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Biomedical subjects

L Hughes

Publications and source records attributed to L Hughes.

At least 37 records · Page 2Linked to original sources
PubMed1996

Gait initiation by patients with lower-half parkinsonism.

Patients with multiple deep cerebral infarcts and white matter degeneration commonly exhibit a hesitant, shuffling gait, with preserved arm swing. This pattern of walking is called lower-half or lower-body parkinsonism. Gait initiation and turning consist of one or more short, hesitant steps in which the feet shuffle across the floor. This abnormality of gait initiation was studied with quantitative motion analysis in five patients, ages 74-87 years. Five men and five women with normal mobility and comparable ages exhibited three key events of gait initiation: (i) activation of tibialis anterior and inactivation of triceps surae produced bilateral ankle dorsiflexion and a sagittal moment of force that propelled the body anteriorly; (ii) abduction of the swing hip occurred simultaneously with event (i); and (iii) abrupt 3-10 degrees flexion of the support hip and knee occurred nearly simultaneously with events (i) and (ii) and produced a transient reduction in vertical force beneath the support foot. Events (ii) and (iii) produced a coronal moment of force about the ankles that propelled the body toward the support foot. Thus, in normal gait initiation, a smooth sequence of postural shifts propels the body anterolaterally toward the support limb, culminating in a forward step. The patients, by comparison, exhibited errant deviations in their postural shifts of gait initiation, and one or more aborted steps frequently preceded the first complete step. Nevertheless, all patients employed the usual three key events in their initial attempt at stepping, consistent with a normal motor strategy of gait initiation. These results and previous clinical observations suggest that the principal locomotor deficit is an impaired generation of postural shifts that mediate changes from one steady-state posture or movement to another.

Aged↗
PubMed1996

Use of a fibrillar polylactic acid homopolymer in sheep cranial defects.

Guided tissue regeneration has been shown to permit osteoconduction in otherwise nonhealing cranial defects. The relative importance of preventing the prolapse of soft tissue versus the infiltration of individual connective tissue cells has not been determined. A fibrillar form of polylactic acid (PLA) was tested in 13-mm-diameter defects in the parietal bones of 12 sheep. The polymer was hypothesized to prevent the prolapse of dura and periosteum but allow entrance of individual cells. Control defects in the same sheep were either filled with autogenous bone shavings or left unfilled. The animals were killed at times ranging from 6 to 25 weeks and the defects examined grossly, radiologically, and histologically. The autogenous bone-filled defects were spanned by trabeculated bone by 6 weeks. The unfilled defects demonstrated prolapse of soft tissues into the defect; however, progressive centripetal bone growth was evident. The fibrillar PLA-filled defects were occupied by a full-thickness mixture of fibrous tissue interspersed with PLA. After 19 weeks, small "fingers" of bone were seen to minimally infiltrate the fibrous tissue. Although separation of the dura and periosteum was maintained by the fibrillar PLA, invasion of fibrous tissue restricted osteoconduction.

Animals↗
PubMed1996

Use of an occupational therapy motor performance checklist by a school health service: a pilot study.

OBJECTIVE: The aim of this pilot study was to assess whether the School Health Service could play a role in identifying the children in most need of community occupational therapy services. METHODOLOGY: A two-tiered referral system, which incorporated a Motor Performance Checklist (MPC) devised by the authors, was used. This checklist consisted of 12 gross and fine motor items and was administered to 123 children in their first year of school. Comparison was made between parent/teacher referrals alone and the two-tiered referral system as measured against a 'gold standard' test (the Bruininks-Oseretsky Test of Motor Proficiency) in a smaller subgroup. RESULTS: Results indicated that the two-tiered referral system incorporating the MPC had a sensitivity of 75% and specificity of 95% while the teacher/parent referrals had a sensitivity of 88% but a low specificity of only 41%. There was no significant difference in sensitivity (z = 0, P > 0.05) but a highly significant difference in specificity (z = 3.56, P < 0.005) between these two systems. CONCLUSIONS: This two-tiered referral system has the potential to impact significantly on paediatric occupational therapy utilization, service delivery and waiting times in the community health setting.

