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Biomedical subjects

M S Edwards

Publications and source records attributed to M S Edwards.

At least 109 records · Page 6Linked to original sources
PubMed1992

Complement and antibody participation in opsonophagocytosis of type IV and V group B streptococci.

Requirements for complement and antibody in neutrophil-mediated killing of serotype IV and V group B streptococci were investigated. Neutrophils from adults were tested in an opsonophagocytic assay with sera from healthy adults, healthy newborns, and hypogammaglobulinemic, agammaglobulinemic, and C4-deficient patients. For all serum sources, the bactericidal index for both serotypes exceeded 84% after 40 min of incubation. Heat inactivation of sera ablated killing. Blockade of neutrophil receptor FcIII effected a maximum of 16% inhibition of opsonophagocytosis, and FcII receptor blockade demonstrated negligible inhibition. When neutrophil complement receptor 1 or 3 blockade was employed, the maximum inhibition detected was 26%. Simultaneous blockade of complement receptors 1 and 3 effected maximum inhibition levels of 25 and 65% for serotypes IV and V, respectively. Blockade of complement receptor 3 and neutrophil receptor FcIII inhibited opsonophagocytosis by 56% for both serotypes. When serum complement concentrations were restricted, neutrophil-mediated killing diminished but was restored by the addition of hyperimmune rabbit antiserum. These findings suggest that complement and antibody are major participants in the opsonophagocytosis of serotypes IV and V group B streptococci. A low prevalence of carriage or mediation of efficient phagocytosis by interactions of neutrophil complement and Fc receptors may contribute to the rarity of human infections caused by these two serotypes.

Adult↗
PubMed1992

Contributions of complement and immunoglobulin to neutrophil-mediated killing of enterococci.

Enterococci have become a frequent causative agent in neonatal sepsis. The relative contributions of antibody and complement and their interactions in the neutrophil-mediated bacterial killing of 11 Enterococcus strains from neonates were investigated. Polymorphonuclear leukocytes (PMNL) from adult and term newborn infants were tested with normal human serum, adult hypogammaglobulinemic serum, and normal newborn serum in a neutrophil bactericidal assay. Neutrophil bactericidal activity for enterococci was not influenced by the serum source but was essentially ablated after heat inactivation of complement in all sera. No differences were observed in the killing capacity of healthy newborn versus adult PMNL regardless of serum source. Representative Enterococcus strains were then tested with agammaglobulinemic serum or C4-deficient serum, resulting in neutrophil bactericidal activities consistently exceeding 90%. A neutrophil bactericidal assay performed with normal rabbit serum and hyperimmune rabbit serum against enterococci showed that antibodies to enterococci enhanced neutrophil-mediated killing of this organism. Thus, neutrophil killing of enterococci appears to be mediated primarily by complement, with antibody playing a less essential but potentially important role. PMNL from adult and healthy term infants functioned with equal efficiency in the neutrophil killing of enterococci.

Adult↗
PubMed1992

Applications of neuroimaging in hydrocephalus.

Hydrocephalus is a common problem in pediatric neurological and neurosurgical practices. In this manuscript, the common imaging appearances of hydrocephalus are discussed in relation to the underlying causes of the hydrocephalus. Moreover, specific findings seen on magnetic resonance imaging (MR) examinations are discussed and contrasted with those on computed x-ray tomography (CT) and ultrasound. Finally the imaging findings associated with treatment of hydrocephalus are discussed. In particular, analysis of shunt function, the diagnosis of shunt failure, and the complications of shunting are stressed.

Cerebral Ventricles↗
PubMed1992

Proliferative characteristics of juvenile pilocytic astrocytomas determined by bromodeoxyuridine labeling.

