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Biomedical subjects

J Reilly

Publications and source records attributed to J Reilly.

At least 37 records · Page 2Linked to original sources

Verbal fluency deficits in children with specific language impairment: slow rapid naming or slow to name?

This study examined aspects of verbal fluency performance of children with Specific Language Impairment (SLI) and typically developing children matched on age and Block Design scores. While children with SLI showed deficits in verbal fluency compared to their peers, they showed the same pattern of performance on phonemic compared to semantic fluency trials. Children with SLI and normally developing children also demonstrated equivalent rates of clustering and switching, measures hypothesized to reflect aspects of frontal lobe functioning, when the overall number of exemplars was taken into account. The absence of a condition by group effect supports general processing limitation accounts of SLI, while the absence of group differences on cluster size and switches supports language-based processing accounts of SLI.

Child↗

A special courage: dealing with the Paddington rail crash.

Supporting traumatized employees requires special skills and techniques if it is to be effective. Unfortunately, there is little to inform or guide organizations on how this should be achieved. The present controversy over the use of trauma management systems and debriefing has not been helpful in informing organizations on the best way to take care of employees who become traumatized during the course of their work. This paper looks at how Sainsbury's Supermarkets Ltd managed traumatization through the activation of its Violence at Work policy and procedures, and finally presents the results of an evaluation exercise that was undertaken following the Paddington rail crash.

Accidents↗

Breast reconstruction among inner city women with breast carcinoma.

Despite the known benefits of breast reconstruction, the numbers of patients undergoing breast reconstruction remains lower than expected. The goal of this study was to survey systematically the experience of inner city breast cancer patients with regard to breast reconstruction in an urban public hospital setting. Between July 1999 and April 2000, 60 patients attending the Kings County Hospital Center Outpatient Breast Cancer Clinic were enrolled in this study. A multidimensional questionnaire was designed to explore the factors that determine breast reconstruction among inner city women. Demographic analysis failed to show any difference in education, insurance status, and economics between women who undergo breast reconstruction (N = 11) and nonreconstructed patients (N = 49). Patients who have undergone reconstruction are satisfied with their results. Reconstructed women have a higher rating of satisfaction with their sex life than nonreconstructed women (p = 0.041). The women without breast reconstruction had a tendency toward more embarrassment when undressing in front of a partner and lower partner satisfaction with their bodies. The most commonly sited reason patients did not undergo breast reconstruction was the lack of knowledge about breast reconstruction before mastectomy. This emphasizes the importance of educating patients on all the options in the management of breast carcinoma.

Adult↗

Stem cell engraftment strategies.

The donor stem cell phenotype and host microenvironment determine the outcome of a stem cell transplant. In a series of transplant studies in syngeneic male to female or congenic Ly5.1/Ly5.2 models in which hosts have received no or minimal irradiation (100 cGy), evidence overwhelmingly supports the concept that syngeneic engraftment is determined by stem cell competition. These approaches can be extended to H-2 mismatched allogeneic mouse combination when antigen pre-exposure and CD40-CD40 ligand antibody blockage are employed. A human trial in patients with resistant neoplasia infusing pheresed blood with 10(8) CD3 cells/kg showed that tumor responses and complete chimerism occur with very low levels of CD34+ cells/kg and that the extent of previous treatment is a critical factor in determining chimerism. A major feature of transplants is the phenotype of the donor stem cell. This phenotype shows dramatic reversible plasticity involving differentiation, adhesion protein expression, and engraftment with cytokine-induced cell-cycle transit. Homing is probably also plastic. Marked fluctuations in engraftment capacity are also seen at different points in marrow circadian rhythm.

Adolescent↗

Neurotrophin channeling of neural progenitor cell differentiation.