Child, Preschool↗
PubMed1995

Improved staging of B-cell non-Hodgkin's lymphoma patients with 99mTc-labeled LL2 monoclonal antibody fragment.

Radioimmunodetection (RAID) with the 99mTc-labeled Fab' fragment of monoclonal antibody (MoAb) LL2 has been reported to have a high lesion detection rate for malignant lymph nodes as well as for visceral and skeletal tumor masses (20). Our purpose in this study was to evaluate the safety and staging efficacy of the 99mTc-labeled Fab' fragment of MoAb LL2 in patients with various grades and stages of B-cell non-Hodgkin's lymphoma (NHL). Thirty adult patients, 13 male and 17 female, ranging in age from 20 to 80 years, with at least one biopsy-proved malignant node (> or = 0.5 cm) and a Karnofsky performance score of > or = 60% were enrolled in this study. Patients underwent selected planar and single photon emission computed tomographic imaging at 6 and 18 h after receiving an i.v. infusion of 0.25-1 mg of LL2 Fab' fragment labeled with 25-30 mCi of 99mTc. RAID findings were compared with physical examination, chest radiography, computed tomography, magnetic resonance imaging, and bone and 67Ga scan findings. The RAID scan was positive in all but three patients. The sensitivity for known lesions was 90% and for suspected lesions, 89%, with an overall positive predictive value of 96%. Twenty-nine of the 30 patients had either low- or intermediate-grade NHL. Fifteen of 16 (94%) low-grade patients were correctly staged by RAID; three of these patients were correctly upstaged. Twelve of the 13 (92%) intermediate-grade patients were correctly staged by RAID; two of these patients were correctly upstaged. The high-grade NHL patient was staged correctly by RAID. Infused doses of 99mTc-labeled LL2 Fab' of 0.5 and 1.0 mg did not affect lesion sensitivity. The RAID sensitivity decreased as the total tumor burden increased > or = 100 g. On the basis of these initial results, the 99mTc-labeled Fab' fragment of MoAb LL2 (LymphoScan) seems to yield useful clinical information, especially for the staging of B-cell NHL patients who do not have bulky disease (i.e., tumor burdens of < or = 100 g).

Adult↗
PubMed1995

Dominant lethal and heritable translocation tests with chlorambucil and melphalan in male mice.

Chemicals used in the treatment of cancer include several that are potent mutagens in a range of in vitro and in vivo assays. For some, genetic effects have also been demonstrated in humans, detected as chromosomal aberrations in peripheral lymphocytes. Because (1) many of these agents are confirmed mutagens, (2) humans are exposed to them in relatively high doses, and (3) an increasing number of early cancer victims are surviving to reproductive age, it is important that information be available on the genetic and reproductive hazards associated with exposure to these agents. Chlorambucil and melphalan are structurally related chemicals that are included in our efforts to identify and assess such hazards among cancer chemotherapy agents. To date, both have been reported to induce specific locus mutations in germ cells of male mice (Russell et al., 1989; Russel et al., 1992b) and melphalan is one of very few chemicals shown to induce such mutations in spermatogonial stem cells. More recently, both chemicals were found to have strong reproductive effects in female mice (Bishop and Generoso, 1995, in preparation). In the present studies, these chemicals were tested for the induction of dominant lethal mutations and heritable translocations in male mice. Both chemicals were found to have reproductive effects attributable to cytotoxicity in specific male germ cell stages and to induce dominant lethal mutations and heritable translocations in postmeiotic germ cells, particularly in mid to early stage spermatids. Thus, relatively extensive data are now available for assessing the genetic and reproductive hazards that may result from therapeutic exposures to these chemicals.

Animals↗
PubMed1995

Biokinetics in humans of RRR-alpha-tocopherol: the free phenol, acetate ester, and succinate ester forms of vitamin E.