Bromodeoxyuridine (BUdR) labeling studies were performed to characterize the biological and clinical behavior of 50 juvenile pilocytic astrocytomas (JPAs) from 47 patients. Each patient received an i.v. infusion of BUdR before tumor resection; the excised tumor specimens were stained by the immunoperoxidase method with anti-BUdR monoclonal antibody to determine the BUdR labeling index (LI), or percentage of S-phase cells. The BUdR LI ranged from 0.22 to 4.3% (less than 1% in 34 and greater than or equal to 1% in 16; mean +/- SE, 1.05 +/- 0.13%). Tumors from younger patients often had higher LIs, but as the age of the patients increased, the frequency of tumors with LIs greater than or equal to 1% decreased. Tumors from male patients had higher LIs than those from female patients (1.36 +/- 0.20% [SE] vs. 0.75 +/- 0.13%; P less than 0.01), and tumors in the cerebellum had higher LIs than those in the hypothalamus (1.39 +/- 0.24% vs. 0.87 +/- 0.15%; P less than 0.05). The LI did not correlate with the gross appearance of the tumor (solid or cystic) or with outcome after the initial diagnosis. Overall, there was no difference in the LIs of primary and recurrent tumors. Four tumors (3 primary and 1 recurrent) that recurred after subtotal resection had a higher mean LI than 32 tumors that did not recur after subtotal resection (2.6 +/- 0.7% vs. 0.74 +/- 0.09%; P less than 0.005). None of 14 totally resected tumors (mean LI, 1.3 +/- 0.2%) has recurred.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Evolution of white matter lesions in neurofibromatosis type 1: MR findings.

To characterize further the evolution of white matter lesions in neurofibromatosis type 1, we reviewed 68 MR images in 43 patients (age, 1-31 years), including 25 follow-up studies (mean interval, 27 months). Lesion number, location, morphology, signal characteristics, and contrast enhancement were assessed. Lesion characteristics and changes thereof were correlated with the patients' ages. Thirty-four patients (79%) had white matter lesions. These lesions were hyperintense on T2-weighted images, were isointense on T1-weighted images, and showed no mass effect or contrast enhancement in 31 patients; in three patients, T1-prolongation was observed (one with significant mass effect). None of the lesions evolved into a glioma. The most common locations were the cerebellum (49%), brainstem (22%), and internal capsule (19%). Nineteen patients had white matter lesions and follow-up studies. Lesions decreased in size or number in seven patients (average age, 13 years), showed no change in three (average age, 12 years), increased in size or number in four (average age, 5 years), and showed a mixed pattern (increased/decreased size/number) in four (average age, 7 years). White matter lesions in neurofibromatosis type 1 frequently increase in size or number early in childhood; this did not indicate neoplasia in our study. The lesions tend to resolve with increasing age. Lesion progression in a child more than 10 years old warrants close follow-up to rule out a neoplasm.

Adolescent↗
PubMed1992

Involvement of multiple chromosome 17p loci in medulloblastoma tumorigenesis.

Loss of heterozygosity for sequences located on chromosome 17p in several tumor types is often associated with mutations in the tumor suppressor gene p53. We previously showed consistent deletion of chromosome 17p12-13.1 in medulloblastoma, a common childhood brain tumor. Using denaturing gradient gel electrophoresis and direct sequencing, we have detected p53 mutations in only two of 20 medulloblastoma specimens. Moreover, additional RFLP studies of these 20 specimens showed loss of heterozygosity at a more distal and distinct site, 17p13.3. Deletion of 17p almost invariably signified a negative prognosis. Our results suggest that p53 mutations may contribute to the pathogenesis of medulloblastoma in relatively few cases. The consistent deletion of other discrete loci on 17p suggests that additional or alternative tumor suppressor genes may contribute to the tumor's phenotype.

Base Sequence↗
PubMed1992

Pineal tumors.

Tissue diagnosis is necessary for optimal treatment of pineal region tumors in children. Preoperative staging should include craniospinal MR imaging with and without gadolinium DTPA enhancement, CSF sampling for cytology, and measurement of biologic tumor markers in serum and CSF. Surgical approach is determined by results of preoperative MR imaging and the extent of resection by the results of staging and intraoperative frozen-section histopathologic evaluation. There is no longer a role for the radiation test dose (2000 cGy) in the management of these tumors. Postoperative treatment is based on histopathology and extent of disease. Benign tumors are treated with surgery only, and nondisseminating focal tumors with surgery and focal radiation therapy. Non-germinoma malignant germ cell tumors are best treated with neoadjuvant chemotherapy followed by radiation therapy given focally for focal disease; craniospinal radiation therapy is reserved for patients with evidence of disseminated disease at the completion of induction chemotherapy.

Astrocytoma↗
PubMed1992

Report on Gardnerella vaginitis.

