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Biomedical subjects

S Walker

Publications and source records attributed to S Walker.

At least 181 records · Page 10Linked to original sources
PubMed1997

Concerted activity of host cell factor subregions in promoting stable VP16 complex assembly and preventing interference by the acidic activation domain.

In contrast to our understanding of the roles of Oct-1 and VP16 in VP16-mediated transcriptional activation, virtually nothing is known of the role of the second cellular component, termed host cell factor (HCF), or of its structure-function relationships. We show that the majority of the internal region of HCF, including the repeats involved in HCF cleavage, is dispensable for complex assembly with VP16 and Oct-1. The N-terminal domain of HCF (HCF.N) had only weak VP16 binding and complex promoting activity, while the C-terminal region (HCF.C) had no intrinsic activity. However, the C-terminal region strongly enhanced complex formation and reduced dissociation kinetics when linked to the N-terminal domain (HCF.NC). The potent activity of the HCF.NC fusion in complex assembly was recapitulated in vivo in yeast and mammalian cells. Moreover, HCF.N could promote increased complex formation when the acidic activation domain of VP16 was deleted. Restoration of the activation domain strongly inhibited complex formation with HCF.N, but the addition of the C-terminal domain of HCF restored strong stable complex formation with intact VP16. The results indicate that this C-terminal domain is critically required to alter the presentation of the acidic domain of VP16. Additional results are consistent with the interpretation that this alteration in acidic domain presentation for complex assembly also facilitates the activation function in VP16. The sequence of an HCF homolog from Caenorhabditis elegans shows it to be a natural HCF.NC construct, reinforcing the conclusions from our functional analysis.

Amino Acid Sequence↗
PubMed1997

Imaging of optic nerve head drusen with the scanning laser ophthalmoscope.

BACKGROUND: Optic nerve head drusen may present diagnostic difficulties in cases of disc swelling. Imaging of the nerve in a search for drusen is often inconclusive, especially in children, where drusen may be buried below the surface of the nerve head. METHODS: A small study was carried out using a scanning laser ophthalmoscope (SLO) with an infrared confocal facility to scan deep within optic discs in an attempt to image drusen. RESULTS: The SLO was able to demonstrate superficial and buried drusen (using the infrared confocal facility). The superiority of the SLO over ultrasound in the presence of lens opacity was revealed, as the SLO simultaneously demonstrated both drusen and the associated anomalous disc features which are not detected by ultrasound. CONCLUSION: The SLO can help in the diagnosis of optic disc drusen especially in difficult cases where lens opacity or buried drusen hinders their definitive diagnosis.

Adolescent↗
PubMed1997

Audit of neonatal screening programme for phenylketonuria and congenital hypothyroidism.

The performance of the neonatal screening programme was audited against clinical standards in the Bath clinical area from 1 April 1994 to 31 March 1996. The standards and policy were agreed by local service provider representatives of the screening and were audited, using laboratory and child health computer systems and medical records. Two annual reports were produced with recommendations for improvement communicated to representatives of the service. Thus the first audit loop has been completed. The audit shows that the coverage of the service is excellent, with all eligible babies being offered screening; those with congenital hypothyroidism or phenylketonuria receive appropriate treatment by the 28 day standard. The process works extremely well, although areas for improvement have been identified, to increase the efficiency of the service. It is concluded that an effective and efficient audit cycle can be established, to monitor and improve the performance of the neonatal screening service.

Age Factors↗
PubMed1997

Effect of cyclosporin A on the allergen-induced late asthmatic reaction.

