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Biomedical subjects

K Hutchinson

Publications and source records attributed to K Hutchinson.

At least 19 recordsLinked to original sources

A comparison of spinal quantitative computed tomography with dual energy X-ray absorptiometry in European women with vertebral and nonvertebral fractures.

Quantitative computed tomography (QCT) was compared to dual X-ray absorptiometry (DXA) measured in the lumbar spine of 508 European women defined as normal without fracture (NoF), or osteoporotic (OP), with either vertebral fracture (VF), or peripheral fracture (PF). The correlations between QCT and DXA BMD measurements were significantly different in normal and in osteoporotic patients, indicating that the two exams do not measure the same bone aspects. According to ROC curves results, QCT Z-scores separate OP from NoF with better sensitivity than all other measurements. A threshold to differentiate OP from NoF was chosen at Z-score = -1 for DXA-BMD and -1.5 for QCT-BMD. VF patients showed a highly significant decrease in BMD by DXA or QCT. PF patients revealed measurements lower than those of normal subjects but greater than those of VF, calling into question the idea of a diffuse osteoporosis causing nonvertebral fractures that is measurable by spinal DXA or QCT. DXA is weakly dependent upon age, and T-score or Z-score are equivalent for evaluating osteoporosis. QCT depends greatly upon age, and Z-score appears to be more efficient.

Absorptiometry, Photon↗

Recurrent ischemic strokes in a patient with Medtronic-Hall prosthetic aortic valve and valve strands.

Fine strands associated with prosthetic heart valves have been demonstrated with transesophageal echocardiography, but the pathologic identity of these strands is unclear. A case of a man with a prosthetic aortic Medtronic-Hall valve with prominent valve strands and recurrent strokes is discussed. The patient underwent valve replacement surgery, and histopathologic examination of the strands identified them as Lambl's excrescences.

Aortic Valve↗

Immunoglobulin G crystalline keratopathy associated with monoclonal gammopathy.

PURPOSE: Two cases of corneal crystal deposition are reported, both caused by a benign monoclonal gammopathy METHODS: Similar corneal pathology is identified in these two patients, both of whom presented with visual acuities of 6/6 or better Consideration of possible causes involved biochemical and haematological testing and assessment. RESULTS: Potential for malignant transformation of monoclonal gammopathy was recognized, hence the need for ongoing haematological follow-up. CONCLUSION: Corneal crystals may be the initial presentation in a patient with monoclonal gammopathy, a rare, but significant, clinical finding.

Blood Sedimentation↗

Morphine and dextrorphan lose antinociceptive activity but exhibit an antispastic action in chronic spinal rats.

Within 3-4 weeks after spinal transection, morphine-induced antinociception, assessed with the tail flick reflex in rats, is profoundly reduced. The cause of this decrement is unknown. The present studies were conducted to determine whether this phenomenon reflects a general loss in opiate activity or a selective decline in opiate antinociception. This was accomplished by assessing the effect of morphine on two different responses, the tail flick reflex and the hindlimb spasticity that develops in chronic spinal rats. Because excitatory amino acid antagonists are also antinociceptive in acute spinal rats, the effect of one such drug, dextrorphan, on these two behaviors was also evaluated in chronic spinal animals. The antinociceptive and antispastic effect of subcutaneous (6 mg/kg) and intrathecal (5 micrograms) morphine injections were assessed in intact and chronic (21-28 days) spinal rats, whereas the effect of subcutaneous (25 and 40 mg/kg) and intrathecal (350 micrograms) dextrorphan was assessed in acute (1 day) and chronic spinal rats. The antinociceptive effect of both drugs was significantly reduced in chronic spinal animals, relative to saline controls. However, each drug treatment produced a significant antispastic effect in the same animals, indicating a selective decline in opiate action. This outcome also suggests that excitatory amino acid antagonists may be useful as adjunct antispastic agents.

Animals↗

A computer program that periodically monitors the ability to interpret the antinuclear antibody test.