Gardnerella vaginitis is one of the most common diagnoses in our outpatient clinic. From January 1, 1989 through July 30, 1989 we had 230 positive cultures for G. vaginitis. Eighty-three compliant patients in this group had unabated symptoms with documented positive cultures for Gardnerella after treatment with metronidazole. This led to the use of alternative regimens of ceftriaxone or clindamycin. A survey of antibiotic choice and post-treatment culture obtained 103 entries from 34 active duty women soldiers and 60 women dependents. This paper presents the results of the survey after an introduction beginning with a 1953 article in U.S. Armed Forces Medical Journal.

Ceftriaxone↗
PubMed1991

Identification of a germ-line mutation in the p53 gene in a patient with an intracranial ependymoma.

We detected a germ-line mutation of the p53 gene in a patient with a malignant ependymoma of the posterior fossa. This mutation, which was found at codon 242, resulted in an amino acid substitution in a highly conserved site of exon 7 of the p53 gene; the same mutation was found in both the germ-line and the tumor tissue. This is the most common region of previously described somatic p53 mutations in tumor specimens and of the germ-line p53 mutations in patients with the Li-Fraumeni cancer syndrome. Evaluation of the patient's family revealed several direct maternal and paternal relatives who had died at a young age from different types of cancer. The association of a germ-line p53 mutation with an intracranial malignancy and a strong family history of cancer suggests that p53 gene mutations predispose a person to malignancy and, like retinoblastoma mutations, may be inherited.

Amino Acid Sequence↗
PubMed1991

Ultrasound-guided aspiration of a neonatal brain abscess.

The authors successfully treated a Serratia marcescens brain abscess in the right parieto-occipital region of a newborn infant born at 27 weeks' gestation and weighing 800 g. Bedside ultrasound-guided aspiration techniques and local anesthesia were used to treat the abscess.

Brain Abscess↗
PubMed1991

Low-dose craniospinal radiation therapy for medulloblastoma.

At the University of California, San Francisco, 65 children with medulloblastoma of the posterior fossa were treated postoperatively with craniospinal irradiation; the dose to the posterior fossa was 54 Gy. The 26 children initially treated had only radiation therapy, receiving 30 to 40 Gy to the spine and 40 to 50 Gy to the brain. Subsequently, 39 children were treated with low-dose craniospinal irradiation and chemotherapy; 24 to 30 Gy was directed to the whole brain and 24 to 26 Gy to the spinal axis. Chemotherapy generally consisted of procarbazine just before, and hydroxyurea during, radiation therapy. Poor-risk and good-risk patients (defined by tumor resection less than 75% or greater than 75%, positive or negative myelogram, positive or negative cerebrospinal fluid analysis, age less than or greater than 2 years, respectively) were evenly distributed between the low-dose and high-dose craniospinal radiation therapy groups. Median follow-up was 51 months (range, 24 to 228 months). Kaplan-Meier actuarial survival for all patients was 73% at 5 years, 70% at 10 years. Freedom from disease progression was 68% at 5 years, 65% at 10 years. Whereas poor-risk patients treated with low-dose craniospinal irradiation and chemotherapy had a 5-year survival of 58% and a 5-year freedom from disease progression of 39%, those figures in the comparable good-risk patients were 83% and 77%, respectively. For both good-risk and poor-risk patients, the posterior fossa was the primary site of recurrence. Tumors recurred in the frontal region, probably under blocks, in three patients receiving low-dose irradiation and in two receiving the higher dose. Reducing the dose of whole-brain and spinal irradiation and giving chemotherapy did not result in a higher rate of recurrence in the brain or spinal cord. Intellectual and social function appeared better in patients receiving the lower dose. We did not study whether chemotherapy benefitted good-risk patients. Craniospinal axis irradiation at a lower dose than conventionally used does not compromise local control or survival in patients with medulloblastoma, and may reduce toxicity.

Adolescent↗
PubMed1991

Hyperfractionated irradiation for adults with brainstem gliomas.

