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Biomedical subjects

S Wade

Publications and source records attributed to S Wade.

At least 19 recordsLinked to original sources

Freeze-substitution of rabbit tibial articular cartilage reveals that radial zone collagen fibres are tubules.

Investigations of the micromorphology of rabbit tibial articular cartilage using scanning and transmission electron microscopy revealed that the collagenous elements in the tissue form fluid-containing tubular structures. The commonly described radial or deep zone longitudinal fibres were found to be tubular structures with internal diameters of 1-2 microm. The walls of the tubules were composed of tightly packed fibrils of collagen. The tangential zone, close to the tibial plateau, was composed mainly of a spongy arrangement of collagen fibrils, containing bunches of tangentially lying small (< 1 microm) diameter tubules. The application of conventional chemical fixation techniques resulted in the fine detail of this tissue being obscured. When the tissue was frozen, followed by cryo-scanning electron microscopy or freeze-drying, prior to observation in the scanning electron microscope the tubule structures were not obviously present. It was only by applying freeze-substitution techniques, followed by critical point drying or resin embedding, that the structure was revealed clearly. Segregation of water into ice crystals did occur during the freezing process, but the formation of those crystals played no part in creating the tubular morphology observed. A similar structure was still revealed following pre-treatment with glycerol, methanol or Triton X-100, provided that concentration of these additives was not too high. The walls of the tubules in the radial region were composed of straight, longitudinally arranged as well as helically arranged, 30 nm diameter fibrils. The lumen of the tubules appears to be lined by a circumferentially arranged array of approximately 10 nm diameter fibres, spaced at regular intervals of 50-70 nm.

Animals

Efficient discovery of inhibitory ligands for diverse targets from a small combinatorial chemical library of chimeric molecules.

Living systems are mainly composed and regulated by compounds in four biochemical classes and their polymers-nucleotides, carbohydrates, lipids, and amino acids. Early combinatorial chemistry libraries consisted of peptides. The present report describes the general bioactivity and biophysical properties of a combinatorial chemical library that used glyco, nucleotidyl, and lipid building blocks. The resulting chimeric combinatorial library of 361 compounds had a confirmed cumulative hit rate of 0.16%, which is 8-fold higher than a commonly claimed industrial benchmark of 0. 02%. It produced 7 structurally confirmed hits for a third of 12 proprietary drug discovery projects, and these comprised a variety of molecular targets. Diversity analyses demonstrated that despite the small number of compounds, a wider range of diversity space was covered by this library of biochemical chimeras than by a branched tripeptide library of the same size and similar generic formula.

Binding Sites

The sleep of older people in hospital and nursing homes.

Disturbed sleep can affect personal wellbeing and impede the rehabilitation and recovery of older people from illness. This paper reports the findings of a pilot study which included examination of sleep quality and sleep patterns of older people in community hospital and nursing home settings. A marked proportion of older people reported sleeping well in nursing care settings, and those in nursing homes slept better than those in the community hospital. The main causes of sleep disturbance in both settings were: needing to go to the toilet, noise, pain, and discomfort; a similar pattern was seen across the different settings. No discernible difference was found in quality of sleep and whether patients felt rested or not between those patients on hypnotic medication and those who were not. The implications of the findings for practice and future research are discussed.

Aged

HIV testing practices of Zimbabwean physicians and their perspectives on the future use of rapid on-site tests.

To improve HIV testing procedures, rapid on-site HIV tests have been introduced in Zimbabwe. At present, little is known about physicians' perspectives on the potential use of rapid tests in their clinics or about their current laboratory-based testing practices. In a sample of 63 general practitioners in Harare, this study found physicians were generally testing individuals, not couples, and an important reason for suggesting a patient be tested was medical symptoms; frequent reasons for patients requesting the test were insurance purposes, being about to get married or having suspicions about a partner. A primary deterrent to physicians testing patients, even when patients requested it, was fear of traumatizing them. Fifty-six per cent of the physicians believed rapid tests would increase the number of HIV tests they performed; significant associations were found between this belief and whether physicians ever chose not to test patients they suspected were HIV-positive (a positive association) and whether they chose not to test specifically out of fear that patients would commit suicide (a negative association). Prior to any expansion of testing with rapid tests, training in counselling and confidentiality measures is essential, given that over half the medical personnel providing counselling to these physicians' patients had received no training in pre- and post-test HIV counselling.