Our laboratory has been developing computer programs that help medical technologists improve their performance of the microscope-based immunofluorescence assay for antinuclear antibodies (ANA). This image-based laboratory test has been associated with poor reproducibility. We have previously described our first program, ANA-Tutor, which systematically teaches the ANA test by using approximately 150 processed digital images of ANA test results. The program we describe here, Pattern Plus Auditor, is a logical extension to ANA-Tutor. Pattern Plus Auditor tests the ability of laboratory personnel to interpret the ANA test, and tracks individual and laboratory performance over time. The program consists of image-based questions that test a variety of ANA staining patterns, including homogeneous, speckled, centromere, nucleolar, mixed patterns, and rare patterns. For each question, the program provides correct answers with explanations and color overlays that highlight key image features. By entering the proper password, users gain access to exam results for individuals and for the laboratory as a whole. Results are available for the current exam, any previous exam, or cumulatively on all exams to date. Intralaboratory testing with computer programs such as Pattern Plus Auditor might be a useful part of quality-assurance procedures for many image-based laboratory tests.

Antibodies, Antinuclear↗

Patterns of coordinated multi-joint movement.

In multi-joint reaching movements, the motor system may choose any one of an infinite set of possible joint rotations to move the hand between given start and target positions. In order to find out whether reaching movements are represented in Cartesian hand coordinates or in joint coordinates, it is necessary to measure whether hand paths or joint paths have lower variability. We have measured hand paths and rotations of shoulder, elbow and wrist joints simultaneously in five subjects reaching in four orientations in the horizontal plane. As in earlier studies, we found a preference for nearly straight hand paths, despite different patterns of joint rotation for different orientations of movement. However, movements in three of four orientations showed a single principal joint, which rotated essentially without reversals. This may reflect optimisation in the motor system, preferring the simplest pattern of joint control for a desired hand path. We used generalised Procrustes analysis to quantify the variability in shape of repeated paths in hand space and joint space. Results showed that hand paths were less variable than the joint angles used to realise them, due to the kinematic redundancy of the limb, suggesting that hand paths, rather than joint angles, are directly represented by the motor system. Nevertheless, movements with straighter hand paths, on average, and those requiring coordinated activity at both shoulder and elbow joints also showed more variability in the shape of the hand path. Other orientations such as movement across the body use primarily a single joint and are less variable at the cost of a slightly curved path. These results suggest that coordinating multiple joints to produce a straight hand path has a definite computational cost. The motor system may perform a trade-off between the benefits of planning reaching movements as straight hand paths and the computational simplicity of executing them using patterns of joint rotation which simplify multi-joint coordination.

Adult↗

Trade union recognition.

An increasing number of organizations are addressing the issue of trade union recognition, particularly NHS trusts considering introducing local pay determination. Burnley NHS Trust developed a strategic approach to the issue, establishing pre-determined outcomes and measurable criteria to determine which organizations--if any--would have recognition extended for the purpose of local pay determination. The staff side case is examined in detail along with three other options: a staff association, recognition for some and recognition for none. Four organizations--representing 95 per cent of the unionized workforce--accepted recognition, with safeguards for 14 others.

Cost-Benefit Analysis↗

A mutant baculovirus with a temperature-sensitive IE-1 transregulatory protein.

We have mapped the mutation responsible for the temperature-sensitive (ts) phenotype of tsB821, a mutant of the baculovirus Autographa californica nuclear polyhedrosis virus (H. H. Lee and L. K. Miller, J. Virol. 31:240-252, 1979), to a single nucleotide which changes alanine 432 of the multifunctional regulatory protein IE-1 to a valine. Mapping was done with a combination of marker rescue and transient expression assays, hybrid gene construction by overlap PCR gene splicing, and nucleotide sequence analysis. Cells infected with tsB821 at high multiplicities of infection showed a spectrum of responses from severe cytopathic effects, including apoptosis, to a lack of obvious signs of infection. Protein synthesis in tsB821-infected cells at the restrictive temperature appeared similar to uninfected cell protein synthesis, but viral DNA replication and budded virus production were observed, albeit in a delayed manner. The dependence of early and late promoter activity on the wild-type IE-1 gene, ie-1, was observed in transient expression assays. However, the dependence of early promoter activity on ie-1 was strongest in the absence of other viral genes. Thus, other viral genes appear to be able to compensate, at least in part, for the lack, or low levels, of ie-1 in transient expression assays using early promoters. The mutant should prove useful in further defining the function(s) of IE-1.

