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Biomedical subjects

M Marshall

Publications and source records attributed to M Marshall.

At least 73 records · Page 4Linked to original sources
PubMed2000

Unpublished rating scales: a major source of bias in randomised controlled trials of treatments for schizophrenia.

BACKGROUND: A recent review suggested an association between using unpublished scales in clinical trials and finding significant results. AIMS: To determine whether such an association existed in schizophrenia trials. METHOD: Three hundred trials were randomly selected from the Cochrane Schizophrenia Group's Register. All comparisons between treatment groups and control groups using rating scales were identified. The publication status of each scale was determined and claims of a significant treatment effect were recorded. RESULTS: Trials were more likely to report that a treatment was superior to control when an unpublished scale was used to make the comparison (relative risk 1.37 (95% CI 1.12-1.68)). This effect increased when a 'gold-standard' definition of treatment superiority was applied (RR 1.94 (95% CI 1.35-2.79)). In non-pharmacological trials, one-third of 'gold-standard' claims of treatment superiority would not have been made if published scales had been used. CONCLUSIONS: Unpublished scales are a source of bias in schizophrenia trials.

Humans↗
PubMed2000

Physical and chemical evidence remaining after the explosion of large improvised bombs. Part 1: firings of ammonium nitrate/sugar and urea nitrate.

Recent criminal acts in the United Kingdom, United States and other countries have demonstrated the dangers to public safety from the criminal use of improvised explosives on a large scale. Four sets of trials were carried out over four years, partly in collaboration with the United States Federal Bureau of Investigation, involving the firing of large bombs, mostly fertilizer based. The principal objectives of the firings were to measure the physical effects of the explosions upon objects representative of those that would be found at a real bomb scene and to recover any chemical traces deposited on these objects. The results are intended for use as an aid in determining the approximate size and type of an explosive employed in a terrorist attack. This paper describes the background behind the trials, the procedures for preparation of witness materials and charges, and the collection and analysis of physical and chemical evidence.

Criminology↗
PubMed2000

Physical and chemical evidence remaining after the explosion of large improvised bombs. Part 2: Firings of calcium ammonium nitrate/sugar mixtures.

Six test firings of large improvised explosive devices were carried out. The principal objectives of the firings were to measure the physical effects of the explosions upon representative objects placed nearby and to recover any chemical traces deposited on these objects. The results are intended for use as an aid in determining the approximate size and type of an explosive employed in terrorist attacks. Three 454 kg charges of a mixture of calcium ammonium nitrate (CAN) fertilizer and sugar, and three 2268 kg charges of a similar mixture, all confined in cylindrical steel containers were fired. Each charge was surrounded by 19 road signs mounted on posts and four vehicles, to act as witness materials. The analysis of aqueous swab extracts taken from the witness materials after firing showed the recovery of nitrate, ammonium and low levels of glucose. No sucrose was detected. Nitrate was usually recovered in greater quantities than ammonium and recovery generally decreased with increasing distance from the charges in any given direction. Quantities recovered from objects placed at the same distance in different directions varied considerably. Patterns of physical damage to the witness materials could be discerned according to their distance from the charge and the size of the charge. The velocities of detonation and air blast effects were measured.

Criminology↗
PubMed2000

Family practice clerkship encounters documented with structured phrases on paper and hand-held computer logs.

Patient encounter logs allow faculty to monitor students' clinical experiences, especially in decentralized clerkships. However, there are generally tradeoffs involving the expressiveness of patient encounter forms, the effort required to complete the forms, and the utility of the forms for informing the clerkship director. The family practice clerkship at Washington University changed the school's standard free text, paper log to a controlled vocabulary paper log, borrowing 93 generic ICD-9 codes and the SNOMED concept of 'process at location' phrases for localized problems. Subsequently, this architecture was used in a Palm computer program. Students using the structured paper logs documented slightly more patient encounters than students using free text logs in the previous year, with similar numbers of problems per patient (1.3 to 1.4) and prevalence of common illnesses, but used the phrase structure and code vocabulary inconsistently. Students using computer logs documented many more patient encounters, but only documented 1.09 problems per patient. Students' documentation of psychosocial diagnoses declined significantly with the computer log. Although the computer program was flexible, the effort required to enter multiple problems exceeded the effort of finding similar codes on a short paper form. This problem confounds efforts to monitor exposure to complex patients and hidden medical problems. Another design for the hand-held computer log is being tested.

Clinical Clerkship↗
PubMed1999

Beta-keratin specific immunological reactivity in feather-like structures of the cretaceous alvarezsaurid, Shuvuuia deserti.

We report small fibrous structures associated with a new specimen of Shuvuuia deserti, which we hypothesize are remnants of feather-like epidermal appendages. Multiple analyses suggest that these structures are epidermally derived and contain epitopes consistent with beta-keratin, a protein expressed only in extant "reptiles" and birds. Morphological, microscopic, mass spectrometric, and immunohistochemical studies are consistent with the interpretation that these structures are related to feathers. These data suggest that proteinaceous components may survive across geological time and support the view that alvarezsaurids (Shuvuuia and its allies) are either a lineage of birds or are a lineage phylogenetically close to them. J. Exp. Zool. (Mol. Dev. Evol.) 285:146-157, 1999.

