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Biomedical subjects

M S Edwards

Publications and source records attributed to M S Edwards.

At least 235 records · Page 13Linked to original sources

Hematoporphyrin derivative photoradiation therapy of the rat 9L gliosarcoma brain tumor model.

The distribution of hematoporphyrin derivative (HPD) in the rat 9L gliosarcoma intracerebral brain tumor model at 4, 24, 48, and 72 hours after intravenous administration was evaluated using a digital video fluorescence microscopy technique. Maximum tissue fluorescence in the normal brain was observed at 4 hours, whereas maximum fluorescence in the tumor regions occurred at 24 hours. Although the fluorescence counts suggested that there was significant uptake of HPD within the tumors when compared to normal brain, only 33% to 44% of each of the eight tumors surveyed showed fluorescence. In response to a laser light dose (633 nm) of 30 J/cm2, six rats that had been sensitized with HPD had a patchy coagulation necrosis involving up to 70% of the total tumor volume. In contrast, four rats given HPD only or exposed to laser only had no areas of necrosis, as observed on histological examination. In a group of 30 rats, no prolongation of survival was observed in response to photoradiation therapy.

Animals↗

Evaluation of desmethylmisonidazole-induced neurotoxicity in the rat using brainstem auditory evoked potentials.

Brainstem auditory evoked responses (BAEPs) and a scale that evaluates clinical signs of neurotoxicity were used to measure the onset of neurotoxic effects seen in rats after chronic injection of 400 mg/kg/day of the radiosensitizer desmethylmisonidazole (DMM) for 5 days/week for 7 weeks. A significant neurotoxic effect was indicated by increases in the latencies of peaks 4 and 5 of the BAEP after the 24th injection of DMM; clinical signs of neurotoxicity were observed after the 30th injection. Histologic examination of brainstems from rats sacrificed after selected number of injections during treatment showed that the onset of lesions in the brainstem was gradual but not extensive. Pentobarbital used as an anesthetic agent had no effect on the induction of neurotoxicity.

Anesthesia↗

Correction of congenital hydrocephalus in utero II: Efficacy of in utero shunting.

To study the effect of in utero ventricular decompression of hydrocephalus on brain development and prognosis, and to evaluate the function and possible complications of different shunt designs, we created fetal hydrocephalus in 28 fetal lambs and 17 fetal monkeys by injecting kaolin into the cisterna magna during the third trimester. One fetal lamb had indwelling intracranial subdural and amniotic cavity pressure catheters placed to study serial changes in the relationship of intracranial pressure (ICP) and amniotic fluid pressure (AFP) from the time of injection until term. Twenty hydrocephalic fetal lambs underwent ventricular decompression--ventriculoamniotic (V-A), N = 10; ventriculo-right atrial (V-RA), N = 9; and ventriculo-pleural (V-PL), N = 1--21 to 25 days after the kaolin was injected; seven hydrocephalic fetuses were left unshunted as controls (CON). Eight fetal monkeys underwent V-A decompression 14 to 21 days after kaolin injection; nine were left unshunted as controls. All animals were delivered by cesarean section near term, assessed for viability and their brains examined grossly and microscopically. After kaolin injection in the fetal lamb, ICP (r = 0.94) and ICP minus AFP (r = 0.93) rose in a linear fashion, while AFP showed no trend (r = 0.22). All unshunted newborn lambs and monkeys had split sutures, dilated ventricles, and thinned cortical mantle. Most shunted lambs showed anatomic improvement with decreased head circumference, overriding sutures, normal-sized ventricles, and improved survival. However, histopathology revealed marked white matter destruction. In contrast, most shunted monkeys showed little anatomic improvement. Both shunted and unshunted monkey brains showed a severe inflammatory ventriculitis. In both lambs and monkeys, shunting was associated with a variety of complications including subdural hematoma, subdural hygroma, shunt infection, shunt occlusion, and improper shunt tip placement. In this experimental model, in utero decompression of obstructive hydrocephalus improves overall survival, improves gross ventriculomegaly, does not improve histopathologic brain damage, and is associated with significant complications. The choice of the optimal shunt design and the effect on postnatal neurologic function requires further study. This work emphasizes the need for continuing research in an animal model prior to human application.

Amniotic Fluid↗

Management of ventriculomegaly in the fetus.