Hyperfractionated irradiation appears to have improved survival for pediatric patients with brainstem gliomas. However, the efficacy and safety of this technique are less well established for adults with brainstem tumors. In 1984 the UCSF Department of Radiation Oncology began treating adults with brainstem gliomas using 100 cGy fractions given twice daily to total doses ranging between 6600-7800 cGy (median dose 7200 cGy). By the end of 1989, a total of 14 patients had been irradiated with follow-up times for surviving patients ranging between 4-69 months (median follow-up 33 months). Tumor histologies included five moderately anaplastic astrocytomas, one highly anaplastic astrocytoma, and eight which were unbiopsied. At the time of this analysis, six patients had failed locally, with five dying as a result of recurrent tumor. There were no deaths caused by complications or intercurrent illness. The 3-year actuarial survival rate was 59%, with a corresponding 3-year actuarial local control rate of 48%. The projected median survival was in excess of 5 years, whereas the actuarial median time to progression was 31 months (134 weeks). The treatments were well tolerated: the mean pretreatment Karnofsky Performance Status was 74% (range 60-90%); at the end of treatment the mean KPS was 78% (range 60-100%). In terms of neurologic status, six patients improved by the end of treatment, seven were stable, and one experienced only minor deterioration without change in KPS. There were no significant long-term complications (specifically, no instances of either radiation brain necrosis or myelitis). Seven patients required prolonged steroid administration after completing radiotherapy; six of these eventually recurred locally. These results appear to be substantially better than those achieved using conventional radiotherapy regimens, and suggest that this technique merits further investigation.

Adult↗
PubMed1991

Deposition and degradation of C3 on type III group B streptococci.

Antibody to the polysaccharide capsule of type III group B streptococci (GBS) and complement are essential to host defense against systemic infection in neonates. Interactions between C3 degradation products and specific neutrophil receptors mediate the attachment and ingestion of these organisms. To evaluate the influence of capsule on C3 disposition, we compared the C3 fragments released from a highly encapsulated clinical isolate (M861) with those from an unencapsulated mutant (COH 31-15) and an asialo mutant (COH 31-21) of type III GBS after opsonization with hypogammaglobulinemic serum. Upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot (immunoblot) analysis, the three strains displayed similar patterns of C3 degradation; both C3b and iC3b were detectable. However, as the duration of opsonization increased, C3 fragment bands became more prominent on the encapsulated strain. The capsule, and specifically sialylation of the capsular polysaccharide of type III GBS, promotes C3 fragment deposition. However, C3 was deposited and degraded to iC3b in the absence of capsule. Opsonization of strain M861 with serum containing antibody specific for the polysaccharide capsule facilitated C3 fragment deposition in the early phases of opsonization. Because iC3b is one of the C3 fragments on an encapsulated strain of type III GBS, the relative deficiency of neonatal neutrophil receptors for this ligand may contribute to the virulence of this organism. Sufficient concentrations of antibody may enhance opsonization by facilitating C3 deposition as well as by interacting with Fc receptors on neutrophils.

Antibodies, Bacterial↗
PubMed1991

Role of neutrophil receptors in opsonophagocytosis of coagulase-negative staphylococci.

The role of neutrophil complement receptors in the opsonophagocytosis of 10 strains of coagulase-negative staphylococci was investigated. Polymorphonuclear leukocytes from adults as well as term and premature newborn infants were tested with normal human serum, adult hypogammaglobulinemic serum, and pooled premature infant serum in an opsonophagocytic assay. Neutrophils from premature infants demonstrated significantly lower killing capacity (62%) than neutrophils from adults (86%) or term infants (84%; P less than 0.02). Maximum inhibition of opsonophagocytosis by adult or infant neutrophils occurred with an FcIII receptor blockade (80%), whereas a blockade of complement receptors produced minimal inhibition. Opsonophagocytic activity for the coagulase-negative staphylococci was not influenced by the serum source but was influenced by reducing the serum concentration below 5%. Abrogation of the complement activity of normal human serum by heating or the addition of ethylenediamine tetraacetate reduced opsonophagocytosis by 100 and 96%, respectively, whereas selective inhibition of the classical complement pathway reduced opsonophagocytosis by only 40%. Thus, opsonophagocytosis of coagulase-negative staphylococci by human sera appears to be mediated primarily by neutrophil Fc receptors, but complement is also required. The inefficiency of these interactions with neutrophils from premature infants may partially explain the enhanced susceptibility of very-low-birth-weight neonates to disseminated, coagulase-negative staphylococcal infections.

Adult↗