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Biomedical subjects

J Wilson

Publications and source records attributed to J Wilson.

At least 307 records · Page 17Linked to original sources

Intermittent horizontal saccade failure ('ocular motor apraxia') in children.

BACKGROUND: Ocular motor apraxia (OMA) in childhood is a poorly understood condition involving a failure of horizontal saccades. OMA is thought to be rare but the literature indicates wide clinical associations. OMA is often identified by abnormal head movements, but failure of reflexive quick phases has been reported in all but a few patients. The extent of this oculomotor disorder was examined in a large group of children with diverse clinical backgrounds. METHODS: The degree of quick phase failure during horizontal vestibular and optokinetic nystagmus was measured using DC electro-oculography and video in 74 affected children, aged 17 days to 14 years. RESULTS: All children showed an intermittent failure of nystagmic quick phases, except for total failure in one case. Other visuomotor abnormalities were common including saccadic hypometria (85%), low gain smooth pursuit (70%), neurological nystagmus (28%), strabismus (22%), and vertical abnormalities (11%). Non-ocular abnormalities were common including infantile hypotonia (61%), motor delay (77%), and speech delay (87%). There was a wide range of clinical associations including agenesis of the corpus callosum, Joubert syndrome, Dandy-Walker malformation, microcephaly, hydrocephalus, vermis hypoplasia, porencephalic cyst, megalocephaly, Krabbe leucodystrophy, Pelizaeus Merzbacher disease, infantile Gaucher disease, GM1 gangliosidosis, infantile Refsum's disease, propionic acidaemia, ataxia telangiectasia, Bardet-Biedl syndrome, vermis astrocytoma, vermis cyst, carotid fibromuscular hypoplasia, Cornelia de Lange syndrome, and microphthalmos. Perinatal and postnatal problems were found in 15% including perinatal hypoxia, meningitis, periventricular leucomalacia, athetoid cerebral palsy, perinatal septicaemia and anaemia, herpes encephalitis, and epilepsy. Only 27% were idiopathic. CONCLUSION: Quick phase failure is a constant feature of OMA, whereas abnormal head movements were detected in only about half, depending on the underlying diagnosis. This oculomotor sign is better described as an intermittent saccade failure rather than as a true apraxia. It indicates central nervous system involvement, has wide clinical associations, but it is not a diagnosis.

Adolescent↗

In vivo analysis of fluid transport in cystic fibrosis airway epithelia of bronchial xenografts.

An in vivo human bronchial xenograft model system was used to simultaneously analyze electrolyte and fluid transport defects in fully differentiated human cystic fibrosis (CF) and non-CF proximal airways. CF airways demonstrated three discernible defects when compared with non-CF, including 1) a lack of adenosine 3',5'-cylic monophosphate (cAMP)-inducible Cl- secretion, 2) a fourfold higher basal fluid absorption rate, and 3) an altered regulation of fluid absorption in response to amiloride-stimulated changes in Na+ transport. A unique finding in this study demonstrated that treatment of epithelia with amiloride led to a greater than threefold decrease in the rate of fluid absorption in CF tissues as contrasted to a greater than threefold increase in the rate of fluid absorption in non-CF tissues. The removal of apical Na+ from amiloride-treated non-CF xenografts was capable of ablating this amiloride-induced increase in fluid absorption. In light of the recent interactions demonstrated between CF transmembrane conductance regulator (CFTR) and the rat epithelial, amiloride-sensitive Na+ channel, these findings implicate additional complexities between the Na+ conductance pathways and fluid transport in normal and CF proximal airways. Such findings suggest that CFTR may also regulate amiloride-insensitive Na+ channels.

Absorption↗

Ability of biolectric impedance to predict fat-free mass in prepubertal children.

Measurements of body composition are being made increasingly widely in pediatrics. Tetrapolar whole body impedance (BI) is particularly suitable as a method of estimating body composition in children and is therefore the subject of great interest at present. However, the ability of BI to accurately estimate fat-free mass (FFM) in children is unclear, and users of BI are faced with a growing choice of prediction equations for estimation of FFM. Studies in adults have suggested that choice of prediction equation can have a profound effect on the estimate obtained. The aim of the present study was to measure the ability of four published pediatric BI equations to predict FFM in 98 Caucasian prepubertal children (mean age 9.0 y). For three of the published equations, limits of agreement between predicted and reference FFM were wide and distinct biases were apparent. With mean FFM of 25 kg, the equation of L. Cordain et al. overestimated reference FFM (95% CI +2.1 to +3.1 kg), whereas those of P. Deurenberg et al. (95% CI -1.9 to -2.9 kg) and F. Schaefer et al. (95% CI -1.4 to -2.5 kg) systematically underestimated reference FFM. The equation of Houtkooper et al. (95% CI -0.2 to +0.8 kg) predicted FFM with negligible bias and had narrower limits of agreement relative to the reference method than the other three equations tested. We conclude that the ability of BI to predict body composition in children depends on the equation chosen and that the general applicability of BI equations cannot be safely assumed. Cross-validation of BI equations is recommended before they are used routinely for estimation of body composition in children.

