Article showed how not to read economic evaluations.
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Biomedical subjects
Publications and source records attributed to J Henderson.
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Intrauterine viral infection commonly presents as nonimmune hydrops fetalis or intrauterine growth restriction. Cytomegalovirus (CMV) and parvovirus are commonly recognized causes of fetal infection using serology and cultures. We used the polymerase chain reaction (PCR) to evaluate the frequency of fetal viral infection and the associated clinical course and outcome. Specimens (amniotic fluid, fetal blood, pleural fluid, tissue) from 303 abnormal pregnancies at risk for viral infection and 154 controls were analyzed using primers for CMV, herpes simplex virus, parvovirus B19, adenovirus, enterovirus, Epstein-Barr virus, and respiratory syncytial virus. Viral genome was detected in 144/371 samples (39%) or 124/303 patients (41%), with adenovirus (n = 74 patients; 24%), CMV (n = 30 patients; 10%), and enterovirus (n = 22 patients; 7%) most common. Only 4/154 (2.6%), unaffected control patients' samples were PCR positive. We conclude that diagnosis of fetal viral infection by PCR is common in abnormal pregnancies. Adenovirus and enterovirus may cause fetal infection that have been previously unrecognized.
We report the results of a retrospective study of the role of intensive care unit (ICU) admission in the management of 367 children who underwent bone marrow transplantation (BMT) at a tertiary referral institution. 39 patients (11%) required 44 ICU admissions for a median of 6 d. 70% received marrow from unrelated donors, half of which were mismatched; 80% had leukaemia and two-thirds were considered high-risk transplants. Respiratory failure was the major reason for admission to ICU. 75% of admissions required mechanical ventilation (for a median of 5 d) and 20 patients had lung injury as defined by the criteria of the Seattle group. None of 11 patients with proven viral pneumonitis survived (P = 0.06) and only one of 20 patients with lung injury survived (P < 0.01). Six of seven patients with a primary neurological problem survived (P < 0.001); these appear to represent a good outcome group. Age, the presence of graft-versus-host disease, the use of inotropes, isolated renal or hepatic impairment, and paediatric risk of mortality (PRISM) score were not predictive of outcome. In total, 12 patients (27% of admissions) survived and were discharged from hospital 30d or more after admission and eight (18%) survived >6 months. ICU admission can be beneficial to selected children post-BMT but it may be less useful in proven viral pneumonitis. Where mechanical ventilation is required, the duration of this support should be limited unless there is rapid improvement.
The Drosophila protein Groucho is involved in the regulation of cell-determination events during insect neurogenesis and segmentation. A group of mammalian proteins, referred to as transducin-like Enhancer of split (TLE) 1 through 4, share with Groucho identical structures and molecular properties. The aim was to determine whether individual TLE proteins participate in the regulation of cell determination in mammals like their Drosophila counterpart. It is here reported that TLE family members are expressed in combinatorial ways during the in vitro differentiation of mouse P19 embryonic carcinoma cells (a model for neural determination) and rat CFK2 cells (a model for chondrocytic determination). TLE1 is up-regulated and TLE2 and TLE4 are down-regulated to different extents during early stages of differentiation. In contrast, later stages correlate with up-regulation of TLE2 and TLE4, and decreased expression of TLE1. Individual TLE proteins are also expressed in combinatorial as well as complementary patterns during the development of the cerebral cortex and spinal cord of mouse embryos. In particular, TLE1 is robustly expressed in both neural progenitor cells and postmitotic neurons of the outer layers of the cortical plate, whereas TLE4 expression marks preferentially postmitotic neurons of the inner layers. Taken together, these results strongly suggest non-redundant roles for individual TLE proteins during both cell-determination and cell-differentiation events.
MORGAN is an integrated system for finding genes in vertebrate DNA sequences. MORGAN uses a variety of techniques to accomplish this task, the most distinctive of which is a decision tree classifier. The decision tree system is combined with new methods for identifying start codons, donor sites, and acceptor sites, and these are brought together in a frame-sensitive dynamic programming algorithm that finds the optimal segmentation of a DNA sequence into coding and noncoding regions (exons and introns). The optimal segmentation is dependent on a separate scoring function that takes a subsequence and assigns to it a score reflecting the probability that the sequence is an exon. The scoring functions in MORGAN are sets of decision trees that are combined to give a probability estimate. Experimental results on a database of 570 vertebrate DNA sequences show that MORGAN has excellent performance by many different measures. On a separate test set, it achieves an overall accuracy of 95 %, with a correlation coefficient of 0.78, and a sensitivity and specificity for coding bases of 83 % and 79%. In addition, MORGAN identifies 58% of coding exons exactly; i.e., both the beginning and end of the coding regions are predicted correctly. This paper describes the MORGAN system, including its decision tree routines and the algorithms for site recognition, and its performance on a benchmark database of vertebrate DNA.
