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Biomedical subjects

D Webster

Publications and source records attributed to D Webster.

At least 37 records · Page 2Linked to original sources
PubMed2000

Brain abscess at the University Hospital of the West Indies.

Surgical infections of the central nervous system are still attended by high rates of morbidity and mortality, although substantial progress has been made since the advent of computed tomography (CT) scanning technology. In this retrospective review of 25 surgically treated patients with either brain abscess or subdural empyema at the University Hospital of the West Indies, the majority of patients were male and between the ages of 10 and 30 years with a mean age of 16.9 years. Almost half the patients had a hemiparesis on presentation while 60% had fever. Subdural empyema was more common than a localized intracerebral abscess which was most frequently located in the frontal lobe. The most common predisposing factors were sinusitis and congenital heart disease. Streptococci spp and Staphylococci spp were the most frequently isolated organisms. All patients underwent CT scanning and surgical intervention. The mortality rate was 20%, and 21% of the survivors had late seizures. There must be a high index of clinical suspicion and early referral to specialist centres where neuroradiological investigation and prompt neurosurgical intervention can be carried out to minimize morbidity and mortality.

Adolescent↗
PubMed1999

Quality evaluation of newborn screening programs.

In the last four decades in many countries and regions all over the world newborn screening programs have been developed. Traditionally, most programs focus on phenylketonuria and congenital hypothyroidism. However, with development of new technologies, screening for a large variety of other disorders has become available. The decision-making process on what to screen or not to screen for is usually driven by personal interest of the professionals involved, by local legislation and access to funding, resulting in large differences among countries. In general, quality evaluation is only applied to the pure laboratory analytical phase. Less attention is given to the pre-analytical phase (e.g. timely sampling, maximum coverage) and the post-analytical phase (follow-up and treatment, evaluation of long-term effects, cost-effectiveness, etc.). In order to gain more insight into the current situation worldwide we developed a questionnaire which was sent to leading screening centers in more than 30 countries. As expected, the results show large differences in degree of organization, turnover times, completeness of coverage and follow-up. There appears to be no relationship between screening procedures and the degree of legislation or the system of funding. In presenting the more detailed results we hope to be of service to program organizers.

Asia↗
PubMed1999

Quality assurance and standardization: summary of the satellite meeting, Turku, Finland, 11-12 June 1999.

The Quality Assurance (QA) and Standardization satellite meeting addressed five major issues in newborn screening: (i) Pre- and post-analytical phases are important in the overall quality of screening, and quality assurance programs should include these aspects. (ii) It is possible to run a single screening program using laboratories on more than one site, as is done in Europe, California and Cuba. Special quality assurance procedures are necessary for success. (iii) It is possible to achieve improved analytical quality and international comparison of results by use of common reference materials such as the amino acid materials developed in Europe and the US. It will be important to use tested paper with defined performance characteristics. (iv) It is appropriate for newborn screening programs to be accredited, but it will also be important to develop criteria for pre- and post-analytic phases of screening. (v) A new QA program is being developed for Latin America. The Australasian QA program now includes amino acids and acylcarnitines in a form suitable for tandem mass spectrometry blind QA. The European Society for Paediatric Endocrinology has developed guidelines for CAH screening.

Accreditation↗
PubMed1999

Genotyping of CYP21, linked chromosome 6p markers, and a sex-specific gene in neonatal screening for congenital adrenal hyperplasia.