Animals↗
PubMed1999

What do service planners and policy-makers need from research?

Nine policy preoccupations have been identified in a recent study of dementia care policies in all European countries. These are used to structure a set of issues which researchers might usefully address to assist service planners and policy-makers. Areas where there is already a research literature are identified. Some description and commentary on the application of current policies in the UK is provided to illustrate the need for research. It is suggested that service planners and policy-makers march to some distant drum which is only remotely related to research, if at all. However, the importance of a research base is stressed with the suggestion that research in related fields could usefully be transferred.

Aged↗
PubMed1999

Reliability of the Salford Needs Assessment Schedule for Adolescents.

BACKGROUND: For adolescents, there is no specific needs assessment instrument that assesses significant problems that can benefit from specified interventions. A new instrument (S.NASA) was developed by incorporating and adapting three well established adult needs assessment instruments. The S.NASA covers 21 areas of functioning including social, psychiatric, educational and life skills. METHOD: Client and carer interviews were conducted by different researchers. A week later the interviews were repeated using a crossover design. Significant (cardinal) problems were generated from the clinical interviews using a pre-defined algorithm. Final need status (three categories) was made by clinicians assessing the cardinal problems against defined interventions. The interventions were generated from discussions with clinicians and a survey of appropriate professionals working with adolescents. RESULTS. Pre-piloting led to the final version being administered to 40 adolescents from secure units, forensic psychiatric and adolescent psychiatric services. There were 25 males and 15 females, mean age 15.5 years. Overall there were moderate to good inter-rater and test-retest reliability coefficients, the test-retest reliability coefficients for the total scores on the needs assessment interviews ranged from 0.73 to 0.85. Consensual and face validity was good, the adolescents and staff finding the instrument useful and helpful. CONCLUSIONS: This new needs assessment instrument shows acceptable psychometric properties. It should be of use in research projects assessing the needs and the provision of services for adolescents with complex and chronic problems.

Adolescent↗
PubMed1999

Can a standardized needs assessment be used to improve the care of people with severe mental disorders? A pilot study of 'needs feedback'.

The care programme approach (CPA) was introduced in the United Kingdom in 1991 to ensure that the needs of people with mental health problems are met appropriately. Many community psychiatric nurses (CPNs) act as 'key workers' under the CPA. Recent evidence suggests that the CPA is not particularly effective at meeting the needs of this vulnerable group, but it might be possible to enhance the CPA by introducing a more 'needs-led' approach to the planning of nursing care. 'Needs feedback' is a technique for enhancing the CPA. Needs feedback begins with a standardized assessment of patients' psychiatric and social needs by a nurse specialist. The patient's CPN is then provided with information on: (a) the needs identified; (b) why these needs have been identified; (c) the interventions required to meet the identified needs; and (d) how these interventions may be obtained. In the pilot study reported in this paper, 20 patients with severe mental disorder were evaluated before and after their CPN received needs feedback. All patients were living in the community and being managed by CPNs under the CPA. Outcome was assessed 6 months after the feedback in terms of: mental state, social behaviour and number of 'unmet' needs. Needs feedback was found to be compatible with the CPA in that it proved acceptable to CPNs and patients. Significant improvements were seen in the number of 'unmet' needs and the level of anxious/depressive symptoms. Improvements approaching significance were seen for social functioning and negative psychiatric symptoms, but not for positive psychiatric symptoms. This pilot study suggests that needs feedback may improve the quality of nursing assessment and care planning within the CPA. Further controlled investigations of needs feedback are justified.

Adult↗
PubMed1999

Evaluation of biomarker modulation by fenretinide in prostate cancer patients.

An NCI-sponsored, phase II trial of N-(4-hydroxyphenyl)- retinamide (4-HPR) in patients with organ-confined prostate cancer in the period prior to radical prostatectomy was carried out. Thirty-seven men with the histologic diagnosis of prostate cancer planning to have radical prostatectomy entered the study after informed consent and were given 4-HPR (or matching placebo) as a single daily dose (two 100-mg capsules of 4-HPR or two capsules of placebo daily) for 3 weeks prior to surgery. Four men dropped out for unrelated reasons. Thirty-three men completed the study. At the time of surgery, repeat biopsies of the prostate were performed to study the effects of the drug on potential surrogate endpoint biomarkers (SEBs) of malignancy within the tissue. The panel of potential SEBs of malignancy include p53, cytomorphometric indices, ploidy, PNCA, erbB-2, erbB-3, EGF receptor, TGF-alpha tumor-associated glycoprotein-72, fatty acid synthetase and Lewis Y antigen. Twenty-three patients had matching pre- and posttherapy lesions and were considered informative. Results from the patients indicate significant differential expression of biomarkers in pretreatment specimens of uninvolved prostatic tissue (normal-appearing epithelia) prostatic intraepithelial neoplasia (PIN) and prostate cancer. The mean erbB-2 expression was 0.58 in uninvolved vs. 1.04 in PIN (p = 0.002); while the mean erbB-2 expression was 1.35 in prostate cancer (p = 0.0007, uninvolved vs. prostate cancer). A similar pattern of increased biomarker expression between uninvolved and PIN or prostate cancer tissues can be observed for EGF receptor (mean = 1.21, 1.87 and 1.76 for uninvolved, PIN and prostate cancer, respectively) and erbB-3 (mean = 0.81, 1.59 and 1.30 for uninvolved, PIN and prostate cancer, respectively). There were no statistically significant differences in biomarkers observed in the 4-HPR-treated patients when compared with placebo-treated control patients. There was a posttreatment up-regulation of biomarkers observed in both groups of patients. This observation is most likely explained by an effect due to the diagnostic sextant biopsy equally affecting both groups of patients. Results from this study do not demonstrate a chemoprevention effect of 4-HPR on tissue-based SEBs at the dose given.