We studied 24 human fetuses with cerebral ventriculomegaly by serial obstetric ultrasound to define the natural history of fetal ventricular enlargement and to develop a management strategy. In 10 fetuses, ventriculomegaly was associated with other severe anomalies; nine of these families chose to terminate the pregnancy. In three other severely affected fetuses in whom ventriculomegaly was detected serendipitously late in gestation, routine obstetrical management was performed; none survived. Eleven fetuses had ventriculomegaly without associated severe anomalies. Ventriculomegaly remained stable or of moderate severity throughout gestation in nine, resolved gradually in one, and progressed in one who did not have signs of increased intracranial pressure at birth. All of these fetuses were viable; three patients required shunting in the neonatal period, and two others by 5 months of age. Although obstetric ultrasound usually can detect anomalies associated with fetal ventriculomegaly, three fetuses with isolated ventriculomegaly had midline brain malformations that could not be distinguished in utero from hydrocephalus, even in retrospect. Prenatal diagnosis improves perinatal management by allowing counseling, and selective pregnancy termination, or selection of the timing, mode, and place of delivery to optimize outcome. Most fetuses with ventriculomegaly do not require intervention before birth.

Abnormalities, Multiple↗

Class specificity of naturally acquired and vaccine-induced antibody to type III group B streptococcal capsular polysaccharide: determination with a radioimmunoprecipitin assay.

A radioimmunoprecipitin test was developed to determine the immunoglobulin class distribution of naturally acquired and vaccine-induced antibody to the native capsular polysaccharide of type III group B streptococci (III-GBS). In sera from adults and pregnant women with naturally acquired antibody, the mean percentage of antigen bound by immunoglobulin G (IgG) was 74.9 and 78.6, respectively, whereas antigen bound by IgM comprised less than 10% of the total. In contrast, early-convalescent-phase sera (mean, 16.3 days) from neonates responding to III-GBS infection with an increase in specific antibody had significantly more IgM (mean, 36%; P less than 0.001, unpaired t test). However, in late convalescence, the immunoglobulin class distribution in sera from these neonates was similar to that of naturally immune adults. Four weeks after immunization with III-GBS polysaccharide vaccine, sera from adults with low (less than 2 micrograms/ml) preimmunization antibody levels in their sera and from those with moderate (mean, 5.5 micrograms/ml) preimmunization levels contained specific antibody predominantly of the IgG class. Although the percentage of IgG-specific antibody was greater in sera from naturally immune adults than in that from vaccinees with a presumed primary immune response, the major portion of antigen bound by sera at 4 weeks postimmunization (62.5%) was associated with IgG. These observations support the opinion that immunization of pregnant women with III-GBS capsular polysaccharide could be efficacious for the prevention of invasive neonatal III-GBS disease.

Adult↗

Argon laser surgery of pediatric neural neoplasms.

The argon microsurgical laser offers a less traumatic and often more hemostatic technique for the ablation of neural and tumor tissues. Our experience in 15 microsurgical procedures is discussed. The argon laser was essential in the removal of small, moderately vascular, strategically placed intracranial and spinal lesions. In each of these cases, the laser either permitted a complete resection or augmented the amount of tumor resected over that which could be removed by standard microsurgical technique. The laser was not beneficial in operations on large lesions or those with markedly increased blood flow. There were no early or late complications related to the use of the argon laser. Further advances in laser technology will afford significant improvements over the presently available techniques of laser microneurosurgery.

Argon↗

Effect of microsurgical and carbon dioxide and argon laser resection on recurrence of the intracerebral 9L rat gliosarcoma.

The intracerebral 9L rat brain tumor was resected from 38 rats with the use of standard microsurgical techniques, the carbon dioxide laser, or the argon laser. The extent of resection was evaluated by histological examination, and the effect on survival of the three methods was compared. All three methods achieved histologically verifiable gross total resection, and tumor recurrence after resection by all three methods occurred at the same rate.

Animals↗

5-Fluorouracil and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) followed by hydroxyurea, misonidazole, and irradiation for brain stem gliomas: a pilot study of the Brain Tumor Research Center and the Childrens Cancer Group.

