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Biomedical subjects

M S Edwards

Publications and source records attributed to M S Edwards.

At least 181 records · Page 10Linked to original sources

Bromodeoxyuridine: a comparison of its photosensitizing and radiosensitizing properties.

The photo- and radiosensitizing properties of bromodeoxyuridine (BUdR) were assessed in vitro using the 9L rat brain tumor cell line. Pretreatment of 9L cells with 10 microM BUdR for 24 hours followed by irradiation with ultraviolet (UV) light resulted in a dose-enhancement ratio of 3.8:1 compared with UV radiation alone. X-radiation of BUdR-pretreated cells produced a dose-enhancement ratio of 1.7:1. Alkaline elution analysis of deoxyribonucleic acid (DNA) from cells treated with BUdR and UV irradiation showed the presence of DNA single-strand breaks and DNA-protein cross-links. Analysis of DNA from cells treated with BUdR and then x-irradiated showed no increase in DNA single-strand breaks compared with cells treated with x-radiation alone; no DNA-protein cross-links could be detected. The possible clinical relevance of these findings is discussed.

Animals↗

Prognostic implications of the proliferative potential of low-grade astrocytomas.

The proliferative potential of low-grade astrocytomas was estimated in 47 patients. Each patient received an intravenous infusion of bromodeoxyuridine (BUdR), 150 to 200 mg/sq m, at the time of craniotomy to label cells in deoxyribonucleic acid (DNA) synthesis; the percentage of S-phase cells, or BUdR labeling index (LI), of each tumor was determined immunohistochemically. In 29 patients (60%), the tumors had BUdR LI's of less than 1%, indicating a slow growth rate; only three (10%) of these patients died of recurrent tumor during a follow-up period of up to 3 1/2 years. In contrast, of the 18 patients (40%) whose tumors had BUdR LI's of 1% or more, 12 (67%) had a recurrence and nine died during the same follow-up period. These results show that the proliferative potential, as reflected by the BUdR LI, is an important prognostic factor that separates low-grade astrocytomas into two groups and provides a more scientific rationale for selecting treatment for individual patients.

Astrocytoma↗

Natural history of fetal ventriculomegaly.

The natural history of in utero ventriculomegaly was defined by a retrospective review of the outcome of 47 fetuses evaluated during a 5-year period by the Fetal Treatment Program at the University of California. In 20 fetuses, a diagnosis of ventriculomegaly associated with other severe abnormalities was made early in pregnancy. Termination of pregnancy was elected in 19 of 20 cases, and no fetus survived. In five fetuses, the diagnosis was made late in pregnancy and was associated with severe abnormalities. Fetuses were handled in a routine obstetric fashion and none survived. Of the other 22 fetuses 19 had stable and two had progressive ventriculomegaly; in one case, ventriculomegaly resolved in utero. Nineteen of these fetuses have survived, 13 with normal intellectual development and six with moderately to severely delayed development. Associated abnormalities were detected with ultrasonography in 74% of fetuses; there was a 20% false-negative rate of detection. Ventriculomegaly was isolated and progressive in two fetuses. In both cases, fetuses were delivered at term, and postnatally a shunting procedure was performed. Both children are neurologically normal. From our results and a review of the literature, which supports our findings, we were unable to define a group of fetuses with in utero ventriculomegaly that would benefit from in utero shunting.

Abortion, Therapeutic↗

Symptomatic hydrocephalus: initial findings in brainstem gliomas not detected on computed tomographic scans.

In a retrospective review of 85 patients younger than 18 years of age with a diagnosis of brainstem glioma treated between 1974 and 1987, seven (8.3%) initially had hydrocephalus and no evidence of tumor on CT scans. Intrinsic brain tumors, six in the pons and one in the diencephalon, were discovered later, either on follow-up CT scans or on magnetic resonance images obtained despite persistently normal CT scan findings. The initial radiologic study of choice for children and adolescents with hydrocephalus should be magnetic resonance imaging, including axial and sagittal T1- and T2-weighted images. If a CT scan is obtained first and hydrocephalus but not tumor is found, magnetic resonance image should be obtained to rule out the possible presence of an intrinsic brainstem tumor.

Adolescent↗

Opsonophagocytic killing antibody to Pseudomonas aeruginosa mucoid exopolysaccharide in older noncolonized patients with cystic fibrosis.

The principal cause of morbidity and mortality in cystic fibrosis is persistent respiratory colonization with mucoid strains of Pseudomonas aeruginosa. To investigate possible mechanisms of resistance to this organism, we studied serum from 16 older (greater than or equal to 12 years) patients not colonized with mucoid P. aeruginosa, 11 older (greater than or equal to 14 years) colonized patients, 10 younger (less than or equal to 11 years) noncolonized patients, and 20 healthy adults. The samples from the older patients not colonized with mucoid P. aeruginosa contained antibody specific to the mucoid-exopolysaccharide antigen, which could mediate bacterial killing in conjunction with complement and white cells (titers of 4 to 80). These opsonophagocytic killing antibodies were not detected in samples from the 20 normal controls (P less than 0.0001 vs. noncolonized older patients) or 9 of 10 younger (less than or equal to 11 years) noncolonized patients (P = 0.0072 vs. noncolonized older patients). Although the patients with chronic colonization had higher titers of serum opsonophagocytic killing antibody than did the older noncolonized patients (P = 0.0005), these antibodies were not specific to the mucoid-exopolysaccharide antigen. We conclude that there is an association between mucoid-exopolysaccharide-specific opsonophagocytic killing antibody and a lack of detectable P. aeruginosa colonization in a subset of older, relatively healthy patients with cystic fibrosis.