Attitude of Health Personnel

The family burden of injury interview: reliability and validity studies.

OBJECTIVE: To assess the reliability and validity of a new instrument, the Family Burden of Injury Interview (FBII) was designed to assess the impact of childhood traumatic head injuries (THI) on the family. PARTICIPANTS: 99 Mothers of school-age children who experienced THI. RESULTS: The FBII Total Score revealed group differences between families of children with severe THI and families of children with moderate THI. The measure also showed concurrent and predictive relationships to measures of the general impact of injury on families and maternal and child functioning. CONCLUSION: The FBII is a promising tool for measuring the impact of injury-related stressors on the family.

Child

Evaluation of gross and fine motor functions in children with hemidecortication: predictors of outcomes and timing of surgery.

The purpose of this study is three-fold: First, to determine the levels of gross and fine motor functions in children before and after hemidecortication, using standardized measurement tools; second, to investigate if predictors of these outcomes can be characterized; and third, to explore if both clinical measures and functional magnetic resonance imaging (MRI) potentially can identify optimal timing of surgery. The Gross Motor Function Measure and the Quality of Upper Extremity Skills Test are shown to be comprehensive, standardized outcome measures of movement performance in affected children. Age at surgery and interval between age at seizure onset and age at surgery could be the most reliable predictors of clinical outcomes. Functional MRI studies are valuable in exploring the potential of the cortical reorganization that sustains residual sensorimotor function. The combination of clinical measures with functional MRI is a promising method of inquiry into developmental and plasticity processes.

Adolescent

[Epidemiology of systemic inflammatory response syndrome, infection and septic shock in surgical intensive care patients].

This paper uses definitions of a consensus conference (ACCP/CCM) describing the epidemiology of SIRS, sepsis and septic shock in surgical ICU patients. During a period of 2 years a total of 656 patients were prospectively enrolled into the study. 335 patients (51.1% of the total population) developed SIRS (systemic inflammatory response syndrome); in 65 of these patients infection could be documented, i.e. they met the criteria of sepsis, 47 of these 65 septic patients developed septic shock, with mortality of 53.2%. SIRS is associated with a high sensitivity but a low specificity in predicting the outcome of ICU patients. Moreover, SIRS and sepsis appear to be of minor clinical relevance. On the contrary, septic shock describes a very high risk group of patients which should be characterized more closely in future studies.

Adolescent

Clinical use of three-dimensional video measurements of eye movements.

Noninvasive measurements of three-dimensional eye position can be accurately achieved with video methods. A case study showing the potential clinical benefit of these enhanced measurements is presented along with some thoughts about technological advances, essential for clinical application, that are likely to occur in the next several years.

Aged

Acute psychosocial impact of pediatric orthopedic trauma with and without accompanying brain injuries.

BACKGROUND: The acute psychosocial effects of orthopedic injuries on children and their families are poorly understood. Previous studies have relied on retrospective reports or failed to take into account accompanying brain injuries. The purpose of the present study was to examine prospectively the psychosocial impact of pediatric orthopedic traumatic fractures with and without accompanying brain injuries. METHODS: Participants were 108 children 6 to 12 years old with orthopedic injuries requiring hospitalization: group 1 (n=80) had fractures only, group 2 (n=28) also had moderate or severe brain injuries. Using standardized measures and parent interviews, we obtained preinjury estimates of family functioning and child behavior problems and postinjury measures of parental distress, family stresses, and child behavior. RESULTS: Parents reported significant clinical distress (35% in group 1, 57% in group 2), family burdens (group 2 > group 1), and child behavioral changes (41% in group 1, 89% in group 2). Multiple regression analyses indicated that preinjury family status and brain injuries predicted postinjury parental and family distress. CONCLUSION: Pediatric orthopedic injuries have greater social effects on children with accompanying brain injuries and poorer preinjury family functioning.