Twenty-eight evaluable children with the diagnosis of brain stem glioma were treated with 5-fluorouracil and CCNU before posterior fossa irradiation (5500 rads); during irradiation, the children received hydroxyurea and misonidazole. The treatment was well tolerated, and minimal toxicity was produced. The median relapse-free survival was 32 weeks, and the median survival was 44 weeks. Analysis of covariates showed that, in patients between the ages of 2 and 19 years, survival was longest in the older children (P less than 0.02). Tumor histology, sex, extent of operation (if any), Karnofsky score, and radiation dose did not correlate with survival.

Adolescent↗

Kaolin-induced congenital hydrocephalus in utero in fetal lambs and rhesus monkeys.

A model of congenital hydrocephalus in utero in fetal lambs and rhesus monkeys has been produced by the intracisternal injection of kaolin. Initial attempts to produce hydrocephalus using silicone oil were unrewarding. Hydrocephalus had developed by 2 weeks post-injection and could be followed by ultrasonography. The pathological findings were similar to those reported using kaolin in other species. Ventriculoamniotic shunting, when successful, was capable of partially reversing the deleterious effects of hydrocephalus. The major drawback of the present model is that hydrocephalus is produced during the second rather than the first trimester of pregnancy. However, kaolin produces mainly an obstructive hydrocephalus without other associated brain or systemic anomalies.

Animals↗

Supratentorial malignant gliomas of childhood. Results of treatment with radiation therapy and chemotherapy.

Twenty-seven patients aged 1 to 18 years harboring supratentorial (20 in the cerebrum and seven in the thalamus) malignant gliomas were treated between 1975 and 1982. There were four glioblastomas multiforme, 14 anaplastic astrocytomas, and nine malignant gliomas. All patients had a subtotal resection or biopsy as the initial procedure and received postoperative radiation therapy (RT). Fifteen of 27 patients were treated by RT alone; 14 had tumor progression with a median time to tumor progression (MTP) of 65 weeks. Twelve patients were treated with chemotherapy as an adjuvant to RT; only seven had tumor recurrence, with an MTP of 130 weeks. Of the 21 patients with recurrent tumors in both groups, 18 were treated with chemotherapy alone, or chemotherapy with a second surgical procedure or second course of RT. For all histological grades of tumor, the MTP for first recurrence was 75 weeks and the median survival time was 180 weeks. Age at initial diagnosis was found to be a statistically significant prognostic factor, with patients younger than 10 years of age surviving longer than patients aged over 10 years (p = 0.02).

Adolescent↗

Use of the argon surgical laser in neurosurgery.

The argon surgical laser has been used in 68 neurosurgical procedures that included the removal of intracranial and intraspinal tumors, spinal cord fenestration for syringomyelia, and the production of dorsal root entry zone lesions. Characteristics that make the argon surgical laser a useful microneurosurgical instrument include the availability of a fiberoptic delivery system, a laser spot size that can be varied continuously between 0.15 and 1.5 mm, a single laser-aiming and treatment beam, the transmission of argon laser light through aqueous media such as irrigating or cerebrospinal fluids, and improved hemostasis compared to conventional techniques. The argon laser is limited primarily by its relatively low power output (less than 16 W), which makes the excision of large tumors difficult. However, even with these limitations, which can be used to advantage in the proper setting, the authors' laboratory and clinical experience suggests that the argon surgical laser may be useful in certain microneurosurgical operations.

Adolescent↗

Acutely thrombosed aneurysm of the middle cerebral artery presenting as intracranial hemorrhage in a 3-year-old child. Case report.

Spontaneous thrombosis of aneurysms occurs rarely in children, and, to our knowledge, there are no reports of aneurysms presenting as an embolic event in a child. We describe the case of a 3-year-old boy whose symptoms initially suggested an ischemic event to the dominant hemisphere. Initial computerized tomography scans indicated an intracranial hemorrhage. Subsequent radiographic study revealed evidence of emboli and, at exploration, a large acutely thrombosed aneurysm of the left middle cerebral artery associated with arterial occlusion was found. Entrapment of the aneurysm and thrombectomy provided excellent operative results.

Cerebral Angiography↗

Computerized tomography of cranial sutures. Part 1: Comparison of suture anatomy in children and adults.