Body Composition↗

Requirement of basement membrane for the suppression of programmed cell death in mammary epithelium.

Apoptosis is an active mechanism of cell death required for normal tissue homeostasis. Cells require survival signals to avoid the engagement of apoptosis. In the mammary gland, secretory epithelial cells are removed by apoptosis during involution. This cell loss coincides with matrix metalloproteinase activation and basement membrane degradation. In this paper we describe studies that confer a new role for basement membrane in the regulation of cell phenotype. We demonstrate that the first passage epithelial cells isolated from pregnant mouse mammary gland die by apoptosis in culture, but that cell death is suppressed by basement membrane. The correct type of extracellular matrix was required, since only a basement membrane, not plastic or a collagen I matrix, lowered the rate of apoptosis. Attachment to a matrix per se was not sufficient for survival, since apoptotic cells were observed when still attached to a collagen I substratum. Experiments with individually isolated cells confirmed the requirement of basement membrane for survival, and demonstrated that survival is enhanced by cell-cell contact. A function-blocking anti-beta1 integrin antibody doubled the rate of apoptosis in single cells cultured with basement membrane, indicating that integrin-mediated signals contributed to survival. We examined the cell death-associated genes bcl-2 and bax in mammary epithelia, and found that although the expression of Bcl-2 did not correlate with cell survival, increased levels of Bax were associated with apoptosis. We propose that basement membrane provides a survival stimulus for epithelial cells in vivo, and that loss of interaction with this type of matrix acts as a control point for cell deletions that occur at specific times during development, such as in mammary gland involution.

Animals↗

Transvascular and interstitial migration of neutrophils in rat mesentery.

OBJECTIVE: The consequential implications of the leukocyte-endothelial cell adhesion reaction, as well as the subsequent migratory activity of the leukocytes within the interstitium proper, are currently known only in general phenomenological terms. Our objective was to carry out a detailed quantitative analysis of transendothelial and interstitial migration. METHOD: We incorporated several new features, such as the video recording of time-lapse photography in conjunction with the time history of individual leukocytes under the influence of representative stimulators and inhibitors. The mesentery was suffused with the chemical activator N-formyl-met-leu-phe (fMLP, 5 x 10(-8) M) and histamine (10(-6) M) for periods up to 3 h. This leads to an attachment of neutrophils preferentially to the walls of small postcapillary venules followed by migration into the adjacent interstitium. RESULTS: The time interval between the initial neutrophil adhesion to the luminal side of the venules and their first appearance on the abluminal side of the venule wall was about 25 min. The time interval for the actual physical migration across the endothelium was only about 1-2 min. There was an initial increase in the number of neutrophils migrating across the wall per unit time after the application of fMLP. However, this effect then gradually decreased over the course of 1 h. In the extravascular tissue, the neutrophils appeared to migrate along random pathways with an average trajectory away from the venular wall. When histamine (1 microM) was applied topically in conjunction with fMLP, the overall migratory flux across the venular wall increased, although the cells migrated comparatively short distances into the interstitium. After pretreatment with phalloidin (25 micrograms/kg), an actin cross-linking agent, neutrophil adhesion and migration in response to fMLP stimulation was reduced. The mast cell stimulator 48/80 (25 mg/ml) resulted in rapid degranulation, which was accompanied by an insignificant increase in neutrophil diapedesis. After fMLP stimulation there was reduced neutrophil emigration in the presence of mast cell inhibitors, such as lodoxamide (1 microgram/kg) and ketotifin (microgram/kg). CONCLUSIONS: Our results demonstrate that both the endothelial cells and interstitial mast cells are involved in the rate of transvascular migration of leukocytes across postcapillary venules and into the interstitium.

Animals↗

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Delivery of Health Care↗

Chimeric synthetic peptides as antigens for detection of antibodies to HIV-1 and HIV-2.