The act of defining neuropoietic progenitor/stem cells is still in its early phases. Epidermal growth factor (EGF) stimulates extended proliferation of aggregates of subventricular striatal cells, taken from E15 mouse striatum, termed neurospheres in liquid culture. We have shown here and in previous work, using either immunohistochemistry or RT-PCR, that neurosphere cells express 13 cytokines (32 tested) and 20 cytokine receptors (28 tested), with 11 potential paracrine and nine potential autocrine loops. The neurotrophin receptors, Trk A, B, and C, were all expressed. Using a newly developed FACS single cell deposition technique, we evaluated the capacity of single EGF stimulated neurosphere cells to respond to the ligands for Trk A and B, nerve growth factor (NGF), and brain-derived neurotrophin factor (BDNF). Addition of NGF or BDNF to EGF for 14 days had no effect, but removal of EGF at day 14 with subsequent addition of BDNF or NGF resulted in an increase in neuronal and astroglial, but not oligodendrocyte, colony cells at 21 and 28 days of culture for BDNF, and of both cell types at 28 days for NGF. Tri-lineage colonies increased at day 21 with BDNF and at day 28 for both NGF and BDNF. Gross colony morphology also showed changes with neurotrophin addition, forming multiple individual cell balls or filamentous spreads. When EGF was withdrawn, a threshold effect was observed, with small, but not large, colonies ceasing growth. BDNF and NGF showed no effects on cell proliferation when compared to EGF controls, as determined by 5'-bromo-2-deoxyuridine (BrdU) incorporation and thus, they appear to affect differentiation of progenitor cells. These data indicate a sequential action of cytokines with EGF maintaining viability and proliferation and blocking differentiation. Removal of EGF is then permissive for the differentiating effects of BDNF and NGF. These data further indicate that the majority of EGF neurosphere clones have neurotrophin dependent tri-lineage potential.

Animals↗

Breast cancer audit: adapting national audit frameworks for local review of clinical practice.

OBJECTIVE: To assess the value of using a nationally devised data set for breast cancer audit at a local level for reviewing clinical practice. DESIGN: Audit proforma based on the Scottish Cancer Therapy Network (SCTN) minimum data set and database completed prospectively from January 1999. SETTING: Hairmyres Hospital, a district general hospital within Lanarkshire Acute Services NHS Trust. SUBJECTS: The inclusion criteria were those developed by SCTN for the core minimum data set for breast cancer (SCTN 1999). RESULTS: The results indicate that the SCTN minimum data set can be usefully employed to collect prospective data on breast cancer. The data set is sensitive enough to identify any problem areas, which can be reviewed at greater detail when required. This datset is a robust mechanism for collecting meaningful and comparable data both at a local and national level. CONCLUSIONS: The use of SCTN's minimum data set has been successful for local review of practice. This has led to the identification of "out-liers" from the normal range of process indicators and further internal examination of these at a local level by individual clinicians is under way. This exercise has also proved fruitful in identification of other fields, which can be added to the data set to refine the data collected. The database provided by SCTN is easily manipulated allowing for refinement where required. Breast cancer audit carried out in this way is a useful way of reflecting on clinical practice throughout the multidisciplinary team.

Breast Neoplasms↗

Thioridazine for schizophrenia.

