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Biomedical subjects

E Jones

Publications and source records attributed to E Jones.

At least 37 records · Page 2Linked to original sources

Intravenous administration of replication-incompetent adenovirus to rhesus monkeys induces thrombocytopenia by increasing in vivo platelet clearance.

A replication-incompetent adenovirus vector was administered to rhesus macaques at 1, 3 and 6 x 1012 particles/kg doses to investigate its toxicity. Platelet count decrements of 28%, 82% and 90%, respectively, were observed, with corresponding platelet half-lives of 69.0, 25.2 and 22.2 h (compared with 111 h in untreated animals). The platelet decline was equivalent for all three doses for 8 h, and platelet count recovery began as early as 8 h after infusion for low-dose recipients, or as late as 24 h for the medium and high dose recipients. These observations suggest that thrombocytopenia is a saturable, reversible consumptive process.

Adenoviridae↗

Simultaneous measurement of instantaneous heart rate and chest wall plethysmography in short-term, metronome guided heart rate variability studies: suitability for assessment of autonomic dysfunction.

Instantaneous heart rate and chest wall motion were measured using a 3-lead ECG and an air pressure chest wall plethysmography system. Chest wall plethysmography traces were found to accurately represent the breathing pattern as measured by spirometry (average correlation coefficient 0.944); though no attempt was made to calibrate plethysmography voltage output to tidal volume. Simultaneous measurements of heart rate and chest wall motion were made for short periods under metronome guided breathing at 6 breaths per minute. The average peak to trough heart rate change per breath cycle (AVEMAX) and maximum correlation between heart rate and breathing cycle (HRBRCORR) were measured. Studies of 44 normal volunteers indicated clear inverse correlation of heart rate variability parameters with age (AVEMAX R = -0.502, P < 0.001) but no significant change in HRBRCORR with age (R = -0.115). Comparison of normal volunteers with diabetics with no history of symptoms associated with autonomic failure indicated significant lower heart rate variability in diabetics (P = 0.005 for AVEMAX) and significantly worse correlation between heart rate and breathing (P < 0.001 for HRBRCORR). Simultaneous measurement of heart rate and breathing offers the possibility of more sensitive diagnosis of autonomic failure in a simple bedside test and gives further insight into the nature of cardio-ventilatory coupling.

Adult↗

Screening for vulnerability to psychological disorders in the military: an historical survey.

OBJECTIVES: To evaluate attempts in the military to screen for vulnerability to psychological disorders from World War I to the present. METHODS: An extensive literature review was conducted by hand-searching leading medical and psychological journals relating to World Wars I and II. Recent publications were surveyed electronically and UK archives investigated for British applications. RESULTS: Despite the optimism shown in World War I and the concerted efforts of World War II, follow-up studies showed that screening programmes did not succeed in reducing the incidence of psychological casualties. Furthermore, they had a counter-productive effect on manpower, often rejecting men who would have made good soldiers. Continued experimentation with screening methods for psychiatric vulnerability failed to yield convincing results during the post-war period. CONCLUSIONS: Although well-measured variables, such as intelligence, have been shown to predict success in training and aptitude, no instrument has yet been identified which can accurately assess psychological vulnerability. Previous attempts have failed because of false-positives, false-negatives and reluctance in the target population because of stigma. Early findings suggest that psychological surveillance, if not screening, may yield valuable results when applied to military populations exposed to stress.

History, 20th Century↗

Responsiveness to staff support: evaluating the impact of individual characteristics on the effectiveness of active support training using a conditional probability approach.