The bioavailability of RRR-alpha-tocopherol from the oral administration of RRR-alpha-tocopherol itself and its acetate and succinate esters was determined in healthy human subjects. Venous blood samples were withdrawn periodically over a 51-h period following oral administration of a gelatin capsule containing an equimolar mixture of RRR-alpha-tocopherol and RRR-alpha-tocopheryl acetate. In a second study, subjects received a capsule containing an equimolar mixture of RRR-alpha-tocopheryl acetate and RRR-alpha-tocopheryl succinate. In Study 1, RRR-alpha-tocopherol was absorbed at similar rates from both the free phenol, and the acetate ester and maximum plasma levels occurred at 12 h in most subjects. The extent of absorption of RRR-alpha-tocopherol varied considerably between subjects in absolute terms, but the relative absorption from the two forms was remarkably consistent, and a ratio of 1.0 was found for parameters of relative bioavailability in plasma. The concentration of RRR-alpha-tocopherol from each form was maximal at approximately 27 h in red blood cells and, as seen with the plasma data, there was a large interindividual variability. In Study 2, there was no significant difference in the extent of absorption of RRR-alpha-tocopherol from the acetate ester and the succinate ester, although there was an apparently higher initial rate of absorption from the acetate ester.

Administration, Oral↗
PubMed1995

Rarefied white matter in patients with Alzheimer disease.

Magnetic resonance head scans of 94 patients with probable Alzheimer disease (AD) and 45 patients with possible AD were examined prospectively to determine the prevalence and significance of rarefied cerebral white matter (leukoaraiosis) in patients with AD. Only 8.7% of patients with probable AD and 11.1% of patients with possible AD exhibited large confluent areas of subcortical leukoaraiosis. The remaining patients had variable degrees of leukoaraiosis surrounding the lateral ventricles. The magnitude of leukoaraiosis correlated with the patient's age but not with the Hachinski Ischemic and Mini Mental Status scores. Postmortem studies of two Alzheimer patients showed that their large confluent areas of subcortical leukoaraiosis consisted of rarefied white matter, gliosis, and arteriosclerotic small arteries. Eight additional Alzheimer patients who underwent autopsy had similar but less pronounced white matter changes limited to the periventricular regions of the cerebral hemispheres. Large confluent areas of rarefied subcortical white matter occur in a small minority of Alzheimer patients and are probably not caused by AD.

Aged↗
PubMed1995

Recovery of DNA, RNA and protein from gels with microconcentrators.

The use of a new product, Microcon/Micropure (a centrifugal ultrafiltration device combined with a microporus insert), for the purification of DNA, RNA, peptides and proteins from gels is described. Using this system, DNA can be recovered from agarose gel in concentrated, contamination-free form in only 15 min. Results of studies on the effects of fragment size and various pretreatment of the gel slice on DNA recovery are presented. The Microcan/Micropure combination can also be used for the recovery of macromolecules from polyacrylamide gels. Optimized protocols for the recovery of RNA, oligonucleotides and proteins from polyacrylamide gels using a crush and elute method, along with a study of critical parameters, are presented.

Centrifugation↗
PubMed1994

Factors influencing the amplitude and frequency of essential tremor.

Quantitative electromyography (EMG) and triaxial accelerometry were used to measure hand tremor, finger tremor, and forearm motor unit activity in 36 men and 23 women with essential tremor. Hand tremor was studied with and without 300-g mass loading. Tremor and EMG were recorded twice, with a 3-min rest interval, to assess the spontaneous intertrial variability in tremor amplitude, frequency, and motor unit entrainment. In general, the minimum detectable differences in tremor amplitude, frequency, and motor unit entrainment were roughly 30%, 5%, and 10% of the initial sample means, respectively, assuming a sample size of 30 patients, a statistical power of 0.9, and a significance level of 0.05. Linear regression analyses were performed to test the hypotheses that (a) there is an age-associated decrease in tremor frequency that is independent of symptom duration and (b) tremor frequency and motor unit entrainment make independent contributions to tremor amplitude. Our data supported both hypotheses.

Adolescent↗
PubMed1994

Essential tremor entrains rapid voluntary movements.

The effect of essential tremor on the timing of rapid wrist flexion was examined in 10 patients with moderate to severe disability. The mean reaction time and motor time of the patients did not differ from the mean values of 10 healthy age- and sex-matched controls. The latencies of the triphasic agonist and antagonist EMG bursts did not differ between patients and controls. The initiation of movement was time-locked to the tremor cycle in all patients. The initial agonist muscle activation occurred in phase with the rhythmic bursts of EMG, but the onset of rapid wrist flexion occurred when the momentum of essential tremor opposed the volitional movement. Essential tremor has subtle effects on motor control that transcend oscillation per se. These effects probably contribute to the impaired performance of fine motor tasks in patients with advanced disease.