BACKGROUND: Thioridazine is a piperidine phenothiazine used for the treatment of people with schizophrenia. It has often been considered the drug of choice in the elderly because of reputed lower levels of extrapyramidal adverse events. It may, however, be more likely to cause cognitive adverse events, such as delirium or worsening of memory, and, on rare occasions, thioridazine has caused pigmentary retinopathy. OBJECTIVES: To examine the effects of thioridazine for those with schizophrenia, and, in particular, elderly people with schizophrenia. SEARCH STRATEGY: Electronic searches of Biological Abstracts (1980-1999), CINAHL (1982-1999), The Cochrane Library (Issue 3, 1999), The Cochrane Schizophrenia Group's Register (January 1999), EMBASE (1980-1999), MEDLINE (1966-1999), PsycLIT (1974-1999) and Sociofile (1974-1999) were undertaken. References of all identified studies were searched for further trials. Pharmaceutical companies and authors of trials were contacted. SELECTION CRITERIA: All randomised clinical trials that compared thioridazine to other treatments for people with schizophrenia or other psychoses. DATA COLLECTION AND ANALYSIS: Citations and, where possible, abstracts were independently inspected by reviewers, papers ordered, re-inspected and quality assessed. Data were independently extracted. Data were excluded if loss to follow up was greater than 40%. For homogeneous dichotomous data the Relative Risk (RR), 95% confidence interval (CI) and, where appropriate, the number needed to treat (NNT) were calculated on an intention-to-treat basis. For continuous data, weighted mean differences were calculated (WMD). All data were inspected for heterogeneity. MAIN RESULTS: 560 people from 11 studies were randomised to thioridazine or placebo. For change in global state, small, short term studies (three months or less) found no difference between groups (RR 0.66 CI 0.35-1.23, n=100). At six months, however, two small studies (n=65) favoured thioridazine (RR 0.34 CI 0.21-0. 56, NNT 2 CI 1-6). Fourteen percent in the thioridazine group left early compared to 32% of people allocated to placebo (RR 0.43 CI 0. 31-0.61, NNT 6 CI 4-10, n=510). Few differences in terms of adverse effects, between thioridazine and placebo, were apparent. Limited data from trials suggest that thioridazine is not strongly anticholinergic (blurred vision RR 2.01 CI 0.56-7.25, n=224). Thioridazine is not sedating (at three months to one year RR 2.48 CI 0.96-6.4, n=122). No data were presented on retinal changes. Two thousand three hundred ninety-seven patients from 26 studies were randomised to thioridazine versus typical antipsychotics. For the outcome 'no better or worse', those allocated to thioridazine were no better off than people given control typical neuroleptics (RR 0. 97 CI 0.78-1.21, n=771). There were no clear differences between thioridazine and other drugs for the outcome 'Mental state - no better or worse' on the BPRS by three months (RR 1.3 CI 0.8-2.11, n=208). Twenty-one studies (n=1737) had 19% attrition in both groups. Few differences were seen in the lists of adverse effects. As expected from the placebo comparison, thioridazine does not cause more anticholinergic-type symptoms than other drugs. About half of people given thioridazine felt drowsy or sedated but this was no different from other drugs (RR 1.06 CI 0.93-1.2, n=909). Parkinsonism was less common in the thioridazine group in the short term (RR 0.29 CI 0.12-0.7, n=340). One small study (n=40) found no clear differences between thioridazine and clozapine. REVIEWER'S CONCLUSIONS: Although there are shortcomings and gaps in the data, there appears to be enough consistency over different outcomes and periods to confirm that thioridazine is an antipsychotic of similar efficacy to other commonly used neuroleptics for people with schizophrenia. Its adverse events profile is similar to that of other drugs, but it may have a lower level of extrapyramidal problems. (ABSTRACT TRU

Aged↗

II. Hypersociability in Williams Syndrome.

Studies of abnormal populations provide a rare opportunity for examining relationships between cognition, genotype and brain neurobiology, permitting comparisons across these different levels of analysis. In our studies, we investigate individuals with a rare, genetically based disorder called Williams syndrome (WMS) to draw links among these levels. A critical component of such a cross-domain undertaking is the clear delineation of the phenotype of the disorder in question. Of special interest in this paper is a relatively unexplored unusual social phenotype in WMS that includes an overfriendly and engaging personality. Four studies measuring distinct aspects of hypersocial behavior in WMS are presented, each probing specific aspects in WMS infants, toddlers, school age children, and adults. The abnormal profile of excessively social behavior represents an important component of the phenotype that may distinguish WMS from other developmental disorders. Furthermore, the studies show that the profile is observed across a wide range of ages, and emerges consistently across multiple experimental paradigms. These studies of hypersocial behavior in WMS promise to provide the groundwork for crossdisciplinary analyses of gene-brain-behavior relationships.

Adolescent↗

Expression of growth factors, cytokines and matrix metalloproteinases in frozen shoulder.

