Regular balloon inflation for patients with chronic bronchitis: a randomised controlled trial.
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Aged↗
Biomedical subjects
L Gray
Publications and source records attributed to L Gray.
Phase III clinical evaluation of gadoteridol injection: experience in pediatric neuro-oncologic MR imaging.
Twenty-two pediatric patients with known CNS neoplasms underwent magnetic resonance (MR) imaging before and after intravenous injection of 0.1 mmol/kg gadoteridol injection as part of a Phase IIIB open label multicenter clinical trial. Intravenous administration of this neutral, nonionic contrast agent was found to be safe in children. No clinically relevant changes in vital signs or laboratory values (including complete blood count, blood chemistry, serum electrolytes, thyroid and metabolic panel and clotting function) were attributed to the administration of gadoteridol injection. There were no systemic complaints. The imaging characteristics of gadoteridol in pediatric CNS disease appeared similar to those of gadopentetate dimeglumine. Contrast enhancement was present in 17 of 22 patients (77%). The administration of gadoteridol injection provided additional clinically relevant information including improved visualization and delineation of the primary lesion, detection of additional lesions, determination of tumor recurrence and narrowing the list of differential considerations in all 17 enhancing studies as well as in 2 of 5 studies without signal intensity enhancement. The very low toxicity, inherent to this nonionic low osmolal paramagnetic contrast formulation may allow administration of increased doses at increased infusion rates for an increased number of indications with improved sensitivity.
Adolescent↗
Aspiration after stroke: lesion analysis by brain MRI.
Aspiration is a common problem following stroke, resulting in feeding difficulties and aspiration pneumonia. Despite past studies using clinical assessments and computed tomographic (CT) scans of the head, the correlation of stroke location with aspiration remains unclear. Since brain magnetic resonance imaging is more sensitive than CT for many stroke types, we have correlated MRI lesions with aspiration in patients who have sustained a stroke. We selected patients with acute stroke who underwent brain MRI and a swallowing evaluation. Aspiration was present in 21 of 38 patients (55%). Patients with just small vessel infarcts had a significantly lower occurrence of aspiration (3 of 14, 21%) compared to those with both large- and small-vessel infarcts (15 of 20, 75%, p = 0.002). Multivariate analysis of several specific brain areas failed to identify a significant association between stroke location and the occurrence of aspiration. These findings suggest that patients who have experienced stroke should be individually evaluated for swallowing dysfunction regardless of stroke location or size, since even small-vessel strokes can be associated with aspiration in greater than 20% of cases.
Adult↗
Multidimensional scaling of head and neck metastases.
A mathematical analysis, called multidimensional scaling, was applied to two sets of data on metastases from head and neck cancers. The analysis places lymph nodes in an imaginary space (here termed a 'nodalgram') such that distances between nodal clusters are proportional to differences in the occurrence of tumor metastases. Two-dimensional scaling explains 93% of the variance in clinical data from 1008 patients and 91% of the variance in pathological data from a different set of 415 patients. These independent results are closely correlated, and both explain vastly more of the data than expected by chance. The dimensions of the nodalgram are not related to anatomical coordinates of the nodes, suggesting that a representation of these structures in an abstract space explains the spread of cancers better than an analysis of spread in real space. Surprisingly, a plot of the extent to which metastases from different primary sites spread along the nodalgram dimensions is closely related to the normal anatomical locations of the primaries. This shows that although the nodalgram may be difficult to interpret, it must have some biological significance. In conclusion, multidimensional scaling successfully quantifies a pattern in the spread of head and neck cancers.
Algorithms↗
An auditory psychometric function from newborn chicks.
This study shows how the hearing of newborn chicks can be quantified with receiver operating characteristics (ROCs). A detailed auditory psychometric function was constructed from areas under ROCs, derived from delays in ongoing vocalizations elicited by pulsing pure tones. Over 20,000 delays were analyzed from 160 birds tested at four frequencies (0.25-2 kHz), eight intensities (-3 to 18 dB above estimated threshold), and two ages (0 and 4 days posthatch). Areas under these ROCs increase in an S-shaped function over intensity, as expected. Maximum responsiveness at approximately 75% correct shows that these neonates never achieve the near-perfect performance of mature listeners. Thresholds appear best estimated by the level required for 65% correct. Results replicate previous findings, showing that thresholds mature at low frequencies before high. Although there is no simple way to alleviate decreasing responsiveness caused by habituation over trials, improved performance results from presenting different frequencies, but only in the younger birds, and primarily with louder stimuli.