Adenocarcinoma↗
PubMed1999

Evaluation of a new type of direct digital radiography machine.

OBJECTIVE: To evaluate a recently developed low-dose, large-field, direct digital X-ray scanning system for medical use. METHOD: Radiation dose, image quality, diagnostic capability and clinical utility of the unit were compared with those of conventional radiography. RESULTS: Radiation doses ranged from 3% to 5% of conventional radiographic values, and a mean of 1 line-pair per millimetre could be detected. Ease of use, anatomical coverage and tolerance to patient motion were advantages. However, image quality was inferior to that of conventional radiographs, with limited fine detail visibility and penetration. Only 67 of 156 (42.9%) pathological features seen on conventional radiographs were detected, including 13 of 41 fractures (31.7%) and 11 of 18 pneumothoraces (61.1%). CONCLUSION: Although image quality and diagnostic performance were not ideal, potential roles in triage, foreign body detection and possibly screening were promising. Radiographic factors may have affected sensitivity. This machine demonstrated useful attributes that may, with improvement, be beneficial in the imaging of trauma and other patients.

Adolescent↗
PubMed1999

Lipoproteins inhibit macrophage activation by lipoteichoic acid.

Regulation of lipid metabolism during infection is thought to be part of host defense, as lipoproteins neutralize endotoxin (LPS) and viruses. Gram-positive infections also induce disturbances in lipid metabolism. Therefore, we investigated whether lipoproteins could inhibit the toxic effects of lipoteichoic acid (LTA), a fragment of gram-positive bacteria. LTA activated RAW264.7 macrophage cells, stimulating production of tumor necrosis factor (TNF) in a dose-dependent matter, but produced less TNF than that seen after LPS activation. High density (HDL) or low density lipoprotein (LDL) alone inhibited the ability of LPS to stimulate TNF production, but had little effect on the activation by LTA. When a maximally effective dose of LTA was mixed with lipoproteins and 10% lipoprotein-depleted plasma (LPDP), the ability of LTA to stimulate macrophage production of TNF was inhibited. HDL, LDL, and the synthetic particle, Soyacal, when mixed with LPDP, were able to inhibit the ability of LTA to activate macrophages. Lipopolysaccharide-binding protein (LBP) substituted for LPDP in catalyzing lipoprotein neutralization of LTA by HDL. Antibody to LBP inhibited the ability of LPDP to induce LTA neutralization by HDL.Thus, lipoproteins can prevent macrophage activation by fragments from both gram-positive and gram-negative microorganisms.-Grunfeld, C., M. Marshall, J. K. Shigenaga, A. H. Moser, P. Tobias, and K. R. Feingold. Lipoproteins inhibit macrophage activation by lipoteichoic acid.

Animals↗
PubMed1998

Oncogenes, growth factors and phorbol esters regulate Raf-1 through common mechanisms.

We have uniformly examined the regulatory steps required by oncogenic Ras, Src, EGF and phorbol 12-myristate 13-acetate (PMA) to activate Raf-1. Specifically, we determined the role of Ras binding and the phosphorylation of serines 338/339, tyrosines 340/341 and the activation loop (491-508) in response to these stimuli in COS-7 cells. An intact Ras binding domain was found to be essential for Raf-1 kinase activation by each stimulus, including PMA. Brief treatment of COS-7 cells with PMA was found to rapidly promote accumulation of the active, GTP-bound form of Ras. Furthermore, loss of the serine 338/339 and tyrosine 340/341 phosphorylation sites also blocked Raf-1 activation by all stimuli tested. Loss of the serine 497 and serine 499 PKCalpha phosphorylation sites failed to significantly reduce Raf-1 activation by any stimulus including PMA. Alanine substitution of all other potential phosphorylation sites within the Raf-1 activation loop had little or no effect on kinase regulation by Ras[V12] or vSrc although some mutants were less responsive to PMA. These results suggest that in mammalian cells, Raf-1 can be regulated by a variety of different stimuli through a common mechanism involving association with Ras-GTP and multiple phosphorylations of the amino-terminal region of the catalytic domain. Phosphorylation of the activation loop does not appear to be a significant mechanism of Raf-1 kinase regulation in COS-7 cells.

Amino Acid Sequence↗