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Biomedical subjects

B Jones

Publications and source records attributed to B Jones.

At least 163 records · Page 9Linked to original sources
PubMed1998

Radiobiologically based assessments of the net costs of fractionated focal radiotherapy.

PURPOSE: To assess the potential changes in the net costs of focal radiotherapy techniques at differing doses per fraction and interfraction intervals. METHODS: Linear quadratic radiobiological modeling is used with appropriate variations in the radiosensitivity and tumor cell proliferation parameters. The notional cost of treatment is calculated from the number of fractions, cost per fraction and the cost of treatment failure, which is itself related to (1-TCP) where TCP is the tumor cure probability. Additional Monte Carlo calculations from ranges of radiobiological parameters have been used to simulate the cost of treatment of tumor populations. RESULTS: The optimum dose per fraction (and optimum overall cost) for conventional (nonfocal) radiotherapy is generally at low doses of around 2 Gy per fraction. The use of hyperfractionated and accelerated radiotherapy in addition to focal radiotherapy techniques appear to be indicated for more radioresistant tumors and if tumor proliferation is extremely rapid, but the need for treatment acceleration is much reduced where effective focal techniques are used. CONCLUSIONS: Radiobiological and economic modeling can be used to guide clinical choices of dose fractionation techniques providing the key radiobiological parameters are known or if the ranges of likely parameters in a tumor population are known. Focal radiotherapy, by the introduction of changes in the physical dose distribution, produces an upward shift in the optimum dose per fraction and a reduced dependency on overall treatment time.

Cell Division↗
PubMed1998

Choosing among generalized linear models applied to medical data.

When testing for a treatment effect or a difference among groups, the distributional assumptions made about the response variable can have a critical impact on the conclusions drawn. For example, controversy has arisen over transformations of the response (Keene). An alternative approach is to use some member of the family of generalized linear models. However, this raises the issue of selecting the appropriate member, a problem of testing non-nested hypotheses. Standard model selection criteria, such as the Akaike information criterion (AIC), can be used to resolve problems. These procedures for comparing generalized linear models are applied to checking for difference in T4 cell counts between two disease groups. We conclude that appropriate model selection criteria should be specified in the protocol for any study, including clinical trials, in order that optimal inferences can be drawn about treatment differences.

Clinical Trials as Topic↗
PubMed1998

Application of single-needle blastomere biopsy in human preimplantation genetic diagnosis.

We have tested and subsequently successfully applied a single-needle approach to obtain blastomere biopsies from human preimplantation embryos for preimplantation genetic diagnosis (PGD). The method was first evaluated in a mouse system and shown to be compatible with a high degree of in vitro and in vivo development of biopsied mouse embryos. Furthermore, we showed that biopsied mouse embryos after transfer to recipient mice underwent implantation, normal development and delivery. Litters were followed through puberty and adulthood and shown to be normal with regard to sexual function and also a panel of biochemical and morphological parameters including organ histology. Successful human preimplantation diagnosis, followed by pregnancies and birth of healthy babies, was established with two out of three couples carrying a risk to transmit chromosomal abnormalities leading to severe disease. This is the first report of the successful use of a single-needle approach in human PGD. Considering its simplicity, we conclude that the single-needle approach is an attractive alternative for biopsies in PGD.

Adult↗
PubMed1998

Developmental loss of effect of a Chromosome 15 QTL on alcohol acceptance.

Human alcohol abuse and alcoholism have clear developmental features, suggesting the possibility of changes over time in heritability and in quantitative genetic architecture, and raising prospects of identifying individual genes or quantitative trait loci (QTLs) that display different influence on alcohol-related phenotypes at different ages. The identification of specific loci showing such age-related changes will open up opportunities of focused association studies and of genotype manipulation by various mating procedures. Most animal model research in alcohol assesses the phenotypes of the animals at an early age; developmental studies are rare. Here we report on a QTL on Chromosome (Chr) 15 of the mouse that has been shown in several populations, including BXD recombinant inbred strains, an F2, and genotypically selected lines, to affect a measure of alcohol consumption. In the present study, we measured alcohol acceptance in the genotypically selected animals and in an F4 sample at about 100 days and again at about 300 days of age. In both groups, and in both sexes, significant differences were observed at 100 days between animals that were homozygous for the "increasing" haplotype defining the QTL region and those homozygous for the "decreasing" haplotype. At 300 days of age, the effect is absent in females and has diminished or disappeared in males. The results provide a further confirmation of the Chr 15 QTL in young mice, offer a new perspective on the development of alcohol-related phenotypes, and have strong implications for research design.

Alcohol Drinking↗
PubMed1998

Echocardiographic evidence of concentric left ventricular enlargement in female weight lifters.

