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Biomedical subjects

R Moore

Publications and source records attributed to R Moore.

At least 109 records · Page 6Linked to original sources

Epidemiology of sepsis syndrome in 8 academic medical centers.

CONTEXT: Sepsis syndrome is a leading cause of mortality in hospitalized patients. However, few studies have described the epidemiology of sepsis syndrome in a hospitalwide population. OBJECTIVE: To describe the epidemiology of sepsis syndrome in the tertiary care hospital setting. DESIGN: Prospective, multi-institutional, observational study including 5-month follow-up. SETTING: Eight academic tertiary care centers. METHODS: Each center monitored a weighted random sample of intensive care unit (ICU) patients, non-ICU patients who had blood cultures drawn, and all patients who received a novel therapeutic agent or who died in an emergency department or ICU. Sepsis syndrome was defined as the presence of either a positive blood culture or the combination of fever, tachypnea, tachycardia, clinically suspected infection, and any 1 of 7 confirmatory criteria. Estimates of total cases expected annually were extrapolated from the number of cases, the period of observation, and the sampling fraction. RESULTS: From January 4, 1993, to April 2, 1994, 12759 patients were monitored and 1342 episodes of sepsis syndrome were documented. The extrapolated, weighted estimate of hospitalwide incidence (mean+/-95% confidence limit) of sepsis syndrome was 2.0+/-0.16 cases per 100 admissions, or 2.8+/-0.17 per 1000 patient-days. The unadjusted attack rate for sepsis syndrome between individual centers differed by as much as 3-fold, but after adjustment for institutional differences in organ transplant populations, variation from the expected number of cases was reduced to 2-fold and was not statistically significant overall. Patients in ICUs accounted for 59% of total extrapolated cases, non-ICU patients with positive blood cultures for 11%, and non-ICU patients with negative blood cultures for 30%. Septic shock was present at onset of sepsis syndrome in 25% of patients. Bloodstream infection was documented in 28%, with gram-positive organisms being the most frequent isolates. Mortality was 34% at 28 days and 45% at 5 months. CONCLUSIONS: Sepsis syndrome is common in academic hospitals, although the overall rates vary considerably with the patient population. A substantial fraction of cases occur outside ICUs. An understanding of the hospitalwide epidemiology of sepsis syndrome is vital for rational planning and treatment of hospitalized patients with sepsis syndrome, especially as new and expensive therapeutic agents become available.

Adult↗

A comparison of the inflammatory potential of particulates derived from two composite materials.

In order to develop total joint prostheses with moduli of elasticity close to bone while retaining excellent strength characteristics, composite materials are being developed. Composites consist of graphite fibers embedded in a polymer matrix. We studied the inflammatory potential of particulates derived from two composites with different matrix components, polysulfone (PFS) and polyetherketoneketone (PEKK), in the rat subcutaneous air pouch model. Neat components of the composites were studied separately in the air pouch. Particulates also were studied in culture using the macrophage cell line RAW 264.7, adherent synovial cells (ASC), and human polymorphonuclear neutrophils (PMNs). Particles derived from the PEKK-containing composite material consistently were less inflammatory than the PFS composite-derived particles, as measured by PMN infiltration, neutral metalloprotease activity, tumor necrosis factor (TNF) activity, and prostaglandin E2 (PGE2) accumulation. Results from the neat materials confirmed the findings in the composite-derived material. PEKK composite-derived material produced less TNF from macrophage cultures, but there were no significant differences noted in PGE2 production from ASC or in superoxide anion generation from PMNs. Particles from both PSF and PEKK produced minimal inflammatory responses in the rat subcutaneous air pouch. PEKK elicited a response virtually the same as the saline control and significantly less than that produced by particles of PSF.

Animals↗

Elevated synthesis of biglycan and decorin in an ovine annular lesion model of experimental disc degeneration.

The aim of this study was to extend our earlier observations on the changes that occur in the proteoglycans (PGs) of discs subjected to experimental injury to the annulus fibrosus (AF). We employed the alginate bead culture method to examine the metabolism of the dermatan sulphate (DS) containing PGs by cells derived from different regions of ovine discs that had been subjected to experimental annular injury. This was compared with the metabolism of the DS-PGs by cells isolated from equivalent regions of normal sham-operated discs. Six months after induction of the annular lesion, AF cells isolated from the lesion produced significantly higher levels of decorin and biglycan in alginate bead culture than did cells from equivalent zones of the controls. Decorin and biglycan were identified in culture media samples by immunoblotting, using specific antibodies (6-B-6, LF-96), and also by positive identification of their de-glycosylated core proteins. The core protein of the DS-PGs has been shown to inhibit type I/II collagen fibrillogenesis, to negatively regulate the action of transforming growth factor-beta (TGF-beta) and to diminish cellular proliferation in vitro; events which may be detrimental to tissue repair. The findings are therefore consistent with our previous observation the annular lesions in the avascular inner annulus have no capacity to heal.

