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Biomedical subjects

C Childs

Publications and source records attributed to C Childs.

At least 19 recordsLinked to original sources

Ex-vivo expansion of bone marrow progenitor cells for hematopoietic reconstitution following high-dose chemotherapy for breast cancer.

The use of hematopoietic growth factors, stromal monolayers, and frequent medium exchange allows the expansion of hematopoietic progenitors ex-vivo. We evaluated the use of ex-vivo expanded progenitor cells for hematopoietic reconstitution following high dose chemotherapy (HDC) in breast cancer patients. Patients with high-risk Stage II or metastatic breast carcinoma underwent bone marrow aspirations using general anesthesia. A total of 675-1125 x 10(6) mononuclear cells (MNC) were seeded for ex-vivo expansion for 12 days in controlled perfusion bioreactors (Aastrom Biosciences, Inc.). The bone marrow cultures, which included the stromal cells collected with the aspirate, were supplemented with erythropoietin, granulocyte-macrophage-colony stimulating factor (GM-CSF)/IL-3 fusion protein (PIXY 321), and flt3 ligand. Stem cell transplant was performed with expanded cells after HDC. A median bone marrow volume of 52.9 mL (range 42-187 mL) was needed to inoculate the bioreactors. Median fold expansion of nucleated cells (NC) and colony forming unit granulocyte-macrophage (CFU-GM) was 4.9 and 9.5, respectively. The median fold expansion of CD34+lin- and long-term culture-initiating culture (LTC-IC) was 0.42 and 0.32, respectively. Five patients were transplanted with ex-vivo expanded NC. Median days to an absolute neutrophil count > 500/microL was 18 (range 15-22). Median days to a platelet count > 20,000/microl was 23 (range 19-39). All patients had sustained engraftment of both neutrophils and platelets. Immune reconstitution was similar to that seen after HDC and conventional stem cell transplantation. We conclude that ex-vivo expansion of progenitor cells from perfusion cultures of small volume bone marrow aspirates, allows hematopoietic reconstitution after HDC.

Adult

Toxic shock syndrome toxin-1 (TSST-1) antibody levels in burned children.

Young children with burns are at risk of developing a toxic shock-like illness during the first 2-3 days after the injury. The staphylococcal exotoxin, toxic-shock syndrome toxin-1 (TSST-1) is implicated in development of this illness. Low levels or absence of anti-TSST-1 antibodies may indicate susceptibility to this illness. Anti-TSST-1 antibody levels were measured in consecutive cases admitted to the children's burns unit. Results of antibody levels in 38 of the youngest children, aged 0.04-4.0 years are reported. At the time of admission to the unit 50% of the children had IgG antibodies to TSST-1. A higher number of young burned children had antibodies to TSST-1 than expected.

Bacterial Toxins

Tympanic membrane temperature as a measure of core temperature.

BACKGROUND: Ear thermometers are becoming popular as a method for measuring deep body (core) temperature. AIM: To determine the variability of a single user's tympanic membrane (ear) temperature measurements. SUBJECTS: Forty-two, afebrile, healthy children, and 20 febrile children with acute burns. RESULTS: In afebrile children measurements made in both ears (and within just a few minutes of each other) differed by as much as 0.6 degree C. Operator measurement error, sw of three consecutive measurements, in the same ear, was 0.13 degree C. In the group of febrile, burned children, core temperature was measured hourly at a number of sites (ear, rectum, axilla, bladder). A peak in core temperature occurred approximately 10-12 hours after the burn. Measurement error was calculated in 14 febrile, burned children with a peak temperature in excess of 38 degrees C. For the left ear, measurement error was 0.19 degree C and for the right ear, 0.11 degree C. In the febrile children agreement between the ears was poor. The limits of agreement were 0.4 degree C to -0.8 degree C. It was not possible to predict the occasions when the temperature differences between the ears would be large or small. CONCLUSIONS: The measurement error of one recording from the next is probably acceptable at about 0.1 to 0.2 degree C. To limit the variations in temperature of one ear to the other, measurements should be restricted to one of the ears whenever possible and the same ear used throughout the temperature monitoring period. Nurses and parents should take more than one temperature reading from the same ear whenever possible.

Adolescent

The European Directory of Burns Research.

The European Directory of Burns Research is a database of research activity in Europe. This ongoing database, established under the auspices of the Research Committee of the European Burns Association (EBA), provides basic information on research studies in progress or completed. The first issue, for the period 1995/1996, present information received after return of 118 questionnaires from researchers working in 27 countries in Europe and its close neighbours. This is not a large number of responses and may reflect problems with access to groups working in burns, but ignorant of the request for information on research activities. The aim is to maintain and update the database annually through distribution and return of a simple questionnaire. Information will be available to EBA members on request but the accuracy and detail of the database will ultimately be influenced by the co-operation of the burns research community.

Animals

Is there an evidence-based practice for burns?