BACKGROUND: The allergen-induced late asthmatic reaction (LAR) is associated with mucosal inflammation involving several cell types including activated T lymphocytes and eosinophils. In contrast, the early asthmatic reaction (EAR) is considered to results from rapid allergen-induced release of bronchoconstrictor mediators from IgE sensitised mast cells. Cyclosporin A has efficacy in chronic severe corticosteroid-dependent asthma and is believed to act principally by inhibiting cytokine mRNA transcription in T lymphocytes. However, it has effects on other cell types in vitro, including the inhibition of exocytosis/degranulation events in mast cells. It was therefore hypothesised that cyclosporin A would attenuate both the EAR and LAR in subjects with mild asthma. METHODS: Twelve sensitised atopic asthmatic subjects with documented dual asthmatic responses were studied in a double blind, placebo controlled, crossover trial. On two separate study visits subjects received two oral doses of either cyclosporin A or matched placebo before inhaled allergen challenges. The forced expiratory volume in one second (FEV1) was measured half hourly for eight hours and blood eosinophil counts were analysed three, six, and 24 hours after the challenge. Treatment effects on blood eosinophil counts as well as the EAR and LAR, respectively defined as the areas under the curve (AUC) of FEV1 changes from baseline between 0-1 and 4-8 hours after challenge, were compared by non-parametric crossover analysis. RESULTS: Cyclosporin A reduced both the LAR (median AUC -41.9 1.h (interquartile range -82.7 to -12.4) for cyclosporin A and -84.5 1.h (-248.9 to -39.1) for placebo; p = 0.007) and the late increase in blood eosinophils (median 0.2 x 10(9)/1 (0.15 to 0.4) for cyclosporin A and 0.4 x 10(9)/1 (0.25 to 0.55) for placebo; p = 0.024) but had no effect on the EAR. The reduction of the LAR by cyclosporin A correlated significantly with prechallenge blood concentrations of cyclosporin A (r = 0.6, p = 0.028). CONCLUSIONS: These data are consistent with the concept that cyclosporin A has anti-inflammatory actions in asthma resulting from inhibition of mRNA transcription of eosinophil-active cytokines, predominantly in T lymphocytes. Cyclosporin A, possibly in its inhaled form, or other agents which prevent cytokine gene transcription may therefore have potential in ameliorating the inflammatory component of asthma.

Adult↗
PubMed1997

Screening for drugs of abuse (II): Cannabinoids, lysergic acid diethylamide, buprenorphine, methadone, barbiturates, benzodiazepines and other drugs.

Requirements for the provision of an efficient and reliable service for drugs of abuse screening in urine have been summarized in Part I of this review. The requirements included rapid turn-around times, good communications between requesting clinicians and the laboratory, and participation in quality assessment schemes. In addition, the need for checking/confirmation of positive results obtained for preliminary screening methods was stressed. This aspect of the service has assumed even greater importance with widespread use of dip-stick technology and the increasing number of reasons for which drug screening is performed. Many of these additional uses of drug screening have possible serious legal implications, for example, screening school pupils, professional footballers, parents involved in child custody cases, persons applying for renewal of a driving licence after disqualification for a drug-related offence, doctors seeking re-registration after removal for drug abuse, and checking for compliance with terms of probation orders; as well as pre-employment screening and work-place testing. In many cases these requests will be received from a general practitioner or drug clinic with no indication of the reason for which testing has been requested. This also raises the serious problems of a chain of custody, provision of two samples, stability of samples, and secure and lengthy storage of samples in the laboratory-samples may be requested by legal authorities several months after the initial testing. The need for confirmation of positive results is now widely accepted but it may be equally important to confirm unexpected negative results. Failure to detect the presence of maintenance drugs may lead to the patient being discharged from a drug treatment clinic and, if attendance at the clinic is one of the terms of continued employment, to dismissal. It seems likely that increasing abuse of drugs and the efforts of regulatory authorities to control this, will lead to the manufacture of more designer drugs. Production of substituted phenethylamines was facilitated by the drug makers' cook book, 'PIHKAL' (Phenethylamines I Have Known And Loved) by Dr Alexander Shulgin and Ann Shulgin, and production of substituted tryptamines is promised in their next book, TIHKAL. Looking to the future, laboratories will need to ensure that they can detect and quantitate an ever-increasing number of drugs and related substances. The question of confidence in results of drugs of abuse testing raised in 1993 by Watson has assumed even greater importance as a result of attention focused on the OJ Simpson trial in Los Angeles. Toxicological investigations are likely to be challenged more frequently in the future. Even if analyses have been performed by GC-MS, there is a need to establish the level of match between the spectrum of the unknown substance and a library spectrum which is considered acceptable for legal purposes. It will also be essential to ensure that computer libraries contain spectra for all substances likely to be encountered in drugs of abuse screening.

Barbiturates↗
PubMed1997

Short-term response to counseling and case management intervention in a domestic violence shelter.

