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Biomedical subjects

J Evans

Publications and source records attributed to J Evans.

At least 199 records · Page 11Linked to original sources

Use of amplitude-modulated breathing for assessment of cardiorespiratory frequency response within subrespiratory frequencies.

We present a new technique which uses amplitude-modulated breathing patterns to obtain estimates of frequency response between respiration and heart rate within subrespiratory frequencies. Frequency response between respiration and heart rate has been previously estimated using broadband respiration and metronomic breathing. However, the estimates obtained using these techniques show low coherence between respiration and heart rate within the subrespiratory frequencies (< 0.12-0.15 Hz). The advantages of amplitude-modulated breathing are: enhancement in the degree of perturbation within subrespiratory frequencies as indicated by relatively higher coherencies between respiration and heart rate (approximately equal to 0.7), and the subjects do not have to breathe at very low breathing frequencies or resort to breath holds. Use of a squared sine wave carrier modulated by sinusoidal functions enabled us to obtain energy distributions at subrespiratory frequencies without using demodulation. Results obtained at eight subrespiratory frequencies from ten subjects show that the new technique is easy to implement and produces relatively higher coherence between respiration and heart rate. The advantage of the new technique in terms of enhancing the level of perturbations within subrespiratory frequencies is particularly important, because it is in this frequency range that the interpretation of variability in heart rate in terms of autonomic origins is incompletely understood and is confounded by respiratory interactions.

Adult↗

BD8 certification of visually impaired people.

BACKGROUND: There is debate as to the completeness of the blind and partial sight registers in England and Wales. The purpose of this study was to estimate the proportion of eligible visually impaired people attending the hospital eye service who have a BD8 certificate and to identify factors associated with not being certified. METHODS: Cross sectional survey of patients attending outpatients by medical record review analysed by multiple logistic regression. RESULTS: 51% (43%, 58%) of patients identified as eligible for registration did not have a BD8 certificate. The severity of visual impairment and the main diagnosis in terms of requirements for treatment, permanence of visual loss, and visual field loss were independently associated with non-certification. A partially sighted patient is estimated to be three times more likely to not have a BD8 certificate as a blind patient of similar diagnosis (adj OR: 3.4 (95% CI: 1.7, 6.8)). A patient whose impairment is due to abnormal visual fields is estimated to be greater than three times more likely to be non-certified than one with low visual acuity of similar severity and cause (adj OR: 3.6 (95% CI: 1.0, 12.7)). People whose impairment is potentially reversible are estimated to be eight times (8.3 (2.2, 31.4)) more likely not to have a certificate compared with people who had permanent non-treatable visual loss; and in those with permanent visual loss, a requirement for ongoing treatment was found to be associated with a lower odds of certification. CONCLUSIONS: These data strongly suggest that epidemiological data collected during registration are biased towards permanent, non-treatable causes of visual loss and those which affect central rather than peripheral vision. Certain subgroups of the visually impaired are likely to be at greater risk of non-certification. BD8 guidelines need to be simplified.

Aged↗

Smooth muscle actin and myosin expression in cultured airway smooth muscle cells.

In this study, the expression of smooth muscle actin and myosin was examined in cultures of rat tracheal smooth muscle cells. Protein and mRNA analyses demonstrated that these cells express alpha- and gamma-smooth muscle actin and smooth muscle myosin and nonmuscle myosin-B heavy chains. The expression of the smooth muscle specific actin and myosin isoforms was regulated in the same direction when growth conditions were changed. Thus, at confluency in 1 or 10% serum-containing medium as well as for low-density cells (50-60% confluent) deprived of serum, the expression of the smooth muscle forms of actin and myosin was relatively high. Conversely, in rapidly proliferating cultures at low density in 10% serum, smooth muscle contractile protein expression was low. The expression of nonmuscle myosin-B mRNA and protein was more stable and was upregulated only to a small degree in growing cells. Our results provide new insight into the molecular basis of differentiation and contractile function in airway smooth muscle cells.

Actins↗

Patterns and associates of hyperphagia in patients with dementia.