In this study we investigated resting left ventricular structure and function in elite female weight-lifters. Fifteen National Squad members [mean age (SD) 25 (6) years] were compared to a recreationally active control group [n = 46, 23 (3) years]. Subjects were matched for body mass, body surface area and fat free mass, but the controls were slightly taller (P<0.01). Athletes and controls demonstrated similar resting heart rates and blood pressures. Septal wall (ST), posterior wall (PWT) and left ventricular internal dimension in diastole and systole (LVIDd and LVIDs, respectively) were measured from M-mode echocardiograms. Calculations were made for left ventricular mass (LVM), mass-volume ratio (m:V), wall-thickness-cavity dimension ratio (h:R) and systolic function. Left ventricular filling velocities were determined via Doppler echocardiography. ST [9.0 (1.1) v.s. 7.7 (1.0) mm] and PWT [8.7 (1.4) v.s. 7.5 (1.3) mm] were greater, whereas LVIDd [46.2 (2.8) v.s. 48.4 (3.4) mm] was smaller in the weight-lifters (P<0.05). After allometrically adjusting for differences in height, the weight-lifters had a greater ST, PWT and LVM (P<0.05) and similar LVIDd. Both m:V and h:R were increased in the weightlifters (P<0.05). All functional data were within normal limits and no group differences were observed. The female weight-lifters demonstrated a concentric left ventricular enlargement that was not detrimental to left ventricular performance at rest.

Adult↗
PubMed1998

Fibrillary glomerulonephritis in a renal allograft.

Fibrillary glomerulonephritis is an uncommon disease seen in approximately 1% of all native kidney biopsy specimens. We present here a case of a 40-year-old white woman with the rapid loss of graft function secondary to fibrillary glomerulonephritis within 7 days of receiving a living-related renal allograft. This case emphasizes the values of combining urinalysis with prompt allograft kidney biopsy in recipients with an elevated serum creatinine posttransplantation. When one encounters rapidly progressing glomerulonephritis or a pulmonary-renal syndrome in the immediate posttransplantation period, fibrillary glomerulonephritis must be considered in the differential diagnosis. Because of a high recurrence rate and no available treatment to modify a potentially malignant course of this disease, we recommend caution when considering these patients for transplantation.

Actin Cytoskeleton↗
PubMed1998

Detection of Chlamydia trachomatis cervical infection by urine tests among adolescents clinics.

PURPOSE: To compare urine ligase and polymerase chain reaction (LCR, PCR) tests for diagnosis of Chlamydia trachomatis cervical infection with PCR and nucleic acid probe (GPA) on cervical specimens in adolescents, as well as risk factors for C. trachomatis infection and prevalence of infection at enrollment. METHODS: Urine and cervical specimens were collected from women aged 13-20 years attending adolescent clinics, and interviews were administered. Urine specimens were tested by PCR and LCR, and cervical specimens by GPA and PCR. Prevalence rates of C. trachomatis infection and gonorrhea were compared by demographic, behavioral, and clinical risk factors. RESULTS: Of 415 women tested, 86 (20.7%) were infected with C. trachomatis as indicated by positive cervical PCR results. A higher prevalence of C. trachomatis infection was seen among adolescents who douched monthly or more frequently, or had gonorrhea; prevalence declined from 25.8% in the first 7 months to 16.3% in the last 14 months of the study (p = .017). A statistically significant protective effect for reported condom use was not observed. Sensitivity of urine PCR was 89.5% and specificity was 100% relative to cervical PCR, compared to 84.9% and 99.4% (urine LCR) and 65.4% and 98.0% (cervical GPA). Sensitivity of urine PCR was higher in women with discharge; urine LCR sensitivity was higher in women < 19 years of age. CONCLUSIONS: Polymerase chain reaction and LCR assays on urine specimens were sensitive, specific, and noninvasive tests in this population of adolescents with high C. trachomatis infection prevalence. Chlamydia trachomatis infection was associated with douching monthly or more frequently. Prevalence of infection declined over the period during which the study was conducted.

Adolescent↗
PubMed1998

Extramedullary T lymphoblastic transformation of chronic myeloid leukaemia occurring after double allogeneic transplantation.

The clinical course of chronic myeloid leukaemia (CML) is characterised by a chronic phase followed by an acute phase or blast crisis. Lymphoid transformation accounts for 20-30% of such events, with the majority of cases being of B cell origin. Extramedullary transformation occurs in approximately 10% of cases. We report a case of T cell lymphoblastic transformation in CML presenting as an extramedullary mass after allogeneic stem cell transplant. This case supports the growing evidence that CML arises in the pluripotent stem cell.

Adult↗
PubMed1998

Estimation of tumour hypoxic fraction from clinical data sets compatible with accelerated repopulation.