Frozen shoulder is a chronic fibrosing condition of the capsule of the joint. The predominant cells involved are fibroblasts and myofibroblasts which lay down a dense matrix of type-I and type-III collagen within the capsule. This subsequently contracts leading to the typical features of pain and stiffness. Cytokines and growth factors regulate the growth and function of the fibroblasts of connective tissue and remodelling of the matrix is controlled by the matrix metalloproteinases (MMPs) and their inhibitors. Our aim was to determine whether there was an abnormal expression or secretion of cytokines, growth factors and MMPs in tissue samples from 14 patients with frozen shoulder using the reverse transcription/polymerase chain reaction (RT/PCR) technique and to compare the findings with those in tissue from four normal control shoulders and from five patients with Dupuytren's contracture. Tissue from frozen shoulders demonstrated the presence of mRNA for a large number of cytokines and growth factors although the frequency was only slightly higher than in the control tissue. The frequency for a positive signal for the proinflammatory cytokines Il-beta and TNF-alpha and TNF-beta, was not as great as in the Dupuytren's tissue. The presence of mRNA for fibrogenic growth factors was, however, more similar to that obtained in the control and Dupuytren's tissue. This correlated with the histological findings which in most specimens showed a dense fibrous tissue response with few cells other than mature fibroblasts and with very little evidence of any active inflammatory cell process. Positive expressions of the mRNA for the MMPs were also increased, together with their natural inhibitor TIMP. The notable exception compared with control and Dupuytren's tissue was the absence of MMP-14, which is known to be a membrane-type MMP required for the activation of MMP-2 (gelatinase A). Understanding the control mechanisms which play a part in the pathogenesis of frozen shoulder may lead to the development of new regimes of treatment for this common, protracted and painful chronic fibrosing condition.

Cytokines↗

Lymphohematopoietic stem cell engraftment.

Traditional dogma has stated that space needs to be opened by cytoxic myeloablative therapy in order for marrow stem cells to engraft. Recent work in murine transplant models, however, indicates that engraftment is determined by the ratio of donor to host stem cells, i.e., stem cell competition. One hundred centigray whole body irradiation is stem cell toxic and nonmyelotoxic, thus allowing for higher donor chimerism in a murine syngeneic transplant setting. This nontoxic stem cell transplantation can be applied to allogeneic transplant with the addition of a tolerizing step; in this case presensitization with donor spleen cells and administration of CD40 ligand antibody to block costimulation. The stem cells that engraft in the nonmyeloablated are in G0, but are rapidly induced (by 12 hours) to enter the S phase after in vivo engraftment. Exposure of murine marrow to cytokines (IL-3, IL-6, IL-11 and steel factor) expands progenitor clones, induces stem cells into cell cycle, and causes a fluctuating engraftment phenotype tied to phase of cell cycle. These data indicate that the concepts of stem cell competition and fluctuation of stem cell phenotype with cell cycle transit should underlie any new stem cell engraftment strategy.

Animals↗

Comparison of frequencies of atrial fibrillation after coronary artery bypass grafting with and without the use of cardiopulmonary bypass.

This study compared the incidence of postoperative atrial fibrillation in a group of 34 patients undergoing coronary artery bypass graft surgery without the use of cardiopulmonary bypass and cardioplegia with a control group of 747 patients undergoing coronary artery bypass graft surgery using cardiopulmonary bypass and standard cardioplegia. A trend toward a lower incidence of postoperative atrial fibrillation was found in the group that underwent coronary artery bypass graft surgery without the use of cardiopulmonary bypass (n = 0.06).

Adrenergic beta-Antagonists↗

Comparison of free solution capillary electrophoresis and size exclusion chromatography for quantitating non-covalent aggregation of an acylated peptide.

There are few methods available for the rapid and precise quantitation of non-covalent aggregation. The very methods used to measure the aggregation can easily disrupt the weak forces holding an aggregate together. This paper describes the novel application of free solution capillary electrophoresis (CE) for the quantitation of a biologically inactive non-covalent aggregate of C8GLIP (Des-amino-histidine-7-arginine-26 N(epsilon)-octanoyl-lysine-34-human glucagon-like insulinotropic peptide), an acylated peptide. The CE results are compared to a more traditional approach using size exclusion chromatography (SEC). Under the conditions explored in this paper, SEC showed a significantly slower apparent rate of aggregation than CE. This is due to the disruption of the aggregate during the SEC process. The cause of the disruption is complex and is potentially related to the separation process itself, on-column dilution effects, and/or interactions of the aggregate with the column packing or SEC components. Analysis times and dilution are greatly reduced by CE, and, because there is no potentially interactive stationary phase and because both the protein and the walls of the capillary are negatively charged, potential disaggregation due to surface interactions is reduced. Thus, CE is shown to be superior to SEC for this peptide in that disruption of the aggregate is minimized.

Acylation↗

The association of sexual and physical abuse with somatization: characteristics of patients presenting with irritable bowel syndrome and non-epileptic attack disorder.