Two chimeric peptides incorporating immunodominant sequences from both HIV-1 (LGIWGCSGKLICTT) and HIV-2 (LNSWGCAFRQVCHT) were synthesized. Peptides KS1-KS2 and KS2-KS1 represented sequences from the two viruses in both possible orders, separated by two glycine residues as spacers. These peptides were evaluated as antigens in an ELISA using a panel of specimens derived from HIV-1 (n = 25) and HIV-2 (n = 25) infected individuals and seronegative people (n = 38). The results were compared to plates coated with individual peptides KS1 and KS2 and to plates coated with two peptides (KS1 and KS2) together. Data demonstrated that individually, KS1 and KS2, are good antigens and can detect antibodies to their respective viruses quite efficiently. However, when coated together, their ability to detect antibodies to both HIV-1 and HIV-2 was reduced, as evidenced by a decrease in OD values obtained. The chimeric peptides KS1-KS2 and KS2-KS1 detected antibodies to HIV-1 and HIV-2; however, their sensitivity of detection was variable and dependent upon the order of their sequence. For both peptides, antibodies directed to the C-terminal portion were detected with higher sensitivity than those directed to the N-terminal part of the peptides. This may be related to peptide adsorption to the solid surface and epitope accessibility to the antibodies. Such chimeric antigens may be very useful for simultaneous detection of antibodies to HIV-1 and HIV-2.

AIDS Serodiagnosis↗

Allograft vascular disease: comparison of heart and other grafted organs.

A striking resemblance exists between the vasculopathy in several different allografts. The arteriopathy of epicardial coronary arteries is diffuse, involving proximal, distal, and small branch segments in a generally concentric pattern of intimal thickening. Smooth muscle cells in a lipid- and glycosaminoglycan-rich matrix are the predominant components of this expanded intima. Varying amounts of collagen are present, more being present late posttransplant. A superficial and, to a lesser degree, deep, bandlike infiltrate of T cells and macrophages is uniformly present, although it is somewhat more prominent in early lesions as compared to more severely narrowed arteries from longer-term, susceptible grafts. The media is likewise altered by areas of lipid and glycosaminoglycan deposition associated with smooth muscle cell loss and phenotypic modulation. The media is altered in an outside-to-inside direction, with percolation of adventitial leukocytes into the outer media. Virtually all of the coronary features are seen in the medium to large arteries of liver, pancreas, and kidney allografts. Chronic rejection in lung allografts is manifest by obliterative bronchiolitis; vascular changes, although architecturally similar, are somewhat less common and result in less-severe luminal narrowing. The role of allograft vasculopathy in chronic lung rejection is thus less certain. A finding perhaps unique to epicardial coronary arteries of heart allografts is the presence of eccentric lesions more typical of native atherosclerosis. Many of the latter grafts probably have preexistent, undetected donor disease. Sequential evaluation of vascular changes is limited in human biopsy material by their general absence in endomyocardial or core liver needle specimens. Fortunately, vascular changes can be detected in some renal and pancreas core needle biopsies, and these findings may provide an avenue for monitoring the effectiveness of immunosuppressive therapy, antiviral or lipid-altering therapies, or modifications of smooth muscle cell proliferation and glycosaminoglycan deposition yet to be developed.

Heart Transplantation↗

Evaluation of oxygen delivery with the use of nasopharyngeal catheters and nasal cannulas.

The purpose of this pilot study was to examine the differences between nasopharyngeal catheter and nasal cannula oxygen delivery systems in infants. Eleven subjects requiring supplemental oxygen were enrolled in the study. All infants received both therapies at three separate gas flow rates (0.5, 0.3, and 0.2 liters per minute). Infants had higher heart rates when receiving nasal cannula oxygen than when receiving nasopharyngeal catheter oxygen (p < .05). There were no significant differences between the two therapies when comparing pulmonary mechanics, hypopharyngeal oxygen concentrations, and respiratory rates. However, when oxygen was delivered at the higher flow (0.5 liters), heart rate, tidal volume, and oxygen concentration were higher, and respiratory rates were decreased for both methods (p < .05). Because minimal differences were found between these two methods, either may be an appropriate choice for delivering supplemental oxygen.

Heart Rate↗

The critical thinking abilities of RNs entering university courses.

The critical thinking abilities of groups of registered nurses (n 143) who were entering the post-registration Bachelor of Nursing or one of the four graduate diploma in nursing courses offered by Griffith University were assessed using the Watson-Glaser Critical Thinking Appraisal Test. The mean scores of the Bachelor of Nursing student group, none of whom had attended university, were significantly lower than the mean scores of the graduate diploma students who had no experience of tertiary education. There was not a significant difference in the mean scores of the group who were accepted into the graduate diploma courses on the basis of previous university studies and the group whose acceptance was based on prior learning in non-tertiary courses and/or clinical nursing experience. There were also no significant differences in the mean scores of groups of students entering the four graduate diploma courses. Some implications of these findings for students and for the development and implementation of curricula are discussed.

Curriculum↗

Bioglass middle ear prosthesis: long-term results.