Animals↗

Consensus analysis: reliability, validity, and informant accuracy in use of American and Mandarin Chinese pain descriptors.

A quantitative method for validating qualitative interview results and checking sample parameters is described and illustrated using common pain descriptions among a sample of Anglo-American and mandarin Chinese patients and dentists matched by age and gender. Assumptions were that subjects were members of a sociocultural group (e.g. ethnic or professional/lay) and answered questions independently about a monotonic domain (e.g. pain). Subjects answered 18 true/false items derived from and selected to reflect pain perceptions consistent with published and unpublished interview data. Estimates of consistency in use of descriptors within groups, validity of description, accuracy of individuals compared with others in their group, and minimum required sample size were calculated using Cronbach's alpha, factor analysis, and Bayesian probability. Ethnic and professional differences within and across groups were also tested using multidimensional scaling (MDS) and hypothesis testing. Consensus (consistency of subject response by group) was .99 among Anglo-Americans and .97 among Chinese. Mean subject accuracy was .81 for Americans and .57 for Chinese, indicating the need for larger numbers of Chinese to supplement each others' statements. However, larger numbers of subjects were recruited than actually required for each ethnic group at .95 confidence limits. MDS showed similarities in use of descriptors within ethnic groups, while there were differences (p < .001) between Chinese and American groups. Use of covalidating questionnaires that reflect results of qualitative interviews are recommended in order to estimate sample parameters such as intersubject agreement, individual subject accuracy, and minimum required sample sizes.

Adult↗

Conversion from cyclosporin to tacrolimus in a patient with prolonged acute tubular necrosis.

Acute tubular necrosis (ATN) is a common condition of following cadaveric renal transplantation with an incidence in many series of nearly 50%. The aetiology is uncertain; however, it would appear to be related to damage to the transplant kidney either prior to retrieval, During cold preservation or during re-warming of the kidney at the time of anastamotic construction. There is no specific therapy for ATN and treatment is comprised of an expectant policy with supportive dialysis and fluid restriction. Renal function improves in the majority of cases, though there may be delayed function for several weeks. We report a case of dialysis-dependent ATN that had persisted for 5 months following transplantation. Following conversion to tacrolimus there was immediate improvement in renal function, and after a month of tacrolimus therapy the patient was dialysis-independent.

Adult↗

Perirenal MR high signal--a new and sensitive indicator of acute ureteric obstruction.

PURPOSE: This study was carried out to determine the incidence of perirenal magnetic resonance (MR) high signal in acute ureteric obstruction as demonstrated by half-Fourier acquisition single shot turbo spin-echo (HASTE) MR. In addition, we evaluated the sensitivity of this perirenal MR high signal as a predictor of acute ureteric obstruction. MATERIALS AND METHODS: A prospective evaluation of 55 consecutive patients with suspected ureteric obstruction was carried out using the HASTE MR sequence. Images were compared to concurrent IV urography (IVU) or to computed tomography (CT) where these were available. Acute and chronic ureteric obstruction were differentiated by clinical evaluation. RESULTS: Forty-one patients had obstructed kidneys. HASTE MR accurately predicted the presence of acute ureteric obstruction in 20/23 (87%) based on presence of perirenal MR high signal. None of these showed evidence of contrast medium extravasation on the concurrent i.v. urogram. 15/18 (83%) chronically obstructed kidneys demonstrated no perirenal high signal on HASTE MR, and the remaining three showed only a trace of perirenal high signal. CT showed perirenal stranding in only 2/8 patients with acutely obstructed kidneys. CONCLUSION: In acute ureteric obstruction, HASTE MR shows perirenal high signal intensity much more commonly than IVU shows extravasation or CT showing perirenal stranding. The origin of this MR signal is uncertain but may represent oedema, lymphatic distension or free fluid from forniceal rupture. HASTE MR can accurately distinguish between acute and chronic ureteric obstruction based on the degree of perirenal high signal.

Acute Disease↗

Treatment of human prostate tumors PC-3 and TSU-PR1 with standard and investigational agents in SCID mice.