BACKGROUND: Active support training was fully conducted in 38 community houses accommodating 106 adults with intellectual disabilities (ID; group 1), but not in a further 36 accommodating 82 adults with ID (group 2). The aims of the present study were to analyse whether staff became more effective in supporting resident activity after the implementation of active support, and whether there was evidence of differential responsiveness by people with differing status in relation to adaptive behaviour, psychiatric diagnosis, challenging behaviour or autism. METHODS: Observations of staff:resident interaction and resident engagement in activity were taken before and after active support training. Changes in Yule's Q statistics, indicating the likelihood that resident engagement in activity followed staff giving residents verbal instruction or non-verbal assistance, were compared for the two groups. In addition, changes in similar statistics were compared for residents within group 1: (1) with Adaptive Behaviour Scale (ABS) scores above and below 180; and (2) with and without severe challenging behaviour, the triad of social impairments and mental illness. RESULTS: Yule's Q for engagement given non-verbal assistance significantly increased post-training among group 1, but not among group 2. Similar significant increases were found among group 1 residents with ABS scores below 180 without challenging behaviour, with and without the triad of social impairments, and without mental illness, but not with an ABS score above 180, with challenging behaviour and with mental illness. CONCLUSION: The present analysis reinforces previous studies on the effectiveness of active support training for adults with more severe ID (i.e. with ABS scores below 180). Active support was as effective for people with the triad of social impairments as for those without it. However, the effectiveness of support offered to people with challenging behaviour or mental illness did not significantly increase.

Adult↗

An evaluation of two Mexican food guides.

In Mexico, the food guide developed by The National Institute of Nutrition for the Mexican population is 'The Pyramid of Health'. In the northwestern Mexican state of Baja California, the Nutrition Institute of Baja California (INUBAC) developed and validated another food guide. This guide, named 'The Apple of Health', is based on current nutrition research and the typical food patterns. The purpose of this article was to evaluate and compare (1) the graphical impact, (2) the understanding of the overall message, and (3) the ability to apply the information from both food guides, using a diet design score and focus group interviews, among women from two different education levels living in Baja California. Results showed that mean diet design percentage scores obtained by the participants using The Pyramid of Health were 64.1 and using The Apple of Health 76.7. No statistical difference was found between the two education levels. The majority of the focus group participants expressed that the most appealing food guide was The Apple of Health because of its color and graphic art. However, the Pyramid was more familiar to the participants. The study subjects strongly recommended The Apple of Health food guide as an educational tool for the whole family.

Adult↗

A new scale to assess radiographic success of secondary alveolar bone grafts.

OBJECTIVES: To propose a new scale for evaluating the position of the bone graft within the cleft and assess its inter- and intraobserver reliability. DESIGN: Sixty-six patients (70 cleft sites) over a 14-year period were assessed, 90% of patients retrospectively and 10% prospectively. The radiographs were reviewed by two clinicians in controlled conditions twice, with 1 week between assessments. Both clinicians were blind to patient identity. OUTCOME MEASURES: A new scale subdividing the position of the bone into one of six categories was used. The radiographs were also assessed using the Bergland scale. RESULTS: Using the Bergland scale, 62.9% of the cleft sites were type I, 21.4% type II, 4.3% type III, and 5.7% type IV. It was not possible to assess 5.7% of the clefts with this scale because the canine was unerupted. Using the Chelsea alveolar bone graft scale, 58% were category A, 20% B, 7% C, 3% D, 3% E, and 9% F. CONCLUSIONS: The above scale can be used to determine accurately the position of bone within the cleft site. It can be used in the mixed dentition prior to eruption of the canine. It demonstrated moderate to substantial inter- and intraobserver reliability and offers several advantages, compared with other scales.

Adolescent↗

A genomewide scan for loci predisposing to type 2 diabetes in a U.K. population (the Diabetes UK Warren 2 Repository): analysis of 573 pedigrees provides independent replication of a susceptibility locus on chromosome 1q.

