PubMed Health⌕ Search

Biomedical subjects

S L Pomeroy

Publications and source records attributed to S L Pomeroy.

33 records · Page 2Linked to original sources
PubMed1995

Hemorrhagic vasculopathy after treatment of central nervous system neoplasia in childhood: diagnosis and follow-up.

PURPOSE: To review the clinical data, imaging findings, and intermediate outcomes of a series of children with hemorrhagic vasculopathy after treatment for intracranial neoplasia. METHODS: We retrospectively analyzed the medical records and imaging examinations of 20 pediatric patients (ages 1 to 15 years) with intracranial neoplasia in whom delayed intracranial hemorrhage developed after cranial irradiation or radiation combined with systemic or intrathecal chemotherapy. Patients with intracranial hemorrhage from other identifiable causes were excluded. Histopathologic analysis was available in four patients. RESULTS: Twenty patients with delayed intracranial hemorrhage received cranial irradiation alone (n = 9) or combined radiation and chemotherapy (n = 11) for primary brain tumors (n = 13), leukemia (n = 6), or lymphoma (n = 1). Imaging findings were consistent with hemorrhages of varying ages. The hemorrhages were not associated with tumor recurrence nor second tumors. Except for location of the hemorrhage, no significant relationship was established between outcome and original diagnosis, radiation dose (range, 1800 to 6000 centigray), chemotherapeutic agent or dosage, age at treatment, or interval between therapy and hemorrhage (mean, 8.1 years). Only brain stem hemorrhage was associated with a poor outcome. CONCLUSION: In children with central nervous system neoplasia who have undergone cranial irradiation, or radiation combined with chemotherapy, delayed intracranial hemorrhage may develop.

Adolescent↗
PubMed1995

Axonal growth and fasciculation linked to differential expression of BDNF and NT3 receptors in developing cerebellar granule cells.

In the developing cerebellum, young granule neurons in the external germinal layer respond preferentially to BDNF, while mature neurons within the inner portion of the cerebellum respond preferentially to NT3. Here we show that this anatomic distinction reflects a developmentally regulated switch at the level of neurotrophin receptor gene expression. The salient feature of the developmental switch is a change in the ration of mRNA transcripts encoding functional BDNF and NT3 receptor tyrosine kinases. The ratio of the BDNF receptor trkB to the NT3 receptor trkC reverses from 5:1 in neonatal cerebellum to 1:3 in adult cerebellum. TrkB and TrkC are closely related transmembrane tyrosine protein kinases. However, activation of BDNF and NT3 receptors in cerebellar granule neurons do not give equivalent biological responses. In aggregate cell culture and single cell assays, BDNF enhances axonal outgrowth of early granule cells by influencing neurite elongation. In contrast, NT3 alters the morphology of outgrowth. Collectively, these findings suggest that regulation of neurotrophin receptors during cerebellar development is important for the timing and morphology of axonal growth.

Animals↗
PubMed1994

Expression of the neurotrophin receptor TrkC is linked to a favorable outcome in medulloblastoma.

Medulloblastoma, the most common malignant brain tumor of childhood, has a variable prognosis. Although half of the children and young adults with the disease survive longer than 10 years after diagnosis, the others relapse and die despite identical therapy. We have examined the expression of neurotrophins and their receptors in medulloblastoma samples snap frozen in the operating room to preserve RNA integrity. All tumors (n = 12) were found to express mRNA encoding neurotrophin 3 and its receptor TrkC. The level of trkC expression was highly variable, with a more than 50-fold difference between the highest and lowest values. By Kaplan-Meier analysis, patients with tumors expressing high levels of trkC mRNA had significantly longer intervals without disease progression than those with low levels (log-rank, P = 0.03) and a more favorable overall survival (log-rank, P = 0.05). Thus, trkC expression is a prognostic indicator for patients with medulloblastoma.

Brain-Derived Neurotrophic Factor↗
PubMed1994

Stereotactic radiotherapy for pediatric and adult brain tumors: preliminary report.

