Biomedical subjects

I F Pollack

Publications and source records attributed to I F Pollack.

At least 73 records · Page 4Linked to original sources

PubMed1997

Basic fibroblast growth factor expression as a predictor of prognosis in pediatric high-grade gliomas.

Clinical and histopathological factors fail to adequately predict outcomes in children with high-grade gliomas, indicating a need to identify relevant biological markers of tumor behavior to guide therapeutic decision-making. Basic fibroblast growth factor (bFGF) is a mitogenic and angiogenic factor that has been observed to be overexpressed in a significant percentage of malignant gliomas, although the prognostic significance of this expression is unknown. To address this issue, the expression status of bFGF was examined immunohistochemically in a series of 27 archival pediatric malignant non-brainstem gliomas treated consecutively at our institution between 1975 and 1992. Tumors were categorized based on expression levels, and the association between expression status and outcome was examined. Sixteen cases showed high levels of expression of bFGF, and 11 showed low levels. There was no correlation between expression status and either tumor histology, patient age, or tumor location. However, there was a significant difference in outcome between patients with high levels of bFGF immunoreactivity and those with low expression. Median progression-free survival was >66 months in the low bFGF group as compared to 6 months in the high bFGF group (P = 0.006). Median overall survival was >66 months in the low bFGF group as compared to 18 months in the high bFGF group (P = 0.03). Tumor bFGF expression seems to be strongly associated with outcome in children with high-grade gliomas and, consequently, may serve as a biological correlate of patient prognosis in conjunction with other prognostic variables.

Adolescent↗

PubMed1997

A phase I study of high-dose tamoxifen for the treatment of refractory malignant gliomas of childhood.

Recent studies have indicated that the proliferation of malignant gliomas is in part dependent on excessive activation of protein kinase C (PKC)-mediated pathways. Conversely, inhibiting PKC may provide a novel approach for blocking glioma growth. The antiestrogen tamoxifen, a moderately potent PKC inhibitor, has been shown in vitro to block the proliferation of malignant glioma cell lines at concentrations several-fold higher than those typically attained during the treatment of breast cancer; such serum concentrations may be achieved with doses > 40 mg/m2 b.i.d. The safety and efficacy of these high doses for producing disease control in patients with malignant gliomas has recently been noted anecdotally, although a rigorous study of this agent has been lacking. To address this issue, we examined the safety and efficacy of high-dose tamoxifen in a series of children with malignant gliomas that had progressed after conventional therapy. An initial group was treated with 60 mg/m2 p.o. b.i.d. and a second group with 100 mg/m2 b.i.d. Steady-state serum tamoxifen and metabolite levels were measured in most patients. Toxicity with the regimen was minimal; two patients treated at the higher dose required reduction to the lower dose because of asymptomatic prolongation of the QT interval on an electrocardiogram. Although none of the patients exhibited clear-cut tumor regression, 4 of 14 patients had stabilization of previously progressive disease for at least 3 months; the longest survivor lived for 17 months after beginning tamoxifen. The moderate efficacy of this agent in otherwise end-stage disease coupled with its low toxicity and the relative ease of oral administration provides a rationale for proceeding with larger studies of this agent in patients with malignant gliomas, possibly as a means for potentiating the effects of conventional chemotherapeutic agents, which to date have shown limited efficacy in the treatment of these tumors.

Administration, Oral↗

PubMed1996

Continuous intraoperative electromyographic monitoring of cranial nerves during resection of fourth ventricular tumors in children.

The authors reviewed the results of continuous intraoperative electromyographic (EMG) monitoring of muscles innervated by cranial nerves in 17 children whose preoperative imaging studies showed compression or infiltration of the fourth ventricular floor by tumor to determine how intraoperative EMG activity correlated with postoperative cranial nerve morbidity. Bilateral lateral rectus (sixth) and facial (seventh) nerve musculature were monitored in all children. Cranial nerve function was documented immediately postoperatively and at 1 year. Of the 68 nerves monitored, nine new neuropathies occurred in six children (sixth nerve in four children and seventh nerve in five). In five new neuropathies, intraoperative EMG activity could be correlated in one of four sixth nerve injuries and four of five seventh nerve injuries. Electromyographic activity could not be correlated in four children with new neuropathies. Of 59 cranial nerves monitored that remained unchanged, 47 had no EMG activity. Twelve cranial nerves (three sixth nerves and nine seventh nerves) had EMG activity but no deficit. Of four children with lateral rectus EMG activity, three had new seventh nerve injuries. Lateral rectus EMG activity did not predict postoperative abducens injury. The absence of lateral rectus EMG activity did not assure preserved abducens function postoperatively. Likely because of the close apposition of the intrapontine facial nerve to the abducens nucleus, lateral rectus EMG activity was highly predictive of seventh nerve injury. Although facial muscle EMG activity was not an absolute predictor of postoperative facial nerve dysfunction, the presence of facial muscle EMG activity was associated statistically with postoperative facial paresis. The absence of facial muscle EMG activity was rarely associated with facial nerve injury. The authors speculate that EMG activity in the facial muscles may have provided important intraoperative information to the surgeon so as to avoid facial nerve injury.