BACKGROUND: Physical symptoms are commonly presented for treatment in the absence of physical pathology. This study tests predictions arising from the theory that childhood sexual abuse leads to emotional distress, illness orientation and social dysfunction as adults and that one or more of these effects, in turn, leads to presentation of functional (i.e. unexplained) symptoms. METHODS: Two groups of patients with physical symptoms in the absence of organic disease (non-epileptic attack disorder or irritable bowel syndrome) were contrasted with organically diseased groups with comparable symptoms (epilepsy and Crohn's disease, respectively). RESULTS: Despite their contrasting clinical presentation, irritable bowel and non-epileptic attack groups were similar in recalling more sexual and physical abuse, as both children and adults, than their comparison groups. They were also similar in being more emotionally and socially disturbed and illness-orientated, but these putative mediating variables could not account for the relationship of abuse with presentation of functional symptoms. CONCLUSIONS: Adults presenting functional neurological and abdominal symptoms are characterized by history of abuse. The current focus on childhood sexual abuse should be broadened to include sexual, and particularly physical, abuse in adulthood as well as childhood. The intervening processes that link abuse to somatization remain to be identified but are unlikely to include adult emotional and social disturbance or general illness-orientation.

Adult↗

c-kit proto-oncogene exon 8 in-frame deletion plus insertion mutations in acute myeloid leukaemia.

Genomic DNA from 60 cases of acute myeloid leukaemia (AML) was screened for mutations in the c-kit gene. DNA from all 21 exons was subjected to polymerase chain reaction (PCR) amplification and analysis by conformation sensitive gel electrophoresis (CSGE); exons showing altered CSGE patterns were then sequenced. Mutations were identified only in those patients with inv(16) (3/7 cases) or t(8;21) (1/2 cases) and comprised three in-frame deletion plus insertion mutations (exon 8) and one point mutation (exon 10, GTA --> ATA, Val530Ile). Exons 8 and 10 were then analysed in 31 further cases of inv(16) (n = 14) and t(8;21) (n = 17), revealing four additional exon 8 in-frame deletion plus insertion mutations, all of which were in cases of inv(16). All exon 8 in-frame deletion plus insertion mutations (n = 7) involved the loss or replacement of the codon for Asp419 which is highly conserved cross species and is located in the receptor's extracellular domain. The high frequency of the c-kit proto-oncogene exon 8 deletion plus insertion mutations in AML suggests an essential role for this region of the receptor's extracellular domain. The association with inv(16) invites speculation as to the link between these two changes in the pathogenesis of AML.

Acute Disease↗

Office-based insertion of pressure equalization tubes: the role of laser-assisted tympanic membrane fenestration.

OBJECTIVE: To describe the role of the hand-held otoscope combined with a flashscanner CO2 laser, OtoLAM (ESC/Sharplan, Yokneam, Israel), for pressure equalization tube (PET) insertion in an office setting. STUDY DESIGN: Prospective, multisite, clinical cohort trial (Institutional Review Board approved; informed consent) in the setting of pediatric otolaryngology outpatient departments at four tertiary care children's hospitals. METHODS: Selected for the study were 54 patients (96 ears), ages 6 months to 23 years, who met standard indications for PET insertion using cold-knife myringotomy and tube insertion under general anesthesia. PETs were indicated for recurrent otitis media, chronic otitis media with effusion, and eustachian tube dysfunction-all unresponsive to medical therapy. Topical anesthesia was achieved with iontophoresis (n = 1) or topical anesthesia: 8% tetracaine on an Otowick (Xomed Surgical Products, Jacksonville, FL, catalogue No. 400141) against the tympanic membrane for 45 to 180 minutes (n = 53). Laser-assisted tympanic membrane fenestration was performed with the OtoLAM set at single pulse, 2.0- to 2.6-mm spot size, and between 3 and 18 W. Insertion of grommets was accomplished using the otomicroscope and an "alligator" microforceps. Restraints with papoose were used in 79% of children with a mean age of 34.4 months (SD = 60.9 mo). Clinical, parent/patient, and physician satisfaction and comparative cost impact outcomes are described. RESULTS: All ears but three (3%) underwent successful placement of a PET. Pain was described as "absent" in 39%, "present but tolerable" in 30%, and "severe" in 30% of children at the time of procedure; 5 minutes after the procedure pain was described as "absent" in 75%, "present but tolerable" in 22%, and "severe" in 3%. Tube plugging (3 of 74 available ears; 4%) or persistent otorrhea (1 of 74 ears; 1.4%) occurred infrequently at the 1-month follow-up. Before PET insertion, hearing loss was noted in 66% of cases (mild, 38%; moderate, 22%; and severe, 6%). Mild hearing loss was noted in only 8% and moderate hearing loss in 2% of 47 (50%) of the ears at the 3-month follow-up. Ninety-two percent of parents were highly satisfied with the procedure in preference to PETs in the operating room under general anesthesia, and 97% preferred OtoLAM with PET insertion, rather than further courses of antibiotics; only one parent would rather have had the PET insertion under general anesthesia. Cost savings to health care organizations, particularly payers, and to parents are substantial (32%-48%) and warrant attention. Cost to the physician is manageable only if an appropriate approach to the third party payers results in a substantial increase in reimbursements. CONCLUSIONS: The data indicate excellent clinical effectiveness, reduced risk, and high parent and physician satisfaction. Strong incentives for physicians to use this technique are in all stakeholders' best interests. These incentives need to evolve as soon as possible for the more widespread acceptance of OtoLAM with PET insertion in an office setting for appropriately selected patients.