Adolescent↗

Cerebral ptosis with contralateral arteriovenous malformation: a report of two cases.

We describe two patients with chronic unilateral ptosis and contralateral hemispheric arteriovenous malformations. Both patients were brought to our attention after a subacute or acute neurological deterioration. Analysis of prior photographs showed the ptosis progressed up to the time of presentation and significantly resolved following surgical removal of the arteriovenous malformation. The partially reversible and chronic nature of the ptosis in these two patients represents a particularly unusual forms of cerebral ptosis.

Adolescent↗

Magnetic resonance imaging and management of a pineal region dermoid.

We report the case of a 19-year-old man harboring a pineal region dermoid, of which only eight other cases have been reported. A diagnosis was made with magnetic resonance imaging (MRI), which showed a marked high signal intensity on both T-1 and T-2 weighted images that is consistent with the lipid character of the lesion. Residual tumor could be seen on postoperative MR images. MRI is an accurate, noninvasive modality for the diagnosis and follow-up evaluation of these tumors.

Adult↗

Type III group B Streptococcus: functional interaction with IgG subclass antibodies.

The functionally active IgG subclasses and the portion of the antibody molecule mediating opsonophagocytosis of type III, group B Streptococcus (III-GBS) have not previously been investigated. Serum from a healthy adult immunized with III-GBS vaccine was subjected to ion exchange chromatography, yielding 2,950 mg of IgG/dl and 1,440 micrograms of III-GBS-specific antibody/ml. Papain digestion for selective cleavage of IgG1 and IgG3 yielded an IgG2-rich pool that contained 31% of the initial IgG but 69% of the antibody to III-GBS. This pool retained opsonophagocytic activity of antibody to III-GBS at levels similar to that for the initial IgG pool. Analysis of F(ab')2 fragments of pepsin-digested IgG revealed that the level of alternative pathway-mediated opsonophagocytosis of III-GBS was similar to that mediating functional activity in the initial IgG preparation. Therefore, IgG2 is an active opsonin for III-GBS, but divalency appears to be required for alternative pathway-mediated opsonophagocytosis.

Antibodies, Bacterial↗

Structural and sequence patterns in the loops of beta alpha beta units.

The conformation and sequences of the 129 loops of 70 beta alpha beta units from 17 alpha/beta proteins were analysed for patterns. Many different conformations of the loop regions were observed, but 18 of the loops could be classified into one of four loop families with distinctive conformation and sequence patterns. (i) Adjacent alpha beta loops with one residue between the alpha-helix and beta-strand. The residue is a glycine with conformationally restricted phi/psi angles; (ii) adjacent alpha beta loops of three residues with a conformationally restricted glycine as the first of the loop followed by an analine or histidine residue and a third residue with helical phi/psi angles; (iii) adjacent beta alpha loops of 3/4 residues previously reported to bind nucleotides and which have three glycine residues in the loop region; (iv) non-adjacent beta alpha loops of 0 residues with a serine or threonine as the last residue of the beta-strand. The analysis provides information for the model building of loops and prediction of secondary structure from amino acid sequences.

Amino Acid Sequence↗

Interaction of soluble fibronectin with group B streptococci.

Fibronectin binds to a variety of bacterial species, and we hypothesized that differential fibronectin binding might influence the invasive potential of group B streptococci (GBS). Human plasma fibronectin purified by a standard two-step chromatographic procedure was radiolabeled with 3H. Fifty GBS strains (invasive, colonizing, or bovine) representing serotypes Ia (10 strains), Ib (6 strains), Ia/c (6 strains), II (10 strains), III (11 strains), IV (1 strain), and nontypable (6 strains) were tested. No source or serotype variability was detected among GBS strains, and binding was uniformly less than 1.5% of available fibronectin. Lack of detectable binding occurred at both the log and stationary growth phases and persisted despite treatment with trypsin or neuraminidase or opsonization with immunoglobulin G containing high levels (greater than 40 micrograms/ml) of antibody specific for the Ia, II, or III GBS capsular polysaccharides. Incubation with GBS did not inhibit fibronectin binding to the Cowan 1 strain of Staphylococcus aureus. Strain COH 31-15, an isogenic, type III, capsule-deficient mutant of COH 31r/s, also failed to bind fibronectin. In contrast to other streptococci, GBS do not have readily detectable receptors for soluble fibronectin as part of their surface structures. If present, binding sites for soluble fibronectin are deep to surface structures, obscured from host defense systems, or require the presence of other factors to facilitate their recognition of fibronectin. The uniform ability of GBS to resist binding to soluble fibronectin could be a significant virulence factor in the pathogenesis of invasive infections of infants.