PURPOSE: Stereotactic radiotherapy is a new modality that combines the accurate focal dose delivery of stereotactic radiosurgery with the biological advantages of conventional radiotherapy (1.8-2.0 Gy/day using 25-30 fractions). The modality requires sophisticated treatment planning, dedicated high-energy linear accelerator, and relocatable immobilization devices. We report here our early experience using stereotactic radiotherapy for intracranial neoplasms. METHODS AND MATERIALS: Between June 1992 and September 1993, we treated 82 patients with central nervous system lesions using stereotactic radiotherapy, delivered from a dedicated 6 MV stereotactic linear accelerator. A head fixation frame provided daily relocatable setup using a dental plate for all patients over 8 years of age. A modified head frame, which does not require a mouthpiece, was used for children requiring anesthesia. The patients ranged in age from 9 months to 76 years. Thirty-three patients were children less than 21 years of age. Selection criteria for the protocol included: (a) focal, small (< 5 cm) radiographically distinct lesions known to be radiocurable (pituitary adenoma, craniopharyngioma, meningioma, acoustic neuroma, pilocytic astrocytoma, retinoblastoma), and (b) lesions located in regions not amenable to surgery or radiosurgery such as the brain stem or chiasm. Standard fractionation and conventional doses were delivered. Patients with low-grade astrocytoma, oligodendroglioma, or ependymoma were treated using a dose escalation regime consisting of conventional doses plus a 10% increase. RESULTS: Although follow-up is 16 months (range 3-16 months), posttreatment radiographic studies in 77 patients have been consistent with changes similar to those found after conventional radiation therapy. To date, reduction of up to 50% of the original volume has been noted in 19 out of 77 patients, and 4 patients had a complete response, 2 with dysgerminoma, and 1 each with astrocytoma and retinoblastoma. In 56 patients disease was either stable or the follow-up was too short for evaluation. While the follow-up is relatively short, there have been no in-field or marginal recurrences. The only unexpected radiographic findings were in three patients with pilocytic astrocytomas, who developed asymptomatic edema in the treatment volume. Accuracy in daily fractionation was excellent. In over 2000 patient setups with 41,000 scalp measurements, reproducibility was found to be within 0.41 mm (median) of baseline readings, allowing for precise immobilization throughout the treatment course. The treatment in all cases was well tolerated with minimal acute effects. Our stereotactic radiotherapy facility can provide fractionated therapy for 10-12 patients a day efficiently and accurately. CONCLUSIONS: The treatment and relocatable stereotactic head frames were well tolerated with minimal acute effects. No long-term sequelae have been noted, although the observation period is short. To fully define the role of stereotactic radiotherapy, we are conducting prospective studies to evaluate neurocognitive and neuroendocrine effects. We expect that this innovative approach will make a significant impact on the treatment of intracranial neoplasms, particularly in children.

Adolescent↗
PubMed1994

The p53 tumor suppressor gene and pediatric brain tumors.

Mutations of the p53 tumor suppressor gene are common in astrocytomas that occur in adults but are rarely found in astrocytomas or medulloblastomas of children. This difference may contribute to the overall better prognosis of astrocytomas in children and potentially make pediatric astrocytomas and medulloblastomas more sensitive to antitumor therapy.

Astrocytoma↗
PubMed1994

Advances in radiation therapy for craniopharyngiomas.

The overall survival for patients with craniopharyngioma is excellent. However, conventional treatments that include aggressive surgery and standard irradiation have been associated with significant morbidity. Focal radiation treatment with stereotactic radiosurgery has a role in selected cases, but may also be damaging to sensitive normal tissues such as the optic chiasm. Stereotactic radiotherapy (SRT) is a technique that allows for conventionally fractionated radiation under stereotactic guidance. Thus, highly focal and precise radiotherapy is now coupled with fractionation, enabling the treatment of selected tumors with a potentially improved therapeutic index. Dose optimization with SRT for focally discrete tumors should result in equivalent local control and survival compared to patients treated with conventional irradiation. We anticipate a significant decrease in late effects, especially neuropsychological and neuroendocrine sequelae.