Both the PC-3 and the TSU-PR1 prostate tumor models were found to be satisfactory for chemotherapeutic investigations in ICR-SCID mice. The 30 to 60 mg fragments implanted took in all mice (as judged by 100% takes in the controls of all experiments as well as the passage mice). The tumor volume doubling time was 4.0 days for PC-3 and 2.5 days for TSU-PR1. Nine agents were evaluated IV against early stage subcutaneous PC-3 tumors, with Nano-piposulfan being the only agent highly active (4.9 log kill). Three other agents were moderately active: Taxol (1.5 log kill), Cryptophycin-8 (1.6 log kill), Vinblastine (1.0 log kill). Five agents were inactive: VP-16, Adriamycin, CisDDPt, 5-FUra, and Cyclophosphamide. Ten agents were evaluated IV against early stage subcutaneous TSU-PR1 tumors. Three agents were highly active, producing > 6 log kill and cures: Taxol (5/5 cures), Cryptophycin-8 (5/5 cures), Vinblastine (2/4 cures). Two other agents were moderately active: Nano-piposulfan (1.2 log kill), and Cyclophosphamide (1.1 log kill). Five agents were inactive: VP-16, Adriamycin, CisDDPt, 5-FUra, and BCNU. In part, activity was determined by the ability of the SCID mice to tolerate meaningful dosages of the agents. Agents producing granulocyte toxicity (e.g., Adriamycin) were poorly tolerated and appeared less active than expected. Vinblastine, producing little or no granulocyte toxicity was very well tolerated and appeared to be more active than expected.

Aged↗

Discovery of cryptophycin-1 and BCN-183577: examples of strategies and problems in the detection of antitumor activity in mice.

Historically, many new anticancer agents were first detected in a prescreen; usually consisting of a molecular/biochemical target or a cellular cytotoxicity assay. The agent then progressed to in vivo evaluation against transplanted human or mouse tumors. If the investigator had a large drug supply and ample resources, multiple tests were possible, with variations in tumor models, tumor and drug routes, dose-decrements, dose-schedules, number of groups, etc. However, in most large programs involving several hundred in vivo tests yearly, resource limitations and drug supply limitations have usually dictated a single trial. Under such restrictive conditions, we have implemented a flexible in vivo testing protocol. With this strategy, the tumor model is dictated by in vitro cellular sensitivity; drug route by water solubility (with water soluble agents injected intravenously); dosage decrement by drug supply, dose-schedule by toxicities encountered, etc. In this flexible design, many treatment parameters can be changed during the course of treatment (e.g., dose and schedule). The discovery of two active agents are presented (Cryptophycin-1, and Thioxanthone BCN 183577). Both were discovered by the intravenous route of administration. Both would have been missed if they were tested intraperitoneally, the usual drug route used in discovery protocols. It is also likely that they would have been missed with an easy to execute fixed protocol design, even if injected i.v.

Animals↗

Predicting bacteremia in patients with sepsis syndrome. Academic Medical Center Consortium Sepsis Project Working Group.

The goal of this study was to develop and validate clinical prediction rules for bacteremia and subtypes of bacteremia in patients with sepsis syndrome. Thus, a prospective cohort study, including a stratified random sample of 1342 episodes of sepsis syndrome, was done in eight academic tertiary care hospitals. The derivation set included 881 episodes, and the validation set included 461. Main outcome measures were bacteremia caused by any organism, gram-negative rods, gram-positive cocci, and fungal bloodstream infection. The spread in probability between low- and high-risk groups in the derivation sets was from 14.5% to 60.6% for bacteremia of any type, from 9.8% to 32.8% for gram-positive bacteremia, from 5.3% to 41.9% for gram-negative bacteremia, and from 0.6% to 26.1% for fungemia. Because the model for gram-positive bacteremia performed poorly, a model predicting Staphylococcus aureus bacteremia was developed; it performed better, with a low- to high-risk spread of from 2.6% to 21.0%. The prediction models allow stratification of patients according to risk of bloodstream infections; their clinical utility remains to be demonstrated.

Adult↗

Digital tomosynthesis in breast imaging.

PURPOSE: To describe and evaluate a method of tomosynthesis breast imaging with a full-field digital mammographic system. MATERIALS AND METHODS: In this tomosynthesis method, low-radiation-dose images were acquired as the x-ray source was moved in an arc above the stationary breast and digital detector. A step-and-expose method of imaging was used. Breast tomosynthesis and conventional images of two imaging phantoms and four mastectomy specimens were obtained. Three experienced readers scored the relative lesion visibility, lesion margin visibility, and confidence in the classification of six lesions. RESULTS: Tomosynthesis image-reconstruction algorithms allow tomographic imaging of the entire breast from a single arc of the x-ray source and at a radiation dose comparable with that in single-view mammography. Except for images of a large mass in a fatty breast, the tomosynthesis images were superior to the conventional images. CONCLUSION: Digital mammographic systems make breast tomosynthesis possible. Tomosynthesis may improve the specificity of mammography with improved lesion margin visibility and may improve early breast cancer detection, especially in women with radiographically dense breasts.