Knowledge of normal suture anatomy and development is vital in order to understand abnormal suture development and to be able to distinguish sutures radiographically from normal anatomical structures and possible skull fractures. The anatomy of the sutures and synchondroses of 150 normal pediatric and adult patients was studied using high-resolution computerized tomography scanning. Sutures of both the calvaria and skull base were most accurately identified in axial and coronal high-resolution thin-section scans when bone window algorithms were used. Developmental changes of the sutures and synchodroses , the inner and outer tables, and the diploic space were all well delineated. Vault sutures could be identified routinely in children, but their presence in adults varied considerably. With increasing age, parasutural sclerosis developed and sutures were more closely apposed.

Adolescent↗

Computerized tomography of cranial sutures. Part 2: Abnormalities of sutures and skull deformity in craniosynostosis.

Preoperative computerized tomographic (CT) scans of 24 children who had surgery for either single or multiple craniosynostoses were compared with skull radiographs and operative and pathological findings. In addition to providing accurate imaging of calvarial and skull base deformities secondary to premature suture closure, high-resolution CT with bone definition algorithms supplied valuable detail of anatomical changes at the abnormally developed suture. The CT findings varied with the location of the suture. Thickened bony ridges predominated at the sagittal suture, focal bone thickening and erosions were more likely to be found at the metopic suture, and parasutural sclerosis was the prevalent finding on one side of the lambdoid suture. No evidence of the suture could be detected in the majority of patients with complete coronal craniosynostosis. Radiographs of the skull were shown to be a relatively insensitive means of imaging the zone of limited fusion, especially the lambdoid suture. An excellent correlation was found between the CT scan and the operative and pathological findings. There was histological evidence of progressive suture fusion in virtually all patients. An asymmetrically narrowed lucent zone with parasutural sclerosis or bony ridges seen on CT scans correlated well with fibrous union of the suture found on histological examination. The authors conclude that high-definition CT used in conjunction with bone windows and thin and coronal slices for the evaluation of sagittal sutures is a useful imaging method for the evaluation of craniosynostosis.

Cranial Sutures↗

Surgical treatment of syringomyelia. Favorable results with syringoperitoneal shunting.

The authors reviewed the clinical findings, radiological evaluation, and operative therapy of 39 patients with syringomyelia. Syringoperitoneal (SP) shunting was used in 15 patients and other procedures were used in 24 patients. Follow-up periods ranged from 1 1/2 to 12 years. During the period of this study, metrizamide myelography in conjunction with early and delayed computerized tomography scanning replaced all other diagnostic procedures in patients with syringomyelia. Preoperative accuracy for the two procedures was 87%. The most common symptoms were weakness (79%), sensory loss (67%), pain (38%), and leg stiffness (28%). Surgery was most effective in stabilizing or alleviating pain (100%), sensory loss (81%), and weakness (74%); spasticity, headache, and bowel or bladder dysfunction were less likely to be reversed. Approximately 80% of patients with idiopathic and posttraumatic syringomyelia and 70% of those with arachnoiditis improved or stabilized. Better results were obtained in patients with less severe neurological deficits, suggesting the need for early operative intervention. A higher percentage of patients had neurological improvement with SP shunting than with any other procedure, especially when SP shunting was the first operation performed. Patients treated with SP shunts also had the highest complication rate, most often shunt malfunction. These results indicate that SP shunting is effective in reversing or arresting neurological deterioration in patients with syringomyelia.

Adolescent↗

Pain relief from dorsal root entry zone lesions made with argon and carbon dioxide microsurgical lasers.

Argon and carbon dioxide microsurgical lasers were used to produce lesions in the dorsal root entry zone (DREZ) experimentally in six cats and surgically in 21 patients who had denervation pain syndromes. The technique of producing lesions, the histological and physiological changes seen in the cat spinal cord, and the results of treatment in the clinical series are discussed. Lesions were produced within the DREZ without new involvement of the dorsal column system or corticospinal tract in all but one patient. Based on their subjective evaluation, two-thirds of the patients were relieved of more than 50% of their preoperative pain. These experimental results and clinical experience suggest that the argon and carbon dioxide lasers effectively produce localized microsurgical lesions in the DREZ. The concept that an abnormality involving either neurons in the substantia gelatinosa or internuncial fibers in Lissauer's tract is responsible for pain in patients with primary sensory nerve deafferentation is discussed.

Adult↗