Adaptation, Psychological

Effect of food processing on iron availability of African pearl millet weaning foods.

The effects of different cereal precooking process (roasting and extrusion cooking) on iron availability and protein digestibility of four African weaning foods were investigated using in vitro methods. In two weaning foods based on pearl millet, cowpea and peanut, the cereal was extruded (A) or roasted (B). In two other weaning foods having a similar composition, a low proportion of milk powder was added and the cereal extruded (C) or roasted (D). The mean +/- SD iron values (mg/100 g) were: A, 5.56 +/- 0.18; B, 9.12 +/- 0.93; C, 5.89 +/- 0.23; D, 9.04 +/- 0.85. When the pearl millet was roasted, the iron content was higher than in the extruded weaning foods (P < 0.01). However, the percent of available iron of the roasted weaning foods was very low (B, 1.64 +/- 0.01; D, 0.91 +/- 0.02). The iron availability of the extruded weaning foods, A and C, was 3.5 times and 6.5 times higher than the corresponding roasted weaning foods, B and D, respectively. This represented 332.4 +/- 4.4 and 375.1 +/- 5.8 micrograms of available iron/100 g for A and C, respectively versus 149.5 +/- 0.9 and 82.2 +/- 1.8 micrograms of available iron/100 g for B and D, respectively. No significant differences in polyphenol contents were found according to the precooking process of the cereal. The extruded weaning foods showed a higher protein digestibility of approximately 10% than the roasted ones (P < 0.05). A positive correlation was found between in vitro iron availability and protein digestibility (r = 0.976, P < 0.02). Despite a high content of iron, the iron availability of roasted pearl millet weaning foods was quite low. Extrusion cooking of the cereal improved the protein digestibility and iron availability of pearl millet weaning foods; however, the amount of available iron remained insufficient to meet the iron requirements of infants whatever the cereal processing.

Cooking

Psychosocial characteristics of inner-city children with asthma: a description of the NCICAS psychosocial protocol. National Cooperative Inner-City Asthma Study.

Previous research has demonstrated a significant reciprocal relationship between psychosocial factors and asthma morbidity in children. The National Cooperative Inner-City Asthma Study investigated both asthma-specific and non-specific psychosocial variables, including asthma knowledge beliefs and management behavior, caregiver and child adjustment, life stress, and social support. This article presents these psychosocial characteristics in 1,528 4-9-year-old asthmatic urban children and their caretakers. Caretakers demonstrated considerable asthma knowledge, averaging 84% correct responses on the Asthma Information Quiz. However, respondents provided less than one helpful response for each hypothetical problem situation involving asthma care, and most respondents had more than one undesirable response, indicating a potentially dangerous or maladaptive action. Both adults and children reported multiple caretakers responsible for asthma management (adult report: average 3.4, including the child); in addition, children rated their responsibility for self-care significantly higher than did adults. Scores on the Child Behavior Checklist indicated increased problems compared to normative samples (57.3 vs. 50, respectively), and 35% of children met the criteria for problems of clinical severity. On the Brief Symptom Inventory, adults reported elevated levels of psychological distress (56.02 vs norm of 50); 50% of caretakers had symptoms of clinical severity. Caretakers also experienced an average of 8.13 undesirable life events in the 12 months preceding the baseline interview. These findings suggest that limited asthma problem-solving skills, multiple asthma managers, child and adult adjustment problems, and high levels of life stress are significant concerns for this group and may place the inner-city children in this study population at increased risk for problems related to adherence to asthma management regimens and for asthma morbidity.

Adult

A One-Bead One-Peptide Combinatorial Library Method for B-Cell Epitope Mapping

The one-bead one-peptide combinatorial library method represents a powerful approach to the discovery of binding peptides for various macromolecular targets. It involves the synthesis of millions of peptides on beads such that each bead displays only one peptide entity. The peptide-beads that interact with a specific macromolecular target are then isolated for structure determination. We have applied this method to discovering peptide ligands for several murine monoclonal antibodies: (i) anti-beta-endorphin (continuous epitope), (ii) anti-vmos peptide, (iii) anti-human insulin (discontinuous epitope), and (iv) surface immunoglobulins (&mu;kappa) of two murine B-cell lymphoma cell lines (antigen unknown).