The purpose of this study was to review the University of Florida's long-term results with Bioglass middle ear prostheses. Between April 1984 and November 1987, 37 patients were implanted with Bioglass prostheses (25 total and 12 partial ossicular replacements). Twenty-one patients had postoperative data of at least 24 months (range, 24 to 126 months; mean, 86 months; median, 100 months), and five patients had > 10 years' follow-up. In three cases, portions of fractured prostheses extruded, leaving an intact tympanic membrane. One patient with a total ossicular prosthesis was reexplored at 38 months for conductive hearing loss and found to have a prosthesis fracture (n = 1). There were no extrusions of intact prostheses, even in patients in whom the prosthesis was placed directly under the tympanic membrane or graft (n = 12). After 24 months, the mean pure-tone average air-bone gap was 24 dB (24% had ABG < or = 10 dB; 53% had ABG < or = 20 dB). Air-bone gap closures were stable over time. Our results demonstrated that Bioglass middle ear prostheses have excellent long-term tissue compatibility. The four failures are attributed to fractures in early experimental prototypes.

Audiometry, Pure-Tone↗

Biofeedback: a noninvasive treatment for incontinence after radical prostatectomy.

OBJECTIVE: Will a program using biofeedback help patients with post radical prostatectomy incontinence to achieve continence by increasing their ability to contract pelvic floor muscles? STUDY DESIGN: Twenty-seven patients who had undergone incontinent radical prostatectomy were evaluated for urinary incontinence and treated at the Urology Biofeedback Laboratory at our institution. Patients were assessed by urodynamic studies including uroflow, postvoid residual measurement, and cystometrogram before biofeedback was initiated. The protocol provided for 10 weekly sessions of 15 minutes' duration with additional reinforcement sessions at 1, 3, 6, and 12 months. Subjective symptoms related to urgency, frequency, nocturia, and number of pad changes were reported by patients before treatment and at each visit. Digital evaluation of the pelvic floor muscle contraction was objectively graded from 0 to 3 (nil to strong) and was completed before and after treatment. These subjective and objective findings were used to determine success of treatment. RESULTS: Of the 27 patients completing the full treatment course, 13 (48%) had complete success, 7 (26%) had significant improvement but were not completely dry, and 7 (26%) had failure, for a total improvement rate of 74%. CONCLUSIONS: A biofeedback training program is an effective, minimally invasive, and well-accepted method that can be offered as a first-line option to patients who have undergone radical prostatectomy and want to improve the postsurgical problem of urinary incontinence. Patient motivation is an important factor in success. Nurses have an opportunity to use their expertise in this program to assist these patients to return to continence.

Aged↗

Pegylated megakaryocyte growth and development factor abrogates the lethal thrombocytopenia associated with carboplatin and irradiation in mice.

Megakaryocyte growth and development factor (MGDF) is a potent inducer of megakaryopoiesis in vitro and thrombopoiesis in vivo. The effects of MGDF appear to be lineage-selective, making this cytokine an ideal candidate for use in alleviating clinically relevant thrombocytopenias. This report describes a murine model of life-threatening thrombocytopenia that results from the combination treatment of carboplatin and sublethal irradiation. Mortality of this regimen is 94% and is associated with widespread internal bleeding. The daily administration of pegylated recombinant human MGDF (PEG-rMGDF) significantly reduced mortality (to < 15%) and ameliorated the depth and duration of thrombocytopenia. The severity of leucopenia and anemia was also reduced, although it was not clear whether these effects were direct. Platelets generated in response to PEG-rMGDF were morphologically indistinguishable from normal platelets. PEG-rMGDF administered in combination with murine granulocyte colony-stimulating factor completely prevented mortality and further reduced leukopenia and thrombocytopenia. These data support the concept that PEG-rMGDF may be useful to treat iatrogenic thrombocytopenias.

Animals↗

Genomic organization of the mouse fibroblast growth factor receptor 3 (Fgfr3) gene.

The fibroblast growth factor receptor 3 (Fgfr3) protein is a tyrosine kinase receptor involved in the signal transduction of various fibroblast growth factors. Recent studies suggest its important role in normal development. In humans, mutation in Fgfr3 is responsible for growth disorders such as achondroplasia, hypoachondroplasia, and thanatophoric dysplasia. Here, we report the complete genomic organization of the mouse Fgfr3 gene. The murine gene spans approximately 15 kb and consists of 19 exons and 18 introns. One major and one minor transcription initiation site were identified. Position +1 is located 614 nucleotides upstream from the ATG initiation codon. The translation initiation and termination sites are located in exons 2 and 19, respectively. Five Sp1 sites, two AP2 sites, one Zeste site, and one Krox 24 site were observed in the 5'-flanking region. The Fgfr3 promoter appears to be contained within a CpG island and, as is common in genes having multiple Sp1-binding sites, lacks a TATA box.

Animals↗