Improved molecular understanding of the pathogenesis of type 2 diabetes is essential if current therapeutic and preventative options are to be extended. To identify diabetes-susceptibility genes, we have completed a primary (418-marker, 9-cM) autosomal-genome scan of 743 sib pairs (573 pedigrees) with type 2 diabetes who are from the Diabetes UK Warren 2 repository. Nonparametric linkage analysis of the entire data set identified seven regions showing evidence for linkage, with allele-sharing LOD scores > or =1.18 (P< or =.01). The strongest evidence was seen on chromosomes 8p21-22 (near D8S258 [LOD score 2.55]) and 10q23.3 (near D10S1765 [LOD score 1.99]), both coinciding with regions identified in previous scans in European subjects. This was also true of two lesser regions identified, on chromosomes 5q13 (D5S647 [LOD score 1.22] and 5q32 (D5S436 [LOD score 1.22]). Loci on 7p15.3 (LOD score 1.31) and 8q24.2 (LOD score 1.41) are novel. The final region showing evidence for linkage, on chromosome 1q24-25 (near D1S218 [LOD score 1.50]), colocalizes with evidence for linkage to diabetes found in Utah, French, and Pima families and in the GK rat. After dense-map genotyping (mean marker spacing 4.4 cM), evidence for linkage to this region increased to a LOD score of 1.98. Conditional analyses revealed nominally significant interactions between this locus and the regions on chromosomes 10q23.3 (P=.01) and 5q32 (P=.02). These data, derived from one of the largest genome scans undertaken in this condition, confirm that individual susceptibility-gene effects for type 2 diabetes are likely to be modest in size. Taken with genome scans in other populations, they provide both replication of previous evidence indicating the presence of a diabetes-susceptibility locus on chromosome 1q24-25 and support for the existence of additional loci on chromosomes 5, 8, and 10. These data should accelerate positional cloning efforts in these regions of interest.

Chromosome Mapping↗

Normal pathogen-specific immune responses mounted by CTLA-4-deficient T cells: a paradigm reconsidered.

CTLA-4 is a critical negative regulator of T cell responses and CTLA-4-deficient (CTLA-4(-/-)) mice die of a lymphproliferative disease. Nevertheless, RAG-2-deficient mice reconstituted with a mixture of CTLA-4(-/-) and normal (CTLA-4(+/+)) bone marrow survive in the absence of any signs of disease, although 50% of their T cells do not express CTLA-4. Using such mixed chimeras, we analyzed the role of CTLA-4 in specific T cell responses to lymphocytic choriomeningitis virus, Leishmania major and mouse mammary tumor virus, which cause acute, chronic and persistent infections, respectively. The populations of antigen-specific CTLA-4(-/-)CD4(+) and CTLA-4(-/-)CD8(+) T cells became activated, expanded and contracted indistinguishably from CTLA-4(+/+)CD4(+) and CTLA-4(+/+)CD8(+) T cells after infection with all three pathogens. Thus, CTLA-4 is not involved in the down-regulation of specific T cell responses and peripheral deletion in a T cell-autonomous fashion.

Abatacept↗

Outcome of intracytoplasmic sperm injection in azoospermic patients: stressing the liaison between the urologist and reproductive medicine specialist.

OBJECTIVES: To analyze the outcome of intracytoplasmic sperm injection (ICSI) cycles in infertile couples in whom the main diagnosis of infertility was azoospermia of obstructive and nonobstructive origin. METHODS: Eighty-three consecutive ICSI cycles were carried out with retrieved testicular or epididymal spermatozoa, 60 cycles in 32 patients with obstructive azoospermia and 23 cycles in 12 patients with nonobstructive azoospermia. Fifty-four testicular biopsies (testicular sperm extraction) and 18 epididymal aspirations (microepididymal sperm aspiration) were performed.Results. Motile spermatozoa were recovered in 65 cycles (90.3%). In another 3 (4.2%), nonmotile spermatozoa were retrieved. In 4 patients (5.5%), sperm could not be recovered. In 11 cycles, frozen sperm from a previous procedure were used. A significantly lower fertilization rate (64% versus 73%, P = 0.02), clinical pregnancy rate (13% versus 47%, P <0.001), and good embryo quality rates (35% versus 56%, P = 0.009) were observed in patients with nonobstructive azoospermia. In patients with obstructive azoospermia, no significant differences were observed when the outcome was analyzed on the basis of the sperm origin (ie, from testicular sperm extraction or microepididymal sperm aspiration). CONCLUSIONS: When combining testicular sperm extraction or microepididymal sperm aspiration with ICSI in patients with obstructive azoospermia, the results in terms of fertilization, implantation, and pregnancy rates were similar to those found in patients with nonazoospermic obstruction who underwent ICSI with ejaculated sperm. Patients with nonobstructive azoospermia had lower fertilization, embryo quality, and pregnancy rates than did those with obstructive azoospermia, probably because of severe defects in spermatogenesis, leading to poor gamete quality. The urologist and reproductive endocrinologist now have an excellent therapeutic option to offer men with previously intractable infertility.