We investigated the feasibility and diagnostic utility of genotyping 9 CYP21 mutations, linked chromosome 6p markers, and a dimorphic X-Y marker from neonatal screening samples. Blood-impregnated filter papers (Guthrie cards) from 603 randomly chosen New Zealand neonates were genotyped blind to 17-hydroxyprogesterone (17-OHP) levels. Another 50 samples from Swiss and North American infants with correlative hormonal data were also genotyped. DNA was extracted, and gene-specific PCR was performed. CYP21 PCR products were subjected to ligase detection reaction, simultaneously analyzing 9 CYP21 mutations; PCR products of other genes were subjected to direct gel analysis. CYP21 genotyping indicated a heterozygote rate of 2.8% for classic mutations (excluding CYP21 deletions), and 2.0% for nonclassic mutations in New Zealanders. Ten full-term affected neonates showed a wide range of 17-OHP levels (15-1400 nmol/L). Sick or preterm infants or infants screened on the first day of life with high 17-OHP proved genetically unaffected. Genetic linkage disequilibrium was found between two CYP21 mutations and chromosome 6p markers. Guthrie cards can be used to accurately genotype CYP21 and other relevant markers, potentially enhancing the specificity and sensitivity of congenital adrenal hyperplasia screening. CYP21 heterozygote frequency for classic mutations is higher than expected based on genotype compared with that predicted by hormonal newborn screening.

17-alpha-Hydroxyprogesterone↗
PubMed1999

Comparisons of magnitude estimation scaling of rock music by children, young adults, and older people.

The present study concerned the perceptual processing of complex auditory stimuli in 10 children (M age = 8.1) as compared to 10 young adults (M age = 19.3) and 10 older adult subjects (M age = 54.2). The auditory stimulus used was 10 sec. of rock music (Led Zeppelin, 1969). All three groups provided numerical responses to nine intensities of the rock music stimulus (10, 20, 30, 40, 50, 60, 70, 80, 90 dB above threshold). Analysis showed that the children reported a wider range of numerical responses than both adult groups. The mean numerical responses for the children ranged from .54 to 54.24. For the young adults the range was .76 to 11.37, and for the older subjects it was 1.6 to 23.31. Results suggest that the children were not bound by the same set of rules as the adults with regard to magnitude estimation scaling of the loudness of the rock music stimulus. Their internal scaling mechanisms appeared to be more flexible and broader based than those of the adults who participated in this study.

Acoustic Stimulation↗
PubMed1998

High prevalence of thymic tissue in adults with human immunodeficiency virus-1 infection.

The thymus in adults infected with the HIV-1 is generally thought to be inactive, both because of age-related involution and viral destruction. We have revisited the question of thymic function in adults, using chest-computed tomography (CT) to measure thymic tissue in HIV-1-seropositive (n = 99) or HIV-1-seronegative (n = 32) subjects, and correlating these results with the level of circulating CD4(+) and CD8(+) T cells that are phenotypically described as naive thymic emigrants. Abundant thymic tissue was detectable in many (47/99) HIV-1-seropositive adults, aged 20-59. Independent of age, radiographic demonstration of thymic tissue was significantly associated with both a higher CD4(+) T cell count (P = 0.02) and a higher percentage and absolute number of circulating naive (CD45RA+CD62L+) CD4(+) T cells (P < 0.04). The prevalence of an abundant thymus was especially high in younger HIV-1-seropositive adults (</= 39 yr) with CD4 counts in the range 300-500 cells/microl and in older subjects (> 40 yr) regardless of CD4 count (P = 0.03). These studies suggest that the thymus is functional in some but not all adults with HIV-1 disease.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Comparison of the rate of sequence variation in the hypervariable region of E2/NS1 region of hepatitis C virus in normal and hypogammaglobulinemic patients.

The hypervariable region (HVR) of the E2/NS1 region of hepatitis C virus (HCV) varies greatly between viral isolates with high rates of genomic change reported during the course of chronic infection. The HVR is thought to encode a structurally unconstrained envelope protein containing several linear B cell epitopes recognized by neutralizing antibody. It has been postulated that amino acid changes in the HVR could result from humoral immune pressure leading to the selection of escape mutants. The aim of this study was to compare the rates of nucleotide and amino acid variation in the HVR of control patients to patients with common variable immunodeficiency (CVID) where the effect of the humoral immune system is reduced. Five controls and four patients with CVID were studied. Serum samples were taken over periods of between 1 and 6 years. HCV was detected by polymerase chain reaction (PCR) with primers derived from conserved flanking regions of the HVR. PCR products were cloned into a plasmid vector and recombinant clones identified by restriction enzyme digestion. Purified DNA from at least three individual clones from each time point was sequenced by the dideoxynucleotide chain-termination method. Consensus sequences were extracted from the three clones, and the DNA and deduced protein sequences were compared. Control patients had a mean rate of nucleotide change of 6.954 nucleotide substitutions per year, compared with patients with CVID with a rate of 0.415 nucleotide substitutions per year (P < .02). The corresponding rates for amino acid variation were 3.868 amino acid substitutions per year for the control patients compared with 0.185 amino acid substitutions per year for the patients with CVID. These findings suggest that in the absence of humoral immune selective pressure, the frequency of occurrence of genetic variation in the major viral species is reduced. The mutations occur, but in the absence of immune selection remain as minor species. The evolution of viral mutants capable of evading the host's immune system may contribute to the ability of HCV to establish chronic infection.