By extrapolation to zero time, the initial and final slopes of data sets which probably demonstrate the existence of accelerated repopulation during radiotherapy can be used to estimate the lower limits of the initial tumour hypoxic fraction. The slow repopulation phase (initial slope) is assumed to reflect treatment in mixed oxic and hypoxic conditions and the later fast repopulation (final slope) phase that of a well-oxygenated cell population. The method assumes that accelerated repopulation in tumours results from an improvement in oxygen status during radiotherapy, but quantitative knowledge of repopulation factors is not required in the calculations. Using the data of (a) Withers et al. (for head and neck squamous cell cancer) and (b) Maciejewski & Majewski (for bladder cancer), the lower limits of initial hypoxic fraction appear to be between 10 and 52%, the exact values depending on the value assumed for the oxygen-enhancement ratio (OER) of the hypoxic compartment. The analysis also suggests that the half-life of effective tumour reoxygenation is probably less than 5 days.

Cell Hypoxia↗
PubMed1998

The immune response to soluble D10 TCR: analysis of antibody and T cell responses.

In order to evaluate the potential of TCR as vaccines for immunomodulation, the immunogenicity of soluble versions of D10 TCR has been investigated in mice. Soluble D10 TCR containing the extracellular domains were produced either as dual chain (dc) TCR lacking transmembrane and cytoplasmic regions or as a TCR-IgG1 chimeric protein. Soluble single chain (sc) D10 TCR contained only the Valpha and Vbeta segments joined by a peptide linker. Syngeneic D10 dcTCR or D10 TCR-IgG1 immunizations of AKR mice induced antibody responses to D10 clonotypic epitopes and to constant region epitopes that are not exposed on D10 cells. Only clonotypic antibodies were produced after D10 scTCR immunizations. Immunization of AKR mice with D10 dcTCR and D10 TCR-IgG1 primed I-Ak- and I-Ek-restricted CD4+ T cells recognizing constant region epitopes, but there was no detectable response to the variable region. Comparison of the in vitro proliferative responses of CD4+ T cells from D10 scTCR-primed H-2 congenic mice revealed that H-2u was a responder haplotype for the variable region. How the immunogenicity of particular regions of the TCR appears to be shaped by tolerance induction in vivo and the implications for immunotherapy with soluble TCR vaccinations are discussed.

Adjuvants, Immunologic↗
PubMed1998

Laboratory values improve predictions of hospital mortality.

OBJECTIVE: To compare the precision of risk adjustment in the measurement of mortality rates using: (i) data in hospitals' electronic discharge abstracts, including data elements that distinguish between comorbidities and complications; (ii) these data plus laboratory values; and (iii) these data plus laboratory values and other clinical data abstracted from medical records. DESIGN: Retrospective cohort study. SETTING: Twenty-two acute care hospitals in St Louis, Missouri, USA. STUDY PARTICIPANTS: Patients hospitalized in 1995 with acute myocardial infarction, congestive heart failure, or pneumonia (n = 5966). MAIN OUTCOME MEASURES: Each patient's probability of death calculated using: administrative data that designated all secondary diagnoses present on admission (administrative models); administrative data and laboratory values (laboratory models); and administrative data, laboratory values, and abstracted clinical information (clinical models). All data were abstracted from medical records. RESULTS: Administrative models (average area under receiver operating characteristic curve=0.834) did not predict death as well as did clinical models (average area under receiver operating characteristic curve=0.875). Adding laboratory values to administrative data improved predictions of death (average area under receiver operating characteristic curve=0.860). Adding laboratory data to administrative data improved its average correlation of patient-level predicted values with those of the clinical model from r=0.86 to r=0.95 and improved the average correlation of hospital-level predicted values with those of the clinical model from r=0.94 for the administrative model to r=0.98 for the laboratory model. CONCLUSIONS: In the conditions studied, predictions of inpatient mortality improved noticeably when laboratory values (sometimes available electronically) were combined with administrative data that included only those secondary diagnoses present on admission (i.e. comorbidities). Additional clinical data contribute little more to predictive power.

Clinical Laboratory Information Systems↗
PubMed1998

The impact of scalar variable and process on athlete-control comparisons of cardiac dimensions.

