Detection of persistent measles virus infection in Crohn's disease: current status of experimental work.
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Biomedical subjects
Publications and source records attributed to D Wilson.
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PURPOSE: To assess the accuracy of radiologic interpretation, in the absence of clinical information, in the differentiation of benign and malignant sigmoid strictures at barium enema examination. MATERIALS AND METHODS: On two occasions, four independent observers retrospectively assessed examination findings in 78 patients with documented sigmoid strictures (43 benign, 35 malignant). Each stricture was graded by using a five-point scale (definitely malignant to definitely benign). RESULTS: No significant difference existed between the areas under the receiver operating characteristic curves for the two assessments with any observer. Consensus findings indicated agreement among at least three of the four observers in 68 (87%) and 66 (85%) cases at the first and second assessments, respectively. One benign stricture was called malignant at both assessments. When consensus existed, the positive predictive value for malignant strictures was 96% at both assessments (sensitivity, 63% and 66%). Nine malignant strictures were called benign, three at both assessments. When consensus existed, the positive predictive value for benign strictures was 84% and 88% at the first and second assessments, respectively (sensitivity, 88% and 86%, respectively). CONCLUSION: The differentiation between a benign and a malignant sigmoid stricture can be made in most cases at barium enema examination. When a stricture appears malignant, the diagnosis is usually correct, but caution is advised when a stricture appears benign.
Over the past two decades, changes in the health services designed to improve access to and quality of asthma care have occurred in South Africa. The aim of this study was to investigate the incidence of fatal and near-fatal asthma (NFA) from 1980-1997 in an urban part of South Africa. A retrospective analysis of fatal asthma and NFA in the Cape Town City Council area was performed. Mortality data were obtained from death notification records. Data on NFA were obtained from the records of patients admitted for asthma to intensive care units (ICUs) at major academic hospitals serving the area. There were 1,506 deaths (mean age 56 yrs) from asthma reported; 39 and 3% occurred in people under 55 and 15 yrs, respectively. Average annual asthma mortality rate (8.1 +/- 1.9 per 100,000 population) was highest amongst people of mixed race (10.1 +/- 2.0), followed by Blacks (6.8 +/- 3.1) and Whites (5.0 +/- 1.9, p<0.001). Asthma mortality declined by 0.28 deaths per 100,000 population per year; rates decreased in all ethnic groups. Most deaths (72.3%) were outside a health facility and a higher number of deaths occurred on weekends (223 deaths x day(-1)) than weekdays (207 deaths x day(-1), p=0.014). Paediatric asthma ICU admissions declined by 1.81 children yr(-1). The annual number of adults admitted to ICU for asthma, and the proportion requiring intermittent positive pressure ventilation did not change. These results indicate that the incidence of fatal and near-fatal asthma in this area has declined over the period and this may reflect improved asthma management. However, the relatively high asthma mortality rate in people of mixed race and the predominance of deaths outside health facilities and on weekends suggest problems with access to care.
Individuals who are involved with the death of a person with a terminal illness will often classify the death as either 'good' or 'bad'. Families and healthcare practitioners assess many factors when determining their 'success' or 'failure' in assisting someone in the terminal phase. Palliative care nurses are particularly vulnerable to self-assessments about care of the dying, because death is a daily occurrence. Feelings of failure, unmet expectations and feeling of regret about not being able to prevent a traumatic death may be a source of stress for palliative care nurse and may affect their abilities to function effectively. This article reports the findings of a study involving interviews with 20 palliative care nurses to determine their perceptions of a good and bad death. The study also examined the expectations they hold of themselves and that they believe others hold of them in helping patients to attain a good death. Clinical implications are discussed based on these findings.
Cerebellar liponeurocytoma is a rare tumor of the posterior fossa that has many morphological similarities to medulloblastoma and neurocytoma. Recently the World Health Organization working group for classification of central nervous system neoplasms adopted the term "cerebellar liponeurocytoma" to provide a unified nomenclature for a tumor variously labeled in the literature as lipomatous medulloblastoma, lipidized medulloblastoma, medullocytoma. neurolipocytoma, lipomatous glioneurocytoma, and lipidized mature neuroectodermal tumor of the cerebellum. The rarity of this tumor and paucity of pertinent information regarding its biological potential and natural history have resulted in the application of various treatment modalities. It is suggested in the available literature that these lesions have a much more favorable prognosis than typical medulloblastomas, and that adjuvant therapy for liponeurocytoma need not be as extensive as that administered for medulloblastomas.