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STUDY OBJECTIVE: To examine the effect of deprivation, crowding, maternal smoking, and breast feeding on morbidity from wheeze and diarrhoea in the first six months after birth. DESIGN: A geographically located population survey using maternal responses on self completion questionnaires. SETTING: The three health districts of Bristol. SUBJECTS: 8501 infants from the Avon Longitudinal Study of Pregnancy and Childhood (ALSPAC) in which all women expecting a baby between April 1991 and December 1992 in Bristol were invited to participate. MAIN OUTCOME MEASURES: The prevalence and severity of wheeze at six months after birth. The prevalence of diarrhoea and the duration of the worst bout at six months after birth. RESULTS: Logistic regression analyses using a conceptual hierarchical framework showed that wheeze was significantly more likely to be reported for infants if they lived in rented accommodation (OR = 1.20, 95% CI = 1.04, 1.39), if they lived in crowded housing conditions (OR = 1.26, 95% CI = 1.06, 1.49), if they were one of a number of siblings (OR = 1.78, 95% CI = 1.52, 2.07), and if their mothers smoked (OR = 1.38, 95% CI = 1.21, 1.58). They were significantly less likely to have wheeze if they were breast fed (OR = 0.68, 95% CI = 0.59, 0.79). Each of these factors was independently related to the prevalence of wheeze. For infants with wheeze those who were breast fed for three or more months were significantly less likely to have three or more episodes in the first six months after birth (OR = 0.76, 95% CI = 0.58, 0.99). A higher prevalence of diarrhoea in infancy was associated with living in rented accommodation (OR = 1.25, 95% CI = 1.10, 1.41) and lower maternal education (OR = 0.76, 95% CI = 0.69, 0.84) and a lower prevalence with breast feeding (OR = 0.42, 95% CI = 0.37, 0.48). An episode of diarrhoea was significantly less likely to last for six or more days if an infant lived in mortgaged accommodation (OR = 1.34 95% CI = 1.03, 1.75) and was breast fed for three or more months (OR = 1.34 95% CI = 1.03, 1.75). CONCLUSION: Deprivation was associated with heightened morbidity from common conditions such as wheeze and diarrhoea for this geographical cohort of infants in England in the 1990s. Results supported evidence suggesting that breast feeding is protective against such conditions and is particularly associated with reduced severity and duration. Implications for future research and policy are discussed.
The present investigation was conducted to help determine whether source activity of the direct recorded N1 response differed from that of the gamma band response (GBR). Auditory evoked cortical potential data from two patients with intractable epilepsy undergoing prolonged video EEG monitoring after implantation of subdural electrodes is reported in this investigation. Evoked responses were recorded to 1000-Hz tone bursts. The data were then filtered digitally to resolve the GBR. The voltage fields were subsequently viewed topographically. Although both responses originated in the supratemporal cortex, the N1 and GBR voltage field patterns differed. These results are consistent with the view that the sources of N1 and the GBR are different, suggesting that these components emanate from functionally distinct neuronal pools.
Recovery nystagmus (RN) describes a spontaneous nystagmus with a fast-phase beating toward the ipsilesional ear. The mechanisms underlying RN implicate central vestibular system compensation processes. The presence of RN is significant because it implies that function has returned from the affected peripheral vestibular system. A case is described where RN was recorded. The processes underlying RN are described.
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We report four patients with various degrees of chronic, tonic, mildly painful, or non-painful, kyphoscolioses in orthostatism, which developed weeks, or months, after one or several laminectomies for lumbar disk hernia, in the absence of recurring radicular pain or acute lumbar pain. No family history or personal antecedent, of focal or generalized dystonia was found and the dystonia was not seen in any of the four patients pre-operatively, or during the immediate post-operative period. Only ill-defined lumbar 'discomfort', unlike their pre-operative lumbago, was reported by the patients, before and during the occurrence of the pathologic trunk posture on standing. Asymmetric lumbar muscle tonic contraction and hypertrophy was found on physical examination. In all patients, the kyphoscoliosis was maximal when standing, partially disappeared when seated, and completely when lying down. One patient responded well to clonazepam, but the other three showed no improvement with either clonazepam or local injections of botulinum toxin; L-dopa was ineffective in all cases, and trihexiphenidyle in three.