Female↗

Demonstration of changes in fetal liver erythropoiesis using echo-planar magnetic resonance imaging.

This study investigated the variation in magnetic resonance characteristics of the fetal liver during a time of changing erythropoietic function. Echo-planar imaging was carried out in 25 normal pregnant women at 20 and 26 wk gestation. The signal intensity from regions of the fetal liver, background image, and maternal back muscle and the highest signal intensity from the maternal spinal cord were measured and compared with the signal intensity of amniotic fluid. Data are expressed as ratios, in arbitrary units (median pixel values; interquartile range shown in parentheses), and analyzed with the use of Wilcoxon's signed-rank test. At 20 wk, the signal intensity ratio of liver to amniotic fluid was 0.309 (0.231-0.365). At 26 wk, the ratio was 0.544 (0.429-0.616). The change was highly significant (P < 0.0001). No change in the signal intensity ratios of amniotic fluid compared with other measured parameters was noted. These data are consistent with known changes in fetal liver erythropoiesis occurring between 20 and 26 wk gestation and have potential use in early noninvasive physiological assessment of the fetus.

Adult↗

Expression of hepatocyte growth factor/scatter factor and its receptor, MET, suggests roles in human embryonic organogenesis.

Hepatocyte growth factor/scatter factor (HGF/SF) is secreted by mesenchymal cells and elicits proliferation, motility, differentiation, and morphogenesis of epithelia and other cells. These effects are mediated by binding to MET, a receptor tyrosine kinase. Genetically engineered mice lacking HGF/SF die in utero due to a failure of placental and hepatocyte differentiation, but little information exists regarding the expression of this signaling system in human development. Using reverse transcriptase-polymerase chain reaction, Western blots, and immunohistochemistry, we report that HGF/SF and MET are expressed during critical early periods of human organogenesis from 6 to 13 wk of gestation. Organs that expressed both genes included liver, metanephric kidney, intestine, and lung, each of which develop by inductive interactions between mesenchyme and epithelia. Of all organs studied, the placenta contained the highest levels of HGF/SF protein, and MET was detected in trophoblastic cells of chorionic villi as early as the 5th wk of gestation. Finally, examination of a human multicystic dysplastic kidney demonstrated that malformed, hyperproliferative tubules expressed MET, whereas HGF/SF protein was immunolocalized to the same epithelia and also to the surrounding undifferentiated cells. Hence HGF/SF might be an important growth factor in normal human embryogenesis and may additionally play a role in human organ malformations.

Animals↗

Patients' opinion of mammography screening services: immediate results versus delayed results due to interpretation by two observers.

OBJECTIVE: The purpose of this study was to evaluate by random questionnaire mailings the preferences of women who have undergone mammography in our region regarding communication of mammography screening results. MATERIALS AND METHODS: Questionnaires were mailed to 400 randomly selected women who were more than 35 years old and who had been treated at our institution for medical or surgical reasons. Questions regarding use of mammography screening at our institution versus services at other locations were included. The questionnaire described two possible mammography services; either a double reading service that would provide delayed reports (DRDR) with the benefit of extra cancers detected, and a service that provides immediate reports given directly to the patient by an on-site radiologist. The presentation of the services was reversed in half the questionnaires to avoid bias. Patients' choices were collected, as were demographic data. The choice of one system over the other was evaluated using the one-sample lest for binomial probability. The chi-square test was used to determine if the order of questions on the survey or the site of patients' screening mammography affected responses. RESULTS: The response rate was 42% (n = 168). Of these, one response informed us of the death of a patient. Of the remaining 167 respondents, 75% (n = 126) preferred the DRDR system, 13% (n = 22) preferred the system providing immediate results (p < .0001), and the other 19 respondents did not select a preference. Of the 167 respondents, 156 answered the question regarding previous screening mammography experience. Of the 105 patients who had undergone screening mammography at our institution, 78% (n = 82) preferred the DRDR system. Of the 51 patients who had undergone mammography elsewhere or who had never undergone mammography, 75% (n = 38) preferred the DRDR system. We found that ordering of presentation of the systems in the questionnaire had no effect on responses. Likewise, whether a respondent had undergone mammography at our institution had no effect on responses (p = 1.0). CONCLUSION: A statistically significant number of women who responded to our questionnaire preferred the DRDR system of reporting screening mammographic results. Educational material about double reading that we included with each patient's questionnaire could account for these results. If the use of a second interpreter is feasible and is done for batch interpretation of screening mammograms, then education of patients about this process may increase acceptance of a delayed mammographic report.