This study examined patterns and associates of excessive eating (hyperphagia) in a community-based registry of patients with dementia. From patients enrolled in the Mayo Clinic Alzheimer's Disease Patient Registry (n = 439), 39 were identified with excessive eating reported on the Behavior Symptom Checklist at some time during their illness. They were matched for age, gender, duration of disease, and Global Deterioration Scale (GDS) score to "normal eaters." Annualized weight change was determined based on weight from the 6 months before the evaluation to weight 6 months after the evaluation. Annualized weight change scores were not significantly different between excessive eaters and normal eaters nor between wanderers and nonwanderers. In cross-sectional analysis, univariate modeling suggested age at onset, GDS, and Mini-Mental State Examination score to be significant predictors of excessive eating. Using multivariate logistic model with backward elimination, only age of onset and GDS were retained as associates of excess eating. Rater type also emerged as a significant predictor for excessive eating with family raters reporting this behavior in 16% of patients compared to 5% for other raters. In chi-square analyses excessive eating was associated with greater frequency of wandering, unpredictable behavior, inappropriate dressing, inappropriate bodily concerns, and threatening self-harm. Associates of excess eating were subsequently examined separately in wandering and nonwandering excessive eaters. Logistic modeling suggested that among nonwanderers, patients who were younger but more severely demented were likely to have reported excessive eating. These results suggest hyperphagia to be present in approximately 10% of a community-based cohort of patients with dementia and associated with increasing functional decline. Excessive eating does not appear to arise from memory dysfunction, but for wanderers may result from needing increased caloric intake because of increased activity levels. Thus, for wandering excessive eaters, it may be appropriate to endure the eating to ensure appropriate caloric intake. Nonwandering excessive eaters were younger, had greater dementia severity, and had more unpredictable behavior. They may have dementia with prominent frontal lobe involvement and may respond to any food stimulus respective of hunger. Restricting food exposure may be an effective management intervention for them.

Aged↗

Prenatal diagnosis of mosaic trisomy 8 with investigations of the extent and origin of trisomic cells.

A case of trisomy 8 mosaicism, which presented at obstetric ultrasound at 18 weeks' gestation with a distended bladder and absence of amniotic fluid, is described. Analysis of DNA microsatellite polymorphisms indicates that the trisomic cell line most likely arose as the result of a post-fertilization non-dysjunction event in early development of a chromosomally normal pre-implantation embryo. The distribution of normal and trisomy 8 cells suggests that in this pregnancy there has been either uneven allocation of abnormal cells to the extra-embryonic mesoderm, or selection against the proliferation of trisomic cells in trophoblast derived cell lineages. This prenatal detection of trisomy would not have been possible if only analysis of direct preparations had been undertaken.

Adult↗

Combined phacoemulsification and trabeculectomy versus trabeculectomy alone: a comparison study using mitomycin-C.

BACKGROUND AND OBJECTIVE: To compare the results of combined phacoemulsification and trabeculectomy (PEM/TRAB) plus mitomycin-C with those of trabeculectomy alone (TRAB) plus mitomycin-C. PATIENTS AND METHODS: The authors retrospectively reviewed 42 eyes in 38 consecutive patients who underwent combined PEM/TRAB with mitomycin-C. An age-matched control group of 42 patients who underwent TRAB with mitomycin-C during the same time period was randomly selected from 248 consecutive patients. All patients had a minimum of 12 months of follow-up. RESULTS: Mean preoperative intraocular pressure (IOP) and number of glaucoma medications were similar for the two groups (22.8 +/- 6.9 mm Hg vs 22.9 +/- 6.8 mm Hg, 2.12 +/- 0.8 vs 2.26 +/- 1.0 medications, combined PEM/TRAB vs TRAB, respectively). Postoperative IOP was significantly lower at all follow-up intervals. At final follow-up after a mean of 21.8 +/- 6.0 months, IOP averaged 13.9 +/- 5.1 mm Hg in the PEM/TRAB group and 12.3 +/- 4.7 mm Hg in the TRAB group. Bleb survival was excellent in both groups, although slightly higher in the TRAB group (37 of 42 PEM/TRAB vs 41 of 42 TRAB). Both groups required significantly fewer glaucoma medications at final follow-up (0.38 +/- 0.6 vs 0.5 +/- 0.8, PEM/TRAB vs TRAB). Complications were similar between the two groups. CONCLUSION: The success rate for combined PEM/TRAB appears to approach that of TRAB alone.

Aged↗

Patterns of immunodominance in HIV-1-specific cytotoxic T lymphocyte responses in two human histocompatibility leukocyte antigens (HLA)-identical siblings with HLA-A*0201 are influenced by epitope mutation.

Primary human immunodeficiency virus (HIV) infection is controlled principally by HIV-specific cytotoxic T lymphocytes (CTL) to a steady-state level of virus load, which strongly influences the ultimate rate of progression to disease. Epitope selection by CTL may be an important determinant of the degree of immune control over the virus. This report describes the CTL responses of two HLA-identical hemophiliac brothers who were exposed to identical batches of Factor VIII and became seropositive within 10 wk of one another. Both have HLA-A*0201. The CTL responses of the two siblings were very dissimilar, one donor making strong responses to two epitopes within p17 Gag (HLA-A*0201-restricted SLYNTVATL and HLA-A3-restricted RLRPGGKKK). The sibling responded to neither epitope, but made strong responses to two epitopes presented by HLA-B7. This was not the result of differences in presentation of the epitopes. However, mutations in both immunodominant epitopes of the p17 Gag responder were seen in proviral sequences of the nonresponder. We then documented the CTL responses to two HLA-A*0201-restricted epitopes, in Gag (SLYNTVATL) and Pol (ILKEPVHGV) in 22 other HIV-infected donors with HLA-A*0201. The majority (71%) generated responses to the Gag epitope. In the 29% of donors failing to respond to the Gag epitope in standard assays, there was evidence of low frequency memory CTL responses using peptide stimulation of PBMC, and most of these donors also showed mutations in or around the Gag epitope. We concluded that HLA class I genotype determines epitope selection initially but that mutation in immunodominant epitopes can profoundly alter the pattern of CTL response.