Child↗
PubMed1992

Vital imaging of glomeruli in the mouse olfactory bulb.

We have monitored the pattern of identified glomeruli in the olfactory bulbs of newborn, juvenile, and adult mice over intervals of several hours to several weeks. Our purpose was to assess the development and stability of these complex units in the mammalian brain. Glomeruli can be observed by vital fluorescent staining and laser-scanning confocal microscopy without causing acute or long-term damage to brain tissue. Repeated observation of bulbs in the same animals between birth and 3 weeks of age showed that this region of the brain develops by progressive addition of these units to the original population. This increment occurs by the genesis of smaller new glomeruli between larger existing ones; no elimination of glomeruli was observed during this process. Finally, no addition (or loss) of glomeruli occurred in adult animals over a 2 week interval; once established, the number, size, and pattern of glomeruli are evidently stable.

Aging↗
PubMed1990

Seizures and other neurologic sequelae of bacterial meningitis in children.

BACKGROUND: Although the mortality rate among children with bacterial meningitis has decreased dramatically in recent decades, some patients are left with neurologic sequelae. It has not been clearly established which features of the acute illness predict the chronic neurologic sequelae, including late seizures or epilepsy. METHODS: We followed 185 infants and children prospectively during and after acute bacterial meningitis. The mean duration of follow-up was 8.9 years (range, 0.1 to 15.5). During the first six years standard neurologic examinations were performed; telephone interviews were conducted thereafter. RESULTS: One month after meningitis, 69 children (37 percent) had neurologic abnormalities. Many of these signs resolved within a year, leaving only 26 children (14 percent) with persistent deficits: 18 (10 percent) had only sensorineural hearing loss, and 8 (4 percent) had multiple neurologic deficits. Thirteen children (7 percent) had one or more late seizures not associated with fever. The presence of persistent neurologic deficits indicative of cerebral injury was the only independent predictor of late afebrile seizures (P less than 0.001). CONCLUSIONS: After bacterial meningitis only children with permanent neurologic deficits are at high risk for epilepsy. Those with normal examinations after the acute illness have an excellent change of escaping serious neurologic sequelae, including epilepsy.

Acute Disease↗
PubMed1990

Postnatal construction of neural circuitry in the mouse olfactory bulb.

We have undertaken a quantitative analysis of the mouse olfactory bulb to address several major questions concerning the development of neural circuitry in the postnatal mammalian brain. These are: (1) To what degree are new elements and circuits added during maturation? (2) How long do such processes go on? and (3) Does postnatal development involve a net addition of circuits and their constituent elements, or is there elimination of some portion of an initial surfeit? Using male mice of known age, weight, and length, we measured the overall size of the bulb, the numbers of processing units (glomeruli) within the bulb, the extent and complexity of postsynaptic dendrites within the glomeruli, and the number of synapses in different regions of the bulb. Between birth and the time mice reach sexual maturity at 6-7 weeks of age, the bulb increases in size by a factor of 8, the number of glomeruli by a factor of 4-5, the length of mitral cell dendritic branches by a factor of 11, and the number of glomerular and extraglomerular synapses by factors of 90 and 170, respectively. Each of these parameters increases steadily from birth, in concert with the enlargement of the olfactory mucosa, the overall growth of the brain, and indeed, of the entire animal. We found no evidence of an initial surfeit of processing units, dendritic branches, or synapses. Further elaboration of neural circuitry by each of these measures is also apparent from the time of sexual maturity until the animals reach their full adult size at about 10-12 weeks of age. The developmental strategy in this part of the mouse brain evidently involves prolonged construction that persists until the growth of the body is complete. This ongoing elaboration of neural circuitry in the postnatal mammalian brain may be relevant to understanding a number of unexplained developmental phenomena, including critical periods, the ability of the juvenile brain to recover from injuries that would cause severe and permanent deficits in older animals, and the special ability of the maturing brain to encode large amounts of new information.

Aging↗
PubMed1988

Neuron/glia relationships observed over intervals of several months in living mice.

