The domino transplant: transplant recipients as organ donors.
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Adolescent↗
Biomedical subjects
S Miller
Publications and source records attributed to S Miller.
Population-based study of the pattern of molecular markers of minimal residual disease in childhood and adult acute lymphoblastic leukemia: an assessment of the practical difficulty of representative sampling for trial purposes. Northern Region Haematology Group.
BACKGROUND: The prevalence, in unselected patients with acute lymphoblastic leukaemia (ALL), of clonal rearrangements suitable for minimal residual disease (MRD) studies has not been formally investigated. PROCEDURE: This was a prospective, demographic study of the frequency of molecular markers of MRD in all patients with ALL presenting over 5 years within the Northern Health Region of England (population 3.1 million). Presentation marrow samples were examined to detect informative markers. RESULTS: One hundred twenty-four children (age <15 years) developed non-Burkitt ALL. No material was available for study in 21. Eighty-six had clonal gene rearrangements (BCR/ABL, immunoglobulin heavy chain (IGH) and/or T cell receptor (TCR) gene rearrangements). All entered remission; 84 (68% of the original cohort) survived to become eligible for MRD studies. One hundred sixteen adults developed ALL, of whom 48 were not studied due to insufficient cellular material in the bone marrow aspirate or to logistical problems in central referral of samples from other hospitals. Material from elderly adults (age >55 years) was less likely to be sent for analysis, 36% vs. 59% (P = 0.024). Thirty-eight had BCR/ABL and/or IGH/TCR gene rearrangements. Thirty-one (27% of the original cohort) entered remission and became eligible for MRD studies. Informative gene rearrangements were more common in children than adults (83% vs. 63%, P < 0.003). CONCLUSIONS: The results reveal substantial potential, unintentional, selection bias. Large-scale multicentre studies of MRD in children may well produce clinically relevant and representative data. Those who mount similar studies in adults should not assume they will be similarly representative or as successful in accrual of material.
Adolescent↗
Immune recognition of porin and lipopolysaccharide epitopes of Salmonella typhimurium in mice.
We investigated the antigenic specificity of the humoral immune response to infection by Salmonella typhimurium, by competitive inhibition enzyme-linked immunosorbent assay and Western immunoblots. A panel of eight murine monoclonal antibodies, raised to OmpC and OmpD porins and lipopolysaccharide (LPS)-O antigens, was used to define the specificity of the polyclonal immune response in mice. The monoclonal antibody panel recognized five distinct epitopes; these were localized to surface-exposed loops of OmpC and OmpD porin, to the "eye-let" forming loop L3 of OmpC/OmpD, and to LPS-O4 and O5 factors. The immune mouse serum raised to infections with S. typhimurium LT-2 strain WB600 (wild-type) competitively inhibited the binding of biotin-labelled monoclonal antibodies to the epitopes that they recognize, indicating that all five epitopes were targets of the host immune response to natural infection. However, only two epitopes, one within a surface-exposed loop of OmpC porin, and the other in the LPS-O4 factor, were immunodominant. Furthermore, the bacterial LPS core and O-antigen structure influenced the immune response to the porins. Surface epitopes of porins were dominant in the rough strain SH5014 (rfa), whereas the immune recognition of LPS epitopes was predominant in mice infected with the smooth, wild-type strain (WB600). Finally, the immune response to LPS epitopes O4 and O5 was more pronounced in mice immunized with heat-killed cells than those infected with live S. typhimurium.
Animals↗
Resolution of Ga-67 citrate uptake in the left neck mass of Hodgkin's disease and reversion of double scoliosis of cervical-thoracic and lower lumbar vertebrae.
