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Biomedical subjects

S Miles

Publications and source records attributed to S Miles.

At least 19 recordsLinked to original sources
PubMed2006

Experiences and views of specialist registrars in geriatric medicine on 'do not attempt resuscitation' decisions: a sea of uncertainty?

BACKGROUND: Recent cultural changes place doctors under increasing pressure to work with their patients to reach decisions about end-of-life care. AIM: To survey the experience, practice and opinions of specialist registrars (SPRs) in geriatric medicine regarding 'do not attempt resuscitation' (DNAR) decisions. DESIGN: Postal questionnaire survey. METHODS: A questionnaire was mailed to all members registered as trainees (n = 408) with the British Geriatrics Society in November 2003; a reminder was sent nine weeks later. Responses were analysed using both quantitative and qualitative (thematic) approaches. RESULTS: Response rate was 62% (251/408), of whom 235 were still SpRs. Respondents played a major role in DNAR decision-making in their day-to-day clinical practice. Over a third of respondents did not feel that locally available guidelines were helpful. More than half sometimes disagreed with their consultants' decision, and a fifth were concerned about the possibility of complaints regarding the decisions they made. The majority felt uncomfortable discussing the issue with the patient, and were more likely to discuss the issue with relatives than with patients. DISCUSSION: Further support and training may improve confidence and positive experiences in relation to DNAR decision-making among training-grade doctors in the UK.

Adolescent↗
PubMed2005

A framework for measuring costs to society of IgE-mediated food allergy.

Both immunoglobulin E (IgE)-mediated food allergy and food intolerance can lead to many changes in personal behaviour and health care resource use which have important economic consequences. These costs will impact directly, indirectly and intangibly on both individuals and society in general. It is important to measure the cost of illness (COI) of food allergy as a first step in developing and evaluating measures to reduce and control the burden of illness. This paper outlines a framework for assessing COI of food allergy from different viewpoints. It offers a structure for identifying the different cost impacts on allergic and nonallergic consumers, food producers and society as a whole, and for scoping, measurement and valuation of relevant costs. Within this structure, the existing literature is reviewed. This review illustrates the lack of information and clear methodology for assessing costs of food allergy. The paper concludes that there is a need for a more structured research programme to generate data essential for future evaluations of procedures and technologies for the diagnosis, treatment and management of food allergy.

Cost of Illness↗
PubMed2001

Evidence that the entire Golgi apparatus cycles in interphase HeLa cells: sensitivity of Golgi matrix proteins to an ER exit block.

We tested whether the entire Golgi apparatus is a dynamic structure in interphase mammalian cells by assessing the response of 12 different Golgi region proteins to an endoplasmic reticulum (ER) exit block. The proteins chosen spanned the Golgi apparatus and included both Golgi glycosyltransferases and putative matrix proteins. Protein exit from ER was blocked either by microinjection of a GTP-restricted Sar1p mutant protein in the presence of a protein synthesis inhibitor, or by plasmid-encoded expression of the same dominant negative Sar1p. All Golgi region proteins examined lost juxtanuclear Golgi apparatus-like distribution as scored by conventional and confocal fluorescence microscopy in response to an ER exit block, albeit with a differential dependence on Sar1p concentration. Redistribution of GalNAcT2 was more sensitive to low Sar1p(dn) concentrations than giantin or GM130. Redistribution was most rapid for p27, COPI, and p115. Giantin, GM130, and GalNAcT2 relocated with approximately equal kinetics. Distinct ER accumulation could be demonstrated for all integral membrane proteins. ER-accumulated Golgi region proteins were functional. Photobleaching experiments indicated that Golgi-to-ER protein cycling occurred in the absence of any ER exit block. We conclude that the entire Golgi apparatus is a dynamic structure and suggest that most, if not all, Golgi region-integral membrane proteins cycle through ER in interphase cells.

Autoantigens↗
PubMed2001

Viral interleukin 6 stimulates human peripheral blood B cells that are unresponsive to human interleukin 6.

Cellular responsiveness to human interleukin 6 (hIL6) requires the expression of two receptor molecules: IL6-specific receptor (CD126'IL6R') and a nonspecific signal-transducing molecule (CD130'gp130'). Regulation of responsiveness to hIL6 is generally controlled by CD126'IL6R' expression. A viral homologue of hIL6 (vIL6) is encoded by human herpesvirus-8 and has biologic activity similar to hIL6 on a number of cell lines. vIL6 differs from hIL6 in its receptor utilization, requiring only CD130'gp130'. Total human B cells isolated from peripheral blood, which are predominantly CD126'IL6R'-negative, as well as sorted CD126'IL6R'-negative B cells, could be stimulated by recombinant vIL6, but not by hIL6, as indicated by induction of IL6-like signaling (STAT3 phosphorylation). This suggests that the ability of vIL6 to stimulate B cells expressing little or no CD126'IL6R' allows it to act on a larger pool of target B cells, compared to human IL6.