Journal Article↗

PubMed1996

Monostotic fibrous dysplasia of the thoracic spine. A case report.

STUDY DESIGN: This case report details the diagnosis and treatment of a 12-year-old boy with progressive paraparesis from monostotic fibrous dysplasia of the thoracic spine. OBJECTIVES: The authors discuss their experience in the context of previous reports to recommend the optimal management of this disease. SUMMARY OF BACKGROUND DATA: Isolated vertebral involvement with fibrous dysplasia is exceedingly rare, with only 15 case reports describing the clinical presentation and treatment of these patients. The various treatments reported have included biopsy, decompression, curettage, and excision with or without fusion. A consensus for management has not been achieved. METHODS: The patient developed progressive neurologic deterioration from a combination of epidural extension of dysplastic tissue and a severe subluxation with kyphosis. Evaluation included plain radiographs, magnetic resonance imaging, computed tomography-assisted biopsy, and a bone scan. The patient was successfully treated with complete resection of both the bony and soft tissue components of the lesion by a single-stage combined approach involving posterior resection, instrumentation, and fusion to achieve rapid decompression and immediate stabilization followed by anterior resection with strut graft fusion to obtain a complete resection and prevent a delayed progressive kyphotic deformity. RESULTS: The patient's neurologic symptoms and signs rapidly resolved postoperatively. Graft incorporation with normal alignment was radiographically demonstrated at 3 months and maintained at 12 months. He has no pain or disability at 17 months follow-up. CONCLUSIONS: The authors recommend radical removal of all involved bone accompanied by internal fixation and bone grafting to achieve long-term stabilization in patients with monostotic fibrous dysplasia of the spine accompanied by neurologic deficits, instability or progressive pain.

Child↗

PubMed1996

Intracranial ependymomas of childhood. Lack of correlation of histopathology and clinical outcome.

The histopathology of 66 children with the diagnosis of ependymoma who were operated on at our institution between 1954 and 1994 were reviewed. We performed an initial analysis using the entire study cohort to determine which histopathological features associated with each other in a statistically significant fashion in an attempt to identify combinations of features that together might be useful in predicting outcome. A detailed outcome analysis was then performed on the 37 most recent cases who survived the postoperative period, in whom pre- and post-imaging studies as well as long term follow-up were obtained, in order to identify the histopathological features and combinations of features that were predictive of overall and progression-free survival. Five- and ten-year progression-free survivals were 45.1% and 36.1%, respectively. Overall survivals were 57.1% and 45.0%, respectively. Of the eight individual histopathological features, only the presence of necrosis was found to correlate with a less favorable overall and progression-free survival (PFS) (p = 0.06 and 0.03, respectively). In addition, the combination of necrosis with vascular proliferation or nuclear pleomorphism was associated with a worse PFS (p = 0.01 and 0.02, respectively). However, when other clinical predictive factors were included in a multivariate regression analysis, none of the histological features or combinations of features were independently associated with outcome. In addition, no relationship was found between the pattern of rosettes (true rosette, pseudorosette, or perivascular pseudorosette) and clinical outcome. In conclusion, although this study found an association between certain histopathological features and clinical outcome in children with ependymomas, these relationships did not reach statistical significance on multivariate analysis and, thus, do not provide sufficient evidence for modifying therapy based on histopathology alone.

Adolescent↗

PubMed1996

Vascularized fronto-orbital advancement.