Adolescent↗

A qualitative investigation of women's perceptions of premenstrual syndrome: implications for general practitioners.

BACKGROUND: Many women consult general practitioners each year, seeking treatment for premenstrual syndrome. This qualitative study presents evidence of women's own perceptions of this problem, which may assist in the provision of individualized health care. AIM: To explore women's constructions of premenstrual syndrome using grounded analysis. METHOD: A qualitative, semi-structured interview study carried out in Northern Ireland. Thirteen women were interviewed individually. Thereafter, 33 women participated in group discussions. Five health visitors then commented individually on the findings. RESULTS: Seven themes emerged from the analysis. These themes suggested that women tend to view the menstrual cycle holistically and that premenstrual syndrome is regarded as debilitating by only a small minority of women. Participants indicated an awareness of the intra- and inter-personal variability of menstrual experience. They were ambivalent about menstruation, viewing it as natural but, at the same time, unnatural in terms of day-to-day existence. Talking to other women served two functions, first by providing a yardstick against which to evaluate their own experiences, and secondly by providing support and advice. In contrast, women tended to talk about menstruation only to selected men, mainly partners, primarily in the interests of educating them. Women viewed menstruation as potentially disempowering by virtue of its uncontrollability, and felt that both a positive attitude and the use of a range of remedies were important for women wishing to become empowered with respect to this aspect of their lives. CONCLUSIONS: Women's own constructions of premenstrual syndrome differ markedly from those as presented in medical textbooks and research literature: secondary sources that have significantly impacted upon general practitioners' attitudes towards this condition. The provision of a range of treatment options, including support groups, is suggested, on the basis of evidence gathered using qualitative methods, as likely to be viewed by women as more appropriate than offering treatment based on the evidence provided by traditional randomized controlled trials.

Adult↗

The fluctuating phenotype of the lymphohematopoietic stem cell with cell cycle transit.

The most primitive engrafting hematopoietic stem cell has been assumed to have a fixed phenotype, with changes in engraftment and renewal potential occurring in a stepwise irreversible fashion linked with differentiation. Recent work shows that in vitro cytokine stimulation of murine marrow cells induces cell cycle transit of primitive stem cells, taking 40 h for progression from G0 to mitosis and 12 h for subsequent doublings. At 48 h of culture, progenitors are expanded, but stem cell engraftment is markedly diminished. We have investigated whether this effect on engraftment was an irreversible step or a reversible plastic feature correlated with cell cycle progression. Long-term engraftment (2 and 6 mo) of male BALB/c marrow cells exposed in vitro to interleukin (IL)-3, IL-6, IL-11, and steel factor was assessed at 2-4-h intervals of culture over 24-48 h using irradiated female hosts; the engraftment phenotype showed marked fluctuations over 2-4-h intervals, with engraftment nadirs occurring in late S and early G2. These data show that early stem cell regulation is cell cycle based, and have critical implications for strategies for stem cell expansion and engraftment or gene therapy, since position in cell cycle will determine whether effective engraftment occurs in either setting.

Animals↗