Adult↗

Topographical variation in the catabolism of aggrecan in an ovine annular lesion model of experimental disc degeneration.

An established model of experimental disc degeneration (Osti et al., Spine 15:762, 1990; Melrose et al., J Orthop Res 10:655, 1992) was used in this study. Four 2-year-old sheep received anterolateral incisions (4 x 10 mm) in the outer one-third of the annulus fibrosus of their L2-L3 and L4-L5 discs (lesion group). The annulus was not incised in another four sham-operated animals. After 6 months the sheep were killed, lumbar discs were dissected into lateral halves of the annulus fibrosus and the nucleus pulposus. Cells were isolated from disc tissues enzymatically and were grown in alginate bead culture to examine the proteoglycan metabolism of cells from lesion and control zones. The media of lesion zone cultures contained relatively high levels (compared with sham cultures) of catabolic fragments of the large, high-buoyant-density proteoglycans as demonstrated by Western blotting using monoclonal antibodies (5-D-4, 3-B-3, 1-C-6) and biotinylated hyaluronan and also by gel chromatography. Furthermore, cells from the vicinity of the lesion site also synthesized significantly lower levels (compared with sham cultures) of aggrecan that was retained within the alginate beads. Collectively, these data indicated that focal depletion of large, high-buoyant-density proteoglycans was evident within lesion sites in this model of experimental disc degeneration. The introduction of an annular lesion therefore significantly affected the proteoglycan metabolism of endogenous disc cell populations. The unique hydrodynamic and viscoelastic properties of the intervertebral disc are dependent to a large degree on the tissue levels of aggrecan. The focal depletion of aggrecan by annular lesions therefore may represent an important predisposing factor to the subsequent degeneration of these intervertebral discs.

Aggrecans↗

Abdominal wall hernia in autosomal dominant polycystic kidney disease.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is a common cause of renal impairment with a number of well recognized extrarenal associations. A high incidence of abdominal wall hernia was noted in patients with ADPKD. METHODS: A retrospective review of the notes of all patients with ADPKD on the South Wales renal replacement therapy database was performed. These patients were compared with age- and sex-matched patients with renal failure but without ADPKD and with general surgical patients. RESULTS: The prevalence of hernia in patients with ADPKD was 38 of 85 (45 per cent) compared with seven of 85 (8 per cent) for other forms of renal failure and three of 85 (4 per cent) for general surgical controls (P < 0.001). There were significantly greater numbers of inguinal (P < 0.001), incisional (P = 0.019) and paraumbilical (P = 0.007) hernias in patients with ADPKD compared with the other two groups. CONCLUSION: These results show a significantly greater incidence of hernia, which could be an additional manifestation of the underlying defect in extracellular matrix production identified in patients with ADPKD.

Adult↗

Imagery and hypnosis in the treatment of cancer patients.

Many patients with cancer often seek some means of connecting their mental activity with the unwelcome events occurring in their bodies, via techniques such as imagery and hypnosis. Hypnosis has been shown to be an effective method for controlling cancer pain. The techniques most often employed involve physical relaxation coupled with imagery that provides a substitute focus of attention for the painful sensation. Other related imagery techniques, such as guided imagery, involve attention to internally generated mental images without the formal use of hypnosis. The most well-known of these techniques involves the use of "positive mental images" of a strong army of white blood cells killing cancer cells. Despite claims to the contrary, no reliable evidence has shown that this technique affects disease progression or survival. Studies evaluating more broadly defined forms psychosocial support have come to conflicting conclusions about whether or not these interventions affect survival of cancer patients. However, 10-year follow-up of a randomized trial involving 86 women with cancer showed that a year of weekly "supportive/expressive" group therapy significantly increased survival duration and time from recurrence to death. This intervention encourages patients to express and deal with strong emotions and also focuses on clarifying doctor-patient communication. Numerous other studies suggest that suppression of negative affect, excessive conformity, severe stress, and lack of social support predict a poorer medical outcome from cancer. Thus, further investigation into the interaction between body and mind in coping with cancer is warranted.

Attitude to Health↗