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Biomedical subjects

M S Edwards

Publications and source records attributed to M S Edwards.

At least 163 records · Page 9Linked to original sources

Proliferative characteristics of intracranial and spinal tumors of developmental origin.

The proliferative potential of 17 intracranial and spinal tumors (six craniopharyngiomas, four chordomas, three mature teratomas, one immature teratoma, one embryonal carcinoma, one choriocarcinoma, and one dermoid tumor) was assessed. The patients received a 30-minute to 60-minute infusion of bromodeoxyuridine (BUdR) (200 mg/m2 intravenously [IV]) at the time of surgery but before a biopsy of the tumor was performed, to label cells in the DNA synthesis phase. The labeling index (LI) was calculated by determining the percentage of BUdR-labeled cells. The mean LI of the squamous epithelial elements of mature teratomas, craniopharyngiomas, and the dermoid tumor were 3.1 +/- 1.2%, 1.9 +/- 0.9%, and 2.9 +/- 1.9%, respectively. As in normal epithelium, the labeled cells were located in the basal layer. These results and the clinical findings suggest that the proliferation kinetics of these tumors are similar to those of normal skin and differ from those of rapidly growing malignant neoplasms. The other tissue elements (i.e., respiratory epithelium and cartilage) also demonstrated "organized" proliferation patterns similar to those of the corresponding normal tissues. An immature teratoma, an embryonal carcinoma, and a choriocarcinoma each had a high LI (24.6 +/- 5.3%, 32.3 +/- 3.8%, and 17.0 +/- 4.6%, respectively), and no organized pattern of proliferation was observed. In contrast, the mean LI of the four chordomas varied from 1.5% to 5.8%, and there was an even larger variation in the LI of different areas in individual tumors (from less than 1% to 7.5%). This finding suggests that even "slow-growing" chordomas sometimes can be locally aggressive and show a high incidence of recurrence, regardless of morphologic similarities.

Adolescent↗

The proliferative potential of human ependymomas measured by in situ bromodeoxyuridine labeling.

Twelve patients with ependymomas received a 30- to 60-minute intravenous infusion of bromodeoxyuridine (BrdU), 150 to 200 mg/m2 at surgery, to label tumor cells in the DNA synthesis phase. Labeled cells were detected in excised tumor specimens by indirect immunoperoxidase staining using anti-BrdU monoclonal antibody as the first antibody. The BrdU labeling index (LI, defined as the percentage of labeled cells in relation to the total number of cells scored) was calculated for each specimen. All four spinal cord ependymomas had a BrdU LI of less than 1%, which is consistent with our clinical experience that most such tumors grow slowly and have an excellent prognosis. Five of the eight intracranial ependymomas also had a low BrdU LI of approximately 1% or less, and three had a BrdU LI of 3.2%, 3.4%, and 4.8%. The latter three tumors, only one of which was diagnosed as a malignant ependymoma at the time of study, were either recurrent or recurred within 2 years after gross or subtotal removal. Cytologic analysis of cerebrospinal fluid (CSF) was performed in five cases; CSF seeding of tumor cells was found in only one patient, who had a malignant ependymoma. A high BrdU LI did not always correlate with CSF seeding. Measurement of the LI using BrdU and anti-BrdU monoclonal antibodies can provide more accurate information on the proliferative potential of individual tumors and may lead to a more rational grading system of ependymomas. The results of such studies do not always predict the potential for CSF seeding.

Adult↗

Role of fibronectin in diagnosing bacterial infection in infancy.

Plasma fibronectin levels and complete blood cell counts were assessed prospectively among 100 infants less than 3 months of age with the provisional diagnosis of "possible sepsis". Seven of the ten infants with culture-proved bacteremia, meningitis, or urinary tract infection had low plasma fibronectin levels as did 12 (13%) of 90 infants with superficial or no documented bacterial infection. The positive predictive value of a low plasma fibronectin level in conjunction with leukocytosis and elevated band ratio for discriminating serious bacterial infection was 71%. Normal white blood cell counts or fibronectin level alone or in combination predicted the absence of serious bacterial infection with an accuracy of at least 94%. Plasma fibronectin determination provides a useful adjunct to the complete blood cell count for the rapid evaluation of extent of illness in young infants with possible sepsis.