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This paper reports on changes in mandibular condylar growth in sheep fitted with experimental functional appliances. The paper also addresses the similarities of mandibular condylar growth in sheep and humans. Experimental functional appliances were developed, constructed and applied to four, four-month old, male sheep. Another four sheep served as matched controls. All animals received fluorochrome bone labels during the study and their weight gain also was recorded. Fifteen weeks later, all animals were sacrificed and each temporo-mandibular joint and left metacarpus were removed. Undecalcified mid-sagittal sections of the joint and metacarpus were prepared for fluorescence microscopy. The mandibular condylar growth vector in sheep was found to be in a postero-superior direction. Condylar growth in the control sheep during the experimental period varied from 8.8 to 11.9 mm, with the mean being 10.6 mm, which is quantitatively similar to two years of condylar growth in human adolescents. In the experimental sheep, the condylar growth varied from 8.5 to 13.3 mm, with the mean being 11.4 mm. When metacarpal growth and weight gain were taken into consideration using multivariant analysis, the coefficients for growth in the postero-superior and posterior direction were found to be high, with adjusted r2 as 0.84 and 0.82 respectively. The induced condylar growth was estimated to be largest in the posterior direction (2.30 mm), which is also similar to previous reports in humans. These findings suggest the appropriateness of using sheep as a model for quantitative histological analysis when investigating the mechanisms of functional appliance treatment.
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A 70-year-old woman developed a glioblastoma in the irradiated field 7 years after stereotactic radiosurgery for meningioma. Glioma induction has been previously reported after external beam radiation for leukaemia, pituitary adenoma, tinea capitus, and meningioma. This radiosurgery-induced malignancy may portend further reports of tumour induction. The theoretical risk of tumour induction by low doses of radiation to normal neural tissue after radiosurgery is now confirmed. Reports of additional cases of radiosurgery-induced tumours might temper the use of this increasingly used technique for benign surgically accessible lesions.
Enzymatic phosphorylation and dephosphorylation reactions were used to modify a genetically engineered variant of spider dragline silk. The approximately 25 kDa protein was phosphorylated with cyclic AMP-dependent kinase and dephosphorylated with calf intestinal alkaline phosphatase. Phosphorylation inhibited beta-sheet assembly of the protein and enhanced solubility to about 5 mg/mL in water, compared to about 20% of this level upon enzymatic dephosphorylation. The cyclability of the phosphorylation-dephosphorylation system was confirmed by MALDI with a model peptide. Kinetic studies conducted with [gamma-(32)P]ATP illustrate that the phosphorylation reaction proceeds over 6 h. Secondary structure of the phosphorylated and dephosphorylated proteins was determined by CD and FTIR. The results illustrate that an enzymatic phosphorylation event can be used to control the solution structure of a protein like silk, which has a tendency to prematurely precipitate due to the formation of beta-sheets.
OBJECTIVE: To describe the short-term changes in CD4 lymphocyte counts after the interruption of antiretroviral HIV therapy in order to increase the understanding of CD4 lymphocyte dynamics, and so that appropriate monitoring strategies can be designed. METHODS: We studied 35 HIV-infected patients with late-stage disease who had therapy interruptions leading to high viral load levels, median greater than 750 000 RNA log10 copies/ml, and in whom two CD4 cell counts (median 28 days apart) were available before beginning a salvage regimen. RESULTS: Overall, there was a substantial decline in CD4 cell counts from a median of 125 to 83 cells/mm3 in the average 28 day period, with median proportionate and absolute losses of 26% and 24 cells/mm3 per month, respectively (P < 0.008). This tended to be greater in individuals studied sooner after interrupting therapy (P = 0.03) and in those with CD4 cell counts above the pre-therapy baseline (P = 0.06). There was a strong negative correlation between the proportionate increase in viral load and the absolute change in CD4 cell count (-0.66, P = 0.0002). CONCLUSION: Patients with relatively advanced HIV infection interrupting antiretroviral therapy after failing a protease inhibitor-containing regimen require frequent monitoring because CD4 cell counts appear to fall quite rapidly, at least in the first few weeks after interruption.
BACKGROUND: Highly active antiretroviral therapy (HAART) is now widely used in clinical practice and gives rise to a range of immunological, virological and clinical responses. OBJECTIVES: To describe the immunological, virological and clinical response to HAART and to examine the frequency of modification of the HAART regimen among patients from a single treatment centre. METHODS: Kaplan-Meier estimation and incidence rates were used to describe responses to HAART (a protease inhibitor or non-nucleoside drug in addition to at least two nucleoside analogues) among 421 patients from the Royal Free Hospital in London. RESULTS: The median CD4 cell count at starting HAART was 186 x 10(6) cells/l [interquartile range (IQR) 76-310] and viral load was 5.13 log10 copies/ml (IQR 4.66-5.56). At 6 months after starting HAART, 51.1% of patients were estimated to have experienced a 100 x 10(6) cells/l increase in CD4 cell count; the median time for viral load to fall below 400 copies/ml was 3.7 months (95% confidence interval 3.2-4.4). At 6 months after the first viral load was < 400 copies/ml, 16.4% of patients were estimated to have failed on the basis of a single viral load > 400 copies/ml and 12.4% were estimated to have failed if the more stringent definition of two viral loads above the limit of detection was used. Compared with the pre-HAART era, the incidence of death among patients on HAART was one sixth of that level; new AIDS-defining illnesses was one seventh; and hospital admissions was one fifth. In total, 141 patients (33.5%) stopped at least one of the antiretroviral agents included as part of their HAART regimen; the occurrence of side effects was the most common reason (n = 63; 44.7%). CONCLUSION: A good response occurred to an initial HAART regimen. There was a high rate of virological relapse, which varied considerably according to the definition of failure used. Even so, the rates of clinical progression and hospital admissions observed to date were low. Further follow-up of these patients is required to determine their long-term immunological, virological and clinical outcome.