81 women who accessed counseling and case management services at a domestic violence shelter after three sessions reported that abuse decreased, life satisfaction increased, perceived coping ability improved, as did their satisfaction with the services. Shelter users, however, also displayed significant skill deficits in the inability to apprise or respond appropriately to abusive situations. Limitations on understanding how shelter services affect longer-term outcomes were ascribed to high drop out rates and the absence of follow-up measures. Researchers need to address the causes of drop-out and what specific interventions can meet the needs of short-term shelter users.

Adolescent↗
PubMed1997

Omeprazole, amoxicillin and bismuth for peptic ulcer healing and Helicobacter pylori eradication.

A controlled, randomized study was performed in patients with active peptic ulcer disease and positive Helicobacter pylori (Hp) status to assess the clinical efficacy (endoscopic healing and eradication of Hp) of different combined treatments. In the first part of the study a treatment with omeprazole (CAS 73590-58-6) (40 mg once daily) alone (group A) or in combination with tripotassium dicitrato bismuthate (TDB; 240 mg bid, group B) for 4 weeks was evaluated in 20 and 13 patients, respectively. As expected healing rates were high and comparable (75 vs. 85%), however, Hp-eradication was zero in both groups. In the subsequent second part of the trial group A (n = 19) received omeprazole (20 mg bid) for 2 weeks + amoxicillin (CAS 26787-78-0) tablets (1 g bid only 2nd week). Accumulated healing rate increased to 95% but Hp-eradication was 37%. From group B only 8 patients participated in a second 4-week course of monotherapy with TDB. Whereas healing occurred in all individuals, Hp-eradication was still low (12.5%). In addition plasma levels (omeprazole, Bi) and urinary excretion (Bi) were monitored to test whether drug interaction and/or noncompliance of the patients could help to explain the clinical findings. Systemic availability of Bi was increased by the coadministration of omeprazole and plasma levels of omeprazole were in general higher in Hp-positive patients if compared to those of Hp-negative patients. The following conclusions could be drawn from the 4 parts of the study: Treatment of peptic ulcer disease with omeprazole either alone or in combination with TDB is effective for ulcer healing but not for eradicating Hp. Omeprazole seems to decrease the Hp-eradicating potential of Bi probably due to a drug interaction. A second treatment course with TDB is apparently not of much benefit. One week pretreatment with omeprazole does not affect healing but might attenuate Hp-eradication rate of subsequent combined treatment with amoxicillin. One week coadministration of amoxicillin is not sufficient. The magnitude of omeprazole's plasma levels has no effect on Hp-eradication rates. As the numbers of patients in this study was relatively small these conclusions need to be confirmed by larger trials.

Adult↗
PubMed1997

Impact of parental anxiety on child emotional adjustment when a parent has cancer.

PURPOSE/OBJECTIVES: To describe the relationships among parent anxiety, child anxiety, and emotional adjustment in children who have a parent with cancer. DESIGN: Correlational. SETTING: A large cancer center in the southeastern United States. SAMPLE: Thirty-three child/parent with cancer dyads. METHODS: Research packets were mailed to child/parent dyads who agreed to participate in the study. Parents completed a demographic questionnaire, a Spielberger State-Trait Anxiety Scale, and a Personality Inventory for Children (PIC). Children completed the child version of the Spielberger State-Trait Anxiety Scale. MAIN RESEARCH VARIABLES: Parent anxiety, child anxiety, and child adjustment. FINDINGS: Children who have a parent with cancer and parents who have experienced cancer report significantly higher state and trait anxiety compared to a normed population sample. Parental reports on the PIC indicated that latency-aged children (i.e., 6-12 years) showed significantly greater internalization and somatic symptoms compared to the sample norm. Parent state anxiety was negatively correlated with children's internalization and somatic symptoms. Parental anxiety accounted for the greatest variance in child adjustment. IMPLICATIONS FOR NURSING PRACTICE: These study findings may provide nurses with a better understanding of the vulnerability of children who have a parent with cancer and can build a foundation for the development of supportive interventions for these children.

Adaptation, Psychological↗
PubMed1996

Cationic facial amphiphiles: a promising class of transfection agents.