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Some patients with symptomatic carotid stenoses of greater than 70 % benefit from carotid endarterectomy. This study was designed to compare the accuracy of duplex ultrasound with angiography in assessing the degree of carotid stenosis in 73 patients with symptoms of recent carotid territory ischaemia. Ultrasound was found to be most accurate in the group of patients with normal vessels or mild stenoses (0-29 %) when there was 90 % concordance between ultrasound and angiography. Ultrasound was found to be least accurate in the group of patients with severe stenoses (70-99 %) in whom it was more likely to underestimate than to overestimate the degree of stenosis. Only one patient said to have < 30 % stenosis on ultrasonography had a > 70 % stenosis on IADSA. Our results indicate that patients with normal arteries or mild disease shown by ultrasound have a very small chance of having surgically amenable lesions in the neck. Ultrasound is reliable as an exclusory screening test. However, all other stenoses should also be investigated by catheter angiography if surgery is considered. Taking angiography as the reference, only 52 % of patients with severe stenoses, which might be taken as an indication for surgery, were correctly identified on ultrasonography. Ultrasound alone is a poor technique for identifying patients for surgery and a combination of ultrasound screening with angiography for > 30 % stenoses detected by ultrasound is recommended.
The localisation of maize (Zea mays L.) auxin-binding protein (ABP1) has been studied using a variety of techniques. At the whole-tissue level, tissue printing indicated that ABP1 is expressed to similar levels in all cells of the maize coleoptile and in the enclosed leaf roll. Within cells, the signals from immunofluorescence and immunogold labelling of ultrathin sections both indicated that ABP1 is confined to the endoplasmic reticulum (ER), none being detected in either Golgi apparatus or cell wall. This distribution is consistent with targeting motifs in its sequence. These observations are discussed with reference to the various reports which place a population of ABP1 on the outer face of the plasma membrane, including those suggesting that it is necessary on the cell surface for rapid, auxin-mediated protoplast hyperpolarisation. We have tested the ER, namely that auxin binding induces a conformational change in ABP1 leading to concealment of the KDEL retention motif. Using double-label immunofluorescence the characteristic auxin-induced rise in Golgi-apparatus signal was found, yet no change in the distribution of the ABP1 signal was detected. Maize suspension cultures were used to assay for auxin-promoted secretions of ABP1 into the medium, but secretion was below the limit of detection. This can be ascribed at least partly to the very active acidification of the medium by these cells and the instability of ABP 1 in solution below pH 5.0. In the insect-baculovirus expression system, in which cell cultures maintain pH 6.2, a small amount of ABP1 secretion, less than 1% of the total, was detected under all conditions, Insect cells were shown to take up auxin and no inactivation of added auxin was detected, but auxin did not affect the level of ABP1 in the medium. Consequently, no evidence was found to support the model for auxin promotion of ABP1 secretion. Finally, quantitative glycan analysis was used to determine what proportion of ABP1 might reach the plasma membrane in maize coleoptile tissue. The results suggest that less than 15% of ABP1 ever escapes from the ER as far as the cis-Golgi and less than 2% passes further through the secretory pathway. Such leakage rates probably do not require a specialised mechanism allowing ABP1 past the KDEL retrieval pathway, but we are not able to rule out the possibility that some ABP1 is carried through associated with other proteins. The data are consistent with the presence of ABP1 both on the plasma membrane and in the ER. The relative sizes of the two pools explain the results obtained with immunofluorescence and immunogold labelling and illustrate the high efficiency of ER retention in plants.
This study describes a new Hidden Markov Model (HMM) system for segmenting uncharacterized genomic DNA sequences into exons, introns, and intergenic regions. Separate HMM modules were designed and trained for specific regions of DNA: exons, introns, intergenic regions, and splice sites. The models were then tied together to form a biologically feasible topology. The integrated HMM was trained further on a set of eukaryotic DNA sequences and tested by using it to segment a separate set of sequences. The resulting HMM system which is called VEIL (Viterbi Exon-Intron Locator), obtains an overall accuracy on test data of 92% of total bases correctly labelled, with a correlation coefficient of 0.73. Using the more stringent test of exact exon prediction, VEIL correctly located both ends of 53% of the coding exons, and 49% of the exons it predicts are exactly correct. These results compare favorably to the best previous results for gene structure prediction and demonstrate the benefits of using HMMs for this problem.
One way to improve students' access to and retention in post-secondary degree progams is to assess their readiness for such programs accurately. To place deaf and hard-of-hearing students in preparatory courses and to determine their readiness for degree programs more accurately, a direct measure of writing was developed for deaf and hard-of-hearing students at a large technical university. The purpose of this study was to estimate the concurrent and predictive validity of this measure. The Test of Written English (Educational Testing Service, 1992) served as the criterion in the concurrent validity study, and student success in the university's gateway freshman composition course served as the criterion in the predictive validity study. Results provide evidence of the concurrent and predictive validity of the measure, supporting its use for course placement and early planning purposes.
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Over the years, a variety of empirical regimens have evolved using intratympanic gentamicin to treat the vertigo associated with Meniere's disease. Although these regimens have been effective, their application is not without risk. Many of the problems associated with intratympanic medications could be overcome with the use of a sustained release vehicle. This article examines the role of such vehicles in the treatment of Meniere's disease and how sustained release vehicles might impact future treatment for this disabling disease.