Fronto-orbital advancement is the procedure of choice for correction of fronto-orbital recession resulting from coronal synostosis in children. However, long-term follow-up evaluations often reveal "undercorrection" of the deformity with development of recurrent recession of lateral supraorbital regions. One factor that may contribute to this process is devascularization of the fronto-orbital bar during its reshaping and advancement. If subsequent revascularization is suboptimal, excessive resorption or inadequate growth of the bar may lead to supraorbital recession. On the basis of studies of temporal bone grafts, which have shown that vascularized grafts are superior to free bone grafts in terms of bone graft survival, we postulated that maintaining vascularization of the fronto-orbital bar would favor better healing and growth that would translate to more favorable aesthetic results. Herein, we review the vascular anatomy of the fronto-orbital region and report the application in six patients of a technique for fronto-orbital advancement that preserves a significant portion of this blood supply. Technical caveats involved in the successful application of this approach are discussed. The attachment of the periosteum to the lateral two thirds of the supraorbital bar allows additional stability. This prevented the use of plates and screws in these patients.

Bone Transplantation↗

PubMed1996

Direct injury to the cervical spine of a child by a lap-shoulder belt resulting in quadriplegia: case report.

Most pediatric cervical spine injuries from seat-belt restraints result from hyperflexion of the neck without direct injury to the spine from the restraining device. We report what we believe to be the first case of direct injury to the cervical spine by the shoulder component of a lap-shoulder seat belt. This resulted in quadriplegia. The mechanism of injury and recommendations to obviate such injuries are discussed.

Accidents, Traffic↗

PubMed1996

High-grade astrocytomas in children: radiologically complete resection is associated with an excellent long-term prognosis.

High-grade astrocytomas comprise approximately 10% of intracranial tumors in children. A better prognosis in children than in adults has been reported for patients with these neoplasms, although the reasons for this survival advantage are uncertain. To determine whether any consistent factors were associated with long-term survival, we reviewed the records of 31 children with high-grade non-brain stem gliomas who were treated at our institution between 1975 and 1992. Histology was reviewed and classified according to the World Health Organization scheme, and neuroimaging studies were examined to determine the extent of resection, in both instances by individuals who were unaware of the patients' outcomes. The median overall survival for the 28 patients who survived the perioperative period was 18.5 months; 10 (36%) are currently alive, with a median follow-up of 70.5 months. The median progression-free survival (PFS) was 10.5 months; eight patients (29%) remain progression-free with a median follow-up of 78 months. The extent of resection at initial operation was associated most closely with PFS and overall survival as revealed by multivariate analysis. The 14 patients who underwent subtotal (< 90%) resection and the 7 who underwent near-total (90-99%) resection had median PFS of 5.5 and 11 months, respectively (P = 0.38), and overall survival of 10.5 and 25 months, respectively (P = 0.02). None of the seven patients who underwent gross total removal of tumor as confirmed by postoperative imaging had disease progression, with a median follow-up of 84 months (P < 0.0001). All of the tumors that underwent gross total resection were situated within the cerebral hemispheres; five of the seven patients had seizures as a presenting symptom. Both tumor location and seizures were significantly associated with outcome as determined by univariate analysis, but because of the overwhelming impact of resection extent on outcome, these factors were not independently associated with outcome as revealed by multivariate analysis. Histology was associated with outcome in the subgroup of patients with incompletely resected hemispheric tumors, in which children with anaplastic astrocytoma had a significantly better PFS than those with glioblastoma multiforme (P = 0.009). In summary, our results support the role of cytoreductive surgery in the treatment of cerebral hemispheric high-grade astrocytomas in children, which may encompass a biologically distinct group of tumors that, by virtue of their location and growth characteristics, are amenable to aggressive resection. The prognosis for children with deep-seated lesions and for those with subtotally resected hemispheric lesions is generally poor with conventional therapy.

Adolescent↗

PubMed1996

Incidence of increased intracranial pressure after early surgical treatment of syndromic craniosynostosis.