A 6-yr-old boy underwent a total body Ga-67 citrate imaging study because of a large mass of Hodgkin's lymphoma in the left neck and the left anterior chest wall region. The images showed intense uptake in the left neck extending anteroinferiorly to the left upper chest wall corresponding to the left neck and chest region. In addition, there was mild cervical-upper thoracic scoliosis with convexity to the right and mild scoliosis of the lower lumbar scoliosis with concavity to the left. After three cycles of chemotherapy, in the follow-up Ga-67 citrate total body images seven months after his first Ga-67 citrate imaging, the intense uptake in the left neck and the left upper chest wall had been resolved and the scoliosis of the cervical-thoracic and lower lumbar spine had also been reversed to normal. This case shows that a Ga-67 citrate imaging study is useful for first diagnosis and subsequent monitoring of the therapeutic effects in a follow-up imaging. Also Ga-67 citrate imaging provided evidence that the scoliosis had been reversed.
Antineoplastic Combined Chemotherapy Protocols↗
Effects of simvastatin and pravastatin on gonadal function in male hypercholesterolemic patients.
Inhibition of cholesterol biosynthesis by hydroxymethyl glutaryl coenzyme A (HMG-CoA) reductase inhibitors could, in theory, adversely affect male gonadal function because cholesterol is a precursor of steroid hormones. The objective of this randomized double-blind trial was to compare the effects of simvastatin, pravastatin, and placebo on gonadal testosterone production and spermatogenesis. After a 6-week placebo and lipid-lowering diet run-in period, 159 male patients aged 21 to 55 years with type IIa or IIb hypercholesterolemia, low-density lipoprotein (LDL) cholesterol between 145 and 240 mg/dL, and normal basal levels of testosterone were randomly assigned to treatment with simvastatin 20 mg (n = 40), simvastatin 40 mg (n = 41), pravastatin 40 mg (n = 39), or placebo (n = 39) once daily. After 24 weeks of treatment, mean total cholesterol levels were decreased 24% to 27% and mean LDL cholesterol was decreased 30% to 34% in the 3 active-treatment groups (P < .001 for all comparisons to placebo). At 24 weeks, there were no statistically significant differences between the placebo group and any of the active-treatment groups for the change from baseline in testosterone, human chorionic gonadotropin (hCG)stimulated testosterone, free testosterone index, follicle-stimulating hormone (FSH), luteinizing hormone (LH), or sex hormone-binding globulin (SHBG). Moreover, there were no statistically significant differences at week 12 or week 24 for the change from baseline in sperm concentration, ejaculate volume, or sperm motility for any active treatment relative to placebo. Both simvastatin and pravastatin were well tolerated. In summary, we found no evidence for clinically meaningful effects of simvastatin or pravastatin on gonadal testosterone production, testosterone reserve, or multiple parameters of semen quality.
Adult↗
Heart preservation of non-heart-beating donors by in situ perfusion: comparison of artificial oxygen carrier perfluorocarbons with University of Wisconsin solution in a big animal model.
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Adenosine↗
Unilateral true vocal fold paralysis: cause of right-sided lesions.
At the Georgetown University Center for the Voice, 778 patients were referred for evaluation between July 1, 1990, and June 30, 1995. During this 5-year period, right true vocal fold paralysis or paresis was diagnosed in 24 of these patients (3%). Videostroboscopy, voice analysis, and patient records were reviewed. Ages ranged from 23 to 80 years, and sex distribution approximated a 1:1 ratio. The patients presenting symptoms included hoarseness, dysphagia, choking, voice pitch change, voice weakness, fatigability, and breathiness. Sources of the vocal fold dysfunction included iatrogenic, traumatic, central, and infectious causes.
Adult↗
Conventional high resolution versus fast T(2)-weighted MR imaging of the heart: assessment of reperfusion induced myocardial injury in an animal model.