Aged↗
PubMed1994

Pulse oximetry is accurate in acute anemia from hemorrhage.

HYPOTHESIS: Pulse oximetry is an accurate, noninvasive assay of oxygen saturation percentage (SaO2) in acutely severe anemia (less than 5 g/dL). DESIGN: A paired comparison of SaO2 by pulse oximetry (SpO2) and arterial blood gas analysis (SaO2) in patients with either acute gastrointestinal bleeding or blunt trauma with hematocrit of less than 20%. SETTING: An academic emergency department in a tertiary referral hospital with a Level I trauma center. PARTICIPANTS: Seventeen nonhypoxic patients were identified with initial hematocrit of less than 20% over a 9-month period. MEASUREMENTS AND MAIN RESULTS: Determination of SaO2 by pulse oximetry and arterial blood analysis was not statistically significantly different (P < .05) over a range of hemoglobin levels from 2.3 to 8.7 g/dL. The observed mean difference between SpO2 and SaO2 was 0.53 +/- 0.23% (mean +/- SEM; n = 17). The 95% confidence interval associated with this difference score ranged from 0.044 to 1.014. CONCLUSION: Despite reports that pulse oximetry is inaccurate below a hemoglobin concentration of 5 g/dL, our study suggested that this technology is accurate and reliable at 2.3 g/dL for nonhypoxic SaO2 values (SaO2 of more than 93%). The anemic endpoint where pulse oximetry either becomes inaccurate or simply fails to work has not been determined. Pulse oximetry overestimates SaO2 on average by 0.53% over a range of hemoglobin concentrations from 2.3 to 8.7 g/dL.

Acute Disease↗
PubMed1994

A district epilepsy service, with community-based specialist liaison nurses and guidelines for shared care.

In order to improve epilepsy services, Doncaster Hospital doctors and general practitioners agreed upon a collaborative approach. A district epilepsy service was inaugurated around specialist services based in a hospital clinic. Guidelines were produced to clarify respective roles and to assist non-specialist hospital doctors and general practitioners in epilepsy management. A novel feature of the new service was the appointment of a community-based specialist liaison nurse. The new service is perceived to be effective, and the contribution of the specialist nurse to represent an important advance in epilepsy care. It has been possible to supervise complicated changes in medication successfully at home with a reduction in the need to attend clinic or GP. Counselling and support for patients and families, previously lacking, has been a major contribution. Evaluation to determine the extent to which the service meets the needs of those in the local population with epilepsy is planned. This document describes the first 5 years of the service and the scope and content of the specialist liaison nurse's role.

Adolescent↗
PubMed1994

Is the construction of an ileoanal pouch associated with the development of arthritis?

The construction of an ileoanal pouch in patients who have undergone total colectomy for ulcerative colitis is claimed to be associated with the development of arthritis. The pattern and prevalence of reported musculoskeletal symptoms in the 15 patients with ileoanal pouches attending our hospital was not significantly different to a control group of 60 patients with an ileostomy for inflammatory bowel disease. There was no clinical or serological evidence of arthritis in the eight patients from the study group reporting symptoms. We conclude that the majority of symptoms occurring following pouch construction are not attributable to an inflammatory arthropathy.

Adolescent↗
PubMed1994

A strategy for the design of membrane-permeable folypoly-gamma-glutamate synthetase inhibitors: "bay-region"-substituted 2-desamino-2-methyl-5,8-dideazafolate analogs.