The genetic events underlying the development of prostate cancer are poorly defined. c-Myc is often activated in tumors that have progressed to metastatic status, so events that promote this process may be important. Bin1 is a nucleocytoplasmic adaptor protein with features of a tumor suppressor that was identified through its ability to interact with and inhibit malignant transformation by c-Myc. We investigated a role for Bin1 loss or inactivation in prostate cancer because the human Bin1 gene is located at chromosome 2q14 within a region that is frequently deleted in metastatic prostate cancer but where no tumor suppressor candidate has been located. A novel polymorphic microsatellite marker located within intron 5 of the human Bin1 gene was used to demonstrate loss of heterozygosity and coding alteration in 40% of informative cases of prostate neoplasia examined. RNA and immunohistochemical analyses indicated that Bin1 was expressed in most primary tumors, even at slightly elevated levels relative to benign tissues, but that it was frequently missing or inactivated by aberrant splicing in metastatic tumors and androgen-independent tumor cell lines. Ectopic expression of Bin1 suppressed the growth of prostate cancer lines in vitro. Our findings support the candidacy of Bin1 as the chromosome 2q prostate tumor suppressor gene.
The methymycin and pikromycin series of antibiotics are structurally related macrolides produced by several Streptomyces species, including Streptomyces venezuelae ATCC 15439, which produces both 12-membered ring macrolides methymycin, neomethymycin, and 14-membered ring macrolides pikromycin and narbomycin. Cloning and sequencing of the biosynthetic gene clusters for these macrolides from three selected Streptomyces strains revealed a common genetic architecture of their polyketide synthases (PKSs). Unlike PKS clusters of other 14-membered ring macrolides such as erythromycin and oleandomycin, each of the pikromycin series producers harbors a six module PKS cluster, in which modules 5 and 6 are encoded on two separate proteins instead of one bimodular protein, as well as a thioesterase II gene immediately downstream of the main PKS gene. The results shed new light on the evolution of modular PKSs and provide further evidence on the regulation of methymycin and pikromycin production in S. venezuelae ATCC 15439.
Our understanding of early human development has been impeded by the general difficulty in obtaining suitable samples for study. As a result, and because of the extraordinarily high degree of evolutionary conservation of many developmentally important genes and developmental pathways, great reliance has been placed on extrapolation from animal models of development, principally the mouse. However, the strong evolutionary conservation of coding sequence for developmentally important genes does not necessarily mean that their expression patterns are as highly conserved. The very recent availability of human embryonic samples for gene expression studies has now permitted for the first time an assessment of the degree to which we can confidently extrapolate from studies of rodent gene expression patterns. We have found significant human-mouse differences in embryonic expression patterns for a variety of genes. We present detailed data for two illustrative examples. Wnt7a, a very highly conserved gene known to be important in early development, shows significant differences in spatial and temporal expression patterns in the developing brain (midbrain, telencephalon) of man and mice. CAPN3, the locus for LGMD2A limb girdle muscular dystrophy, and its mouse orthologue differ extensively in expression in embryonic heart, lens and smooth muscle. Our study also shows how molecular analyses, while providing explanations for the observed differences, can be important in providing insights into mammalian evolution.
To determine the accuracy of the SF-36 summary mental and physical health scales in reflecting their underlying subscales using the traditional method of scoring based on factor coefficients derived through principle components analysis and orthogonal rotation. A representative Australian population survey containing the SF-36 was used to obtain factor coefficients from principle components analysis and orthogonal rotation for scoring the physical component summary (PCS) and the mental component summary (MCS) of the SF-36 in the traditional way. In addition two other methods were used to produce coefficients. The first method used maximum likelihood extraction and oblique rotation. The second method fit a structural equation model to the data in a confirmatory factor analysis. The coefficients derived by each of the methods were applied to the data of a second representative population survey. This survey also provided data on physical and mental health status which allowed comparison of the summary scores and underlying subscales according to various health states. Neither of the scoring methods based on the exploratory factor analyses methods (orthogonal and oblique) produced summary scale scores, by age group, that adequately reflected the underlying subscales. When coefficients derived using structural equation modeling were fit to the data in a confirmatory factor analysis the MCS and PCS accurately reflected their underlying subscale scores. They also produced MCS and PCS scores for the various health states as would be expected from the underlying subscales. The traditional methods of scoring the SF-36 summary scales produce results that would not be expected from the underlying subscales. The problem was only corrected by fitting a structural equation model to the data in a confirmatory factor analysis. The results advise caution in the use of the SF-36 summary scales and suggests that alternative methods of developing factor coefficients need to be employed in studies using the SF-36 summary scales.