Adult↗

Comparison of the WHO/ISUP classification and cytokeratin 20 expression in predicting the behavior of low-grade papillary urothelial tumors. World/Health Organization/Internattional Society of Urologic Pathology.

It has not been possible to identify those low-grade papillary transitional cell bladder tumors that will recur based on conventional histopathologic assessment. Both the new World Health Organization/International Society of Urologic Pathology (WHO/ISUP) classification of transitional cell papillary neoplasms and the pattern of tumor cytokeratin 20 (CK20) immunostaining have been suggested as means of improving prognostication in low-grade transitional cell tumors. Forty-nine low-grade, noninvasive papillary transitional cell tumors were identified for the period between 1984 and 1993. The recently described WHO/ISUP classification was applied, and the tumors were classified histologically as papilloma, papillary neoplasm of low malignant potential (LMP) or low-grade papillary carcinoma. After CK20 immunostaining, the expression pattern in the tumor was classified as normal (superficial) or abnormal. Of 49 tumors, 20 were classified as papillary neoplasms of LMP and five of these patients (25%) experienced a recurrence. Of 29 tumors classified as low-grade papillary carcinoma, 14 (48.2%) recurred. In 46 of 49 cases, the CK20 immunostaining could be evaluated. Sixteen tumors showed normal (superficial) pattern of CK20 expression, and four (25%) of these patients experienced a recurrence. In contrast, of 30 patients with abnormal CK20 staining of their tumors, 15 (50%) patients had one or more recurrences. In this study, papillary neoplasms of LMP (as per the WHO/ISUP classification system) had a lower recurrence rate than low-grade papillary transitional cell carcinoma. Similarly low-grade urothelial tumors showing a normal CK20 expression pattern recurred less frequently than tumors with an abnormal pattern of CK20 staining. Neither of these differences was statistically significant, and recurrences were observed in 20% of patients whose tumors were both classified as papillary neoplasms of LMP and showed normal CK20 immunostaining; thus they do not allow a change in our current management of patients with low-grade papillary urothelial tumors, with close follow-up for all patients.

Adult↗

Diffuse calcification of the airways.

Airway calcification is usually restricted to the cartilaginous conducting portion of the bronchial tree. Alternatively, calcification of the alveoli is a relatively common consequence of calcium and phosphate imbalance. We wish to report an unusual case in which diffuse calcification of the entire bronchial tree, absent alveolar calcification, was identified in a patient with renal dysfunction. Pathologists should not exclude metastatic calcification when considering the etiology of bronchial calcification.

Adult↗

Deletion of the CD4 silencer element supports a stochastic mechanism of thymocyte lineage commitment.

The mechanism of T cell lineage commitment remains controversial; to examine it we deleted the CD4-silencer element in the germ line of a mouse using a combination of gene targeting and Cre/LoxP-mediated recombination. We found that these mice were unable to extinguish CD4 expression either in immature thymocytes or mature CD8+ cytotoxic T cells (CTLs), which resulted in the development of major histocompatibility complex class II-restricted double-positive CTLs in the periphery. This finding strongly supports a stochastic over an instructive mechanism of coreceptor down-regulation.

Animals↗

Bacterial contamination of uniforms.

Microbiological sampling of nurses' uniforms was undertaken using a Casella slit sampler. Staphylococcus aureus, Clostridium difficile and vancomycin-resistant enterococci were detected on uniforms both before and after a span of duty. Recommendations for provision and changing of nurses' uniforms are made.

Clostridioides difficile↗

The mutagenic potential of acetonitrile in the bone marrow and peripheral blood of the mouse.