Doubts and questions about clinical decision making need to be answered. Evidence-based medicine aims to provide answers by systematically finding information from the vast assortment of research papers in the literature and bringing it together to use in everyday practice and in the best interests of the patient. Although clinical (and experimental) studies have a variety of methodologies, ranging from small descriptive studies to large multi-centre trials all are vital in describing or posing questions about the array of responses elicited when human beings are burned and subsequently treated. When it comes to treatment (be it a drug, a dressing, an enteral feed for example) the 'gold standard' for establishing whether it is effective is the randomized controlled trial (RCT). Using contemporary information retrieval systems and the numerous establishments set up to help track down information of research in medicine relevant to health practice and policy the numbers of RCTs, systematic reviews and meta-analyses of burn care have been established. Whilst the numbers of RCTs are increasing there is little evidence that burn care is an evidence-based practice.

Bandages

Suprasternal Doppler ultrasound for assessment of stroke distance.

An assessment of a non-invasive technique for measurement of stroke distance was made using a portable Doppler ultrasound machine. The aim was to determine the measurement error of repeated stroke distance measurements (Within-observer variability) and to assess measurement agreement between two operators (between-observer variability). The measurement error (within-observer variability) for both operators was similar at approximately 2 cm. However, the measurements of the two operators (between-observer variability) did not agree well. Using the mean (SD) of three readings by each operator, the mean difference between the operators was -0.21 cm (1.96) giving a 95% confidence interval for the differences of -4.0 to +3.6 cm. There were significant positive and negative correlations between stroke distance and a variety of variables (age, height, weight, heart rate), but the relations were weak. The results indicate that the Doppler ultrasound technique for measurement of stroke distance would best be used to study trend changes in an individual patient, or subject, by a single operator.

Aging

A comparison of phenotypic properties of Staphylococcus aureus isolated from burned children and other patient groups.

This study aimed to determine whether strains of Staph. aureus isolated from children on our paediatric burns unit were different from strains isolated from other patient groups. Of particular interest was the incidence of toxin production amongst the different patient groups and the potential association with toxic shock syndrome (TSS). Wound isolates of Staph. aureus were collected from three patient groups: (1) hospital inpatients, (2) community patients and (3) patients from a regional burns unit. One hundred isolates were collected from each group (n = 300). Each isolate was tested for enterotoxin and TSST-1 production, phage type, antibiogram and tryptophan dependence. The results were compared, to determine whether there were any differences between the isolates from each of these patient groups. There were some variations in antibiotic sensitivity patterns and phage type of the isolates between the different patient groups but there was no significant difference in the incidence of toxin production, which was an important observation. The 100 isolates collected from this burns unit were derived from 58 patients. The colonization patterns of the Staph. aureus showed that 12 patients were colonized by more than one isolate and that these were a mixture of toxin-positive and toxin-negative strains. The medical records were examined for evidence of TSS; there was a higher incidence of toxic episodes in the patients colonized with strains which produced TSST-1 toxin.

Anti-Bacterial Agents

A microprocessor based photoplethysmograph for use in clinical practice.

A microprocessor-based system of photoplethysmography and its use in measuring skin blood flow is described. The system was designed specifically for use over long periods and for the analysis of the output to be handled by a personal computer. The photoplethysmograph described in this paper is shown to be a qualitative method for assessment of changes in peripheral skin blood flow. There is potential for use of this instrument in a variety of clinical conditions.

Adult

Oxygen consumption during sleep in atopic dermatitis.

Measurements of oxygen consumption (VO2) were made during sleep in 10 patients with atopic dermatitis. Two groups of healthy children acted as controls. All subjects were studied in bed in an environmental temperature of 24-26 degrees C, and sleep was confirmed during continuous electroencephalographic monitoring. Mean (SD) values of VO2 in sleeping patients who were not scratching ranged from 4.0 (0.4) to 7.4 (0.7), which was not statistically significantly different from control values which ranged from 3.24 (0.3) to 5.56 (0.4). During scratching (while asleep), which occurred in nine out of 10 patients with atopic dermatitis, the mean values of VO2 ranged from 4.5 (0.04) to 10.4 (2.7), and this was significantly higher than the non-scratching patients and the control values. Scratching during sleep in children with atopic dermatitis is associated with increased VO2.

Adolescent

KBM-7, a human myeloid leukemia cell line with double Philadelphia chromosomes lacking normal c-ABL and BCR transcripts.