Journal Article

Library of libraries: approach to synthetic combinatorial library design and screening of "pharmacophore" motifs.

Construction of synthetic combinatorial libraries is described that allows for the generation of a library of motifs rather than a library of compounds. Peptide libraries based on this strategy were synthesized and screened with model targets streptavidin and anti-beta-endorphin antibody. The screens resulted in observation of expected motifs providing evidence of the effectiveness of the suggested approach.

Amino Acid Sequence

Application of a dual color detection scheme in the screening of a random combinatorial peptide library.

Selectide Technology is a random synthetic combinatorial library method in which millions of random compounds are screened in parallel for their ability to bind to a tagged macromolecular target. The library consists of millions of beads and each individual bead expresses a unique chemical compound such as a peptide. In the standard enzyme-linked colorimetric detection scheme, the positive bead which turns color is isolated for microsequencing. In this paper, a dual color detection scheme using two sequential orthogonal probes is described. This dual color system enables one to rapidly differentiate false positive beads from true positive beads, resulting in a much more efficient use of the microsequencer.

Amino Acid Sequence

Relationship of 24-hour urinary free cortisol to 4-hour salivary morning and afternoon cortisol and cortisone as measured by a time-integrated oral diffusion sink.

The relationship between salivary corticosteroids integrated over 4-hour periods and urinary free cortisol collected over 24 hours was investigated in normal controls. Twenty-one normal volunteers wore "oral diffusion sink" sampling devices in their mouths for two 4-hour periods (08:00-12:00 hours and 13:00-17:00 hours) and on the same day collected a 24-hour urine specimen. Time-integrated salivary corticosteroid concentrations were determined from the sample devices and urinary free cortisol was measured. Salivary corticosteroids were not consistently higher in the morning than in the afternoon period and did not differ between men and women. Urinary free cortisol levels were higher in women. No salivary corticosteroids measure was significantly correlated with urinary free cortisol. We conclude that time-integrated salivary corticosteroids do not reflect urinary free cortisol levels in normal controls.

Adult

Assessing the effects of traumatic brain injury on family functioning: conceptual and methodological issues.

Reviewed empirical literature published since 1975 on the effects of pediatric traumatic brain injury (TBI) on the family. Few systematic, hypothesis-driven investigations of the impact of TBI on family functioning have been conducted. However, existing findings indicate that severe TBI can adversely affect families and individual family members. Certain factors, such as poor preinjury functioning and parental psychological disorder, appear to place families at greater risk for long-term disruption. Issues associated with the conceptualization of the impact of TBI on various aspects of family functioning are discussed and methodological considerations are outlined. Special attention is given to novel strategies for studying these complex, multifaceted issues. Finally, a framework is proposed for examining the processes of family adaptation after pediatric TBI to guide future research directions.

Adaptation, Psychological

Serum osteocalcin regulation in protein-energy malnourished children.

To evaluate bone turnover changes occurring during protein-energy malnutrition, serum osteocalcin, a marker of bone formation, has been studied in healthy control, stunted, and severely malnourished (kwashiorkor and marasmus) Senegalese children. Serum osteocalcin levels were dramatically reduced in stunted, kwashiorkor, and marasmic children compared with control children. In addition serum osteocalcin levels of control children living in Senegal were lower (-46%) than those of African children living in France. Interestingly, serum osteocalcin level was not related to its major known regulators (1 alpha,25-dihydroxycholecalciferol, 25-hydroxycholecalciferol, and PTH) nor to stunting, but was related to serum transthyretin and thyroid hormones concentrations. These data suggest that serum osteocalcin level is related to protein-energy status and that bone formation was affected in apparently healthy and in malnourished Senegalese children. Serum osteocalcin could be a potent tool in the study of the alterations of bone formation in malnutrition.

Child, Preschool