Acetonitrile was tested for its ability to induce clastogenic or aneugenic effects through the induction of micronucleated polychromatic erythrocytes (MNPCE) in mouse bone marrow and peripheral blood. Groups of NMRI mice, five males and five females, were administered a single i.p. dose of acetonitrile, corresponding to the maximum tolerated dose (MTD), 100 or 125 mg/kg body wt for males and females, respectively. Bone marrow was sampled at 18, 24 or 36 h after treatment, while peripheral blood was sampled before and 24, 48, 72 and 96 h after treatment. Positive controls were administered cyclophosphamide (65 mg/kg i.p.). Acetonitrile did not increase the incidence of MNPCE in either bone marrow or peripheral blood in male mice or in peripheral blood in females. A small, but statistically significant (P: < 0.05), increase was observed in female bone marrow 36 h after administration, but since this was within the range of the control data it is not considered to be of biological significance. Cyclophosphamide increased the incidence of MNPCE in bone marrow and peripheral blood of both sexes. It is concluded that acetonitrile is neither clastogenic nor aneugenic in the bone marrow of the mouse at the MTD.

Acetonitriles↗

A randomised controlled trial to compare methods of milk expression after preterm delivery.

OBJECTIVES: Primary: to compare sequential and simultaneous breast pumping on volume of milk expressed and its fat content. Secondary: to measure the effect of breast massage on milk volume and fat content. DESIGN: Sequential randomised controlled trial. SETTING: Neonatal intensive care unit, North Staffordshire Hospital NHS Trust. SUBJECTS: Data on 36 women were analysed; 19 women used simultaneous pumping and 17 used sequential pumping. INTERVENTIONS: Women were randomly allocated to use either simultaneous (both breasts simultaneously) or sequential (one breast then the other) milk expression. Stratification was used to ensure that the groups were balanced for parity and gestation. A crossover design was used for massage, with patients acting as their own controls. Women were randomly allocated to receive either massage or non-massage first. MAIN OUTCOME MEASURES: Volume of milk expressed per expression and its fat content (estimated by the creamatocrit method). RESULTS: Milk yield per expression was: sequential pumping with no massage, 51.32 g (95% confidence interval (CI) 56.57 to 46.07); sequential pumping with massage, 78.71 g (95% CI 85.19 to 72.24); simultaneous pumping with no massage, 87.69 g (95% CI 96.80 to 78.57); simultaneous pumping with massage, 125.08 g (95% CI 140.43 to 109.74). The fat concentration in the milk was not affected by the increase in volume achieved by the interventions. CONCLUSIONS: The results are unequivocal and show that simultaneous pumping is more effective at producing milk than sequential pumping and that breast massage has an additive effect, improving milk production in both groups. As frequent and efficient milk removal is essential for continued production of milk, mothers of preterm infants wishing to express milk for their sick babies should be taught these techniques.

Cross-Over Studies↗

Regulation of E-box DNA binding during in vivo and in vitro activation of rat and human hepatic stellate cells.

BACKGROUND: Activation of hepatic stellate cells (HSCs) to a myofibroblastic phenotype is a key event in liver fibrosis. Identification of transcription factors with activities that are modulated during HSC activation will improve our understanding of the molecular events controlling HSC activation. AIMS: To determine if changes in E-box DNA binding activity occur during in vitro and in vivo activation of rat and human HSCs and to investigate mechanisms underlying any observed changes. METHODS: Nuclear extracts were prepared from rat HSCs isolated and cultured from normal and carbon tetrachloride injured rat livers and from HSCs isolated from human liver. EMSA analysis of E-box DNA binding activity was performed on nuclear extracts to determine changes during HSC activation. Western and northern blot analysis of MyoD and Id1 basic helix-loop-helix (bHLH) proteins was performed to confirm expression in HSC. RESULTS: HSC activation was associated with inducible expression of two low mobility E-box binding complexes that were immunoreactive with an anti-MyoD antibody. MyoD mRNA expression was found at similar levels in freshly isolated and activated HSCs; in contrast, MyoD protein expression was elevated in activated HSCs. Activation of rat HSCs was accompanied by reduced expression of the inhibitory bHLH protein Id1. CONCLUSIONS: In vitro and in vivo activation of rat and human HSCs is accompanied by induction of MyoD binding to E-box DNA sequences which appears to be mechanistically associated with elevated MyoD protein expression and reduced expression of the inhibitory Id1 protein. Clarification of the role of MyoD and Id1 proteins in HSC activation and liver fibrogenesis is now required.

Adult↗