Amino Acid Sequence↗

The Homeless Prenatal Program: a model for empowering homeless pregnant women.

The Homeless Prenatal Program (HPP) is one of the first programs in the country to provide comprehensive prenatal services to homeless pregnant women. A formative evaluation was conducted in 1992, indicating that HPP is achieving its program goals of improving birth outcomes and transforming the lives of its clients. Results of the qualitative evaluation are presented, including HPP's service model and approach to empowerment. In this model, empowerment has two central tenets, derived from the special needs of women who are pregnant and homeless: the "mother-child connection," and the principle of "giving back."

Child↗

Identification and characterization of tox21A: a mite cDNA encoding a paralytic neurotoxin related to TxP-I.

A cDNA library established from polyadenylated RNA isolated from the predatory mite Pyemotes tritici was screened for cDNAs homologous to tox34, a cDNA encoding an insect-selective paralytic neurotoxin known as TxP-I. Most of the cDNA inserts of homologous clones were shorter or of equal length to tox34 but a few were longer. Further investigation into the nature of these longer clones led to the identification, sequencing and expression of a distinct cDNA referred to as tox21A. This cDNA is predicted to encode a polypeptide which shares approximately 83% amino acid identity with TxP-I. Larvae infected with a recombinant baculovirus expressing tox21A are paralyzed during infection in a manner similar to larvae infected with tox34-expressing recombinants. The tox21A cDNA may represent a duplicated and diverged copy of the TxP-I gene.

Amino Acid Sequence↗

The time course of action of three differing doses of noberastine, a novel H1-receptor antagonist, on histamine-induced skin wheals and the relationship to plasma drug concentrations in normal human volunteers.

1. The time course and magnitude of effect of the novel H1-receptor antagonist noberastine, structurally modified from astemizole to achieve a more rapid onset while retaining a good duration of action, has been investigated using histamine-induced skin wheals in healthy volunteers. 2. The pharmacokinetics and pharmacodynamics of three doses (10, 20 and 30 mg) have been studied in a double-blind, placebo controlled, randomised cross-over trial involving 12 healthy male volunteers. 3. All doses of noberastine caused inhibition of histamine-induced skin wheals, which were significantly different from placebo (P < 0.0001) when assessed as the area under the percent inhibition of the response vs time curves. 4. Following single dose administration of 10, 20 and 30 mg noberastine significant inhibition of histamine-induced skin wheals occurred and this effect persisted beyond 24 h. 5. At the higher (20 and 30 mg) doses studied significant inhibition of the histamine-induced skin wheal occurred by 1 h of dosing, whereas this did not occur until 2 h following the 10 mg dose. 6. An increase in plasma concentrations of noberastine was seen after administration of all doses, with mean (s.d.) concentrations of 4.14 (3.70), 8.38 (7.81) and 12.66 (11.82) ng ml-1 1 h following administration of 10, 20, and 30 mg respectively. 7. Visual analogue scale measurements of drowsiness identified no sedative effects above those of placebo at any of the dose levels. 8. We conclude that noberastine is an effective H1-receptor antagonist in the human as assessed by its effect on histamine-induced skin wheals.

Adult↗

Thermal stabilities of globular proteins.

Statistical thermodynamic theory has recently been developed to account for the stabilities of globular proteins. Here we extend that work to predict the dependence on temperature. Folding is assumed to be driven by solvophobic interactions and opposed by the conformational entropy. The temperature dependence of the solvophobic interaction is taken from the transfer experiments on amino acids by Tanford and Nozaki and on model solutes by Gill and Wadsö. One long-standing puzzle has been why proteins denature upon heating, since the solvophobic force to fold strengthens with increasing temperature. This is resolved by the theory, which predicts two first-order phase transitions. "Cold denaturation" is driven principally by the weakening of the solvophobic interaction, but normal denaturation is driven principally by the gain of conformational entropy of the chain. Predictions of the thermodynamic state functions are in reasonable agreement with the calorimetric experiments of Privalov and Khechinashvili. Comparison of the theory with experiments suggests that there may be an additional enthalpic driving force toward folding which is not due to the solvophobic interactions.

Drug Stability↗