PURPOSE: This study compared linear left ventricular dimensions and mass (LVM), before and after normalizing for body dimensions via allometric and ratio-standard scaling. METHODS: Height (HT; m), body mass (BM; kg), body surface area (BSA; m2), and fat-free mass (FFM; kg) were measured in elite male weight lifters (N = 11) and age-matched controls (N = 45). Septum (ST), posterior wall (PWT), and internal dimension in diastole (LVIDd) were measured from M-mode echocardiographic traces and used to calculate LVM. Via multivariate allometric scaling, common group power function exponents were identified for all cardiac dimensions related to all body size scalars. t-tests were used to compare group differences in absolute and scaled data. RESULTS: BM, FFM, and BSA, as well as absolute LVM (262 +/- 54 vs 206 +/- 39) and ST (11 +/- 1 vs 9 +/- 1), were greater in the athletes (P < 0.05). All exponents conformed to dimensionality theory within 95% confidence limits. Fat-free mass presented the highest multiple R value and the least residual sum of squares of any scalar variable. If FFM was used to scale, no difference in LVM remained (P > 0.05). CONCLUSIONS: Data suggest that any group effect on cardiac dimensions is substantially altered by the scaling procedure. The choice of the most appropriate variable and process for partitioning out any effect of body dimensions on cardiac dimensions in similar studies requires attention.

Adult↗
PubMed1998

Frontonasal dysplasia with optic disc anomalies and other midline craniofacial defects: a report of six cases.

The association of optic disc abnormalities with basal encephaloceles, specifically of the sphenoethmoidal type, and midline facial clefts has rarely been reported, although the association of midline facial clefts with encephaloceles is well described. We now report six cases of children, three males and three females, presenting with a sphenoethmoidal encephalocele, optic disc anomalies, midline facial clefting, hypertelorism, complete or partial agenesis of the corpus callosum, and endocrinological disturbances, including diabetes insipidus and pituitary dysfunction. This report underlines the importance of careful ophthalmic and endocrinological investigation of children with midline clefts associated with basal encephaloceles. These cases may represent a distinct entity within the spectrum of frontonasal dysplasia.

Abnormalities, Multiple↗
PubMed1998

Duane's retraction syndrome and juvenile Batten's disease: a new association?

BACKGROUND: Although Duane's retraction syndrome (DRS) represents less than 5% of strabismus patients presenting to an ophthalmology department, it is a difficult management problem that is often poorly treated. The developmental defect has been isolated to early in the embryonic period, but to date a chromosomal location is still uncertain. Neuronal ceroid lipofuscinosis (NCL) or Batten's disease is a lysosomal storage disease with autosomal recessive inheritance, which has been categorized according to the age of onset of symptoms. METHODS/RESULTS: We report on a patient with DRS who developed juvenile Batten's disease. CONCLUSIONS: These two abnormalities can both be inherited, but their association has not been previously documented.

Child, Preschool↗
PubMed1998

Cystatin A expression reduces bile salt-induced apoptosis in a rat hepatoma cell line.

We have previously demonstrated abrogation of bile salt-induced apoptosis by cathepsin B inhibitors. However, caspases have been strongly implicated in apoptosis, and the mechanistic interface between caspase and cathepsin B activation is unclear. Thus our aims were to determine the mechanistic relationship between caspases and cathepsin B in bile salt-induced apoptosis in a rat hepatoma cell line. Expression of cystatin A was used to inhibit cathepsin B, whereas Z-Val-Ala-Asp-fluoromethyl ketone (Z-VAD-FMK) was used to inhibit caspases. Cystatin A expression prevented cathepsin B activation and apoptosis during treatment with glycochenodeoxycholate (GCDC), a toxic bile salt. Caspase N-acetyl-Asp-Glu-Val-Asp-7-amino-4-methylcoumarin (DEVD-AMC) hydrolytic activity increased in both wild-type and cystatin A-transfected cells treated with GCDC, demonstrating caspase activation despite inhibition of cathepsin B. In contrast, Z-VAD-FMK blocked both DEVD-AMC hydrolytic activity and cathepsin B activity during GCDC treatment. Our data demonstrate that 1) bile salt-induced apoptosis can be inhibited by the cystatin A transgene and 2) caspase and cathepsin B activation are linked mechanistically with cathepsin B downstream of caspases.

Amino Acid Chloromethyl Ketones↗
PubMed1998

The clinical radiobiology of brachytherapy.

The unique geometrical features of brachytherapy, together with the wide variety of temporal patterns of dose delivery, result in important interactions between physics and radiobiology. These interactions exert a major influence on the way in which brachytherapy treatments should be evaluated, both in absolute and comparative terms. This article reviews the main physical and radiobiological aspects of brachytherapy and considers examples of their influence on specific types of treatment. The issues relating to the optimization of high dose rate brachytherapy are presented, together with the implications of multiphasic repair kinetics for low dose-rate and pulsed high dose rate brachytherapy. The opportunities for application of radiobiological principles to improve various brachytherapy techniques, together with the integration of brachytherapy with teletherapy, are also outlined. Equations for the numerical evaluation of brachytherapy treatments are presented in the Appendices.

Brachytherapy↗