Cardiac image quality in terms of spatial resolution and signal contrast was assessed for conventional and newly developed T(2)-weighted fast spin-echo imaging with high k-space segmentation. The capability in revealing regional myocardial edema and cellular damage was examined by a porcine model using histopathologic correlation. Twelve porcine hearts were excised from slaughtered animals and instantly perfused with 1000 mL cold cardioplegic solution. After 4 h of cold ischemia the hearts were reperfused for one hour using a "Langendorff" perfusion model followed by MR imaging at 1.5 Tesla. Three additional pig hearts served as controls and were studied by MR directly after harvesting. Histopathological analysis of regional tissue changes was performed macro- and microscopically. Short axis T(2)-weighted (3000/45 and 90) high quality fast spin-echo (FSE) images were recorded without cardiac action and signal intensity was correlated with histology. These images also served as gold standard for evaluation of newly developed faster sequences allowing measuring times shorter than 20 s. Fast T(2)-weighted imaging comprised single-slice fast spin echo (moderate echo train length of 23 echoes, FSE(m)), and multi-slice single-shot half-Fourier fast spin-echo (71 echoes, FSE(HASTE)) sequences, supplemented by versions with inversion recovery preparation (FSE(m)IR and FSE(HASTE)IR). Systolic function after reperfusion was restored in 10 porcine hearts. Tissue alterations included myocardial edema and contraction band necrosis which was found to be most severe in myocardium with maximum T(2) SI. Especially FSE(m) and FSE(m)IR sequences allowed differentiation of all categories of tissue damage on a high level of significance. In contrast, single-shot FSE(HASTE) and FSE(HASTE)IR sequences did not provide sufficient image quality to discriminate moderate and severe myocardial damage (p > 0.05). Different degrees of myocardial injury after ischemia and reperfusion can be staged by MR imaging, especially using conventional high resolution T(2)-weighted FSE sequences. The animal study indicates that fast T(2)-weighted FSE(m) and FSE(m)IR sequences lead to superior image quality and diagnostic accuracy compared to FSE(HASTE) and FSE(HASTE)IR imaging.
Analysis of Variance↗
Incorporating physical activity advice into primary care: physician-delivered advice within the activity counseling trial.
INTRODUCTION: The Activity Counseling Trial (ACT) was designed to compare the effectiveness of physician advice alone with physician advice plus behavioral counseling, provided by ACT-trained health educators, to increase levels of physical activity in healthy, sedentary patients. The objective was to determine health care providers' adherence to the ACT protocol for delivering initial "physician" advice on physical activity and to determine providers' satisfaction with the protocol. METHODS: Fifty-four physicians or physician assistants from 11 primary care practices located in California, Texas, and Tennessee volunteered to participate as ACT-trained physicians. Providers were trained to integrate 3 to 4 minutes of initial physical activity advice into the routine office visits of sedentary patients, aged 35 to 75 years, with no acute or serious chronic conditions. This advice included assessment of current physical activities, advising the patient about an appropriate physical activity goal, and referring the patient to the health educator. Providers initialed forms to document delivery of advice, and ACT health educators recorded their advice on a computerized tracking system. A provider survey measured length of time spent advising patients about physical activity and provider satisfaction with the program. RESULTS: Ninety-nine percent of patients received the initial physician advice about physical activity. Eighty-three percent of the providers spent less than 5 to 6 minutes, and 46% spent the recommended 3 to 4 minutes providing advice. Sixty-three percent said the advice resulted in little or no increase in the length of an office visit, and 83% said participation was an asset to their clinics. CONCLUSIONS: Providers incorporated brief physical activity advice into routine primary care visits with little disruption. Their response to the ACT advice protocol was positive and participation in the study was viewed as beneficial.
Adult↗
Activity of DNA polymerase alpha in aging human fibroblasts.