Adult↗
PubMed2001

Parental language input to children at stuttering onset.

Many programs for the indirect management of stuttering in early childhood counsel adjustment of parental language models, which are presumed to play an exacerbating influence on vulnerable children's fluency. We examined the relative levels of linguistic demand in maternal language to stuttering and nonstuttering children, adjusted for each child's current level of linguistic development. No significant or observable differences were detected in the relative level of linguistic demand posed by parents of stuttering children very close to onset of symptoms. Empirical support for current advisement and potential ramifications are discussed.

Adult↗
PubMed2000

Changes in human immunodeficiency virus type 1 virus load during mobilization and harvesting of hemopoietic progenitor cells. Adult AIDS Clinical Trials Group 285 Study Team.

Genetic modification of hemopoietic progenitor cells ex vivo, followed by the infusion of the genetically modified cells into the human immunodeficiency virus-1 (HIV-1) infected donor, has been proposed as a treatment for HIV-1 infection. The current study was undertaken to evaluate the effect of hemopoietic stem cell mobilization and harvesting on HIV-1 replication in persons with HIV-1 infection. Eighteen HIV-1-infected persons received recombinant granulocyte colony-stimulating factor (G-CSF; Filgrastim) 10 microg/kg per day, for 7 days. On days 4 and 5, peripheral blood mononuclear cells were harvested by leukapheresis. The CD4+ lymphocyte count at entry was >500/microL for 6 subjects, 200 to 500/microL for 6 subjects, and <200/microL for 6 subjects. For 9 of 18 subjects, plasma HIV-1 RNA levels increased 4- to 100-fold (>0.6 log(10)) above baseline between days 4 and 7 and returned to baseline by day 27. Significant increases of plasma HIV-1 RNA levels occurred in 5 subjects despite 3-drug antiretroviral therapy. Changes in CD4+ and CD34+ cells during mobilization and harvesting were similar in all subjects whether they had or did not have increased plasma HIV-1 RNA levels. Thus, mobilization and harvesting of bone marrow progenitor cells from persons infected with HIV-1 induced a transient increase in viral replication in some patients but was not associated with adverse effects. (Blood. 2000;95: 48-55)

Adult↗
PubMed2000

Treatment of poor-prognosis early rheumatoid arthritis. A randomized study of treatment with methotrexate, cyclosporin A, and intraarticular corticosteroids compared with sulfasalazine alone.

OBJECTIVE: To determine whether a regimen of methotrexate, cyclosporin A, and corticosteroids introduced at onset in poor-prognosis rheumatoid arthritis (RA) can produce a significant improvement in outcome compared with standard monotherapy with sulfasalazine (SSZ). METHODS: Eighty-two consecutive patients presenting with new, untreated RA of less than 12 months' duration who fulfilled criteria for poor long-term outcome were randomized to receive either combination therapy (n = 40) or SSZ alone (n = 42). The primary outcome measures were remission and American College of Rheumatology (ACR) criteria for 20% improvement at 48 weeks. RESULTS: After 48 weeks, the numbers of patients who met the ACR criteria for 20% improvement were not significantly different between the two groups (combination 58% versus SSZ 45%), and similar numbers of patients had persisting clinical remission (approximately 10% both groups). During the first 3 months, there were significantly greater reductions in parameters of disease activity in the combination group. By 24 weeks, the swollen and tender joint counts, C-reactive protein levels, and erythrocyte sedimentation rates had fallen significantly in both groups, with a greater improvement in the swollen and tender joint count in the combination group. At 48 weeks, the radiographic damage score had increased by a median of 1 (range 0-42.5) in the combination group and 1.25 (range 0-72.5) in the SSZ group (P = 0.28; although there were significant differences in the scores for the right hand). There were significantly fewer withdrawals due to lack of efficacy in the combination group than in the SSZ group (1 of 40 versus 10 of 42; P = 0.007). In the combination group, dose reduction was needed in 22.5% because of hypertension and in 22.5% because of elevated creatinine levels. Over 48 weeks, serum creatinine increased in both groups, but particularly in the combination arm. CONCLUSION: In poor-prognosis RA patients, "aggressive" combination therapy led to more rapid disease suppression but did not result in significantly better ACR response or remission rates. This suggests that in poor-prognosis disease, an approach based on identifying patients with poor treatment responses before extra therapy is added ("step-up" approach) may be more appropriate than the use of combination therapy in all patients from the outset.

Adrenal Cortex Hormones↗
PubMed1999

Human herpesvirus 8-encoded interleukin 6 activates HIV-1 in the U1 monocytic cell line.