Chromatography, Affinity↗

Extensive Actinomyces naeslundii infection in a child.

A case of extensive Actinomyces naeslundii infection in a globally retarded patient is reported. To our knowledge, this uncommon Actinomyces species has not previously been described as a cause of widespread disease. Mental retardation and thoracic scoliosis were identified as features predisposing to infection.

Actinomycosis↗

Management of infratentorial brain tumors.

Because 60-70% of brain tumors in children occur in the posterior fossa, the pediatric neurosurgeon must be familiar with the specialized techniques necessary for successful surgery in this region. We discuss the preoperative evaluation, surgical techniques, and postoperative management for children harboring infratentorial brain tumors. Using this approach to treatment, we have had no operative mortalities, a 2% rate of infection, a 15% rate of transient neurologic deficit, and a 5% rate of permanent neurologic deficit.

Child↗

Current management of brain stem gliomas.

Brain stem gliomas constitute 10-20% of central nervous system tumors in children. Management of these tumors remains controversial. In general, the prognosis for long-term survival is poor, but brain stem gliomas represent a heterogeneous population of tumors, some of which have a better prognosis than others. Improvements in diagnostic imaging techniques, particularly the availability of magnetic resonance imaging, provide the means to differentiate among these populations. Advances in radiation therapy may provide the means to improve survival. In this article we review the reported series and the present state of the art for the diagnosis and management of children with brain stem gliomas.

Adrenal Cortex Hormones↗

A mouse model of chronic pulmonary infection with Pseudomonas aeruginosa and Pseudomonas cepacia.

A mouse model of chronic pulmonary infection with either Pseudomonas aeruginosa or Pseudomonas cepacia was developed to compare bacteriologic and pathologic features of these infections. Experimental pneumonia was established in Swiss mice by transoral intratracheal inoculation of 10(3)-10(4) colony-forming units of mucoid P. aeruginosa or P. cepacia enmeshed in agarose beads. Unilateral infection with either strain was tolerated without morbidity. By 10 days postinoculation, the mean colony-forming units per infected lung was 3.8 X 10(5) for P. aeruginosa and 1.0 X 10(5) for P. cepacia. Bacterial counts remained stable through 21 days with no significant difference between organisms. Acute and chronic inflammatory histopathologic changes similar to many found in the lungs of cystic fibrosis patients were present in 95% of lung specimens. The changes occurred with both organisms but were more extensive with mucoid P. aeruginosa. This model represents an important tool for study of the contribution of complement, antibody, and adoptive transfer of T cell-mediated immunity to the pathogenesis of chronic pneumonia with Pseudomonas species, and represents the first successful model of chronic pulmonary infection with P. cepacia.

Animals↗

Autogeneic skull bone grafts to reconstruct large or complex skull defects in children and adolescents.

Autogeneic split or free skull bone grafts harvested at the time of operation were used to repair large or complex skull defects in 19 children; in 2 children, autogeneic fresh rib grafts were also used. Follow-up examinations for periods of 1 and 7 years showed that the use of autogeneic grafts is superior to the use of materials such as acrylic or metals for cranioplasty in children.

Adolescent↗

Craniometaphyseal dysplasia associated with hydrocephalus: case report.

Craniometaphyseal dysplasia is a rare bone disorder that may cause a variety of neurological abnormalities; hydrocephalus has not been observed with this disorder, however. A case of craniometaphyseal dysplasia associated with hydrocephalus is reported, and possible causes are discussed.

Bone Diseases, Developmental↗

Brachytherapy of recurrent tumors of the skull base and spine with iodine-125 sources.

Thirteen patients with recurrent, previously irradiated tumors of the skull base or spine were reirradiated with 125I sources implanted interstitially using microsurgical or stereotactic techniques. Patients harbored difficult, end-stage recurrences of chordoma, meningioma, malignant meningioma, fibrosarcoma, invasive pituitary adenoma, and malignant schwannoma. In two other patients with malignant meningioma, the dose of external radiation was augmented by implanting 125I sources during the initial operation for excision of the lesion or at a separate surgical procedure after conventional teletherapy. Microsurgical implantation of 125I sources into basal tumors was limited by the difficulties inherent in operating in this region; it is not possible to visualize the entire tumor that requires implantation. Three of five chordomas stabilized or regressed; these patients probably benefited from the procedure. Two patients with recurrent malignant meningiomas had long term remission after interstitial brachytherapy. Interstitial 125I brachytherapy for recurrent tumors at the base of skull or adjacent to the spine can be more successful only if more aggressive surgical exposures of these regions are attempted. Implantation of sources for a "boost" dose, either microsurgically during the initial surgical resection of the lesion before conventional teletherapy or stereotactically after conventional teletherapy, may be a valuable adjunct to external irradiation for the control of potentially devastating tumors (such as chordomas and malignant meningiomas) before they recur with the severe consequences seen in the patients reported here.

Adenoma↗