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Biomedical subjects

P Knight

Publications and source records attributed to P Knight.

At least 37 records · Page 2Linked to original sources

Assessing selfcare status in quadriplegia: comparison of the quadriplegia index of function (QIF) and the functional independence measure (FIM).

The purpose of this study was to compare the quadriplegia index of function (QIF) to the functional independence measure (FIM) in assessing the daily performance of selfcare activities by individuals with cervical spinal cord injury. This study evaluated feeding, grooming and bathing activities in 22 C4-C7, Frankel A-D spinal cord injury patients between 3 and 12 months postinjury. The manual muscle test (MMT) was performed on 17 of these subjects during the same window of time as the QIF and the FIM. An upper extremity motor score (UEMS) was derived from the MMT. In order to relate motor power to functional ability, the UEMS was used as a measure of neurological function to test the hypothesis that the QIF scores are more highly correlated to motor power than are the FIM scores for this population. Spearman coefficients were calculated to correlate the QIF, the FIM and the UEMS. For the bathing and grooming categories, both the QIF and the FIM showed significant and similar correlations to the UEMS. For the feeding category, however, the QIF had a significantly better correlation to the UEMS than did the FIM (Rho = 0.90 vs 0.53, p < 0.01). Use of the QIF feeding scale may allow the detection of changes in function as individuals recover that the FIM scale would miss. Further evaluation of the remaining selfcare and mobility scales is needed. Modification of the FIM with more sensitive portions of the QIF would improve the discriminative ability of outcome studies and program evaluations.

Adolescent↗

Comparison of intravenous and intranasal administration of epinephrine during CPR in a canine model.

STUDY OBJECTIVES: Epinephrine improves coronary perfusion pressure during CPR. However, administration of epinephrine during CPR may be delayed or omitted if IV or endotracheal access is not established. Therefore, the objective of this study was to determine if intranasal administration of epinephrine during CPR would provide an alternate route of drug administration that is readily accessible and requires no special technical skills. DESIGN AND SETTING: Randomized blinded study performed in a controlled laboratory environment. TYPE OF PARTICIPANTS: Twenty mongrel dogs weighing 19.5 +/- 4.6 kg. INTERVENTIONS: All dogs received either IV epinephrine 0.015 mg/kg or intranasal epinephrine 14 mg per nostril. Phentolamine (5 mg per nostril) was administered intranasally one minute before nasal administration of epinephrine to improve absorption. Each dog underwent three minutes of ventricular fibrillation followed by seven minutes of CPR with a pneumatic chest compression device. Epinephrine was administered at two minutes into CPR. MEASUREMENTS AND MAIN RESULTS: Seven dogs were excluded because of inadequate baseline coronary perfusion pressure or compression device displacement, leaving a total of 13 dogs for analysis (six IV epinephrine, seven intranasal epinephrine). Baseline coronary perfusion pressure (mean +/- SD) was similar for IV epinephrine and intranasal epinephrine (16.9 +/- 7.1 mm Hg versus 18.2 +/- 13.8 mm Hg, respectively, P = .84). For IV and intranasal epinephrine, coronary perfusion pressure increased to 21.4 +/- 9.2 mm Hg and 24.4 +/- 18.7 mm Hg one minute after epinephrine, respectively (P = .73). Five minutes after epinephrine coronary perfusion pressure was 18.2 +/- 8.7 mm Hg and 24.3 +/- 13.9 mm Hg for IV epinephrine and intranasal epinephrine, respectively (P = .38). The rate of successful resuscitation was similar for both groups, five of seven dogs for intranasal epinephrine and four of six dogs for IV epinephrine (P = .66). CONCLUSION: Intranasal epinephrine has similar effects on coronary perfusion pressure and resuscitation compared with standard-dose IV epinephrine. Therefore, the nasal route for administration of epinephrine appears to be an acceptable alternate method of drug delivery during CPR and compares favorably with standard IV therapy in the canine model. Because of the obvious benefits to human patients, these observations suggest further investigation.

Administration, Intranasal↗

Evidence that nebulin is a protein-ruler in muscle thin filaments.

Partial amino acid sequence was obtained from the massive myofibrillar protein nebulin. This consists of repeating motifs of about 35 residues and super-repeats of 7 x 35 = 245 residues. The repeat-motifs are likely to be largely alpha-helical and to interact with both actin and tropomyosin in thin filaments. Nebulin from different species was found to vary in size in proportion to filament length. The data are consistent with the proposal that nebulin acts as a protein-ruler to regulate precise thin filament assembly.

Actin Cytoskeleton↗

Modification of myofibrils by fluorophore-induced photo-oxidation.