Animals↗
Absorption and lymphatic transport of peroxidized lipids by rat small intestine in vivo: role of mucosal GSH.
The absorption and lymphatic transport of peroxidized MaxEPA fish oil was studied using the lymph fistula rat to determine the role of mucosal glutathione (GSH) in intestinal metabolism of luminal lipid hydroperoxides. Decreasing intestinal GSH concentrations with buthionine sulfoximine (BSO, 1.15 +/- 0.20 nmol/g), diethyl maleate (DEM, 0.93 +/- 0.26 nmol/g), phorone (1.46 +/- 0.14 nmol/g), or 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU, 1.54 +/- 0.18 nmol/g) compared with control (2.60 +/- 0.38 nmol/g) resulted in higher luminal recovery of the infused lipid hydroperoxide (% of infused dose): BSO (87.8 +/- 4.8%), DEM (86.1 +/- 1.3%), phorone (78.1 +/- 2.1%), and BCNU (71.7 +/- 4.8%) compared with control (52.8 +/- 4.3%). These results suggest that decreased elimination of luminal peroxidized lipids is associated with decreased tissue GSH. Treatment of rats with BSO, DEM, phorone, or BCNU resulted in dramatic increases in appearance of peroxidized lipids in lymph over 6-h lipid infusion (54.7 +/- 3.7, 57.7 +/- 4.6, 46.4 +/- 2.7, and 42.1 +/- 3.9 nmol, respectively) compared with control (20.5 +/- 3.4 nmol). The results are consistent with decreased intracellular metabolism of absorbed hydroperoxides and enhanced transport into lymph under GSH-deficient conditions. The current findings suggest that the function of the mucosal GSH peroxidase/oxidized glutathione (GSSG) reductase system may play an important role in intestinal handling of luminal lipid hydroperoxides. A compromised function of this detoxication mechanism in GSH-deficient states can significantly alter the metabolic fate of dietary peroxidized lipids.
Absorption↗
An investigation of the relationship between free radical activity and vitamin C metabolism in elderly diabetic subjects with retinopathy.
Abnormalities of both free radical activity and ascorbic acid metabolism have been documented in diabetes, but their biological basis is unclear and their relationship unstudied in any detail. This study was designed to compare changes in antioxidant status and free radical reactions in a group of elderly diabetic patients (with and without retinopathy) with those in a group of age-matched control subjects. No significant differences in thiobarbituric acid (TBA) reactivity, red cell glutathione (GSH) concentrations or diene conjugates (DC) between patients and controls were seen despite significant depletion of ascorbic acid in patients with diabetes, especially in those with retinopathy. The results emphasise the present-day difficulties of measuring free radical activity and demonstrate a marked abnormality in ascorbic acid metabolism in diabetes.
Aged↗
Stroke with negative brain magnetic resonance imaging.
BACKGROUND AND PURPOSE: Magnetic resonance imaging (MRI) of the brain is replacing computed tomography in the diagnostic evaluation of acute ischemic strokes. Past studies have suggested that MRI may not visualize all acute strokes, but few clinical details were included. To better understand the clinical characteristics of strokes not detected by MRI, we collected and reviewed case histories of several patients with acute stroke who had negative MRI scans. METHODS: Patients with a clinical diagnosis of stroke and negative brain MRI scans were ascertained from hospital records dating from 1989 to mid-1991. Patients with transient ischemic attacks, postictal paralysis, functional examinations, central nervous system infections, other nonstroke diagnoses, or equivocal findings were excluded. The MRI scans were performed with a GE Signa 1.5-T magnet in an axial plane (spin-echo repetition time/echo time: 500 msec/20 msec; 2,500 msec, 30 msec/80 msec). One patient received contrast material. RESULTS: We identified seven patients with clinically diagnosed ischemic stroke and negative brain MRI scan. Six of seven patients were scanned within 7 days of symptom onset and two patients within 24 hours. One patient was scanned 3 months after symptom onset. The strokes not detected by MRI were clinically localized to the cortex (n = 3), brain stem (n = 3), and subcortical/lacunar area (n = 1). One patient underwent two MRI scans, one with gadolinium. CONCLUSIONS: These cases, while selected, illustrate some potential limitations of MRI for diagnosing stroke.