A human myeloid leukemia cell line, KBM-7, was developed from a patient in the blastic phase of chronic myeloid leukemia (CML). We characterized its morphology, immunophenotype, cytogenetics, and proliferative capacity. Developed in the absence of exogenous lymphokines, KBM-7 in vitro cloning capacity actually decreased when colony-stimulating factors were added. The cells had an aberrant immature myeloid phenotype, a doubling time of 22 h in suspension cultures and a high cloning efficiency in semisolid system (24 +/- 3)%. Early passages contained one near-haploid (predominant) and one hyperdiploid stem line. Gradually the hyperdiploid stem line became predominant, reaching an average of 49 chromosomes per cell. Cells from passage 89 had two Philadelphia chromosomes [t(9;22)(q34;q11)] and lacked normal copies of chromosomes 9 and 22. Detailed molecular characterization of the breakpoint in the t(9;22)(q34;q11) revealed that KBM-7 had the BCR 2/ABL II splice junction. The cells had high protein kinase (p210BCR-ABL) activity and carried two identified variants of an ABL-BCR message. There was no evidence that normal BCR or c-ABL messages were expressed, assessed with the reverse-transcriptase polymerase chain reaction. When KBM-7 cells were heterotransplanted into nude mice without immunosuppressive pretreatment, one of three mice injected with 1 x 10(7) cells and all mice injected with 1 x 10(8) cells developed slowly growing granulocytic sarcomas within 6-8 weeks. These tumors were locally invasive but did not metastasize. We conclude that the KBM-7 cell line will be of value for investigating molecular events underlying neoplastic transformation in CML, in particular for studying the effects of BCR-ABL and ABL-BCR on the proliferation of CML cells in the absence of normal BCR and c-ABL messages.

Animals

Epstein-Barr virus DNA is abundant and monoclonal in the Reed-Sternberg cells of Hodgkin's disease: association with mixed cellularity subtype and Hispanic American ethnicity.

One hundred twenty-five cases of Hodgkin's disease from the United States (79), Mexico City (31), and Costa Rica (15) were analyzed for the presence of Epstein-Barr virus (EBV) by in situ hybridization to EBER1 transcripts. EBV was more frequently detected in the Reed-Sternberg (RS) cells of mixed cellularity Hodgkin's disease (37 of 48 [77%]) compared with the nodular sclerosis subtype (19 of 71 [27%], P < .001). The presence of EBV was also associated with Hispanic ethnicity (P < .001). In a multivariate analysis, patient age, gender, and geographic location were less predictive of EBV positivity than were mixed cellularity histology (odds ratio = 8.3) and Hispanic ethnicity (odds ratio = 4.3). Southern blot analysis of EBV terminal repeat fragments using the Xho1a probe showed that the viral DNA was monoclonal in 17 of 17 cases having EBER1-positive RS cells. By comparison, EBV DNA was not detected by Southern analysis in 20 cases lacking EBER1 in RS cells, even when occasional background lymphocytes expressed EBER1. Because clonal viral DNA was so readily detected in EBER1-positive cases, the EBV genome is probably amplified at least 50-fold in the infected RS cells. Monoclonality of EBV DNA implies that the RS cells were infected before malignant transformation.

Adolescent

Patterns of Staphylococcus aureus colonization, toxin production, immunity and illness in burned children.

Toxic shock syndrome toxin-one (TSST-1) produced from some but not all strains of Staphylococcus aureus is considered to be responsible for the development of the serious illness, toxic shock syndrome (TSS). The aim of this study was to establish the importance of S. aureus in the aetiology of suspected cases of TSS in acutely burned children. The pattern of colonization of S. aureus, and in particular toxic shock syndrome toxin-one (TSST-1) producing isolates, was studied in 53 burned children admitted as consecutive cases. S. aureus was not normally present on admission. Although it was the most common wound pathogen, it was acquired during the first few days after admission. Antibody status to TSST-1 on admission and at discharge was determined. Only half (49 per cent) of the children had antibodies to TSST-1. When it was possible to obtain paired admission and discharge samples in patients who had been given blood products, an assessment of seroconversion could be made. Two of the four patients given blood products during the resuscitation and postoperative period were antibody negative on admission (the other two were TSST-1 antibody positive). By discharge they had antibodies to TSST-1. Whilst the majority of donated blood products had antibodies to TSST-1 (76 per cent), some (24 per cent) did not. Seven of 53 children (13 per cent) developed a toxic shock-like illness which caused clinical concern.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Bacterial

Acute changes in oxygen consumption and body temperature after burn injury.

This study describes the pattern of oxygen consumption (VO2), rectal temperature (Tr), and acral skin temperature (Tac) in sleeping and resting (awake) burned children nursed in a thermoneutral environment. Measurements of respiratory gas exchange (VO2 and carbon dioxide production (VCO2)) were made using an open circuit, flow through system of indirect calorimetry. Tr and Tac were monitored continuously. Sixteen patients were studied during the first 18 hours after being burned. Three phases of change in VO2, Tr, and Tac are described. The first was a stable period and there was little change from admission values. The second (7-10 hours after burn) was a phase of rapid heat storage. It started with a fall in Tac. Peak values of Tr (38.8-41.1, median 40.0 degrees C) and VO2 (8.5-11.8 ml/min/kg) occurred either in phase 2 or in the later phase 3. At its peak VO2 was 12-61% above values in phase 1. In phase 3, Tac returned towards admission values but Tr and VO2 were variable. These changes suggest that both an increase in metabolic heat production as well as heat conservation at the extremities may be involved in the generation of early fever after a burn.

Body Temperature