Identified neurons and glial cells in a parasympathetic ganglion were observed in situ with video-enhanced microscopy at intervals of up to 130 d in adult mice. Whereas the number and position of glial cells associated with particular neurons did not change over several hours, progressive differences were evident over intervals of weeks to months. These changes involved differences in the location of glial nuclei on the neuronal surface, differences in the apparent number of glial nuclei associated with each neuron, and often both. When we examined the arrangement of neurons and glial cells in the electron microscope, we also found that presynaptic nerve terminals are more prevalent in the vicinity of glial nuclei than elsewhere on the neuronal surface. The fact that glial nuclei are associated with preganglionic endings, together with the finding that the position and number of glial nuclei associated with identified neurons gradually changes, is in accord with the recent observation that synapses on these neurons are normally subject to ongoing rearrangement (Purves, D., J. T. Voyvodic, L. Magrassi, and H. Yawo. 1987. Science (Wash. DC). 238:1122-1126). By the same token, the present results suggest that glial cells are involved in synaptic remodeling.

Animals↗
PubMed1984

Effects of lead on neuromuscular transmission in the frog.

The acute effects of Pb2+ on synaptic transmission at the frog neuromuscular junction were measured using conventional microelectrode techniques. Experiments were performed on preparations bathed in high magnesium/low calcium Ringer solution in order to record subthreshold endplate potentials (EPPs). The effects of Pb2+ on the muscle membrane and postsynaptic membrane were minimal since relatively high doses of Pb2+ caused no significant change in the input resistance of the muscle fiber and in the amplitude of the acetylcholine (ACh) iontophoteric potential when the ACh micropipette was highly localized. However, when the ACh micropipette was moved away from the receptors, the resulting ACh potential was reduced significantly by Pb2+. Pb2+ is a potent blocker of the EPP. Extracellular recordings from motor nerve terminals showed that endplate currents (EPCs) were reduced by Pb2+ while the nerve terminal potentials were unaffected. Therefore, Pb2+ blocks evoked transmitter release at a step following the depolarization of the nerve terminal. The blocking effect on the EPP was overcome when [Ca2+]o was raised. The log-log relationship between [Ca2+]o (abscissa) and EPP amplitude was shifted to the right in the presence of 1 microM Pb2+; the mean +/- S.E. slopes were 4.16 +/- 0.12 (control) and 4.05 +/- 0.13 (Pb2+). Reciprocal plots relating [Ca2+]o-1 to (EPP)-1/5 confirmed that Pb2+ competitively antagonized the action of Ca2+. The dissociation constant between Pb2+ and the Ca2+ receptor site was found to be 0.99 microM. Pb2+ is about 3 X 10(3) times more potent than is Mg2+, about 150 times more potent than is either Mn2+ or Co2+, and about 3 times more potent than Cd2+ is in blocking evoked release of ACh. After Pb2+ decreased the EPP, the MEPP frequency began to increase; this was probably the result of intracellular Pb2+ disrupting the Ca2+ sequestering activity of mitochondria and/or other intraterminal organelles. [Ca2+]i was thereby increased and an increase in MEPP frequency followed. Decreased MEPP amplitudes were observed when the MEPP frequency had been increased by Pb2+. Pb2+ may affect most chemical synapses in a manner which is similar to its effects on the neuromuscular junction and that this may be one of its important neurotoxic effects.

Acetylcholine↗
PubMed1981

Interaction between central gray and nucleus raphe magnus: role of norepinephrine.

Recordings were made from single cells in the nucleus raphe magnus (NRM) of the rat. The response of these cells to electrical stimulation of the periaqueductal gray (PAG) was correlated with their response to iontophoretically applied norepinephrine (NE). It is shown that NE can cause excitation as well as inhibition of NRM neurons, although excitatory response was obtained more often than an inhibitory response. No correlation between the response to PAG stimulation and to NE was obtained. It is concluded that NE is not the transmitter that mediates the interaction between the PAG and NRM.

Animals↗