Bacterial Infections↗

Pressure, biochemical, and culture characteristics of CSF associated with the in utero drainage of various fetal CNS defects.

An attempt has been made to begin delineation of the in utero dynamics of fetal intracranial fluid in the presence of brain malformations. In a series of patients with fetal CNS defects, cephalocentesis was performed at the time of therapeutic abortion or to facilitate vaginal delivery. Intracranial CSF pressures and volumes were quite variable. There did not appear to be any discernible correlation between the type of lesion and the intracranial pressure. Fetal CSF glucose levels were moderately depressed and protein concentrations were very high. Neither virus nor bacteria were cultured from fetal CSF or amniotic fluid of any patients in this series.

Amniotic Fluid↗

Hepatitis B serology--help in interpretation.

This review discusses the serologic markers of hepatitis B virus (HBV) infection. Interpretation of various serologic profiles is provided, and the importance of maternal screening for interruption of perinatal transmission of HBV infection is stressed.

Female↗

Radiotherapy of primary intracranial germinomas: the case against routine craniospinal irradiation.

A retrospective study was performed on all patients with biopsy-proven intracranial germinomas and unbiopsied suprasellar or pineal region tumors treated during the past 30 years in the Department of Radiation Oncology, University of California, San Francisco. A total of 33 patients were treated: 13 with biopsy-proven germinomas, and 20 others who were unbiopsied. All patients were treated with megavoltage equipment; total dose varied between 40-55 Gy. Only two patients were treated with prophylactic spinal irradiation. No patient received initial or adjuvant chemotherapy. Follow-up times for biopsy-proven patients ranged from 0.5 to 16.7 years with a median 5.3 years. No biopsy-proven patient had a recurrence of the tumor or died; thus, actuarial relapse-free and determinate survivals at 5 years were 100%. Although only one patient in this group received prophylactic spinal irradiation, no patient failed in the spinal axis. The 20 unbiopsied patients had follow-up times ranging from 0.1 to 27.5 years with a median of 5.5 years. Six unbiopsied patients died: two from recurrent disease at the primary site, one from distant peritoneal metastases, two from complications of treatment, and one from intercurrent disease. For this group, actuarial relapse-free survival at 5 years was 72%; the corresponding determinate survival was 73%. Nineteen unbiopsied patients were treated without craniospinal irradiation. Only one developed spinal metastases. The results from this and other series indicate that the risk of spinal metastases from intracranial germinoma is too low to warrant routine prophylactic spinal irradiation. However, patients with gross tumor spill causing contamination of the CSF, malignant CSF cytology, or documented subependymal or subarachnoid metastases presumably are at higher risk for leptomeningeal failure. Craniospinal irradiation is recommended for these patients.

Brain Neoplasms↗

A polyclonal human IgG preparation hyperimmune for type III, group B Streptococcus: in vitro opsonophagocytic activity and efficacy in experimental models.

Neonates at risk for disease due to type III, group B Streptococcus (III-GBS) are those born with low serum levels of transplacentally derived, specific III-GBS antibody. Specific antibody is also required in vitro for opsonophagocytosis of III-GBS. Commercially available human immune serum globulins contain only moderate levels of III-GBS antibody. In the present study, IgG that was isolated from the serum of a human volunteer after vaccination with III-GBS polysaccharide contained very high levels of III-GBS antibody. Small amounts of this hyperimmune preparation added in vitro significantly increased the opsonophagocytosis of III-GBS in neonatal sera in the presence of polymorphonuclear leukocytes. Furthermore, small volumes of the preparation were protective in mouse and neonatal rat models of III-GBS disease. The administration of such hyperimmune human IgG preparations should be considered for preventing or treating III-GBS disease in infants.

Animals↗

Functional activity of class-specific antibodies to type III, group B streptococcus.