The late development of intracranial hypertension after an aesthetically successful cranial vault expansion has been noted anecdotally in children with syndromic synostosis. If untreated, this process can lead to neurological and visual deterioration; however, the frequency of this problem is uncertain. In an attempt to detect this process before the onset of irreversible impairment, the authors have since 1991 incorporated routine ophthalmological evaluations into the multidisciplinary follow-up protocol for all patients with complex craniosynostosis. These examinations were performed at initial evaluation and at 6-month intervals thereafter. The present report focuses on the results in 22 consecutive infants with syndromic synostosis who underwent initial surgery between 1991 and 1994. All but 4 children underwent initial cranial reconstruction at 6-18 months of age. Four patients had papilledema preoperatively which in each instance resolved postoperatively. During the follow-up period, 8 children manifested evidence of late intracranial hypertension at a median of 16.5 months after initial operation(s): 4 developed asymptomatic papilledema, 1 had progressive proptosis, and 3 had other subtle clinical signs of increased intracranial pressure (ICP). Further evaluation disclosed a Chiari 1 malformation in 2 children; 4 had a 'beaten copper' appearance on skull radiographs, and 4 underwent lumbar puncture, which in each case demonstrated an opening pressure above 20 cm H2O. Only 3 children exhibited symptoms from the ICP elevation. Six children with a head size < or = the 25th percentile underwent a repeat cranial expansion; after the cranial vault expansion, one child who initially had slit-like ventricles developed ventriculomegaly and, because of persistent papilledema, underwent insertion of ventriculoperitoneal (VP) shunt. Two other patients with a head circumference above the 50th percentile and the development of moderate ventriculomegaly underwent VP shunt insertion alone. All children have had complete resolution of papilledema as well as other symptoms and signs of increased ICP without evidence of optic atrophy or neurological sequelae. This study indicates that the incidence of delayed, asymptomatic increases in ICP among children with complex craniosynostosis is higher than previously estimated. The pathophysiologic bases for this process are discussed. Because the detection of this problem at a presymptomatic stage should optimize the likelihood of a good functional outcome, we strongly recommend close ophthalmological and clinical follow-up as a part of the comprehensive care of all young children with complex craniosynostosis, even after a cosmetically successful cranial expansion.

Craniosynostoses↗

PubMed1996

Comparison of simultaneous versus delayed ventriculoperitoneal shunt insertion in children undergoing myelomeningocele repair.

The timing of cerebrospinal fluid shunt insertion for those neonates with hydrocephalus in association with myelomeningocele remains controversial. To examine whether there was a difference in either the complication rate or mean hospital stay for neonates undergoing myelomeningocele repair and shunting under the same anesthetic (simultaneous group) versus those in whom shunt insertion was delayed for several days after myelomeningocele closure (sequential group), we reviewed the results obtained with these two approaches in a series of 69 consecutive patients who underwent both myelomeningocele closure and shunt insertion at our institution between 1987 and 1993. Twenty-one infants underwent simultaneous myelomeningocele repair and shunting, and 48 underwent sequential procedures. The decision to shunt concurrently with myelomeningocele repair rather than in a delayed fashion was based primarily on surgeon preference rather than initial head circumference, which did not differ significantly between the two groups. The frequency and type of hydrocephalus-related complications (e.g., wound leak, cerebrospinal fluid infection, or shunt malfunction) that occurred during the first 6 months after myelomeningocele closure were compared between the two groups. Neither the overall frequency of complications nor the frequency of cerebrospinal fluid infection, shunt malfunction, or symptomatic Chiari malformation differed significantly between the two groups. In contrast, there was a significantly higher rate of myelomeningocele wound leak in the sequential group versus the simultaneous group (eight versus zero; P = .05). Mean hospital stay for the sequential group was also significantly longer than the simultaneous group (22 days versus 13 days; P = .05). These results suggest that simultaneous myelomeningocele repair and ventriculoperitoneal shunt insertion reduces hospital stay and back wound morbidity in those patients with evidence of hydrocephalus at birth, without an inordinate increase in shunt-related complications.

Cerebrospinal Fluid Shunts↗

PubMed1996

The management of brainstem gliomas in patients with neurofibromatosis 1.