A promising class of compounds for DNA transfection have been designed by conjugating various polyamines to bile-acid-based amphiphiles. Formulations containing these compounds were tested for their ability to facilitate the uptake of a beta-galactosidase reporter plasmid into COS-7 cells. Dioleoyl phosphatidyl ethanolamine (DOPE) formulations of some of the compounds were several times better than Lipofectin at promoting DNA uptake. The most active compounds contained the most hydrophilic bile acid components. The activity is clearly not related to affinity for DNA: the hydrophobic bile acid conjugates were found to form stable complexes with DNA at lower charge ratios than the hydrophilic conjugates. We suggest that the high activity of the best compounds is related to their facial amphiphilicity, which may confer an ability to destabilize membranes. The success of these unusual cationic transfection agents may inspire the design of even more effective gene delivery agents.

Animals↗
PubMed1996

Reading and spelling deficits among children attending a psychiatric day treatment program.

To investigate the specific behavioural and cognitive characteristics which may account for academic deficits in children with psychiatric disorders, 50 children admitted to a day treatment and school program were assessed using behaviour questionnaires for parents and teachers, and tests assessing intelligence (WISC-R), language (CELF-R) and academic performance (Kaufman Test of Educational Achievement). The academic measures Reading Decoding, Reading Comprehension and Spelling formed the dependent variables. Behaviour and cognitive measures which distinguished the sample from normative data constituted the independent variables. Hierarchical multiple regression analyses were performed in order to identify behaviour and cognitive measures accounting for the academic deficits. In the analyses, three measures (Digit Span, Sentence Assembly, Recalling Sentences), probably assessing overlapping cognitive/linguistic functions, accounted for a large proportion of variance for Reading Decoding (0.47), Reading Comprehension (0.63) and Spelling (0.29). None of the behaviour measures accounted for any variance of the academic variables. It is argued that linguistic dysfunction is a primary deficit which underlies problems in academic learning.

Adolescent↗
PubMed1996

Intrathecal clonidine and baclofen in the management of spasticity and neuropathic pain following spinal cord injury: a case study.

Spasticity and pain are common disabling sequelae following spinal cord injury (SCI) and are often difficult to manage. The two problems are also not infrequently related. A variety of pharmacological and other approaches have been described for management of these problems in SCI. This case study reports a 32-year-old woman with an established incomplete C5 tetraplegia (anterior cord syndrome) who developed severe, intractable anal spasm following a hemorrhoidectomy, which persisted despite very good healing. This prevented evacuation of her bowels and resulted in severe rectal pain and episodes of autonomic dysreflexia. Attempts to modify the rate and mode of delivery of intrathecal baclofen through an existing programmable infusion pump failed to reduce anal sphincter spasm or improve symptoms. A right-sided pudendal block with lignocaine provided some relief. Clonidine was added to baclofen in the pump reservoir and both drugs were administered intrathecally in combination. This resulted in an immediate improvement in anal sphincter spasm and pain relief, allowing rapid reestablishment of her normal bowel pattern without need for any supplemental analgesia. It appears that intrathecal clonidine may have an important role in the treatment of spasticity, either as a single or an adjuvant agent, when intrathecal baclofen alone is ineffective or there is increasing tolerance to baclofen. Intrathecal clonidine may also prove useful in the management of intractable neuropathic pain.

Adult↗
PubMed1996

Reflective practice in the accident and emergency setting.

The object of this paper is critically to analyse the issue of reflective practice within the writer's own professional arena. The writer is a senior nurse within an Accident and Emergency (A & E) department. It has long been recognised that a gap exists between theory and practice in nursing. There has been much discussion in the nursing literature about the development of the reflective practitioner and how reflection in practice can assist in closing the theory-practice gap. Nurses have always experienced great difficulty in identifying a theory of practice. Jarvis (1992) states that reflective medicine is a frequently used but infrequently defined concept in nursing at the present time. For both qualified nurses and students alike, reflection can be utilised as a learning process to help them expand and develop their clinical knowledge and skills to directly benefit client care (Dewing 1990). Schon (1987) has identified reflection as a process of knowledge acquisition originating in practice and best suited to solving complex practice based problems. Reflection is an active process of exploration and discovery which often leads to unexpected outcomes (Boud et al 1985). Reflection that occurs in the process of an experience is referred to as reflection-in-action (Schon 1987). Nurses have the ability to think about their actions while they are carrying them out and change the actions should the professional's assessment of the situation change (Schon 1983). Reflection can lead to new understanding and appreciation which can be put to use in future experiences (Dewing 1990). This paper will commence with a brief explanation of how nurse education is developing reflection and experience to assist the student nurse to close the theory-practice gap.