OBJECTIVE: Human herpesvirus 8 (HHV-8) encodes a viral interleukin 6 (vIL-6) which is structurally and functionally similar to human interleukin 6 (hIL-6). Since hIL-6 has been shown to upregulate the expression of HIV-1, the objectives of this study were to examine the ability of vIL-6 to upregulate HIV-1, and to determine the interactions of this virokine (viral cytokine) with the components of the interleukin 6 (IL-6) receptor complex. DESIGN AND METHODS: Recombinant HHV-8 vIL-6 (rvIL-6) was assayed for bioactivity in the IL-6-dependent cell line MH60.BSF2. HIV-1 p24 production by the U1 monocytic and ACH-2 T-cell lines, which are chronically infected with HIV-1, was used to assess the ability of vIL-6 to affect HIV-1 expression. hIL-6 and vIL-6 receptor utilization was determined by quantifying HIV-1 p24 production after neutralization of components of the IL-6 receptor complex, CD126'IL-6R' and CD130'gp130', on U1 cells with blocking antibodies. RESULTS: HHV-8 rvIL-6 was seen to have IL-6-like bioactivity in MH60.BSF2 cells, and readily upregulated HIV-1 p24 production in U1 monocytic cells, but not in ACH-2 T cells. The vIL-6 appeared to utilize the IL-6-specific component of the IL-6 signaling complex, CD126'IL-6R', in U1 cells. CONCLUSIONS: HHV-8 vIL-6 clearly has the potential to upregulate HIV-1 expression in monocytic cells, and therefore may play a role in AIDS pathogenesis in individuals infected with both viruses.

Animals↗
PubMed1998

Clinical research designs for emerging treatments for Alzheimer disease: moving beyond placebo-controlled trials.

The design of clinical trials must evolve as new therapies become available. The demonstrated efficacy and clinical use of donepezil and vitamin E for Alzheimer disease (AD) has shifted the options for AD research design. There is now a compelling case for alternatives to trials that include a treatment arm with no active therapy (ie, a placebo control). With an existing therapy, such as donepezil or vitamin E, new drugs that are clearly superior to those drugs should be sought. Combination therapy is a likely strategy for the future, implying that clinical trials, if possible, should replicate actual practice. The long duration of future AD trials also will make placebo-controlled trials more difficult to justify and more difficult to recruit for. Add-on or active-control designs represent the alternative approaches. We believe that definitive clinical trials of new AD drugs that use one or the other of these designs would be more likely to bring about therapeutic advances than would comparisons with inactive treatments. Our argument is not a general rejection of placebo-control designs. Our recommendations apply only to the circumstances in which the field of AD drug therapy now finds itself.

Alzheimer Disease↗
PubMed1998

Seroprevalence of HHV-8 antibodies in HIV-positive homosexual men without Kaposi's sarcoma and their clinical follow-up.

Human herpesvirus 8 (HHV-8) has been associated with Kaposi's sarcoma (KS). Because KS is most frequently seen in HIV-positive homosexual men, we retrospectively evaluated the seroprevalence of HHV-8 in this risk group and compared the clinical history and clinical course of the HHV-8-negative and HHV-8-positive groups. The study was performed by analyzing banked serum samples from asymptomatic HIV-positive men. HHV-8 seropositivity was determined by an indirect immunofluorescence test. A total of 56% of patients (42/75) were seropositive for anti-HHV-8 IgG antibodies as opposed to 12% of 40 age-matched HIV-negative controls. Median CD4 counts at study entry were significantly lower in the HHV-8-positive group than in the HHV-8-negative group (520 vs 686); however, the percentage decrease during a 30-month follow-up did not differ significantly. KS developed in two patients during follow-up; both were HHV-8-positive and had CD4 counts of less than 200/microL at the time of clinical manifestation. One HHV-8-positive patient in whom AIDS developed died of infectious complications. The longest follow-up in the HHV-8-positive cohort without development of KS was 81 months. We conclude that HHV-8 has a high seroprevalence in asymptomatic, homosexual, HIV-positive persons. An HHV-8 infection can precede the development of KS by many years. Immunosuppression below a certain threshold may trigger the clinical manifestation of KS.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Treatment of pain in cognitively impaired compared with cognitively intact older patients with hip-fracture.