The excitation of fluorophores in the vicinity of a myofibril stops both shortening in the presence of ATP and Ca2+, and the extraction of the A-band by NaCl in the presence of Mg pyrophosphate. Shortening is more quickly affected than extraction. These effects can be induced by fluorescently-tagged antibodies bound in the A-band. Both depolymerization of the thick filament and the interaction between the myosin head and actin appear to be modified. Enzymatic lowering of the oxygen concentration in the bathing solution during excitation reduces these effects, indicating that they are due to photo-oxidation catalysed by excitation of the fluorophore. The results suggest that care needs to be exercised to minimize the consequences of these changes on the outcome of fluorescence-based assays of activity. Irradiated myofibrils that do not shorten, hydrolyse ATP at a rate comparable to those that contract, so they may be useful as a model system for the study of crossbridge activity in the ordered array of proteins of the myofibril.

Actins↗

Permanent junctional reciprocating tachycardia misdiagnosed as 'cardiomyopathy'.

In a nine-year-old female, cardiac failure was erroneously attributed to idiopathic cardiomyopathy and cardiac transplantation was planned. The actual cause of cardiac failure was permanent junctional reciprocating tachycardia (PJRT), a rare form of supraventricular tachycardia. The diagnostic error was discovered before transplantation was performed and the arrhythmia was treated surgically. This resulted in return of near normal cardiac function.

Cardiomyopathies↗

Effects of position changes on transcutaneous carbon dioxide tension in neonates with respiratory distress.

Routine neonatal care includes frequent position changes. Recent research has concluded that positions other than supine may result in beneficial physiologic responses. Specifically, several studies suggest that neonates may ventilate more effectively in a prone rather than in a supine position. This study tested the hypothesis that transcutaneous carbon dioxide tension (TcPCO2) would be lower in the prone than in the supine position in neonates with respiratory distress. Fourteen ventilated infants were studied. TcPCO2 was measured and recorded in prone, supine, and right-side-lying positions for each subject. There were no statistically significant differences in mean TcPCO2 values between the three positions (F = .45; df 2,39; P = .64). The relationship between TcPCO2 and PaCO2 values was stable (r = .88) during the studies. The results indicate that changing a neonate's position does not significantly alter transcutaneous carbon dioxide tension.

Blood Gas Monitoring, Transcutaneous↗

Control of infection due to Klebsiella pneumoniae in an intensive care nursery.

Because of an increased incidence of necrotizing enterocolitis (NEC) temporally related to Klebsiella pneumoniae colonization noted in several infants, a study was undertaken to identify the source and to eradicate the infection. Twenty infants in the neonatal intensive care unit (NICU) and 51 in the well-baby nursery were prospectively studied. Cultures were done on all infants. In addition, cultures were done on all employees and parents who regularly visited. Our results showed an increased incidence of infection during this period--8.3% as compared with 4.79% overall. Colonization with K pneumoniae was eradicated, at least temporarily, by establishing a cohort system in both the NICU and the well-baby nursery and by the administration of antibiotics to all infants in these nurseries. Colonized parents and employees were also treated. Follow-up cultures showed clearing of Klebsiella, and the cohort system was abolished. Serotyping of all affected infants later showed that different strains were present, making it unlikely that there was a common source for the Klebsiella. (Initially the source of infection had been thought to be a mother whose premature triplets were colonized. We feel that the eradication of this organism and the subsequent decline in NEC was enhanced by the combination of cohorting and handwashing. The selected use of antibiotics may have prevented an extension of the outbreak, but this could not be proven.

Alabama↗

Negative staining of myosin molecules.

A reproducible method has been developed for the negative staining of myosin molecules. The dimensions of stained molecules are in close agreement with those obtained by metal shadowing. Sharp bends in the tail, indicative of hinge regions, were observed at two positions 44 nm and 76 nm from the head-tail junction. The tail was often ill-defined at the position of the first (44 nm) bend. The bend positions may be sites of proteolytic cleavage that result in the production of long and short myosin subfragment S2. About half the molecules exhibited bending to various degrees at one or both of these positions, but cases where the tail folded back on itself in a 180 degrees bend were comparatively rare (approximately equal to 10%). However, in the absence of EGTA, a large fraction of the molecules (approximately equal to 80%) exhibited 180 degrees bends. A small region, approximately 20 nm long, at the tip of the tail often appears to be significantly different from the rest. The heads are about 19 nm long and roughly pear-shaped. Although sometimes straight, more often they show a pronounced curvature. Both senses of curvature were observed, but those curved in a clockwise manner were the most common, indicating preferential binding of one side of the head to the carbon substrate. An analysis of the different combinations of head shapes in individual molecules indicates that each head can rotate independently around its long axis. No preferred angle of orientation between the two heads in a molecule, or between either head and the tail could be found. Substructure has been observed within the heads.