Aged↗
The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part III. Reliability of a standardized MRI evaluation of Alzheimer's disease.
The Consortium to Establish a Registry for Alzheimer's Disease (CERAD) has developed procedures for standardized imaging and reporting of magnetic resonance (MR) findings in Alzheimer's disease (AD) for use by neuroradiologists in multiple medical centers using a variety of MR equipment and field strengths. After initial pretesting, we revised the protocol, expanded the summary rating scale to seven points, and added more illustrations. Fourteen participating neuroradiologists evaluated 28 MR scans of elderly patients, giving us the basis for judging interrater agreement. We obtained acceptable intraclass correlations (greater than 0.79) for rating the size of the lateral and third ventricles and the temporal horn. Less satisfactory intraclass correlations occurred when rating other areas, including (1) global atrophy of the brain (0.70); (2) dilatation of the sulci of the temporal lobe (0.66); (3) frequency, location, and severity of white matter lesions (0.77); (4) sylvian fissure enlargement (0.70); and (5) cerebral sulcal dilatation (0.64). We also saw considerable variation in the reporting of cortical and lacunar infarcts. Despite careful design of the rating methodology and readings by experienced neuroradiologists, we did not find satisfactory interrater agreement for interpreting MR findings in elderly subjects. These findings may explain the difficulties encountered in applying similar subjective rating techniques that meet with success at one institution to multicenter studies. More objective and reproducible procedures are needed for interpretation of neuroimaging findings of AD in multicenter studies.
Alzheimer Disease↗
The paperless essay: one way to teach writing and computer skills in medical school.
We designed an assignment for first-year medical students that included instruction in writing and in computer use, two important subjects that are usually neglected in the traditional curriculum. As part of a neuroscience course, students wrote an essay using a word processor and submitted it to the instructor via the campus computer network. If requested by the instructor, the students submitted a revision of their essays without a grade penalty. As a result of completing the assignment, students learned the importance of revision and were stimulated to learn more about computers. With only slight modification of medical school courses, faculty can place more emphasis on writing skills and computer literacy.
Computer Literacy↗
Adenylate cyclase toxin from Bordetella pertussis. Conformational change associated with toxin activity.
Adenylate cyclase (AC) toxin from Bordetella pertussis interacts with and enters eukaryotic cells to catalyze the production of supraphysiologic levels of cyclic AMP. Although the calmodulin-activated enzymatic activity (ability to convert ATP to cyclic AMP in a cell-free assay) of this molecule is calcium independent, its toxin activity (ability to increase cyclic AMP levels in intact target cells) requires extracellular calcium. Toxin activity as a function of calcium concentration is biphasic, with no intoxication occurring in the absence of calcium, low level intoxication (200-300 pmol of cyclic AMP/mg of Jurkat cell protein) occurring with free calcium concentrations between 100 nM and 100 microM and a 10-fold increase in AC toxin activity at free calcium concentrations above 300 microM. The molecule exhibits a conformational change when free calcium concentrations exceed 100 microM as demonstrated by shift in intrinsic tryptophan fluorescence, an alteration in binding of one anti-AC monoclonal antibody, protection of a fragment from trypsin-mediated proteolysis, and a structural modification as illustrated by electron microscopy. Thus, it appears that an increase in the ambient calcium concentration to a critical point and the ensuing interaction of the toxin with calcium induces a conformational change which is necessary for its insertion into the target cell and for delivery of its catalytic domain to the cell interior.
Adenylate Cyclase Toxin↗
Disturbed handling of ascorbic acid in diabetic patients with and without microangiopathy during high dose ascorbate supplementation.
