the Kaplan-Meier log-rank test confirmed this difference. CONCLUSIONS: This multicenter observational study reveals the common occurrence of anemia and the large use of blood transfusion in critically ill patients. Additionally, this epidemiologic study provides evidence of an association between transfusions and diminished organ function as well as between transfusions and mortality.

APACHE↗

PubMed2002

Attentional control in the aging brain: insights from an fMRI study of the stroop task.

Several recent studies of aging and cognition have attributed decreases in the efficiency of working memory processes to possible declines in attentional control, the mechanism(s) by which the brain attempts to limit its processing to that of task-relevant information. Here we used fMRI measures of neural activity during performance of the color-word Stroop task to compare the neural substrates of attentional control in younger (ages: 21-27 years old) and older participants (ages: 60-75 years old) during conditions of both increased competition (incongruent and congruent neutral) and increased conflict (incongruent and congruent neutral). We found evidence of age-related decreases in the responsiveness of structures thought to support attentional control (e.g., dorsolateral prefrontal and parietal cortices), suggesting possible impairments in the implementation of attentional control in older participants. Consistent with this notion, older participants exhibited more extensive activation of ventral visual processing regions (i.e., temporal cortex) and anterior inferior prefrontal cortices, reflecting a decreased ability to inhibit the processing of task-irrelevant information. Also, the anterior cingulate cortex, a region involved in evaluatory processes at the level of response (e.g., detecting potential for error), showed age-related increases in its sensitivity to the presence of competing color information. These findings are discussed in terms of newly emerging models of attentional control in the human brain.

Aged↗

PubMed2002

Assessment of beliefs in the effectiveness of acupuncture for treatment of psychiatric symptoms.

OBJECTIVES: Research has demonstrated that beliefs or expectancies can exert a powerful influence on treatment and/or drug effects. As patients participate in more complementary and/or alternative treatments for psychiatric conditions, it is important to assess the role of belief or expectancy on response to nontraditional treatment approaches. The Acupuncture Beliefs Scale was developed to assess belief in the efficacy of acupuncture for both physical and psychiatric symptoms and conditions. Development and psychometric properties of the scale are described. DESIGN AND SUBJECTS: Research personnel solicited statements regarding the potential experience and effects of acupuncture. These items were collapsed into a set of 36 items, with some rotated to avoid response bias. Outpatients diagnosed with bipolar disorder and undergraduates completed the scale (n = 118). RESULTS: The scale yielded excellent internal consistency (coefficient alpha = 0.97), and item-total score correlations between 0.37 and 0.83. Principal component analysis with a varimax rotation revealed three significant and meaningful factors that were consistent across both subject groups. Factors appeared to capture general endorsement of acupuncture treatment, beliefs in the scientific value and credibility of acupuncture treatment, and beliefs about the procedures and physical experience of acupuncture. CONCLUSIONS: The Acupuncture Beliefs Scale is a 36-item self-report scale that may be useful for measurement of beliefs in the effectiveness of acupuncture treatment.

Acupuncture Therapy↗