OBJECTIVE: To compare the experience of pain and treatment of pain in cognitively impaired and cognitively intact older adults after surgical repair of a hip fracture. DESIGN: Prospective comparative survey design. PARTICIPANTS: A convenience sample of 88 hip fracture patients (53 cognitively impaired, 35 cognitively intact) from three Midwestern urban hospital orthopedic units was interviewed between days 2 and 5 postoperatively. Subjects whose Folstein Mini-Mental State Exam (MMSE) score was less than or equal to 23 were categorized as impaired. RESULTS: Pain report and intensity did not differ significantly between the two groups. One-third of the subjects in both groups rated pain as severe or worse. Cognitively impaired subjects scored significantly higher on the Checklist of Nonverbal Pain Indicators observed with movement (CNPI-m) than did cognitively intact subjects. Cognitively impaired subjects received significantly less opioid analgesics than cognitively intact subjects in the first and second 48 hours postoperatively. Both groups received less than 25% of the mean prescribed amount of opioid analgesics. Age, MMSE, and CNPI-m score accounted for 27% of the variance in the amount of opioid analgesic administered in the first 48 hours postoperatively. CONCLUSIONS: Pain is treated poorly in older postoperative patients. Cognitive impairment and age strongly influence the amount of analgesic nurses administer to older patients after surgical repair of hip fracture. Provision for patient comfort is a fundamental ethical obligation of healthcare providers. Clinicians need to pursue this goal more aggressively, especially for cognitively impaired, postoperative older adults.

Acetaminophen↗
PubMed1998

Open-label phase I study of combination therapy with zidovudine and interferon-beta in patients with AIDS-related Kaposi's sarcoma: AIDS Clinical Trials Group Protocol 057.

The aim of this study was to identify a safe and tolerable dose of recombinant interferon-beta (IFN-beta) used in conjunction with a fixed dose of zidovudine in patients with early-stage, good-prognosis AIDS-related Kaposi's sarcoma. We conducted a phase I, dose-escalation controlled trial of 22.5, 45 of 90 million units of IFN-beta given by daily subcutaneous injection with 500 mg per day of oral zidovudine. At the time of this study, this was standard of care for HIV infection. Patients were sequentially enrolled at three medical centers. Tumor response, drug tolerance, antiviral studies and CD4 changes were assessed. Four patients were enrolled at each dose level, and escalation proceeded when at least four patients had tolerated two weeks of therapy without dose-limiting toxicity. ACTG Kaposi's sarcoma tumor response criteria were used to assess response. Fifteen patients were enrolled. The combination of IFN-beta and zidovudine was well tolerated, and the dose-limiting toxicities were local skin necrosis and systemic symptoms. Despite generally good prognostic characteristics, only two patients achieved a clinical complete response and three addition patients had stable disease for a prolonged period of time (range 24-44 weeks). There was no correlation between baseline CD4 cell counts and tumor response, nor between the antiviral effect of IFN-beta as measured by decreases in immune-complex dissociated p24 antigen and tumor response. Higher doses of IFN-beta did not result in more tumor responses or in greater antiviral activity. The maximum tolerated dose of IFN-beta in combination with 500 mg per day of zidovudine was 45 million units by subcutaneous injection per day. IFN-beta is well tolerated in patients with AIDS-related Kaposi's sarcoma when used in conjunction with zidovudine. However, the antitumor response rate in good-prognosis patients is low. Further studies of this agent should be in the context of four-drug antiretroviral regimens where viral suppression is greatest and any antitumor activity of IFN-beta may be observed.

Anti-HIV Agents↗
PubMed1997

The clinical introduction of genetic testing for Alzheimer disease. An ethical perspective.

OBJECTIVE: Primary caregivers should be aware of recent progress in the genetics of Alzheimer disease (AD) and of the clinical and ethical considerations raised regarding the introduction of genetic testing for purposes of disease prediction and susceptibility (risk) analysis in asymptomatic individuals and diagnosis in patients who present clinically with dementia. This statement addresses arguments for and against clinical genetic testing. PARTICIPANTS: The 20 participants were selected by the investigators (S.G.P., T.H.M., A.B.Z., and P.J.W.) to achieve balance in the areas of genetics, counseling, ethics, and public policy, and to include leadership from related consensus projects. The consensus group met twice in closed meetings and carried on extensive correspondence over 2 years (1995-1997). The project was supported by the National Human Genome Research Institute of the National Institutes of Health. EVIDENCE: All 4 involved chromosomes were discussed in group meetings against a background of information from several focus group sessions with AD-affected families. The focus groups comprised volunteers identified by the Cleveland Area Chapter of the Alzheimer's Disease and Related Disorders Association and represented a variety of ethnic populations. CONSENSUS PROCESS: The first draft was written in April 1996 by the principal investigator (S.G.P.) after the consensus group had met twice. The draft was mailed to all consensus group members 3 times over 6 months for extensive response and redrafting by the principal investigator until all members were satisfied. CONCLUSIONS: Except for autosomal dominant early-onset families, genetic testing in asymptomatic individuals is unwarranted. Use of APOE genetic testing as a diagnostic adjunct in patients already presenting with dementia may prove useful but it remains under investigation. The premature introduction of genetic testing and possible adverse consequences are to be avoided.

Advisory Committees↗