During the past decade intense investigation has focused on cellular aging with the expectation of discovering factors that regulate the replication complex and contribute to the onset and progression of cellular aging. The most striking feature of cellular aging is the failure of sensing diploid cells to enter or complete S phase of the cell cycle. The G1/S phase transition is an initial critical step in the regulation of proliferation in eukaryotic cells, and significant advances have been made toward understanding the basic mechanisms of aging by identifying components of the macromolecular assemblies participating in the G1/S transition. These studies have identified multiple DNA polymerases and their accessory factors, and have provided important strategies for investigating the molecular events that contribute to aging processes. DNA replication, repair and recombination in eukaryotic cells require the action of a variety of DNA polymerases, at least six of which are known, alpha, beta, gamma, delta, epsilon, and zeta. Among them the highly conserved DNA polymerase alpha-primase (pol alpha-primase) is the only enzyme capable of initiating DNA replication at chromosomal origin sites and at sites of initiation of discontinuous synthesis of Okazaki fragments on the lagging side of the replication fork. Numerous protein factors that play strategic roles in DNA replication have been identified and the understanding of their regulation has been an important step for identifying the elements that are involved in, and possibly necessary for, governing cellular senescence and aging. In this review we summarize the current information regarding DNA pol alpha modulation during aging. We focus in particular on the coordinated actions of DNA pol alpha in the presence of other cellular proteins involved in the replication complex in the hope that understanding pol alpha interactions with components of the replication complex may provide insight into the mechanisms by which aging and age-related diseases occur.
Aging↗
The ets protein PEA3 suppresses HER-2/neu overexpression and inhibits tumorigenesis.
Because HER-2/neu overexpression is important in cancer development, we looked for a method of suppressing the cell transformation mediated by HER-2/neu overexpression. We have identified that the DNA-binding protein PEA3, which is encoded by a previously isolated gene of the ets family, specifically targeted a DNA sequence on the HER-2/neu promoter and downregulated the promoter activity. Expression of PEA3 resulted in preferential inhibition of cell growth and tumor development of HER-2/neu-overexpressing cancer cells. This is a new approach to targeting HER-2/neu overexpression and also provides a rationale to the design for repressors of diseases caused by overexpression of pathogenic genes.
3T3 Cells↗
Flow injection spectroscopic analysis of model drugs using on-line UV-diode array, FT-infrared and 1H-nuclear magnetic resonance spectroscopy and time-of-flight mass spectrometry.
A prototype flow injection analysis (FIA) system for the characterisation of compounds via a combination of diode array UV, 1H NMR, FT-IR spectroscopy and time-of-flight (TOF) mass spectrometry has been investigated using a number of pharmaceuticals and related compounds as model compounds. This combination of spectrometers allowed the on-flow collection of UV, 1H NMR, IR and mass spectra together with atomic composition data, enabling almost complete structural characterisation to be performed. Practical detection limits with the current system were in the region of 50 micrograms, however, the use of state of the art spectrometers would result in a significant reduction in the amount of material required.
Flow Injection Analysis↗
Researching children: issues arising from a phenomenological study with children who have diabetes mellitus.
In Britain the incidence of diabetes mellitus in children is increasing. These children are health care consumers and will continue to be throughout their lives. It is important that their views are sought regarding their health care condition. A phenomenological study was undertaken with six children aged 7-12 years regarding their experience of living with diabetes. This research highlighted several issues regarding the conduct of research with children. Access to children required negotiation with the ethics committee and the parents. It was also important to seek the consent of the children via the signing of a consent form, as well as an on-going process throughout the conduct of the research. In addition, appropriate communication methods had to be utilized, acknowledging the age and abilities of individual children. The use of both verbal and non-verbal communication skills were important, but the use of non-verbal skills appeared to be the most significant. Researchers should not be bound by the supposed abilities of children and should take care not to underestimate the awareness and maturity that some children possess when addressing issues of concern to themselves. When given the opportunity, children were keen to express their views and were very articulate in doing so. There is much scope for future research studies seeking children's perceptions about their health care condition.
Behavioral Research↗
What use are ethical codes? An analysis of three possible rationales for the use of ethical codes in medical schools and a review of the evidence relating to them.
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Behavior↗
Peripheral renal angiomyolipoma with extension into the renal vein.