Amino Acid Sequence↗

Salmonella osteomyelitis in sickle cell disease children in the east end of London.

Five cases of Salmonella osteomyelitis are presented in children with sickle cell disease living in the East End of London. Four of these had involvement of the long bones and one (an infant) presented with hand-foot syndrome. Four required surgical drainage of pus and all required lengthy therapy with antibiotics. Factors contributing to the increased susceptibility of these patients to invasive disease with Salmonella sp. are discussed as are the clinical features, surgical and antibiotic management and possible preventative measures.

Anemia, Sickle Cell↗

Biochemical and pharmacological profile of a tetrasubstituted furanone as a highly selective COX-2 inhibitor.

1. DFU (5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulphonyl)phenyl-2(5H)-furan one) was identified as a novel orally active and highly selective cyclo-oxygenase-2 (COX-2) inhibitor. 2. In CHO cells stably transfected with human COX isozymes, DFU inhibited the arachidonic acid-dependent production of prostaglandin E2 (PGE2) with at least a 1,000 fold selectivity for COX-2 (IC50 = 41 +/- 14 nM) over COX-1 (IC50 > 50 microM). Indomethacin was a potent inhibitor of both COX-1 (IC50 = 18 +/- 3 nM) and COX-2 (IC50 = 26 +/- 6 nM) under the same assay conditions. The large increase in selectivity of DFU over indomethacin was also observed in COX-1 mediated production of thromboxane B2 (TXB2) by Ca2+ ionophore-challenged human platelets (IC50 > 50 microM and 4.1 +/- 1.7 nM, respectively). 3. DFU caused a time-dependent inhibition of purified recombinant human COX-2 with a Ki, value of 140 +/- 68 microM for the initial reversible binding to enzyme and a kappa 2 value of 0.11 +/- 0.06 s-1 for the first order rate constant for formation of a tightly bound enzyme-inhibitor complex. Comparable values of 62 +/- 26 microM and 0.06 +/- 0.01 s-1, respectively, were obtained for indomethacin. The enzyme-inhibitor complex was found to have a 1:1 stoichiometry and to dissociate only very slowly (t1/2 = 1-3 h) with recovery of intact inhibitor and active enzyme. The time-dependent inhibition by DFU was decreased by co-incubation with arachidonic acid under non-turnover conditions, consistent with reversible competitive inhibition at the COX active site. 4. Inhibition of purified recombinant human COX-1 by DFU was very weak and observed only at low concentrations of substrate (IC50 = 63 +/- 5 microM at 0.1 microM arachidonic acid). In contrast to COX-2, inhibition was time-independent and rapidly reversible. These data are consistent with a reversible competitive inhibition of COX-1. 5. DFU inhibited lipopolysaccharide (LPS)-induced PGE2 production (COX-2) in a human whole blood assay with a potency (IC50 = 0.28 +/- 0.04 microM) similar to indomethacin (IC50 = 0.68 +/- 0.17 microM). In contrast, DFU was at least 500 times less potent (IC50 > 97 microM) than indomethacin at inhibiting coagulation-induced TXB2 production (COX-1) (IC50 = 0.19 +/- 0.02 microM). 6. In a sensitive assay with U937 cell microsomes at a low arachidonic acid concentration (0.1 microM), DFU inhibited COX-1 with an IC50 value of 13 +/- 2 microM as compared to 20 +/- 1 nM for indomethacin. CGP 28238, etodolac and SC-58125 were about 10 times more potent inhibitors of COX-1 than DFU. The order of potency of various inhibitors was diclofenac > indomethacin approximately naproxen > nimesulide approximately meloxicam approximately piroxicam > NS-398 approximately SC-57666 > SC-58125 > CGP 28238 approximately etodolac > L-745,337 > DFU. 7. DFU inhibited dose-dependently both the carrageenan-induced rat paw oedema (ED50 of 1.1 mg kg-1 vs 2.0 mg kg-1 for indomethacin) and hyperalgesia (ED50 of 0.95 mg kg-1 vs 1.5 mg kg-1 for indomethacin). The compound was also effective at reversing LPS-induced pyrexia in rats (ED50 = 0.76 mg kg-1 vs 1.1 mg kg-1 for indomethacin). 8. In a sensitive model in which 51Cr faecal excretion was used to assess the integrity of the gastrointestinal tract in rats, no significant effect was detected after oral administration of DFU (100 mg kg-1, b.i.d.) for 5 days, whereas chromium leakage was observed with lower doses of diclofenac (3 mg kg-1), meloxicam (3 mg kg-1) or etodolac (10-30 mg kg-1). A 5 day administration of DFU in squirrel monkeys (100 mg kg-1) did not affect chromium leakage in contrast to diclofenac (1 mg kg-1) or naproxen (5 mg kg-1). 9. The results indicate that COX-1 inhibitory effects can be detected for all selective COX-2 inhibitors tested by use of a sensitive assay at low substrate concentration. The novel inhibitor DFU shows the lowest inhibitory potency against COX-1, a consistent high selectivity of inhibition of COX-2 over COX-1 (>300 fold) with enzyme, whole cell and whole blood assays, with no detectable loss of integrity of the gastrointestinal tract at doses >200 fold higher than efficacious doses in models of inflammation, pyresis and hyperalgesia. These results provide further evidence that prostanoids derived from COX-1 activity are not important in acute inflammatory responses and that a high therapeutic index of anti-inflammatory effect to gastropathy can be achieved with a selective COX-2 inhibitor.