Adult↗
PubMed1998

An ecological model for school-based mental health services for urban low-income aggressive children.

An ecological model for school-based mental health services that targets urban low-income aggressive children--a highly vulnerable and underserved population--is presented. The goals of the model are to increase children's and teachers' involvement in the delivery of services and to increase the integration of these services into existing school resources and activities. The model proposes that mental health service providers work in collaboration with teachers to deliver services that (1) can be managed by existing school resources and personnel, (2) are related to empirically based factors associated with reduced aggression and increased social functioning, and (3) are group administered to increase the number of children served and to reduce stigmatization associated with mental health services. The model is individualized and flexible by acknowledging that contexts for aggression differ across classrooms and children and by providing services specific to those contexts. Two studies are presented illustrating the application of this model to decrease aggression and increase academic engagement in low-income urban public schools.

Achievement↗
PubMed1998

Host response to EBV infection in X-linked lymphoproliferative disease results from mutations in an SH2-domain encoding gene.

X-linked lymphoproliferative syndrome (XLP or Duncan disease) is characterized by extreme sensitivity to Epstein-Barr virus (EBV), resulting in a complex phenotype manifested by severe or fatal infectious mononucleosis, acquired hypogammaglobulinemia and malignant lymphoma. We have identified a gene, SH2D1A, that is mutated in XLP patients and encodes a novel protein composed of a single SH2 domain. SH2D1A is expressed in many tissues involved in the immune system. The identification of SH2D1A will allow the determination of its mechanism of action as a possible regulator of the EBV-induced immune response.

Antigens, CD↗
PubMed1998

SPECT (HMPAO) support for activation of the medial prefrontal cortices during toe graphaesthesia.

This experiment was designed to test the construct validity of psychometric analyses that suggested a strong functional association between the accuracy for toe graphaesthesia and selective activation of neurons within the medial prefrontal regions. Single Photon Emission Computerized Tomography (SPECT) profiles were obtained for three volunteers (2 men, 1 woman) after they had been exposed to a toe graphaesthesia task or had been exposed to the control setting. The two measurements for each participant were separated by at least one week. Qualitative evaluation, using criteria employed for clinical diagnoses, of serial coronal, sagittal, and horizontal sections clearly indicated a specific increase in uptake of tracer within the rostral one-third to one-half of the medial prefrontal cortices of all three subjects during the toe graphaesthesia task compared to that during baseline conditions. The results are consistent with our neuropsychological research which indicates that toe graphaesthesia may be an accurate and useful indicator of the functional integrity of the medial surfaces of the anterior cerebral hemispheres.

Adult↗
PubMed1998

Orbital psuedotumour with intracranial extension. A case report.

Inflammatory pseudotumour of the orbit is an unusual condition of unknown aetiology which rarely extends beyond the orbit. To our knowledge 19 cases with intracranial extension have been reported, none of which involved the pituitary fossa or sphenoid sinus. Most required cytotoxic agents, surgery or radiotherapy in addition to corticosteroids. We present a case of orbital pseudotumour with extension into the pituitary fossa, sphenoid sinus and cavernous sinuses with vascular compression. Marked clinical improvement occurred on steroid therapy alone.

Adult↗
PubMed1997

FT Raman microscopy of untreated natural plant fibres.