Abnormalities of ascorbic acid metabolism have been reported in experimentally-induced diabetes and in diabetic patients. Ascorbate is a powerful antioxidant, a cofactor in collagen biosynthesis, and affects platelet activation, prostaglandin synthesis and the polyol pathway. This suggests a possible close interrelationship between ascorbic acid metabolism and pathways known to be influenced by diabetes. We determined serum ascorbic acid and its metabolite, dehydroascorbic acid, as indices of antioxidant status, and the ratio, dehydroascorbate/ascorbate, as an index of oxidative stress, in 20 matched diabetic patients with and 20 without microangiopathy and in 22 age-matched control subjects. Each study subject then took ascorbic acid, 1 g daily orally, for six weeks with repeat measurements taken at three and six weeks. At baseline, patients with microangiopathy had lower ascorbic acid concentrations than those without microangiopathy and control subjects (42.1 +/- 19.3 vs 55.6 +/- 20.0, p less than 0.01, vs 82.9 +/- 30.9 mumol/l, p less than 0.001) and elevated dehydroascorbate/ascorbate ratios (0.87 +/- 0.46 vs 0.61 +/- 0.26, p less than 0.01, vs 0.38 +/- 0.14, p less than 0.001). At three weeks, ascorbate concentrations rose in all groups (p less than 0.0001) and was maintained in control subjects (151.5 +/- 56.3 mumol/l), but fell in both diabetic groups by six weeks (p less than 0.01). Dehydroascorbate/ascorbate ratios fell in all groups at three weeks (p less than 0.0001) but rose again in the diabetic groups by six weeks (p less than 0.001) and was unchanged in the control subjects. Dehydroascorbate concentrations rose significantly from baseline in all groups by six weeks of ascorbic acid supplementation (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Administration, Oral↗
Rapid development of a sensory attribute in young chickens.
Development of a consistent pattern in responses to frequency changes is revealed with individual differences scaling. Newborn chicks respond to changes in a background tone to which they have become habituated with momentary delays in their otherwise regular peeping. Durations of these delays are used as measures of perceived difference between all possible pairs of five frequencies between 500 and 608 Hz. Coordinates of five points are calculated to create a map of these frequencies such that distances between points are maximally correlated with delays. A steeply sloped s-shaped curve describes the rapid emergence, from the beginning to the middle of the first postnatal day, of maps that explain significantly more of the input data than expected by chance. This implies that over a few hours birds come to reliably rank different frequencies along a consistent scale. Controlled rearing conditions of decreased external stimulation or early exposure to frequency changes have no effect on this development. In conclusion, scaling is a replicable way to evaluate the development of consistent responses to frequency changes. Similar processes are likely important in other aspects of perceptual development, learning, and memory.
Acoustic Stimulation↗
Development of a frequency dimension in chickens (Gallus gallus).
Multidimensional scaling is used to examine the consistency of neonates' responses to frequency changes. Chickens at 0 and 4 days of age were presented with all possible transitions between pairs of five pure tones at 500, 525, 551, 578, and 608 Hz. Subjects were habituated to one stimulus, and the duration of an unconditioned delay in their otherwise ongoing peeps was measured after the frequency of the stimulus was changed. Durations of these delays can be used as measures of how different animals perceive two frequencies to be. Scaling solutions show that a nonrandom, adult-like ordering of frequencies emerges between 0 and 4 days of age.
Age Factors↗
The role of torsion in cervical spine trauma.
A dynamic servocontrolled torsion machine has been used to characterize cervical injury due to pure rotation of the head. Resultant force moment, torque, and applied rotation have been measured. Torque applied to the base of the skull resulted in injury to the atlantoaxial joint. No evidence of lower cervical injury was observed by computed tomography, magnetic resonance imaging, in situ fluoroscopy, or visual inspection. Torque applied directly to the lower cervical spine induced ligamentous injury and unilateral facet dislocation; however, the torque to injure the lower cervical spine was significantly greater than the torque to injure the atlantoaxial joint. It was concluded that pure rotation of the head does not mediate lower cervical ligamentous injury because of the comparative weakness of the atlantoaxial joint.
Aged↗
Reduced osmotic thirst in healthy elderly men.