The functional activity of naturally acquired IgG and IgM with specificity for the capsular polysaccharide of type III, group B Streptococcus (III-GBS) was compared. Sera collected during convalescence from 14 infants who had developed specific antibodies following III-GBS infection were employed for separation of IgG from IgM by ion-exchange chromatography. Bactericidal killing of III-GBS was similar for IgG- and IgM-rich samples (37 and 42%, respectively) in reactions containing a mean of 1.0 or 1.9 micrograms/ml of III-GBS specific IgG or IgM antibody. Purified IgA lacked opsonophagocytic activity for III-GBS. These results indicate that III-GBS-specific IgG and IgM antibodies in infant sera promote opsonophagocytosis at low concentrations, and that their functional capacity is comparable.

Antibodies, Bacterial↗

Treatment of recurrent brain stem gliomas and other central nervous system tumors with 5-fluorouracil, CCNU, hydroxyurea, and 6-mercaptopurine.

Twenty-one patients with recurrent malignant central nervous system gliomas were treated with a combination of 5-fluorouracil, CCNU, hydroxyurea, and 6-mercaptopurine. Thirteen patients had brain stem gliomas, 3 patients had spinal cord gliomas, 3 patients had thalamic gliomas, and 2 patients had cerebellar astrocytomas. All patients had received radiation therapy, and 4 brain stem patients had also been treated with chemotherapy. Sixteen patients (76%) responded to treatment with either stabilization of disease or improvement. Nine of the 13 patients with brain stem gliomas (71%) had response or stabilization of disease. The median time to tumor progression (TTP) for the brain stem patients who responded or had stabilization of disease was 25 weeks. The median survival from recurrence for the brain stem glioma patients was 27 weeks. Patients with cerebellar, thalamic, and spinal cord tumors did very well, with an 87% response or stabilization of disease and a median TTP of 122 weeks.

Adolescent↗

Treatment of extraneural metastatic medulloblastoma with a combination of cyclophosphamide, adriamycin, and vincristine.

Seven patients with extraneural metastases from medulloblastoma were treated with a combination of cytoxan, adriamycin, and vincristine (CAV). None of the patients had evidence of active neural axis disease. All patients with bone metastases responded with a reduction in bone pain and improvement on the radionuclide bone scan. One patient presenting with lymph node metastases showed initial reduction in the size of the palpable nodes. In this group, the median time to the development of extraneural metastasis was 18 months from the time of original diagnosis of central nervous system medulloblastoma. The median duration of response to CAV, after extraneural metastasis, was 17 months (4-65 months). Four of seven patients died of disease-related causes, one patient presumed well was lost to follow-up, and two of seven are still without evidence of active disease at 37 and 65 months. The combination of CAV is well tolerated and provides reasonably good palliation for extraneural medulloblastoma.

Adolescent↗

Partial characterization of a soluble mitogenic factor from medulloblastoma.

To determine how medulloblastoma cells might influence the proliferation and phenotype of normal stromal cells, normal human leptomeningeal cells were treated in culture with medulloblastoma-conditioned medium; their ability to incorporate tritiated thymidine and synthesize collagen was measured. The treated leptomeningeal cells had a significantly greater uptake of tritiated thymidine and grew faster than control leptomeningeal cells. Immunofluorescence studies demonstrated a greater intensity of staining for procollagen type III in the cell layer of the treated cultures than in control cultures; diethylaminoethyl (DEAE)-cellulose chromatography of the medium showed that the treated cells synthesized predominantly type III collagen, whereas control cells synthesized type I collagen. Analysis of the medulloblastoma-conditioned medium revealed that the soluble factor responsible for these effects in an acid- and heat-stable protein. The increased proliferation and altered collagen synthesis induced in leptomeningeal cell cultures by a soluble factor from a medulloblastoma are examples of how tumor and stromal elements interact, and may be related to the process of desmoplasia often observed in medulloblastomas in vivo.

Cell Division↗

Treatment of medulloblastoma with procarbazine, hydroxyurea, and reduced radiation doses to whole brain and spine.