Clinical Competence↗
PubMed1996

Topical diclofenac relieves pain from corneal rust ring.

A prospective double-masked placebo controlled trial to assess the potential benefit of topical diclofenac in the treatment of corneal rust ring of 40 patients attending the eye casualty department was carried out. Patients allocated to the diclofenac group had significantly reduced pain scores at 48 hours after starting treatment compared with patients allocated to the placebo group (p = 0.008 and p = 0.042 for visual analogue and Likert pain scales respectively). No difference was noted between groups in terms of rate of epithelial healing or degree of inflammation. Topical diclofenac offers improved analgesia in the treatment of corneal rust ring.

Administration, Topical↗
PubMed1996

Continuous extradural infusion of ropivacaine for prevention of postoperative pain after major orthopaedic surgery.

We studied 151 patients undergoing total hip or knee arthroplasty, or cruciate ligament reconstruction in a multicentre study in Australia and New Zealand. Patients were openly allocated randomly to one of five treatment groups or to a control group. General anaesthesia was induced after introduction of extradural block with 0.5% ropivacaine. After surgery, patients received an extradural infusion of 0.2% ropivacaine at 6, 8, 10, 12 or 14 ml h-1 or received no postoperative extradural infusion (control group). All patients had access to i.v. PCA morphine for supplementary analgesia. Morphine consumption was lower in all treatment groups compared with the control group, decreasing with increasing ropivacaine infusion rate. Median VAS scores were lower in all ropivacaine infusion groups compared with the control group for the first 10 h of the study; however by the end of the study, VAS scores were similar in all groups. The higher ropivacaine infusion rates caused a slower convergence of spread of the initial sensory block and a higher degree of motor block. The overall incidence of side effects was similar, with the exception of a higher incidence of urinary retention and hypotension in the groups receiving the higher rates of ropivacaine. The quality of treatment scores were similar for all treatment groups (Br. J. Anaesth. 1996; 76: 606-610).

Adult↗
PubMed1996

Effect of cetirizine and prednisolone on cellular infiltration and cytokine mRNA expression during allergen-induced late cutaneous responses.

BACKGROUND: The ability of cetirizine to inhibit eosinophil infiltration into the sites of allergen-induced cutaneous late-phase reactions is controversial. A previous skin biopsy study gave negative results with 15 mg of cetirizine as a single dose. OBJECTIVE: To confirm these findings we have used cetirizine (30 mg daily) for 5 days and compared the results with prednisolone (20 mg daily for 5 days) as a positive control. The effect of these agents on mRNA positive cells for interleukin-3 (IL-3), interleukin-4, interleukin-5 and granulocyte/macrophage-colony stimulating factor (GM-CSF) was also evaluated. METHODS: A double-blind, placebo-controlled cross-over study (n = 12) was followed. After each treatment 30 biological units (BUs) of Dermatophagoides pteronyssinus or Phleum pratense were injected intradermally and the early (15 min) and late-phase response sizes (6 and 24 h) were measured. Skin biopsies were taken at 24 h for immunocytochemistry and in situ hybridization. RESULTS: Cetirizine but not prednisolone inhibited the early-phase response (37%, P = 0.004). In contrast prednisolone, but not cetirizine, significantly inhibited the size of the late-phase reaction at 24 h (70%, P = 0.021). This was associated with significant decreases in total (MBP+) and activated (EG2+) eosinophils (P = 0.019 and 0.014, respectively), as compared with placebo. There were also clear but non-significant reductions in interleukin-3, interleukin-4, interleukin-5 and granulocyte/macrophage-colony stimulating factor mRNA+ cells. CONCLUSION: Prednisolone, but not cetirizine, inhibited both the magnitude of the allergen-induced late-phase response and the accompanying local eosinophil infiltration. These corticosteroid effects were associated with a reduction in cells expressing mRNA for 'TH2-type' cytokines.

Adult↗