Animals↗

Purification and properties of native titin.

A procedure has been developed for the extraction and purification of the massive myofibrillar protein titin without exposing it to denaturing conditions. The form of the molecule that has been isolated is soluble at high ionic strength and alkaline pH, but precipitates in low salt or at pH values below 7. Sedimentation velocity experiments indicate that titin is a highly asymmetric molecule with a sedimentation coefficient of 13.4 S. This asymmetry is confirmed by electron microscopy of rotary-shadowed specimens, which shows string-like structures of diameter 40 A and lengths up to 8000 A. Significant differences were observed depending on whether the electron microscope specimens were prepared by spraying or by layering of the titin onto a mica substrate; we tentatively attribute these differences to elasticity in the titin, revealed by the high shearing forces that accompany spraying. In accord with this, the circular dichroism spectrum of titin indicates that its secondary structure is largely random coil, a conformation characteristic of elastic proteins such as elastin. Negative staining of titin again shows long string-like structures, but these can now be seen to have an appearance similar to a string of beads, where the spacing between successive beads is about 40 A. Very similar beaded strings have been observed also associated with negatively stained separated native thick filaments; these are found running alongside the cross-bridge regions and in coils near the filament ends. Since the periodicity of the strings is similar to that of end-filaments, recently identified structures at the tips of thick filaments, it is likely that end-filaments are formed from titin. Titin comprises approximately 9% of the myofibrillar mass, which means that it is the third most abundant protein in muscle. The possible role of titin in forming elastic filaments within myofibrils is discussed.

Animals↗

Structure of the myosin projections on native thick filaments from vertebrate skeletal muscle.

Rabbit psoas muscle filaments, isolated in relaxing buffer from non-glycerinated muscle, have been applied to hydrophilic carbon films and stained with uranyl acetate. Electron micrographs were obtained under low-dose conditions to minimize specimen damage. Surrounding the filament backbone, except in the bare zone, is a fringe of clearly identifiable myosin heads. Frequently, both heads of individual myosin molecules are seen, and sometimes a section of the tail can be seen connecting the heads to the backbone. About half the expected number of heads can be counted, and they are uniformly distributed along the filament. The majority of heads appear curved. The remainder could be curved heads viewed from another aspect. Three times as many heads curve in a clockwise sense than in an anticlockwise sense, suggesting a preferential binding of one side of the head to the carbon film. The two heads of myosin molecules exhibit all the possible combinations of clockwise, anticlockwise and straight heads, and analysis of their relative frequencies suggests that the heads rotate freely and independently. The heads also adopt a wide range of angles of attachment to the tail. The lengths of heads cover a range of 14 to 26 nm, with a peak at 19 nm. The average maximum width is 6.5 nm. Both measurements are in excellent agreement with values for shadowed molecules. Since our data are from heads adsorbed to the film in relaxing conditions and the shadowed molecules were free of nucleotide, gross shape changes are not likely to be produced by nucleotide binding. The length of the link between the heads and the backbone was found to vary between 10 nm and 52 nm, with a broad peak at about 25 nm. Thus, the hinge point detected in the tail of isolated molecules was not usually the point from which the crossbridges swung out from the filament surface. The angle made by the link to the filament axis was between 20 degrees and 80 degrees, with a broad maximum around 45 degrees. These lengths and angles concur with our observation of an average limit of the crossbridges from the filament surface of 30 nm. This is sufficient to enable heads in the myofibril lattice to reach out beyond the nearest thin filament and should allow considerable flexibility for stereospecific binding to actin in active muscle.

Animals↗

Delayed, distant arterial injury after brachial artery catheterization.

The occurrence of iatrogenic arterial injury secondary to catheterization for angiographic studies has been well documented in the literature for over a decade. It has been well established that patients should be carefully evaluated post-catheterization and if absence of the pulse distal to the arteriotomy site is discovered, most should undergo exploration for identification and correction of the problem. Between 0.3 and 24% of patients undergoing brachial artery catheterization have been found to have a diminished or absent radial pulse after the procedure. In the vast majority of cases the problem has been solved by local exploration of the arteriotomy site. However, in a small but definite number of cases late thrombotic complications have become manifest, and in two cases reported in 1981 and in the case report to follow, thrombotic complications have become manifest months later, secondary to injury well proximal to the arteriotomy site.

Brachial Artery↗