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Angiomyolipoma↗
Functional aerobic impairment in adolescents seropositive for HIV: a quasiexperimental analysis.
OBJECTIVE: To determine the degree to which cardiorespiratory insufficiency limits physical performance in adolescents seropositive for human immunodeficiency virus (HIV). DESIGN: Quasiexperimental, case series design. SETTING: Rehabilitation physiology laboratory. PARTICIPANTS: Seventeen adolescents (12 women, 5 men; age, 18 +/- 2 yr; weight, 74.7 +/- 19.3 kg; height, 170 +/- 9 cm) with HIV infection (viral load, 22,043 +/- 55,869 copies/mL; CD4 count, 499 +/- 210/mL) who were free of comorbid conditions limiting treadmill performance. MAIN OUTCOME MEASURES: Spirometric measurements of oxygen uptake and anaerobic threshold obtained from a peak exercise treadmill test using the modified Bruce protocol. RESULTS: Measured peak oxygen consumption (VO2) was 42% +/- 19% lower than expected (p < .025), suggesting a significant functional aerobic impairment (FAI) or peak VO2 less than 73% of expected values. Peak VO2 was only slightly higher (p < .05) than the oxygen uptake requirements for the most intense activities of daily living (ADL). Anaerobic threshold was only slightly higher (p < .05) than minimum ADL intensities. CONCLUSIONS: Cardiorespiratory insufficiency and FAI limited the ability to perform even low levels of physical activity in these adolescents with mild HIV seropositivity. Disability identified by quantification of FAI may affect implementation of the American with Disabilities Act and public health policy.
Adolescent↗
[The MR signal behavior of a 4-week-old occlusive myocardial infarct in an animal experiment].
PURPOSE: To correlate signal behaviour in T1- and T2-weighted images after Gd-DTPA with regional histopathology in occlusive myocardial infarction (MI). METHODS: Ligation of a diagonal branch of the LAD was performed in seven sheep. Four weeks later 0.1 mmol Gd-DTPA/kg were injected in five sheep 15 min before cardiac arrest and the sheep were slaughtered. In vitro imaging was performed at 1.5 T included T1- and T2-weighted spin echo sequences in long and short axis views. Signal intensities (SI) were determined in 36 myocardial segments per slice and compared to macro- and microscopy. RESULTS: In all animals an antero-lateral infarct region was evident histologically. This region presented with increased T2 SI and T1 SI after Gd-DTPA. The number of segments with increased SI in T1-weighted images was higher (n = 195 segments) compared to segments with increased T2 SI (n = 122 segments). Granulation tissue could be differentiated from rarely vascularized connective tissue at a high level of significance (p < 0.001) by T1 and T2 SI analysis. Wall thickness was significantly decreased in necrotic myocardium (3.8 +/- 1.2 mm) compared to normal tissue (9.8 +/- 1.1 mm, p < 0.001). CONCLUSION: In four-week-old occlusive MI the extent of necrosis can be accurately assessed by analysis of post contrast T1-weighted images. Considering regional T2 SI, granulation tissue can be differentiated from regions with predominant fibrous organisation.
Animals↗
[Variability in the MR tomographic determination of myocardial function and perfusion parameters in health subjects].
PURPOSE: The aim of the study was to evaluate myocardial function and perfusion patterns using magnetic resonance imaging in normal subjects. MATERIALS AND METHODS: 22 healthy volunteers were examined. Cine-mode acquisitions along all three axes of the heart were generated and perfusion was measured on a mid-ventricular short-axis view. Myocardial wall thickening was scored and contrast enhancement during the first pass was analysed. RESULTS: For myocardial wall thickening increasing values from base (24-86%) to apex (63-106%) were found. Contrast enhancement patterns showed regional variability. In addition marked individual differences were detectable. CONCLUSION: Perfusion patterns should be interpreted only in combination with functional parameters. Standard values for perfusion measurements cover very large range as a result of the high individual variability.
Adult↗