The appropriate management of brainstem tumors in patients with neurofibromatosis 1 (NF1) has been problematic because the natural history of these lesions remains poorly defined. To formulate rational guidelines for the evaluation and treatment of these tumors, we reviewed the outcome of 21 patients with brainstem mass lesions followed in our NF clinic during the last 9 years. We subdivided the imaging features of these lesions into four groups: (1) diffuse enlargement of the brainstem with hypointensity on T1-weighted MR images and hyperintensity on T2-weighted images (n = 9); (2) focal enhancing masses (n = 7); (3) intrinsic tectal tumors (n = 5); and (4) focal nonenhancing areas of hypointensity on T1-weighted MR images (n = 2). Two cases exhibited two types of lesions. Twelve patients presented with, or developed, symptoms that were referable to the mass; in nine, the lesion was asymptomatic. A distinguishing feature of these tumors was their generally indolent biological behavior. With a median follow-up of 3.75 years, only 10 patients have had radiographic (n = 9) or clinical (n = 3) evidence of disease progression. In seven of these patients, the tumor subsequently stabilized in size or regressed without intervention. Only four patients, each with a focal enhancing tumor, received specific therapy for the tumor; this consisted of biopsy (n = 1), excision (n = 3), and adjuvant radiotherapy (n = 2). Each of these lesions was a low-grade glioma histologically and each remained stable in size after treatment (median follow-up = 4.25 years). Four patients with tectal tumors underwent insertion of a CSF shunt for hydrocephalus, but required no specific treatment for the tumor. None of the patients with diffuse brainstem lesions or focal areas of hypointensity required any intervention for the tumor. All 21 patients are presently alive and well. We conclude that the biological behavior of brainstem lesions in patients with NF1 differs significantly from that of lesions with a similar appearance in patients without this disorder. Although these lesions may at some time in their course exhibit clinical and radiographic progression, most do not require specific intervention. The lesions that are most likely to progress and require therapy are focal enhancing tumors; however, even lesions in this subgroup may stabilize in size or regress spontaneously without intervention. Based on these results, we recommend that intervention be limited to those lesions that exhibit rapid or unrelenting growth on serial images or that produce significant clinical deterioration.

Adolescent↗

PubMed1996

A combined frontoorbital and occipital advancement technique for use in total calvarial reconstruction.

The management of infants with bilateral coronal synostosis and resultant brachyturricephaly poses a significant therapeutic challenge. The application of total calvarial reconstruction to the treatment of this problem has represented a major recent innovation that has substantially improved the cosmetic results in this patient population. However, rigid fixation of the reconstructed calvaria is often required to maintain the correction achieved and to provide protection for the underlying brain. The requirement of extensive fixation constitutes a significant disadvantage for the use of this procedure in infants and young children. In this report, the authors describe an approach to the treatment of this problem that incorporates a series of tongue-in-groove osteotomies to provide increased stability to advancements of both the frontal and occipital regions in conjunction with cranial height reduction, while minimizing the need for metallic fixation. With this approach, the reconstructed skull is sturdy enough to resist the compressive force applied by the weight of the child's head immediately after surgery, but retains the ability to expand progressively. The authors have found the cosmetic results to be extremely gratifying. In this article they present their experience with this technique in seven children.

Adult↗

PubMed1996

Blocking of glioma proliferation in vitro and in vivo and potentiating the effects of BCNU and cisplatin: UCN-01, a selective protein kinase C inhibitor.

Seven-hydroxystaurosporine (UCN-01) is a derivative of the nonselective protein kinase inhibitor staurosporine that exhibits significant selectivity for protein kinase C (PKC) in comparison to a variety of other intracellular kinases and appears to be well tolerated in vivo at concentrations sufficient to achieve effective inhibition of PKC. Because recent studies have indicated that the proliferation of malignant gliomas may result from activation of PKC-mediated pathways and, conversely, may be inhibited by blocking PKC, the authors examined the efficacy of this agent as an inhibitor of proliferation in three established and three low-passage malignant glioma cell lines in vitro. A striking inhibition of proliferation was produced by UCN-01 in each of the cell lines, with a median effective concentration of 20 to 100 nM, which correlated with the median in vitro PKC inhibitory concentration of 20 to 60 nM for this agent in the U-87 and SG-388 glioma cell lines. Inhibition-recovery studies of clonogenic activity indicated that UCN-01 had both cytostatic and cytotoxic effects on the treated cells. Proliferation resumed after short-term (6- and 24-hour) exposures to this agent; in contrast, with longer exposures, recovery of proliferative activity was severely compromised. In addition, UCN-01 enhanced the inhibition of glioma cell proliferation achieved with conventional chemotherapeutic agents, exhibiting synergistic effects with cisplatin and additive effects with 1,3-bis(2-chloroethyl)-1-nitrosourea. In vivo studies in which UCN-01 was administered by continuous intraperitoneal infusion in subcutaneous and intracranial intraparenchymal nude rat models demonstrated significant activity against U-87 glioma xenografts at dose levels that were well tolerated. It is concluded that UCN-01 is an effective agent for the inhibition of glioma proliferation in vitro and in vivo and has potential for clinical applicability in the treatment of human gliomas.