In response to water deprivation or heat stress, healthy elderly men experience reduced thirst compared with a young control group. Because water deprivation and heat stress produce hypertonicity as well as reduced extracellular fluid volume, the aim of this study was to determine whether the elderly also experience reduced thirst in response to hypertonicity without extracellular fluid volume depletion. To achieve this, after an overnight fast, healthy community-dwelling nonsmoking old (65-78 yr, n = 7) and young (20-32 yr, n = 7) men received 120-min hypertonic (0.855 M) and isotonic (0.154 M) saline infusions (0.06 ml.min-1.kg-1) in double-blind randomized order at least 2 wk apart. Both groups had increased thirst (P less than 0.001) and water intake (P less than 0.05) after the hypertonic saline infusion compared with the isotonic saline infusion. However, despite similar plasma sodium increases and less plasma volume expansion during the hypertonic saline infusion compared with the young group, the old group was less thirsty (P less than 0.01) and drank less room-temperature tap water (young 11.1 +/- 1.2 ml/kg, old 3.9 +/- 0.6 ml/kg, P less than 0.001). This reduced thirst in the old group seemed to be mainly due to a lower thirst sensitivity (P less than 0.05) to hypertonicity, although there was also a tendency toward an increased thirst threshold. Plasma arginine vasopressin increases were similar for the old and young groups with hypertonic saline, without significant changes during the isotonic saline infusion in either group.
Adult↗
Synthesis and secretion of high- and low-molecular-weight forms of the enzyme-releasing peptide (ERP) from the macrophage-like cell line THP-1.
Neutrophil enzymes have been implicated as a source of lung injury in patients with the adult respiratory distress syndrome (ARDS) and with emphysema. We studied a human alveolar macrophage-derived peptide messenger, the enzyme-releasing peptide (ERP), which causes neutrophils to secrete their enzymes. The secretion and synthesis of ERP was studied in human alveolar macrophages and in the macrophage-like cell lines THP-1, HL-60, and U937. All four cell types secrete an ERP-like peptide. THP-1 cells secrete a higher concentration of the peptide than do macrophages. The secretion of ERP by THP-1 is suppressed by the protein synthesis inhibitors actinomycin D and cycloheximide. While the macrophages secrete ERP, they do not synthesize it. These studies suggest that ERP is synthesized by an alveolar macrophage precursor and stored in the mature macrophage for later release. 12-O-tetradecanoylphorbol-13-acetate (TPA) suppresses ERP secretion by THP-1 cells, but it does not modify secretion in macrophages. Escherichia coli-derived lipopolysaccharide and dimethyl sulfoxide do not modify secretion in either cell type. The THP-1 cells secrete a high- and low-mass-ratio (Mr) form of ERP-like proteins. The low Mr but not the high Mr form stimulates neutrophils to secrete their granule enzymes. We conclude that human alveolar macrophages secrete ERP but do not synthesize it. It is likely that ERP is made by an alveolar macrophage precursor in a high Mr form that is cleaved prior to secretion by the macrophages.
Antibodies, Monoclonal↗
Central auditory processing disorder: a case study.
We carried out extensive audiologic, electrophysiologic, and neuropsychologic testing on a young woman who complained that she had difficulty hearing in her educational environment. Conventional audiometric results, including pure-tone, speech, and immittance audiometry, were all within normal limits. The subject performed normally on tests involving the processing of rapidly changing temporal information, interaural time and intensity difference detection, and both absolute and relative sound localization. Early, middle, late and task-related auditory evoked potentials were essentially normal, although some asymmetry was observed in the middle latency (MLR) and late (LVR) responses. There was, however, a consistent left-ear deficit on dichotic sentence identification, on threshold and suprathreshold speech measures in the left sound field when various types of competition were delivered in the right sound field, and on cued-target identification in the left sound field in the presence of multitalker babble. Results suggest a central auditory processing disorder characterized by an asymmetric problem in the processing of binaural, noncoherent signals in auditory space. When auditory space was structured such that the target was directed to the left ear, and the competition to the right ear, unwanted background was less successfully suppressed than when the physical arrangement was reversed.
Acoustic Impedance Tests↗