The application of FT-Raman microscopy to the non-destructive analysis of natural plant fibres is demonstrated with samples of flax, jute, ramie, cotton, kapok, sisal and coconut fibre. Vibrational assignments are proposed and characteristic features of each material are presented. Samples were not pre-treated chemically before analysis and were used directly from their respective storage collection; the adaptation of the Raman microscopic technique to the identification of specimens of natural fibres in archaeological burial sites is explored for its forensic potential.

Cellulose↗
PubMed1997

Sedation, analgesia, and anesthesia issues in the pediatric patient.

Pediatric and adolescent patients facing analgesia, anesthesia, and surgical procedures require different considerations than adults do. The preoperative, intraoperative, and postoperative time periods are discussed. Analgesia considerations outside the operating room are covered. The practicing podiatric physician will be able to assess better the physical needs of the pediatric patient by understanding and incorporating their emotional needs.

Adolescent↗
PubMed1996

Hematopoietic potential of cryopreserved and ex vivo manipulated umbilical cord blood progenitor cells evaluated in vitro and in vivo.

The hematopoietic potential of cryopreserved and ex vivo manipulated umbilical cord blood (UCB) samples was evaluated in vitro and in vivo. Phenotypic analysis shows that approximately 1% of cord blood mononuclear cells express high levels of CD34 antigen on their surface (CD34hi), but none of a panel of lineage antigens (Lin-), suggesting that they are hematopoietic progenitor cells that have not yet committed to a specific lineage. Approximately 1% of CD34hi/Lin- cells are primitive hematopoietic progenitors that produce B lymphoid and multiple myeloid progeny for up to 7 weeks in stromal cell cultures. Twenty-one percent (+/- 13%) of CD34hi/Lin- cells also express low levels of the Thy-1 antigen and are threefold to fourfold enriched over CD34hi/Lin- cells in primitive hematopoietic potential as measured by long-term culture and phenotypic analysis. One-week liquid cultures of CD34-enriched UCB progenitor cells in the presence of interleukin (IL)-3, IL-6, and stem cell factor (SCF) results in a two-fold to threefold expansion of progenitors capable of reinitiating long-term stromal cell cultures. Only the CD34hi/Thy-1+/Lin- cell population was capable of maintaining progenitors with secondary transfer potential in long-term stromal cell cultures and is thus postulated to contain all of the primitive hematopoietic stem cells in UCB. The in vivo transplantation potential of UCB was also measured. Ex vivo manipulated UCB progenitor cells were used to engraft irradiated human thymus fragments implanted in severe combined immunodeficiency (SCID) mice. Thymic engraftment with >5% donor-derived cells and a normal CD4/CD8 distribution was observed in 19 of 23 tissues tested. UCB cells from in vitro expansion cultures engrafted with efficiencies comparable to nonexpanded cells. Similar results were obtained for UCB engraftment of human bone fragments implanted in SCID mice. In all cases, engraftment was achieved in competition with endogenous competitor stem cells and across major histocompatibility barriers. Taken together, this data demonstrates that human UCB is a rich source of multipotent hematopoietic progenitors that can be cryopreserved, enriched by physical methods, and expanded in a limited fashion without measurable loss of long-term culture or in vivo engrafting potential as measured in these assays.

Animals↗
PubMed1996

N-methyl-D-aspartate antagonists limit aminoglycoside antibiotic-induced hearing loss.

The use of aminoglycoside antibiotics is limited by ototoxicity that can produce permanent hearing loss. We report that concurrent administration of N-methyl-D-aspartate (NMDA) antagonists markedly attenuates both the hearing loss and destruction of cochlear hair cells in guinea pigs treated with aminoglycoside antibiotics. These findings indicate that aminoglycoside-induced hearing loss is mediated, in part, through an excitotoxic process. The high correlation (Spearman correlation coefficient: 0.928; P < 0.01) obtained between the relative cochleotoxicities of a series of aminoglycosides in humans and the potencies of these compounds to produce a polyamine-like enhancement of [3H]dizocilpine binding to NMDA receptors is consistent with this hypothesis, and provides a simple in vitro assay that can predict this aspect of aminoglycoside-induced ototoxicity.

Animals↗