Alkaloids↗

PubMed1996

The effect of early craniocervical decompression on functional outcome in neonates and young infants with myelodysplasia and symptomatic Chiari II malformations: results from a prospective series.

The indications for hindbrain decompression in neonates and young infants with spinal dysraphism who experience brain stem dysfunction in association with Chiari II malformations have remained controversial. This largely reflects the fact that the postoperative outcome in such patients has often been poor, which has supported the belief that much of the brain stem compromise in these patients is congenital and inherently irreversible. However, in a previous retrospective review of our operative results between 1975 and 1989, we noted that a significant component of the brain stem dysfunction in these children was an acquired phenomenon that potentially was reversible with prompt operative intervention. Accordingly, we hypothesized that with early craniocervical decompression, excellent functional outcome could be achieved in a majority of neonates and young infants with symptomatic Chiari II malformations. On the basis of this premise, we prospectively treated all such patients since 1989 with urgent brain stem decompression after other potential causes for brain stem dysfunction, such as progressive hydrocephalus, had been ruled out. All children underwent limited suboccipital craniectomies, cervical laminectomies extending beneath the inferior extent of the cerebellar tissue, and dural decompressions. The outcome in these patients has been favorable in comparison with previous studies. Ten of the 13 children treated according to this protocol recovered normal or nearly normal brain stem function shortly after decompression; 1 child had mild residual unilateral lower cranial nerve paresis. None of these children required a tracheostomy for ventilatory support, and only one required a temporary gastrostomy. The other three children all exhibited bilateral vocal cord paralysis and severe central hypoventilation by the time decompression was performed and failed to have any meaningful recovery of function. We conclude that early recognition of the symptoms of brain stem compromise in neonates and young infants with spinal dysraphism coupled with urgent evaluation and decompression are effective in producing prompt resolution of the brain stem dysfunction in most affected patients. Conversely, the prognosis for recovery is poor in children who exhibit bilateral vocal cord paralysis by the time of decompression.

Arnold-Chiari Malformation↗

PubMed1995

Frameless stereotactic guidance. An intraoperative adjunct in the transoral approach for ventral cervicomedullary junction decompression.

METHODS: The application of a video-interactive frameless stereotactic guidance system for the treatment of ventral cervicomedullary junction compression is described in a patient with basilar invagination, odontoid dysgenesis, and a Chiari malformation who had irreducible impingement on the ventral brainstem by a partially fused mass of bone made up of the malformed odontoid peg, the inferior clivus, and dorsally protruding osteophytes at the odontoid-clival junction. RESULTS: This technology permitted instantaneous feedback of the surgeon's orientation in all planes, facilitating extensive removal of the dens and clival tip to achieve adequate ventral brainstem decompression. In view of the distortion of the craniovertebral anatomy produced by the patient's anomalies, the ability to visualize three dimensionally the location of the vertebral arteries also added an element of safety to the lateral bone removal. Similarly, the ability to localize the rostral limit of the clivus that needed to be resected and the caudal extent of C2 that needed to be removed to achieve an adequate decompression helped ensure that the extent of bone removal was appropriately tailored to the patient's anatomy. CONCLUSION: The authors believe this technique represents a significant advance over standard radiographic intraoperative localization techniques during transoral approaches to the ventral cervicomedullary junction for patients in whom the odontoid is fixed in position in relation to the clivus. This is based on the speed with which localization can be obtained, the accuracy of the information provided, the ability to obtain localization in multiple planes simultaneously, and the lack of radiation exposure during the procedure.

Brain Stem↗

PubMed1995

Rejection of mesencephalic retinal xenografts in the rat induced by systemic administration of recombinant interferon-gamma.