Previous attempts to design inhibitors of mammalian folylpolyglutamate synthetase (FPGS) have resulted in three classes of active compounds, all of which have charged moieties in the side chain, but structural alteration of the rest of the folate molecule has not seemed to be an avenue for drug discovery. However, groups in the side chain of folate analogs that bear charge distributions different from that of glutamic acid appear to prevent efficient transport into mammalian cells on the reduced folate carrier system. We now report that substituents at the 7-, 2'-, or 3'-position of 2-desamino-2-methyl-4-hydroxyquinazoline antifolates decrease or prevent the catalysis of diglutamate formation by FPGS but are compatible with efficient binding to the reduced folate carrier system. Thus, 5,8-dideazafolates with a 3'-alkyl group had a lower Vmax for FPGS than did the corresponding unsubstituted quinazolines, by a factor of 4-12, but these compounds inhibited the reaction of control FPGS substrates, indicating that the 3'-groups had much larger effects on catalytic activity than on binding to enzyme. A 7-methyl substituent affected the Vmax of a series of 5,8-dideazafolate compounds by a factor of 2-8, but this decrease in the catalytic rate was also accompanied by an increase in the Km of the substituted compounds by a factor of 10-100. The extent of the effect of a 7-methyl substituent on Vmax appeared to be dependent on the size of the substituent at N10. Different substituents at the 2'-position affected the kinetics of the FPGS reaction with one of three patterns, i.e., 1) a 2'-fluoro substituent both increased Vmax and decreased Km slightly, 2) either -OH or -NH2 decreased the Vmax without affecting the Km, and 3) 2'-Cl-, -CH3, -CF3, or -OCH3 substituents were found to both decrease Vmax and increase Km. Substitutions at the 7-, 2'-, or 3'-position had only minor effects on the ability of 2-desamino-2-methyl-4-oxoquinazolines to interfere with the transport of [3H]methotrexate into L1210 cells. Hence, these classes of compounds are likely to be efficiently transported by the reduced folate carrier system. We conclude that the region of the folate molecule bounded by the 7-, 6-, 9-, 10-, 3'-, and 2'-positions, the "bay region," is of major importance both for the binding of folates and folate analogs to FPGS and for the assumption of a conformation of the enzyme-substrate complex compatible with catalysis.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

Outbreak of Hantavirus pulmonary syndrome in the southwestern United States. Response of pathologists and other laboratorians.

During late spring and early summer of 1993, national and international media called worldwide attention to a cluster of deaths in the southwestern United States. These patients succumbed to a rapidly progressive severe respiratory distress syndrome. After notification of state and national health agencies in mid-May, a major effort was launched to determine the cause of this often fatal respiratory distress syndrome, to advise the public on safety measures, and to determine the method of spread of this "mystery illness." Within weeks of recognition of the early cases, the Centers for Disease Control and Prevention announced the probable agent, a Hantavirus. This report details the response of pathologists, medical technologists, and other laboratory scientists to this new viral epidemic, with emphasis on activities that occurred within New Mexico.

Adolescent↗
PubMed1993

A computerized system for morphometric analysis of digitized images of histologically prepared arterial cross sections.

A method is described for computerized, operator-assisted, morphometric measurement of histologically prepared arterial cross sections. The system is composed of an image cytometer equipped with a one power lens and a digitizing camera interfaced with an imaging board residing in a PC computer. Algorithms were developed for automated segmentation of the areas of interest. The method is rapid, objective, accurate and requires minimum operator intervention. It gives reliable and reproducible results in the measurement of all elements of the cross section including circumference, area of the media, circumference of the internal elastic lamina, area of the lumen and percent occlusion of the lumen by the intimal thickening. While manual measurements using computerized planimetric methods give similar results, this method is an order of magnitude faster (1-2 min vs. 10-20 min per cross section) thus facilitating the study of large numbers of specimens. A blinded re-measurement of 284 sections of artery for reproducibility yielded r values of 0.86-0.97.

Adult↗
PubMed1993

Peer group interactions and the student-perceived climate for caring.

Using the descriptive mode of qualitative inquiry, this study was conducted with 10 junior nursing students at five baccalaureate schools of nursing to describe a climate for caring as it is experienced within the context of peer group interactions. The findings from this study indicate that a climate for caring is experienced through peer group behaviors that are perceived as caring, and during peer group interactional episodes that are characterized by giving assistance. Based on the data from these participants, student vulnerability and personal knowledge of peers are suggested as factors that mediate the ability of junior nursing students to experience a climate for caring during peer group interactions.

Education, Nursing, Baccalaureate↗