Administration, Oral↗

Men in nursing: issues of gender segregation and hidden advantage.

The small but growing number of men in the nursing profession does not herald a progressive integration of masculine and feminine sex roles. The evidence presented in this paper suggests that even in female-dominated occupations such as nursing, patriarchal gender relations which reflect a high valuation of all that is male and masculine, play a significant role in situating a disproportionate number of men in administrative and elite specialty positions. At the heart of this gender dynamic is the need to separate the masculine from the lesser valued feminine. Male nurses do this by employing strategies that allow them to distance themselves from female colleagues and the quintessential feminine image of nursing itself, as a prerequisite to elevating their own prestige and power. They are aided in this task by patriarchal cultural institutions that create and perpetuate male advantage, as well as by women nurses themselves who, consciously or unconsciously, nurture the careers of men colleagues.

Career Mobility↗

Risk factors for optic nerve disease in communities mesoendemic for savannah onchocerciasis, Kaduna State, Nigeria.

Ophthalmic examinations on 6831 individuals aged 5 years or more, living in 34 guinea savannah communities mesoendemic for onchocerciasis, in Kaduna State, Nigeria, revealed a relatively high prevalence (9%) of optic nerve disease (OND). Further investigations were performed to determine what proportion of this burden of OND might be due to onchocercal infection. Information on history of cerebro-spinal meningitis (CSM), past use of diethylcarbamazine (DEC) and chloroquine, consumption of cassava and locally produced alcohol was collected for all individuals by questioning. In addition, a nested case-control study of 81 cases of OND and 136 age and sex-matched controls was performed to investigate whether syphilis or a variety of other neurological disorders were responsible for a substantial proportion of cases of OND. Our data suggest that in this population, onchocercal infection is the single most important cause of OND and may account for 50% of all cases. Some 13% of cases were associated with signs suggestive of glaucoma. DEC use might be responsible for up to 30% of all OND. We found no evidence to suggest that any of the following are important causes of OND in the communities studied: CSM, syphilis, neurological syndromes such as polyneuropathy or other generalized neurological disease, consumption of raw cassava, consumption of locally prepared alcohol.

Adolescent↗

The implications of recognizing large-vessel involvement in elderly patients with giant cell arteritis.

Giant cell arteritis is associated with a markedly increased risk of aortic aneurysm formation or aortic rupture, particularly in the thoracic aorta. Although this association is not new, it has gained renewed attention recently. In this paper, the nature of aortic aneurysm formation in association with giant cell arteritis is discussed, along with the implications of recognizing large-vessel involvement in elderly patients with giant cell arteritis.

Aged↗

Lyme disease.

The number of reported cases of Lyme disease in the United States has increased steadily since 1982, and the increase coincides with a growth in deer populations in endemic regions. Application of careful epidemiologic principles has led to the identification of two new pathogens that produce syndromes closely related to Lyme disease. Coinfection with other pathogens such as Babesia has been shown to alter the clinical course of Lyme disease. Better understanding of the pathogenesis of Lyme disease has provided clues into the mechanisms responsible for persistent symptoms and will serve as a foundation for the design and implementation of appropriate therapic recommendations. A safe vaccine for the prevention of Lyme disease in humans has been developed, and clinical vaccine efficacy trials are close to completion.

Humans↗