Previous studies have shown that mesencephalic retinal xenografts can be induced to undergo rejection following various systemic and local manipulations of the host immune system. In each of these paradigms, the development of major histocompatibility complex (MHC) antigen expression on cells in and around the graft is correlated with the onset of rejection. We therefore examined the effect on graft viability of systemic administration of high-dose interferon-gamma a potent inducer of MHC antigen expression on cells within the brain. Postnatal Day 1 (P1) Sprague-Dawley rats received mesencephalic grafts of Embryonic Day 13 CD-1 mouse retina. Beginning at P30, one group of rats received daily injections of rat recombinant interferon-gamma intraperitoneally; litter-matched control animals received injections of vehicle alone. Rats were sacrificed on P51. Each of the animals with detectable grafts that had received interferon-gamma showed a strong rejection response characterized by perivascular cuffing with mononuclear cells in and around the graft and infiltration of the graft and the surrounding host brain by lymphocytes and MHC class I- and class II-antigen positive cells resembling reactive microglia. In contrast, only 2 of the 11 control grafts showed evidence of rejection. The rejection rate in the interferon-treated group was significantly higher than in the control group (Fisher's exact test, P = 0.0012). These results suggest that interferon-gamma is involved in the initiation and/or subsequent maintenance of the rejection response to cross-species transplants.

Animals↗

PubMed1995

The role of frameless stereotactic techniques in the treatment of pediatric CNS lesions.

The surgical management of children with deep-seated lesions within the brain and skull base or with superficial lesions within functionally important regions of the brain is often challenging. In order to optimize the functional outcome of an affected child, it is essential not only to adequately treat the offending lesion, but also to minimize injury to the surrounding brain. In this study, we examined the applicability of a video-interactive frameless stereotactic system for intraoperative localization and treatment of a variety of pediatric central nervous system problems, including craniotomy for tumor (n = 14), vascular malformation (n = 3), or cortical resection for intractable epilepsy (n = 4); ventricular puncture for shunt insertion in a patient with slit ventricles (n = 2); transoral odontoid resection (n = 1); cannulation of a brainstem syrinx (n = 1); removal of a foreign body (n = 1); and posterior craniocervical decompression (n = 1). The efficacy of the system was judged on several criteria: (1) the accuracy of the targeting achieved; (2) whether the system facilitated treatment of the lesions of interest; and (3) whether neurologic function was preserved. In general, the accuracy of the system for target localization was within 2-4 mm when rigid head fixation was employed intraoperatively. In such cases, frameless stereotactic guidance was extremely helpful in providing rapid and reliable assistance with operative planning, which facilitated the treatment of a variety of lesions in critical areas of brain with minimal neurologic morbidity. Limitations of this technology and potential solutions to these shortcomings are discussed. We conclude that the application of frameless stereotaxis for intraoperative localization represents a major advance in the treatment of a variety of intracranial processes in children by providing a means for accurately directing the approach to and removal of a targeted lesion while minimizing injury to the surrounding brain.

Astrocytoma↗

PubMed1995

The efficacy of tamoxifen as an antiproliferative agent in vitro for benign and malignant pediatric glial tumors.

Recent studies have suggested that the triphenylethylene antiestrogen tamoxifen inhibits the proliferation in vitro of a substantial percentage of cell lines derived from adult high-grade gliomas, potentially acting through inhibition of the second messenger protein kinase C. These findings have formed the impetus for clinical trials of this agent in adults with malignant gliomas. However, it has previously remained uncertain whether tamoxifen has a similar inhibitory effect on the proliferation of pediatric high-grade gliomas, and whether low-grade gliomas, which constitute the majority of glial neoplasms in children, are also inhibited by this agent. To address these issues, the present study examined the effect of tamoxifen on proliferation and viability in a series of low-passage cell lines derived both from low-grade and high-grade pediatric gliomas. This agent was tested in three malignant gliomas, two pilocytic astrocytomas, two non-pilocytic low-grade astrocytomas, 1 mixed glioma, and 1 oligodendroglioma. Tamoxifen produced a dose-dependent inhibition of proliferation in two of the three malignant glioma cell lines and in each of the low-grade glioma cell lines with a 50% effective dose of approximately 3 micrograms/ml (5.4 microM), which is comparable to the IC50 for inhibition of PKC activity by this agent. No significant cytotoxicity was encountered at this concentration. However, complete elimination of proliferation was achieved with a dose of 10 micrograms/ml (17.8 microM), which produced a direct cytotoxic effect. We conclude that tamoxifen inhibits proliferation of cell lines derived from both low-grade and high-grade pediatric glial tumors in vitro at concentrations that may be achievable clinically with high-dose oral therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Agents, Hormonal↗