Forty-seven patients with medulloblastoma were treated postoperatively with procarbazine, followed by craniospinal radiation therapy in combination with hydroxyurea. The radiation dose to the posterior fossa was 55 Gy; the spinal cord received 25 Gy and the whole brain 25 to 35 Gy (mean 33 Gy). Seventeen tumors recurred. Only one initial recurrence was in the spinal subarachnoid space; 10 (59%) were in the posterior fossa, and four (24%) were supratentorial. The estimated 5-year disease-free survival probability was 55%; the 5-year overall survival rate was 66%. Myelotoxicity occurred in 38% of patients, but in only one case was it severe enough to warrant reducing the total dose of radiation. It was concluded that good-risk medulloblastoma patients may be treated with radiation dosages as low as 25 Gy to the spinal axis and to the whole brain without increasing the risk of recurrence outside the posterior fossa. Chemotherapy with procarbazine followed by radiation therapy and hydroxyurea during radiation therapy was well tolerated and may play a role in reducing radiation dosages outside the posterior fossa.

Adolescent↗

Pineal region tumors in children.

The authors believe that the preferred treatment for pineal region tumors in children requires definitive surgery with a histological diagnosis and that a conservative approach consisting of shunting and radiation therapy no longer seems to be appropriate. The results are reported of a retrospective review of the presentation, treatment, and outcome of 36 children under the age of 18 years treated between 1974 and 1986. Eleven children had germinomas (two-cell type), seven had astrocytomas, and the remaining 18 had 15 histologically different tumor types. Surgery was performed on 30 patients; there were no deaths, but a 10% rate of persistent morbidity was found. The median follow-up period was 4 years. Nine (82%) of 11 patients with germinomas are alive without evidence of recurrence; one child died from recurrent tumor in the pineal region and another is presently being treated for recurrent tumor of the spinal cord. Six (86%) of the seven patients with astrocytoma are well after biopsy and radiation therapy. Of the remaining 18 children, five (28%) died from tumor progression. The cerebrospinal fluid (CSF) tumor markers alpha-fetoprotein and beta-human chorionic gonadotropin were helpful in determining the presence of malignant germ-cell tumors, particularly those with a poor prognosis. Magnetic resonance imaging was useful for diagnosis and for planning the operative approach. Magnetic resonance images showed the presence of pineal region tumors in four children with hydrocephalus who had no evidence of tumor on computerized tomography scans. Because the great variety of tumor types found in the pineal region must be treated in different ways and because improved microsurgical and stereotaxic surgical techniques have made mortality and morbidity rates acceptably low, a biopsy diagnosis should be obtained in all patients. Preoperative assessment of CSF tumor markers and cytology is useful for the identification of patients who have a poor prognosis.

Adolescent↗

Treatment results of juvenile pilocytic astrocytoma.

Treatment results for 36 patients with juvenile pilocytic astrocytoma treated from 1942 through 1985 at the University of California, San Francisco, were reviewed. Twenty-two tumors were located in the posterior fossa, 10 were in the hypothalamic region, and four were in the cerebral hemispheres. Twenty-eight patients were less than 18 years of age. The overall survival rate was 83% and 70% at 10 and 20 years, respectively. All 12 patients who had total tumor resection remain disease-free; only two of the 12 received postoperative irradiation. The 10- and 20-year freedom-from-progression for the 19 patients who had incomplete resection and received at least 40 Gy of postoperative irradiation was 74% and 41%, respectively. All patients who failed treatment had local recurrence. One patient developed diffuse meningeal seeding, after four local recurrences in the posterior fossa over a 23-year period. Six patients failed treatment and had a repeat biopsy at the time of recurrence or at postmortem examination, and three showed histological progression of the tumor to an anaplastic astrocytoma. Based on this study and others in the literature, a protocol has been adopted whereby patients who have total tumor resection are not treated with postoperative irradiation. Patients who have incomplete tumor resection and are older than 3 years of age are currently treated with postoperative partial-brain irradiation, to a dose of 45 to 60 Gy. In general, young children with incomplete resection are followed closely with computerized tomography or magnetic resonance imaging and are treated with chemotherapy or irradiation if tumor progression is documented.

Adolescent↗